An unusually painful nodule.

A 36-year-old man presented with a 3-year history of a painful, solitary lesion on the left thigh [Figure 1]. The lesion was exquisitely painful and tender. Cold air aggravated the pain. There was no history of bleeding or discharge. There was history of application of hot oil to relieve the pain which was followed by scarring of the surrounding skin. On examination, there was a solitary papule measuring 5 mm in diameter on medial aspect of the left thigh, surrounded by an annulus of scar tissue.

Figure 1

Solitary papule on left thigh

Excision biopsy was done. Histopathological examination of H and E stained sections showed a well-circumscribed tumor surrounded by a fibrous stroma in the dermis [Figure 2]. The tumor was composed of sheets of uniform cells with eosinophilic cytoplasm and round to ovoid central nuclei. Numerous dilated, cavernous, thin-walled vascular spaces of varying sizes surrounded by few layers of cells were distributed throughout the tumor [Figures 3 and 4]. Cytologic atypia was absent.

Figure 2

Well-circumscribed tumor surrounded by a fibrous stroma in the dermis (H and E, ×4)

Figure 3

Dilated, cavernous, thin-walled vascular spaces of varying sizes throughout the tumor (H and E, ×10)

Figure 4

Vascular space surrounded by layers of cells (H and E, ×40)

Questions

What is the diagnosis?

What are the proposed mechanisms behind its etiopathogenesis?

What are the histopathological variants seen in this condition?

What are the mimickers of this clinic-pathological entity?

How can the condition be managed?

Answers

Ans 1: Diagnosis: Glomangioma, a variant of glomus tumor.

The clinical presentation may mimic several clinical entities but the diagnosis is essentially histopathological. Glomus tumors are tumors of the myoarterial plexus composed of vascular channels surrounded by proliferating glomus cells.[1] They can be classified into: (1) the glomus tumor proper, a well circumscribed solitary cellular lesion; and (2) the glomangioma or glomovenous malformation which histologically resembles a venous malformation with lesional vessels rimmed by glomus cells.

There is an equal sex incidence; however, extradigital glomus tumors are more common in men (4:1). They can occur at any age but are the most common in the third or fourth decades of life. They may be solitary or multiple (10%). They occur in areas rich in glomus bodies such as the digits, but can be extradigital (61%) involving the extremities, back, face and internal organs such as gastrointestinal tract, bone, mediastinum, trachea, and nerve.[23]

The glomus tumor is a benign lesion usually presenting as a small (less than 2 cm), blue-red papule or nodule. A classic triad of pain, pinpoint tenderness with blunt palpation, and hypersensitivity to cold are noted.[4] Pain may be due to entrapment of myelinated nerve fibers by glomus cells.[5]

Ans 2: Glomus tumors of the digits may represent neoplastic proliferations originating from pre-existing normal glomus cell populations in the glomus body, which is a specialized arteriovenous anastomosis (Sucquet-Hoyer canal) involved in the regulation of temperature. However, occurrence of tumors at unusual sites suggests that some may arise from pluripotent mesenchymal cells or smooth muscle cells.[2]

Ans 3: Microscopically, glomus tumors show varying proportions of glomus cells, blood vessels and smooth muscle and are classified accordingly into solid glomus tumor (25%), glomangioma (60%) and glomangiomyoma (15%).[6] Most cases of glomus tumor are well circumscribed, and a classic solid lesion is composed of sheets of uniform cells forming nests, sheets, and trabeculae. The cells have pale or eosinophilic cytoplasm with well-demarcated borders that are accentuated with reticulin or periodic acid–Schiff staining and round or ovoid punched-out central nuclei. The population of glomus cells usually comprises 2-3 rows in classic solitary lesions with interspersed branching vascular channels of varying sizes lined by endothelial cells. In glomangioma, they are dilated, cavernous and thin-walled. Glomangiopericytoma exhibits prominent hemangiopericytoma-like vascular features while glomangiomyoma shows prominent spindle-shaped smooth-muscle cells. The stroma is often edematous, myxoid, or hyalinized and may contain numerous small nerve twigs.[56] Mitotic figures may be present. Immunohistochemical studies reveal consistent expression of vimentin, muscle actin, and variably of desmin. Malignant glomus tumors show features such as large size (>2cm), deep location, marked atypia, high mitotic rate with atypical mitotic figures.[2]

Ans 4: Solitary glomus tumors may clinically be confused with eccrine spiradenoma but can be distinguished histologically by the presence in the latter of two populations of cells, focal ductal differentiation, and positivity for epithelial markers. Leiomyomas are composed of interlacing bundles of smooth muscle fibers with centrally located, thin, very long, blunt-edged, “eel-like” nuclei.[267]

From a histologic viewpoint hidradenoma may resemble glomus tumors when sweat ducts acquire erythrocytes, but can be distinguished by their keratin expression. Pseudoangiomatous intradermal nevi may occasionally resemble a glomus tumor, but in the former there is always evidence of nesting, maturation, and positivity of lesional cells for S-100.[26]

Ans 5: MRI is the most sensitive imaging modality in the evaluation of glomus tumors, especially those presenting as focal areas of pinpoint tenderness. It helps define the extent of the lesion and its relationship to other anatomic structures.[24] Plain radiography, angiography, thermography, ultrasound, and scintigraphy have all been used to diagnose glomus tumors with limited diagnostic success.[3]

Complete excision is thought to be curative for solitary lesions. Alternate therapy, such as hypertonic saline injection, electrodessication, CO2, argon and flashlamp pulsed dye laser, and sclerotherapy, have all been advocated.[24]