Multiple Glomus Tumors

Table. Epidemiologic and Clinical Aspects in Six Patients With Multiple Glomic Tumor

Sex	First Appearance	Present Age (Years )	Race	Type	Number of Lesions and Location	Pain	Family History	Patient’s Origin
Male	Age 25	36	B	Regional	Plate comprising 10 lenticular violet nodules on left buttock	No	None	PGRJ
Male	Congenital	29	B	Diffuse	Four soft tumor normochromic lesions ranging from 10–20 cm in diameter on back and right inguinal region	Yes	None	PGRJ
Male	Age 3	12	W	Diffuse	Eight lesions with maculae and bluish lenticular nodules on back, left arm, right forearm, and legs	Yes	None	H Jesus
Male	Congenital	24	W	Diffuse	Ten lesions as bluish lenticulonummular nodules on back and arms	Yes	Father and aunt on father’s side	HSVP
Male	Age 25	45	W	Regional	Three lesions as bluish lenticular nodules on arms	No	None	Private Clinic
Male	Age 15	16	M	Regional	Eight lesions as brown-bluish lenticular nodules on arm and right forearm	Yes	None	EPM
B=black; W=white; M=mixed; PGRJ=Policlínica Geral do Rio de Janeiro; H Jesus=Hospital Jesus; HSVP=Hospital São Vicente de Paulo; EPM=Escola Paulista de Medicina

Discussion
Although statistics are scarce, the glomus tumor is relatively infrequent, representing 1.6% of the cases in a series of 500 primary tumors of soft body parts 14 and 1%–4.5% of hand tumors in different evaluations. 15 In the wide context of a general hospital such as the São Vicente de Paulo Hospital, we found eight glomus tumors (0.035%), with one MGT case (0.0043%), in 23,000 histopathologic exams, demonstrating that the disease is really very rare.
In the early stages of study of glomus tumor one hypothesis was a preponderance of the single presentation in women and multiple lesions in men, which did not persist after a study of large series. 16, 17 Surprisingly, our sample consisted only of men. MGT usually appears before age 21, during childhood or adolescence, with occasional congenital emergence. 17, 18 The diagnosis in black individuals is infrequent, perhaps because the greater number of articles are from Europe and the United States where the white population prevails. 19 The familial occurrence of MGT shows itself through dominant autosomal inheritance with incomplete penetration of the regional form in some patients. 18, 20

Solitary or multiple glomus tumor may present with different patterns: regional, disseminated, or congenital in plaques.
As observed in our series, MGT presents varied clinic forms with stains, wheals, and nodules—isolated or in confluent plaques—of bluish, red, purple, or brown color, almost always less than 3 cm in diameter. 16–18 Larger tumorous lesions (as in case 2) or telangiectatic plaques are eventually found. 16, 17, 21 In the multiple form the number of lesions vary, from less than 10 to 90, although a record of a case with 500 lesions exists. 16, 17, 22 The significant, painful symptomatology is certainly the main diagnostic element in SGT; in contrast, in MGT the algesic manifestations are generally discreet, if present at all. 16, 18, 23 Painful and painless lesions can coexist in the same individual, and also, instead of pain, local itching may be experienced. 16, 17, 24
The distribution of the tumors on the skin is random, usually on the trunk and members; there is a balance in the literature among the number of diffuse and regional presentations, those restricted to one member or a cutaneous segment. 16, 17 The congenital form in plaques is infrequent, with fewer than 20 reports in the literature. 25 The subungual presentation, usually found in SGT, is not usually detected in the multiple form. 2, 17, 26 The association of tegumentary and visceral lesions is extremely rare, mentioned in only one patient. 2, 16, 27 Usually the disease presents stable behavior, with the eventual appearance of new tumors being related to small traumatisms, repeated pregnancy, or appearing spontaneously. 16, 28 Although less common, partial regression of the lesions was noticed in one case. 29
The association with other illnesses is not usual; a concurrence was described with multiple neurofibromatosis, 30 Gardner-Diamond syndrome (autoerythrocytic sensitization), 31 Kasabach-Merritt syndrome (thrombocytopenia by entrapping of platelets in voluminous cavernous hemangiomas), 32 and Coats’ disease (progressive exudative chronic retinopathy). 33 The main differential diagnosis for MGT would be the several hemangiomas, especially the blue rubber bleb nevus (multiple cavernous hemangioma) that occurs with cutaneous and digestive lesions, as well as of the nervous system, with frequent hemorrhages. 34
Among the imaging methods, ultrasound scans and magnetic resonance imaging are particularly useful for the superficial and deep delimitation of the tumors, as well as for the location of occult painful lesions. 35, 36 Angiography is currently less often used due to its invasive nature, a certain technical difficulty, and high cost. 36 The simple x-ray offers little information, detecting merely a major increase in soft parts, voluminous tumors, or rare lesions adjacent to bones that cause destruction of bone fabric by compressive growth. 2, 26, 37
The histopathologic diagnosis of glomus tumor is made by the discovery of the glomus cells—rounded or edgy, sometimes fusiform, with pale cytoplasm, and a large central nucleus. These cells organize themselves in proliferations of variable density that vary from masses with intense cellularity to dispersed cells in strings and small agglomerates. Concurrently, vascular spaces with a single layer of endothelial, flat, and prolonged cells are found, ranging from small clefts to wide spaces. The stroma oscillates between scarce to abundant, with occasional areas of myxoid degeneration. The neoplasm is usually well delimited, with an eventual pseudo-capsule from the tissue reaction, although with sporadic reports of infiltrative tumors, poorly delimited. Mastocytes and myelinated and nonmyelinated nerve fibers are found surrounding the neoplasia in varying quantities. 2, 38–40
The histopathologic classification proposed in 1988, 41 based on 507 analyzed cases, suggests the following division: glomus tumor (prevalence of glomus cells), glomangioma (intense vascular component), and glomangiomyoma (presence of smooth muscular fibers among the glomus cells). The MGTs are almost always richly vascularized, with our sample comprising six glomangiomas The glomus cells are well characterized as modified smooth muscular cells. They originate from the cutaneous glomus, arteriovenous anastomoses, which are present in the dermis and observed mainly in the hands and feet. 38, 42 This identification is confirmed by the immunohistochemistry—since the glomic cells react to muscle-specific actin and vimentin, but not to desmin—and by electron microscopy, with the presence of basal lamina around the cells, pyknotic vesicles adjacent to the plasmatic membrane, fine filaments arranged in strips, and dense intracytoplasmic bodies. 38–40, 42, 43
Although it is believed that the glomus tumor is derived from glomic cells, it has been speculated that undistinguished mesenchymal cells, under unknown stimulation, may originate glomus tumors, particularly multiple lesions or in visceral locations. 38–40
The therapeutic management of MGT consists of surgical removal of the lesions (when painful or unaesthetic), providing information about the illness to the patient, and periodic observation. 44 Lasers have also been used experimentally in the management of MGT, 45 as well as sclerosant agents, 46, 47 electron beam irradiation, 48 and infrared coagulation. 49 The current trend has been the combination of several methods, seeking the best therapeutic and aesthetic result. 36
As glomus tumors are an uncommon illness, the present series of six patients allowed the demonstration of the wide variety of epidemiologic, clinical, and histopathologic aspects described in the literature, with the presentation of elements that may help its recognition and diagnosis.
Acknowledgments: The authors wish to thank Augusto Teixeira, Christina Guerra, Olga Harris, Cláudia Maia, and Omar Santos for contributions in the evaluation of the patients.