Uterine Cervical Sarcoma With a Novel RET-SPECC1L Fusion in an Adult

Weisman, Paul; Altınok, M. Tayfun; Carballo, Erica V; Kushner, David M.; Kram, Jessica J. F.; Ladanyi, Marc; Chiang, Sarah; Buehler, Darya; Michelson, Elizabeth L Dickson

doi:10.1097/pas.0000000000001437

Cited by 22 publications

(15 citation statements)

References 15 publications

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“…A subset of NTRK -rearranged soft tissue tumors show some overlapping histologic characteristics with NTRK sarcomas of the uterus (fascicular spindle cell proliferations with stromal and perivascular hyalinization and S100/CD34 expression),27 however, the relationship between the 2 remains unclear. Similarly, some spindle cell uterine tumors with fibrosarcoma-like morphology harbor targetable non- NTRK fusions, including COL1A1::PDGFB , FGFR1::TACC1 , and SPECC1L::RET 3,4,38. The relationship between these tumors and those that are driven by NTRK fusions remains to be fully elucidated, but all of these tumor types may ultimately fall under the same broad diagnostic category of “fibrosarcoma-like uterine sarcomas.” Additional studies examining their morphology, clinical behavior, and molecular characteristics (eg, methylation profiles) will be helpful to classify them and better understand how they are related.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, some spindle cell uterine tumors with fibrosarcoma-like morphology harbor targetable non-NTRK fusions, including COL1A1::PDGFB, FGFR1:: TACC1, and SPECC1L::RET. 3,4,38 The relationship between these tumors and those that are driven by NTRK fusions remains to be fully elucidated, but all of these tumor types may ultimately fall under the same broad diagnostic category of "fibrosarcoma-like uterine sarcomas." Additional studies examining their morphology, clinical behavior, and molecular characteristics (eg, methylation profiles) will be helpful to classify them and better understand how they are related.…”

Section: Ntrk Fusions and Related Tumorsmentioning

confidence: 99%

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NTRK-Rearranged Uterine Sarcomas: Clinicopathologic Features of 15 Cases, Literature Review, and Risk Stratification

Costigan

Nucci

Dickson

et al. 2022

American Journal of Surgical Pathology

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NTRK-rearranged uterine sarcomas are rare spindle cell neoplasms that typically arise in the uterine cervix of young women. Some tumors recur or metastasize, but features which predict behavior have not been identified to date. Distinguishing these tumors from morphologic mimics is significant because patients with advanced stage disease may be treated with TRK inhibitors. Herein, we present 15 cases of NTRK-rearranged uterine sarcomas, the largest series to date. Median patient age was 35 years (range: 16 to 61). The majority arose in the uterine cervix (n = 14) and all but 2 were organ-confined at diagnosis. Tumors were composed of an infiltrative, fascicular proliferation of spindle cells and most showed mild-to-moderate cytologic atypia. All were pan-TRK positive by immunohistochemistry (13/13); S100 (11/13) and CD34 (6/10) were usually positive. RNA or DNA sequencing found NTRK1 (10/13) and NTRK3 (3/ 13) fusions with partners TPR, TPM3, EML4, TFG, SPECC1L, C16orf72, and IRF2BP2. Unusual morphology was seen in 2 tumors which were originally diagnosed as unclassifiable uterine sarcomas, 1 of which also harbored TP53 mutations. Follow up was available for 9 patients, of whom 3 died of disease. By incorporating outcome data of previously reported tumors, adverse prognostic features were identified, including a mitotic index ≥ 8 per 10 high-power fields, lymphovascular invasion, necrosis, and NTRK3 fusion. Patients with tumors which lacked any of these 4 features had an excellent prognosis. This study expands the morphologic spectrum of NTRK-rearranged uterine sarcomas and identifies features which can be used for risk stratification.

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Section: Discussionmentioning

confidence: 99%

Section: Ntrk Fusions and Related Tumorsmentioning

confidence: 99%

NTRK-Rearranged Uterine Sarcomas: Clinicopathologic Features of 15 Cases, Literature Review, and Risk Stratification

Costigan

Nucci

Dickson

et al. 2022

American Journal of Surgical Pathology

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“…Although mesenchymal tumors with kinase fusion were first described in superficial soft tissues,10 a wide range of anatomic sites, including deep soft tissue, thoracic cavity, gynecologic tract, and gastrointestinal tract, can be involved by these tumors 3,19,20,25–29. The HN region can occasionally be affected, however, to date, merely 9 HN cases have been reported as single case reports or small series, including 7 with NTRK1 fusion, and 1 each with NTRK3 fusion, and RET fusion 3,8,10,11,26,30.…”

mentioning

confidence: 99%

“…[21][22][23][24] Although mesenchymal tumors with kinase fusion were first described in superficial soft tissues, 10 a wide range of anatomic sites, including deep soft tissue, thoracic cavity, gynecologic tract, and gastrointestinal tract, can be involved by these tumors. 3,19,20,[25][26][27][28][29] The HN region can occasionally be affected, however, to date, merely 9 HN cases have been reported as single case reports or small series, including 7 with NTRK1 fusion, and 1 each with NTRK3 fusion, and RET fusion. 3,8,10,11,26,30 We herein describe the clinicopathologic features of a large cohort of 15 cases with HN mesenchymal tumors harboring kinase fusions, including 3 cases of IFS with canonical ETV6:: NTRK3 fusion, 1 IFS-like tumor with RBPMS::MET fusions, and 12 other mesenchymal tumors with NTRK1, NTRK3, BRAF, or RET gene rearrangements.…”

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confidence: 99%

Head and Neck Mesenchymal Tumors with Kinase Fusions

Suurmeijer

Agaram

et al. 2022

American Journal of Surgical Pathology

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Mesenchymal tumors harboring various kinase fusions were recently recognized as emerging entities mainly in the soft tissues. We herein investigate the clinicopathologic and molecular characteristics of head and neck mesenchymal tumors harboring kinase fusions. The study cohort included 15 patients with a median age of 13 years (ranging from congenital to 63 y). The kinase genes involved in descending order were NTRK1 (n=6), NTRK3 (n=5), BRAF (n=2), and 1 each with MET, and RET. The anatomic locations were broad involving all tissue planes, including skin (n=4), intraosseous (n=4), major salivary glands (n=2), sinonasal tract (n=2), soft tissue of face or neck (n=2), and oral cavity (n=1). The histologic spectrum ranged from benign to high grade, in descending order including tumors resembling malignant peripheral nerve sheath tumor (MPNST)-like, fibrosarcoma (infantile or adult-type), lipofibromatosis-like neural tumor (LPFNT), inflammatory myofibroblastic tumor-like, and a novel phenotype resembling myxoma. Perivascular hyalinization/stromal keloid-like collagen bands and staghorn vasculature were common features in MPNST-like and LPFNT-like tumors. Two tumors (1 each with NTRK1 or BRAF rearrangement) were classified as high grade. By immunohistochemistry, S100 and CD34 positivity was noted in 71% and 60%, frequently in MPNST-like and LPFNT-like phenotypes. Pan-TRK was a sensitive marker for NTRK-translocated tumors but was negative in tumor with other kinase fusions. One patient with a high-grade tumor developed distant metastasis. Molecular testing for various kinase fusions should be considered for S100+/CD34+ spindle cell neoplasms with perivascular hyalinization and staghorn vessels, as pan-TRK positivity is seen only in NTRK fusions.

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“…RET fusion positive neoplasms may also exhibit fibroblastic or neural-like differentiation and have phenotypic overlap with NTRK-related neoplasms (99). Recently a cervical sarcoma with a novel RET-SPECC1L fusion has been described (100). Rare spindle cell sarcomas with recurrent MEIS1-NCOA2 fusions have also been recently described (101).…”

Section: S51 Iccr Reporting Dataset:uterine Mesenchymal Tumorsmentioning

confidence: 99%

Data Set for Reporting of Uterine Malignant and Potentially Malignant Mesenchymal Tumors: Recommendations From the International Collaboration on Cancer Reporting (ICCR)

Nucci

Webster

Croce

et al. 2022

International Journal of Gynecological Pathology

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The International Collaboration on Cancer Reporting (ICCR) seeks to produce standardized, evidence-based protocols for the reporting of tumors with the aim of ensuring that all cancer reports generated worldwide will be of similar high quality and record the same elements. Herein, we describe the development of the data set for the reporting of uterine malignant and potentially malignant mesenchymal tumors by a panel of expert pathologists and a single clinician and provide the commentary and rationale for the inclusion of core and noncore elements. This data set, which incorporates the recent updates from the 5th edition of the World Health Organization Classification of Female Genital Tumors, addresses several subjects of debate including which mesenchymal tumors should be graded, how to document extent of invasion, mitotic counts, and the role of ancillary testing in tumor diagnosis and patient management. The inclusion of elements is evidence-based or based on consensus of the expert panel with clinical relevance being the guiding standard.

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Uterine Cervical Sarcoma With a Novel RET-SPECC1L Fusion in an Adult

Cited by 22 publications

References 15 publications

NTRK-Rearranged Uterine Sarcomas: Clinicopathologic Features of 15 Cases, Literature Review, and Risk Stratification

NTRK-Rearranged Uterine Sarcomas: Clinicopathologic Features of 15 Cases, Literature Review, and Risk Stratification

Head and Neck Mesenchymal Tumors with Kinase Fusions

Data Set for Reporting of Uterine Malignant and Potentially Malignant Mesenchymal Tumors: Recommendations From the International Collaboration on Cancer Reporting (ICCR)

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