Adult NTRK-rearranged spindle cell neoplasms of the viscera: with an emphasis on rare locations and heterologous elements

Tsai, Jen‐Wei; Lee, Jen‐Chieh; Hsieh, Tsung Han; Huang, Shih‐Chiang; Lee, Pei-Hang; Liu, Tingting; Kao, Yu-Chien; Chang, Chingching; Weng, Te‐Fu; Li, Chien‐Feng; Lin, Jung-Chia; Liang, Cher‐Wei; Su, Yu‐Li; Chang, Ian Yi‐Feng; Wang, Yuting; Chang, Nien-Yi; Yu, Shih-Chen; Wang, Jui-Chu; Huang, Hsuan‐Ying

doi:10.1038/s41379-021-01005-3

Cited by 21 publications

(48 citation statements)

References 58 publications

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“…In addition, we herein reported a novel histologic appearance of hypocellular hypovascular myxoid tumor with KIF5B::RET fusion which is composed entirely of bland stellated cells resembling myxoma (ie, myxoma-like), hence expanding the histopathologic spectrum of mesenchymal tumors with kinase fusions. Adenosarcoma-like pattern, a feature described exclusively in gynecologic tract and prostate, is not seen in the HN region 19,20. Characteristic histologic features being repeatedly observed in mesenchymal tumors with kinase fusions of soft tissue, especially in those with a MPNST-like appearance or those with overlapping features of LPFNT, include perivascular hyalinization, keloid-like hyalinizing collagen bands, and staghorn (hemangiopericytoma-like) vasculature 1,3,9,11,13.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

confidence: 99%

Head and Neck Mesenchymal Tumors with Kinase Fusions

Suurmeijer

Agaram

et al. 2022

American Journal of Surgical Pathology

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“…12,31 CDKN2A deletion, as detected by targeted NGS in our case 2, has been suggested as a recurrent additional genetic alternation associated with NTRK-Ó 2022 John Wiley & Sons Ltd., Histopathology, 82, 633-645. rearranged spindle cell neoplasms. 3,4,35,34 This genetic alternation has not been previously documented in RET-fused mesenchymal neoplasms. Whether it was related to RET rearrangement or conferred a worse prognosis is unclear.…”

Section: Discussionmentioning

confidence: 63%

“…This is similar to adult visceral NTRK-rearranged mesenchymal tumours, which exhibited a marked tendency to occur in the cervix. 34 Histologically, all three cases displayed a morphological spectrum typical of fibrosarcoma. In addition, case 1 in the kidney demonstrated foci of irregular alveolar oedema-like structures and areas with microcystic and reticular arrangements; case 2 in the small bowel demonstrated staghorn-type vessels and foci of band- like stromal hyalinisation, as well as scattered inflammatory cells infiltrate.…”

Section: Discussionmentioning

confidence: 89%

“…These features overlap with those of adult NTRK-rearranged mesenchymal tumours in visceral locations including the uterus, gastrointestinal tract, and thorax, which most often showed high-grade fibrosarcomatous or MPNST-like histology and harboured either NTRK1 or NTRK3 rearrangements; of these, approximately half of the cases behaved unfavourably. 34,35 Adenosarcoma-like patterns or phyllodes-like structures, as well as heterologous differentiation, which have been rarely described in NTRK1-rearranged tumours in uterine cervix or prostate, have not been identified in RETrearranged tumours. 34 With regard to the two nonvisceral adult RET-rearranged mesenchymal tumours previously reported, one occurred in the deep dermis of the forearm in a 35-year-old male patient and showed a CD34/S100 protein-positive spindle-cell tumour with perivascular hyalinisation and keloidal collagen fibres.…”

Section: Discussionmentioning

confidence: 99%

“…34,35 Adenosarcoma-like patterns or phyllodes-like structures, as well as heterologous differentiation, which have been rarely described in NTRK1-rearranged tumours in uterine cervix or prostate, have not been identified in RETrearranged tumours. 34 With regard to the two nonvisceral adult RET-rearranged mesenchymal tumours previously reported, one occurred in the deep dermis of the forearm in a 35-year-old male patient and showed a CD34/S100 protein-positive spindle-cell tumour with perivascular hyalinisation and keloidal collagen fibres. This tumour harboured a NCOA4:: RET fusion.…”

Section: Discussionmentioning

confidence: 99%

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Recurrent RET fusions in fibrosarcoma‐like neoplasms in adult viscera: expanding the clinicopathological and genetic spectrum

Zhao

Yin

et al. 2022

Histopathology

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Aims: RET-fused mesenchymal neoplasms mostly affect the soft tissue of paediatric patients. Given their responsiveness to selective RET inhibitors, it remains critical to identify those extraordinary cases occurring in the visceral organs of adults. In this study, we report three RET-rearranged spindle-cell tumours occurring in the visceral organs of adults. Methods and Results: Clinicopathological features were assessed and partner agnostic targeted nextgeneration sequencing on clinically validated platforms were performed. The patients were 18, 53, and 55 years old and included one male and two females. The tumours were located in the kidney (case 1), small intestine (case 2), and ureter (case 3), with maximum diameters of 14, 5, and 1 cm, respectively. Histologically, all tumours displayed a morphological spectrum typical of fibrosarcoma, including moderately to highly cellular, nonpleomorphic, ovoid to spindle-shaped cells arranged in long fascicles or haphazardly within collagenised to myxohyaline stroma. Foci of irregular alveolar oedema-like structures and areas with microcystic and reticular arrangements were identified in the renal tumour. Staghorn-type vessels and foci of band-like stromal hyalinisation were observed in the small intestine tumour. Cases 1 and 2 were high-grade and pursed a highly aggressive clinical course, while case 3 was of intermediate grade with no tumour recurrence or metastasis 14 years after surgery. All three tumours expressed CD34, which was coexpressed with S100 protein in cases 2 and 3. Molecular genetic testing revealed PRKAR1A::RET, KIF5B::RET, and SPECC1L::RET inframe gene fusions. Conclusion: Our study expands the clinicopathological and genetic spectrum of mesenchymal neoplasms associated with RET fusions.

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Uncommon Uterine Mesenchymal Neoplasms and Mixed Epithelial-Mesenchymal Lesions

Pinto,

Bennett

2024

Gynecologic and Obstetric Pathology

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Adult NTRK-rearranged spindle cell neoplasms of the viscera: with an emphasis on rare locations and heterologous elements

Cited by 21 publications

References 58 publications

Head and Neck Mesenchymal Tumors with Kinase Fusions

Head and Neck Mesenchymal Tumors with Kinase Fusions

Recurrent RET fusions in fibrosarcoma‐like neoplasms in adult viscera: expanding the clinicopathological and genetic spectrum

Uncommon Uterine Mesenchymal Neoplasms and Mixed Epithelial-Mesenchymal Lesions

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