Head and Neck Mesenchymal Tumors with Kinase Fusions: A Report of 15 Cases With Emphasis on Wide Anatomic Distribution and Diverse Histologic Appearance

Abstract

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.

Figure 1.. Infantile fibrosarcoma (IFS) in the head and neck region.

(A) An IFS-like neoplasm with RBPMS::MET fusion originated from the facial soft tissue showing fascicular arrangement of bland spindle cells in a herringbone pattern (case #4). (B) An IFS contains bland ovoid cells arranged in loose fascicles with staghorn (hemangiopericytoma-like) vasculature (case #3). (C-D) This IFS of a newborn baby (case #1) shows ovoid cells with enlarged nuclei and prominent nucleoli, brisk mitotic activity (blue arrowheads), and focal tumor necrosis (N). Weak cytoplasmic positivity is noted on pan-TRK immunostain (D).

Figure 2.. Mesenchymal tumors with kinase fusion: lipofibromatosis-like neural tumor, malignant peripheral nerve sheath tumor (MPNST)-like, and adult-type fibrosarcoma-like patterns.

(A-D) A scalp tumor with NTRK1 fusion (case #6) is composed of a peripheral zone resembling lipofibromatosis-like neural tumor (L) and a central zone of solid growth (S). At higher power, the peripheral zone is composed of short fascicles of bland spindle to ovoid cells infiltrating adipose tissue (B). The central zone resembles MPNST and is composed of sheets of bland spindle cells arranged in ill-formed fascicles. Marked perivascular hyalinization (C) and dense keloid-like fibrosis (D) are frequent findings. (E-H) Case #11, an MPNST-like tumor with NTRK3 fusion. The tumor cells form loose fascicles. Perivascular hyalinization is present. The tumor is positive for CD34 (F), S100 (G), and pan-TRK (cytoplasmic staining, H). (I-J) Case #14 shows an adult-type fibrosarcoma-like pattern with fascicles of spindle cells arranged in a herringbone pattern (I). Branching staghorn (hemangiopericytoma-like) vessels is seen in this tumor (J).

Figure 3.. Mesenchymal tumors with kinase fusions displaying rare histologic patterns resembling inflammatory myofibroblastic tumor and myxoma.

(A-B) a skull base tumor with ETV6::NTRK3 fusion is cystic and hemorrhagic. The solid areas contain oval to plump tumor cells arranged in a vague syncytial pattern heavily infiltrated by mixed inflammatory cells, including lymphocytes, histiocytes, plasma cells, and eosinophils. Insert: pan-TRK immunostain shows cytoplasmic positivity. (C-D) An intraosseous hypocellular hypovascular myxoid tumor of the skull base with KIF5B::RET fusion resembling myxoma histologically (case #16). The tumor is composed of bland stellate cells in an abundant myxoid background.