The Utility of Immunohistochemical Markers for the Differential Diagnosis of Metastatic Melanoma in the Central Nervous System
Mehmet Gamsizkan, Hasan Aktug Simsek, Tarik Tihan, Ismail Yilmaz, Ann Griffin, Onder Onguru. GATA, Ankara, Turkey; Eskisehir Military Hospital, Eskisehir, Turkey; UCSF, San Francisco, CA; GATA Haydarpasa Education and Research Hospital, Istanbul, Turkey
Background: Some melanomas metastatic to the central nervous system (CNS) pose little diagnostic difficulty while many others are challenging due to ambiguous histological and immunohistochemical features. In such cases, aberrant immunohistochemical staining results complicate differential diagnosis. In order to determine the most appropriate immunohistochemical panel for diagnosis, we analyzed immunohistochemical features of CNS metastatic melanomas.
Design: We included 48 patients with CNS metastatic melanomas (31 male, 17 female; median age= 57) from a total of 77 patients identified from a database search. All cases were immunostained with S100, EMA, Sox-2, Sox-10, CAM5.2, O13, Melan-A, HMB45 and MITF by using tissue microarray.
Results: Twenty seven tumors harbored melanin pigment, while 21 were amelanotic. Metastatic melanomas were positive for S-100 protein(98%), Sox-10(96%), HMB45(88%), Melan-A(79%), MITF(77%) and Sox-2(54%). MITF immunostaining was weak in one-third the cases in which this antibody was positive. Interestingly, we found convincing EMA positivity in 6 (13%), and 013 positivity in 2 (4%) of the cases. All tumors were negative for CAM 5.2. There was a positive association between HMB45 immunostaining and presence of melanin pigment (p=0.037).
Conclusions: Among individual markers, S-100 protein and Sox-10 appear the most sensitive but least specific since other entities have similar staining patterns. However, since 100% of our cases were positive for either of these stains, negative staining in both markers appears incompatible with the diagnosis of metastatic melanoma. The staining for Sox-2 poses significant diagnostic difficulty since most malignant gliomas are also positive with this antibody. Rare positivity with EMA and O13 are also confounding, and the weak staining with MITF can pose difficulties in the interpretation. Finally, stain for HMB45 may not be necessary if the tumor does not harbor pigment on H&E evaluation.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 251, Wednesday Afternoon