Novel fusion sarcomas including targetable NTRK and ALK.
Ann Diagn Pathol
; 54: 151800, 2021 Oct.
Article
in English
| MEDLINE | ID: covidwho-1321982
ABSTRACT
BACKGROUND:
Challenging emerging entities with distinctive molecular signatures may benefit from algorithms for diagnostic work-up.METHODS:
Fusion sarcomas (2020-2021, during pandemic) were diagnosed by clinicoradiology, morphology, phenotype, and next-generation sequencing (NGS).RESULTS:
Six fusion sarcomas in two males and four females involved the chest-wall, neck, or extremities; ages ranged 2-73, median 18â¯years. Sizes ranged 5.3-25.0, median 9.1â¯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).CONCLUSIONS:
Recent 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.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Sarcoma
/
Soft Tissue Neoplasms
/
Thoracic Neoplasms
/
Biomarkers, Tumor
/
Gene Fusion
/
Femoral Neoplasms
/
Head and Neck Neoplasms
Type of study:
Case report
/
Diagnostic study
/
Prognostic study
Language:
English
Journal:
Ann Diagn Pathol
Journal subject:
Pathology
Year:
2021
Document Type:
Article
Affiliation country:
J.anndiagpath.2021.151800
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