Primary <scp>NTRK</scp>‐rearranged spindle cell  neoplasm of bone harboring an <i><scp>HMBOX1</scp>::<scp>NTRK3</scp></i> gene fusion

Wang, Zhe; Wang, Jian

doi:10.1002/gcc.23132

Cited by 2 publications

(3 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…21,22 To date (including eight cases from the current study), 15 patients with mesenchymal spindle cell tumors originating from bone and harboring kinase fusions were reported in the literature after excluding prototypical cases of IMT. 4,6,7,15,[23][24][25][26] The clinicopathologic features, fusion events, and IHC profile of these cases are summarized in Table 3. Four tumors presenting in children below the age of 2 years were classified by default as IFS/IFS-like tumors.…”

Section: Clinical Outcomementioning

confidence: 99%

Kinase fusion positive intra‐osseous spindle cell tumors: A series of eight cases with review of the literature

Suurmeijer,

Xu,

Torrence

et al. 2023

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

Mesenchymal spindle cell tumors with kinase fusions, often presenting in superficial or deep soft tissue locations, may rarely occur in bone. Herein, we describe the clinicopathologic and molecular data of eight bone tumors characterized by various kinase fusions from our files and incorporate the findings with the previously reported seven cases, mainly as single case reports. In the current series all but one of the patients were young children or teenagers, with an age range from newborn to 59 years (mean 19 years). Most tumors (n = 5) presented in the head and neck area (skull base, mastoid, maxilla, and mandible), and remaining three in the tibia, pelvic bone, and chest wall. The fusions included NTRK1 (n = 3), RET (n = 2), NTRK3 (n = 2), and BRAF (n = 1). In the combined series (n = 15), most tumors (73%) occurred in children and young adults (<30 years) and showed a predilection for jaw and skull bones (40%), followed by long and small tubular bones (33%). The fusions spanned a large spectrum of kinase genes, including in descending order NTRK3 (n = 6), NTRK1 (n = 4), RET (n = 2), BRAF (n = 2), and RAF1 (n = 1). All fusions confirmed by targeted RNA sequencing were in‐frame and retained the kinase domain within the fusion oncoprotein. Similar to the soft tissue counterparts, most NTRK3‐positive bone tumors in this series showed high‐grade morphology (5/6), whereas the majority of NTRK1 tumors were low‐grade (3/4). Notably, all four tumors presenting in the elderly were high‐grade spindle cell sarcomas, with adult fibrosarcoma (FS)‐like, malignant peripheral nerve sheath tumor (MPNST)‐like and MPNST phenotypes. Overall, 10 tumors had high‐grade morphology, ranging from infantile and adult‐types FS, MPNST‐like, and MPNST, whereas five showed benign/low‐grade histology (MPNST‐like and myxoma‐like). Immunohistochemically (IHC), S100 and CD34 positivity was noted in 57% and 50%, respectively, while co‐expression of S100 and CD34 in 43% of cases. One‐third of tumors (4 high grade and the myxoma‐like) were negative for both S100 and CD34. IHC for Pan‐TRK was positive in all eight NTRK‐fusion positive tumors tested and negative in two tumors with other kinase fusions. Clinical follow‐up was too limited to allow general conclusions.

show abstract

Section: Clinical Outcomementioning

confidence: 99%

Kinase fusion positive intra‐osseous spindle cell tumors: A series of eight cases with review of the literature

Suurmeijer,

Xu,

Torrence

et al. 2023

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

show abstract

“…Reported sites include uterus (especially uterine cervix), 5,6 intrathoracic cavity (lung, pleura, and heart), 7,8 gastrointestinal (GI) tract, 9 prostate, 8 and bone. 10 In addition, its manifestation in adulthood has also been well documented. 8,11,12 Largely due to the morphological heterogeneity and nonconsistent immunophenotype, NTRK-rearranged spindle cell neoplasm poses a considerable diagnostic challenge to pathologists, especially with regard to those occurring at unusual sites.…”

mentioning

confidence: 99%

“…However, occurrence in the visceral organs has also been described, albeit very rare. Reported sites include uterus (especially uterine cervix), 5,6 intrathoracic cavity (lung, pleura, and heart), 7,8 gastrointestinal (GI) tract, 9 prostate, 8 and bone 10 . In addition, its manifestation in adulthood has also been well documented 8, …”

mentioning

confidence: 99%

Primary NTRK-rearranged Spindle Cell Neoplasm of the Gastrointestinal Tract: A Clinicopathological and Molecular Analysis of 8 Cases

Gao,

Xu,

Zhu

et al. 2024

American Journal of Surgical Pathology

Self Cite

View full text Add to dashboard Cite

NTRK-rearranged spindle cell neoplasm occurs predominantly in the superficial or deep soft tissues of extremities or trunk. Occurrence in the visceral organs is extremely rare. Herein, we describe 8 cases of NTRK-rearranged spindle cell neoplasm that arose primarily in the gastrointestinal tract. Patients included 5 males and 3 females with age at presentation ranging from 6 to 63 years (median: 29.5 years). Tumors occurred in the colon (n=3), small intestine (n=2), rectum (n=2), and stomach (n=1). Tumor size ranged from 3.5 to 9 cm (median: 5 cm). Morphologically, 4 tumors were low-grade, composed of haphazard or intertwining fascicles of spindle cells, with prominent interstitial collagen fibers and ring-like perivascular hyalinization being present in 2 tumors. The other 4 tumors were histologically high-grade sarcomas, consisting of sweeping fascicles of atypical spindle cells showing increased cellularity and brisk mitotic activity. Immunohistochemically, 6/6 cases (100%) showed diffuse and strong cytoplasmic staining of pan-TRK. Variable expression of TrkA, CD34, and S100 was noted in 5/5 (100%), 5/8 (62.5%), and 4/7 (57.1%) cases, respectively. Fluorescence in situ hybridization analysis showed NTRK1 rearrangement (n=7) and NTRK2 rearrangement (n=1). In cases with available materials, RNA sequencing identified LMNA::NTRK1 (n=3), TPM3::NTRK1 (n=2), and STRN::NTRK2 (n=1) fusions. At follow-up (range: 4 to 30 months; median: 12.5 months), 6 of 7 patients who underwent surgery had no evidence of disease at last follow-up. One patient was succumbed to the disease at 12 months despite adjunctive treatment with TRK inhibitor larotrectinib after surgery. One patient was treated with larotrectinib alone. He showed significant response at 7 months after treatment. NTRK-rearranged spindle cell neoplasm represents an exceptionally rare entity in the gastrointestinal tract. The presence of interstitial collagen fibers and ring-like perivascular hyalinization and co-expression of CD34 and S100 are diagnostic clues to low-grade neoplasms. However, high-grade sarcomas pose a considerable diagnostic challenge to pathologists owing to the lack of specific features. The final diagnosis relies on molecular assays. Patients with advanced disease may benefit from TRK inhibitor treatment.

show abstract

Primary NTRK‐rearranged spindle cell neoplasm of bone harboring an HMBOX1::NTRK3 gene fusion

Cited by 2 publications

References 28 publications

Kinase fusion positive intra‐osseous spindle cell tumors: A series of eight cases with review of the literature

Kinase fusion positive intra‐osseous spindle cell tumors: A series of eight cases with review of the literature

Primary NTRK-rearranged Spindle Cell Neoplasm of the Gastrointestinal Tract: A Clinicopathological and Molecular Analysis of 8 Cases

Contact Info

Product

Resources

About