Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Wiesner, T; Murali, R; Fried, I; Cerroni, L; Busam, K; Kutzner, H; Bastian, BC.
A distinct subset of atypical Spitz tumors is characterized by BRAF mutation and loss of BAP1 expression.
Am J Surg Pathol. 2012; 36(6):818-830
Doi: 10.1097/PAS.0b013e3182498be5
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- Führende Autor*innen der Med Uni Graz
- Wiesner Thomas
- Co-Autor*innen der Med Uni Graz
- Cerroni Lorenzo
- Fried Isabella
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- Abstract:
- We recently reported that germline mutations in BAP1 cause a familial tumor syndrome characterized by high penetrance for melanocytic tumors with distinct clinical and histologic features. Melanocytic neoplasms in affected individuals harbored BRAF mutations, showed loss of BAP1 expression, and histologically resembled so-called "atypical Spitz tumors" (ASTs). ASTs are an ill-defined and probably heterogenous group of melanocytic tumors that display histologic features seen in both Spitz nevi and melanomas. Their biological behavior cannot be reliably predicted. In view of the histologic similarities of the familial tumors and ASTs, we hypothesized that a subset of ASTs might harbor genetic alterations seen in the familial tumors. To address this hypothesis, we analyzed 32 sporadic ASTs for BRAF mutations and for BAP1 expression. Nine (28%) sporadic ASTs showed loss of BAP1 expression, of which 8 (89%) had concomitant BRAF mutations. Only 1 of the BAP1-positive ASTs (4%) had a BRAF mutation (P<0.0001). BRAF-mutated, BAP1-negative tumors were primarily located in the dermis and were composed entirely or predominantly of epithelioid melanocytes with abundant amphophilic cytoplasm and well-defined cytoplasmic borders. Nuclei were commonly vesicular and exhibited substantial pleomorphism and conspicuous nucleoli. The combination of BRAF mutation and loss of nuclear BAP1 expression thus characterizes a subset of ASTs with distinct histologic features. The typical morphology of these tumors and BAP1 immunohistochemistry provide pathologic clues that will enable accurate identification of this subset. Future studies are necessary to determine whether this subset has a predictable clinical behavior.
- Find related publications in this database (using NLM MeSH Indexing)
- Adolescent -
- Adult -
- Biomarkers, Tumor - metabolism
- Cell Nucleus - metabolism Cell Nucleus - pathology
- Child -
- Child, Preschool -
- Cytoplasm - metabolism Cytoplasm - pathology
- Epithelioid Cells - metabolism Epithelioid Cells - pathology
- Family Health -
- Female -
- Humans -
- Male -
- Melanocytes - metabolism Melanocytes - pathology
- Middle Aged -
- Mutation -
- Nevus, Epithelioid and Spindle Cell - diagnosis Nevus, Epithelioid and Spindle Cell - genetics Nevus, Epithelioid and Spindle Cell - metabolism
- Proto-Oncogene Proteins B-raf - genetics Proto-Oncogene Proteins B-raf - metabolism
- Skin Neoplasms - diagnosis Skin Neoplasms - genetics Skin Neoplasms - metabolism
- Tumor Suppressor Proteins - genetics Tumor Suppressor Proteins - metabolism
- Ubiquitin Thiolesterase - genetics Ubiquitin Thiolesterase - metabolism
- Young Adult -
- Find related publications in this database (Keywords)
- Spitz nevus
- atypical Spitz tumor
- epithelioid melanocytic tumor
- melanoma
- BAP1
- BRAF
- pathology
- genetics
- immunohistochemistry