HISTORY AND PHYSICAL EXAMINATION
A 51-year-old man complained of constant pain at the tip of his left third toe. His symptoms had started insidiously 5 years previously when he experienced sudden attacks of mild pain. He visited an orthopaedic surgeon who diagnosed gout arthritis of the third toe and had subsequently been receiving oral anti-inflammatory agents and allopurinol with no improvement. The attacks of pain became more frequent and intense and during the last year, the pain became constant. The patient experienced exacerbations of pain when even mild pressure was applied to the tip of the toe to the extent that he was unable to walk. He did not notice any relationship between the pain and temperature changes, and he did not recall any preceding trauma. There was no history of malaise, fatigue, fever, night sweats, or weight loss. His past medical history was unremarkable.
Physical examination indicated an otherwise healthy man. Inspection of the left foot showed a mild bluish discoloration of the lateral lip of the distal phalanx of the left third toe. Palpation of the tip was not tolerated by the patient. No mass or fluctuation could be palpated on the left third toe and there was no increase in the local temperature. Sensation was normal in the left third toe and left foot, and the left posterior tibial nerve elicited a negative Tinel's sign.
All laboratory investigations, including complete blood count, erythrocyte sedimentation rate, C-reactive protein, and complete serum chemistry panel were within normal limits.
Radiographic investigations included plain radiographs, ultrasonography (Fig 1), bone scans, computed tomography (CT) scans (Fig 2) and magnetic resonance imaging (MRI) scans (Fig 3). Based on the history, physical examination, laboratory findings and imaging studies, what is the differential diagnosis
Plain radiographs of the left foot were unremarkable. Ultrasonographic images showed a well-defined, hypoechoic soft tissue lesion along the dorsum of the distal phalanx with areas of internal flow suggesting a somewhat vascular nature (Fig 1). Bone scan with 99m-technetium (Tc99m) methylene diphosphonate of the entire skeleton appeared normal. Axial and coronal CT scans (Fig 2) showed an area of erosion along the dorsolateral margin of the third distal phalanx of the left third toe. The soft tissues appeared intact. Magnetic resonance images showed a small, soft-tissue lesion along the dorsal aspect of the third distal phalanx, greater laterally than medially, measuring approximately 6 mm in maximum diameter and eroding the cortex of the phalanx. The lesion was low on T1-weighted images (Fig 3A) and high on T2-weighted images (Fig 3B) with prominent diffuse enhancement on postgadolinium images (Fig 3C). The adjacent marrow showed no signal abnormality.
- Glomus tumor
- Neurilemoma (Schwannoma) Traumatic neuroma
- Mucoid cyst
A biopsy of the lesion in the lateral distal phalanx of the third left toe was done and photomicrographs obtained (Fig 4). Based on the history, physical findings, radio- graphic images, and histologic pictures, what is the diagnosis and how should this lesion be treated?
The resected specimen, measuring 0.6 × 0.4 × 0.2 cm was firm and pinkish in color. Microscopically, the lesion was composed of nests or sheets of uniform cells with round regular nuclei and inconspicuous nucleoli without mitosis. The cytoplasm was eosinophilic and the stroma was hyalinized. Focally, the nuclei became larger. The tumor cells had mainly a perivascular location. Intense staining of cells was observed with vimentin and smooth muscle actin.
Subungual glomus tumor of the left third toe
DISCUSSION AND TREATMENT
Glomus tumors are rare benign neoplasms, which can be the source of unexplained tenderness and cold sensitivity in the digits.1-21 They were first described by Wood21 in 1812 as “painful subcutaneous nodules” characterized by intermittent severe pain, susceptibility to temperature changes, long duration, small size, and firm consistency. He noted that excision resulted in cure.21 In 1924, Masson14 interpreted the histopathologic characteristics of the lesion.
The differential diagnosis of the lesion included other soft tissue lesions that may present with similar symptoms, clinical findings, and radiological picture. Lesions that had to be ruled-out included a neurilemoma, a traumatic neuroma, a hemangioma, and a mucoid cyst. The histological evaluation, in correlation with the clinical and radiological interpretation, helps differentiate between these lesions.
A neurilemoma (schwannoma) is a benign, encapsulated nerve sheath tumor.9,19,20 It occurs at any age but is most commonly observed in adult men and women in the third to fifth decades of life.9,19,20 This tumor typically arises from the spinal nerve roots and the cervical, sympathetic, vagus, peroneal, and ulnar nerves and consequently appears in the head, neck, and the flexor surfaces of the upper and lower extremities.9,19,20 Pain and neurological symptoms are uncommon unless the tumor becomes large. Detection of neurilemomas by conventional radiography is difficult unless they are large, calcified, or produce erosions to adjacent bone.19 Magnetic resonance imaging studies may show an eccentric mass arising from a peripheral nerve or only show an indeterminate soft tissue mass of low intensity on T1 and high intensity on T2-weighted images.9,19 Histologically, the lesion is composed of Antoni A (highly ordered cellular component) and Antoni B (loose myxoid component) areas.9
A traumatic neuroma is an exuberant but non-neoplastic proliferation of a nerve occurring in response to injury or surgery.20 Traumatic neuromas represent the consequence of the nerve injury itself and the abortive attempt at natural repair.19 Clinically, they present as firm nodules that are occasionally tender or painful. Magnetic resonance findings include a fusiform mass with a non-homogeneous signal intensity.19 The histologic hallmark of a neuroma is the identification of the damaged nerve and the participation of all the elements of the nerve fascicles.20
Hemangioma is the most frequent soft tissue tumor and the most common tumor in infancy and childhood.19 Based on the vascular channel that dominates the histo- logic appearance, hemangiomas are classified as capillary, cavernous, and venous.19 The lesion may occur in cutaneous, subcutaneous or intramuscular locations.9,19 Patients with large tumors may complain of symptoms of vascular engorgement, including pain, heaviness, and swelling. Plain radiographs may reveal small phleboliths. Hemangioma and glomus tumor share the same MRI features; nevertheless, hemangiomas have a more superficial location in the papillary dermis and epidermis.3,19
A mucoid cyst is a ganglion type cyst emanating from an arthritic distal interphalangeal joint.9 Mucoid cysts are classically located in the proximal nail fold and are painless.3 Nail deformity is common.9 On MRI, the lack of enhancement after intravenous gadolinium administration and the presence of a pedicle communicating with the adjacent distal interphalangeal joint are features that favor the diagnosis of a mucoid cyst.3,19
Glomus tumors are believed to arise from a neuromyo- arterial apparatus called the glomus body. This normal anatomical structure is a remarkable arteriovenous anastomosis, or shunt, between terminal vessels found in the reticular layer of the dermis, thought to function in skin circulation and thermoregulation.1-3,5,8,15-18,20 It is also referred as a neurovascular nodule.8 Though glomus bodies are distributed throughout the body in any part of the dermis, they are most heavily concentrated in the digits and palms and soles of hands and feet.2,3,15,17 The nail beds of fingers and toes contain 93 to 501 glomus bodies per square cm.3
Glomus tumors are uncommon, representing less than 1.5% of all benign soft tissue neoplasms of the extremities.4,8,17,20 They most commonly appear in middle-aged individuals, but can occur in any age from 9 to 85 years.4,10,15,17,18,20 The incidence in men and women is similar.4,15-17,20 The classic subungual lesions of the hand are thought to occur more commonly in middle aged women, while men are more likely to have lesions in other locations.4,15-17,20 Little can be said about the gender distribution of glomus tumors in the feet because of the paucity of reported cases.17
Glomus tumors present as painful subungual lesions of the hand more than 75% of the time, but have been reported in multiple other sites throughout the upper and lower extremities including the subungual regions of the toes and the plantar surfaces of the heal, arch, and fore- foot.2,4,10,17,20 They have also been described in other anatomical sites including the trunk, the patellar ligament, the submucosal tissues, and even deep to skin in muscles and joints.1,2,4,5,10,13,15-18,20 Glomus tumors appear in solitary or multiple forms.4,16,18,20 Solitary tumors occur the most frequently and are usually painful.16,20 Multiple lesions are more common in children, may not be associated with pain, and can have a familial inheritance pattern.10,15,16,20 In adults, 2% to 3% of reported patients have multiple lesions.15,16
Patients with glomus tumors are known to present with the classic triad of paroxysmal excruciating pain, point tenderness, and hypersensitivity to temperature, especially cold.1,8,13,15-18,20 All components of the clinical triad are not present in each patient, but pain is the common presenting characteristic of all lesions.4,10,17,20 Episodes of pain may be fleeting or can last as long as 3 hours.10,16,17,20 However, rare painless glomus tumors of the hand have been reported.2
On physical examination, a mass may not be noted at the time symptoms start. If a mass is noted it is usually well circumscribed, less than 1 cm in diameter, and located deep in the dermis.16 Reddish purple discoloration is a characteristic finding for lesions located in superficial sub- cutaneous tissues, depending on the vascularity of the tumor.1,8,13,15,16 When the tumor is present in a deeper location, the discoloration is not present.1,8,13 Subungual lesions can also present with a bluish hue beneath the nail bed and some present with disturbance of nail growth, such as ridging and deformation.16,17 Other less frequent findings on physical examination include Horner's syndrome, osteopenia, overgrowth of an extremity or atrophy, and hypoplasia of the involved extremity secondary to chronic disuse.2,5,15-17
Without the classic history and physical findings, glomus tumors may pose a diagnostic dilemma. If the history of pain is short or if the tumor is subcutaneous, it may be difficult to locate.2 Clinical tests can be helpful. The Love12 test is suggestive of the diagnosis and helps locate the lesion. It is described as the use of the tip of a pencil, pin, toothpick, or other fine instrument to elicit pinpoint tenderness over the affected region while eliciting no pain in an immediately adjacent pinpoint area. Hildreth7 describes the disappearance of pain after placing a tourniquet proximally on the extremity, ostensibly relating to the vascular nature of the lesion. The test is virtually pathognomonic for the presence of a glomus tumor. In addition, placing the affected part in cold water can be used to reproduce the symptoms of temperature sensitivity.3,17
A number of imaging techniques have been used in the diagnosis of glomus tumors, including plain radiography, arteriography, thermography, scintigraphy, ultrasonography, and MRI. The plain radiographic appearance of the involved digit is often unremarkable. However, in many subungual lesions, radiolucent erosions along the phalangeal border may be detected.17 Diagnosis is particularly difficult when the lesion presents in an unusual location, such as the foot.15 Conventional arteriography, thermography, and scintigraphy are no longer indicated.3,15 However, Tc99m-bone scan is sometimes indispensable in eliminating an osteoid osteoma.3 High resolution real time ultrasound finds tumors as small as 3 mm in diameter and aids in their localization. However, small and flattened subungual lesions are difficult to detect with ultrasound, which also has low specificity and is operator dependent.1,3,8,11,13,15 Magnetic resonance imaging has been used successfully to diagnose glomus tumors, which typically appear as well-delineated masses, with low signal on T1-weighted images and high signal on T2-weighted images. After intravenous gadolinium administration, they tend to enhance vigorously as they are partly vascular in etiology.15,17 Magnetic resonance imaging can be particularly helpful in the detection of early lesions, which are often smaller and more difficult to diagnose definitively by other means.8,17 However, findings on MRI are not specific for the diagnosis of glomus tumors and may include other well circumscribed solid neoplasms.15 Diagnosis of some glomus tumors with MRI imaging can also be difficult because the signal intensity of the tumor can mimic that of the nail bed.3
On gross inspection, glomus tumors are less than 1 cm in diameter, well circumscribed, and with a fibrous capsule. They are soft in consistency and are blue or pink-red depending on the vascularity of the lesion.4,10,16,20 Microscopically, glomus tumors are composed of vascular structures and glomus cells in varying proportions. The vessels are lined with endothelium and can be capillary sized or tortuous and dilated. Surrounding them are clusters of glomus cells, which are the distinguishing feature of this neoplasm.4,10,16,20 Glomus cells are small, uniform rounded cells with centrally placed round regular nuclei, which give rise to an image that suggests that the nuclei are punched out of the same mold. These cells have lightly eosinophilic or amphiphilic cytoplasm, hard to see nucleoli, and no division figures. Each cell is surrounded by a basal lamina, seen best on periodic-acid Schiff (PAS) or toluidine blue stain.4,10,16,20
The tumor is classified into four subtypes based on the relative prominence of glomus cells, vascular structures, and smooth muscle. These types are: glomus tumor proper or solid glomus tumor, glomangioma, glomangiomyoma, and glomangiosarcoma.4,10,16,20 Glomus tumors of all sub- types typically express smooth muscle actin and have abundant pericellular Type IV collagen production. Vimentin can be identified in all glomus tumors.4,10,16,20 In our patient, a panel of antibodies was used for the differential diagnosis of this tumor from sweat gland tumors, paraganglioma, and hemangiopericytoma. The used antibodies were vimentin, smooth muscle actin, desmin, S-100 protein, epithelial membrane antigen, Cam 5.2, carcinoembryonic antigen, chromogranin, and CD34. Intense staining of cells was observed with vimentin and smooth muscle actin, which is compatible with the diagnosis of glomus tumor.
Delay in the correct diagnosis of glomus tumors is common and has been reported to range from 4 months to 15 years from the onset of symptoms.1,3,8,13,15-17 Common misdiagnoses include traumatic neuroma, ingrown toe-nail, entrapment neuropathy, infection, melanoma, fibroma, fasciitis, gout, intraligamentous cysts, mucoid degeneration, granulation tissue, cartilage metaplasia, hamartomatous malformation, eccrine spiradenoma, skin adnexal tumor, and clinical depression.2,11,15,17 The most common lesion confused with a glomus tumor is a traumatic neuroma, which may be the result of trauma that cannot be recalled.2 Plexiform neurofibromas have also been found to cause symptoms that mimic those of glomus tumors. In the palm, a neurilemmoma can also produce the same symptom pattern.2 It is obvious that lesions that have an atypical presentation are more likely to present a diagnostic dilemma, and differentiation must be made from other painful lesions.17
Once the diagnosis of glomus tumor is made, surgical excision is the definite treatment. Complete excision of the tumor offers immediate pain relief with little chance of recurrence.2,5,8,15-17,19 The biological behavior of the tumor is usually benign. Malignant glomus tumors are exceedingly rare, comprising less than 1% of glomus tumors.4 Local invasion of the capsule and intravascular spread of tumor cells are rare.15,16 If a recurrence does occur, it is usually secondary to incomplete excision, rather than to infiltrative growth, and patients will note the return of symptoms within months after surgery.15,16 Subungual tumors have a high recurrence rate (14%) because it is difficult to distinguish the tumor from the surrounding tissue and completely excise it.16 Tumors in other areas rarely recur because they are frequently encapsulated and easy to distinguish from the surrounding tissue, making complete excision possible.16
In our patient, surgical exploration of the lateral distal phalanx of the left third toe was done under digital block (xylocaine 2%) using a digit tourniquet. A 2-cm longitudinal incision was made directly lateral to the lateral nail fold. Under 3.5 loupe magnification, a round, 0.6-cm maximum diameter well-encapsulated mass with pinkish hue was isolated adjacent to the lateral nail bed and removed in its entirety. The patient experienced immediate symptom relief after surgery and 12 days later was allowed to resume activities as tolerated. At 1 year followup, the patient is completely asymptomatic, satisfied with the result of the operation, and has no evidence of a recurrent or residual mass.
Glomus tumors are rare benign lesions, most often found in the digits, and are curable by simple surgical excision. Because glomus tumors are rare in the lower extremity and frequently mimic other orthopaedic conditions their diagnosis is commonly delayed or missed. A detailed physical examination and appropriate diagnostic studies, such as plain radiography, ultrasonography, and MRI, can prevent delay in diagnosis and treatment. This patient shows that glomus tumors should be included in the differential diagnosis of atypical and unexplained localized forefoot pain.