3/27/2017. Pulmonary Pathology Specialty Conference. Disclosure of Relevant Financial Relationships. Clinical History:
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1 Pulmonary Pathology Specialty Conference Saul Suster, M.D. Medical College of Wisconsin Disclosure of Relevant Financial Relationships USCAP requires that all planners (Education Committee) in a position to influence or control the content of CME disclose any relevant financial relationship WITH COMMERCIAL INTERESTS which they or their spouse/partner have, or have had, within the past 12 months, which relates to the content of this educational activity and creates a conflict of interest. Dr. Saul Suster declares he has no conflict(s) of interest to disclose. Clinical History: A 56 year old woman was seen for shortness of breath and chest pain. CT scan showed a large anterior mediastinal mass. A core biopsy was interpreted as a poorly-differentiated carcinoma, rule out metastatic disease. Following a thorough clinical workup, no evidence of tumor could be identified elsewhere. A thoracotomy with removal of a 12 cm. anterior mediastinal mass was performed. 1
2 AE1/AE3 CD117 p63 Ki-67 2
3 The American Journal of Surgical Pathology Vol.6 Number 5 July 1982 Diagnosis: Dale C. Snover, M.S. Gerald D. Levine, M.B., Ch.B., M. Me., (Pathol.)* Juan Rosai, M.D. Five distinctive histologic variants Am J Surg Pathol Vol. 6: , Poorly-differentiated, non-keratinizing squamous cell carcinoma arising from thymic epithelial cells Identical histologic features to poorly-differentiated nasopharyngeal carcinoma (lymphoepithelioma) Rare tumor (total 37 cases described in the literature) Aggressive behavior with recurrences and metastases and fatal outcome in a high percentage of patients 19 cases: 11 men and 8 women, aged years Gross: large bulky and infiltrative masses with areas of hemorrhage and necrosis Treatment: resection + chemotherapy + radiation therapy Follow-up: 10 patients had local recurrence and 16 had distant metastases to regional lymph nodes, bone, lung and brain 14 died of tumor between 1-6 years after diagnosis Suster S, Rosai J: Thymic carcinoma: clinicopathologic study of 60 cases. Cancer Vol.67: , Poorly Differentiated Non-Keratinizing Thymic Squamous Cell Carcinoma Study of 25 cases: 20 men and 5 women aged years (mean: 60) Chest pain and shortness of breath with large anterior mediastinal mass on chest imaging Size: 3-12 cm (average 6 cm) Masaoka stage at diagnosis: Stage I (3), Stage II (11), Stage III (2) 3 cases were small and well-circumscribed, devoid of invasion 22 cases were frankly invasive 3
4 Poorly Differentiated Non-Keratinizing Thymic Squamous Cell Carcinoma Islands, sheets and cords of atypical tumor cells with round to oval, vesicular nuclei and prominent centrally placed eosinophilic nucleoli Prominent comedo-like areas of necrosis Two patterns: - (with dense lymphoid stroma) - Desmoplastic stroma (devoid of lymphocytes) Desmoplastic type 4
5 Immunohistochemical Stains: Positive: Cytokeratin AE1/AE3, CK5/6, CK18, MOC31, p40, p63 in all cases CD117 (21/25); CD5 (20/25) p16 (16/25) Ki-67 (average 35% nuclear positivity) Chromogranin focal positivity (6/25 cases) EBER in-situ hybridization (2/25) CD117 CD1a CD20 p16 EBER ISH Ki-67 5
6 Molecular Studies: Variants Tumor enriched DNA was extracted from FFPE blocks for all 25 cases and sequenced with the Ion AmpliSeq Cancer Hotspot Panel v2. Adequate material could be obtained for next gen sequencing assay in 21 cases. Variants were analyzed using Torrent Suite and annotated with the GenomOncology Workbench. 24 variants were detected that correspond to benign germline SNP 18 variants were identified that were interpreted as diseaseassociated None of the variants identified represent classical driver genes Conclusion: Out of the 18 variants identified, the majority of cases harbored only 1 variant The most frequent variants were KDR Q47M, KIT M541L and PIK3CA I391M Poorly-differentiated non-keratinizing thymic squamous cell carcinoma is a distinctive entity with reproducible morphologic features and immunohistochemical profile The tumors can either have a lymphocyte-rich stroma (i.e., lymphoepithelioma-like) or be desmoplastic Unlike their nasopharyngeal counterpart, these tumors do not appear to be EBV-driven No actionable driver mutations could be identified in this cohort on next gen sequencing using a 50-gene panel Important Information Regarding CME/SAMs The Online CME/Evaluations/SAMs claim process will only be available on the USCAP website until September 30, No claims can be processed after that date! After September 30, 2017 you will NOT be able to obtain any CME or SAMs credits for attending this meeting. 6
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