Are You Confident of the Diagnosis?
Characteristic findings on physical examination
Glomuvenous malformations (GVMs) are of two distinct types: the single lesion and the multiple variant type.
Single or solitary lesions present as acral or subungual blue-to-red blanchable nodules or papules in the deep dermis or subcutis. Lesions are typically smaller than 2cm and are painful. Pain, as the presenting symptom, is often in response to temperature changes or pressure.
The multiple variant type is divided into localized, disseminated, and congenital forms. The multiple localized type presents as blue-to-purple compressible nodules, grouped in a segmental distribution, on an extremity (Figure 1). The disseminated type consists of clusters of lesions, distributed over the body with no specific grouping. Finally, the congenital type is either grouped papules that coalesce into indurated plaques, or a cluster of discrete nodules. The multiple variant can present with or without pain.
Expected results of diagnostic studies
Typical routine laboratory studies are not useful. In the multiple type with dissemination, a complete blood count is indicated to examine the platelets, as the multiple disseminated type can have platelet sequestration similar to the Kassabach-Merrit syndrome.
For single tumors, radiography may reveal an increased distance between the dorsal phalanx and the underside of the nail. Additionally, bony erosions are present in up to 60% of lesions. The best imaging technique is magnetic resonance imaging (MRI). Either standard or high-resolution MRI is utilized for imaging glomus tumors. This can be beneficial in defining the extent of the lesions and their relationship to anatomic structures prior to therapeutic interventions. Ultrasound has also shown to be beneficial.
The differential diagnosis includes: blue nevi (non painful and not compressable), blue rubber bleb nevus syndrome (no glomus cells histologically), eccrine spiradenoma (histologically distinct), Kaposi sarcoma (not painful, not compressable, and histologically distinct), leiomyoma (clinically may resemble, but can be differentiated histologically and through immunohistochemistry), Maffucci syndrome, neurilemmoma, and other venous malformations.
Histologically, glomus tumors contain numerous vascular channels lined with flattened endothelial cells (Figure 2). Peripheral to the endothelial cells are layers of round glomus cells, arranged in distinct rows resembling a string of pearls. Multiple glomangiomas have only one to two layers of cells. Glomangiomyomas typically have a thickened muscularis medi in addition to the one to two layers of cells.
Who is at Risk for Developing this Disease?
Both the single and multiple variations account for 1%-5% of all soft tissue tumors of the hand. Extracutaneous sites have been reported, including involvement of the gastrointestinal tract, trachea, nerve, bone, mediastinum, liver, pancreas, and ovary.
With the single variant, lesions typically present in the distal extremities in young adults aged 20-40 years .
The multiple or disseminated versions are classically seen in children.
What is the Cause of the Disease?
Glomus tumors are thought to arise from the glomus body, which is a vascular thermoregulatory unit of the fingers and toes. Most are solitary and sporadic. Multiple GVMs occurring in a widespread or segmental distribution can be inherited in an autosomal dominant pattern with incomplete penetrance (90% by age 20 years). Affected individuals and carriers have heterozygous germline mutations in the GLMN gene that cause a premature stop codon and a truncated glomulin protein.
There is evidence that the GVMs themselves result from a somatic second hit to the GLMN gene that leads to a loss of heterozygosity and a localized complete absence of glomulin function (type 2 mosaicism). Approximately two-thirds of patients with GVMs have a family history of similar lesions, as compared with 1% of the individuals with other types of venous malformations.
Systemic Implications and Complications
Single GVMs are limited to the digit involved and do not have systemic involvement. The multiple variant can rarely have systemic involvement. A directed history and physical, as well as appropriate imaging, should be perfomed.
The treatment of choice for isolated cutaneous GVMs is surgical excision. The typical method is nail avulsion, followed by excision. The “trap door” technique has been recently reported as a nail-plate-conserving surgical approach with good results. The surgical approach may, however, be impractical in cases of multiple or large segmental lesions.
Sclerotherapy with sodium tetradecyl sulfate, polidocanol, and hypertonic saline has been reported to be effective in patients with multiple GVMs that are located on the extremities, whereas the use of sclerosants, including polidocanol, pure ethanol, and Ethibloc (a mixture of zein, sodium amiotrizoate tetrahydrate, oleum papaveris, and propylene glycol) was unsuccessful in a series of seven patients with large facial GVMs.
Ablative therapy with argon and carbon dioxide lasers is of potential benefit for small superficial lesions. Treatment with the pulsed dye laser may also help to flatten GVMs and provide pain relief. Long-pulse 595nm pulsed dye laser treatment has been reported to be successful. Nd:YAG laser treatment has been reported to be successful in three cases of the multiple variant.
Optimal Therapeutic Approach for this Disease
The treatment of choice for the single variant is surgery .
For the multiple variant, the surgical approach may be impractical. Laser treatments offer the best inital approach, but may require several treatments. The depth of the lesions should guide the laser platform choice. Sclerotherapy has been documented as an effective treatment modality based on the location of the lesion(s).
For single tumors, if the lesion is completely excised, the risk of recurrence is low. Malignant transformation is rare. Nail plate dystrophy is a common complication of surgical excision.
For the multiple variants, some treatments have been shown to be effective; however, there is no gold standard for treatment for these lesions. The risk of recurrence or incomplete treatment is high.
Patients with multiple lesions may have systemic involvement, especially of the of the gastrointestinal tract, trachea, nerve, bone, mediastinum, liver, pancreas, and ovary. These patients will need appropriate evaluation by utilizing imaging; the need for follow-up will depend on the degree of systemic involvement, symptoms, and choice of therapy.
Unusual Clinical Scenarios to Consider in Patient Management
Glomus tumors have been reported to be present in the liver in two case reports. While rare, they are in the differential for hepatic masses. These cases presented with epigastric pain and nausea, without skin findings. Additionally, there are single case reports of congenital GVMs and the association of chylous ascites and pleural effusions, although these are rare.
What is the Evidence?
Henning, JS. “Glomovenous malformations”. Dermatol Online J. vol. 13. 2007 Jan 27. pp. 17(Case report and review of current literature on multiple GVM)
Blume-Peytavi, U, Adler, YD, Gellen, CC. “Multiple familial cutaneous glomangioma: a pedigree of 4 generations and critical analysis of histologic and genetic differences of glomus tumors”. J Am Acad Dermatol. vol. 43. 2000. pp. 633(Genetic evaluation and pedigree analysis to isolate the familial syndrome)
Brouillard, P. “Four common glomulin mutations cause two thirds of glomuvenous malformations (“familial glomangiomas”): evidence for a founder effect”. J Med Genet. vol. 42. 2005. pp. e13(For the first time, delineates the mutation associated with GVM)
Paris, K, Kossard, S. “Multiple hereditary glomangiomas: Successful treatment with sclerotherapy”. Australas J Dermatol. vol. 43. 2002. pp. 43(Treatment with sclerotherapy; review article showing some success)
Mounayer, C. “Facial glomangiomas: large facial venous malformation with glomus cells”. J Am Acad Dermatol. vol. 45. 2001. pp. 239(Discusses presentation, treatment options)
Pahwa, M. “Glomus tumor of the nail bed treated with the “trap door” technique: A report of two patients”. J Dermatolog Treat. vol. 21. 2010 Sep. pp. 298-300. (Novel surgical technique to preserve the nail plate)
Hughes, R. “Nd:YAG laser treatment for multiple cutaneous glomangiomas: report of 3 cases”. Arch Dermatol. vol. 147. 2011 Feb. pp. 255-6. (Review of laser treatments and discusses settings for Nd:YAG)
Lin YC. “Recurrent digital glomus tumor: analysis of 75 cases”. Dermatol Surg. vol. 36. 2010 Sep. pp. 1396-1400. (Largest case series; analyzes the presentation and treatment of cases)
Vergili-Kalner, IJ. “Long-pulse 595nm pulsed dye laser for the treatment of glomus tumor”. Dermatol Surg. vol. 36. 2010 Sep. pp. 1463-5. (Laser treatment paper discussing treatment consideration and settings)
Filice, ME. “Glomus tumor of the lung: case report and literature review”. Pathologica. vol. 100. Feb 2008. pp. 25-30.
Copyright © 2017, 2013 Decision Support in Medicine, LLC. All rights reserved.
No sponsor or advertiser has participated in, approved or paid for the content provided by Decision Support in Medicine LLC. The Licensed Content is the property of and copyrighted by DSM.