BRAF Mutation in “Sarcomas”: A Possible Method To Detect Melanomas
Nicole A Cipriani, Patrick J McLaughlin, Darrell R Borger, G Petur Nielsen. Massachusetts General Hospital, Boston, MA
Background: BRAF is commonly mutated in melanomas (over 60%), as well as some thyroid and colon carcinomas. BRAF mutation has been anecdotally reported in up to 2% of sarcomas. Immunohistochemically, some poorly-differentiated melanomas lose melanocytic markers and some sarcomas demonstrate no lineage of differentiation. Making a definitive diagnosis of melanoma versus sarcoma in this setting can be challenging. This study addresses the rate of BRAF mutation in patients with sarcomas and in patients with both melanoma and sarcoma.
Design: A clinico-pathologic database was queried for patients with sarcoma, with or without melanoma. SNaPshot mutational analysis was performed on formalin-fixed paraffin-embedded tumor tissue from: 1) 50 patients with sarcoma-only, without melanoma; 2) 13 patients with both sarcoma and melanoma (melanoma tissue was not available for 3 of these patients).
Results: In the sarcoma-only group (n=50), BRAF mutation was not identified. Nine sarcoma-only patients had other molecular aberrations. In the sarcoma-melanoma group (n=13), two sarcomas showed BRAF mutation, both undifferentiated sarcomas. Tissue from the two corresponding melanomas was not available for comparison. Three melanomas showed BRAF mutation but the corresponding sarcomas did not. Three sarcomas and one melanoma showed other molecular aberrations.
Conclusions: Rate of BRAF mutation in sarcoma is low. In patients with sarcoma WITHOUT melanoma, the rate in this study is 0%. Interestingly, BRAF mutation was only identified in sarcomas from patients who also had melanomas. Both sarcomas were high grade, poorly differentiated, did not stain for melanocytic markers, and occurred chronologically after the melanomas. In one case, the melanoma was in the left buttock with left groin metastases; the “sarcoma” was in the left pelvis. In the other case, the melanoma was in the left breast; the “sarcoma” was in the left lung. The presence of BRAF mutation in these tumors raises the possibility that poorly differentiated sarcomatoid malignancies with BRAF mutation may represent melanomas. Further investigation into this topic is warranted. BRAF mutational analysis should be considered in patients with poorly differentiated malignancies (especially those with histories of melanoma), as a positive result may indicate melanocytic differentiation.
Category: Bone & Soft Tissue
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 6, Monday Morning