In the peripheral arterial chapter 1, primary vascular tumors were described with an emphasis on the lesions that affect arteries and capillaries. The goal of this chapter is to expand upon that chapter to include peripheral tumors of venous and lymphatic origin. It is well known that the classification of peripheral vascular tumors is very difficult and that the schemes have changed over time. These schemes have been based on a wide variety of characteristics, including morphologic criteria and clinical behavior. Classification challenges include both determining if a lesion is a tumor (hemangioma) or a vascular malformation (hamartoma) and further in determining if a tumor is benign or malignant. To further complicate the matter, many lesions contain both arterial and venous elements. We have attempted to include tumors with primarily venous components or those that arise in a vein. Because of this overlap, some of these lesions were already described in the arterial chapter 1 and are not discussed here. In this chapter, lesions are classified by the criteria of Calonje and Fletcher,¹ which take into account both pathologic appearance and clinical behavior.

Benign Lesions

Clinical Features. Intravascular papillary endothelial hyperplasia is a benign lesion that is believed to arise as an unusual form of organizing thrombus (Figure 39-1). It was first described by Masson in 1923² as a “vegetant intravascular hemangioendothelioma,” which he found in a thrombosed hemorrhoidal vein and can be mistaken for a host of other vascular lesions, including angiosarcoma. Masson believed he had found a benign neoplastic lesion; however, in 1932, Henschen³ identified a similar vascular growth which he believed was a reactive process. The tumor was then renamed intravascular capillary endothelial hyperplasia in 1976 by Enzinger and Clearkin.⁴

Masson’s tumor has no gender predilection and can occur at many different locations, including the head, neck, trunk, and fingers. Early studies showed no age predilection, but more recent analysis shows frequent occurrences in young adults.¹ The tumor commonly appears as an asymptomatic nodule that is sharply demarcated and slightly raised over the surrounding skin. Rare case reports have described origins in the renal vein^5,6,7,8,9 Although the literature indicates that this tumor was initially considered solely an intravascular lesion, a more recent analysis¹⁰ identified three variations in presentation, which are (1) primary-pure form located inside an isolated blood vessel; (2) secondary formation inside a preexisting vascular lesion such as a hemangioma, and (3) extravascular (very rare). Masson’s tumor tends to be small (0.2–2.0 cm) and rarely recurs after surgical excision.

Histology. Masson’s tumor histologic appearance depends on which of the three lesion types is being analyzed. The primary form is described as a dilated vascular space, typically a thin-walled vein. The secondary form takes on properties of the vascular lesion from which it arises. Last, the extravascular form has no apparent vascular structure. All forms contain papilla that are either free floating in the vascular lumen or occasionally connected by a stalk to the vessel wall. These papillae are covered by a layer of epithelial cells in which mitotic figures and cellular atypia are rarely encountered. There is no associated necrosis of the tissues, and the epithelial cells that line the stalk tend to form a monolayer. The stalks themselves are hypocellular and composed of hyaline-like material with few capillaries. Surrounding the stalks are numerous erythrocytes with associated thrombus, although some reports have noted that this latter feature is not always present. Another important histologic clue in the diagnosis of Masson’s tumor is the paucity, or complete lack, of inflammatory cells. This feature helps to distinguish the lesion from many other diseases such as atypical pyogenic granuloma (PG). It has also been noted that the lesion never extends out of the vessel.

Pathogenesis. The pathogenesis of Masson’s tumor is incompletely understood. The predominating opinion is that it is an unusual presentation of a thrombus undergoing organization.⁴¹¹ This theory is supported by Hashimoto,¹⁰ who noted in 1983 that “in most of our cases, thrombotic material seemed to serve as a matrix for the development of this papillary endothelial proliferation.” Further evidence was provided by Kreutner,¹² who used electron microscopy to identify ultrastructural similarities between Masson’s tumor and vessels in granulation tissue. An alternative hypothesis suggests that the tumor begins as a vascular lesion, which then gives rise to the associated thrombus because of the decreased velocity of blood flow and outright stasis. Further study is needed to clarify this issue.

Vascular Ectasias

Clinical Presentation. First described in 1900,¹³ Klippel-Trenaunay syndrome (KTS) classically consists of a triad of findings: varicose veins, telangiectatic nevi (common birthmark or port-wine stain), and hypertrophy of bones and soft tissues in the affected limb (Figures 39-2 and 39-3). Two of three of these findings are needed for diagnosis. It has also been noted that deep venous and lymphatic malformations are frequently associated with KTS but are not included in the diagnostic criteria. The most common abnormality in KTS is in the nevus, which interestingly, may occur at a site distant to the affected limb. If these findings occur in the presence of a hemodynamically significant arteriovenous communication, it is considered a separate disease entity termed Parkes-Weber syndrome. Although the vast majority of these cases are sporadic, some evidence exists to suggest a multifactorial inheritance pattern.¹⁴ This is based on both the rare observation of multiple cases within one family in addition to the increased incidence of other vascular malformations among first-degree relatives of affected individuals. Recent research has also linked two genetic defects in an angiogenic factor (VG5Q) to patients with KTS.¹⁵

Pathogenesis. The cause of this disease process is not clear. It has been speculated in the past that the cause of the syndrome is atresia or obstruction of the deep veins of the affected limb.^16,17 These changes are presumed to cause venous hypertension and lead to the triad described above. In a more recent study,¹⁸ it was reported that the majority (84%) of patients with this condition do not have deep venous obstruction and, surprisingly, have found increased venous blood flow in the affected limb. The authors also note a large, lateral, valveless venous channel in nearly 70% of patients. These findings support their conclusion that this syndrome could be caused by a generalized mesodermal abnormality during fetal development, which leads to late regression of veins in the affected limb. The late regression would expose the limb to higher blood flows, which could explain the findings in KTS. The authors also note an increased presence of other congenital abnormalities (e.g., hypospadias, syndactyly) in these patients that is not explained by the presence of an isolated vascular anomaly. Bliznak and Staple¹⁹ presented another hypothesis, theorizing that abnormalities in fetal development to either the intermediolateral tract or the sympathetic ganglia of the patient could be responsible for the syndrome.

Treatment. The treatment of KTS is controversial. Most authors conclude that conservative measures (compression stockings, pneumatic compression devices, and elevation) help with the symptoms of venous and lymphatic insufficiency and reduce episodes of trauma to superficial vascular structures, thus preventing significant hemorrhage. The use of surgical procedures to treat patients with symptomatic varicose veins or associated vascular malformations has produced mixed results. Lindenauer²⁰ used multiple techniques (stripping, ligation, or excision) in the treatment of symptomatic varicose veins and found that more than 90% of his patients had worsening of symptoms. Baskerville et al²¹ found that excision and stripping led to temporary improvement in symptoms but that new lesions formed in the vast majority of patients. Gloviczki et al²² concluded that extreme caution is necessary when deciding to intervene on lesions in this disorder, especially vascular malformations. In rare cases with severe or life-threatening complications, radiotherapy has been used with some success.²³

A recent article by Jacob et al²⁴ provides a series of recommendations. As stated above, the mainstay of therapy is conservative. In the specific case that a patient has symptomatic varicose veins and a patent deep venous system, the abnormal veins can be removed, with a fair chance of recurrence. They further recommend that a leg length discrepancy of more than 2 cm in a growing child is an indication for epiphysiodesis. Prophylactic antibiotics and anticoagulation may be needed for recurrent thrombophlebitis and venous thrombosis.

Venous Lakes

Venous lakes, first described by Bean and Walsh in 1965,²⁵ are dark blue cutaneous lesions that typically occur on the ears, face, lips, and neck of elderly men. The lesions are more common with increasing sun exposure. Histologically, the lesions consist of thin walls that include one layer of endothelial cells (Figure 39-4). Their bluish color arises from significant stagnation of blood within the lesion. The lesions typically have no muscle and very little fibrous supporting tissue. They are supplied with blood from small venous channels. These lesions tend to empty off blood with continuous external pressure, which then returns roughly 20 to 30 seconds after pressure is released. These lesions are considered benign but can hemorrhage significantly if their surface is disturbed. For this reason, as well as cosmetic considerations, many methods of treatment, including various types of lasers, cryotherapy, infrared coagulation, sclerotherapy, and surgical excision, are used.^26,27,28

Intravenous Pyogenic Granuloma

Clinical Presentation. PGs (lobular capillary hemangioma) were discussed in detail in the previous arterial vascular tumor chapter 1. Intravenous PGs (IVPGs), or intravenous lobular capillary hemangioma, are a subset of PGs that present as solitary tumors. These lesions were first described by Cooper et al²⁹ in 1979 and typically involve the veins of the neck and upper extremities. In the initial case series of 18 patients, the age range at presentation was 15 to 66 years, with an average of 38 years. A slight female predilection was noted, and patients reported that the lesions presented as an asymptomatic cutaneous lesion.

On ultrasound examination,³⁰ these lesions are “moderately echogenic with small hypoechogenic areas.” Magnetic resonance imaging can also be used to evaluate the intensity of the lesions as well as the intravascular topography, which resembles that of a vascular tumor.

Histology. Two histologic patterns were discussed in the original article,²⁹ classic and edematous. The classic pattern consists of an intraluminal polyp, consisting of small capillaries surrounded by flattened or rounded epithelial cells connected to the wall of a vein by a stalk. The edematous pattern consists of dilated capillaries located in the stalk as well as infiltration of the stroma with inflammatory cells (Figure 39-5).

Differential Diagnosis and Treatment. The differential diagnosis of this disorder includes thrombus, venous aneurysm, intravascular papillary endothelial hyperplasia (Masson’s tumor), angiosarcoma, angiolymphoid hyperplasia with eosinophilia, and histiocytoid hemangiomas. These lesions can be differentiated from IVPG based on the pathologic characteristics described above. The treatment for these lesions is surgical excision,^29,31 which should include a segment of the associated vein to prevent recurrences. IVPG is considered a benign lesion, and the etiology is unknown.

Arteriovenous Hemangioma

Arteriovenous hemangiomas (AVHs) are benign cutaneous vascular tumors believed to be first described by Biberstein and Jessner³² in 1956 as “cirsoid aneurysms.” Similar tumors were described by Girard et al³³ in 1974, who called them AVHs. In his series of 69 patients, he noted that the lesions were typically located more superficially in the dermis and involved smaller vessels compared with cirsoid aneurysms. Most recently, Carapeto et al³⁴ and Connelly and Winkelmann³⁵ provided yet a third similar description using the term acral arteriovenous tumors. This term was created primarily for further description of the location of the lesions, not to replace the term AVH, which the authors also believed was an appropriate term for this tumor. Recently, these lesions have been classified into “deep” and “superficial” categories.³⁶ Although there is discrepancy in the literature, whereas the cirsoid aneurysms appear to be classified as deep AVH, the lesions described by the other authors above are referred to as superficial. The majority of the lesions occur sporadically, although a few familial cases have been observed. A locus on chromosome 5 is being investigated.³⁷

Clinical Presentation. The superficial lesions typically present as small red, blue, or flesh-colored papules on the face or extremities (Figures 39-6, 39-7, 39-8, 39-9, 39-10, 39-11, 39-12, 39-13). They tend to be firm and nonpulsating and blanch with prolonged pressure. In the Girard et al³³ series, 93% of the lesions were solitary. The sizes in their study ranged from 1 mm to 3 cm (median, 6 mm). The vast majority are asymptomatic and removed for cosmetic reasons; however, 10% of patients note mild pain or pruritus. The typical age at presentation is 40 to 50 years, and there is no gender predilection overall, although individual studies show great variability. Typically, the lesions are present for 5 years before patient presentation. In fact, in the Girard et al³³ series, the 69 patients presented with 24 different diagnoses from their referring provider. Histopathologic evaluation is essential for accurate diagnosis.

The deep lesions tend to present in the head and neck of younger patients and are associated with tissue hypertrophy and high-output cardiac failure (Kasabach-Merritt syndrome).

Histology. The pathology of the two types of lesions is similar overall, although there tends to be a higher degree of arteriovenous shunting and variability of the deep tumors. Under microscopic examination, AVHs appear as a well-circumscribed mass in the superficial to middle dermal layer, although the original description of cirsoid aneurysms noted a deeper location. The lesions are usually well circumscribed but do not contain a capsule.³⁵ Additionally, they are composed of multiple thin- and thick-walled vascular channels in a fibromuscular stroma and lined by endothelial cells. The series by Connelly and Winkelmann³⁵ also noted occasional true arteries and veins adjacent to the lesion. Girard et al³³ reported that 26% of lesions contained arteriovenous connections and that all lesions showed some level of capillary and endothelial proliferation. His series also noted associated thrombi (19%), edema (28%), and fibrosis (44%) in the tumors. Four of the 69 patients were observed to have a significant inflammatory component to their lesions, including invasion of lymphocytes, histiocytes, eosinophils, and plasma cells. One series noted an increase in the number of mast cells in both the stroma and vascular channels.³⁸ These specific tumors were classified as inflammatory AVHs. No epidermal invasion, hyperkeratosis, nerve involvement, or presence of glomus cells was noted.

Diagnosis and Treatment. As stated earlier, the diagnosis of AVH depends on pathologic analysis because they clinically resemble many other lesions, including venous lakes, cavernous hemangiomas, vascular spiders, PGs, venous ectasias, and angiokeratomas as well as many others. The treatment is surgical excision. Recurrence has not been noted in the superficial group but is common with incomplete resection of deep lesions.

Microvenular Hemangioma

Clinical Presentation. Microvenular hemangioma (MH) was first described by Bantel³⁹ in 1989 under the description microcapillary angioma, although the actual name was first reported by Hunt et al⁴⁰ 1991 in a series of 10 cases and has subsequently been reported by very few authors.^41,42,43 MH is one of many recent dermal blood vessel lesions that have been identified. Originally, the lesion was considered to be of significant importance because of its clinical similarity to the malignant vascular tumor, Kaposi sarcoma. MH is very rare and typically presents in young or middle-aged adults as an asymptomatic, red to purple, slow growing papule or nodule. The tumors range from 0.5 to 30 mm in diameter and occur most commonly on the extremities or trunk. With one exception, all patients have presented with solitary lesions. These tumors are self-limited and have not been noted to recur after excision. In one interesting case,⁴³ multiple MHs were discovered in a patient with POEMS (polyneuropathy, organomegaly, organ enlargement, endocrinopathy, monoclonal gammopathy or monoclonal plasma proliferative disorder, skin changes) syndrome. Human herpesvirus-8 was found in both the lymphocytes and endothelial cells of the tumors.