Application of ancillary studies in soft tissue cytology using a pattern‐based approach

Abstract

The cytologic diagnosis of soft tissue neoplasms has undergone many advances due to the development of numerous useful immunohistochemical markers and molecular assays that target specific molecular alterations. Ancillary tests, when used in conjunction with clinical, radiologic, and cytomorphologic features, allow for more accurate classification and refinement of differential diagnoses of soft tissue neoplasms. Soft tissue tumors encompass a diverse group of tumors showing a wide range of cytomorphologies that can be broadly grouped as lipomatous, myxoid, spindled, pleomorphic, round cell, and epithelioid. This pattern-based classification enables the formation of appropriate differentials; however, entities that share these basic morphologic patterns may vary greatly in their clinical behavior. The breadth of soft tissue tumors that can be diagnosed on cytologic preparations continues to increase with identification of defining molecular alterations that can be detected by conventional means (eg, fluorescence in situ hybridization) or by immunohistochemical surrogates. Furthermore, the emergence of high-throughput molecular techniques (eg, next generation sequencing) has potential roles for additional discovery and diagnostic applications. This review highlights the diagnostic role of ancillary tests in the context of a pattern-based approach to soft tissue cytology. Cancer Cytopathol 2018;000:000-000. © 2018 American Cancer Society.

EWSR1 fusions: Ewing sarcoma and beyond

“…It should also be noted that because EWSR1 and FUS can substitute for one another, testing for FUS rearrangement (also conventionally by FISH) should be considered if EWSR1 FISH is unexpectedly negative. Practical applications of ancillary testing in the differential diagnosis of round cell sarcomas and other soft‐tissue tumor differentials have been extensively reviewed, and the practicing cytopathologist should adhere to the judicious selection of immunohistochemical panels and molecular assays that are guided by clinical context and morphology. With increased adoption of next‐generation sequencing assays, the selection of single tests may no longer be relevant in the future.…”

Immunocytochemistry for diagnostic cytopathology—A practical guide

“…Although the primary site in the majority of these cases is the lung (TTF1+), neuroendocrine carcinomas from other sites are also often positive for this marker 162,167 . The differential diagnosis includes Merkel cell carcinoma and small round blue cell tumours 168–174 …”

“…Small cell morphology can be seen in many tumours, including carcinomas, lymphoma, melanoma and small round blue cell tumours. The primary ICC panel in such a scenario can include keratin, desmin, S100, TdT, and CD99; however, additional ancillary tests such as molecular testing may be necessary to further classify these neoplasms 170–174,176 (Table 14).…”

“…The first panel should at least include a pankeratin, CD45 and S100 followed by additional markers based on the initial staining profile 176,243,249 . Keratin will be at least focally positive in carcinomas; however, certain sarcomas, such as synovial sarcoma, epithelioid sarcoma, and epithelioid angiosarcoma, can express keratins 172,243,245 . Many sarcomas cannot be characterised by ICC alone and need additional ancillary tests such as translocations/chromosomal alterations for a diagnosis and with a small sample definite classification of sarcomas may not always be possible (Table 15).…”

Diagnostic challenges in the gray-zone lesions of fine-needle aspiration cytology

“…[ 22 ] Molecular advances helped in the development of useful surrogate IHC markers of molecular changes. [ 23 ] ICC, FISH, and sequencing-based methods can be excellent ancillary diagnostic modalities. Table 3 enumerates the IHC and molecular markers of soft-tissue tumors frequently subjected to FNAC.…”