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An Immunohistopathologic Study to Profile the Folate Receptor Beta Macrophage and Vascular Immune Microenvironment in Giant Cell Arteritis
Published on: February 8, 2019
Immunohistochemical evaluation of microphthalmia-associated transcription factor expression in giant cell lesions
Raja R Seethala1, John R Goldblum, David G Hicks
1University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA. seethalr@uphs.upenn.edu
Abstract:
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.
Insights
Microphthalmia-associated transcription factor (Mitf) is expressed in giant cells of various bone lesions, suggesting a role in their formation. This contrasts with osteopetrosis, where Mitf is absent, supporting mononuclear cell origin for giant cells.
Area of Science:
- Pathology
- Cell Biology
- Oncology
Background:
- Microphthalmia-associated transcription factor (Mitf) is crucial for osteoclast differentiation.
- Dysfunctional Mitf is linked to osteopetrosis.
- Giant cells in various tumors are traditionally considered monocyte-derived.
Purpose of the Study:
- To investigate Mitf expression in diverse giant cell lesions.
- To determine if Mitf differentiates monocyte-derived giant cells from other giant cell types.
- To explore Mitf's role in the multinucleation of giant cells.
Main Methods:
- Immunohistochemical analysis of Mitf expression using a monoclonal antibody.
- Evaluation of 89 giant cell lesions, including giant cell tumor of bone, PVNS, and aneurysmal bone cysts.
- Comparison with osteopetrosis and non-giant cell tissues.
Main Results:
- Mitf was variably expressed in most giant cell lesions of presumed monocyte origin (80-100% in most).
- No Mitf immunoreactivity was observed in osteopetrosis or non-monocyte-derived giant cells.
- Mitf expression was rare in mononuclear cells without giant cell formation.
Conclusions:
- Giant cells in various lesions likely originate from adjacent mononuclear cells.
- Mitf expression supports its involvement in the multinucleation process of these cells.
- Mitf can serve as a marker to distinguish monocyte-derived giant cells.
