White : Diseases of the Skin - Vascular Disorders

Table of Contents
This Chapter	All Chapters

Gary M. White & Neil H. Cox

Diseases of the Skin

15	Vascular Disorders

VENOUS MALFORMATIONS

Venous malformations, cutaneomucosal venous malformations, and blue rubber bleb nevus syndrome

Etiology and pathogenesis

Venous malformations are generally apparent at birth, a minority being familial. They are usefully divided into two main groups. Capillary malformations

These include the following.

• Venous malformations - these may have deep local extension but do not have an association with separate internal lesions.

• Cutaneomucosal venous malformations (CMVM) - in which similar lesions affect mucosae such as the gastrointestinal tract, and other organs such as the liver, pancreas, and spleen. On the basis of familial cases, mutation in the gene VMCM1 on chromosome 9p.21, coding for the protein TIE2/TEK, has been identified as the cause in most familial cases but not in all.

It has recently been suggested that the blue rubber bleb nevus syndrome (Bean syndrome) may be a variant of CMVM. There is also some overlap with Maffucci syndrome.

Clinical

Multiple, protuberant, blue, compressible, cutaneous nodules are characteristic (Fig.15.10). Most patients are white and the onset is usually at birth or in childhood. The lesions may be noted on ultrasound in the prenatal period. Extracutaneous venous malformations may occur virtually anywhere but characteristically affect the gastrointestinal tract and skeletal system. The gastrointestinal tract involvement may cause chronic asymptomatic blood loss or life-threatening hemorrhage. Subcutaneous masses may be noted. MRI or other imaging studies may be needed. Limb lesions may cause hypertrophy, and osseous lesions may cause joint pain or bony erosion.

Differential diagnosis

The main differentials are as follows.

•	Other types of vascular malformation, especially glomuvenous malformation (discussed later). Mixed types of malformation cause particular difficulty, as they may have red (superficial and capillary) as well as blue (deeper and venous) colors.
•	Deeply situated (therefore blue - colored) infantile hemangiomas (IHs) - features that may help in distinguishing venous malformations from IHs include the following.

•	Sex incidence - equal in venous malformations, female excess in IHs.
•	Color-either may be blue, but a red patch at birth suggests IH.

•	Course - significant proliferation then involution occurs in IHs; venous malformations are usually obvious at birth and are more stable over time.
•	Pathology-IHs have small dense vessels that stain positive with proliferation markers and Glut-1.

•	Radiology - several differences may be apparent.
•	Genotyping - an advancing ; see etiology section earlier in this section.

Treatment

No treatment is needed. If treated early in the macular stage, the pulsed dye laser can remove each lesion. Otherwise, surgery is the only remedy.

Glomuvenous malformation (multiple glomangiomas, multiple glomus tumors)

Glomuvenous malformations (GVMs; Fig.15.11) are inherited in about two-thirds of cases, and are due to mutations in the VMGLOM gene on chromosome 1p21 - 22, a gene that appears to alter differentiation of vascular smooth muscle cells via its protein product, glomulin. The lesions may develop in childhood, adolescence, or adulthood. Many are similar to venous malformations but have sometimes abundant, glomus cells histologically. The term multiple glomus tumors is technically incorrect and would be best dropped.
A recent study used clinical criteria, histology, and mutations in the TIE2 or glomulin gene to separate these entities, with the following results.

•	Glomuvenous malformations are often inherited (64%), whereas this applies to only just over 1% of venous malformations.
•	Glomuvenous malformations are mainly acral and in the skin and subcutis, whereas venous malformations are around joints or involve deeper tissues such as muscle.

•	Glomuvenous malformations are often multilobular, cobblestoned or plaque-like, and are not easily compressed, whereas venous malformations are softer, blue, and compressible.
•	Compression may aggravate the associated pain of GVMs if this is present, while venous malformations are more likely to be painful on waking or after physical activity.

No treatment is needed. Excision may be done for painful lesions if not extensive. Infrared coagulation has been used.

Fig. 15.11 Glomuvenous malformation (GVMs). (a) GVMs on the buttocks and trunk. (b) GVM on the arm of a child.

Venous lake

Dark-blue, soft, compressible, benign, vascular papules in the sun-exposed skin of an elderly person are characteristic of venous lakes (Fig.15.12). The ears, lips, and face are favored sites. They are often solitary and up to about 5mm in diameter when they occur on the lip, but are often smaller and multiple at other facial sites. Treatment with cryotherapy or electrocautery (with risk of a scar) may be tried. Pulsed, tunable dye and argon lasers have been used, as has infrared coagulation. Sclerotherapy with polidocanol was effective in the treatment of lip venous lakes.

Figure 15.12 Venous lakes. These soft, compressible blebs are common in the elderly. The lips, ears (a), and face (b) are common sites.

Arterial and mixed malformations

Arteriovenous malformations account for about 5% of vascular anomalies. Arteriovenous fistulae are usually traumatic or created surgically (e.g. for hemodialysis access).

PRACTICE POINTS

•	Most vascular malformations can be compressed: this is particularly helpful in diagnosis of darker lesions, such as venous lakes, which may otherwise be diagnosed as melanocytic.
•	In distinguishing between glomuvenous malformations (without internal involvement) versus blue rubber bleb nevus syndrome (with likely gastrointestinal involvement and risk of internal bleeding),firm or tender lesions suggest the former, while oral mucosal lesions indicate the latter.

•	Venous malformations - these may have deep local extension but do not have an association with separate internal lesions.
•	Cutaneomucosal venous malformations (CMVM) - in which similar lesions affect mucosae such as the gastrointestinal tract, and other organs such as the liver, pancreas, and spleen. On the basis of familial cases, mutation in the gene VMCM1 on chromosome 9p.21, coding for the protein TIE2/TEK, has been identified as the cause in most familial cases but not in all.