Head and Neck Round Cell Sarcomas: A Comparative Clinicopathologic Analysis of 2 Molecular Subsets: Ewing and CIC-Rearranged Sarcomas

Currently considered a variant of Ewing sarcoma, adamantinoma-like Ewing sarcoma is a rare malignancy that shows classic Ewing sarcoma-associated gene fusions but also epithelial differentiation. Here we present the 6th reported case of adamantinoma-like Ewing sarcoma involving the thyroid gland. Sections of the thyroid tumor from a 20-year old woman showed sheets, lobules and trabeculae of primitive, uniform, small round blue cells that diffusely expressed pankeratin, p40 and CD99. Fluorescent in situ hybridization revealed an EWSR1 gene rearrangement and an EWSR1-FLI1 fusion was detected by RT-PCR. Neck lymph nodes were not involved, and the patient was treated with a Ewing sarcoma chemotherapy protocol and radiation and is disease free 7 months after surgery. The unusual histology and immunohistochemical profile of adamantinoma-like Ewing sarcoma makes diagnosis and classification very challenging. We also present a literature review of adamantinoma-like Ewing sarcoma involving the thyroid.

Section: Discussionmentioning

confidence: 99%

Adamantinoma-Like Ewing Sarcoma of the Thyroid: A Case Report and Review of the Literature

Morlote

Harada

Lindeman

et al. 2019

“…There are also rare subsets of undifferentiated round cell sarcomas that share histologic similarities with EWS but lack EWSR1 rearrangement. These occur exclusively in the soft tissue, commonly in the neck but also in the scalp, submandibular region and tonsil [65]. The histology of these sarcomas differs slightly from EWS in that they often show geographic necrosis, mild nuclear pleomorphism with prominent nucleoli, clear cell areas, and focal myxoid matrix.…”

Section: Ewing Sarcomamentioning

confidence: 99%

Clinical Utility of In Situ Hybridization Assays in Head and Neck Neoplasms

Luk

Selinger

Cooper

et al. 2018

Head and neck pathology present a unique set of challenges including the morphological diversity of the neoplasms and presentation of metastases of unknown primary origin. The detection of human papillomavirus and Epstein-Barr virus associated with squamous cell carcinoma and newer entities like HPV-related carcinoma with adenoid cystic like features have critical prognostic and management implications. In salivary gland neoplasms, differential diagnoses can be broad and include non-neoplastic conditions as well as benign and malignant neoplasms. The detection of specific gene rearrangements can be immensely helpful in reaching the diagnosis in pleomorphic adenoma, mucoepidermoid carcinoma, secretory carcinoma, hyalinizing clear cell carcinoma and adenoid cystic carcinoma. Furthermore, molecular techniques are essential in diagnosis of small round blue cell neoplasms and spindle cell neoplasms including Ewing sarcoma, rhabdomyosarcoma, synovial sarcoma, biphenotypic sinonasal sarcoma, dermatofibrosarcoma protuberans, nodular fasciitis and inflammatory myofibroblastic tumor. The detection of genetic rearrangements is also important in lymphomas particularly in identifying 'double-hit' and 'triple-hit' lymphomas in diffuse large B cell lymphoma. This article reviews the use of in situ hybridization in the diagnosis of these neoplasms.

“…4d). On comparing the OS between the HN MPNST study group (n = 13) to other head and neck soft tissue sarcomas (OHNSTS) from our database with confirmed molecular diagnosis (Ewing sarcoma n = 8, Ewing-like sarcoma with CIC-rearrangements n = 11, rhabdomyosarcoma n = 97 and synovial sarcoma n = 34) [31][32][33][34][35], MPNST patients had the worst outcome (p < 0.0001) (Fig. 5).…”

Section: Survival Analysismentioning

confidence: 99%

A Clinicopathologic Study of Head and Neck Malignant Peripheral Nerve Sheath Tumors

Owosho

Estilo

Huryn

et al. 2017

Self Cite

Head and neck high grade malignant peripheral nerve sheath tumors (HN-MPNSTs) are rare highly aggressive soft tissue sarcomas that show overlapping morphologic and immunophenotypic features with melanoma and other high grade sarcomas, resulting in diagnostic challenges, particularly in sporadic settings. Recent discoveries have implicated loss of function mutations in the polycomb repressive complex 2 (PRC2) components, including EED or SUZ12 genes, as one of the leading pathogenetic mechanisms in high grade MPNST. MPNSTs with PRC2 loss are associated with complete loss of trimethylation at lysine 27 of histone H3 (H3K27me3), which emerged as a reliable immunohistochemical marker in the diagnosis of sporadic and radiation induced MPNST. As the diagnosis of MPNST in the HN is particularly challenging to distinguish from melanoma and other sarcoma types, we carried out a clinicopathologic analysis on HN-MPNST patients managed at our institution over a 20-year period (1997-2016), using the latest diagnostic criteria including H3K27me3 staining and other molecular investigations. The overall survival of HN-MPNST was compared with other HN soft tissue sarcomas. The diagnosis of HN-MPNST was confirmed in 13 patients (seven males and six females), with a mean age of 31 years; with 3 (23%) patients being of pediatric age. The most common site was the neck soft tissue (77%). Two-thirds of patients (n = 9) had stigmata of NF1, three had prior radiotherapy and only one developed a de novo MPNST. All except one tumor (86%) tested showed loss of H3K27me3 expression, including all non-NF1 patients. The 2 and 5-year DSS rates were 50 and 30%. The 2-year DFS rate was 21%. Adverse predictors on DSS included adult age (p = 0.011), prior-history of RT (p = 0.003) and recurrence (p = 0.003). Compared to other molecularly confirmed subsets of HN sarcomas (Ewing and Ewing-like sarcoma, rhabdomyosarcoma and synovial sarcoma), HN-MPNST had the worst overall survival (p < 0.0001). We conclude that HN-MPNSTs are highly aggressive sarcomas associated with an unfavorable outcome and the utility of H3K27me3 IHC stains in the evaluation of MPNST is a reliable ancillary diagnostic adjunct.