Primary Mesenchymal Tumors of the Thyroid Gland: A Modern Retrospective Cohort Including the First Case of TFE3-Translocated Malignant Perivascular Epithelioid Cell Tumor (PEComa)

Abstract

Primary mesenchymal tumors of the thyroid gland are extremely rare, with only case reports and small case series documented in the English literature, many of which were published prior to the era of molecular pathology. In the current study, we aim to present a contemporary multi-centric cohort of thyroid mesenchymal tumors. Nineteen primary thyroid mesenchymal tumors were collected from three tertiary centers. Their clinicopathologic features, immunoprofile, molecular alterations, and outcome were described. Eight cases were classified as benign or intermediate with solitary fibrous tumor being the most common histotype (n = 3). The remaining 11 cases were malignant, including three angiosarcomas, one epithelioid hemangioendothelioma, one adamantinoma-like Ewing sarcoma, one biphasic synovial sarcoma, one malignant melanocytic peripheral nerve sheath tumor (melanotic schwannoma), one myxofibrosarcoma, and two undifferentiated pleomorphic/spindle sarcomas (one of which was radiation-induced). Six tumors showed characteristic diagnostic translocations. We herein also described the first case of thyroid malignant perivascular epithelioid cell tumor (PEComa) with RBM10-TFE3 fusion in a 35-year-old female patient. Thyroid mesenchymal tumors, benign or malignant, are rare with a broad spectrum of possible diagnoses. A comprehensive examination to include histology, immunohistochemistry, and molecular testing is essential for the correct diagnosis and to distinguish them from anaplastic thyroid carcinoma. PEComa may occur as a primary tumor of the thyroid gland, expanding the histologic spectrum of thyroid mesenchymal tumors.

Keywords: Angiosarcoma; Perivascular epithelioid cell tumor (PEComa); Sarcoma; Solitary fibrous tumor; Thyroid.

Fig. 1

Benign and intermediate risk mesenchymal tumors of the thyroid gland. A–B A 1.5 cm angiolipoma presents as a multilobulated mass involving the thyroid gland. At high power, the tumor shows an ill-defined border admixed with thyroid follicles (F) at the periphery and contains a mixture of capillaries and mature adipose tissue. C–D A solitary fibrous tumor of the thyroid gland is composed of bland spindle cells in a fibrotic background infiltrating between thyroid follicles. Insert: The tumor is positive for STAT6 by immunohistochemistry

Fig. 2

Primary sarcoma of the thyroid gland. A–D An epithelioid angiosarcoma with interlacing vascular channels lined by epithelioid tumor cells infiltrating an adenomatoid nodule. F: follicles. Immunophenotypically, the tumor is positive for vascular marker ERG (B) and CD31 (C), as well as cytokeratin AE1/AE3 (D). E A synovial sarcoma of the thyroid gland with SS18-SSX1 translocation is composed of monotonous spindle cells. F An adamantinoma-like Ewing sarcoma of the thyroid gland harboring EWSR1-FLI1 fusion. The tumor contains sheets of uniform small round cells. Scattered keratin pearls (arrow) are also seen. Insert: CD99 immunostain shows membranous immunopositivity in this tumor. G–H A malignant melanocytic peripheral nerve sheath tumor (melanotic schwannoma) presents as an encapsulated mass. Abundant melanocytic pigment (arrows) and scattered microcalcification are noted. The tumor is diffusely positive for S100 (insert)

Fig. 3

A primary malignant perivascular epithelioid cell tumor of the thyroid gland with RBM10-TFE3 fusion. A Macroscopically, the tumor presents as a multilobulated white to beige mass with infiltrative border limited to the thyroid gland. Tumor emboli (red arrowheads) are grossly visible. Scale bar: 1 cm. B–D Hematoxylin and Eosin stain. The tumor shows multifocal vascular invasion (blue arrows), focal tumor necrosis (N), and scattered mitotic activity (black arrow). At high power, the tumor cells have epithelioid cytomorphology with abundant clear to eosinophilic cytoplasm, round to oval nuclei, and prominent nucleoli, arranged as trabeculae and nests, separated by a delicate capillary network. Immunohistochemistry studies show that the tumor is positive for TFE3 (E), smooth muscle actin (focal, F), cathepsin-K (G), and melan-A (H)