PDGFRB and NOTCH3 Mutations are Detectable in a Wider Range of Pericytic Tumors, Including Myopericytomas, Angioleiomyomas, Glomus Tumors, and Their Combined Tumors.

Pericytic tumors are subclassified as myopericytomas, myofibromas, angioleiomyomas, and glomus tumors according to the current World Health Organization classification. These pericytic tumors form a continuous morphologic spectrum, including those with combined morphology. However, to our knowledge, no widely accepted criteria for classifying tumors with combined morphology are available. Recent studies have identified platelet-derived growth factor receptor-beta (PDGFRB) gene mutations in a subset of myofibromas, myopericytomas, and myopericytomatoses but not in angioleiomyomas. NOTCH receptor 3 (NOTCH3) mutations have been reported in a subset of infantile myofibromatosis. To assess their potential role in classifying pericytic tumors, we investigated PDGFRB and NOTCH3 mutations in 41 pericytic tumors of variable morphology, including some combined forms. Our results show these mutations to be present in a variety of pericytic tumors, such as myopericytomas (PDGFRB, 3/11; NOTCH3, 4/11), myopericytomatoses (1/2; 1/2), myofibromas (3/6; 0/6), angioleiomyomas (2/13; 3/13), and glomus tumors (5/9; 1/9). Point mutations were identified in 3 tumors in PDGFRB exon 12 (Y562C, S574F, and G576S), 12 tumors in PDGFRB exon 14 (M655I, H657L, and N666K), and 9 tumors in NOTCH3 exon 25 (A1480S/T, D1481N, G1482S, T1490A, E1491K, G1494S, and V1512A). All PDGFRB mutations and NOTCH3 G1482S, T1490A, and G1494S mutations were classified as "deleterious/damaging" by ≥4 of 6 pathogenicity prediction tools in silico. Five-mutation-positive tumors, including 1 myopericytoma-angioleiomyoma, 2 myopericytomatoses-myofibroma, 1 myofibroma-myopericytoma and 1 angioleiomyoma-myopericytoma, were of combined morphology. Therefore, we found PDGFRB and NOTCH3 mutations to be detectable in a much wider variety of pericytic tumors than previously reported and confirmed myopericytomas, myofibromas, angioleiomyomas, and glomus tumors as members harboring PDGFRB or NOTCH3 mutations. Our results thus suggest that PDGFRB or NOTCH3 mutations are not useful for subclassifying members of the pericytic tumor family.

Incidental superficial soft tissue epithelioid angioleiomyoma.

Epithelioid angioleiomyoma (EALM) is rare in the skin and subcutaneous tissues. To the best of our knowledge, only two previous cases of this tumor have been reported. We document here the case of an 83-year-old woman who underwent complete removal of a squamous cell carcinoma of the retromolar trigone and lymph node dissection of the neck. An incidental EALM was observed in the adipose tissue. The tumor formed a unilocular, poorly demarcated neoplasm measuring 0.3 cm, and showed cavernous angiomatous spaces with villiform growth of large epithelioid cells arranged in clusters. Besides the epithelioid cells of muscular origin, bundles of well-differentiated smooth muscle cells were observed. Epithelioid cells accounted for 70% of the total. The neoplasm originated in the wall of a medium-sized vein. Epithelioid and spindle cells were positive for alpha-smooth muscle actin, calponin, h-caldesmon, and muscle-specific actin. The endothelial cells lining the vascular spaces showed intense and diffuse positivity for CD31 and ERG. The main differential diagnosis includes metastatic carcinoma, melanoma, perivascular epithelioid cell neoplasm, myopericytoma, glomangiomyoma, epithelioid glomus tumor, and epithelioid leiomyosarcoma. This report expands the morphological spectrum of the EALM. Awareness of this uncommon morphologic variant of angioleiomyoma and the use of adequate techniques can avoid misdiagnosis.

Inoperable Renal Malignant Glomus Tumor, the answers for all the "W's"?

Glomus tumor, arising from glomus bodies (specialized neurovascular structures involved in thermoregulation), commonly occurs in extremities and rarely in viscera. The spectrum of glomus tumors range from benign tumors to tumors with uncertain malignant potential to tumors of the malignant subtype. A vast majority of visceral glomus tumors are benign. Most common visceral tumors arise in the gastrointestinal tract. Glomus tumors of the kidney are a rare entity of which malignant glomus tumors are exceedingly rare. The index patients in the existing case reports were middle-aged males. We report our experience with malignant glomus tumor of the left kidney in a 60-year-old female, with computed tomography (CT) showing involvement of renal vein and inferior vena cava (IVC). Percutaneous biopsy was performed as imaging did not conform to the appearance of a conventional renal tumor and was reported as malignant glomus tumor after immunohistochemistry. After informed decision, the patient and family elected to proceed with surgery. However, intraoperatively, the left renal mass was found to infiltrate the pancreas, duodenum, aorta, and root of the colonic mesentery due to which surgery was aborted. Biopsy obtained intraoperatively again confirmed diagnosis of left renal malignant glomus tumor. She had an uneventful postoperative recovery. Options of treatment were reviewed by a multidisciplinary board. In light of no proven benefit for systemic therapy, she was referred for supportive care. She was under follow-up and she expired after 7 months due to progressive disease. Our literature review focuses on the clinicopathologic features and the current standard of management of malignant renal glomus tumors.

A case of mediastinal mesenchymal tumor with pericytic neoplasm feature that responded to radiation therapy.

Here, we report a case of mediastinal mesenchymal tumor with a pericytic neoplasm feature that responded to radiation therapy. A 43-year-old man visited our hospital with a complaint of esophageal obstruction and chest pain. Chest computed tomography revealed a middle mediastinal tumor and a mesenchymal tumor was diagnosed with a pericytic neoplasm feature by video-assisted thoracoscopic biopsy. The definitive treatment for soft tissue tumor is surgical resection; however, the mediastinal tumor was unresectable because of esophageal and tracheal invasion. Radiation therapy was administered and there was a partial tumor response and 2 years disease-free status. With a review of the literature, we discuss the clinical and pathological characteristics of this rare tumor and its treatment.

Myopericytoma arising from myopericytosis-a hitherto unrecognized entity within the lung.

Two cases of myopericytosis combined with pericytoma originating within the lung are reported. These are rare pulmonary tumors. The differential diagnosis for hemangiopericytoma and pericytic tumors with glomus elements is discussed. Both myopericytic lesions mimic other lesions, which are more commonly seen in the lung. Based on the expression of vascular growth factor receptors 2 and 3, an antiangiogenic therapy was suggested for the patient with the myopericytoma. A treatment with an angiogenesis inhibitor resulted in a regression of the tumor, but not the precursor lesion. Probably a more specific therapy using tyrosine kinase inhibitors for VEGFR2/3 might better control these myopericytic proliferations.

Myopericytoma-like tumors of the lung: Report of two cases.

Myopericytoma is a benign neoplasm presenting cells with different shapes, from oval to spindle, and myoid showing with perivascular growth, which frequently originates from the skin and soft tissues of distal extremities, trunk, head, and neck regions. These tumors rarely have been reported to occur in visceral sites. There is only one case of myopericytoma showing pulmonary involvement with multiple nodules. Although most myopericytomas behave in a benign manner, some cases of malignant myopericytoma arising in both superficial soft tissue and visceral locations have been described. We describe two cases of pulmonary tumors with myopericytoma-like features.

Myopericytoma proliferating in an unusual anastomosing multinodular fashion.

We herein describe a case of myopericytoma that proliferated in an unusual fashion. Myopericytoma is described as a group of rare, benign, dermal or subcutaneous tumors that are characterized histologically by a striking, concentric, perivascular proliferation of spindle cells and showing apparent differentiation towards perivascular myoid cells. Myopericytoma forms a morphological continuum with myofibroma/myofibromatosis, glomus tumor and angioleiomyoma. The patient was a 64-year-old woman who demonstrated a recurrent ulcer on an atrophic plaque on her left shin. A histopathological examination of the plaque demonstrated that tumor cells proliferated in an anastomosing multinodular fashion along the vessels in the dermis and subcutaneous tissue. In those nodules, there were numerous, small, concentric proliferations of myoid-appearing spindle cells around small vascular lumina. The present case is an unusual example of myopericytoma, manifesting in a characteristic anastomosing, multinodular, infiltrating fashion.