Littérature scientifique sur le sujet « Pulmonary adenocarcinoma, immunohistochemistry, molecular biology »

Introduction: Oral metastases are rare and represent 1% oro-facial neoplasms. The lung is the most common primary site for oral metastatic tumors. The diagnosis is based on histological analysis. Oral metastases have been associated with poor prognosis and is no longer a proven treatment. It was found in a 58-year old man diagnosed with lung cancer with a voluminous mandibular tumefaction following dental avulsion. The panoramic X-ray showed an area of ​​osteolysis compared to the extraction site. The histological and immunohistochemistry of the lesion showed a positivity of the marker CK7 and a negativity of TTF1, in favor of a lung origin. The biomolecular analysis revealed a mutation on the BRAF gene confirming the metastasis primitive origin. Treatment by surgical resection was performed palliatively. Comments: The diagnosis of an oral metastasis remains difficult and is based on the histological analysis and finding immune markers. Molecular biology is sometimes required for theranostics. Treatment options include surgical resection, radiotherapy, and/or chemotherapy. They are sometimes limited to preserve the quality of life. The prognosis of patients with oral metastases is very poor. Conclusion: Oral metastases are rare, and the diagnosis remains difficult.

Background The pro-tumoral action of the cluster of differentiation 147 (CD147), which is associated with the chemotherapy resistance of lung adenocarcinoma, is partly due to accelerated tumor cell glycolysis. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) metabolic parameters included maximal standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), which are non-invasive markers of the glucose metabolism of tumor cells in vivo. This study aimed to clarify the correlation between PET metabolic parameters and CD147 expression, and to evaluate the prognostic value of CD147 expression in resectable lung adenocarcinoma patients. Methods A total of 89 lung adenocarcinoma chemotherapy-naive patients who underwent 18F-fluorodeoxyglucose positron emission tomography and computerized tomography scan before pulmonary surgery were retrospectively analyzed. The PET metabolic parameters were calculated by 18F-FDG PET imaging, and CD147 expression was analyzed by immunohistochemistry. SUVmax, SUVmean, MTV, and TLG compared for their performance in predicting the expression of CD147 were illustrated with statistical analysis. All patients were then followed-up for survival analysis. Results The SUVmax was significantly correlated with the CD147 expression and was the primary predictor for the CD147 expression of lung adenocarcinoma. A cut-off value of the SUVmax, 9.77 allowed 85.1% sensitivity and 64.3% specificity for predicting the CD147 positive lung adenocarcinoma. CD147 expression was correlated with tumor differentiation and metastasis. Univariate survival analysis showed that CD147 expression was significantly associated with a shorter overall survival (OS) time. Multivariate analysis revealed that CD147 was an independent prognostic factor of lung adenocarcinoma patients. Conclusion The SUVmax of a primary tumor measured with 18F-FDG PET may be a simple and non-invasive marker for predicting CD147 expression in lung adenocarcinoma. CD147 is an independent prognostic factor related to OS of postoperative lung adenocarcinoma patients.

Introduction. Cystic lung diseases are rare (orphan) diseases. Lung cysts are an important X-ray and morphological sign that contributes to the correct diagnosis. The aim of the researchwas to describe histologic features and computed tomography findings in patients with pulmonary Langerhans cell histiocytosis (PLCH), lymphangioleiomyomatosis (LAM), primary malignant lung tumors, and endometriosis of the lung. Materials and methods. We evaluated video-assisted surgical lung biopsies from 139 patients, with 86 patients having LAM, 47 having PLCH, and in threes having primary peripheral lung adenocarcinoma and endometriosis of the lung. The average age of patients with LAM was 41±10 years, LCG – 32±11 years, lung adenocarcinoma – 62±3.5 years, and endometriosis of the lung – 32±4.1 years. All patients had undergone high-resolution computed tomography of the lungs (HRCT) before the biopsy was obtained. We performed histological and immunohistochemical examinations of lung tissue specimens. Antibodies to CD1a, SMA, HMB-45, CD207 (langerin), CD10, receptors to progesterone, and estrogen were used in the study. Results. We described HRCT, histological, and immunohistochemical features of cystic lung diseases, including characteristics of the walls of cystic cavities in patients with PLCH, LAM, primary malignant lung tumors, and endometriosis of the lung. Conclusion. The variety of causes of lung cysts required a differential diagnosis, considering the patients’ ages, HRCT data indicating the localization of the pathological process, histology, and immunohistochemistry if necessary. Keywords: сystic lung diseases, computed tomography, pathological anatomy, Langerhans cell histiocytosis, lymphangioleiomyomatosis, malignant tumors, endometriosis

Background:Bone metastases (BM) are tumor cells that originate in a primary malignant tumor and are localized remotely in bone tissue. They more or less faithfully reproduce the morphological and biological characteristics of the primary tumor. Histological analysisis essential to confirm the diagnosis of BM and to identify the primary tumor if possible and sometimes to help in the selection of treatment.Objectives:The aim of this work is to study the contribution of bone biopsy during revealing BM in diagnostic strategy and therapeutic decision.Methods:We retrospectively studied the files of 105 patients hospitalized in a Rheumatology department of for BM revealing from January 2000 until December 2015. For each patient we collected epidemioclinical and anatomopathological data to arrive at the diagnosis of primary neoplasm and histological type.Results:The patients were divided into 86 men (81.9%) and 19 women (18.1%) with a sex ratio (M / F) of 4.52. The average age of our patients was 64.91 ± 13.29 years. Pain was the most frequent reason for consultation found in 97.1%. This pain was either of bone site (61.9%) or of radicular topography (41.9%). Bone swelling or a pathological fracture revealed BM in 4.8% and 8.6% of the cases, respectively. The onset of neurological damage was noted in 13.3% of the cases.Histologically, the bone biopsy performed in 64 patients made it possible to specify the histological type (carcinoma, adenocarcinoma) in 64% of the cases and to lead to primary cancer in 57.8%. A non-radio-guided percutaneous bone biopsy was performed in 44 patients (68.75%) including 41 osteo-medullary biopsy in iliac crest (BOM) and 3 in the sternum, a bone biopsy directed under scanner in 16 cases (25%) and a surgical bone biopsy in 4 cases.The BOM was positive in 21 cases (51.2%) showing a poorly or moderately differentiated adenocarcinoma or carcinoma. It allowed referral to a primitive in 20 cases: a prostatic origin in 11 cases, a pulmonary origin in 5 cases, a digestive origin in 2 cases, a mammary origin in one case and a neuroblastoma in one case.Conclusion:Thanks to improved sampling and immunohistochemistry techniques, the precise histological type and location of the primary tumor could be identified, there by improving the quality of care for patients with increased life expectancy.Disclosure of Interests:None declared

Background: Smoking habit is a common cause of pulmonary Langerhans cell histiocytosis (PLCH) and lung cancer and both diseases may coexist in the lung and share genetic alterations, such as V600E BRAF mutations. We collected a small series of three cases of PLCH-associated lung adenocarcinoma in order to evaluate the molecular setup in both components and underline the critical role of careful tissue selection for predictive molecular driver testing. Methods: Three cases of PLCH-associated adenocarcinoma were collected from consultation files. Clinical data from referring physicians and clinical data were obtained. The surgical biopsies were tested by immunohistochemistry and molecular analysis after separate dissection of adenocarcinoma cells and Langerhans histiocytes. Results: There were three active smoking men with a median age at diagnosis of 60.6 years. PLCH was disclosed at imaging during work-up for suspected lung cancer. Molecular analysis revealed KRAS (G12C and G13C) mutations in two cases and V600E BRAF mutation in one case of PLCH. Immunostaining with the V600E BRAF mutation specific primary antibody VE1 correctly recognized BRAF-mutated LCH. One case was wild-type in both diseases. Two similar cases were found in the literature, one of which showed a discrepant KRAS (G12D) mutation in adenocarcinoma and a V600E BRAF mutation in LCH; Conclusions: This case series of PLCH-associated adenocarcinoma underline the possibility to disclose identical genetic alterations in co-existing benign and malignant pathologies, then potentially creating erroneous interpretation of molecular analysis leading to inadequate therapeutic options in case of incorrect diagnostic recognition and inappropriate selection of both components through microdissection.

Idiopathic pulmonary fibrosis (IPF) and lung cancer share common risk factors, epigenetic and genetic alterations, the activation of similar signaling pathways and poor survival. The aim of this study was to examine the gene expression profiles of stromal cells from patients with IPF and lung adenocarcinoma (ADC) as well as from normal lung. The gene expression levels of cultured stromal cells derived from non-smoking patients with ADC from the tumor (n = 4) and the corresponding normal lung (n = 4) as well as from patients with IPF (n = 4) were investigated with Affymetrix microarrays. The expression of collagen type IV alpha 1 chain, periostin as well as matrix metalloproteinase-1 and -3 in stromal cells and lung tissues were examined with quantitative real-time reverse transcriptase polymerase chain reaction and immunohistochemistry, respectively. Twenty genes were similarly up- or down-regulated in IPF and ADC compared to control, while most of the altered genes in IPF and ADC were differently expressed, including several extracellular matrix genes. Collagen type IV alpha 1 chain as well as matrix metalloproteinases-1 and -3 were differentially expressed in IPF compared to ADC. Periostin was up-regulated in both IPF and ADC in comparison to control. All studied factors were localized by immunohistochemistry in stromal cells within fibroblast foci in IPF and stroma of ADC. Despite the similarities found in gene expressions of IPF and ADC, several differences were also detected, suggesting that the molecular changes occurring in these two lung illnesses are somewhat different.

Background: Primary pulmonary enteric adenocarcinoma (PEAC) is a rare non-small cell lung cancer subtype sharing morphologic and immunohistochemical features with colorectal adenocarcinoma. Given the frequency of lung metastases in colorectal cancer, the differential diagnosis of PEAC according to routine morphological and immunohistochemical findings may be difficult. Genome sequence by next-generation sequencing has recently introduced new perspectives to better define the diagnosis and tumor sensitivity to treatments, while the rarity of this subtype of cancer still limits the current knowledge of its molecular features and provides no information to address patients to tailored therapies. Methods: We diagnosed a rare case of subcutaneous metastasis as a first symptom of a PEAC. Formalin-fixed paraffin-embedded samples of the primary tumor and subcutaneous metastases were examined by immunohistochemistry, and subsequently by targeted next-generation sequencing analysis. Results: Morphological and immunohistochemical findings suggested a rare case of metastatic pulmonary adenocarcinoma with enteric aspects. Next-generation sequencing analysis performed on both the primary tumor sample and the cutaneous lesion identified two pathogenic variants on CDKN2A and KRAS in both of them. However, the metastasis showed two additional pathogenic mutations located in SMAD4 and FLT3 genes. Conclusions: We describe for the first time an extensive molecular analysis on a rare case of PEAC with an unusual cutaneous metastasis. Our observation suggests that a specific pattern of mutations is harbored in this neoplasm, and that additional molecular studies may provide further information to identify prognostic and hopefully predictive genes of response to treatment.

Introduction: Pulmonary adenocarcinoma is a major cause of mortality worldwide. The majority of patients present with advanced stage disease, and minimally invasive procedures are desirable for diagnosis and treatment plans. Herein, we report our experience with percutaneous/transthoracic needle aspiration (TT-NA) in the cytologic diagnosis of pulmonary adenocarcinoma. Material and Methods: After institutional review board approval, the cytopathology electronic data system was searched for all consecutive TT-NA of the lung masses from January 2011 to November 2015. Patients’ medical records were reviewed and cytologic materials were evaluated. Results: A total of 151 specimens were identified, with a mean age of 62.8 years; 62.9% of the patients had a prior history of malignancy. Carcinoma/adenocarcinoma was the most common (80%) diagnosis. The targeted lesions were predominantly located in the lung (56.3%, 81/151) and pleural based (27.8%, 42/151). The mean size of the lesions was 3.6 cm. Cytology specimens were adequate in 70.9% of the cases, while 72.8% (110/151) of the cases also had concurrent core biopsy. A malignant diagnosis was rendered in the majority of the cases (64.9%). In 71% of the cases, immunohistochemistry/histochemistry studies were successfully performed. Molecular/genetic studies were requested in 80% of the cases and had adequate material. Complications of the procedure were seen in 9.9% of the patients including pneumothorax (7.9%) and hemoptysis (1.9%). Conclusion: TT-NA is a relatively safe and reliable technique in the assessment of pulmonary lesions.

Pur essendo il carcinoma del polmone la causa principale di morte per cancro a livello mondiale, non ci sono ancora marcatori affidabili in grado di stratificare da un punto di vista prognostico i pazienti affetti da adenocarcinoma del polmone. Né l’aspetto istologico né fingerprint genetici sono in grado di fornire una stratificazione prognostica dei pazienti che sia riproducibile e clinicamente utile. Per questo motivo, abbiamo costruito un pannello ad hoc di 6 marcatori immunoistochimici (TTF1, SP-A, Napsin A, MUC5AC, CDX2 e CK5). Testando questi marcatori, che sono fortemente correlati con le "cellule di origine" putative dell’adenocarcinoma polmonare (TTF1, SP-A e Napsin A indicano un'origine alveolare, mentre MUC5AC, CDX2 e CK5 indicano un'origine bronchiolare), ci proponiamo di identificare diversi sottogruppi prognostici tra i pazienti affetti da adenocarcinoma del polmone. Come secondo obiettivo, abbiamo correlato l’espressione di questi marcatori con le comuni mutazioni genetiche e l’aspetto istologico degli adenocarcinomi polmonari testati. A tal fine, abbiamo raccolto un'ampia coorte di pazienti sottoposti a intervento chirurgico per adenocarcinoma polmonare e, usando i tessuti fissati in formalina e inclusi in paraffina , abbiamo studiato: i) il pattern di crescita istologico (lepidico, acinare, papillare, micropapillare, solido e mucinoso) al microscopio ottico, ii) la presenza di mutazioni "hot spot" di geni candidati (ad esempio EGFR, KRAS, PI3K) tramite tecnologia Sequenom e iii) il pannello di 6 marcatori immunoistochimici. Le differenze tra i gruppi così ottenuti sono state valutate con il test di Mann-Whitney per le variabili continue e il test del chi-quadrato o test esatto di Fisher per le variabili categoriali. Per rilevare possibili fattori predittivi di sopravvivenza, abbiamo usato il modello di rischio proporzionale di Cox per descrivere rischi proporzionali con intervalli di confidenza al 95%. Come importante risultato, abbiamo identificato 4 sottogruppi differenti basati sull’espressione del pannello immunoistochimico: alveolari, bronchiolari, misti e tipo "nullo", che risultano fortemente correlati con diversi parametri clinico-patologici e soprattutto con la sopravvivenza globale. In particolare, se gli adenocarcinomi a fenotipo alveolare sorgono con maggiore frequenza nei pazienti giovani e nel sesso femminile e presentano più frequentemente mutazioni del gene EGFR, le neoplasie a fenotipo bronchiolare sono maggiormente associate alla presenza di invasione vascolare, istologia mucinosa e mutazioni del gene KRAS; infine, i fenotipi bronchiolari e “nulli” sono associati con una prognosi peggiore. In assenza di marcatori prognostici clinici, la stratificazione prognostica basata sulla "cellula di origine" è risultata più predittiva della prognosi dei parametri isto-morfologici e del fingerprint genetico e rappresenta un parametro predittivo indipendente di sopravvivenza nell'analisi multivariata
Lung carcinoma is the leading cause of cancer related-death worldwide, but reliable prognostic markers to correctly stratify the prognosis of patients with lung adenocarcinoma are still lacking. Neither morphology nor genetic fingerprints can fully achieve consistent and clinically informative stratifications. We aimed to evaluate a new immunohistochemical panel composed by 6 markers (TTF1, SP-A, Napsin A, MUC5AC, CDX2 and CK5). Using these markers, that are strongly correlated with the two possible putative “cell of origin” of lung adenocarcinoma (TTF1, SP-A and Napsin A indicate an alveolar origin, whereas MUC5AC, CDX2 and CK5 indicate a bronchiolar origin), we aim at identifying different prognostic subgroups among patients with such tumors. As a second aim, we have correlated these markers with common genetic mutations and classical morphology. We collected a large cohort of adenocarcinoma patients and, using formalin-fixed paraffin-embedded tissue, we have studied: i) the morphological appearance (lepidic, acinar, papillary, micropapillary, solid and mucinous) by light microscopy, ii) the presence of “hot spot” mutations of candidate genes (i.e. EGFR, KRAS, PI3K) by Sequenom technology and iii) the 6 immunohistochemical markers panel. Between-group differences were evaluated using the Mann–Whitney U test for continuous variables and the chi-square test or Fisher’s exact test for categorical variables. To detect possible predictors of survival, we used the Cox proportional hazard model to describe proportional hazards with 95% confidence intervals. As major finding, we identified 4 different subgroups based on markers’ expression: “alveolar” type, “bronchiolar” type, “mixed” type and “null” type, that resulted strongly correlated with different clinic-pathological parameters and above all with Overall Survival (OS). Particularly, if the alveolar-type arose more in young and female patients, and harbor typically EGFR mutations, bronchiolar-type tumors were more frequently associated with vascular invasion, a mucinous histology and KRAS mutations; at last, Bronchiolar and Null types were associated with a worse prognosis. In the absence of reliable prognostic markers, our 6 “cell of origin” markers’ classifier appears more predictable than the classical morphologic parameters and the genetic fingerprint, and is an independent predictor of survival in a multivariate analysis.