Intense Micropthalmia Transcription Factor (MITF) Expression Is a Marker of Mastocytosis
Christopher M Carter, May R Arroyo, Robert W Allan. University of Florida College of Medicine, Gainesville, FL
Background: Micropthalmia-associated transcription factor (MITF) is a basic helix-loop helix leucine zipper transcription factor that is critical for the development of melanocytes, osteoclasts and mast cells. It is frequently used in dermatopathology as a marker of melanocytic lesions as melanocytes intensely express this marker. Recently it has been demonstrated the activating mutations in codon 816 of the tyrosine kinase receptor KIT, found in the majority of patients with systemic mastocytosis, markedly upregulates MITF expression. We sought to determine if overexpression of MITF by immunohistochemistry could be used to evaluate neoplastic mast cell disorders.
Design: Archival formalin-fixed paraffin embedded (FFPE) tissue blocks from patients with mast cell lesions (cutaneous, bone/soft tissue and bone marrow) at this institution were retrieved for MITF immunohistochemistry (C5/D5 IgG1 clone) using standard methods (Ventana Benchmark XT). Nuclear and cytoplasmic expression of MITF was semi-quantitatively scored (intensity: 0-negative, 1+- minimal, 2+- moderate, 3+- strong; extensiveness in target cells 0- 0%, 1- <50%, 2- 50%-75%, 3- >75%). Pertinent clinicopathologic information was recorded. Negative controls consisted of 52 cases from various anatomic sites stained with MITF to assess for background mast cell staining.
Results: A total of 7 patients with adequate tissue blocks were identified for MITF staining (age range 11months- 81 years, mean 54.6 years, M:F 2:5) from different anatomic sites (cutaneous- urticaria pigmentosa n=2, diffuse cutaneous n=1), bone/soft tissue (mastocytoma of bone n= 1), bone marrow n= 3 (systemic mastocytosis n=2, atypical mastocytosis associated with myelodysplastic syndrome n=1). 5 of the 7 cases showed strong staining in >75% of the mast cells (3+); the two negative cases representing the mastocytoma of bone and urticaria pigmentosa in an 11 mo. old. No significant nuclear or cytoplasmic staining (only minimal 1+ intensity) was observed in any of the 52 negative control cases.
Conclusions: Intense extensive nuclear expression of MITF is present in the majority of mast cell tumors (5/7); such staining may be a reliable method to distinguish benign from neoplastic mast cells. Furthermore, intense MITF by mast cell neoplasms is a potential pitfall in the diagnosis of melanocytic lesions. A larger study correlating MITF expression with mast cell phenotype and activating C-kit mutation status is needed to clarify the significance of intense MITF expression in mast cell neoplasms.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 105, Tuesday Morning