Articles de revues : « Pre-neoplastic lesion »

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Gobran, Mai A., Soheir El-Ghoneimey, Safaa A. S. Ibrahim et Sabah Mohamedhanafy. « Systemic Lupus Erythematosus as a Risk Factor for Cervical Cancer and its Precursor Conditions : Assessment Using Pap Smear and Histopathology ». Gynecology and Obstetrics Research – Open Journal 8, n^o 1 (30 décembre 2022) : 1–7. http://dx.doi.org/10.17140/goroj-8-155.

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Background Cancer of the cervix is a common cause of malignancy. Its association with systemic lupus erythematosus (SLE) is debatable. Objective Early detection of cervical pre-neoplastic lesion in SLE patients. Method A case control study was performed on 64 SLE group and 64 control group using a colposcopy, pap smear and histopathological examination. Conclusion This study revealed that preneoplastic and neoplastic lesions of the cervix were higher in the SLE group.

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Malik, Ayesha Imtiaz, Farrukh Kamal, Munazza Iqbal, Aasmaa Qureshy et Farah Kalsoom. « Distribution of various histopathological patterns of ovarian lesions in different age groups ». Pakistan Journal of Medical and Health Sciences 16, n^o 7 (30 juillet 2022) : 213–16. http://dx.doi.org/10.53350/pjmhs22167213.

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The spectrum of ovarian pathologies embraces wide age range among females because the risk of developing ovarian lesion starts from birth and follows diverse patterns through-out the life.1,2 The rate of development of complications, recurrence, progression to malignancy, morbidity and mortality, also varies according to the age of presentation of various ovarian pathologies.3,4,5 The prevalence of cystic lesions of ovary is more in reproductive age group as compared to post-menopausal women.6,7 Malignant neoplasms have more been observed in an advanced age group.8,9,10 The current study is aimed to observe the distribution of various histopathological patterns of ovarian lesions in different age groups. This study may be beneficial in stratifying patients, into different risk based groups and prognosis associated groups, depending upon the age of patient at the time of presentation. Methods: Total 150 cases of ovarian lesions were selected by convenient sampling in current descriptive study, carried out at Pathology department of Fatima Jinnah Medical University, Lahore from May, 2019 till June, 2020. Routine H & E stained sections, from specimens of total abdominal hysterectomy with unilateral or bilateral salpingo-oophorectomy, unilateral or bilateral oophorectomy and salpingo-oophorectomy procedures, done either for primary ovarian lesion or other than primary ovarian pathology, in all age groups, were included. Results: A majority of ovarian lesions 123 (82%) were observed in the reproductive age group, mostly being non-neoplastic (89.5%). Out of 19 post-menopausal patients, 12 presented with malignant neoplasms. All patients belonging to pre-pubertal age group had non-neoplastic pathologies. Conclusion: The malignant ovarian tumors are prevalent in post-menopausal patients while reproductive age group predominantly exhibits non-neoplastic and benign ovarian lesions. The pre-pubertal age group commonly present with non-neoplastic ovarian pathologies. Keywords: Histopathological patterns of ovarian lesion, Malignant ovarian tumors, Reproductive age group.

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Bagga, Neha, Poonam Elhence, Meenakshi Rao, Aasma Nalwa, Sudeep Khera, Jyotsna Naresh Bharti, Pratibha Singh et Shashank Shekhar. « A prospective study of cervical lesions diagnosed by liquid based cytology in Western Rajasthan, India population ». International Journal of Research in Medical Sciences 7, n^o 12 (27 novembre 2019) : 4573. http://dx.doi.org/10.18203/2320-6012.ijrms20195521.

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Background: Carcinoma cervix is the second most common malignancy of women in India after breast cancer. The present study was conducted to determine the spectrum of cervical lesions by liquid-based cytology in Western Rajasthan population.Methods: It is a Prospective study on 1087 cervical samples carried over a period of 1 year. Cervical samples were taken and processed by SurePath™ LBC.Results: Of total 1087 cases 959 were negative for intraepithelial lesion or malignancy (88.22%). 88 cases (8.09%) were reported as unsatisfactory. Among the non- neoplastic cases- bacterial vaginosis was reported in 209 cases (21.8%), Candida in 77 cases (8.02%), both Candida and bacterial vaginosis in 12 cases (1.25%), reactive cellular changes in 193 cases (20.12%), and Trichomonas vaginalis in 01 case. Among pre-malignant and malignant lesions, 40 cases (4.17%) the distribution was as follows-atypical squamous cells of undetermined significance 16(1.67%), atypical squamous cell-cannot rule out high grade 08 cases (0.83%), Low grade squamous intraepithelial lesion 04 cases (0.42%), high grade squamous intraepithelial lesion 07 cases (0.73%), Atypical glandular cell favoring neoplastic 01 case (0.15%), and squamous cell carcinoma 04 cases (0.42%). Histopathological co-relation of premalignant and malignant lesions was further studied.Conclusions: Liquid based cytology is an effective screening and diagnostic procedure for cervical abnormalities. Among pre-malignant and malignant lesions, histo-pathological correlation increased with increased grade of severity of lesions. To the best of knowledge, this is the largest study of liquid based cytology in the Western Rajasthan.

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Thakkar, Kunal, Swati Ramteke-Jadhav, Rajeev Kasaliwal, Saba Samad Memon, Virendra Patil, Puja Thadani, Nilesh Lomte et al. « Sellar surprises : a single-centre experience of unusual sellar masses ». Endocrine Connections 9, n^o 2 (février 2020) : 111–21. http://dx.doi.org/10.1530/ec-19-0497.

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Background Most common incidentally detected sellar-suprasellar region (SSR) masses are pituitary adenomas, followed by craniopharyngioma, rathke’s cleft cyst, hypophysitis, and meningioma. Besides these, certain unusual SSR lesions can sometimes present as diagnostic challenges, where diagnosis is often made post-operatively on histopathology, the pre-operative suspicion of which might have influenced the management strategies. Series describing such masses are few. Objective To present clinical, biochemical, and radiological characteristics and management outcomes of rare SSR lesions other than pituitary adenomas, craniopharyngioma, rathke’s cleft cyst, hypophysitis, and meningioma. Design, setting, patients Retrospective case record analysis of patients with uncommon SSR masses (from January 2006 to December 2016). Results Our series consisted of ten patients, five with neoplastic and five with non-neoplastic lesions. Neoplastic masses included granular cell tumor (n = 2), astrocytoma (n = 1), malignant peripheral nerve sheath tumor (MPNST, n = 1), and metastasis from occult papillary carcinoma of thyroid (n = 1), while non-neoplastic masses were aspergillus abscess (n = 1), sterile abscess (n = 1), and tubercular abscess (n = 1), aneurysm of left internal carotid artery (n = 1), and ruptured dermoid cyst (n = 1). All patients (except one) presented with headache and/or visual disturbance. Only one patient had acromegaly while most others had hypopituitarism. We describe detailed MRI characteristics of each of the lesion. Seven patients underwent trans-sphenoidal surgery. Post-operatively, five patients had permanent diabetes insipidus, while two patients died in early post-operative period. Conclusion Our series expand the differential diagnostic considerations of SSR lesions. Most of the rare SSR masses present with symptoms of mass effects and hypopituitarism. Except for some non-neoplastic lesions like sellar abscesses, aneurysms, and dermoid cysts which can have some specific imaging characteristics that can provide clue to pre-operative diagnosis, most of the other neoplastic masses have overlapping radiological features, and pre-operative suspicion remains difficult.

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de Godoy Fernandes, Giovana, Bruna Pedrina, Patrícia de Faria Lainetti, Priscila Emiko Kobayashi, Verônica Mollica Govoni, Chiara Palmieri, Veridiana Maria Brianezi Dignani de Moura, Renée Laufer-Amorim et Carlos Eduardo Fonseca-Alves. « Morphological and Molecular Characterization of Proliferative Inflammatory Atrophy in Canine Prostatic Samples ». Cancers 13, n^o 8 (14 avril 2021) : 1887. http://dx.doi.org/10.3390/cancers13081887.

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Proliferative inflammatory atrophy (PIA) is an atrophic lesion of the prostate gland that occurs in men and dogs and is associated with a chronic inflammatory infiltrate. In this study, we retrospectively reviewed canine prostatic samples from intact dogs, identifying 50 normal prostates, 140 cases of prostatic hyperplasia, 171 cases of PIA, 84 with prostate cancer (PC), 14 with prostatic intraepithelial neoplasia (PIN) and 10 with bacterial prostatitis. PIA samples were then selected and classified according to the human classification. The presence of PIA lesions surrounding neoplastic areas was then evaluated to establish a morphological transition from normal to preneoplastic and neoplastic tissue. In addition, the expression of PTEN, P53, MDM2 and nuclear androgen receptor (AR) were analyzed in 20 normal samples and 20 PIA lesions by immunohistochemistry and qPCR. All PIA lesions showed variable degrees of mononuclear cell infiltration around the glands and simple atrophy was the most common histopathological feature. PIA was identified between normal glands and PC in 51 (61%) out of the 84 PC samples. PIA lesions were diffusely positive for molecular weight cytokeratin (HMWC). Decreased PTEN and AR gene and protein expression was found in PIA compared to normal samples. Overall, our results strongly suggest that PIA is a frequent lesion associated with PC. Additionally, this finding corroborates the hypothesis that in dogs, as is the case in humans, PIA is a pre neoplastic lesion that has the potential to progress into PC, indicating an alternative mechanism of prostate cancer development in dogs.

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Akhtar, Zahid Mahmood, Madiha Arshad et Rabia Altaf. « Frequency of Thyroid Lesions at Pathology Department of King Edward Medical University Lahore ». Pakistan Journal of Medical and Health Sciences 16, n^o 3 (26 mars 2022) : 146–48. http://dx.doi.org/10.53350/pjmhs22163146.

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Background: Thyroid gland is notorious for carrying commonest endocrine pathologies and also for commonest endocrine malignancy. It is the 5th most common cancer in human beings. This makes to carry out current study to get insight of frequency of thyroid lesions at tertiary care level. Methods: This was a descriptive cross-sectional study. The study was done at the Department of Pathology, King Edward Medical University Lahore with the collaboration of four surgical units of Mayo Hospital Lahore from 2010 to 2019. Total 1601 cases were included. Information about age, sex and diagnosis was entered in the pre designed proforma. SPSS version 22 was used for data analysis. Descriptive analysis was done and the results were presented as frequencies, percentages and ratios. The results were then studied against local and international data. Results: This study revealed non neoplastic and neoplastic lesions as 1323 (82.63%) and 278 (17.37%) respectively. Bulk of the lesions 61.6% were between the age bracket of 20-39 years. Mean±SD for age was 34.22±11.42 years. Female to male ratio(F:M) was in favour of females as 9.81:1. Among the non neoplastic lesions, MNG 1151(87%) was a dominant lesion followed by TH 82(6%). LT 29(2.19%) and HT 26(1.96%) were other important lesions. F:M ratio was 10.80:1. Neoplastic lesions were divided into benign 178(64%) and malignant tumors 100(36%). FA was the leading benign neoplasm 164(59%). Rest of the benign tumors shared a minor fraction except HCA 12(4.31%). Among the malignant category, Papillary carcinoma 69(24.82%) dominated over MC 12(4.31%). FC 7(2.51%) and AC 6(2.15%) were other significant findings. F:M ratio in malignancy was 3.16:1 which was significantly lower than 13.83:1 in benign tumors. Conclusion: MNG is the dominant lesion among the non neoplastic lesions while in the neoplastic category FA was leading as benign neoplasm. Papillary carcinoma turned out to be the commonest malignant tumor. Major share of all the lesions were seen between 20-39 years. Keywords: MNG, Papillary carcinoma, Follicular adenoma, neoplastic lesions

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Machiwal, Kishan, Bhawika Menghani, Neena Kasliwal et M. P. Sharma. « Histopathological spectrum of lesions in gastrointestinal endoscopic biopsies in Jawahar Lal Nehru Medical College and associated group of Hospitals, Ajmer, Rajasthan ». International Journal of Research in Medical Sciences 10, n^o 12 (25 novembre 2022) : 2831. http://dx.doi.org/10.18203/2320-6012.ijrms20223084.

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Background: The gastrointestinal tract which extends from the esophagus to anus is a common site for numerous pathological processes from non-neoplastic, pre-neoplastic, to neoplastic. Gastrointestinal tumors including both benign and malignant tumors are the major cause of morbidity and mortality worldwide. Endoscopy in combination with endoscopic biopsy plays an important role in detecting early cancers and/or high-grade dysplasia and in the diagnosis of upper and lower gastrointestinal tract neoplasms and therefore aids in their early management.Methods: This study was done for 1 year from July 2018 to June 2019 (retrospectively) and over a period of 1 year from July 2019 to June 2020 (prospectively). All endoscopic biopsies samples were received in the department of pathology at J. L. N. Medical College and Associated Group of Hospital, Ajmer, Rajasthan.Results: The mean age of patients were 51.91±18.86 years and highest incidence of gastrointestinal (GI) disease was seen between the age group of 51-60 years. The male: female (M: F) ratio was 1.46: 1. Non neoplastic lesions are more common than neoplastic lesions. Inflammatory lesion was the most commonly observed lesion followed by malignant lesions. The sensitivity of endoscopy is 96.25%, specificity is 68.67%, the positive predictive value is 74.76% and the negative predictive value is 95%. Accuracy for diagnosis by endoscopy is 82.21%.Conclusions: Endoscopic biopsy correlation reflects important advances in understanding the pathophysiology of disease and prognosis and survival rates after staging in the case of carcinomas. It provides diagnostic information and aids in improving patient management.

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Zhang, Jianjun, Dan Su, Junya Fujimoto, Lisa Ying, Chi-Wan Chow, Wenyong Sun, Jianhua Zhang et al. « Multiregion whole exome seuquencing of pre- and early neoplastic lung lesions. » Journal of Clinical Oncology 35, n^o 15_suppl (20 mai 2017) : e20042-e20042. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e20042.

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e20042 Background: The widespread use of CT for lung cancer screening and other reasons has resulted in a dramatic increase in the number of indeterminate ground glass opacities (GGOs). While many of GGOs can be resected with minimal morbidity, the cost has been called into question. Furthermore, multifocality is a relatively common, which makes decisions on extent of surgical resection and potential benefit less clear. Chemoprevention is a theoretically appealing approach to reduce lung cancer incidence and mortality. However, randomized trials have been disappointing to date. This may be due to the constellation of many factors including lack of reliable biomarkers to identify high-risk patients, lack of appropriate molecular targets and appropriate drugs because of our rudimentary knowledge on early carcinogenesis of lung cancers. It has been postulated that atypical adenomatous hyperplasia (AAH) represents preneoplastic lesion that can progress to adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and further to frankly invasive adenocarcinoma (ADC). However, the biology of these lesions is poorly understood and the definition and management of these lesions remain controversial. Methods: Study on early carcinogenesis is hampered by the small size of lesions and challenge of obtaining longitudinal samples at different stages of disease progression. Multiregion sequencing can depict genomic events relative to molecular time with early events ubiquitously present in all regions and late mutations confined to spatially separated regions of lesions. Using this approach, our recent work has reported that 20/21 canonical cancer gene mutations were early genetic events. Results: With intent to delineate the pivotal molecular events driving early carcinogenesis of lung cancer, we have collected 154 resected GGOs with including AAH (N = 40), AIS (N = 39), MIA (N = 55) and ADC (N = 20) based on the IASLC/ATS/ERS classification from 89 patients including 38 patients presenting with multifocal GGOs and 18 patients carry more than one type of pathology. Two to five spatially separated regions from each of the 154 lesions are subjected to whole exome sequencing. Conclusions: The data will be ready to present at the meeting.

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Chaudhary, Aishwarya, et Aarti B. Bhattacharya. « The Study on the Clinico-pathological Spectrum of Non-neoplastic and Neoplastic Lesions in Cholecystectomy Specimens at a Tertiary Care Centre ». Annals of Pathology and Laboratory Medicine 9, n^o 2 (5 mars 2022) : A44–49. http://dx.doi.org/10.21276/apalm.3118.

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Background: Most commonly used surgical procedure for gall-bladder pathology is cholecystectomy. Gall-bladder diseases incidence has increased over the past decade and are cause for a number of histopathological changes like pre-neoplastic conditions and ultimately culminating into the neoplasia. Histopathologic examination of the specimen serves as the absolute diagnosis of the non-neoplastic and neoplastic lesions as pre-operative imaging techniques fail to identify the lesions Aim: To analyse the clinico-pathological spectrum of various non- neoplastic and neoplastic lesions occurring in cholecystectomy specimens with and without gall bladder calculus. Materials & Method: An observational, cross-sectional study was conducted between 2019 to 2020 at a tertiary care centre in Safedabad, Barabanki, UP. A total of 135 cholecystectomy specimens were evaluated for histopathological examination. After histopathological reporting all cases were clinicopatholically related. Data was analysed using SPSS software, the demographic data were presented as frequency, percentage; continuous variables with mean and standard deviation. Results: 74.8% were females (n=101) and 25.2% were males (n=34) with mean age of 42.96 years. Gall-bladder stone was present in 85.2% of patients (n=115) and absent in 14.8% patients (n=20). Neoplastic lesion in 7 of the patients, 5 patients with adenocarcinoma, 1 patient with adenosquamous carcinoma and 1 patient with papillary adenocarcinoma. Gall-bladder carcinoma were diagnosed in our study; the poorly differentiated GBC revealed high Ki67 Score. Conclusion: Gall-bladder diseases can have a varied presentation both clinically and histopathologically. Hence, a complete and meticulous macroscopic and microscopic examination of all cholecystectomy specimens should be mandatory for better patient care.

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Kaplanoğlu, Veysel, Deniz Sözmen Ciliz, Hatice Kaplanoğlu et Eda Elverici. « Aneurysmal Bone Cyst of the Calcaneus ». Journal of Clinical Imaging Science 4 (31 octobre 2014) : 60. http://dx.doi.org/10.4103/2156-7514.143732.

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Aneurysmal bone cysts (ABCs) are benign, non-neoplastic, expansile, vascular, locally destructive lesions. The lesion may arise de novo (65%) or secondarily (35%) in pre-existing benign or malignant lesions (giant cell tumor, osteoblastoma, chondroblastoma, angioma, and others). The calcaneus is a rare localization for ABC, comprising only 1.6% of the cases. In this paper, we present a case of a female patient with a 3-month history of heel pain that got worse and was accompanied by swelling and difficulty in walking. The magnetic resonance images of the postero-lateral calcaneus showed a contrast-enhanced cystic lesion located in the medullary cavity; exophytic portion of the tumor extended into the soft tissue causing distinctive cortical thinning. Heterogeneous hyperintense septae formations and blood level components were also detected. After correlation with pathology results, the lesion was diagnosed as an ABC. Since an ABC of the calcaneus is a rarely seen phenomenon, we present the radiologic findings in this case and a review of the literature.

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Chandrakoshi, Gautam, Sanjuna D, Ajay Patidar et Nikita Singh. « Cytomorphological features of salivary gland lesions based on the Milan system of reporting in a tertiary care center ». Asian Journal of Medical Sciences 13, n^o 8 (1 août 2022) : 226–30. http://dx.doi.org/10.3126/ajms.v13i8.44001.

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Background: Fine-needle aspiration cytology (FNAC) of the salivary glands is a well-established technique that aids in pre-operative identification of abnormalities and to distinguish between neoplastic and non-neoplastic salivary gland lesions. Milan system for reporting of salivary gland cytology uses a standardized tiered system for categorization of salivary gland lesions. Aims and Objectives: The present research was aimed to study the prevalence of various salivary gland lesions cytologically and classify them based on the Milan system. Materials and Methods: The current retrospective descriptive study was done in the Department of Pathology, Shyam Shah Medical College, Rewa, M.P. A total of 57 FNAC slides were retrieved, re-examined, and re-classified according to the Milan system. Results: In the present study, a total of 57 cases of salivary gland lesions were included and categorized under the Milan system of salivary gland cytology. 5.3% of the smears in our study were non-diagnostic (Category I). The most common category was IVa comprising benign neoplastic lesions with 36.8%. Non-neoplastic lesions (Category II) were seen in 24.6% cases, whereas 14% of the lesions belonged to category IVb (suspicious for malignancy). Malignant lesions (Category VI) comprised 8.8% of all the cases. Conclusion: The most common and least common category of salivary gland lesion was Category IVa and Category IVb, respectively. The adoption of Milan classification system for reporting salivary gland FNAC is a critical step in categorizing these lesions for risk stratification and enhancing the communication among clinicians and pathologists, the ultimate result being improved patient care and management.

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Laville, David, Francois Casteillo, Violaine Yvorel, Olivier Tiffet, Jean-Michel Vergnon, Michel Péoc’h et Fabien Forest. « Immune Escape Is an Early Event in Pre-Invasive Lesions of Lung Squamous Cell Carcinoma ». Diagnostics 10, n^o 7 (21 juillet 2020) : 503. http://dx.doi.org/10.3390/diagnostics10070503.

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Bronchial dysplasia is the pre-neoplastic lesion recognized for invasive squamous cell carcinoma. The mechanisms leading to invasive squamous cell carcinoma for this lesion are not fully known. Programmed Death-Ligand 1 (PD-L1) expression by the bronchial dysplasia neoplastic epithelium might suggest a response to immunotherapy. The objective of this work is to further characterize PD-L1 and CD8 expression in bronchial dysplasia and bronchial metaplasia compared to normal bronchial epithelium. Immunohistochemical analysis of PD-L1 and CD8 staining were characterized in bronchial dysplasia of 24 patients and correlated with clinical data. We also compared PD-L1 expression in dysplasia samples to 30 normal epithelium and 20 samples with squamous bronchial metaplasia. PD-L1 was never expressed in normal epithelium and in metaplastic epithelium whereas 37.5% of patients with bronchial dysplasia were stained by PD-L1 (p < 0.001). PD-L1 expression was not related to the degree of dysplasia or a medical history of invasive squamous cell carcinoma, while CD8 expression and its localization were related to medical history of squamous cell carcinoma (p = 0.044). Our results show that PD-L1 is expressed in roughly one third of patients with bronchial dysplasia and is not expressed in normal and metaplastic epithelium. This suggests that PD-L1 is expressed in preneoplastic lesions of squamous cell carcinoma.

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Elhossiny, Ahmed M., Eileen Carpenter, Padma Kadiyala, Yaqing Zhang, Filip Bednar, Arvind Rao, Timothy Frankel et Marina Pasca Di Magliano. « Abstract A006 : Integrating single cell and spatial transcriptomics define gene signature for pancreatic ductal adenocarcinoma pre-neoplastic lesion ». Cancer Research 82, n^o 22_Supplement (15 novembre 2022) : A006. http://dx.doi.org/10.1158/1538-7445.panca22-a006.

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Abstract Pancreatic Cancer Ductal Adenocarcinoma (PDAC) is one of the deadliest cancers with 5-year survival of 11%. Understanding the intratumor heterogeneity is a pivotal piece to unravel the complexity of PDAC. While single cell RNASeq identifies the heterogeneous cell populations within the tumor tissue, spatially characterizing the transcriptomic profile of neoplastic and pre-neoplastic populations within the tissue remains a challenge, as the spatial dimension is usually lost upon tissue dissociation. We identified an approach to integrate spatial transcriptomics data with single cell RNASeq data. To characterize the cell populations within the tissue we performed single cell RNASeq on disease pathology-free pancreas tissue and primary PDAC samples. We profiled the transcriptomic profile of Acinar, Ductal, Acinar-to-Ductal (ADM), and Pancreatic Intraepithelial Neoplasia (PanINs) regions of interest (ROIs) across the tissue using the Nanostring GeoMx platform. Differential gene expression analysis using linear mixed-effect models of the cell-type specific ROIs defined pan-marker gene sets for each cell type, which were mapped to UMAP projections of single cell RNA sequencing data using AUCell scoring. As expected, the acinar pan-markers gene set derived from the spatial transcriptomics mapped to the manually annotated acinar population in the single cell data. On the other hand, Ductal, ADM, and PanIN pan-marker gene sets were mapped to distinct clusters that previously were not well-defined by single cell sequencing. The analysis coupled with orthogonal validation using RNAScope revealed gene signatures uniquely specific to ADM lesions and PanINs, respectively. Interestingly, our list included known markers as well as novel findings, supporting the validity of the findings. Furthermore, RNA velocity analysis using scVelo revealed a trajectory of cell evolution originating from acinar cells passing through the newly-defined ADM population and ending towards the ductal population derived from tumor samples. Overall, this integration approach of spatial and single cell transcriptomics can further define the characteristics that differentiate neoplastic and pre-neoplastic populations, as well as the potential drivers for tumorigenesis that could be therapeutically targeted. Citation Format: Ahmed M. Elhossiny, Eileen Carpenter, Padma Kadiyala, Yaqing Zhang, Filip Bednar, Arvind Rao, Timothy Frankel, Marina Pasca Di Magliano. Integrating single cell and spatial transcriptomics define gene signature for pancreatic ductal adenocarcinoma pre-neoplastic lesion [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A006.

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Espina, Virginia A., Kirsten H. Edmiston et Lance A. Liotta. « Evaluation of autophagy as a therapeutic target for DCIS. » Journal of Clinical Oncology 30, n^o 27_suppl (20 septembre 2012) : 189. http://dx.doi.org/10.1200/jco.2012.30.27_suppl.189.

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189 Background: Survival of intraductal, preinvasive proliferating cells under stress may promote genetic instability and the selection of invasive carcinoma cells. Our analysis of the mechanisms used by DCIS cells to survive in the hypoxic, nutrient deprived intraductal niche has revealed autophagy as a therapeutic target. Methods: DCIS spheroid forming cells have been isolated and propagated from fresh human DCIS lesions. We characterized the DCIS cells by organ culture, xenograft transplantation, molecular cytogenetics (300,000 SNPs) and 59 signal pathway profiling endpoints (Reverse Phase Protein Microarray [RPMA]). Results: DCIS spheroid forming cells were tumorigenic in xenograft models. Autophagy is up-regulated in: human DCIS lesions, DCIS spheroid-forming cells, and the xenograft tumors they generate. Autophagy is a means for intraductal neoplastic cells, accumulating in the duct, to digest intracellular contents and generate energy to survive in the face of severe metabolic, oxidative, and hypoxic stress. Suppression of autophagy by chloroquine kills human DCIS spheroid forming cells in culture and prevents them from forming tumors in xenografts (p < .0003). Based on these preclinical insights we have opened a neoadjuvant therapy trial for DCIS (NCT01023477 PINC Trial) to examine the safety and effectiveness of oral 30-day chloroquine for patients with any stage/grade DCIS. At the conclusion of treatment, all patients receive standard of care surgical therapy. MRI is performed before and after the treatment period. Endpoints compared before, versus after, therapy are lesion shrinkage, pathologic regression, disruption of lesion autophagy and proliferation (Ki67), induction of apoptosis, and suppression of xenograft tumorigenicity. Each patient serves as her own control because effectiveness is judged by comparing the patient’s DCIS lesion before and after oral therapy. Conclusions: We hypothesize that the intraductal pre-neoplastic cellular niche will be preferentially sensitive to a short term, anti-autophagy based prevention therapy which targets survival pathways used by pre-invasive carcinomas. Our unique trial design offers a means to functionally screen investigational agents that kill premalignant breast lesions.

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Wojtasiński, Konrad, Agata Borsukiewicz, Krzysztof Szcześniak, Martyna Osiak et Andrzej Wojtowicz. « Częstość występowania i różnorodność patologicznych zmian w jamie ustnej u pacjentów leczonych w Zakładzie Chirurgii Stomatologicznej WUM w latach 2012–2017. Badanie retrospektywne ». Chirurgia Plastyczna i Oparzenia / Plastic Surgery & ; Burns 8, n^o 4 (décembre 2020) : 93–101. http://dx.doi.org/10.15374/chpio2020012.

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Introduction A large number of lesions of various etiopathogenesis may be found in the oral cavity. They range from benign inflammatory-hyperplastic changes to malignant tumors. The following study aims to statistically show the frequency and type of changes depending on the age and sex of patients treated in the Department of Dental Surgery of the Medical University of Warsaw. Material and methods 612 results of histopathological examinations of sections or entire lesions of the oral cavity collected from patients in the years 2012–2017 were analyzed. The results were analyzed in terms of gender, age and the site of tissue collection. Neoplasms and 8 other groups of lesions of the mucosa were distinguished. Results The most common lesion was fibroma (35%), followed by a chronic inflammatory process (15.4%), and salivary gland cysts (11.9%). Papillomas (HPV) accounted for 10.5%, epilemomas 9.64%, tumors 6.54%, cysts and ulcers 4.74% and 4.25%, respectively. Pre-neoplastic lesions were found in 70 cases. These included ulcerations, leukoplakia, changes with metaplasia, dysplasia and pseudo-neoplastic hyperplasia. The most common localization of pathological changes in the oral cavity was related to the gums. Conclusions Many lesions of various etiology may present with a similar clinical manifestation. Therefore, in order to correctly diagnose pathological changes in the oral cavity, it is necessary to conduct a thorough medical history and physical examination, and identify the factors that may have caused the lesion. A particular group of pathological changes of the oral mucosa are ulcers which, despite a conservative approach, do not respond to treatment. In such cases a neoplasm should be suspected and a section of the lesion be obtained for histopathological evaluation which is the only reliable method that allows a final diagnosis.

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Nwaorgu, O. G. B., E. E. U. Akang, B. M. Ahmad, F. N. Nwachokor et A. N. Olu-Eddo. « Pharyngeal lipoma with cartilaginous metaplasia (chondrolipoma) : a case report and literature review ». Journal of Laryngology & ; Otology 111, n^o 7 (juillet 1997) : 656–58. http://dx.doi.org/10.1017/s0022215100138241.

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AbstractThe relative rarity of pharyngeal lipomas and paucity of clinical manifestations in the early stages of tumour growth conspire to task the diagnostic acumen of the clinician. A high index of suspicion and meticulous examination are essential in order to arrive at the diagnosis, which may be achieved pre-operatively by computerized axial tomography, revealing a mass lesion with a characteristic low attenuation value. A case of pharyngeal chondrolipoma in a 25-year-old male is reported. It is suggested that this conceptually intriguing and rarely encountered lesion can be explained on the basis of neoplastic transformation of the second to fourth pharyngeal cleft mesenchymal rests displaying both adipose and cartilaginous differentiation. Alternatively, the cartilage could represent vestigial remnants of non-neoplastic pharyngeal cleft tissue entrapped within a primarily lipomatous neoplasm. Slow growth may occur over a period of several years, prior to overt clinical manifestation.

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Marzullo, Andrea, Gabriella Serio, Luigi Madami, Federica Pezzuto, Francesco Fortarezza, Nicola Quaranta, Maria Luisa Fiorella et al. « Intraoperative frozen section as a reliable ancillary technique in salivary gland surgery : A cross sectional study ». F1000Research 7 (27 février 2018) : 231. http://dx.doi.org/10.12688/f1000research.13043.1.

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Background.Salivary glands tumours are uncommon, frequently benign lesions, prevalently located in the parotid gland (80%). Surgical decision making is based on the patient’s history, examination findings, imaging and fine needle aspiration (FNA). FNA is a pre-operative method with good ability in detecting malignancy. During surgery, therefore, Frozen section (FS) can differentiate benign lesions from malignant tumours, to reduce incorrect treatments, to increase the chances of conservative surgery and to better evaluate surgical margins. The aim of our study is to demonstrate the accuracy of the FS procedure in surgery of the salivary glands and to stress the need for dedicated pathology units specialized in lesions of the oral cavity.Methods. The study included 499 patients who underwent surgery from May 2005 and October 2014. An intra-operative frozen section procedure was done for 288 of them. All frozen sections were compared with the final results. The cases were classified by site, nature of the lesion and histotype, according to the WHO classification. Comparison was made between the intra-operative and the definitive diagnosis.Results.Of the 288 FS procedures, 259 were for neoplastic lesions, 199 of which benign and 60 malignant, and 29 for non-neoplastic lesions. Of the 259 neoplastic FS results, 2 were shown to be false positives and 2 were diagnosed as different malignant types. Of the 29 non-neoplastic FS results, 4 were false negatives.Conclusions.Our results showed that the accuracy of frozen section procedure is 98% for salivary glands tumors. The highest concordance between frozen section and the definitive diagnosis was for inflammatory processes (99%), pleomorphic adenoma (98%), Warthin’s tumor (97%) and malignant neoplasms (96%). In conclusion, based on these findings, frozen section of the salivary glands may be proposed as a routine procedure and should be used in decision-making.

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Araghi, Farnaz, Sahar Dadkhahfar, Mohammadreza Tabary, Azadeh Rakhshan et Mehdi Gheisari. « Progressive Primary Plate-Like Osteoma Cutis of the Scalp ». Skin Appendage Disorders 7, n^o 3 (2021) : 216–19. http://dx.doi.org/10.1159/000512785.

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Osteoma cutis (OC) or cutaneous ossification refers to uncommon bone formation in the skin. Primary OC develops without any predisposing factor or pre-existing lesion, whereas secondary OC sets out as a dystrophic ossification following traumatic, cicatricial, and neoplastic factors or other cutaneous inflammations. Herein, we report a rare case of long-standing progressive primary OC of the scalp resected in 3 sessions with no recurrence after 1 year.

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Oleśna, Aleksandra, Michał Wlaźlak, Janusz Strzelczyk et Marian Danilewicz. « Pancreatic cysts or pancreatic cystic neoplasms ? An analysis of 145 cases. » Polish Journal of Surgery 90, n^o 4 (20 juin 2018) : 1–4. http://dx.doi.org/10.5604/01.3001.0012.1267.

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Introduction Frequency of detection of pancreatic cystic lesions increased recent years. The majorities are pseudocysts, the remaining cysts are mainly neoplasms. Proven risk of malignancy affects intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN). Material and methods 145 patients operated on at the Department of General and Transplant Surgery in Barlicki Hospital in Lodz, Poland, in 2007-2016 due to pancreatic cystic lesion. The type of surgery, histopathological diagnosis and basic demographic data were analyzed. Results Nonneoplastic cyst (mainly pseudocysts) was found in 66.9% of patients, neoplasms were detected in 33.1%. The mean age was significantly higher in patients with neoplasms than without neoplasm (57.06 years vs. 50.88 years, p = 0.009). Neoplastic cyst occurred more frequently in women (68.75% of women, 31.25% of men, p = 0.001), Nonneoplastic cyst was found significantly more often in men (64.95% of men, 35.05% of women, p = 0.001). Malignant tumor was found in 14.58% of neoplasms cases. Pancreatic resections in neoplastic cysts were performed in 77,08%. In patients with nonneoplastic cysts drainage operations were performed most frequently (80.41%). Conclusions Neoplastic cysts are more common in women. The average age in the group of patients with neoplasms is higher than in the group with nonneoplastic cysts. In women with pancreatic cystic lesion without history for pancreatitis, the probability of neoplasms diagnosis is high. Discussion Pancreatic cystic tumors are treated radically due to the lack of sufficiently sensitive and specific pre-operative examinations. The natural history of mucinous neoplasms (IPMN and MCN) ranges from dysplasia to cancer. There are no guidelines that could be in satisfactory way used in follow up patients with pancreatic cysts.

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Recht, Lawrence D., Griffith Harsh IV et Harvey J. Cohen. « The rationale for early detection and treatment of brain tumors in survivors of childhood cancer ». Oncology Reviews 3, n^o 1 (14 décembre 2011) : 51. http://dx.doi.org/10.4081/oncol.2009.51.

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Survivors of childhood cancer have a relatively high risk of developing second cancers. The incidence of brain tumor in these patients approaches 1% at 10 years, over 80-fold that in the general population. This high incidence increases the likelihood that early detection of brain tumors in survivors of childhood cancer is feasible. By analogy with other epithelial cancers, detection and treatment of brain tumors at a pre-neoplastic or premalignant stage may render screening and treatment cost effective for certain high-risk populations. Our animal studies with a clinically appropriate model of this condition suggest that there is a pre-neoplastic, pre-malignant brain tumor lesion that is potentially both detectable and effectively treated. The possibility of detecting such a treatable antecedent to brain tumors provides the rationale for genomic and proteomic screening of tumor tissue, CSF, plasma and urine in this animal model, of tumor tissue and body fluids of patients with known brain tumors at various stages, and of body fluids of survivors of childhood cancer.

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Diaconu, Claudia, Monica State, Mihaela Birligea, Madalina Ifrim, Georgiana Bajdechi, Teodora Georgescu, Bogdan Mateescu et Theodor Voiosu. « The Role of Artificial Intelligence in Monitoring Inflammatory Bowel Disease—The Future Is Now ». Diagnostics 13, n^o 4 (15 février 2023) : 735. http://dx.doi.org/10.3390/diagnostics13040735.

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Crohn’s disease and ulcerative colitis remain debilitating disorders, characterized by progressive bowel damage and possible lethal complications. The growing number of applications for artificial intelligence in gastrointestinal endoscopy has already shown great potential, especially in the field of neoplastic and pre-neoplastic lesion detection and characterization, and is currently under evaluation in the field of inflammatory bowel disease management. The application of artificial intelligence in inflammatory bowel diseases can range from genomic dataset analysis and risk prediction model construction to the disease grading severity and assessment of the response to treatment using machine learning. We aimed to assess the current and future role of artificial intelligence in assessing the key outcomes in inflammatory bowel disease patients: endoscopic activity, mucosal healing, response to treatment, and neoplasia surveillance.

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Lorigados, Carla A. B., Ana Carolina C. B. Fonseca Pinto, Julia Maria Matera et Diego F. A. Modena. « Malignant perineal tumors in dogs : the contribution of computed tomography for staging and surgical planning ». Pesquisa Veterinária Brasileira 38, n^o 12 (décembre 2018) : 2241–45. http://dx.doi.org/10.1590/1678-5150-pvb-5822.

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ABSTRACT: The contribution of computed tomography for staging and surgical planning of malignant perineal tumors in dogs is discussed. Five dogs diagnosed with malignant perineal neoplasms underwent to computed tomography (CT) examination. The CT image enabled investigation of cleavage planes between neoplastic lesions and adjacent structures such as the rectum, anus, vagina, urethra and perineal muscles. Accurate assessment regional lymph nodes and adjacent bone structures was also possible. All tumors evaluated in this region presented heterogeneous appearance in pre and postcontrast CT images, but only the anal sac adenocarcinomas presented lymphadenopathy. Computed tomography proved to be a valuable tool for tumor staging and determination of lesion extension and invasion of adjacent tissues, providing significant contributions to clinical and surgical therapeutic planning.

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KROUPIS, C., G. THOMOPOULOU, T. G. PAPATHOMAS, N. VOURLIDIS et A. C. LAZARIS. « Population-based study of human papillomavirus infection and cervical neoplasia in Athens, Greece ». Epidemiology and Infection 135, n^o 6 (7 juin 2007) : 943–50. http://dx.doi.org/10.1017/s095026880700876x.

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SUMMARYThe aim of our study is to describe the prevalence of the different HPV types in women with pre-neoplastic lesions of the cervix in Greece. Cervical scrapes from 841 women were obtained for both cytological evaluation and analysis for the presence of HPV DNA. PCR was performed on specimens from these 841 women. The Pap test results were normal or showed benign cellular changes in 45·8% of the women, atypical squamous cells of undeterminated significance (ASCUS) in 23·2%, low-grade squamous intra-epithelial lesion (LSIL) in 27·9% and high-grade squamous intra-epithelial lesion (HSIL) in 3·1%. HPV DNA was demonstrated in 23·6% of cytologically normal women. We detected HPV in 60% of the total samples. Of these, HPV-16 was the most common HPV DNA detected. Interestingly, HPV-58 was inversely correlated with positive cytological findings. A clear pattern of decreasing prevalence of HPV with age was also observed. Our results indicate that HPV infections, especially those with HPV-16, represent a significant public health concern in Greece.

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Barros, Rita, Vânia Camilo, Bruno Pereira, Jean-Noel Freund, Leonor David et Raquel Almeida. « Pathophysiology of intestinal metaplasia of the stomach : emphasis on CDX2 regulation ». Biochemical Society Transactions 38, n^o 2 (22 mars 2010) : 358–63. http://dx.doi.org/10.1042/bst0380358.

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IM (intestinal metaplasia) of the stomach is a pre-neoplastic lesion that usually follows Helicobacter pylori infection and that confers increased risk for gastric cancer development. After setting the role played by CDX2 (Caudal-type homeobox 2) in the establishment of gastric IM, it became of foremost importance to unravel the regulatory mechanisms behind its de novo expression in the stomach. In the present paper, we review the basic pathology of gastric IM as well as the current knowledge on molecular pathways involved in CDX2 regulation in the gastric context.

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Gruia, Alexandra, Patrycja Gazinska, Diana Herman, Valentin Ordodi, Calin Tatu et Peter George Mantle. « Revealing a Pre-neoplastic Renal Tubular Lesion by p-S6 Protein Immunohistochemistry after Rat Exposure to Aristolochic Acid ». Journal of Kidney Cancer and VHL 2, n^o 4 (7 septembre 2015) : 153–62. http://dx.doi.org/10.15586/jkcvhl.2015.38.

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Aristolochic acid (AA) has, in the last decade, become widely promoted as the cause of the Balkan endemic nephropathy and associated renal or urothelial tumours, although without substantial focal evidence of the quantitative dietary exposure via bread in specific households in hyperendemic villages. Occasional ethnobotanical use of Aristolochia clematitis might be a source of AA, and Pliocene lignite contamination of well-water is also a putative health risk factor. The aim of this study was two-fold: to verify if extracts of A. clematitis and Pliocene, or AA by itself, could induce the development of renal or urothelial tumours, and to test the utility of the ribosomal protein p-S6 to identify preneoplastic transformation. Rats were given extracts of A. clematitis in drinking water or AA I, by gavage. After seven months, renal morphology was studied using conventional haematoxylin and eosin and immunohistochemistry for ribosomal p-S6 protein. Plant extracts (cumulative AA approximately 1.8 g/kg b.w.) were tolerated and caused no gross pathology or renal histopathological change, with only faint diffuse p-S6 protein (except in the papilla) as in controls. Cumulative AA I (150 mg/kg b.w. given over 3 days) was also tolerated for seven months by all recipients, without gross pathology or kidney tumours. However, p-S6 protein over-expression was consistent particularly within the renal papilla. In one case given AA I, intense p-S6 protein staining of a proximal tubule fragment crucially matched the pre-neoplastic histology in an adjacent kidney section. We briefly discuss these findings, which compound uncertainty concerning the cause of the renal or upper urinary tract tumours of the Balkan endemic nephropathy.

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Kamal, Meherbano. « Cervical Pre-cancers : Biopsy and Immunohistochemistry ». Cytojournal 19 (14 juin 2022) : 38. http://dx.doi.org/10.25259/cmas_03_13_2021.

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The existence of precursor lesions for invasive cervical cancer has been recognized for more than 50 years. Our understanding of the pathobiology and behavior of cervical cancer precursors has evolved considerably over the past five decades. Furthermore, the terminology used to classify pre-invasive lesions of the cervix has frequently changed. The realization that human papillomavirus (HPV) infections constitute a morphologic continuum has prompted efforts to include them within a single classification system, specifically the squamous intraepithelial lesions (SILs) which have now been embraced by the surgical pathologists. The reduced number of specific pathological categories has made clinical decision-making more straightforward. The generic criteria for SIL have two important histological parameters: Alterations in the density of superficial epithelial cells and superficial squamous atypia. The flat condyloma or cervical intraepithelial neoplasia (CIN) I is generally associated with intermediate and high-risk HPV types as against the low-risk viruses that cause exophytic/papillary growth patterns of condylomas. The diagnosis of low-grade SIL (LSIL) (flat and exophytic condylomas) requires first excluding benign mimics of LSIL and second to confirm the characteristic cytologic atypia. For high-grade SILs (HSILs), the extent and degree of atypia generally exceed the limits of that described in flat or exophytic condylomas (LSILs). Less maturation, abnormal cell differentiation, loss of cell polarity, and increased mitotic index with abnormal mitotic figures occupying increasing thickness of the epithelium define a lesion as CIN II or CIN III. Atypical immature metaplasia associated with inflammation and atrophy is a challenge in cervical biopsy interpretation. Careful attention to the growth pattern of the epithelium, the distribution of the atypia, nuclear spacing, and the degree of anisokaryosis and the presence of enlarged hyperchromatic nuclei help in differentiating a non-neoplastic from a neoplastic process. This chapter describes in depth the diagnostic difficulties in the interpretation of cervical biopsies. It also provides useful criteria in distinguishing benign mimics from true precancerous lesions and the role of biomarkers such as the p16ink4 and Ki-67 in the differential diagnosis of precursor lesions and the reactive and metaplastic epithelium.

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Foss, Francine M., Christiane Querfeld, Pierluigi Porcu, Youn H. Kim, Theresa Pacheco, Ahmad Sami Halwani, Jennifer DeSimone et al. « Phase 1 trial evaluating MRG-106, a synthetic inhibitor of microRNA-155, in patients with cutaneous t-cell lymphoma (CTCL). » Journal of Clinical Oncology 35, n^o 15_suppl (20 mai 2017) : 7564. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.7564.

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7564 Background: MRG-106 is an oligonucleotide inhibitor of miR-155, a microRNA with a strong mechanistic link to CTCL, selected based on its activity in mycosis fungoides (MF) cell lines. The objective of this first-in-human study is to evaluate the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics (PK), and preliminary efficacy of MRG-106 in MF patients. Methods: This Phase 1 trial employs a dose-escalation design to evaluate either intratumoral (IT, 75 mg/dose) or subcutaneous (SC, ≤ 900 mg/dose) administration of MRG-106. Patients were required to have biopsy-proven stage I-III MF and plaque- or tumor-stage lesions. Results: Fifteen patients (12M/3F, median age 59 years) have been dosed over 1-4 weeks. All patients tolerated the IT or SC administrations well with only minor local injection reactions in 8 patients. Thirteen of 15 patients completed dosing as scheduled. There were no clinically significant MRG-106 related adverse events with the exception of one grade 3 pruritus. The MTD has not yet been reached. In the IT cohort, a reduction of ≥50% in the baseline Composite Assessment of Index Lesion Severity (CAILS) score was observed in the MRG-106 treated lesions in all 4 evaluable patients who completed dosing; such responses were maintained to the End of Study visit (Day 28 or 35). Histological examination of pre- and post-treatment biopsies of the MRG-106-injected lesion from most patients revealed a trend in reduction in neoplastic cell density and depth; 1 patient had a complete loss of the neoplastic infiltrate. Gene expression analysis of the pre- and post-treatment biopsies showed reduction of the PI3K/AKT, JAK/STAT, and NFkB survival pathways and increased cell death consistent with the expected MRG-106 mechanism of action. In the SC cohorts, 3/8 patients had a maximal decrease in their modified Severity-Weighted Assessment Tool (mSWAT) of > 39% indicative of a significant response. One patient at the 900 mg SC dose level had a possible flare of their disease after 3 doses that resolved after 3 weeks. Conclusions: Based on favorable clinical safety, efficacy and PK data, additional patients are being accrued. Updated results will be presented as available. Clinical trial information: NCT02580552.

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Officer, Kirsty, Mathieu Pruvot, Paul Horwood, Daniela Denk, Kris Warren, Vibol Hul, Nhim Thy, Nev Broadis, Philippe Dussart et Bethany Jackson. « Epidemiology and pathological progression of erythematous lip lesions in captive sun bears (Helarctos malayanus) ». PLOS ONE 15, n^o 12 (1 décembre 2020) : e0243180. http://dx.doi.org/10.1371/journal.pone.0243180.

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This study investigates the occurrence of erythematous lip lesions in a captive sun bear population in Cambodia, including the progression of cheilitis to squamous cell carcinoma, and the presence of Ursid gammaherpesvirus 1. Visual assessment conducted in 2015 and 2016 recorded the prevalence and severity of lesions. Opportunistic sampling for disease testing was conducted on a subset of 39 sun bears, with histopathological examination of lip and tongue biopsies and PCR testing of oral swabs and tissue biopsies collected during health examinations. Lip lesions were similarly prevalent in 2015 (66.0%) and 2016 (68.3%). Degradation of lip lesion severity was seen between 2015 and 2016, and the odds of having lip lesions, having more severe lip lesions, and having lip lesion degradation over time, all increased with age. Cheilitis was found in all lip lesion biopsies, with histological confirmation of squamous cell carcinoma in 64.5% of cases. Single biopsies frequently showed progression from dysplasia to neoplasia. Eighteen of 31 sun bears (58.1%) had at least one sample positive for Ursid gammaherpesvirus 1. The virus was detected in sun bears with and without lip lesions, however due to case selection being strongly biased towards those showing lip lesions it was not possible to test for association between Ursid gammaherpesvirus 1 and lip squamous cell carcinoma. Given gammaherpesviruses can play a role in cancer development under certain conditions in other species, we believe further investigation into Ursid gammaherpesvirus 1 as one of a number of possible co-factors in the progression of lip lesions to squamous cell carcinoma is warranted. This study highlights the progressively neoplastic nature of this lip lesion syndrome in sun bears which has consequences for captive and re-release management. Similarly, the detection of Ursid gammaherpesvirus 1 should be considered in pre-release risk analyses, at least until data is available on the prevalence of the virus in wild sun bears.

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Kane, P. A., V. Ayton, H. L. Walters, I. Benjamin, N. D. Heaton, R. Williams et J. B. Karani. « MnDPDP-enhanced MR imaging of the liver ». Acta Radiologica 38, n^o 5 (septembre 1997) : 650–54. http://dx.doi.org/10.1080/02841859709172396.

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Purpose: To compare lesion detection and characterisation predicted by MnDPDP-enhanced MR imaging with surgical excision and pathological examination. Material and Methods: Ninety patients were intravenously infused at a rate of 2 to 3 ml/min with 5 μmol/kg mangafodipir trisodium (MnDPDP, Teslascan). The patients were examined with spin-echo and gradient-echo T1-weighted MR imaging at 1 h and 24 h after the end of infusion. The results were compared with identical pre-contrast sequences. In 20 of these patients, the pre-operative MR findings were compared with intra-operative ultrasonography and histology of the resected liver specimens. Results: In those with liver metastases, there was a good correlation between MR and the hepatic disease in 11 out of 14 cases. In the group with primary liver tumours, MR findings correlated with hepatic disease in 5 out of 6 cases. Conclusion: Liver lesion characterisation is possible with MnDPDP, and MR contrast enhancement with this agent is considered to be an important adjunct to the radiological assessment of patients with neoplastic liver disease where accurate decisions for surgical planning are imperative.

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Matsumoto, S., T. Takuwa, N. Kondo, Y. Okumura, K. Fukuoka, T. Nakano, S. Hasegawa et F. Tanaka. « EGFR/K-ras mutations in lung adenocarcinoma and atypical adenomatous hyperplasia (AAH) ». Journal of Clinical Oncology 25, n^o 18_suppl (20 juin 2007) : 21074. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.21074.

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21074 Background: Mutations in the epidermal growth factor receptor (EGFR) gene and k-ras gene are found in 10–30% of non-small cell lung cancer, and are useful to predict the efficacy of EGFR-tyrosine kinase inhibitors. Such mutations are also onco- developmentally important especially in lung adenocarcinoma, but the exact incidences of such mutations in adenocarcinoma/AAH and surrounding normal lung. Methods: A total of 45 consecutive patients with lung adenocarcinoma and/or AAH (18 females; mean age, 65 years) who received thoracotomy from August 2005 through December 2006. In each case, EGFR/k-ras mutations were examined in specimens cut from adenocarcinoma/AAH and normal lung; in the present study, pure bronchioalveolar carcinoma (BAC) was reviewed separately from adenocarcinoma. Results: As 12 (27%) of all 45 patients had multiple adenocarcinoma/BAC/AAH lesions, mutations were examined in 59 lesions (41 adenocarcinomas, 7 BACs, 11 AAHs) and 45 normal lung tissues. EGFR and k-ras mutations were documented in 37% (15/41) and 2% (1/41) of adenocarcinomas, and no EGFR/k-ras mutation was documented in any BAC, AAH, or normal lung tissue. Next, clinical characteristics of patients were compared between patients with solitary adenocarcionma/BAC/AAH lesion and those with multiple lesions; non-smoker were more frequently documented in multiple-lesions group (42%) than in solitary-lesion group (15%), and there was no significant difference in other characteristics such as sex and age. Conclusions: EGFR mutation was not documented in non-invasive (BAC) or pre-neoplastic (AAH) lesion in this series, which may suggest that EGFR mutation play a critical role in the development of invasive adenocarcinoma. No significant financial relationships to disclose.

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Bornschein, Jan, Elizabeth L. Bird-Lieberman et Peter Malfertheiner. « The Rationale and Efficacy of Primary and Secondary Prevention in Adenocarcinomas of the Upper Gastrointestinal Tract ». Digestive Diseases 37, n^o 5 (2019) : 381–93. http://dx.doi.org/10.1159/000499706.

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While the primary risk factor for oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett’s oesophagus (BO) is gastro-oesophageal reflux, the infection with Helicobacter pylori (H. pylori) is the dominant risk factor for gastric cancer. Reduction of reflux by dietary measures and proton pump inhibitors has some merits in OAC prevention, and the chemopreventive effect of Aspirin and statins is being widely investigated; however, improved outcome in OAC occurs primarily as the result of secondary prevention. Early detection of neoplastic lesions in Barrett’s metaplasia can be achieved by surveillance endoscopies. Novel endoscopic imaging modalities carry similar importance as the endoscopic treatment techniques as without detection of early lesions, therapy cannot be applied. Minimally invasive approaches are currently being investigated to identify patients with BO who are at particular risk of neoplastic progression. While dietary factors also play an important role in the prevention of gastric cancer and chemoprevention seems to be promising, the most beneficial effect has been shown for the eradication of H. pylori infection, which results in at least a one third reduction of gastric cancer risk. This effect can be further improved if the eradication takes place prior to the development of pre-neoplastic gastric conditions such as mucosal atrophy or intestinal metaplasia (IM). The definition of the “point of no return”, after which eradication is less effective, is of high importance, although H. pylori eradication can still be beneficial even at more advance stages of mucosal changes. For this reason, patients with advanced atrophy and IM should undergo endoscopic surveillance in the same way as patients with BO. There is also need for development of non-invasive tests to identify patients at high risk of progression to gastric cancer to improve outcome of these surveillance approaches.

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Huisman, Bertine W., Merve Cankat, Tjalling Bosse, Alexander L. Vahrmeijer, Robert Rissmann, Jacobus Burggraaf, Cornelis F. M. Sier et Mariette I. E. van Poelgeest. « Integrin αvβ6 as a Target for Tumor-Specific Imaging of Vulvar Squamous Cell Carcinoma and Adjacent Premalignant Lesions ». Cancers 13, n^o 23 (29 novembre 2021) : 6006. http://dx.doi.org/10.3390/cancers13236006.

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Surgical removal of vulvar squamous cell carcinoma (VSCC) is associated with significant morbidity and high recurrence rates. This is at least partially related to the limited visual ability to distinguish (pre)malignant from normal vulvar tissue. Illumination of neoplastic tissue based on fluorescent tracers, known as fluorescence-guided surgery (FGS), could help resect involved tissue and decrease ancillary mutilation. To evaluate potential targets for FGS in VSCC, immunohistochemistry was performed on paraffin-embedded premalignant (high grade squamous intraepithelial lesion and differentiated vulvar intraepithelial neoplasia) and VSCC (human papillomavirus (HPV)-dependent and -independent) tissue sections with healthy vulvar skin as controls. Sections were stained for integrin αvβ6, CAIX, CD44v6, EGFR, EpCAM, FRα, MRP1, MUC1 and uPAR. The expression of each marker was quantified using digital image analysis. H-scores were calculated and percentages positive cells, expression pattern, and biomarker localization were assessed. In addition, tumor-to-background ratios were established, which were highest for (pre)malignant vulvar tissues stained for integrin αvβ6. In conclusion, integrin αvβ6 allowed for the most robust discrimination of VSCCs and adjacent premalignant lesions compared to surrounding healthy tissue in immunohistochemically stained tissue sections. The use of an αvβ6 targeted near-infrared fluorescent probe for FGS of vulvar (pre)malignancies should be evaluated in future studies.

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Rajeswari, Rajavarapu, Kancharla Sushma Chandulee, Kona Suneetha et Boddu Penchala Prasanna. « Cytohistological Correlation of Cervical PAP Smears - A TwoYear Retrospective Study from Ongole, Andhra Pradesh ». Journal of Evidence Based Medicine and Healthcare 8, n^o 21 (24 mai 2021) : 1659–63. http://dx.doi.org/10.18410/jebmh/2021/313.

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BACKGROUND Cervical cancer is one of the most common forms of cancer. In India it is the second most common cancer after breast carcinoma. PAP smear is the best screening method to reveal spectrum of lesions in cervix ranging from inflammatory to the neoplastic process. Because of easy accessibility of cervix, cervical screening is helpful for ready diagnosis of 90 % to 96 % cytological abnormalities even in the pre-invasive stage. We wanted to evaluate the importance of PAP smear examination as a preliminary method accommodating histopathology and assess the spectrum of lesions. METHODS The study was done to identify the target age groups for the early detection of cancerous cervix by PAP smear examination. The study was done on patients who attended government general hospital (GGH), Ongole, from January 2018 to December 2019. Lesions were categorized based on 2014 Bethesda system as negative intraepithelial lesion for malignancy (NILM) / Inflammatory, benign, premalignant, and malignant. The clinicocytological and histopathological examination (HPE) of cervical biopsy of corresponding smears were compared and analysed in the present study. RESULTS Of the 584 cases studied by PAP smear examination, maximum number of patients were between 21 and 60 years of age. Maximum number of patients came with the complaint of white discharge. Highest number of cases reported were NILM / inflammatory (54.18 %), followed by atypical squamous cells of undetermined significance (ASCUS) (20.68 %), high-grade squamous intraepithelial lesion (HSIL) (13.84 %), squamous cell carcinoma (SCC) (6.84 %), low-grade squamous intraepithelial lesion (LSIL) (1.65 %), metaplasia (1.19 %), atypical glandular cells of undetermined significance (AGUS) (0.51 %), adenocarcinoma (0.17 %). CONCLUSIONS Cervical PAP smear screening is simple, cost effective and reliable method for early detection of cervical cancers. Classification of lesions based on Bethesda terminology is most informative and useful. Correlation of PAP smear cervical cytology with gold standard HPE provides greater efficacy in diagnosis. KEYWORDS PAP smears, NILM, ASCUS, AGUS, LSIL, HSIL

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Bharti, Jyotsna Naresh, Poonam Elhence, Meenakshi Rao, Aasma Nalwa et Sudeep Khera. « Risk stratification by application of Milan system for reporting salivary gland cytopathology : A tertiary care experience ». Cytojournal 18 (2 août 2021) : 19. http://dx.doi.org/10.25259/cytojournal_26_2020.

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Objectives: The Milan system for reporting salivary gland cytopathology (MSRSGC) classification has been proposed to improve reproducibility in the management of salivary gland lesions. Fine-needle aspiration cytology (FNAC) is a widely accepted, well-tolerated, cost-effective, minimally invasive diagnostic method for pre-operative evaluation of salivary gland lesion that aids management decisions. The present study aims to reclassify the salivary gland FNAC aspirates by applying MSRSGC and calculating the risk of neoplasm and malignancy for each diagnostic category. Material and Methods: The present study is a retrospective observational study done for 54 months. A total of 168 cases of salivary gland FNA, 54 cases were excised in our institute for histopathology. Retrospective reviews were performed, and the FNAC cases were reclassified according to the Milan system, and the results of FNAC and final histology were correlated, wherever available. Furthermore, the risk of malignancy was calculated for all the diagnostic categories. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy (DA) of FNAC were determined. Results: In the present study, the age of patients ranged from 3 to 86 years, with a mean age of 39 years. Among all the patients, 61.3% were male, and 38.6% were female. However, only 54 salivary gland FNA samples for which histopathology was available were categorized into six categories. Among them, category IV (neoplastic) had a maximum number of cases of 66.6%. The rate of malignancy was calculated for all diagnostic categories as follows: (1) Non-diagnostic: 0.0%, (2) non-neoplastic 0.0%, (3) atypia of undermined significance 100%, (4a) benign 5.5%, (4b) uncertain malignant potential 33.33%, (5) suspicious for malignancy 00%, and (6) malignancy 80%. The sensitivity, specificity, PPV, NPV, and DA for differentiating between benign and malignant neoplasm were 36.3%, 94.4%, 66.6%, 82.9%, and 80%. Two false-positive and seven false-negative neoplastic cases were noted. Conclusion: FNAC is a reliable, minimally invasive diagnostic method with high DA for diagnosing salivary gland lesions. Most salivary gland lesions can be accurately diagnosed on FNAC with adequate sampling and cytopathologists experience.

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Prakash, Surya, Chhaya Rani Shevra et Dwijendra Nath. « Evaluation of angiogenesis as a prognostic marker in prostatic neoplasm especially carcinoma of prostate ». International Journal of Research in Medical Sciences 7, n^o 11 (24 octobre 2019) : 4144. http://dx.doi.org/10.18203/2320-6012.ijrms20194982.

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Background: Prostatic carcinoma shows an unusually wide range of biological potential with well-known disparity between incidence and mortality for disease. Clinico-pathological studies suggests that angiogenesis and tumor neovascularity contributes to pathogenesis of prostate cancer. The aim of this study to present study was done to assess the validity of angiogenesis as a suitable prognostic marker in various prostatic disease specially the neoplasm’s including the malignant ones. Settings and design are Retrospective study.Methods: The present study of evaluation of angiogenesis as a prognostic marker in prostatic neoplasm especially carcinoma of prostate was done with 40 biopsy sample. The biopsy sample were obtained by suprapubic prostatectomy specimen and trans rectal needle biopsy specimen. Tissue sections were subjected to routine H and E staining. For demonstration of angiogenesis staining for reticulin fibers was applied.Results: The microvessels density increases as the severity of lesion increases from benign to pre-neoplastic to frankly malignant. The micro vessel density in malignant lesions is approximately thrice that in benign lesions. Conclusions: Very few studies have been done in prostatic lesions Hence an attempt is made to demonstrate and correlate angiogenesis as a tumour marker.

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Ibrahim, Yasmine F., Marwa MM Refaie, Maha Y. Kamel, Sara M. Ahmed, Rabab A. Moussa, Asmaa MA Bayoumi et Mohamed A. Ibrahim. « Molecular mechanisms underlying the effect of diacerein on trichloroacetic acid–induced hepatic pre-neoplastic lesions in rats ». Human & ; Experimental Toxicology 40, n^o 12_suppl (18 novembre 2021) : S788—S803. http://dx.doi.org/10.1177/09603271211056331.

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Hepatocellular carcinoma (HCC) accounts for more than 5% of all human cancers. Diacerein (DIA), an interleukin (IL)-1β inhibitor, is used for the treatment of osteoarthritis. DIA is a potential anticancer drug acting on several protein targets in the process of apoptosis. The present study aimed to explore the molecular mechanisms underlying the effect of DIA in the treatment of trichloroacetic acid (TCA)–induced pre-neoplastic changes in rats. Rats were allocated into 5 groups and treated for 4 weeks. Group 1: control; received vehicle, Group 2: TCA group; received TCA (1 g/kg, orally for 5 days). Group 3: DIA-treated group; received TCA +DIA (50 mg/kg/day, orally, for 4 weeks). Group 4: positive control group; received TCA (1 g/kg, orally, for 5 days) + 5-fluorouracil (5-FU) (75 mg/kg) intraperitoneally (i.p.), for 4 weeks as a standard anticancer drug. Group 5: received TCA (1 g/kg, orally for 5 days) + DIA (50 mg/kg/day, orally, for 4 weeks) + 5-FU (75 mg/kg, i.p., for 4 weeks). Serum liver enzymes, oxidative stress parameters, inflammatory parameter (IL-1β), and angiogenesis marker vascular endothelial growth factor (VEGF) were assessed along with histopathological evaluation. An apoptotic marker as caspase-3 expression was measured by western blot analysis. Immunoexpression of proliferating cell nuclear antigen (PCNA) and hypoxia-inducible factor-1α (HIF-1α) was evaluated. Results and conclusion: The outcomes proved that at histological level, DIA ameliorated hepatic precancerous lesion via modulation of IL-1β–HIF-1α–VEGF pathway. Conclusion IL-1β mediates angiogenesis indirectly, as it has been shown to induce hypoxia-inducible factor-1α (HIF-1α) which upregulates VEGF.

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Mongelli, Michele, Erica Silvestris, Vera Loizzi, Gennaro Cormio, Gerardo Cazzato et Francesca Arezzo. « A Rare Case of Collision Tumours of the Ovary : An Ovarian Serous Cystadenoma Coexisting with Fibrothecoma ». Diagnostics 12, n^o 11 (17 novembre 2022) : 2840. http://dx.doi.org/10.3390/diagnostics12112840.

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The incidence of epithelial tumours of the ovary ranges from 9–17 per 100,000 and is the highest in high-income countries, with the exception of the Japan. The coexistence of neoplastic Müllerian epithelial and sex cord-stromal elements within a single tumour is extremely rare. We describe the case of a 74-year-old woman with a voluminous left adnexal formation. Pre-operative assessment with ultrasound evaluation made a suspicious diagnosis of benignity of the lesion. Bilateral salpingo-ovariectomy was performed. Intraoperative frozen section analysis results in the diagnosis of fibrothecoma in the context of serous cystadenoma. The diagnosis is confirmed by histological examination. Some authors suggest labelling this phenomenon as collision tumours.

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Aitchison, Alan, John F. Pearson, Rachel V. Purcell, Frank A. Frizelle et Jacqueline I. Keenan. « Detection of Fusobacterium nucleatum DNA in primary care patient stool samples does not predict progression of colorectal neoplasia ». PLOS ONE 17, n^o 6 (3 juin 2022) : e0269541. http://dx.doi.org/10.1371/journal.pone.0269541.

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Background Carriage of certain bacterial species may represent potential biomarkers of colorectal cancer (CRC). Prominent among these is Fusobacterium nucleatum. We explored the association of F. nucleatum DNA in stool samples with the presence of colonic neoplastic lesions in a cohort of primary care patients, and compared our findings with those from an unrelated cohort of colonoscopy patients followed clinically over time. Methods Carriage rates of F. nucleatum in stool samples were assessed in 185 patients referred for a faecal immunochemical test (FIT) by their general practitioners (GPs). Comparisons were made with stool samples from 57 patients diagnosed with CRC and 57 age-matched healthy controls, and with tissue samples taken at colonoscopy from 150 patients with a decade of subsequent clinical follow-up. Findings F. nucleatum DNA was found at a high rate (47.0%) in stool samples from primary care patients, and more often in stool samples from CRC patients (47.4%) than in healthy controls (7.0%), (P = 7.66E-7). No association was found between carriage of F. nucleatum and FIT positivity (P = 0.588). While evidence of stool-associated F. nucleatum DNA was significantly more likely to indicate a lesion in those primary care patients progressed to colonoscopy (P = 0.023), this finding did not extend to the progression of neoplastic lesions in the 150 patients with a decade of follow up. Conclusion The finding of F. nucleatum DNA at similar rates in stool samples from patients diagnosed with CRC and in primary care patients with pre-cancerous lesions supports growing awareness that the presence of these bacteria may be a biomarker for increased risk of disease. However, molecular evidence of F. nucleatum did not predict progression of colonic lesions, which may lessen the utility of this bacterium as a biomarker for increased risk of disease.

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Duc Canh, Tran, Bui Anh Tuyet, Pham Quoc Dat et Nguyen Van Chu. « Preliminary results of endoscopic submucosal dissection in Vietnamese patients with gastric pre-neoplasia lesion. » Journal of Global Oncology 5, suppl (7 octobre 2019) : 91. http://dx.doi.org/10.1200/jgo.2019.5.suppl.91.

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91 Background: Gastric cancer is in the top three most common cancers in Vietnam and the disease is mainly detected in late stage. There is a lack of evaluation of the pre-neoplasia stage of gastric cancer and selection an appropriate and effective treatment remains still in debate. Hence, the study aims to evaluate, for the first time, the safety and efficacy of the application of endoscopic submucosal dissection (ESD) technique on Vietnamese patients with pre-neoplasia lesion in stomach. Methods: We included all patients diagnosed with lower or high-grade gastric dysplasia and hopitalized in the Department of Endoscopic and Functional Exploration in K Hospital from March 2018 to June 2019. Eligible patients were applied by the ESD technique as the standard treatment. We evaluated the efficacy and safety of after the intervention of ESD by the neoplasia recurrence rate after 3 months and the occurrence of adverse events during and after the ESD procedure described in frequency and percentage. Results: During the investigational period, we chose 65 pre-neoplasia gastric patients for the application of ESD technique. The male/female ratio was 1.09 and the mean age of patients was 58.07 years. The duration of hospitalization was about 3 days. We found 57 patients (87.69%) with location of the lesions in pylorus. The average of tumor sizes was 20.46 mm. All patients were treated with curative en bloc resection and no case was found as failure. Out of 65 patients, we found 2 patients (3%) with bleeding complication, no perforation and other post-surgery complication were identified. The average of procedure time was short (67.53 minutes). The histopathological specimen results revealed that 20 patients (30.76%) were diagnosed as cancer and 40 patients (61.53%) were diagnosed as high-grade dysplasia, all patients had a margin negative after ESD. After 3 months of treatment, all patients have no pre-neoplastic recurrence. Conclusions: Our result showed that the ESD technique is relatively safe and effective for Vietnamese patients with pre-neoplasia at stomach.

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Rawal, Gireesha, Preeti Sharma, Surbhi Goyal, Amit Kumar Yadav et Ashish Kumar Mandal. « Intra-testicular epidermoid cyst : a rare case report with clinico-radiological dilemma ». International Surgery Journal 4, n^o 4 (25 mars 2017) : 1487. http://dx.doi.org/10.18203/2349-2902.isj20171168.

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Intra-testicular epidermoid cyst of testis is a benign tumour and accounts for 1-2% of all testicular neoplasms. It is a benign lesion, and should be distinguished from dermoid cyst or teratoma, which have a considerable malignant potential. We describe a rare case of testicular epidermoid cyst in an elderly male presenting with gradually increasing testicular mass since 8 months. Local examination revealed a non-tender, irregular, hard mass in the right testis. All routine laboratory investigations along with tumour markers were within normal limits. Ultrasound showed features of a testicular neoplasm following which orchidectomy was performed. Grossly, cut surface of testis showed a cyst measuring 4x2x1cm and microscopic examination revealed features of an epidermoid cyst. Extesive sampling excluded the possibility of a teratomatous focus. This case is described owing to the rarity of this neoplasm and the unusual clinico-radiological presentation. The pre-operative diagnosis of this tumour can be made if characteristic sonographic and MRI findings are obtained in the absence of which these masquerade neoplastic lesions. Histopathological examination thus is vital for a decisive diagnosis.

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Barz, Melanie, Kaywan Aftahy, Insa Janssen, Yu-Mi Ryang, Georg Prokop, Stephanie E. Combs, Philipp J. Jost, Bernhard Meyer et Jens Gempt. « Spinal Manifestation of Malignant Primary (PLB) and Secondary Bone Lymphoma (SLB) ». Current Oncology 28, n^o 5 (2 octobre 2021) : 3891–99. http://dx.doi.org/10.3390/curroncol28050332.

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Manifestation of malignant lymphoma in the spine is rare; there have only been a few cases reported in the literature. Due to its rarity, there is no gold standard for the management of patients suffering from spinal lymphoma manifestations. Methods: We retrospectively reviewed the data for 37 patients (14 female, 23 male) with malignant lymphoma in the spine receiving intervention in our center from March 2006 until June 2020. Neurological impairment, pain, diagnostics, and/or surgical instability were the criteria for surgery in this patient cohort. Otherwise, only CT-guided biopsies were conducted. Analysis of the patient cohort was based on the Karnofsky performance status scale (KPSS), location of the lesion, spinal levels involved, spinal instability neoplastic score (SINS), surgical treatment, histopathological workup, adjuvant therapy, and overall survival. The following surgical procedures were performed: posterior stabilization and decompression in nine patients; decompression and/or tumor debulking in 18 patients; a two-staged procedure with dorsal stabilization and vertebral body replacement in four patients; decompression and biopsy in one patient; a two-stage procedure with kyphoplasty and posterior stabilization for one patient; posterior stabilization without decompression for one patient; a vertebroplasty and cement-augmented posterior stabilization for one patient; and a CT-guided biopsy alone for two patients. Twenty-one patients (56.78%) had ≥1 lesion in the thoracic spine, 10 patients (27.03%) had lesions in the lumbar spine, two patients had lesions in the cervicothoracic junction, two patients had lesions in the thoracolumbar junction, one patient had a lesion in the lumbosacral junction, and one patient had a lesion in the sacrum. The diagnoses of the histopathological workup were diffuse large B-cell lymphoma in 23 (62.16%) cases, indolent lymphoma in 11 (29.74%) cases, anaplastic T-cell lymphoma in one case (2.70%), T-cell lymphoma in one case (2.70%), and Burkitt lymphoma in one (2.70%) case. The median overall survival was 7.2 months (range 0.1–266.7 months). Pre- and postoperative KPSS scores were 70% (IQR 60–80%). Manifestation of malignant lymphomas in the spine is rare. Similar to the approach taken for spine metastases, a surgical intervention in cases of neurological impairment or manifest or potential instability is indicated, followed by chemoimmunotherapy and radiotherapy.

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Tedeschi, E., S. Cirillo, M. L. Del Basso De Caro, E. M. Covelli et G. Belfiore. « Un caso di Neurofibromatosi di tipo 1 “complicata” da processo espansivo cerebellare maligno con aspetti TC/RM atipici ». Rivista di Neuroradiologia 16, n^o 3 (juin 2003) : 445–48. http://dx.doi.org/10.1177/197140090301600319.

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A 13 year-old boy, previously diagnosed as having Neurofibromatosis Type 1 (NF1) but otherwise healthy, was referred to our Department for headache, vomiting, ataxia and VI-VII left cranial nerve palsy. Emergency head CT scan was performed, immediately followed by contrast-enhanced MR scan with Echo-Planar (EPI) water diffusibility study. A large ovalar mass lesion was evident in the left cerebellar hemisphere, hyperdense on CT, hypointense in T2-weighted images, isointense to grey matter in FLAIR and T1-weighted images, with clear mass effect on the surrounding structures, but only mild peripheral contrast-enhancement in the anterior part of the mass, these features resembling those of a desmoplastic medulloblastoma. However, the EPI Diffusion-weighted images (DWI) and corresponding Apparent Diffusion Coefficient (ADC) maps consistently showed increased water diffusivity, a pattern not compatible with the dense cell-packing typical of medulloblastomas. The pathological analysis of the surgical specimen indeed showed focal neoplastic cell clusters interspersed in a diffusely altered cerebellar cortex. Neoplastic cells exhibited large eosinophilic cytoplasma, hyperchromatic and multinucleolated nuclei, and frequent mitoses, a pattern indicative of anaplastic astrocytoma. The case presented supports the evidence that NF1 is associated with increased risk of developing several different neoplasms, beside the well-known pilocytic astrocytomas of the optic pathway. As these neoplasms may exhibit misleading imaging features at CT or “conventional” MRI study, the assessment of water diffusivity may provide useful data for reaching a correct pre-operative diagnosis, since it reflects the histological architecture of the neoplastic tissue.

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Zavros, Yana, Meghna Waghray, Arthur Tessier, Longchuan Bai, Andrea Todisco, Deborah L. Gumucio, Linda C. Samuelson, Andrzej Dlugosz et Juanita L. Merchant. « Reduced Pepsin A Processing of Sonic Hedgehog in Parietal Cells Precedes Gastric Atrophy and Transformation ». Journal of Biological Chemistry 282, n^o 46 (14 septembre 2007) : 33265–74. http://dx.doi.org/10.1074/jbc.m707090200.

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Sonic hedgehog (Shh) is not only essential to the development of the gastrointestinal tract, but is also necessary to maintain the characteristic acid-secreting phenotype of the adult stomach. Gastrin is the only hormone capable of stimulating gastric acid and is thus required to maintain functional parietal cells. We have shown previously that gastrin-null mice display gastric atrophy and metaplasia prior to progression to distal, intestinal-type gastric cancer. Because reduced levels of Shh peptide correlate with gastric atrophy, we examined whether gastrin regulates Shh expression in parietal cells. We show here that gastrin stimulates Shh gene expression and acid-dependent processing of the 45-kDa Shh precursor to the 19-kDa secreted peptide in primary parietal cell cultures. This cleavage was blocked by the proton pump inhibitor omeprazole and mediated by the acid-activated protease pepsin A. Pepsin A was also the protease responsible for processing Shh in tissue extracts from human stomach. By contrast, extracts prepared from neoplastic gastric mucosa had reduced levels of pepsin A and did not process Shh. Therefore processing of Shh in the normal stomach is hormonally regulated, acid-dependent, and mediated by the aspartic protease pepsin A. Moreover parietal cell atrophy, a known pre-neoplastic lesion, correlates with loss of Shh processing.

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Gissi, Davide, Viscardo Fabbri, Andrea Gabusi, Jacopo Lenzi, Luca Morandi, Sofia Melotti, Sofia Asioli et al. « Pre-Operative Evaluation of DNA Methylation Profile in Oral Squamous Cell Carcinoma Can Predict Tumor Aggressive Potential ». International Journal of Molecular Sciences 21, n^o 18 (14 septembre 2020) : 6691. http://dx.doi.org/10.3390/ijms21186691.

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Background: Prognosis of oral squamous cell carcinoma (OSCC) is difficult to exactly assess on pre-operative biopsies. Since OSCC DNA methylation profile has proved to be a useful pre-operative diagnostic tool, the aim of the present study was to evaluate the prognostic impact of DNA methylation profile to discriminate OSCC with high and low aggressive potential. Methods: 36 OSCC cases underwent neoplastic cells collection by gentle brushing of the lesion, before performing a pre-operative biopsy. The CpG islands methylation status of 13 gene (ZAP70, ITGA4, KIF1A, PARP15, EPHX3, NTM, LRRTM1, FLI1, MiR193, LINC00599, MiR296, TERT, GP1BB) was studied by bisulfite Next Generation Sequencing (NGS). A Cox proportional hazards model via likelihood-based component-wise boosting was used to evaluate the prognostic power of the CpG sites. Results: The boosting estimation identified five CpGs with prognostic significance: EPHX3-24, EPHX3-26, ITGA4-3, ITGA4-4, and MiR193-3. The combination of significant CpGs provided promising results for adverse events prediction (Brier score = 0.080, C-index = 0.802 and AUC = 0.850). ITGA4 had a strong prognostic power in patients with early OSCC. Conclusions: These data confirm that the study of methylation profile provides new insights into the molecular mechanisms of OSCC and can allow a better OSCC prognostic stratification even before surgery.

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Stauffer, Elena, Peter Weber, Theresa Heider, Claudia Dalke, Andreas Blutke, Axel Walch, Gerald Burgstaller et al. « Transcriptomic landscape of radiation-induced murine thyroid proliferative lesions ». Endocrine-Related Cancer 28, n^o 3 (mars 2021) : 213–24. http://dx.doi.org/10.1530/erc-21-0019.

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Thyroid carcinoma incidence rates in western societies are among the fastest rising, compared to all malignant tumors over the past two decades. While risk factors such as age and exposure to ionizing radiation are known, early-state carcinogenic processes or pre-lesions are poorly understood or unknown. This study aims at the identification and characterization of early-state radiation-associated neoplastic processes by histologic and transcriptomic analyses of thyroid tissues derived from a mouse model. Comprehensive histological examination of 246 thyroids (164 exposed, 82 non-exposed) was carried out. Proliferative and normal tissues from exposed cases and normal tissue from non-exposed cases were collected by laser-capture microdissection, followed by RNAseq transcriptomic profiling using a low input 3′-library preparation protocol, differential gene expression analysis and functional association by gene set enrichment analysis. Nine exposed samples exhibited proliferative lesions, while none of the non-exposed samples showed histological abnormalities, indicating an association of ionizing radiation exposure with histological abnormalities. Activated immune response signaling and deregulated metabolic processes were observed in irradiated tissue with normal histology compared to normal tissue from non-exposed samples. Proliferative lesions compared to corresponding normal tissues showed enrichment for mainly proliferation-associated gene sets. Consistently, proliferative lesion samples from exposed mice showed elevated proliferation-associated signaling and deregulated metabolic processes compared to normal samples from non-exposed mice. Our findings suggest that a molecular deregulation may be detectable in histologically normal thyroid tissues and in early proliferative lesions in the frame of multi-step progression from irradiated normal tissue to tumorous lesions.

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Hanna, Matthew G., Patricia Raciti, Alican Bozkurt, Ran Godrich, Julian Viret, Donghun Lee, Philippe Mathieu et al. « Abstract PD11-02 : Subtyping invasive carcinomas and high-risk lesions for machine learning based breast pathology ». Cancer Research 82, n^o 4_Supplement (15 février 2022) : PD11–02—PD11–02. http://dx.doi.org/10.1158/1538-7445.sabcs21-pd11-02.

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Abstract Background. The female mammary gland can develop a myriad of epithelial proliferative lesions including, high risk lesions, in-situ and invasive carcinomas. Identification of these pre-neoplastic and neoplastic conditions in biopsy specimens is crucial for proper patient management and may sometimes pose diagnostic challenges for pathologists. Recent research has shown that machine learning algorithms applied to whole slide images (WSI) can accurately detect and grade various cancers; herein, we devise and test a system that classifies the most common preneoplastic and neoplastic conditions of the female breast from WSIs. Design. De-identified slides were scanned on Leica AT2 whole slide scanners (20x; 0.5 µm/pixel) from MSK database were retrieved. Clinical diagnostic metadata were extracted from the pathology reports. Using a multi-label multiple-instance learning (ML-MIL) approach, a SE-ResNet50 Convolutional Neural Network (CNN) was trained to classify atypical lobular hyperplasia (ALH), atypical ductal hyperplasia (ADH), lobular carcinoma in situ (LCIS), ductal carcinoma in situ (DCIS), invasive lobular carcinoma (ILC), invasive ductal carcinoma (IDC). In additional morphological subtypes including apocrine, mucinous, solid papillary, micropapillary, and tubular carcinoma were trained. The system uses the WSI as an input and outputs a slide level class and heatmap for the presence of the trained classes. A validation dataset separate from the training set was used to assess performance of the trained model. Results. The CNN was trained on 9,751 surgical specimens (biopsy, 6,289; excision, 3,462) comprising 40,637 slides. The system was validated on 3,183 breast specimens (biopsy, 1,934; excision, 1,249) comprising 11,447 digital slides that were not included in the training of the CNN model. Validation performance in terms of Area Under Receiver Operating Characteristic Curve (AUROC) for each class is shown in Table 1. Conclusion. The trained CNN had a high performance in identifying the presence of ADH, ALH, DCIS, IDC, ILC, LCIS, and, apocrine, micropapillary, mucinous, solid papillary, and tubular carcinomas. Further studies expanding classes to include all clinically relevant lesions and morphologies are underway. In addition, the same approach can be used to detect microinvasions and calcifications in breast tissue. Table 1.Area Under Receiver Operating Characteristic Curve for Breast Lesion ClassesClassNum. Positive (specimens)Num. Negative (specimens)AUROCADH24718640.903ALH20918860.950LCIS17520080.958DCIS81920920.956IDC52126620.956ILC7131120.934Apocrine2431590.931Micropapillary17230110.927Mucinous1231710.994Solid Papillary1531680.908Tubular carcinoma831750.990 Citation Format: Matthew G Hanna, Patricia Raciti, Alican Bozkurt, Ran Godrich, Julian Viret, Donghun Lee, Philippe Mathieu, Matthew Lee, Eugene Vorontsov, Tomer Sabo, Felipe C Geyer, Jorge S Reis-Filho, Leo Grady, Thomas Fuchs, Christopher Kanan. Subtyping invasive carcinomas and high-risk lesions for machine learning based breast pathology [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD11-02.

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Hirachand, S., M. Maharjan, M. Lakhey, R. Thapa et S. Kafle. « Accuracy of fine needle aspiration cytology in diagnosis of thyroid swelling ». Journal of Pathology of Nepal 3, n^o 6 (24 octobre 2013) : 433–36. http://dx.doi.org/10.3126/jpn.v3i6.8988.

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Background: Fine needle aspiration cytology has been shown to be simple, safe, cost effective and quick to perform procedure with excellent patient compliance. It is a well established technique for preoperative investigation of thyroid gland swellings with high sensitivity, specificity and accuracy. The aim of this study was to determine the accuracy of fine needle aspiration cytology of thyroid swellings performed at our institution. Materials and Methods: This study was carried out at Kathmandu Medical College and Teaching hospital, department of Pathology over a period of 3 years (January 2010 to December 2012). Two hundred and seventy three patients of all age groups and both sexes who underwent fine needle aspiration cytology for thyroid swelling were evaluated. Out of 273 patients, histopathological diagnosis was available in 45 patients. Results: Fine needle aspiration cytology result revealed 245 cases (89.7%) as non-neoplastic, 21 cases (7.7%) as neoplastic and 7 cases (2.6%) inadequate due to lack of cellularity. The commonest lesion in the thyroid gland was colloid goiter. Among the malignant neoplasms the commonest was papillary carcinoma. Out of 273 patients, histopathological diagnosis was available in 45 patients. Statistical analysis of our data shows the diagnostic accuracy of fine needle aspiration cytology to be 95.7%. Fine needle aspiration cytology showed a sensitivity of 96.4% and a specificity of 94.4%. Conclusion: Fine needle aspiration cytology is a well established technique for pre operative investigation of thyroid gland swellings with high sensitivity, specificity and accuracy. DOI: http://dx.doi.org/10.3126/jpn.v3i6.8988Journal of Pathology of Nepal (2013) Vol. 3, 433-436

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Motomura, D., et R. Bechara. « A138 ENDOSCOPIC SUBMUCOSAL DISSECTION FOR BARRETT’S NEOPLASIA IN A NORTH AMERICAN ACADEMIC CENTRE ». Journal of the Canadian Association of Gastroenterology 4, Supplement_1 (1 mars 2021) : 123–25. http://dx.doi.org/10.1093/jcag/gwab002.136.

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Abstract Background Endoscopic submucosal dissection (ESD) is carving out an increasing role in the treatment of Barrett’s associated neoplastic lesions. Though endoscopic therapy is classically performed with endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA), ESD provides the advantage of en-bloc resections, and greater R0 resection rates, which are defined as negative deep and lateral margins on histology. Aims Our aim is to present procedural outcomes and subgroup analysis from one of the largest single centre cohorts of esophageal ESD in North America, and the first from Canada. Methods All patients undergoing esophageal ESD for Barrett’s neoplasia between Oct 2016 and June 2020 at a single tertiary care centre in Canada were included in the cohort. Demographic, procedural data and lesion characteristics are presented. Subgroup analysis was performed on patients who underwent extensive resection (≥75% of esophageal circumference) and patients who developed strictures. Statistical analysis included chi square testing on categorical variables and unpaired t-test for continuous variables. Binomial univariable logistic regression was performed to investigate factors associated with stricture formation. Results Thirty-four patients underwent esophageal ESD for Barrett’s associated neoplasia during the study period. The median lesion diameter was 5.7 cm (IQR 4.2 -7.5) and median procedure time 129 min (IQR 66–200). The en-bloc resection rate was 97%, and the R0 resection rate was 91%. Curative resection was achieved in 82% of patients. Upstaging from the pre-resection biopsy to post-ESD histology occurred in 59% of cases. Two adverse events occurred (1 delayed bleed, 1 aspiration event). There were no perforations. Procedural outcomes were similar between patients with extensive resections, but patients with ≥75% circumferential resection developed more strictures (65% vs 13%, p=0.001). Stricture formation was associated with extensive resection (OR 15.4, 95%CI[2.50 - 95.01]) and longer lesion diameter (OR 1.73, 95%CI [1.11 - 2.70]). Conclusions Our experience with ESD for Barrett’s related neoplasia shows excellent en-bloc and R0 resection rate, and provides more accurate histological specimens. Curative resection is possible in the vast majority of cases, including those with extensive resections. Further investigation into stricture prophylaxis will be useful as larger resections are attempted. Funding Agencies None

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Jinna, Nikita, Padmashree Rida, Tianyi Su, Zhihong Gong, Song Yao, Mark LaBarge, Rama Natarajan, Tijana Jovanovic-Talisman, Christine Ambrosone et Victoria Seewaldt. « The DARC Side of Inflamm-Aging : Duffy Antigen Receptor for Chemokines (DARC/ACKR1) as a Potential Biomarker of Aging, Immunosenescence, and Breast Oncogenesis among High-Risk Subpopulations ». Cells 11, n^o 23 (29 novembre 2022) : 3818. http://dx.doi.org/10.3390/cells11233818.

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The proclivity of certain pre-malignant and pre-invasive breast lesions to progress while others do not continues to perplex clinicians. Clinicians remain at a crossroads with effectively managing the high-risk patient subpopulation owing to the paucity of biomarkers that can adequately risk-stratify and inform clinical decisions that circumvent unnecessary administration of cytotoxic and invasive treatments. The immune system mounts the most important line of defense against tumorigenesis and progression. Unfortunately, this defense declines or “ages” over time—a phenomenon known as immunosenescence. This results in “inflamm-aging” or the excessive infiltration of pro-inflammatory chemokines, which alters the leukocyte composition of the tissue microenvironment, and concomitant immunoediting of these leukocytes to diminish their antitumor immune functions. Collectively, these effects can foster the sequelae of neoplastic transformation and progression. The erythrocyte cell antigen, Duffy antigen receptor for chemokines(DARC/ACKR1), binds and internalizes chemokines to maintain homeostatic levels and modulate leukocyte trafficking. A negative DARC status is highly prevalent among subpopulations of West African genetic ancestry, who are at higher risk of developing breast cancer and disease progression at a younger age. However, the role of DARC in accelerated inflamm-aging and malignant transformation remains underexplored. Herein, we review compelling evidence suggesting that DARC may be protective against inflamm-aging and, therefore, reduce the risk of a high-risk lesion progressing to malignancy. We also discuss evidence supporting that immunotherapeutic intervention—based on DARC status—among high-risk subpopulations may evade malignant transformation and progression. A closer look into this unique role of DARC could glean deeper insight into the immune response profile of individual high-risk patients and their predisposition to progress as well as guide the administration of more “cyto-friendly” immunotherapeutic intervention to potentially “turn back the clock” on inflamm-aging-mediated oncogenesis and progression.

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Singh, Mohini, Abhishek Bahadur Singh, Abhijeet Singh et S. P. Agarwal. « Correlation of plasma lipid levels and histopathological grading in patients with oral squamous cell carcinoma and its pre-cancerous lesions ». International Journal of Otorhinolaryngology and Head and Neck Surgery 4, n^o 6 (24 octobre 2018) : 1436. http://dx.doi.org/10.18203/issn.2454-5929.ijohns20184356.

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Background: Lower levels of lipid in proliferating tissues and in blood compartments may occur due to ongoing process of oncogenesis. The evidence regarding hypolipidemia as a predisposing factor for malignancy is scarce. Therefore, this study was undertaken to study alteration of plasma lipid levels in patients diagnosed with oral squamous cell carcinoma (OSCC) and its oral pre-cancerous (OPC) lesions and also to compare the plasma lipid profile in different grades of OSCC.Methods: A single centre prospective cross sectional study was carried out among 150 consecutive patients of OSCC and OPC lesions. The diagnosis of all lesions was confirmed histopathologically and grading was also done for each lesion based on degree of differentiation and keratinization of tumour cells. Serum total cholesterol, HDL, TG, LDL was estimated by using semi-automated chemical analyzer. The lipid levels were compared by using unpaired t-test between two strata whereas one way analysis of variance (ANOVA) with Tukey’s post-hoc tests was used among more than two strata. Results: Total cholesterol, TG, HDL, and LDL were significantly reduced in OSCC and OPC groups when compared with the reference values. Serum TC, LDL and HDL levels were found to be decreased with the loss of differentiation in histological grading but with no statistical significance.Conclusions: It can be inferred that there is an inverse relationship between the serum lipid profile values of TC, HDLC, TG, LDL and OSCC as well as OPC patients. The lower serum lipid status may be considered a useful indicator for initial changes occurring in neoplastic cells.

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