Glomuvenous malformation

Overview

Glomuvenous malformation (GVM), also known as "multiple glomus tumors" or "glomangioma", is a localized bluish-purple cutaneous vascular lesion, histologically consisting of distended venous channels with flattened endothelium surrounded by variable number of maldifferentiated smooth muscle-like "glomus cells" in the wall. GVM account for 5% of venous anomalies referred to centers for vascular anomalies.

Source: Atlas of Genetics and Cytogenetics in Oncology and Haematology

Symptoms

There is a wide phenotypic variation between GVM patients, even within the same family (with the same germline mutation). An individual can have an extensive lesion, affecting for example a whole extremity or most of the trunk, while others have minor, scattered papulonodular lesions of a few millimetres in diameter. The lesions are often multiple, and they can affect any body part.

Seven features characterize GVM lesions:

  1. Colour: GVMs can be pink in infants, the most are bluish-purple
  2. Affected tissues: the lesions are localized to the skin and subcutis, and they are rarely mucosal and never extend deeply into muscles
  3. Localization: lesions are more often located on the extremities, although they can be found all over the body
  4. Appearance : lesions are usually nodular and multifocal, raised with a cobblestone-like appearance, except for the rare plaque-like variant. They are often hyperkeratotic
  5. The lesions are not compressible
  6. The lesions are painful on palpation
  7. New lesions can appear with time, likely after trauma

Source: Atlas of Genetics and Cytogenetics in Oncology and Haematology

Causes

GVM are caused by loss of function mutations in the glomulin gene. Although inheritance is considered to be autosomal dominant there is some evidence that suggests a "second hit" somatic mutation (paradominant inheritance) is required for the lesions to develop.

Source: Connective Tissue Gene Tests

Diagnosis

At the histological level, the mural glomus cells are positive for smooth muscle alpha-actin and vimentin, but negative for desmin, Von Willebrand factor and S-100. Under electron microscopy, glomus cells show smooth muscle myofibrils and "dense bodies", characteristics of vascular smooth muscle cells (vSMCs). Thus, these cells are most likely incompletely or improperly differentiated vSMCs.

Source: Atlas of Genetics and Cytogenetics in Oncology and Haematology

Treatment

The gold-standard treatment for GVM consists of surgical resection, as lesions are superficial and rarely affect deeply the underlying muscle, and sometimes sclerotherapy. In contrast to venous malformations, the use of elastic compressive garments often aggravate pain and should thus be avoided.

Source: Atlas of Genetics and Cytogenetics in Oncology and Haematology