Novel uses of immunohistochemistry in the diagnosis and classification of soft tissue tumors

Abstract

Immunohistochemistry plays a key role in the diagnosis of soft tissue tumors. Until recently, however, the primary purpose of immunohistochemistry in this context was simply to attempt to demonstrate a line of differentiation. Unfortunately, most traditional markers (predominantly directed against cytoplasmic determinants) show relatively limited specificity. Over the last decade or so, much more specific immunohistochemical markers for soft tissue tumors have been developed. This review will provide an update of some of the most useful new diagnostic markers, which are significantly changing clinical practice for surgical pathologists, separated into three general categories: (1) lineage-restricted transcription factors, (2) protein correlates of molecular alterations, and (3) diagnostic markers identified by gene expression profiling.

The spectrum of EWSR1-rearranged neoplasms at a tertiary sarcoma centre; assessing 772 tumour specimens and the value of current ancillary molecular diagnostic modalities

“…The increasing discovery of characteristic genetic abnormalities in soft tissue neoplasms has caused a significant challenge for molecular diagnostics laboratories in maintaining accredited ancillary tests (van de Rijn et al , 2014), compounded by the low cost-benefit ratios due to disease rarity (van de Rijn et al , 2014; Mourtzoukou et al , 2015). It is important not to disregard the value of immunohistochemistry (Hornick, 2014), which is highly cost-effective and widely available in standard surgical pathology laboratories. Immunohistochemical markers that act as surrogates for molecular investigations are likely to be more cost-effective and rapid.…”

SOX11: a potentially useful marker in surgical pathology: a systematic analysis of SOX11 expression in epithelial and non‐epithelial tumours

“…Hornick et al classified useful diagnostic markers for tumour diagnosis in surgical pathology into three categories: lineage-restricted transcription factors, proteins correlated with molecular alterations and diagnostic markers identified by gene expression profiling. 22 Antibodies recognising lineage-restricted nuclear transcription factors, such as TTF1, CDX2, PAX8 and SOX10, are increasingly applied in surgical pathology for diagnosis. 7,8,10,23 In neurogenesis it is known that when Notch signalling is inhibited SOX11, downstream from activated proneural bHLH proteins (ASCL1, etc.…”

Cytopathologic features of epithelioid inflammatory myofibroblastic sarcoma with correlation of histopathology, immunohistochemistry, and molecular cytogenetic analysis

“…Histologically, E‐IMS is composed predominantly of large epithelioid tumor cells and is often infiltrated by neutrophils, in contrast to spindled tumor cells admixed with lymphocytes and plasma cells as observed in the classic IMT. The majority of E‐IMS tumors stain positively with an anti‐ALK antibody in a peculiar nuclear membranous pattern, a diagnostic feature that is consistent with the fusion between ALK and a nuclear pore complex protein Ran‐binding protein 2 ( RANBP2 ), which is limited to, and represents most cases of, this particular variant …”

“…The majority of E-IMS tumors stain positively with an anti-ALK antibody in a peculiar nuclear membranous pattern, a diagnostic feature that is consistent with the fusion between ALK and a nuclear pore complex protein Ran-binding protein 2 (RANBP2), which is limited to, and represents most cases of, this particular variant. 10,11,13 To the best of our knowledge, the cytopathology literature regarding IMT or inflammatory pseudotumor is limited to case reports and small series. [14][15][16][17][18][19] Because of its rarity and novelty, E-IMS has not yet come within the scope of cytopathology.…”