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An exploration in pitfalls in interpreting SDHB immunohistochemistry.
Ding, Chien-Kuang Cornelia; Chan, Salina; Mak, Julie; Umetsu, Sarah E; Simko, Jeffry P; Ruiz-Cordero, Roberto; Saunders, Tara; Chan, Emily.
Afiliación
  • Ding CC; Department of Pathology, University of California, San Francisco, CA, USA.
  • Chan S; Cancer Risk Program, Hellen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
  • Mak J; Cancer Risk Program, Hellen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
  • Umetsu SE; Department of Pathology, University of California, San Francisco, CA, USA.
  • Simko JP; Department of Pathology, University of California, San Francisco, CA, USA.
  • Ruiz-Cordero R; Department of Pathology, University of California, San Francisco, CA, USA.
  • Saunders T; Department of Pathology, University of California, San Francisco, CA, USA.
  • Chan E; Department of Pathology, University of California, San Francisco, CA, USA.
Histopathology ; 81(2): 264-269, 2022 Aug.
Article en En | MEDLINE | ID: mdl-35546442
AIMS: Mutations and epimutations in genes encoding the succinate dehydrogenase complex (SDHx) are associated with multiple tumour types in which identification of SDH-deficiency has significant management implications. Immunohistochemistry (IHC) for the succinate dehydrogenase B (SDHB) subunit can help to detect SDH-deficiency, which manifests as complete loss of staining in tumour cells. However, a subset of SDH-deficient tumours can show aberrant cytoplasmic SDHB-IHC staining patterns and be misinterpreted as 'retained', a diagnostic pitfall complicating interpretation. Herein, we characterise in detail aberrant SDHB-IHC staining patterns in SDH-deficient tumours. METHODS AND RESULTS: We identified 23 tumours from patients with known germline SDHx and/or molecularly confirmed SDHx pathogenic/likely-pathogenic variants in their tumour. Of these, eight (35%) showed significant SDHB-IHC staining: one SDHA-, one SDHB-, three SDHC- and three SDHD-mutated cases. In all eight cases, closer inspection revealed differences in intensity and intracellular distribution of SDHB-IHC staining in tumour cells compared to adjacent non-neoplastic cells: non-neoplastic cells showed intense cytoplasmic coarse granular staining; tumour cells in seven of eight cases showed weak to focally strong, cytoplasmic blush to fine granular staining, in > 80% of cells. The remaining case in the initial block showed variably strong non-granular cytoplasmic staining with globular perinuclear accentuation throughout, only subtly distinct from the staining pattern of non-neoplastic cells. SDHB-IHC performed on two additional blocks in this latter case revealed significant intratumoral heterogeneity, including convincing areas of complete loss. CONCLUSIONS: When evaluating SDHB-IHC, care should be taken to distinguish true retained expression from aberrant cytoplasmic expression, which may be difficult to appreciate. Sometimes this may require additional molecular testing.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Paraganglioma / Neoplasias Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Humans Idioma: En Revista: Histopathology Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Paraganglioma / Neoplasias Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Humans Idioma: En Revista: Histopathology Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido