Immunohistochemical evaluation of microphthalmia-associated transcription factor expression in giant cell lesions.

Microphthalmia-associated transcription factor (Mitf), a member of the helix-loop-helix transcription factor subfamily, normally expressed in mononuclear and multinucleated osteoclasts, is involved in the terminal differentiation of osteoclasts. Dysfunction of osteoclast activity resulting from abnormal Mitf expression has been implicated in osteopetrosis. Numerous other giant cells of various types including osteoclast-like giant cells seen in various tumors, traditionally thought to be monocyte derived, are seen in a variety of bone and extraosseous lesions. Using a monoclonal antibody with a standard immunohistochemical technique on paraffin sections, we evaluated expression of Mitf in 89 various giant cell lesions including giant cell tumor of bone (n26), giant cell tumor of tendon sheath/pigmented villonodular synovitis (n24), giant cell reparative granuloma (n3), aneurysmal bone cysts (n11), chondroblastomas (n7), foreign body giant cell reaction (n10), and sarcoidosis (n8). We also evaluated three cases of osteopetrosis and 27 various tissues without monocyte-derived giant cells (nine bone marrows, nine products of conception, seven lymph nodes with sinus histiocytosis, one granulation tissue and one thymus). Nuclear Mitf immunoreactivity was evaluated. Mitf was variably expressed in the monocyte-derived giant cells and/or the adjacent mononuclear cells/histiocytes in 23 (89%) giant cell tumors of the bone, 23 (96%) giant cell tumors of tendon sheath/pigmented villonodular synovitis, three (100%) giant cell reparative granuloma, eight (73%) aneurysmal bone cysts, five (71%) chondroblastomas, eight (80%) foreign-body giant cell reactions, and six (75%) sarcoidoses. No Mitf immunoreactivity was detected in cases of osteopetrosis and giant cells of nonmonocyte origin. Mitf immunoreactivity is rare in tissues with rich mononuclear cells/histiocytes but no monocyte derived giant cells. These findings support the notion that giant cells in giant cell lesions are likely derived from adjacent mononuclear cells and Mitf might play a role in the multinucleation process of such cells.

Immunoprofile of MITF, tyrosinase, melan-A, and MAGE-1 in HMB45-negative melanomas.

A majority of desmoplastic melanomas and some of the other forms of melanomas are S-100 positive and HMB45 negative; this pattern of immunoreactivity is similar to certain nerve-derived tumors such as malignant peripheral nerve sheath tumor. In this study the immunostaining profile of HMB45-negative malignant melanomas was evaluated by a panel of antibodies against markers associated with melanoma and melanocytic differentiation, including microphthalmia transcription factor, tyrosinase, Melan-A, and MAGE-1. Immunodetection was performed on paraffin sections of 22 cases of HMB45-negative malignant melanomas (including 8 spindle cell melanomas, 8 desmoplastic melanomas, and 6 epithelioid melanomas), 8 HMB45-and S-100-positive malignant melanomas, 15 malignant peripheral nerve sheath tumors, 16 schwannomas, and 11 neurofibromas. Of eight HMB45-positive malignant melanomas, all were positive for Melan-A, tyrosinase, and melanocyte-specific transcription factor, and three were positive for MAGE-1. In the 14 HMB-45 negative, nondesmoplastic melanomas, melanocyte-specific transcription factor was positive in 9, Melan-A in 9, tyrosinase in 6, and MAGE-1 in 11. In eight desmoplastic malignant melanomas, MAGE-1 was positive in three, and all other markers were negative. The five markers tested were negative in all but two schwannomas, one with focal melanocyte-specific transcription factor and the other with tyrosinase and weak MAGE-1 reactivity. MAGE-1, melanocyte-specific transcription factor, tyrosinase, and Melan-A are useful markers in the diagnosis of malignant melanocytic lesions when HMB45 is negative. MAGE-1 may be useful in differentiating melanocytic lesions from nerve-derived lesions, but its sensitivity is relatively low. The immunostaining profile of desmoplastic malignant melanomas more closely resembles that of malignant peripheral nerve sheath tumor than that of other types of malignant melanoma. Melanocyte-specific transcription factor is not a useful marker for desmoplastic melanoma.