Dermatology Online Journal

Glomuvenous Malformations (Familial generalized multiple glomangiomas)
Jeremy A Brauer MD, Robert Anolik MD, Julia Tzu MD, Shane Meehan MD, Colette D Lieber MD, Roy G Geronemus MD
Dermatology Online Journal 17 (10): 9

Department of Dermatology, New York University, New York, New York

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Abstract

A 15-year-old boy with a diagnosis of generalized multiple glomangiomas was referred for evaluation and treatment of enlarging and increasingly painful lesions on his right ankle. The patient underwent a series of two treatments with long-pulsed KTP 1064 nm laser that resulted in substantial improvement in appearance and decreased pain. Generalized glomuvenous malformations, or multiple glomangiomas, are the less common presentation of proliferation of glomus cells and may have extracutaneous involvement. Whereas surgical management is often employed and definitive for solitary lesions, interventions such as laser therapy, may be beneficial for improvement of functional impairment and cosmesis as was observed in our patient.

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History

A 15-year-old boy with a diagnosis of generalized, multiple glomangiomas was referred to the Laser and Skin Surgery Center of New York for evaluation and treatment of a vascular nodule on his right leg that had enlarged and become increasingly painful over the last year. He had had no treatments prior to presentation. Eight years earlier, the patient’s mother described blue-grey spots on her son’s face, chest, back, arms, and legs. He was routinely complaining of headaches. The patient was referred to a pediatric dermatologist, who performed a biopsy that showed findings consistent with glomangioma. He was subsequently sent for radiologic imaging and consultations with additional physicians, who included a vascular anomalies specialist. Observation was ultimately recommended, and no further interventions were undertaken. He admits to occasional difficulty breathing because of his asthma and periodic headaches but otherwise denies fatigue, seizures, fevers, chills, sweats, nausea, vomiting, diarrhea, oral or rectal bleeding, and joint or muscle pain.

Past medical history included asthma. He takes loratadine and uses fluticasone propionate and salmeterol inhalation aerosol as needed; he denies any known drug allergies.

The patient has undergone two treatments with a long-pulsed KTP laser at a wavelength of 1064 nm, with alleviation of pain and flattening of the cutaneous nodules that are located on his right leg.

Physical examination

Figure 1	Figure 2

On the anterior, distal aspect of the right leg and ankle are six-to-seven, grouped, tender, rubbery, purple nodules that range in size from 2 mm to 15 mm. Scattered, blue macules 5 mm to 10 mm in size are present on the preauricular aspect of the right cheek, chest, and back.

Laboratory data

Magnetic resonance imaging of the brain with and without contrast showed a very small non-specific area of hyperintensity on T2 signal within the right corona radiata. A computed tomography scan of the chest, abomen, and pelvis was normal.

Histopathology

Figure 3

Within the reticular dermis there are several irregularly dilated thin-walled blood vessels that are lined by glomus cells.

Discussion

First described by Masson in 1924, glomus tumors are benign vascular neoplasms that most often present in young adults as solitary, bluish nodules, or less commonly, as multiple lesions approximately 10 percent of the time [1, 2]. They are categorized based upon histopathologic findings as either glomus tumors, glomangiomas, or glomangiomyomas. However, some believe the latter two terms describe the same entity [3]. More recently, these lesions have been referred to collectively as glomuvenous malformations. Glomus cells are thought of as modified smooth muscle cells that are derived from the Sucquet-Hoyer canals and make up specialized thermoregulatory units comprised of arteriovenous anastomoses and known as glomus bodies [4]. Glomus bodies normally are found in acral skin. However, many glomus tumors arise where glomus bodies are not thought to be present, which suggests that some may arise from differentiation of pluripotent perivascular or smooth muscle cells [5].

Glomuvenous malformations may either be acquired or congenital, and heterozygous germline mutations in the glomulin gene (GLMN), which is localized to chromosome 1p21-22, have been reported in these patients [6, 7, 8]. The most consistent pattern of inheritance is autosomal dominant with incomplete penetrance and variable expressivity [9, 10, 11]. Most reported cases of congenital multiple glomangiomyoma and familial generalized multiple glomangiomyoma are of British or Northern European origin [3, 8, 12].

As previously mentioned, the solitary form is most frequently observed and presents as a small, firm, blue-to-purple, dermal or subcutaneous nodule that usually is less than one centimeter [10]. These lesions often are associated with pain. Owing to the acral location of glomus bodies, the most common presenting location is the hand, specifically the subungual aspect of the finger, followed by the foot and forearm [5]. On the distal aspects of the extremities, glomus tumors may cause considerable paroxysmal pain, which can be spontaneous or triggered by changes in temperature and pressure; it may occur as a result of trauma [2]. There is no gender predilection except for subungual tumors, which are more often found in women, and formultiple lesions, which are more commonly observed in men [7, 14].

Multiple glomus tumors were first reported by Touraine in 1936 and are ten times more frequent in children than they are in adults, with 60 percent of patients reporting a positive family history [7, 13, 15]. These soft, bluish nodules may number anywhere from two to more than one hundred and may be localized, segmental, or disseminated over the entire body [9, 10, 12, 16, 17]. The most commonly involved areas are the trunk and upper extremities and least common are the scalp, face, and genitalia [7]. When localized or segmental in distribution, these lesions tend to involve the extremities and not the trunk and face [7]. These grouped, multiple tumors may be painful; pain, intermittent discoloration, and sweating may precede the development of a tumor [2]. However, multiple glomuvenous malformations are less likely to be painful than are solitary ones [13], with 42 percent to 63 percent of patients complaining of pain [9, 13, 16].

Congenital glomuvenous malformations also tend to be multiple, usually enlarging throughout the patient’s development as grouped papules that coalesce into indurated plaques [17]. Most patients develop satellite lesions later in life, often during puberty [16, 18]. Some patients have a positive family history, with an autosomal dominant mode of inheritance, and some may have associated malformations [9, 11, 13, 18]. Patients may have involvement of internal organs, which include the gastrointestinal tract, trachea, nerve, bone, liver, pancreas, and ovary [5, 13, 19, 20].

Routine laboratory tests and imaging studies are not necessary for solitary lesions. However, in patients with multiple glomangiomas, there is concern for platelet sequestration, and a complete blood count with differential analysis is suggested. Imaging studies may aid in the diagnosis of solitary subungual lesions or internal visceral involvement [21, 22, 23].

Whereas these lesions are not always biopsied, histopathologic features are important in determining the subtype of glomuvenous malformation. Solitary lesions appear as well-circumscribed nodules that are surrounded by a rim of fibrous tissue with vascular spaces that are surrounded by clusters of round or polygonal cells with plump nuclei and scant eosinophilic cytoplasm; these cells are known as glomus cells. Multiple lesions are not as well circumscribed, with an overall appearance that is more representative of a hemangioma. They contain multiple, irregular, dilated, vascular spaces that are larger than those observed in a solitary lesion. Focal, narrow, aggregates of glomus cells are present in the walls of these channels.

Complications of glomus tumors include localized increase in perspiration, gastrointestinal tract and lung perforation, pulmonary hypertension, and hematuria [13, 24].

The treatment of choice for symptomatic solitary glomuvenous malformation is surgical excision; however, this is not always a feasible option for multiple lesions. Described treatment modalities include argon and carbon dioxide laser therapy and sclerotherapy with hypertonic saline or sodium tetradecyl sulfate [25, 26, 27].

References

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