A Primary Pulmonary Glomus Tumor: A Case Report and Review of the Literature

A case of a glomus tumor originating from the lung is reported. A 43-year-old female had undergone resection of a right lung tumor following a clinical diagnosis of carcinoid, sclerosing hemangioma, or other sarcoma. Histologically, the tumor comprised uniform small round to oval cells with centrally located nucleus, a clear cytoplasm, and apparent cell borders. The tumor also showed a focally hemangiopericytomatous pattern with irregularly branching or dilated vessels. Electron microscopy revealed smooth muscle differentiation of the tumor cells. Immunostaining further revealed that the tumor cells expressed smooth muscle actin, h-caldesmon, muscle specific actin (HHF-35), but not cytokeratin, epithelial membrane antigen, synaptophysin, or chromogranin A. Based on these findings, a diagnosis of primary pulmonary glomus tumor was established. Glomus tumors of the lung are very rare and only 21 cases have been reported to date. The histological features of the present tumor and the relevant literature are discussed.


Introduction
Glomus tumors are benign neoplasms derived from the glomus cells surrounding an arteriovenous anastomosis. These anastomoses are most frequently found in the deep dermis of the extremities, such as the subungual regions of the finger tips, palms, wrists, and toes. Glomus tumors accounts for 1.6% of all soft tissue lesions recorded at the Mayo Clinic [1]. The average age of the affected patients at presentation ranges from 20 to 40 years, although these tumors can occur at any age [2]. Although the subungual regions are the most common sites at which glomus tumors arise, they occasionally develop in the organs where glomus bodies are sparse or unrecognized, such as the gastrointestinal tract, lung, bone, adrenal gland, central nervous system, mediastinum, uterus, and vagina [3]. We here describe a rare case of a pulmonary glomus tumor, including its pathological features, and review the current literature on these cancers.

Case Report
A 43-year-old female was admitted to our hospital with an abnormal lung shadow in the right upper field that had been detected three months previously. She was a nonsmoker and had no history of respiratory diseases. Laboratory data and tumor markers were within normal ranges. A chest computed tomography (CT) scan detected a nodular lesion of about 2.0 cm in diameter in the right upper lobe (Figure 1). Preoperative diagnoses included carcinoid, sclerosing hemangioma, and sarcomas not otherwise specified. Thoracoscopic removal of the lung with a frozen section (intraoperative rapid diagnosis) was performed. The tumor comprised blood vessels of varying sizes surrounded by uniformly arranged small round cells with hemorrhage foci. From these findings, we made an intraoperative diagnosis of sclerosing hemangioma.    were revealed along the basement membranes ( Figure 4), suggestive of smooth muscle differentiation of the tumor cells. By immunostaining, the tumor cells were positive for alpha smooth muscle actin, h-caldesmon, muscle specific actin (HHF-35), laminin, type IV collagen, and vimentin, but negative for cytokeratin (AE1/AE3), epithelial membrane antigen (EMA), TTF-1, surfactant apoprotein A, S-100 protein, synaptophysin, and chromogranin A (Figures 3(a)-3(d)). CD34 expression was only occasionally found in the perivascular tumor cells and the MIB-1 index was about 2%. Based on these findings, we made a final diagnosis of a glomus tumor of the lung.

Discussion
Glomus tumors are rare neoplasms that arise from the neuroarterial structure known as the glomus body [31,32] and account for 1.6% of all soft tissue tumors [1]. The normal glomus unit is a neuromyoarterial apparatus that functions to regulate skin circulation and is found subungually in descending order on the finger tip pulp, on the base of the foot and throughout the rest of body. The most common site of glomus tumors is subungual lesion of the fingers, followed by other portions of the distal extremities including the wrist, palm, and foot. Glomus tumors have also been described in locations where the glomus body does not normally exist including the bone, chest wall, eyelid, colon, rectum, cervix, and respiratory tract [3]. We here describe a highly unusual case of a glomus tumor of the lung. To our knowledge, this is the 33th and 21th glomus tumor case to be described originating from the respiratory tract, including the trachea, bronchus, and lung, and the lung alone, respectively. Table 1 summarizes the clinicopathological features of the 33 glomus tumors of the respiratory tract thus far reported .
Histologically, typical glomus tumors are subcategorized as solid glomus tumor, glomangioma, or glomangiomyoma, depending on the relative prominence of glomus cells, vascular structures, and smooth muscle. Glomus cells are small, uniform, and round with a centrally placed, Case Reports in Pathology 5 round nucleus and an amphophilic to lightly eosinophilic cytoplasm. In soft tissues, solid glomus tumors are the most common variant, comprising approximately 75% of reported cases, followed by glomangiomas (approximately 20%) and glomangiomyomas (<5%). Malignant glomus tumors (glomangiosarcomas) are exceedingly rare and fewer than 20 soft tissue cases which have been published [2]. In the respiratory tract, the 33 glomus tumor cases reported to date consist of 26 typical and 7 malignant variants. Subcategorized diagnoses are available for 22 of the 26 typical glomus tumors, which includes 18 solid tumors (81.8%), 3 glomangiomas (13.6%), and one glomangiomyoma (4.5%, Table 1), the incidences of which are very similar to the soft tissue counterparts. The incidence of glomangiosarcomas in the respiratory tract (7/33, 21.2%) appears to be higher than that of the soft tissue counterparts, although it is uncertain whether all of these tumors fulfilled the current strict criteria for glomangiosarcomas [2].
A differential diagnosis of pulmonary glomus tumor must exclude carcinoid tumor, hemangiopericytoma, sclerosing hemangioma, leiomyoma, and paraganglioma. Carcinoids are often confused with glomus tumors since they have a similar morphology, although by immunostaining carcinoids, but not glomus tumors, are positive for cytokeratin and neuroendocrine markers such as chromogranin A and synaptophysin [4,9]. Sclerosing hemangiomas are positive for TTF-1, surfactant apoprotein A, and cytokeratin. Paragangliomas are typically composed of round epithelioid cells with small nuclei and express neuroendocrine markers and S-100 protein [27]. Smooth muscle neoplasms comprise spindle cells with a fascicular pattern and express smooth muscle markers, including alpha smooth muscle actin and h-caldesmon. Hemangiopericytoma is a vascular neoplasm often misdiagnosed as a glomus tumor. These lesions show a characteristic staghorn vasculature pattern and consist of polygonal to spindle cells with elongated nuclei. Hemangiopericytomas are immunohistochemically positive for vimentin and CD34, but negative for cytokeratin and smooth muscle markers. The diffuse CD34 staining pattern found in hemangiopericytomas is very helpful in differentiating them from glomus tumors.
In summary, we here reported a very unusual case of a primary pulmonary glomus tumor. We further find that although these neoplasms histologically resemble carcinoid tumor, hemangiopericytoma, and sclerosing hemangioma, careful morphologic observation and immunostaining for appropriate markers should enable clinicians to distinguish between these lesions.