USCAP 2015 Bone and Soft Tissue Evening Specialty Conference Case

Andrew L. Folpe MD Professor of Pathology and Laboratory Medicine Mayo Clinic, Rochester, MN [email protected] A previously well 36-year-old woman presented with abdominal pain and was found to have a 2 cm mass adjacent to the aorta Imaging Studies

SYN

CGA CD31 SYN

CD31 FLI1 ERG CD34 Angiosarcoma (low-grade?) with aberrant expression of neuroendocrine markers Previously Reported Cases

• Case 1: 45F with multiple pulmonary nodules. Initially diagnosed as “ hyperplasia”. Subsequently found to have an occult angiosarcoma in the C5 vertebral body • Case 2: 29F with a large renal mass. Submitted in consultation as a “primary renal neuroendocrine ” • Case 3: 51F with a history of neck irradiation for lymphoma and a new mass. Originally regarded as “malignant ” Case 1

SYN

CD31 FLI-1 Case 2

CGA SYN

CK CD31 FLI-1 Case 3

SYN CD31

ERG CD34 and Chromogranin

• Synaptophysin • component of • Normally expressed by neurons, endocrine and neuroendocrine cells, and adrenal cortical cells • Present in adrenocortical tumors, neuroendocrine , Merkel cell carcinomas, , , and esthesioneuroblastomas • Typically negative in other SBRCT • Chromogranin • component of dense core granule • Similar distribution to synaptophysin in normal and neoplastic tissues, except adrenal cortex • Generally less sensitive than is synaptophysin • Absent in adrenocortical neoplasms SCCA SYN Aberrant Expression of Neuroendocrine Markers • Synaptophysin • Alveolar • Extraskeletal myxoid chondrosarcoma • • Angiosarcoma • • Alveolar rhabdomyosarcoma • Angiosarcoma Alveolar Rhabdomyosarcoma

• expression in 50% • Expression of at least one NE marker in 43% • Synaptophysin expression in 32% • Chromogranin A expression in 22% • Synaptophysin and chromogranin A expression in 11% Myogenin

CK SYN Extraskeletal Myxoid Chondrosarcoma

SYN Courtesy Dr. Cyril Fisher, London, UK Melanoma

SYN [487] Anomalous Intermediate Filament and Synaptophysin Expression in Melanoma

Ryan C Romano, Jodi M Carter, Andrew L Folpe. Mayo Clinic, Rochester, MN

Background: Malignant (MM) are known to express , among other intermediate filaments (IF). Though anomalous cytokeratin (CK) expression by MM has been reported, its frequency is not well-established and this phenomenon is not well-known. We have seen in consultation a number of MM with anomalous expression of CK, other intermediate filaments, or synaptophysin, and therefore studied a large group of primary and metastatic MM to determine the frequency of these events. Design: 70 MM (22 primaries, 48 metastases) from 68 patients (48M, 20F; mean 59 years, range 17-87 years) were retrieved from our archives. Prior diagnoses were confirmed by re-review of H and E sections and relevant (e.g., , HMB45, Melan-A, tyrosinase) immunohistochemical studies. Available sections were immunostained for CK (OSCAR and AE1/AE3 antibodies), (DES), neurofilament protein (NFP), glial fibrillary acidic protein (GFAP), synaptophysin (SYN), and chromogranin A (CG). Not all cases could be tested for all markers. Results: Cases were predominantly epithelioid (45/70, 64%) or spindle cell/desmoplastic (25/70, 36%). S100 protein, Melan-A, HMB45, and tyrosinase were positive in 57/62 (92%), 33/61 (54%), 27/57 (47%), 24/47 (51%) of cases, respectively. The 5 S100 protein-negative cases were positive for Melan-A, HMB45, and tyrosinase in 2/4 (50%), 2/3 (67%), 1/2 (50%) of cases, respectively. All cases expressed at least one melanocytic marker. Cases were positive for CK (OSCAR, 15/58, 26%; AE1/AE3, 16/40, 40%), DES (11/46, 24%), NFP (5/31, 16%), GFAP (3/32, 9%), and SYN (9/32, 28%), typically only in a minority of cells. CG was negative (0/31, 0%). Expression of more than 1 IF was seen in 17 cases (24%). All S100 protein-negative MM showed anomalous IF expression (CK- 1 case, DES- 3 cases, NFP- 1 case). Anomalous IF or SYN expression was more common in epithelioid (26/45, 58%) as compared with spindle cell/desmoplastic (9/25, 36%) MM. Overall, 50% (35/70) of cases showed anomalous expression of at least one IF or SYN. Conclusions: Anomalous expression of all IF and SYN was found in significant subsets of MM, representing potentially serious diagnostic pitfalls. While the inclusion of consultation cases may inflate the frequency of these findings in this series, similar findings were also seen in institutional cases. MM showing anomalous IF and SYN expression may easily be mistaken for carcinomas, and neuroendocrine tumors. Awareness of this phenomenon, careful histopathological evaluation, and an appropriate melanocytic immunohistochemical panel should facilitate the diagnosis of MM with unusual immunophenotypes. Category: Dermatopathology

Tuesday, March 24, 2015 1:00 PM

Poster Session IV # 82, Tuesday Afternoon Endothelial Markers

• CD31 • Highly sensitive • Very rarely expressed by carcinomas • Expressed by macrophages and platelets • CD34 • Highly sensitive • Expressed by many non-endothelial tumors • FLI1/ERG • Highly sensitive • ERG is more specific than is FLI1, but neither is perfectly specific CD31 Could These Tumors Represent a Specific Entity?

• Distinctive morphology • CD34-negative • Low-grade clinical behavior • Translocation-related? Translocations in Endothelial Neoplasms Summary

• Aberrant expression of neuroendocrine markers may rarely be seen in malignant endothelial tumors • Distinctive morphology and immunophenotype • Genetics remain to be elucidated • May represent a specific entity • Low-grade AS vs hemangioendothelioma