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1

Sica, Gabriel, Patrick L. Wagner, Nassar Altorki, Jeffrey Port, Paul C. Lee, Madeline F. Vazquez, and Anjali Saqi. "Immunohistochemical Expression of Estrogen and Progesterone Receptors in Primary Pulmonary Neuroendocrine Tumors." Archives of Pathology & Laboratory Medicine 132, no. 12 (December 1, 2008): 1889–95. http://dx.doi.org/10.5858/132.12.1889.

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Abstract Context.—Lung and breast carcinomas are among the most prevalent cancers. Advances in cancer therapies can provide survival benefit and be potentially curative, even in metastatic disease. Due to the high prevalence of these carcinomas, it is not unusual to encounter lung nodule(s) in a patient with breast carcinoma, and distinguishing between primary and metastatic disease is critical for management/treatment. Occasionally neuroendocrine differentiation is present in breast carcinoma, making its distinction from pulmonary/nonpulmonary neuroendocrine tumors in the lung difficult. Objective.—To assess estrogen and progesterone receptor expression in the entire spectrum of pulmonary neuroendocrine tumors. Design.—Seventy-one neuroendocrine neoplasms including typical carcinoids (42), atypical carcinoids (7), small cell carcinomas (14), large cell neuroendocrine carcinomas (2), and combined small cell carcinomas (6) were evaluated for estrogen and progesterone receptors. Mammary and non–small cell lung carcinomas were also stained for comparison. Results.—The entire spectrum of neuroendocrine neoplasms demonstrated focal to diffuse estrogen (typical carcinoid, 23; atypical carcinoid, 6; small cell carcinoma, 8; large cell neuroendocrine carcinoma, 2; combined small cell carcinoma, 4) and progesterone (typical carcinoid, 11; atypical carcinoid, 2; small cell carcinoma, 7; large cell neuroendocrine carcinoma, 0; combined small cell carcinoma, 2) expression. There was no correlation between sex and estrogen/progesterone status. Estrogen and progesterone staining were also noted in endothelial cells. Relative to neuroendocrine carcinomas, mammary carcinomas expressed estrogen and progesterone more frequently. Non–small cell carcinomas had greater and similar immunoreactivity for estrogen and progesterone, respectively. Conclusions.—Although estrogen and progesterone receptor staining is frequently associated with breast and gynecologic primaries, it can also be observed in “nontarget” organs. Therefore, presence of estrogen and/or progesterone expression in neuroendocrine tumors involving the lung should not exclude a primary pulmonary neoplasm.
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2

Shilo, Konstantin, Tatiana Dracheva, Haresh Mani, Junya Fukuoka, Isabell A. Sesterhenn, Wei-Sing Chu, Joanna H. Shih, Jin Jen, William D. Travis, and Teri J. Franks. "α-Methylacyl CoA Racemase in Pulmonary Adenocarcinoma, Squamous Cell Carcinoma, and Neuroendocrine Tumors: Expression and Survival Analysis." Archives of Pathology & Laboratory Medicine 131, no. 10 (October 1, 2007): 1555–60. http://dx.doi.org/10.5858/2007-131-1555-mcripa.

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Abstract Context.—α-Methylacyl CoA racemase (AMACR) is an oxidative enzyme involved in isomeric transformation of fatty acids entering the beta-oxidation pathway. AMACR serves as a useful marker in establishing a diagnosis of prostatic malignancy; however, limited information is available in regard to its presence in pulmonary neoplasms. Objective.—To investigate AMACR expression within a spectrum of lung carcinomas and its correlation with patients' survival. Design.—Four hundred seventy-seven pulmonary carcinomas, including 150 squamous cell carcinomas, 150 adenocarcinomas, 46 typical carcinoids, 31 atypical carcinoids, 28 large cell neuroendocrine carcinomas, and 72 small cell carcinomas, were studied immunohistochemically using tissue microarray–based samples. Results.—Overall, pulmonary tumors were positive for AMACR in a significant percentage (47%) of cases. Among tumor types, 22% of squamous cell carcinoma, 56% of adenocarcinoma, 72% of typical carcinoid, 52% of atypical carcinoid, 70% of large cell neuroendocrine carcinoma, and 51% of small cell lung carcinoma were positive for AMACR. Furthermore, the Kaplan-Meier analysis revealed that the patients with AMACR-positive small cell carcinoma had better survival (19% vs 5% after 5 years, P = .04) than patients with AMACR-negative tumors. Such survival advantage was seen for patients with stage I–II (P = .01) but not stage III–IV small cell carcinomas (P = .58). Conclusions.—These results indicate that, similar to prostate cancer, the overexpression of AMACR frequently occurs in pulmonary carcinomas. Additionally, its positive correlation with outcome of stage I–II small cell lung carcinoma warrants further investigation of the AMACR role in the prognosis of this tumor.
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3

Turner, Bradley M., Philip T. Cagle, Irma M. Sainz, Junya Fukuoka, Steven S. Shen, and Jaishree Jagirdar. "Napsin A, a New Marker for Lung Adenocarcinoma, Is Complementary and More Sensitive and Specific Than Thyroid Transcription Factor 1 in the Differential Diagnosis of Primary Pulmonary Carcinoma: Evaluation of 1674 Cases by Tissue Microarray." Archives of Pathology & Laboratory Medicine 136, no. 2 (February 1, 2012): 163–71. http://dx.doi.org/10.5858/arpa.2011-0320-oa.

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Context.—Differentiation of non–small cell carcinoma into histologic types is important because of new, successful therapies that target lung adenocarcinoma (ACA). TTF-1 is a favored marker for lung ACA but has limited sensitivity and specificity. Napsin A (Nap-A) is a functional aspartic proteinase that may be an alternative marker for primary lung ACA. Objectives.—To compare Nap-A versus TTF-1 in the typing of primary lung carcinoma and the differentiation of primary lung ACA from carcinomas of other sites. Design.—Immunohistochemistry for Nap-A and TTF-1 was performed on tissue microarrays of 1674 cases of carcinoma: 303 primary lung ACAs (18.1%), 200 primary squamous cell lung carcinomas (11.9%), 52 primary small cell carcinomas of the lung (3.1%), and carcinomas of the kidney (n = 320; 19.1%), thyroid (n = 96; 5.7%), biliary (n = 89; 5.3%), bladder (n = 47; 2.8%), breast (n = 93; 5.6%), colon (n = 95; 5.7%), liver (n = 96; 5.7%), ovaries (n = 45; 2.7%), pancreas (n = 48; 2.9%), prostate (n = 49; 2.9%), stomach (n = 93; 5.6%), and uterus (n = 48; 2.9%). Cases were evaluated against a negative control as negative, weak positive, and strong positive. Results.—Nap-A was more sensitive than TTF-1 for primary lung ACA (87% versus 64%; P < .001). Nap-A was more specific than TTF-1 for primary lung ACA versus all tumors, excluding kidney, independent of tumor type (P < .001). Conclusions.—Nap-A is superior to TTF-1 in distinguishing primary lung ACA from other carcinomas (except kidney), particularly primary lung small cell carcinoma, and primary thyroid carcinoma. A combination of Nap-A and TTF-1 is useful in the distinction of primary lung ACA (Nap-A+, TTF-1+) from primary lung squamous cell carcinoma (Nap-A−, TTF-1−) and primary lung small cell carcinoma (Nap-A−, TTF-1+).
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4

Grygoruk, O. G., D. A. Tsoi, L. M. Bazulina, and I. V. Vihlyanov. "Small‑cell lung carcinoma. Cytological diagnosis." Malignant tumours 12, no. 1 (April 8, 2022): 36–43. http://dx.doi.org/10.18027/2224-5057-2022-12-1-36-43.

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The purpose of this article is to evaluate the possibilities of cytology for lung neuroendocrine tumors (small‑cell lung carcinoma and carcinoids) diagnostics. Cytology specimens obtained by bronchoscopy (n = 112), biopsy of metastatic lymph nodes (n = 27) or from pleural effusion (n = 8) were collected within over 1 year from 147 patients and studied. Small-cell lung carcinoma was diagnosed in 143 patients, representing 23,9 % of all lung carcinomas. The proportion of carcinoid tumors was 2,7 % of all neuroendocrine tumors. Typical carcinoid was observed in three cases, and atypical carcinoid — in one case. Cytologic features most significant for cytological diagnosis of small‑cell lung carcinoma and carcinoids were identified (n = 11). Discriminant analysis demonstrated that the proportion of accurate cytological diagnosis of small‑cell lung carcinoma and carcinoids was 96,69 %. Cytology is a reliable method for neuroendocrine tumor diagnosis. Immunocytochemistry with neuroendocrine markers along with light microscopy should be used to differentiate small‑cell lung carcinoma metastases from other tumors and non‑malignant pathology in pleural effusion specimens.
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5

Dacic, Sanja. "Molecular Diagnostics of Lung Carcinomas." Archives of Pathology & Laboratory Medicine 135, no. 5 (May 1, 2011): 622–29. http://dx.doi.org/10.5858/2010-0625-rair.1.

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Abstract Context.—The development of targeted therapies in the treatment of lung carcinoma is a rapidly growing area that requires a precise histologic classification of lung carcinomas and the implementation into clinical practice of testing for predictive biomarkers of therapy response. Molecular testing has added another layer of complexity in the routine workup of rather limited diagnostic tumor tissue. Objective.—To review the most important lung carcinoma biomarkers predictive of response and to discuss proposed routine molecular testing in clinical practice. Data Sources.—PubMed (US National Library of Medicine)–available review articles, peer-reviewed original articles, and experience of the author. Conclusions.—Histologic profile, clinical characteristics, and mutational profile of lung carcinoma have all been reported as predictive factors of response to epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs) and other targeted therapies. Recently published results of large clinical trials indicate that mutational profiling, particularly identification of activating epidermal growth factor receptor (EGFR) mutations, is the best predictor for EGFR-TKI response. Despite all these observations, molecular profiling of lung carcinomas has not been standardized or validated in clinical practice. Rapid development of targeted therapies will probably require molecular testing for a panel of mutations to identify molecular subtypes of non–small cell lung carcinomas that will benefit from new therapeutic approaches in personalized patient care.
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6

Capelli, Marco, Giulia Bertino, Patrizia Morbini, Chiara Villa, Stefano Zorzi, and Marco Benazzo. "Neuroendocrine Carcinomas of the Upper Airways: A Small Case Series with Histopathological Considerations." Tumori Journal 93, no. 5 (September 2007): 499–503. http://dx.doi.org/10.1177/030089160709300517.

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Neuroendocrine carcinomas are rare tumors. In the head and neck region they are most common in the larynx, where they represent 0.5-1% of epithelial cancers. Diagnosis requires the recognition of the typical neuroendocrine architecture and morphology and the immunohistochemical confirmation of neuroendocrine differentiation. In the 1991 WHO classification laryngeal neuroendocrine carcinomas have been divided into carcinoids, atypical carcinoids, small cell carcinomas and paragangliomas. Atypical carcinoids in the head and neck region usually show an aggressive behavior analogous to poorly differentiated carcinomas, and are resistant to chemo- and radiotherapy. For this reason, it was recently proposed to change their designation to “moderately differentiated neuroendocrine carcinomas”. We present the clinical and histopathological features of 2 moderately differentiated neuroendocrine carcinomas of the larynx, one large cell poorly differentiated neuroendocrine carcinoma of the oropharynx, and one small cell carcinoma of the minor salivary glands of the tongue. The patient with small cell carcinoma was free from disease 26 months after radical surgery, while the other patients showed liver, lung and bone metastases 18, 26 and 24 months after the diagnosis despite radical surgery or concomitant intra-arterial chemotherapy and radiotherapy.
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7

Gupta, Amit, Ashutosh Tandon, Abhay Kumar, Sunil Kumar, and Usha Rani Singh. "Large Cell Neuroendocrine Carcinoma of Lung metastasizing to Jejunum – A rare presentation with review of Literature." Asian Journal of Medical Sciences 4, no. 2 (May 13, 2013): 47–50. http://dx.doi.org/10.3126/ajms.v4i2.5370.

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Large cell neuroendocrine carcinoma of lung is not one of the commoner varieties of neoplasia found in the lungs. There are around 100 cases in literature which suggest the metastasis of various kinds of lung carcinomas to gastro intestinal tract (GIT). Metastasis of large cell neuroendocrine carcinoma to small bowel is rare. This is a rare case in which the primary neuroendocrine carcinoma of lung presented with metastasis and perforation of small bowel.DOI: http://dx.doi.org/10.3126/ajms.v4i2.5370Asian Journal of Medical Sciences 4(2013) 47-50
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8

Altree-Tacha, David, Jillian Tyrrell, and Faqian Li. "mASH1 is Highly Specific for Neuroendocrine Carcinomas: An Immunohistochemical Evaluation on Normal and Various Neoplastic Tissues." Archives of Pathology & Laboratory Medicine 141, no. 2 (September 15, 2016): 288–92. http://dx.doi.org/10.5858/arpa.2015-0489-oa.

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Context.—High-grade neuroendocrine carcinomas and carcinoids can arise in different sites such as lung, gastrointestinal tract, prostate, and skin. Classic neuroendocrine markers such as CD56, synaptophysin, and chromogranin cannot distinguish carcinoids from high-grade neuroendocrine carcinomas. Recently, mouse monoclonal mASH1 has been shown to help discriminate carcinoids from high-grade neuroendocrine carcinomas in various neoplastic sites. To date, there have been no comprehensive immunohistochemistry studies with mASH1 on nonneuroendocrine neoplasms. Objective.—To evaluate the specificity and sensitivity of mASH1 in various normal and neoplastic tissues, including lung cancers. Design.—Formalin-fixed, paraffin-embedded tissue microarrays consisting of normal tissues and various neoplastic tissues were immunohistochemically evaluated with mASH1. Results.—In normal tissues (n = 30), mASH1 (nuclear staining) was sparsely expressed in the molecular cell layer, white matter, and granular cell layer of cerebellum; C cells in thyroid; and epithelial cells in thymus. In lung cancers, mASH1 stained 1.1% (1 of 93) of adenocarcinomas, 0.9% (1 of 111) of squamous cell carcinomas, 0% (0 of 30) of large cell carcinomas, 66.7% (6 of 9) of large cell neuroendocrine carcinomas, and 82.5% (94 of 114) of small cell carcinomas. In various other neoplastic tissues (n = 1114), mASH1 was expressed in thyroid medullary carcinomas, thymic carcinomas, and brain cancers; mASH1 was also expressed in a very low percentage of breast carcinomas, ovarian cancers, and pancreatic neuroendocrine tumors. All typical carcinoids of various sites were negative (0 of 11), however, in lung atypical carcinoids, mASH1 was expressed in 42.9% (9 of 21). Conclusions.—Although not organ specific, mASH1 is highly specific for high-grade neuroendocrine carcinomas versus carcinoids and other nonneuroendocrine neoplasms.
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9

Henderson, Douglas W. "Lung Carcinomas." Pathology 20, no. 2 (1988): 205. http://dx.doi.org/10.1016/s0031-3025(16)36644-2.

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10

Travis, William D. "Sarcomatoid Neoplasms of the Lung and Pleura." Archives of Pathology & Laboratory Medicine 134, no. 11 (November 1, 2010): 1645–58. http://dx.doi.org/10.5858/2010-0086-rar.1.

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Abstract Sarcomatoid neoplasms of the lung and pleura are rare tumors that present a complex differential diagnosis, making them challenging for surgical pathologists. In the lung, the main tumors are the sarcomatoid carcinomas, including pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma, and pulmonary blastoma. They are characterized by histologic heterogeneity; molecular data support their origin from a pluripotent stem cell that undergoes neoplastic transformation with divergent epithelial and sarcomatous differentiation. Diagnosis is difficult in small biopsy specimens and typically requires a resection specimen. Despite the presence of sarcomatoid features, these tumors are classified as lung carcinomas. Pulmonary blastomas must be distinguished from pleuropulmonary blastomas, which are a unique type of thoracic sarcoma typically occurring in young children. In the pleura, the main tumors to consider are the sarcomatoid and desmoplastic types of malignant mesothelioma, solitary fibrous tumor, and desmoid tumor. While light microscopy is sufficient to diagnose most of these tumors, immunohistochemistry can be useful in selected settings. In particular, it can aid to confirm epithelial differentiation in spindle cell carcinomas and the presence of rhabdomyosarcoma in sarcomatoid carcinomas, mesotheliomas, or pleuropulmonary blastomas. For sarcomatoid and desmoplastic mesothelioma, keratin is the most useful stain because it can highlight invasive growth and mesothelial markers are positive in only the minority of cases. Clinical and radiologic correlation is needed to separate some pleomorphic carcinomas with pleural involvement from sarcomatoid malignant mesothelioma, since these poorly differentiated tumors may not express the usual immunohistochemical markers for carcinoma or mesothelioma.
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11

Tecimer, Tülay, Jeffrey Dlott, Anan Chuntharapai, Alvin W. Martin, and Stephen C. Peiper. "Expression of the Chemokine Receptor CXCR2 in Normal and Neoplastic Neuroendocrine Cells." Archives of Pathology & Laboratory Medicine 124, no. 4 (April 1, 2000): 520–25. http://dx.doi.org/10.5858/2000-124-0520-eotcrc.

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Abstract Background.—Chemokines effect their proinflammatory and growth regulatory roles through interaction with serpentine receptors. One such receptor, CXCR2, binds multiple CXC chemokines, including interleukin 8, GRO-α, GRO-β, GRO-γ, and NAP-2. We have previously identified CXCR2 expression on myeloid cells, notably mature granulocytes, and projection neurons. Objective.—To determine the expression of CXCR2 by cells of the neuroendocrine system. Design.—Archival specimens from normal neuroendocrine tissues and their malignant counterparts were analyzed by immunohistochemistry with monoclonal antibodies specific for CXCR1 and CXCR2. Results.—Immunohistochemical analysis revealed high-level expression of CXCR2 by cells in the pituitary, adrenal medulla, pancreatic islets, thyroid C cells, scattered Kulchitsky cells in the bronchi, and counterpart neuroendocrine cells in the stomach, small bowel, colon, and appendix. Neuroendocrine neoplasms that demonstrated high-level CXCR2 expression included (1) primary carcinoids localized to the stomach, small bowel, colon, appendix, fallopian tube, ovary, and lung; (2) atypical carcinoids of the lung; (3) metastatic carcinoids; (4) pituitary adenomas; (5) pheochromocytomas; and (6) medullary carcinomas of the thyroid. Small cell lung carcinomas, large cell neuroendocrine carcinomas of the lung, small cell carcinoma of the cervix, Merkel cell carcinomas, neuroblastomas, and malignant melanomas lacked evidence of CXCR2 expression. Conclusions.—The expression of CXCR2 by normal neuroendocrine cells and neoplastic counterparts that have retained phenotypic features of this differentiation program suggests that chemokines may play an important role in functions that are characteristic of this cell type. In addition, this raises the possibility that chemokines may modulate secretion of biologically active products of these cells and their neoplastic counterparts.
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Terry, Jefferson, Alessandro De Luca, Samuel Leung, Graeme Peacock, Yuzhuo Wang, W. Mark Elliot, and David Huntsman. "Immunohistochemical Expression of Neurotrophic Tyrosine Kinase Receptors 1 and 2 in Lung Carcinoma: Potential Discriminators Between Squamous and Nonsquamous Subtypes." Archives of Pathology & Laboratory Medicine 135, no. 4 (April 1, 2011): 433–39. http://dx.doi.org/10.5858/2010-0038-oa.1.

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Abstract Context.—The neurotrophic tyrosine kinase receptors NTRK1 and NTRK2 have been implicated in the pathogenesis of lung carcinomas. NTRK receptor expression has been reported in lung carcinomas; however, the clinical utility of immunohistochemical expression of these receptors is unclear. Objective.—To compare the immunohistochemical expression profiles of NTRK1 and NTRK2 in various histologic subtypes of lung carcinomas and correlate with patient outcome. Design.—Six hundred eighty-six unique lung cancer cases (including squamous cell carcinoma, adenocarcinoma, large cell carcinoma, small cell carcinoma, and carcinoid tumor) with clinical outcome data in tissue microarray format were immunohistochemically stained for NTRK1 and NTRK2 using commercially available antibodies, automated immunostaining, and standard protocols. Results.—Expression of both NTRK1 and NTRK2 correlates strongly with squamous histology. NTRK1 and NTRK2 are highly specific markers (1: 92.8%, 2: 96.4%) of squamous lung carcinoma when compared with the other carcinoma subtypes, including adenocarcinoma. Positive NTRK2 staining in squamous carcinoma correlates with improved disease-specific survival (P < .001) and overall survival (P = .047). Conclusions.—NTRK1 and NTRK2 are potentially useful immunohistochemical markers that may be particularly helpful in separating squamous cell carcinoma from adenocarcinoma.
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Lenler-Petersen, P., A. Grove, A. Brock, and R. Jelnes. "alpha-Amylase in resectable lung cancer." European Respiratory Journal 7, no. 5 (May 1, 1994): 941–45. http://dx.doi.org/10.1183/09031936.94.07050941.

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Biochemical analysis and immunohistochemical techniques support the theory that hyperamylasaemia in lung cancer is due to amylase production in carcinoma cells. The vast majority of amylase-producing carcinomas are adenocarcinomas with amylase isoenzyme similar to the salivary type. This prospective study assesses alpha-amylase expression in resectable lung cancer. Seventy four patients with resectable lung cancer were studied. Amylase activity in tumour tissue was analysed and isoamylase identification performed. Immunohistochemical analysis was performed using a polyclonal rabbit antibody against human salivary amylase. Hyperamylasaemia occurred in 13 out of 70 patients. Increased amylase activity in tumour tissue was found in 10 out of 52 cases, of which only two were associated with hyperamylasaemia. With the exception of one large cell carcinoma and one squamous cell carcinoma, the tumours were adenocarcinomas. Immunohistochemical analysis revealed amylase expression in seven adenocarcinomas and two adenosquamous carcinomas. In conclusion, immunohistochemical amylase expression was restricted to carcinomas with adenomatous differentiation. Biochemical analysis confirmed amylase production in 5 of 7 cases examined, the tissue amylase isoenzymes being of salivary type. However, hyperamylasaemia and a slightly increased amylase activity in tumour tissue may be caused by factors other than amylase-producing carcinoma cells.
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Song, Jie, Mei Li, Maria Tretiakova, Ravi Salgia, Philip T. Cagle, and Aliya N. Husain. "Expression Patterns of PAX5, c-Met, and Paxillin in Neuroendocrine Tumors of the Lung." Archives of Pathology & Laboratory Medicine 134, no. 11 (November 1, 2010): 1702–5. http://dx.doi.org/10.5858/2009-0664-oar1.1.

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Abstract Context.—c-Met is important in the pathogenesis, invasion, and spread of several forms of lung cancer, and multiple c-Met inhibitors are undergoing clinical trials. PAX5 has been shown to upregulate c-Met in small cell lung carcinoma (SCLC), and coinhibiting PAX5 and c-Met had a synergic effect in killing tumor cells. Paxillin is a downstream target of activated c-Met, and its activation leads to enhanced cell motility and tumor spread. The expression patterns of these functionally related proteins have not, to our knowledge, been systemically studied in neuroendocrine tumors of the lung. Objective.—To investigate the expression patterns of PAX5, paxillin, c-Met, and phosphorylated c-Met in 4 categories of pulmonary neuroendocrine tumors. Design.—Tissue microarrays of 38 typical carcinoids, 6 atypical carcinoids, 34 SCLCs, and 11 large cell neuroendocrine carcinomas were studied with immunohistochemistry. Results.—Most of the 4 tumor types expressed c-Met, phosphorylated c-Met, and paxillin. PAX5 was frequently expressed in atypical carcinoids, SCLCs, and large cell neuroendocrine carcinomas but tended to be negative in typical carcinoids. Coexpression of PAX5 with c-Met or phosphorylated c-Met was present in most of the atypical carcinoids, SCLCs, and large cell neuroendocrine carcinomas. Significant correlation between PAX5 and paxillin was detected in SCLCs and large cell neuroendocrine carcinomas but not in carcinoid tumors. Conclusions.—The frequent coexpression of PAX5 with c-Met or phosphorylated c-Met in intermediate-grade and high-grade neuroendocrine tumors supports the therapeutic strategy of coinhibiting these proteins. The discrepancy between high-grade and low-grade neuroendocrine tumors in PAX5/paxillin expression correlation may be due to the different underlying molecular genetics of these tumors.
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Zhang, Paul J., Kenneth R. Harris, Bachir Alobeid, and John J. Brooks. "Immunoexpression of Villin in Neuroendocrine Tumors and Its Diagnostic Implications." Archives of Pathology & Laboratory Medicine 123, no. 9 (September 1, 1999): 812–16. http://dx.doi.org/10.5858/1999-123-0812-iovint.

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Abstract Background.—Villin, a 95-kd cytoskeletal protein associated with axial microfilament bundles of brush border microvilli, is mostly restricted to intestinal glandular tumors. Villin immunoexpression was recently observed in a small number of carcinoids of the intestinal tract and lung, but its significance in a broad category of neuroendocrine tumors has not been evaluated. Design.—A total of 114 neuroendocrine tumors of different origins were tested for villin expression. They included gastrointestinal carcinoids (n = 30), lung carcinoids (n = 15), small cell carcinomas of the lung (n = 24), small cell carcinomas of other sites (n = 15), islet cell tumors (n = 8), Merkel cell carcinomas (n = 6), paragangliomas (n = 6), and others (n = 10). Nine round cell sarcomas were tested as well. Results.—Villin immunoreactivity was present in 85% of gastrointestinal carcinoids and small cell carcinomas, but was found in only 40% of lung carcinoids. Other tumors tested were virtually negative for villin. In general, while cytoplasmic reactivity was most common, a characteristic apical membranous pattern simulating brush border was seen in 76% of the gastrointestinal carcinoids and in 50% of the lung carcinoids. Conclusions.—We found that villin was predominantly restricted to gastrointestinal neuroendocrine tumors (excluding islet cell tumors), although a small number of bronchial carcinoids may be positive as well. These results suggest a role for villin in the differential diagnosis of neuroendocrine tumors.
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De Lott, Lindsey B., Carl Morrison, Saul Suster, David E. Cohn, and Wendy L. Frankel. "CDX2 Is a Useful Marker of Intestinal-Type Differentiation: A Tissue Microarray–Based Study of 629 Tumors From Various Sites." Archives of Pathology & Laboratory Medicine 129, no. 9 (September 1, 2005): 1100–1105. http://dx.doi.org/10.5858/2005-129-1100-ciaumo.

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Abstract Context.—CDX2, a critical nuclear transcription factor for intestinal development, is expressed in intestinal epithelium and adenocarcinomas. Objectives.—To determine if CDX2 is a useful marker for intestinal-type differentiation and to correlate tumor histology with CDX2 staining in colorectal adenocarcinomas. Design.—Tissue microarrays from 71 colorectal adenocarcinomas, 31 hepatocellular carcinomas, 47 lung adenocarcinomas, 55 squamous cell carcinomas of the lung, 69 neuroendocrine carcinomas of the lung and 43 of the pancreas, 57 pancreatic adenocarcinomas, and 256 endometrial adenocarcinomas were stained with antibody against CDX2. Results.—CDX2 staining was positive in 51 (71.8%) of 71 colorectal cancers, including 38 (74.5%) of 51 well- or moderately differentiated tumors and 13 (65.0%) of 20 high-grade tumors. Of the high-grade tumors, 5 (71.4%) of 7 mucinous, 3 (100%) of 3 signet ring cell, and 5 (50.0%) of 10 poorly differentiated tumors were positive. Other tumors showing occasional CDX2 staining included 1 of 30 well- or moderately differentiated neuroendocrine carcinomas of the lung and 2 of 43 from the pancreas, 1 of 47 lung adenocarcinomas, 3 of 57 pancreatic adenocarcinomas, and 15 of 256 endometrial carcinomas. Hepatocellular, poorly differentiated neuroendocrine carcinoma of the lung and squamous cell carcinomas of the lung were not immunoreactive for CDX2. Conclusions.—CDX2 is a useful marker for intestinal-type differentiation, is rarely seen in tumors from the other sites evaluated, and may be useful in determining the site of origin for some metastatic tumors. However, CDX2 is not a sensitive marker for poorly differentiated colorectal carcinoma.
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Hahn, F. F., B. A. Muggenburg, and W. C. Griffith. "Primary Lung Neoplasia in a Beagle Colony." Veterinary Pathology 33, no. 6 (November 1996): 633–38. http://dx.doi.org/10.1177/030098589603300601.

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As part of long-term pulmonary carcinogenesis studies in dogs, it is important to analyze the incidence of spontaneous lung neoplasia. Primary lung carcinoma incidence was determined in two control populations of Beagle dogs observed for their life spans. One population comprised 216 dogs (112 males and 104 females) that were controls for life span studies, and another comprised 182 dogs (50 males and 132 females) that were retirees from a breeding colony. Forty lung neoplasms were noted in the 398 dogs; 35 neoplasms were carcinomas classified as papillary adenocarcinoma (20), bronchioloalveolar carcinoma (9), adenosquamous carcinoma (5), or bronchial gland carcinoma (1). The other five neoplasms were a malignant fibrous histiocytoma, three adenomas, and a fibroma. The crude incidence of lung carcinomas averaged for both populations was 8.8% (35/398) and was dominated by a relatively high incidence of lung neoplasia in aged dogs, those dying after the median life span of 13.6 years.
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de Perrot, Marc, Susan Chernenko, Thomas K. Waddell, Yaron Shargall, Andrew F. Pierre, Michael Hutcheon, and Shaf Keshavjee. "Role of Lung Transplantation in the Treatment of Bronchogenic Carcinomas for Patients With End-Stage Pulmonary Disease." Journal of Clinical Oncology 22, no. 21 (November 1, 2004): 4351–56. http://dx.doi.org/10.1200/jco.2004.12.188.

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Purpose To determine the role of lung transplantation in the treatment of patients presenting with bronchogenic carcinoma and end-stage lung disease. Methods An international survey was conducted to determine the outcome of patients with bronchogenic carcinoma in the explanted lung at the time of transplantation. A group of 69 patients was collected from 33 centers. Results Twenty-six patients underwent 29 lung transplantations for advanced multifocal bronchioloalveolar carcinoma (BAC) as the primary indication for transplantation, and 13 developed a recurrence, with an overall 5-year actuarial survival of 39%. Incidental bronchogenic carcinomas classified as stage I (n = 22), II (n = 12), and III (n = 2), or as incidental multifocal BAC (n = 7), were found in the explanted lung of the remaining 43 patients. The 5-year actuarial survival was 51% in patients with stage I carcinomas, and was significantly better than for patients with stage II and III carcinomas (survival of 14%) or with incidental multifocal BAC (survival of 23%). Time from transplantation to recurrence and from recurrence to death was significantly longer in patients with multifocal BAC than in patients with other types of bronchogenic carcinoma. In addition, the site of recurrence was limited to the transplanted lung in 88% of the patients with multifocal BAC, whereas it was always widespread in patients with other types of bronchogenic carcinoma. Conclusion This study demonstrates that long-term survival can be achieved after lung transplantation in patients with stage I bronchogenic carcinoma or with advanced multifocal BAC.
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Rosen, Lauren Elizabeth, and Paolo Gattuso. "Neuroendocrine Tumors of the Breast." Archives of Pathology & Laboratory Medicine 141, no. 11 (November 1, 2017): 1577–81. http://dx.doi.org/10.5858/arpa.2016-0364-rs.

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Primary neuroendocrine tumors of the breast are a rare and underrecognized subtype of mammary carcinoma. Neuroendocrine tumors of the breast occur predominately in postmenopausal women. The tumors are subclassified into well-differentiated and poorly differentiated neuroendocrine tumors, and invasive breast carcinoma with neuroendocrine features. Well-differentiated tumors show architectural similarity to carcinoids of other sites but lack characteristic neuroendocrine nuclei. Poorly differentiated neuroendocrine tumors are morphologically identical to small cell carcinoma of the lung. Neuroendocrine differentiation, seen in up to 30% of invasive breast carcinomas, is most commonly associated with mucinous and solid papillary carcinomas. The diagnosis of neuroendocrine differentiation requires expression of the neuroendocrine markers synaptophysin or chromogranin. The main differential diagnosis is a metastatic neuroendocrine tumor from an extramammary site. Neuroendocrine tumors of the breast are treated similarly to other invasive breast carcinomas. Although no consensus has been reached on the prognosis, most studies suggest a poor outcome.
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de las Mulas, J. Martín, A. Espinosa de los Monteros, L. Carrasco, M. van Niel, and A. Fernández. "Immunohistochemical Distribution Pattern of Intermediate Filament Proteins in 50 Feline Neoplasms." Veterinary Pathology 32, no. 6 (November 1995): 692–701. http://dx.doi.org/10.1177/030098589503200611.

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Twenty-eight epithelial and 22 nonepithelial feline tumors were studied immunohistochemically. Epithelial tumors were 10 squamous cell carcinomas, two basal cell tumors, two sebaceous gland carcinomas, three apocrine gland carcinomas, three thyroid papillary carcinomas, one thyroid solid carcinoma, one renal clear cell carcinoma, one renal papillary carcinoma, one endometrial carcinoma, and four lung bronchioloalveolar carcinomas. Nonepithelial tumors were 10 fibrosarcomas, one liposarcoma, one leiomyosarcoma, one rhabdomyosarcoma, one hemangiosarcoma, two mast cell tumors, one osteosarcoma, three melanomas, and two lymphomas. Commercially available antibodies directed against high- and low-molecular-weight keratins (keratin, RCK-102, NCL-5D3), vimentin, desmin, glial fibrillary acidic protein (GFAP), and neurofilament intermediate filament (IF) proteins were used in the avidin—biotin–peroxidase complex technique on formalin-fixed, paraffin-embedded tumor tissue samples. All epithelial tumors except the endometrial carcinoma expressed some type of keratin protein. Squamous cell carcinomas expressed high-molecular-weight keratins exclusively. Coexpression of high- and low-molecular-weight keratins was observed in one basal cell tumor, sebaceous and apocrine adenocarcinomas, and thyroid, renal, and lung carcinomas. In addition to keratins, vimentin immunoreactivity was found in all basal cell tumors, all sebaceous gland, thyroid papillary, renal, and lung adenocarcinomas, and one of the apocrine gland adenocarcinomas. Immunoreactivity with GFAP antibody was found in one basal cell tumor and one sebaceous gland adenocarcinoma. The endometrial carcinoma did not react with any of the antibodies applied. Nonepithelial tumors analyzed expressed either vimentin (fibrosarcomas, liposarcoma, haemangiosarcoma, mast cell tumors, osteosarcomas, melanomas) or vimentin and desmin (leiomyosarcoma, rhabdomyosarcoma, one fibrosarcoma) IF proteins exclusively. Lymphomas did not react with any of the antibodies employed. These findings indicate that IF proteins antibodies can be included in diagnostic panels of antibodies for immunocharacterization of feline tumors. In addition, they can be used as a basis for the diagnoses of poorly differentiated or undifferentiated feline neoplasms.
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Stieber, P., H. Dienemann, U. Hasholzner, P. G. Fabricius, C. Schambeck, M. Weinzierl, S. Poley, et al. "Comparison of Cyfra 21–1, Tpa and Tps in Lung Cancer, Urinary Bladder Cancer and Benign Diseases." International Journal of Biological Markers 9, no. 2 (April 1994): 82–88. http://dx.doi.org/10.1177/172460089400900204.

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Recently CYFRA 21–1, a new tumor marker measuring a fragment of cytokeratin 19, was introduced and proved to be suitable for therapy monitoring and follow-up of non-small cell lung carcinomas (NSCLC), in particular squamous cell carcinomas. Besides CYFRA 21–1 there are two other tumor markers, tissue polypeptide antigen (TPA) and tissue polypeptide-specific antigen (TPS), which also measure various cytokeratins in serum. In a retrospective study we investigated the clinical significance of these three cytokeratin markers in lung cancer and in carcinoma of the urinary bladder. For this purpose we investigated the sera of 50 healthy persons, 273 patients with various benign diseases, 218 patients with histologically proven lung cancer and 88 patients with carcinoma of the urinary bladder. In a first step the specificity was established for the different reference groups and the cutoff values were fixed at a specificity of 95%. In lung cancer the single and combined sensitivities were calculated versus benign lung diseases (n = 58) as reference group. With single determinations CYFRA 21–1 proved to have the highest sensitivity in lung cancer in general (61%), in non-small cell lung carcinomas (64%), in squamous cell carcinomas (79%), in adenocarcinomas (54%) and in large cell carcinomas (65%). In small cell lung carcinomas (SCLC) NSE was confirmed to be the marker of choice (55%). With combined determinations a clear increase in sensitivity could only be reached in large cell carcinomas (CYFRA 21–1 + TPA: 77%) and in small cell carcinomas (CYFRA 21–1 + NSE: 62%). In cancer of the urinary bladder the sensitivities were established versus benign urological diseases (n = 73). CYFRA 21–1 showed with 38% true positive test results the highest sensitivity compared to TPA (27%) and TPS (23%). From our investigations it was evident that TPA detects at least partially the same substance as CYFRA 21–1 (the sensitivities compared to the markers TPS, CEA, SCC and NSE were rather high, but not as high as for CYFRA 21–1) whereas TPS represents a completely different parameter of clinical chemistry (lowest number of true positive test results over the whole investigation), which apparently measures something completely different. These findings cleary correspond with the very recent results of immunoblotting comparing CYFRA 21–1, TPA and TPS.
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Terada, Tadashi. "Cytokeratin-negative small cell lung carcinoma." Rare Tumors 3, no. 4 (November 1, 2011): 120–21. http://dx.doi.org/10.4081/rt.2011.e38.

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23

Naranjo Gómez, José Manuel, Jose Fernando Val Bernal, Pilar García Arranz, Servando Lazuén Fernández, and Jose Javier Gómez Roman. "Alterations in the Expression of p53, KLF4, and p21 in Neuroendocrine Lung Tumors." Archives of Pathology & Laboratory Medicine 138, no. 7 (July 1, 2014): 936–42. http://dx.doi.org/10.5858/arpa.2013-0119-oa.

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Context.—Neuroendocrine lung neoplasms are a heterogeneous group of tumors with different clinical behavior and prognosis. Objectives.—To evaluate the expression of p53, KLF4, and p21 in neuroendocrine lung neoplasms and to analyze the influence that expression has on the prognosis of those tumors. Design.—All neuroendocrine lung neoplasms (N = 109) resected in our institution were reviewed, with the collection of histologic slides and paraffin blocks of 47 typical carcinoids (43%), 9 atypical carcinoids (8%), 35 large cell neuroendocrine carcinomas (32%), and 18 small cell lung carcinomas (17%), as well as 10 tumorlets (100%). Four tissue microarrays were performed. Follow-up was assessed in all cases (119 of 119; 100%). Results.—p53 protein immunostaining results were negative in both the tumorlets and typical carcinoids and were overexpressed in 11% (1 of 9) of the atypical carcinoids and in 68% (36 of 53) of the carcinomas. KLF4 results were positive in all tumorlets (10 of 10; 100%), 32% (15 of 47) of the typical carcinoids, 44% (4 of 9) of the atypical carcinoids, and 62% (33 of 53) of the carcinomas. p21 expression did not differ among the groups. The lack of KLF4 and p21 expression was associated with an accumulation of aggressive features in typical carcinoids (P = .04 and P = .004, respectively, Fisher exact test). Conclusions.—p53, KLF4, and p21 showed altered expression patterns in pulmonary neuroendocrine neoplasms. Lack of KLF4 and p21 expression was associated with accumulation of aggressive features in typical carcinoids.
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Patra, Anupam, Amitava Sengupta, Supriya Sarkar, and Malay Kumar Maikap. "Atypical Radiographic Presentation of Adenocarcinoma Lung." Bangladesh Journal of Medical Science 13, no. 1 (December 25, 2013): 70–72. http://dx.doi.org/10.3329/bjms.v13i1.13037.

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Adenocarcinoma and squamous cell carcinoma are the most frequently diagnosed histological subtype of bronchogenic carcinomas. Though metastatic lesions in lung are common in both the varieties, cavity formation has been documented only with squamous cell type. Here we are going to report a case of pulmonary adenocarcinoma with multiple nodular metastases in both lungs which show central necrosis mimicking cavities. DOI: http://dx.doi.org/10.3329/bjms.v13i1.13037 Bangladesh Journal of Medical Science Vol. 13 No. 01 January2014: 70-72
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25

Katsetos, Christos D., George Kontogeorgos, Jennian F. Geddes, Mary M. Herman, Hera Tsimara-Papastamatiou, Yunxia Yu, Lazaros I. Sakkas, et al. "Differential Distribution of the Neuron-Associated Class III β-Tubulin in Neuroendocrine Lung Tumors." Archives of Pathology & Laboratory Medicine 124, no. 4 (April 1, 2000): 535–44. http://dx.doi.org/10.5858/2000-124-0535-ddotna.

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AbstractObjective.—To study the immunoreactivity profile of the neuron-associated class III β-tubulin isotype (β III) in epithelial lung tumors.Design.—One hundred four formalin-fixed, paraffin-embedded primary and metastatic lung cancer specimens were immunostained with an anti–β III mouse monoclonal antibody (TuJ1) and an anti–β III affinity-purified rabbit antiserum. Paraffin sections from fetal, infantile, and adult nonneoplastic lung tissues were also examined.Results.—In the fetal airway epithelium, β III staining is detected transiently in rare Kulchitsky-like cells from lung tissues corresponding to the pseudoglandular and canalicular but not the saccular or alveolar stages of development. β III is absent in healthy, hyperplastic, metaplastic, and dysplastic airway epithelium of the adult lung. In contrast, β III is highly expressed in small cell lung cancer, large cell neuroendocrine carcinoma, and in some non–small cell lung cancers, particularly adenocarcinomas. There is no correlation between expression of β III and generic neuroendocrine markers, such as chromogranin A and/or synaptophysin, in pulmonary adenocarcinomas. Also, focal β III staining is present in primary and metastatic adenocarcinomas (to the lung) originating in the colon, prostate, and ovary. β III is expressed to a much lesser extent in atypical carcinoids and is rarely detectable in typical carcinoids and squamous cell carcinomas of the lung. The distribution of β III in small cell lung cancer and adenocarcinoma metastases to regional lymph nodes and brain approaches 100% of tumor cells, which is substantially greater than in the primary tumors.Conclusions.—In the context of neuroendocrine lung tumors, β III immunoreactivity is a molecular signature of high-grade malignant neoplasms (small cell lung cancer and large cell neuroendocrine carcinoma) although its importance in atypical carcinoids must be evaluated further. In addition, β III may be a useful diagnostic marker in distinguishing between small cell lung cancers and certain non–small cell lung cancers (poorly differentiated squamous cell carcinomas), especially in small biopsy specimens. To our knowledge, β III is the only tumor biomarker that exhibits a substantially more widespread distribution in poorly differentiated than in better differentiated pulmonary neuroendocrine tumors. However, the significance of β III phenotypes in non–small cell lung cancer, particularly adenocarcinoma, with respect to neuroendocrine differentiation and prognostic value, requires further evaluation.
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Kasajima, Atsuko, Yuichi Ishikawa, Ayaka Iwata, Katja Steiger, Naomi Oka, Hirotaka Ishida, Akira Sakurada, et al. "Inflammation and PD-L1 expression in pulmonary neuroendocrine tumors." Endocrine-Related Cancer 25, no. 3 (March 2018): 339–50. http://dx.doi.org/10.1530/erc-17-0427.

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In the light of novel cancer immune therapies, the status of antitumor inflammatory response and its regulation has gained much attention in patients with lung cancer. Ample datasets exist for non-small-cell lung cancer, but those for pulmonary neuroendocrine tumors are scarce and controversial. Here, tumor-associated inflammation, CD8+ cell infiltration and PD-L1 status were evaluated in a cohort of 57 resected carcinoids and 185 resected neuroendocrine carcinomas of the lung (58 large cell carcinomas and 127 small cell carcinomas). Data were correlated with clinicopathological factors and survival. Moderate or high tumor-associated inflammation was detected in 4 carcinoids (7%) and in 37 neuroendocrine carcinomas (20%). PD-L1 immunoreactivity was seen in immune cells of 73 (39%) neuroendocrine carcinomas, while tumor cells were labeled in 21 (11%) cases. Inflammatory cells and tumor cells in carcinoids lacked any PD-L1 expression. In neuroendocrine carcinomas, PD-L1 positivity in immune cells, but not in tumor cells, was associated with intratumoral CD8+ cell infiltration (P < 0.001), as well as with the severity of tumor-associated inflammation (P < 0.001). In neuroendocrine carcinomas, tumor-associated inflammation and PD-L1 positivity in immune cells correlated with prolonged survival and the latter factor was also an independent prognosticator (P < 0.01, hazard ratio 0.4 for overall survival,P < 0.001 hazard ratio 0.4 for disease-free survival). Taken together, in neuroendocrine tumors, antitumor inflammatory response and PD-L1 expression are largely restricted to neuroendocrine carcinomas, and in this tumor entity, PD-L1 expression in inflammatory cells is positively correlated to patient survival.
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Pothina, Yugandhar, Gudeli Vahini, M. Lalitha Sree, and Thota Asha. "A Significant Study on EGFR Mutations in Lung Carcinomas." Annals of Pathology and Laboratory Medicine 6, no. 6 (June 24, 2019): A327–333. http://dx.doi.org/10.21276/apalm.2366.

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28

Kalabova, Hana, Josef Dvorak, Radomír Hyspler, Alena Ticha, Lenka Krcmova, Lubor Urbanek, Dagmar Solichova, and Bohuslav Melichar. "Urinary Neopterin in Patients Treated with Gefitinib." Pteridines 18, no. 1 (February 2007): 95–100. http://dx.doi.org/10.1515/pteridines.2007.18.1.95.

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Abstract Inhibitors of epidermal growth factor receptor (EGFR), including low molecular weight inhibitor erlotinib and gefitinib, have been demonstrated to be active antitumor agents in patients with non-small cell lung carcinoma and head and neck carcinomas. Increased concentrations of urinary neopterin, an indicator of systemic immune activation, have also been reported in patients with lung carcinoma and head and neck carcinomas. EGFR blockade has been reported to induce immune activation. We have measured, using high performance liquid chromatography, urinary neopterin in patients with non-small cell lung carcinoma and head and neck carcinomas treated with gefitinib. Intestinal permeability was also investigated at baseline by measuring, using capillary gas chromatography, urinary xylose, mannitol and lactulose after oral challenge. Compared to controls, urinary neopterin was significantly increased in patients with non-small cell lung carcinoma. No significant change in urinary neopterin was observed during the therapy with gefitinib. A significant correlation was observed between urinary neopterin and xylose absorption (rs = -0.58, p <0.05), lactulose/mannitol (rs = 0.75, p <0.01), and lactulose/ xylose (rs = 0.62, p <0.05) ratios. In conclusion, EGFR blockade had no effect on systemic immune activation, evaluated with urinary neopterin. A significant correlation has been observed between urinary neopterin and parameters of intestinal permeability and absorption.
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Borczuk, Alain C. "Uncommon Types of Lung Carcinoma With Mixed Histology: Sarcomatoid Carcinoma, Adenosquamous Carcinoma, and Mucoepidermoid Carcinoma." Archives of Pathology & Laboratory Medicine 142, no. 8 (August 1, 2018): 914–21. http://dx.doi.org/10.5858/arpa.2017-0584-ra.

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Context.— Lung tumors are histologically heterogeneous, but classification of lung carcinoma has prognostic impact and increasingly, specific molecular correlates. Objective.— To update the gross, microscopic, and molecular pathology of unusual lung carcinomas to assure accurate classification. In entities with mixed histology, the recognition of specific features or rare patterns is critical to diagnosis. These diagnoses can identify tumors with aggressive clinical behavior, and diagnostic pitfalls can therefore result in underdiagnosis of these already rare entities. Incorrect classification of more indolent tumors into the more aggressive categories can also occur. In the area of molecular pathology, these unusual tumors have a specific spectrum of molecular alterations. Data Sources.— PubMed searches for lung and sarcomatoid carcinoma, pleomorphic carcinoma, blastoma, carcinosarcoma, and adenosquamous and mucoepidermoid carcinoma were undertaken and this information was integrated with clinical experience of the author. Conclusions.— These uncommon carcinomas have specific clinicopathologic features, and attention to their gross and microscopic pathology leads to classification with important associated molecular findings.
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30

Klemen, H., F. M. Smolle-Jüttner, and H. H. Popper. "Morphological and immunohistochemical study of typical and atypical carcinoids of the lung with clinico-pathological correlation." Endocrine-Related Cancer 1, no. 4 (1994): 53–62. http://dx.doi.org/10.1677/erc.0.0010053.

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ABSTRACT Typical and atypical carcinoids are neuroendocrine epithelial lung tumours which are difficult to distinguish. Confusion has been introduced by designating atypical carcinoids as well differentiated neuroendocrine carcinomas and including some tumours which are large cell neuroendocrine carcinomas. We therefore investigated 32 typical and 23 atypical carcinoids of the lung, and 9 combined forms of atypical carcinoid and small cell carcinoma. The following parameters were each independently correlated in a multivariate analysis with 10-year survival data: nuclear and nucleolar polymorphism, mitotic counts, vascular invasion, lymph node metastasis, structural pattern, location of the tumours, immunohistochemistry, age and sex of the patients. Typical carcinoids were characterized by an absence of vascular invasion and lymph node metastases, and a mean mitotic rate of 0.75/10 high power fields (HPFs), while atypical carcinoids were characterized by vascular invasion and/or metastases, a mean mitotic rate of 4.25/10 HPFs and nuclear pleomorphism. Combined forms of atypical carcinoid and small cell carcinoma were characterized by vascular invasion, metastases and a mean mitotic rate of 20.7/10 HPFs. Vascular invasion, lymph node metastases, mitotic counts and nuclear pleomorphism significantly correlated with 10-year survival data, whereas location, size and structural pattern of the tumour, age and sex did not correlate with survival. All tumours were positive for cytokeratins and at least two out of three general neuroendocrine markers. However, positive reactivity for different peptides, hormones, and neurotransmitters did not correlate with one of the structural subtypes of carcinoid or with patient survival.
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31

Butnor, Kelly J., James L. Burchette, Thomas A. Sporn, Samuel P. Hammar, and Victor L. Roggli. "The Spectrum of Kit (CD117) Immunoreactivity in Lung and Pleural Tumors: A Study of 96 Cases Using a Single-Source Antibody With a Review of the Literature." Archives of Pathology & Laboratory Medicine 128, no. 5 (May 1, 2004): 538–43. http://dx.doi.org/10.5858/2004-128-538-tsokci.

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Abstract Context.—The development of successful chemotherapeutic agents directed against the Kit receptor tyrosine kinase protein has generated intense interest in the Kit (CD117) immunoreactivity of various neoplasms. Immunoreactivity for Kit in small cell lung carcinoma (SCLC) has been well established. However, data on Kit immunostaining in other lung tumors is limited. Likewise, while solitary fibrous tumors of the gastrointestinal tract have been examined for Kit expression, the Kit staining characteristics of their counterpart in the pleura, namely, localized fibrous tumor, are not well known. Objective.—To characterize the Kit immunohistochemical profiles of major types of lung and pleural tumors. Design.—We stained 60 lung carcinomas, including 11 SCLCs, 4 large cell neuroendocrine carcinomas, 22 squamous cell carcinomas, 23 adenocarcinomas, 11 pulmonary carcinoid tumors, 19 pleural malignant mesotheliomas, and 6 localized pleural fibrous tumors with a commonly used polyclonal Kit antibody. Results.—Small cell lung carcinomas demonstrated Kit staining in 82% of cases, nearly all of which demonstrated moderate to intense immunoreactivity. Immunostaining was observed in 25% of large cell neuroendocrine carcinomas. Focal staining was observed in 9% of squamous cell carcinomas and 17% of adenocarcinomas. None of the pulmonary carcinoid tumors were immunoreactive. Moderately intense immunostaining was present in 50% of localized fibrous tumors. Malignant mesotheliomas were nonimmunoreactive for Kit in 95% of cases. Conclusion.—Non–small cell lung carcinomas showed very limited expression of Kit. Lung tumors with neuroendocrine differentiation exhibited a wide spectrum of Kit immunoreactivity, ranging from rare in pulmonary carcinoid tumors to frequent in SCLC. The high frequency of Kit immunostaining in SCLC has important potential therapeutic implications. Demonstration of Kit positivity in some localized fibrous tumors in this study contrasts with absent immunoreactivity in solitary fibrous tumors of the gastrointestinal tract. The paucity of Kit staining in malignant mesothelioma suggests these tumors are unlikely to respond to currently available tyrosine kinase inhibitors.
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Tacha, David, Ryan Bremer, Thomas Haas, and Weiman Qi. "An Immunohistochemical Analysis of a Newly Developed, Mouse Monoclonal p40 (BC28) Antibody in Lung, Bladder, Skin, Breast, Prostate, and Head and Neck Cancers." Archives of Pathology & Laboratory Medicine 138, no. 10 (February 14, 2014): 1358–64. http://dx.doi.org/10.5858/arpa.2013-0342-oa.

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Context.—Immunohistochemistry is important to the pathologist for accurate diagnosis of lung cancer. In recent studies, a rabbit polyclonal p40 (RPp40) antibody demonstrated equivalent staining versus anti-p63 in lung squamous cell carcinoma, and superior specificity because it stains a lesser percentage of lung adenocarcinoma. Objectives.—To develop an anti-p40 mouse monoclonal antibody (MMp40) for immunohistochemistry, and to evaluate its sensitivity and specificity in normal and neoplastic tissues, with emphasis on lung cancer. Design.—The MMp40 (BC28) antibody was developed and tested for specificity and sensitivity on normal (n = 34) and neoplastic tissues (n = 493). Staining of MMp40, p63, and RPp40 were directly compared in lung cancers, and MMp40 was evaluated in breast, bladder, skin, prostate, and head and neck cancers. Benign prostate glands and prostatic intraepithelial neoplasia were also tested in a direct comparison of MMp40 versus p63. Results.—The MMp40 provided equivalent staining versus RPp40 and p63 in lung squamous cell carcinoma, but stained a lesser percentage of lung adenocarcinoma than p63 did. The MMp40 staining was observed in a greater percentage of urothelial carcinomas, squamous and basal cell skin cancers, and head and neck cancers of squamous cell origin. No breast-infiltrating ductal carcinomas or prostatic adenocarcinomas were stained. The MMp40 expression in basal cells of prostate glands and prostatic intraepithelial neoplasia were almost identical to those of p63. Conclusion.—The MMp40 (BC28) monoclonal antibody is a high-quality screening antibody for determining squamous cell carcinoma in lung cancers, skin cancers of squamous or basal cell origin, squamous cell head and neck cancers, and urothelial carcinomas.
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Rekhtman, Natasha. "Lung neuroendocrine neoplasms: recent progress and persistent challenges." Modern Pathology 35, S1 (October 18, 2021): 36–50. http://dx.doi.org/10.1038/s41379-021-00943-2.

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AbstractThis review summarizes key recent developments relevant to the pathologic diagnosis of lung neuroendocrine neoplasms, including carcinoids, small cell lung carcinoma (SCLC), and large cell neuroendocrine carcinoma (LCNEC). Covered are recent insights into the biological subtypes within each main tumor type, progress in pathological diagnosis and immunohistochemical markers, and persistent challenging areas. Highlighted topics include highly proliferative carcinoids and their distinction from small cell and large cell neuroendocrine carcinomas (NECs), the evolving role of Ki67, the update on the differential diagnosis of NEC to include thoracic SMARCA4-deficient undifferentiated tumors, the recent data on SCLC transcriptional subtypes with the emergence of POU2F3 as a novel marker for the diagnosis of SCLC with low/negative expression of standard neuroendocrine markers, and the update on the diagnosis of LCNEC, particularly in biopsies. There has been remarkable recent progress in the understanding of the genetic and expression-based profiles within each type of lung neuroendocrine neoplasm, and it is hoped that these insights will enable the development of novel diagnostic, prognostic, and predictive biomarkers to aid in the pathologic assessment of these tumors in the future.
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Metovic, Jasna, Marco Barella, Fabrizio Bianchi, Paul Hofman, Veronique Hofman, Myriam Remmelink, Izidor Kern, et al. "Morphologic and molecular classification of lung neuroendocrine neoplasms." Virchows Archiv 478, no. 1 (January 2021): 5–19. http://dx.doi.org/10.1007/s00428-020-03015-z.

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AbstractNeuroendocrine neoplasms (NENs) of the lung encompass neuroendocrine tumors (NETs) composed of typical (TC) and atypical (AC) carcinoids and full-fledged carcinomas (NECs) inclusive of large cell neuroendocrine carcinoma (LCNEC) and small cell carcinoma (SCLC). NETs and NECs are thought to represent distinct and separate lesions with neither molecular overlap nor common developmental continuum. Two perspectives were addressed regarding the morphologic and molecular classification of lung NENs: (i) a supervised approach by browsing the traditional classification, the relevant gene alterations, and their clinical implications; and (ii) an unsupervised approach, by reappraising neoplasms according to risk factors and natural history of disease to construct an interpretation model relied on biological data. We herein emphasize lights and shadows of the current classification of lung NENs and provide an alternative outlook on these tumors focused on what we currently know about the biological determinants and the natural history of disease.
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35

Medenica, Milic, Miras Medenica, Olivera Bojovic, Ivan Soldatovic, and Ivana Durutovic. "Changing trends in incidence of lung cancer by histological type in Montenegro." Srpski arhiv za celokupno lekarstvo 142, no. 1-2 (2014): 23–28. http://dx.doi.org/10.2298/sarh1402023m.

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Introduction. Lung cancer is one of the most common malignant neoplasms, as well as the most common cause of death cancer. Most lung cancers are squamous cell carcinomas, small cell carcinomas or adenocarcinomas. Objective. Examining changes in trends of lung cancer incidence in Montenegro by histological type during a 15-year period, from 1997 to 2011. Methods. During the study period, histopathological confirmation was obtained for all primary lung cancer cases in the only hospital for lung diseases in the country. Based on the data from medical records, patients were classified by time period, sex, age groups and smoking history. Descriptive method was used. Results. Ratio between incidences of adenocarcinoma and squamous cell carcinoma changes in males, with a significant increase in the incidence rate of adenocarcinoma and drop in the rate of squamous cell carcinoma (p<0.001). In addition, statistically significant (p<0.05) decrease in the incidence of NSCLC (non-small cell lung cancer) and an increase in the incidence of SCLC (small cell lung cancer) was found. A statistically significant increase in linear trend in the incidence of small cell carcinoma was noted in females (p<0.005). Conclusion. Incidence rates of adenocarcinoma and small cell carcinoma have increased during the study period.
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36

Fang, Yan, Xiao Ping Wang, Huan Ping Lin, and Qiao Xia Wang. "Significance of Clinicopathology and Expression of Heat Shock Protein 72 in Human Primary Lung Carcinomas." Advanced Materials Research 459 (January 2012): 242–46. http://dx.doi.org/10.4028/www.scientific.net/amr.459.242.

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Heat shock protein 72 (HSP72) and glycoprotein 96 (gp96) are highly expressed in cancer tissues. Recent studies indicate the possible roles of HSP72 and gp96 in the development and progression of lung carcinomas but detailed information is still ambiguous. The aim of the study is to investigate the correlation between clinicopathology and immunolocalization of HSP72 and gp96 in human lung carcinoma. Immunohistochemistry demonstrated that HSP72 and gp96 expression in lung carcinomas with metastasis was significantly higher than those with non-metastasis. HSP72 and gp96 expression were significantly associated with the presence of tumor infiltration, lymph node and remote metastasis.
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Chen, Mai-Lin, Xiao-Ting Li, Yi-Yuan Wei, Li-Ping Qi, and Ying-Shi Sun. "Diagnostic Value of Spectral CT Parameters in Differentiating Different Types of Lung Cancer." Journal of Medical Imaging and Health Informatics 10, no. 8 (August 1, 2020): 1804–8. http://dx.doi.org/10.1166/jmihi.2020.3189.

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Background: This study proposed to quantitatively assess the value of spectral CT imaging parameters in differentiating different pathological types of lung cancer. Methods: Eighty five patients with lung cancer (66 non-mucinous adenocarcinomas, 7 Squamous cell carcinomas, 8 small cell carcinomas, 1 mucinous adenocarcinoma, 1 sarcomatoid carcinoma, 1 carcinoid, 1 large cell carcinoma) underwent CT plain scan, contrast enhanced CT scans in arterial phase (a) and venous phase (v) with spectral imaging mode on a GE Revolution Xtream CT scanner. The Spectral CT Imaging parameters: Iodine concentrations (IC) of lesion in arterial phase (ICLa) and venous phase (ICLv), Normalized IC (NICa/NICv)-normalized to the IC in the aorta, slope of the spectral HU curve (λHUa/λHUv) and monochromatic CT number (CT40keVa/CT40keVv, CT70keVa/CT70keVv) enhancement on 40 keV and 70 keV images were calculated. The One-way ANOVA or Kruskal-Wallis test was used to compare quantitative parameters among lung squamous carcinoma, small cell carcinoma and lung adenocarcinoma groups, Bonferroni method was used to correct P value for multiple comparisons. Results: Among the different pathological types of lung cancers, these quantitative parameters of spectral CT imaging CT70keVa has significant difference. The CT70keVa of lung adenocarcinoma was lower than small cell carcinoma (P = 0.048) and squamous cell carcinoma (P = 0.039), respectively. And these CT40keVa, CT70keVa/CT70keVv parameters of lung adenocarcinoma was lower than non-adenocarcinomas (P < 0.05). However, there was no significant difference in spectral CT parameters between small cell lung cancer and squamous cell lung cancer, small cell lung cancer and non-small cell carcinoma (P > 0.05). Conclusion: Spectral CT parameters may be of value in distinguishing different pathological types of lung cancer.
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Björkqvist, A. M., L. Tammilehto, S. Nordling, S. Anttila, K. Mattson, and S. Knuutila. "Mesothelioma and lung carcinomas." Cancer Genetics and Cytogenetics 98, no. 2 (October 1997): 149. http://dx.doi.org/10.1016/s0165-4608(97)90239-9.

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39

Grove, ANNI. "Amylase in lung carcinomas." APMIS 102, no. 1-6 (January 1994): 135–44. http://dx.doi.org/10.1111/j.1699-0463.1994.tb04858.x.

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40

Marchetti, Antonio, Carla Martella, Lara Felicioni, Fabio Barassi, Simona Salvatore, Antonio Chella, Pier P. Camplese, et al. "EGFR Mutations in Non–Small-Cell Lung Cancer: Analysis of a Large Series of Cases and Development of a Rapid and Sensitive Method for Diagnostic Screening With Potential Implications on Pharmacologic Treatment." Journal of Clinical Oncology 23, no. 4 (February 1, 2005): 857–65. http://dx.doi.org/10.1200/jco.2005.08.043.

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Purpose It has been reported that EGFR mutations in lung carcinomas make the disease more responsive to treatment with tyrosine kinase inhibitors. We decided to evaluate the prevalence of EGFR mutations in a large series of non–small-cell lung carcinomas (NSCLCs) and to develop a rapid and sensitive screening method. Patients and Methods We examined 860 consecutive NSCLC patients for EGFR mutations in exons 18, 19, and 21 using a dual technical approach—direct sequencing of polymerase chain reaction (PCR) products and PCR single-strand conformation polymorphism (SSCP) analysis. Moreover, all lung adenocarcinomas were analyzed for K-ras mutations at codon 12 by allele-specific oligoprobe hybriditations. Results There were no EGFR mutations in 454 squamous carcinomas and 31 large cell carcinomas investigated. Thirty-nine mutations were found in the series of 375 adenocarcinomas (10%). Mutations were present in 26% of 86 bronchioloalveolar carcinomas (BACs) and in 6% of 289 conventional lung adenocarcinomas; P = .000002. EGFR mutations and K-ras mutations were mutually exclusive. A multivariable analysis revealed that BAC histotype, being a never smoker, and female sex were independently associated with EGFR mutations (odds ratios: 4.542, 3.632, and 2.895, respectively). The SSCP analysis was accurate and sensitive, allowing identification of mutations that were undetectable (21% of cases) by direct sequencing. Conclusion Mutations in the EGFR tyrosine kinase domain define a new molecular type of lung carcinoma, more frequent in particular subsets of patients. The SSCP assay is a rapid and reliable method for the detection of EGFR kinase domain mutations in lung cancer.
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41

Badve, Sunil S., Rachel Dougherty, Michael Balatico, Kenneth A. Kesler, Patrick Loehrer, and Yesim Gökmen-Polar. "Thymic Carcinomas and Second Malignancies: A Single-Center Review." Cancers 13, no. 10 (May 19, 2021): 2472. http://dx.doi.org/10.3390/cancers13102472.

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Thymic carcinomas account for less than 0.01% of new cancer diagnoses annually and are more aggressive than thymomas. Autoimmune disorders have been associated with thymomas and only recently with thymic carcinomas. Second malignancies are well described after thymomas. The aim of this study was to analyze the incidence of second malignancies in patients with thymic carcinomas. All cases of thymic carcinomas were identified from the pathology archives of Indiana University. Histological materials were reviewed and further correlated with clinical data to identify incidence of second cancers in patients with thymic carcinomas. Histological material was available for review in 92 cases of thymic carcinoma. Clinical data were available for 85 patients. Fourteen of these (16.5%) patients had a second malignancy; these included small cell lung carcinoma, “testicular cancer”, embryonal carcinoma, seminoma, breast carcinoma (two cases), prostatic adenocarcinoma, Hodgkin’s lymphoma, thyroid carcinoma, bladder carcinoma (two cases), renal cell carcinoma, and melanoma. The latter could precede, be concurrent with, or follow the diagnosis thymic carcinoma. The incidence of second cancers in patients with thymic carcinomas is similar to that reported for thymomas. Abnormalities in immunological surveillance may be responsible for this high incidence of second malignancies in thymic tumors.
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42

Jorda, M., F. Mousavi, C. Gomez-Fernandez, Z. Maleki, G. Walker, and P. Ganjei-Azar. "P63 in cytologic material is helpful for detection of squamous differentiation in non-small cell carcinomas of lung and treatment selection." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 18052. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.18052.

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18052 Background: Bevacizumab in combination with carboplatin and paclitaxel improves overall response and survival in patients with advanced or recurrent non-small cell lung carcinoma. However, this drug is not recommended in patients with carcinomas with squamous differentiation. Therefore, identification of squamous cell component is desirable. In many instances, cytology is the diagnostic tool of choice; however, routine cytomorphology is limited in classification of non small-cell carcinomas into squamous and non-squamous subtypes. The aim of this study is to identify the value of immunocytochemistry for p63 in this distinction. Methods: Review of cytology records identified 51 consecutive pulmonary specimens with the diagnosis of non-small cell carcinoma (9 squamous cell carcinomas and 42 carcinomas without squamous differentiation). Histologically, they proved to be 26 squamous cell carcinomas and 25 non-small cell carcinomas without squamous differentiation. P63 immunocytochemical stain was performed on archival alcohol-fixed Papanicolaou stained cytology slides, using standard immunocytochemical methods. Results: Twenty-three (88 %) of the 26 histologically proven squamous cell carcinomas were positive for p63 on cytologic smears. Using p63, we detected 14 carcinomas with squamous differentiation not identified by cytomorphology. Smears from all carcinomas with squamous differentiation were positive for p63. Sensitivity of cytology for the detection of squamous differentiation increased from 35% to 88% using p63 immunocytochemistry (p=0.001, McNemar’s test). Four carcinomas with squamous differentiation were detected only in cytologic and not in corresponding histologic samples. Conclusions: 1- p63 is a useful marker for the detection of squamous differentiation in cytologic pulmonary samples; 2- p63 immunocytochemistry significantly increases the sensitivity for the identification of squamous cell carcinomas of lung from 35% to 88% (p=0.001); 3- p63 immunocytochemistry should be used in all pulmonary cytologic samples with a diagnosis of non-small cell carcinoma to improve therapeutic selection of patients; 4- Cytologic sampling may provide better representation of tumor subtypes. No significant financial relationships to disclose.
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43

Falkenstern-Ge, R. F., S. Bode-Erdmann, G. Ott, M. Wohlleber, and M. Kohlhäufl. "Late Lung Metastasis of a Primary Eccrine Sweat Gland Carcinoma 10 Years after Initial Surgical Treatment: The First Clinical Documentation." Case Reports in Oncological Medicine 2013 (2013): 1–4. http://dx.doi.org/10.1155/2013/167585.

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Background. Sweat gland carcinoma is a rare malignancy with a high metastatic potential seen more commonly in elderly patients. The scalp is the most common site of occurrence and it usually spreads to regional lymph nodes. Liver, lungs, and bones are the most common sites of distant metastasis. Late lung metastasis of sweat gland adenocarcinoma after a time span of 5 years is extremely rare.Aim. We report a patient with late lung metastasis of a primary sweat gland carcinoma 10 years after initial surgical resection.Conclusion. Sweat gland carcinomas are rare cancers with a poor prognosis. Surgery in the form of wide local excision and lymph node dissection is the mainstay of treatment. Late pulmonary metastases with a latency of 10 years have never been reported in the literature. This is the first clinical documentation of late lung metastasis from sweat gland carcinoma with a latency period of 10 years.
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44

Gruver, Aaron M., Mahul B. Amin, Daniel J. Luthringer, Danielle Westfall, Komal Arora, Carol F. Farver, Adeboye O. Osunkoya, Jesse K. McKenney, and Donna E. Hansel. "Selective Immunohistochemical Markers to Distinguish Between Metastatic High-Grade Urothelial Carcinoma and Primary Poorly Differentiated Invasive Squamous Cell Carcinoma of the Lung." Archives of Pathology & Laboratory Medicine 136, no. 11 (November 1, 2012): 1339–46. http://dx.doi.org/10.5858/arpa.2011-0575-oa.

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Context.—Distinction between primary lung carcinomas and metastases from other sites, especially the urinary tract, is a common diagnostic dilemma. As urothelial carcinomas can demonstrate a broad range of morphology and frequently demonstrate squamous differentiation, discerning metastatic urothelial carcinoma to the lung from primary pulmonary squamous cell carcinoma can be challenging. Objective.—To investigate immunostains that may aid in the distinction of urothelial carcinoma metastatic to the lung. Design.—Staining patterns of 14 markers in primary urothelial carcinoma of the bladder and primary squamous cell carcinoma of the lung were examined to establish a diagnostic panel. These antibodies were subsequently tested on tumors taken from 30 patients with a paired urinary tract and metastatic lung lesion. Results.—The best markers to distinguish poorly differentiated metastatic urothelial carcinoma from primary pulmonary squamous cell carcinoma were CK7, CK20, GATA-3, CK14, desmoglein-3, and uroplakin III, with the utility of the latter dependent upon the quantity of tissue available for analysis. The observed percentage positive staining in nonmetastatic urothelial carcinoma versus primary pulmonary squamous cell carcinoma with these antibodies was as follows: CK7 (100% versus 33%), CK20 (54% versus 7%), GATA-3 (78% versus 23%), CK14 (32% versus 77%), desmoglein-3 (11% versus 87%), and uroplakin III (14% versus 0%). Similar expression patterns were observed among the paired cases. Conclusion.—When interpreted in correlation with clinical history and histomorphology, a panel of immunostains including CK7, CK20, GATA-3, CK14, desmoglein-3, and uroplakin III may be a useful adjunct in the distinction of metastatic urothelial carcinoma to the lung.
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45

Badiali, Paolo, Marco Alloisio, and Luciano Lombardi. "Synchronous Triple Carcinoma of the Lung in One Patient." Tumori Journal 73, no. 5 (October 1987): 525–29. http://dx.doi.org/10.1177/030089168707300518.

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A case is reported of the simultaneous occurrence of a squamous cell carcinoma and a small cell carcinoma, both centrally located, in the right upper lobe and a peripheral adenocarcinoma in the right lower lobe. The simultaneous occurrence of three primary lung carcinomas is discussed in the light of a probable common cell origin.
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46

Shi, Jianhui, Haiyan Liu, Xiao-Jun Ma, Zongming Chen, Ming-Xiao He, Yuling Luo, and Fan Lin. "Ribonucleic Acid In Situ Hybridization Is a More Sensitive Method Than Immunohistochemistry in Detection of Thyroid Transcription Factor 1 and Napsin A Expression in Lung Adenocarcinomas." Archives of Pathology & Laboratory Medicine 140, no. 4 (April 1, 2016): 332–40. http://dx.doi.org/10.5858/arpa.2014-0644-oa.

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TTF-1 and napsin A immunomarkers have a crucial role in differentiating lung adenocarcinoma from lung squamous cell carcinoma and in identifying a primary lung adenocarcinoma when working on a tumor of unknown origin.Context.— To investigate the diagnostic sensitivity of ribonucleic acid in situ hybridization (RNAscope) in the detection of expression of these biomarkers in lung adenocarcinomas and to compare RNAscope to immunohistochemical techniques.Objectives.— Both RNAscope and the immunohistochemical assays for TTF-1 and napsin A were performed on tissue microarray sections containing 80 lung adenocarcinomas and 80 lung squamous cell carcinomas. The RNAscope assay for both TTF-1 and napsin A was also performed on 220 adenocarcinomas from various organs.Design.— The RNAscope assay for TTF-1 gave positive results in 92.5% (74 of 80) of the lung adenocarcinomas; in contrast, immunohistochemistry gave positive results in 82.5% (66 of 80) of those cases. The RNAscope assay for napsin A gave positive results in 90% (72 of 80) of lung adenocarcinomas; immunohistochemistry results were positive in 77.5% (62 of 80) of those cases. Napsin A expression was not seen in lung squamous cell carcinomas by either method. In contrast, TTF-1 expression was seen in 3.8% (3 of 80) (1+) and 10% (8 of 80) (1+) of the squamous cell carcinomas by immunochemistry and the RNAscope, respectively. All nonpulmonary adenocarcinoma results were negative for TTF-1 by the RNAscope assay.Results.— Preliminary data suggest that RNAscope is superior to immunohistochemistry in detecting TTF-1 and napsin A expression in primary lung adenocarcinomas. Therefore, performing an RNAscope assay may be considered for both TTF-1− and napsin A− cases with a clinical suspicion of lung adenocarcinoma. The TTF-1 results should be interpreted with caution because a small percentage of squamous cell carcinomas can be focally positive by either assay.Conclusions.—
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Wong, Justin J. M., Paula S. Ginter, Kathrin Tyryshkin, Xiaojing Yang, Jina Nanayakkara, Zier Zhou, Thomas Tuschl, Yao-Tseng Chen, and Neil Renwick. "Classifying Lung Neuroendocrine Neoplasms through MicroRNA Sequence Data Mining." Cancers 12, no. 9 (September 17, 2020): 2653. http://dx.doi.org/10.3390/cancers12092653.

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Lung neuroendocrine neoplasms (NENs) can be challenging to classify due to subtle histologic differences between pathological types. MicroRNAs (miRNAs) are small RNA molecules that are valuable markers in many neoplastic diseases. To evaluate miRNAs as classificatory markers for lung NENs, we generated comprehensive miRNA expression profiles from 14 typical carcinoid (TC), 15 atypical carcinoid (AC), 11 small cell lung carcinoma (SCLC), and 15 large cell neuroendocrine carcinoma (LCNEC) samples, through barcoded small RNA sequencing. Following sequence annotation and data preprocessing, we randomly assigned these profiles to discovery and validation sets. Through high expression analyses, we found that miR-21 and -375 are abundant in all lung NENs, and that miR-21/miR-375 expression ratios are significantly lower in carcinoids (TC and AC) than in neuroendocrine carcinomas (NECs; SCLC and LCNEC). Subsequently, we ranked and selected miRNAs for use in miRNA-based classification, to discriminate carcinoids from NECs. Using miR-18a and -155 expression, our classifier discriminated these groups in discovery and validation sets, with 93% and 100% accuracy. We also identified miR-17, -103, and -127, and miR-301a, -106b, and -25, as candidate markers for discriminating TC from AC, and SCLC from LCNEC, respectively. However, these promising findings require external validation due to sample size.
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48

Zhang, Wei, Qingyu Cai, and Guoli Wei. "Comparison of Differential Diagnosis of Lung Cancer by Diffuse Weighted Imaging and Sagittal Imaging with Short Inversion Recovery Sequence." Journal of Medical Imaging and Health Informatics 11, no. 3 (March 1, 2021): 822–26. http://dx.doi.org/10.1166/jmihi.2021.3356.

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The differential diagnosis of advanced lung cancer is difficult in clinical practice. Our study aims to compare the value of diffusion weighted imaging (DWI) with short-term inversion recovery sequence (STIR) for sagittal imaging in the differential diagnosis of lung cancer. 149 patients with non-small cell lung carcinoma (NSCLC) were enrolled and underwent DWI and STIR sagittal imaging. To quantify cancer types, we evaluated the apparent diffusion coefficient (ADC) value on DWI and the contrast ratio (CRs) on sagittal imaging. The ADC values of subclasses in NSCLC were significantly higher than small cell lung carcinoma (SCLC) (p <0.01). The mean CRs were 1.59 for SCLC and 1.30 for NSCLC with a significant difference (p < 0.01). Large cell carcinomas (LCC) and adenocarcinomas have significant differences compared to small cell carcinomas (SCC) without difference between squamous cell carcinomas (p > 0.05); this is also the case for CRs. Squamous cell carcinoma and adenocarcinoma have significant differences compared to SCC without difference in LCC (p > 0.05). Qualitative evaluation of the feasible thresholds DWI and STIR showed that the thresholds were 0.9810−3 mm2/s and 1.37 respectively. The specificity and accuracy was 78.5% is 85.3% for DWI, which was significantly higher than STIR (56.3% and 61.0%). The combination of DWI and STIR sequences was superior to DWI alone with an accuracy rate of 94.3%. DWI is more helpful than STIR in differentiating SCLC and NSCLC, and their combined use can significantly improve diagnosis accuracy.
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Fawzy, Ahmed, Samira Mahmoud Abd Allah, Mostafa Mohammed Salem, and Lobna Omar Al Farouk. "Immunohistochemical and Histopathological Study of Anaplastic Lymphoma Kinase and Tyrosine-kinase Receptor Expression in Bronchogenic Carcinoma." Open Access Macedonian Journal of Medical Sciences 9, A (February 18, 2021): 106–13. http://dx.doi.org/10.3889/oamjms.2021.5671.

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BACKGROUND: Adenocarcinoma of the lung is the most common tumor type of primary lung cancer and is characterized by heterogeneity on the molecular, clinical, and pathological levels. The presence of an anaplastic lymphoma kinase (ALK) fusion oncogene defines a molecular subset of non-small cell lung cancer with distinct clinical and pathologic features. Furthermore, the tyrosine-kinase receptor (C-kit) is considered to be expressed in various solid tumors, including carcinomas of the lung. AIM: This study aims to correlate immunohistochemical (IHC) expression of ALK and C-kit with pathological features of lung carcinoma and to correlate IHC expression of ALK with IHC expression of C-kit in lung carcinoma. MATERIALS AND METHODS: The material of this study consists of paraffin blocks of 60 cases of patients with bronchogenic carcinoma, IHC staining with ALK and C-kit then analysis of immunoreactivity scoring was done. RESULTS: As regards ALK expression, 3 (5%) cases showed positive expression of ALK and 57 (95%) cases showed negative expression of ALK with no statistically significant correlation between the ALK expression and the histopathological type. While C-kit expression, 4 (6.7%) cases showed positive expression and 56 (93.3%) cases showed negative expression of C-kit with statistically significant correlation between the C-kit expression and the histopathological type. CONCLUSION: There is an association between expression of c-kit and tumor histological type in lung carcinoma. Expression was notably significant among adenocarcinomas and small cell carcinomas.
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50

Abada, Evi. "A Rare Case of GATA3 Positivity in Pleomorphic Lung Carcinoma in a Patient with History of Intracystic Papillary Carcinoma of the Breast: Primary Lung or Metastatic Disease?" Case Reports in Pathology 2021 (January 20, 2021): 1–4. http://dx.doi.org/10.1155/2021/6664804.

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Pleomorphic lung carcinoma is a rare and aggressive neoplasm accounting for <1% of all lung tumors. It is more common in men and consists of spindle and/or giant cells with an epithelial component. In patients with known histories of malignancies at other sites, diagnosis of a new lung lesion may prove challenging with respect to classification as either primary or metastatic disease, especially in cases with overlapping immunohistochemical staining patterns. This was a case of a 67-year-old female with a newly discovered 1.5 cm nodule in her left lower lung lobe. Her past medical history was significant for an intracystic papillary carcinoma of the right breast diagnosed 8 years prior. Histopathologic examination of the new lung lesion revealed highly pleomorphic cells composed predominantly of neoplastic giant cells and atypical mitotic figures, with geographic areas of necrosis. However, no areas reminiscent of intracystic papillary carcinoma or other forms of breast carcinoma were seen. Immunohistochemistry showed that the tumor cells were immunoreactive for GATA3, TTF1, and napsin A and nonimmunoreactive for p40. Therefore, although this index lung tumor did show positivity with GATA3 staining, it was morphologically different from her original intracystic papillary carcinoma of the breast. In addition, intracystic papillary carcinomas are known to rarely metastasize to other organs, and GATA3 staining has been rarely reported in lung carcinomas. In summary, this case typifies the overlapping immunohistochemical staining patterns that may be seen in different tumors and the role of histopathologic morphology in arriving at the correct diagnosis.
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