Adamantinoma‐like Ewing sarcoma of the parotid gland: Cytopathologic findings and differential diagnosis

Adamantinoma‐like Ewing sarcoma (AES) is a rare variant of Ewing sarcoma family of tumors (EFTs), primarily affecting bone and soft tissue. AES has mixed features of Ewing sarcoma (ES)/primitive neuroectodermal tumor (PNET) and adamantinoma with a complex immunoprofile and EWSR1 gene rearrangements. Herein, we report a 72‐year‐old male who presented with left parotid mass, right neck mass and thyroid nodules. Fine needle aspiration of the left parotid mass displayed nests of monotonous epithelioid cells with basaloid features in a background of small round blue cells and lymphocytes. AES can involve head and neck region and is characterized by groups of primitive small round blue cells admixed with groups of epithelioid cells with amphophilic cytoplasm and focal squamous differentiation. The proportion of these components can be variable, creating diagnostic challenges, particularly in unusual anatomic sites such as the parotid gland. However, when additional material is available, CD99 and/or FLI1 immunostains need to be included for diagnostic confirmation.     

The diversity of soft tissue tumours with EWSR1 gene rearrangements: a review

Many soft tissue sarcomas have chromosomal translocations with resultant formation of new fusion genes. Among the genes that can be rearranged, the EWSR1 gene has been identified as a partner in a wide variety of clinically and pathologically diverse sarcomas as well as some non‐mesenchymal tumours. The former include Ewing sarcoma and similar (Ewing‐like) small round cell sarcomas, desmoplastic small round cell tumour, myxoid liposarcoma, extraskeletal myxoid chondrosarcoma, angiomatoid fibrous histiocytoma, clear cell sarcoma of soft tissue and clear cell sarcoma‐like tumours of the gastrointestinal tract, primary pulmonary myxoid sarcoma, extrasalivary myoepithelial tumours and sporadic examples of low‐grade fibromyxoid sarcoma, sclerosing epithelioid fibrosarcoma and mesothelioma. EWSR1 is a ‘promiscuous’ gene that can fuse with many different partner genes, but sometimes this results in phenotypically identical tumours. EWSR1 can, conversely, partner with the same genes in morphologically and behaviourally different neoplasms. This paper reviews the diversity of the several soft tissue tumour types that are associated with rearrangement of the EWSR1 gene.     

A SMARCB1-deficient vulvar neoplasm with prominent myxoid stroma: report of a case showing ERG and FLI1 expression

In the vulvar region, epithelioid sarcoma (ES) is the most frequent SMARCB1-deficient neoplasm, followed by myoepithelial carcinoma (MC). Previous studies have demonstrated that some SMARCB1-deficient vulvar neoplasms cannot be classified as either ES or MC. Herein, we report of a 42-year-old woman with a SMARCB1-deficient neoplasm with prominent myxoid stroma in the vulva. It contained both epithelioid and spindled tumor cells, both of which showed vimentin and EMA expression. Although other markers useful for the differential diagnosis among SMARCB1-deficient tumors were negative, this tumor displayed characteristic expression of ERG and FLI1. As there are no reliable data regarding expression of ERG and FLI1 in MC, which are demonstrated to be often expressed in ES, further classification of cases such as the one reported here requires reliable data regarding their expression status in MC.     

Newly described translocation (18;19)(q23;q13.2) in abdominal wall soft-tissue tumor resembling Ewing sarcoma/primitive neuroectodermal tumor

From a morphologic standpoint, Ewing sarcoma (EWS) is one of a number of pediatric malignancies that are characterized by sheets of small, round, blue cells. Ewing sarcoma can usually be differentiated from other small round blue cell tumors by the presence of a gene rearrangement having a consistent breakpoint within the Ewing sarcoma gene (EWSR1) at 22q12. Although the most common translocation partner is FLI1, located at 11q24, there is a growing list of alternate rearrangements involving different loci. We describe the first example of a soft-tissue sarcoma morphologically and immunohistochemically similar to Ewing sarcoma, but with a novel t(18;19)(q23;q13.2).     

Ewing sarcoma family of tumours: unusual histological variants and immunophenotypic characteristics

Ewing sarcoma family of tumours are typified by small round blue cell morphology with variable but usually minimal neuroectodermal differentiation and non-random translocations involving the EWSR1 gene and a member of the ETS family of genes. Atypical morphological patterns may be seen in up to 20% of cases and include large cell, adamantinoma-like, spindle cell sarcoma-like (synovial sarcoma like), sclerosing, clear cell (hypernephroid)/anaplastic, and vascular like patterns. Immunophenotypically, CD99, vimentin, CAV1 and FLI1 are typically positive. Around half of the cases may express NSE and/or CD57. Low molecular weight cytokeratins (CK), S100, NB84, and CD117 are expressed less commonly (around 20%–40%). EMA, desmin, CD31, and synaptophysin expression are rare. CK7, CK20, D2-40, chromogranin, TDT, TTF, MYF4 appear to be consistently negative. Molecular confirmation is less sensitive. The correct diagnosis requires correlation between morphology and immunostaining, and may require molecular testing.     

Small cell osteosarcoma with Ewing sarcoma breakpoint region 1 gene rearrangement detected by interphase fluorescence in situ hybridization

Because of its characteristic morphologic appearance, small cell osteosarcoma (SCO) can be confused with other small round cell malignancies of the bone, most importantly with Ewing sarcoma, making this distinction difficult. A specific tool used in separating SCO from Ewing sarcoma has been the detection of Ewing sarcoma breakpoint region 1 (EWSR1) gene rearrangements in Ewing sarcoma and their absence in SCO. However, there are rare case reports that have documented the existence of EWSR1 gene rearrangement in SCO. In this report, we describe another case of SCO with an EWSR1 gene rearrangement detected by interphase fluorescence in situ hybridization. Our finding adds support to the existing evidence that SCO is a tumor that can be characterized by EWSR1 gene arrangements. Therefore, we caution the pathology community not to rely solely on molecular studies in distinguishing SCO from Ewing sarcoma.     

Ewing family tumours: a paediatric perspective

Sarcomas are malignant tumours of the connective tissues and are proportionately much more common in children than in adults. The Ewing family of tumours (EFT) is a group of sarcomas sharing rearrangement of the EWSR1 gene on 22q12, and include Ewing sarcoma/primitive neuroectodermal tumour, desmoplastic small round cell tumour, angiomatoid fibrous histiocytoma and clear cell sarcoma. Other tumours harbouring EWSR1 rearrangements include myoepithelial tumours, myxoid liposarcoma and extraskeletal chondrosarcoma. In addition, a group of Ewing-like primitive round cell sarcomas have been recently described in a paediatric population, further expanding the list of EFT. This review will focus on the histopathological, immunohistochemical and molecular genetic features of EFT, with an emphasis on those predominantly occurring in the paediatric population.     

Primary Ewing sarcoma/PNET of the kidney: fine-needle aspiration, histology, and dual color break apart FISH Assay

A 34-year-old previously healthy Hispanic man presented with lower back pain. CT scan revealed an 8-cm space-occupying lesion in the superior pole of the left kidney with numerous small lytic lesions in the skull, vertebrae, ribs, and pelvic bones. CT-guided fine-needle aspiration biopsy revealed a high-grade primitive small round cell tumor with the tumor cells being strongly positive for CD99 and vimentin. The patient subsequently underwent a left nephrectomy. Fluorescence in situ hybridization analysis using a DNA probe for the Ewing Sarcoma breakpoint region 1 (EWSR1) on chromosome 22g12 revealed a rearrangement of the EWSR1 locus. The diagnosis of primary Ewing sarcoma/primitive neuroectodermal tumor of the kidney was established.     

Novel fusion sarcomas including targetable NTRK and ALK

BackgroundChallenging emerging entities with distinctive molecular signatures may benefit from algorithms for diagnostic work-up.MethodsFusion sarcomas (2020–2021, during pandemic) were diagnosed by clinicoradiology, morphology, phenotype, and next-generation sequencing (NGS).ResultsSix fusion sarcomas in two males and four females involved the chest-wall, neck, or extremities; ages ranged 2-73, median 18 years. Sizes ranged 5.3-25.0, median 9.1 cm. These include high grade 1) TPR-NTRK1 of proximal femur with a larger rounded soft tissue mass, previously considered osteosarcoma yet without convincing tumor matrix. A pathologic fracture necessitated emergency hemipelvectomy (NED) and 2) novel KANK1-NTRK2 sarcoma of bone and soft tissue with spindled pleomorphic to epithelioid features (AWD metastases). 3) Novel ERC1-ALK unaligned fusion, a low grade infiltrative deep soft tissue hand sarcoma with prominent-vascularity, myopericytoid/lipofibromatosis-like ovoid cells, and collagenized stroma, was successfully treated with ALK-inhibitor (Crizotinib), avoiding amputation. These NTRK and ALK tumors variably express S100 and CD34 and were negative for SOX10. 4) and 5) CIC-DUX4 round cell tumors (rapid metastases/demise), one with COVID superinfection, were previously treated as Ewing sarcoma. These demonstrated mild pleomorphism and necrosis, variable myxoid change and CD99 reactivity, and a distinctive dot-like-Golgi WT1 immunostaining pattern. 6) A chest wall/thoracic round cell sarcoma, focal CD34/ keratins/CK7, revealed nuclear-STAT6, STAT6-NAB2 by NGS, confirming malignant solitary fibrous tumor, intermediate-risk-stratification (AWD metastases).ConclusionsRecent fusion sarcomas include new KANK1-NTRK2 and ERC1-ALK, the latter successfully treated by targeted-therapy. ALK/NTRK fusion partners TPR and KANK1 suggest unusual high-grade morphology/behavior. Clinicoradiologic, morphologic, and phenotypic algorithms can prompt molecular-targeted immunostains or NGS for final classification and promising inhibitor therapy.     

Role of fine needle aspiration cytology in the diagnosis of a rare case of a poorly differentiated synovial sarcoma with “Rhabdoid” features,including treatment implications

Synovial sarcoma is a high‐grade, soft tissue sarcoma that is relatively chemosensitive. Its exact diagnosis is crucial, including differentiation from its closest diagnostic mimic, ie, Ewing sarcoma, in view of different treatment options, including chemotherapy regimens, for both these tumors. A 15‐year‐old girl presented with a recurrent soft tissue mass in her right popliteal region, which was diagnosed as Ewing sarcoma, based on positive immunoexpression of MIC2/CD99, Fli1 and negative expression of LCA and desmin. During her metastatic “work‐up”, a popliteal lymph node was identified, which was aspirated and examined. Fine needle aspiration cytology smears showed singly scattered and loose, cohesive clusters of cells containing round to polygonal, to short spindle‐shaped nuclei with prominent nuclei, and moderate to abundant cytoplasm, including several “rhabdoid” cells. These features prompted a review of the biopsy of the recurrent tumor, and additional immunohistochemical stains, which revealed positive co‐expression of pan cytokeratin (AE1/AE3), epithelial membrane antigen (EMA), along with a characteristic variable staining pattern of INI11/SMARCB1. Subsequently, by fluorescent in situ hybridization (FISH) technique, performed on the paraffin section of the recurrent tumor, 100% tumor nuclei displayed SS18 rearrangement, while none of the tumor cells displayed EWSR1 rearrangement. Diagnosis of poorly differentiated SS with “rhabdoid” features was confirmed. This constitutes as the first case, describing cytopathologic features of a poorly differentiated SS with “rhabdoid” features, initially misdiagnosed as a Ewing sarcoma, on biopsy and confirmed as SS by FISH technique. The diagnostic and treatment implications in this case are discussed herewith. Diagn. Cytopathol. 2017;45:662–667. © 2017 Wiley Periodicals, Inc.