BRAF V600E Mutations Occur in a Subset of Glomus Tumors, and Are Associated With Malignant Histologic Characteristics.

Glomus tumors are rare mesenchymal neoplasms with a phenotype akin to the modified smooth muscle cells of the glomus body. Most are benign, but rare examples show malignant histologic characteristics and aggressive behavior. We recently encountered a malignant glomus tumor with BRAF V600E mutation. We sought to study a large cohort for this mutation, with particular attention to associated malignant histologic characteristics. Tumors were classified based on WHO criteria as benign, uncertain malignant potential (glomus tumors of uncertain malignant potential-GT-UMP), or malignant. Tumors were screened for BRAF V600E by immunohistochemistry, and positive staining was evaluated further by Sanger sequencing. A total of 102 glomus tumors were included and classified as benign (57, 56%), GT-UMP (15, 15%) and malignant (30, 29%). Tumors occurred in patients aged 8 to 89.9 years (median: 50.2), without sex predilection (55% men). Most occurred in the superficial soft tissue (84%) and upper extremities (55%). Six of 95 tested cases had BRAF V600E mutation (6%), including 0 of 57 benign tumors, 3 of 14 GT-UMP (21%), and 3 of 24 malignant tumors (12%). Follow-up was obtained for 59 cases (median: 75.7 mo, range: 7.8 to 268.5). Three of 11 malignant tumors (27%) had progressive disease: 1 with metastasis to brain and heart, 1 with enlarging residual disease, and 1 with recurrence. Two of 4 GT-UMP (50%) had progressive disease: 1 with metastasis to lung, and 1 with local recurrence (50%). Three of 44 benign tumors (7%) had local recurrence. Two of 5 patients with BRAF V600E had progression, including 1 GT-UMP with local recurrence and 1 malignant tumor with enlarging residual disease. In summary, BRAF V600E mutation was detected in 6% of glomus tumors, all of which were malignant or GT-UMP. This mutation may be associated with a malignant phenotype, although study of additional cases is needed. In patients with progressive disease, BRAF could be a promising therapeutic target.

Glomus tumor of Hoffa's fat pad and its management by arthroscopic excision.

We present a rare case of glomus tumor of Hoffa's fat pad in a 42-year-old woman. Magnetic resonance imaging findings along with the characteristic clinical picture led us to suspect a glomus tumor as the possible etiology. An ischemia test was found to be positive and this further substantiated our diagnosis. An arthroscopic excision was performed and the histology confirmed the diagnosis of glomus tumor of Hoffa's fat pad. The patient responded well to the excision with immediate complete resolution of pain and she remains asymptomatic at the last follow-up after 15 months. To our knowledge, this is the second reported case of glomus tumor of Hoffa's fat pad and the first ever to be managed by simple arthroscopic excision. The tumor poses a great challenge to an orthopedic surgeon. However, knowledge of its characteristic clinical presentation and the recognition of such a rare entity can help achieve an early diagnosis and timely management.

Malignant glomus tumor of the esophagus with mediastinal lymph node metastases.

Extracutaneous malignant glomus tumors are unusual, and their occurrence in the esophagus has been recognized with extreme rarity. We describe a 47-year-old man who presented with progressive dysphagia and weight loss. Upper gastrointestinal endoscopy, a barium esophagram, and chest computed tomography revealed an unusually large, aggressive soft mass at the middle portion of the esophagus. A curative resection (R0 resection) was achieved by means of Ivor-Lewis esophagectomy and mediastinal lymph node dissection. The histopathologic examination and immunohistochemical studies demonstrated a malignant glomus tumor of the esophagus with mediastinal lymph node metastases.

Glomus Tumor of Hoffa's Fat Pad and Its Management by Arthroscopic Excision

We present a rare case of glomus tumor of Hoffa's fat pad in a 42-year-old woman. Magnetic resonance imaging findings along with the characteristic clinical picture led us to suspect a glomus tumor as the possible etiology. An ischemia test was found to be positive and this further substantiated our diagnosis. An arthroscopic excision was performed and the histology confirmed the diagnosis of glomus tumor of Hoffa's fat pad. The patient responded well to the excision with immediate complete resolution of pain and she remains asymptomatic at the last follow-up after 15 months. To our knowledge, this is the second reported case of glomus tumor of Hoffa's fat pad and the first ever to be managed by simple arthroscopic excision. The tumor poses a great challenge to an orthopedic surgeon. However, knowledge of its characteristic clinical presentation and the recognition of such a rare entity can help achieve an early diagnosis and timely management.

Malignant glomus tumor of the stomach with multiorgan metastases: report of a case.

This report presents the case of a 65-year-old female patient with a malignant glomus tumor of the stomach, with metastases to the kidney and brain. The clinical presentation and imaging results are discussed, and the literature on malignant glomus tumors is reviewed.

Cutaneous metastasis from gastric glomus tumour.

A 58-year-old man presented with a 4-month history of a rapidly enlarging asymptomatic tumour on the scalp vertex. Six years earlier, the patient had undergone subtotal gastrectomy for a presumed gastrointestinal stromal tumour (GIST). The tumour extended to the peritoneal surfaces, and foci of vascular invasion were also seen. No adjuvant treatment was given. Owing to diagnostic difficulties with the scalp tumour, a comparison was made with the previous gastric neoplasm. Both had features consistent with glomus tumour, which suggested a revised diagnosis of primary malignant gastric glomus tumour with subsequent cutaneous metastasis to the scalp some years later. This case highlights the features of glomus tumours and is a reminder that although rare, glomus tumours can be malignant and have the potential to metastasize. To our knowledge, this is the only reported case of a primary gastric glomus tumour with secondary metastasis to the skin.

Gastric solid glomus tumor and multiple glomangiomyomas of the large bowel with intravascular spread, multifocal perivascular proliferations and liver involvement.

The authors present a case of multiple glomus tumors (GTs) of the gastrointestinal tract, representing the type of a gastric glomus tumor proper and large bowel glomangiomyomas with myopericytoma-like features, observed in a 46-year old female, with multifocal perivascular proliferations of primitive cells and hepatic involvement. Histologically, the multilobular gastric tumor and hepatic lesions corresponded to a typical glomus tumor, while the tumor situated in the transverse colon, up to 7 cm in diameter, presented as a glomangiomyoma infiltrative (with myopericytoma-like foci), and satellite tumors in the large bowel mucosa, 0.5-0.7 cm in diameter, represented small glomangiomyomas. In addition, the patient demonstrated two types of concomitant vascular lesions: 1/ intravascular spread in the form of neoplastic plugs that obliterated the lumen of medium-size veins, and 2/ microscopic perivascular proliferation of primitive, small cells seen in the vicinity of the main tumor and in the adjacent adipose tissue. The patient has been ill for 2.5 years; she has been subjected to a partial colectomy with a resection of the small intestinal loop, greater omentum and the right ovary, followed by chemotherapy. At present, she is stable, and the infiltration--especially in the epigastric region--has decreased. The picture may confirm the theory that multiple GTs develop in association with multifocal proliferation of perivascular stem cells, as well as that their ability to penetrate into the lumen of large vessels gives origin to satellite tumors, which are not necessarily metastatic. It seems that at present, the group of perivascular SMA+ tumors may include infantile-type myofibromatosis in adults, myopericytoma, glomangio(myo)pericytoma, glomangiomyoma, glomus tumor proper, and glomangioma. Most likely, also some tumors previously classified as hemangiopericytomas belong to this group. The distinctive feature present in at least some of the above listed perivascular tumors is their synchronous or metachronous growth in a particular region and their ability to occupy intravascular space as nodules or solid bands, which in turn may give origin to satellite tumors. Multifocal lesions associated with a short survival in a given patient will obviously support the presence of metastatic disease. In the remaining cases, determination whether the patient has metastatic disease requires deep consideration and caution, also while deciding on treatment to be employed.

Malignant glomus tumor: a case report and review of literature, focusing on its clinicopathologic features and immunohistochemical profile.

Malignant glomus tumor (MGT) is a rare, recently described neoplasm that recapitulates the appearance of the modified smooth cells of the normal glomus body. We report a case of MGT of the hand of a 48-year-old woman. Magnetic resonance imaging (MRI) showed a 2.8-cm, well circumscribed, enhancing mass on the volar aspect of the thenar region of the right hand in immediate continuity with the ulnar artery and nerve. Computed tomography scan (CT-Scan) of the chest was normal. Histologic evaluation revealed a multilobular lesion with prominent branching capillary vasculature and perivascular arrangement of sheets of tumor cells. The tumor cells were round, relatively uniform in size with distinct cell borders and perinuclear cytoplasmic clearing. They were of intermediate to high nuclear grade and showed significant mitotic activity. A wide local excision with negative margins was performed. Multiple lung metastases were evident at 8-month follow-up. To date, forty-five cases of MGT of skin and soft issue have been reported in the literature. Twelve of the forty-five cases developed metastasis. In this report, we emphasize the differential diagnosis of MGT in the skin and deep soft tissue.

Primary pulmonary glomus tumor with contiguous spread to a peribronchial lymph node.

Glomus tumors are uncommon soft tissue tumors. Rare occurrences in visceral organs including the respiratory tract have been reported. The vast majority of these tumors are biologically benign. We report a case of primary pulmonary glomus tumor with atypical features characterized by mild nuclear atypia, local infiltration, and contiguous spread to a peribronchial lymph node. The current literature is reviewed.

Neural infiltration of glomus temporale tumors.

Biologic behavior of glomus temporale tumors in relation to cranial nerve infiltration remains unclear. An analysis of cranial nerve involvement in relation to tumor staging was undertaken in a series of 102 glomus temporale tumors. Frequent neural infiltration was noted to occur in large glomus tumors, and a grading system of infiltration with both pathologic and surgical relevance introduced.

Renin secretion from malignant pulmonary metastatic tumour cells of vascular origin.

1. A pulmonary chemodectoma/glomangiosarcoma that had metastasized from the thigh was studied after removal from a 22 year old Algerian patient with hypertension, high plasma prorenin and signs of secondary aldosteronism. 2. Renin and renin mRNA were localized in sections of the tumour tissue using monoclonal anti-human renin antibody and human renin cDNA probe, respectively. 3. The cells grew prolifically in culture, but, even though their renin content was similar to that of transfected human juxtaglomerular cell tumour cells (approximately 1 pg/microgram DNA), their rate of secretion of renin was much lower (0.05-0.15 cf. 0.5-1.5 pg/h per microgram DNA). 4. Forskolin (10 mumol/l for 24 h) increased secretion of renin from 1.9 +/- 0.36 to 4.1 +/- 0.64 pg/ml per h of culture (P less than 0.001, n = 11), consistent with cAMP being a second messenger in the secretory mechanism. 5. The cells should provide valuable information about intracellular mechanisms for the regulation of renin synthesis and secretion.

Glomangiosarcoma with metastasis to the maxilla.

A thorough review of the literature disclosed very little information on glomangiosarcoma with no reported cases of verified metastases. We present a case which may be the first instance of oral metastatic glomangiosarcoma to be reported in the literature.