Vascular Lesions of the Vulva


Dilatation of preexisting vessels

Acquired lymphangiectasis

Vulvar varices (venous lake)

Angiokeratoma

Vascular hyperplasias

Pyogenic granuloma (lobular capillary hemangioma)

Intravascular papillary endothelial hyperplasia (Masson’s tumor)

Benign neoplasms

Hemangioma

Infantile hemangioma

Congenital hemangioma

Lymphangioma

Glomus tumor

Malignant neoplasms

Kaposi’s sarcoma

Epithelioid hemangioendothelioma

Angiosarcoma

Lymphangiosarcoma





Dilatation of Preexisting Vessels


Dilatation of preexisting vessels includes the following range of lesions: angiokeratomas, lymphangiectasis, venous lake, vulvar varices, and capillary aneurysm. From this group of disorder, angiokeratomas and lymphangiectasis are the lesions most frequently seen in the vulva.


Lymphangiectasis


Lymphangiectasis, also known as acquired lymphangioma, occurs on the vulva and involves the lymphatic channels in the dermis. Young et al. [2] reported only 1 patient with this condition among 1,000 patients seen in their vulval-cutaneous clinic over 7 years. Similarly Stewart et al. [3] identified only eight cases over 15-year period.

Lymphangiectases are the result of permanent dilatation of lymphatic capillaries and develop in areas of the skin affected by obstruction or destruction of lymphatic drainage [3, 4]. The lymphatic plexus of the superficial dermis drains a fixed skin area through the vertical collecting lymphatics to the deep plexus. Damage of the deep lymphatic vessels leads to dilatation of the superficial dermal lymphatics [5]. Causes include surgery, lymphadenectomy, pregnancy, radiotherapy, Crohn’s disease, scleroderma, neoplasia, or infections such as tuberculosis, lymphogranuloma venereum, and filariasis [3, 4, 611].

The age of affected women ranges from 22 to 75 years with a mean of 48 years [5]. The patients can present with pruritus progressing to pain, vulvar wetness, edema, or no symptoms. These lesions typically develop more than 10 years following damage to the lymphatic drainage and can be recurrent. Clinically, lymphangiectases are localized lesions often on the labia majora. The cobblestones appearance is due to thin-walled translucent vesicles filled with clear fluid [3, 4]. On rare occasions, they are hyperkeratotic, pedunculated, and polypoid lesions and may mimic genital warts, herpes infection, or molluscum contagiosum [12]. Some cases are complicated by secondary infection. The goal of treatment is to reduce the underlying lymphedema and to control infection. Excisional surgery and carbon dioxide laser are two major forms of treatment [13, 14].

A special form of lymphangiectasis, localized lymphedema, can be seen on the vulva of morbidly obese women [15]. Also known as massive vulval edema, vulvar lymphedematous pseudotumor, and vulvar hypertrophy with lymphedema, localized lymphedema (elephantiasis) typically present with papillomatous plaques, vulvar enlargement, or massive pedunculated masses (see Chap. 13). The duration of these lesions ranges from 3 months to 36 years, and their sizes range from 0.6 to 45 cm [15].


Histopathology


Lymphangiectases are characterized by the presence of dilated lymphatic vessels within superficial and mid dermis (Fig. 14.1). The overlying epidermis may exhibit hyperkeratosis and acanthosis. There may be red blood cells and lymphocytes within these lymphatic channels. Stromal edema is a histologic feature that is consistently seen in all examined patients with localized massive lymphedema [15]. In addition, multinucleated giant cells, lymphangiectasia, dermal chronic inflammation, and fibrosis are seen in subset of cases [15].

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Fig. 14.1
Lymphangiectasia. Dilated lymphatic vessels are seen within the superficial and mid-dermis

By immunohistochemistry, the lymphatic endothelial cells are positive for D2-40, Prox-1, and CD31, yet they are negative for CD34 [3] (Table 14.2). D2-40 or podoplanin is a relatively specific immunostain for lymphatic endothelium [16]. Prox-1 is a homeobox-containing nuclear transcription factor that has recently been shown to exhibit better specificity for lymphatic endothelium than D2-40 [17].


Table 14.2
Summary of vascular markers in blood vessels and lymphatics




























Immunostain

Blood vessels

Lymphatics

D2-40


+

Prox-1


++

CD31

++

+

CD34

++



Data from Ref. [17]


Differential Diagnosis


Acquired lymphangiectasis has similar clinical and histologic features to lymphangioma circumscriptum, a developmental defect of the deep dermal and subcutaneous lymphatics. Clinical history is essential to differentiate the two since lymphangiomas are present since birth or early childhood, while acquired lymphangiectasis is associated with a number of causes [4, 8]. (See Vignette 3 at the end of this chapter.) While acquired lymphangiectasis affects the superficial and mid lymphatics, lymphangioma circumscriptum affects those within the deep dermis and subcutaneous tissue. The lack of CD34 expression is helpful in distinguishing acquired lymphangiectasia from other vulvar vascular lesions. Angiokeratomas are small and not associated with damage to lymphatic drainage [18]. In addition, angiokeratomas do not recur and do not typically require additional treatment. Vulvar varices, also known as venous lake, would have erythrocytes within a dilated lumen. (See Vignette 1 at the end of this chapter.)


Summary





  • Clinical Presentation



    • These lesions typically develop more than 10 years following damage to the lymphatic drainage and can be recurrent.


  • Histologic Features



    • Dilated lymphatic vessels are seen within the superficial and mid-dermis.


  • Differential Diagnosis



    • Congenital lymphangioma


    • Angiokeratomas


    • Vulvar varices or venous lake


Takeaway Essentials





  • Clinical Relevant Pearls



    • Lymphangiectases are the result of permanent dilatation of lymphatic capillaries and develop in areas of the skin affected by obstruction or destruction of lymphatic drainage.


    • Vulvar lymphangiectasis can be misdiagnosed clinically as warts and thus are nonresponsive to treatment.


  • Pathology Interpretation Pearls



    • While acquired lymphangiectasis affects superficial and mid-lymphatics, lymphangioma circumscriptum or congenital lymphangioma affects those within the deep dermis and subcutaneous tissue.


    • Stromal edema is a histologic feature that is consistently seen in all examined cases of localized massive lymphedema.


  • Immunohistochemical Findings



    • The lymphatic endothelial cells are positive for D2-40, Prox-1, and CD31; yet they are negative for CD34.


    • The lack of CD34 expression is helpful in distinguishing acquired lymphangiectasia from other vulvar vascular lesions.


Angiokeratoma


Angiokeratoma is a group of several unrelated conditions, whose common denominator is the presence of dilated blood vessels in association with epidermal hyperplasia. Four clinical variants of angiokeratomas have been recognized: solitary, Fordyce’s angiokeratoma, Mibelli’s angiokeratoma, and angiokeratoma corporis diffusum. The latter has been associated with different diseases of which Fabry’s disease is the most common.

Angiokeratomas of the vulva are rare and present as keratotic, red to brown papules in patients of 20–40 years of age [1921], but they can be seen in younger individuals [22]. The lesions are typically 2–5 mm, unilateral, multiple, and asymptomatic [19, 20, 23]. Rare case of clitoral involvement has been reported [24]. It is thought that increased local venous pressure results in subepithelial vascular dilation; thus, increased parity, excess body weight, hemorrhoids, pelvic inflammatory disease, prior hysterectomy, varicose veins, and vulvar varicosity are risk factors [19, 20, 25]. These lesions can be treated by surgical excision or physical and chemical cauterization [20].


Histopathology


All variants of angiokeratomas share similar histologic features including the presence of dilated thin-walled blood vessels, lined by a layer of endothelial cells, in the papillary dermis and a variable degree of hyperkeratosis (Fig. 14.2a). The overlying epidermis often exhibits irregular acanthosis with elongated rete ridges partially surrounding the vascular channels (Fig. 14.2b). There is minimal dermal inflammation. Vacuolation of smooth muscle of arterioles and arteries and pilar muscles is seen in lesions associated with Fabry’s disease. Electron-dense lipid bodies can be demonstrated ultrastructurally in the cytoplasm of endothelial cells, pericytes, smooth muscle cells, and fibroblasts [26].

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Fig. 14.2
(a, b) Angiokeratoma. Dilated blood vessels lined by a layer of endothelial cells are seen associated with marked epidermal hyperplasia


Differential Diagnosis


Clinically, angiokeratomas of the vulva may resemble benign as well as malignant melanocytic lesions, seborrheic keratosis, condyloma acuminatum, vulvar intraepithelial neoplasia, pyogenic granuloma, and lymphangioma [18, 19]. The main histologic differential diagnosis would be a hemangioma, which would not have associated epidermal acanthosis that is seen in angiokeratoma. Although a verrucous angioma would have marked epidermal hyperplasia, it has a deep vascular component that is not typically present in angiokeratoma.


Summary





  • Clinical Presentation



    • Rare lesions in individuals 20–40 years of age


    • Keratotic, red to brown papules


    • 2–5 mm, unilateral, multiple, and asymptomatic


  • Histologic Features



    • Dilated thin-walled blood vessels in the papillary dermis that lined by a layer of endothelial cells and associated with epidermal hyperplasia


  • Differential Diagnosis



    • Hemangioma


Takeaway Essentials





  • Clinical Relevant Pearls



    • Four clinical variants of angiokeratomas have been recognized: solitary, Fordyce’s angiokeratoma, Mibelli’s angiokeratoma, and angiokeratoma corporis diffusum (Fabry’s disease).


    • Vulvar lesions are thought to be equivalent to the Fordyce type.


  • Pathology Interpretation Pearls



    • In contrast to hemangioma, there are associated epidermal hyperplasia with angiokeratoma and lack of a deep vascular component.


Hyperplasias


Hyperplasia is defined as an abnormal increase in the absolute number of normal cells, in an appropriately arranged tissue. Inherent in this terminology is the premise that hyperplasia ceases when the initiating stimulus has been removed; thereafter the tissue may or may not completely revert to its normal state. In the vulva the most common hyperplasia is pyogenic granuloma. Other hyperplasias such as intravascular papillary endothelial hyperplasia and reactive angioendotheliomatosis can be seen, but they are not very common in the vulva.


Pyogenic Granuloma


Lobular capillary hemangioma or pyogenic granuloma often presents as a solitary, pedunculated, or sessile growth [27]. Although rare, pyogenic granuloma presents with multiple lesions in the vulva [2830]. Labia majora is commonly involved. In all three reports, the lesions did not recur status post excision [2830].

Pyogenic granuloma has been thought to represent a reactive vascular proliferation in response to a variety of stimuli rather than a true hemangioma [27]. Increased production of tumor angiogenesis factor from trauma or underlying cutaneous disease such as inflammatory dermatoses, viral infection, arthropod bite, and port-wine stain may play a role in the pathogenesis of pyogenic granuloma [31, 32]. Since there is a female predominance, the role of estrogen and progesterone receptors in the development of these lesions has been postulated. However, estrogen and progesterone receptors were found to be negative in a series of 21 cutaneous pyogenic granulomas by Nichols et al. [33].


Histopathology


Pyogenic granuloma, at least in its initial phase, is an exuberant proliferation of vessels of different sizes and shapes, lined by prominent endothelium embedded in an edematous stroma (Fig. 14.3a, b). The overlying epidermis is often ulcerated; thus, the lesion has associated acute as well as chronic inflammatory infiltrate, similar to granulation tissue.

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Fig. 14.3
(a, b) Pyogenic granuloma. An exophytic and lobular proliferation of blood vessels is seen in the dermis


Differential Diagnosis


The clinical differential diagnosis of pyogenic granuloma would include other polypoid lesions including condylomas, angiomas, and verrucous carcinoma. The main histologic differential diagnosis would be granulation tissue and a hemangioma. Some do consider pyogenic granuloma is a subtype of hemangioma. Clinical history is needed to distinguish pyogenic granuloma from granulation tissue.


Summary





  • Clinical Presentation



    • Rarely present as multiple lesions in the vulva


  • Histologic Features



    • Proliferation of vessels of different sizes and shapes, lined by prominent endothelium embedded in an edematous stroma


  • Differential Diagnosis



    • Granulation tissue


    • Hemangioma


Takeaway Essentials





  • Clinical Relevant Pearls



    • These lesions appear not to recur after excision.


    • The presence of multiple pyogenic granulomas is not associated with syndrome or aggressive behavior.


  • Pathology Interpretation Pearls



    • The presence of mitoses and prominent endothelial cells is part of the spectrum of reactive changes.


  • Immunohistochemical Findings



    • Kaposi sarcoma can simulate pyogenic granuloma histologically, and HHV8 immunostain can be helpful in setting apart these lesions.


Intravascular Papillary Endothelial Hyperplasia


Only two cases of intravascular papillary endothelial hyperplasia or Masson’s tumor have been reported in the vulva [34, 35]. One case of Masson’s tumor in the vulva was in a patient undergoing radiation therapy for vulvar cancer [35]. The predisposing factors for Masson’s tumor are not known, but irradiation has been reported to induce similar papillary endothelial proliferation in experimental animals [36]. The lesion commonly presents as a small firm mass in the deep dermis or subcutaneous tissue.


Histopathology


The proliferation of endothelial cells is present within one or more vascular lumina that have been occluded by a thrombus (Fig. 14.1a). In fully developed lesions, numerous papillary fronds lined by a single layer of plump endothelial cells extend from the wall of the vessel into the lumina. The histologic features of intravascular papillary endothelial hyperplasia are not specific, but can be found in multiple vascular proliferations (Fig. 14.4b).

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Fig. 14.4
Masson’s lesion. (a) A well-circumscribed lesion with central thrombosis is seen in the dermis. (b) Irregular vascular spaces lined by plump endothelial cells and with associated hemosiderin deposition


Differential Diagnosis


The differential diagnosis includes pyogenic granuloma, Kaposi’s sarcoma, and angiosarcoma. Pyogenic granuloma is a proliferation of blood vessels of variable sizes and shapes. An infiltrative architecture as well as cytologic atypia would be seen in Kaposi’s sarcoma and angiosarcoma, whereas Masson’s tumor is a circumscribed lesion with a central thrombotic zone.


Summary





  • Clinical Presentation



    • Small firm mass in the deep dermis or subcutaneous tissue


  • Histologic Features



    • Proliferation of endothelial cells is present within one or more vascular lumina that have been occluded by a thrombus.


  • Differential Diagnosis



    • Pyogenic granuloma


    • Kaposi’s sarcoma


    • Angiosarcoma


Takeaway Essentials





  • Pathology Interpretation Pearls



    • The histologic features of intravascular papillary endothelial hyperplasia are not specific, but can be found in multiple vascular proliferations.


Benign Neoplasms



Hemangioma


Cavernous hemangioma appears to be the most common form reported in the vulva [3739]. Massive clitoral enlargement due to a cavernous hemangioma was reported in a young woman [37].


Histopathology


These lesions are comprised of large, dilated, blood-filled vessels lined by flattened endothelium. These vessels can be either in a lobular arrangement or a haphazard fashion. Arteriovenous hemangioma consists of a well-circumscribed proliferation of thick-walled muscle-containing blood vessels, lined by a single layer of endothelial cells involving the upper and mid-reticular dermis (Fig. 14.5a, b).

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Fig. 14.5
(a, b) Arteriovenous hemangioma. A well-circumscribed proliferation of thick-walled muscle-containing blood vessels is seen in the superficial and mid-dermis


Differential Diagnosis


Cavernous hemangioma can be mistaken clinically as vulvar varices (see Vignette 1 at the end of this chapter) as reported in a case of vulvar hemangioma [40]. Lymphangioma would not have blood-filled vessels, and these endothelial cells would be positive for lymphatic markers such as D2-40 and Prox-1.


Summary





  • Clinical Presentation



    • Cavernous hemangioma appears to be the most common form of hemangioma in the vulva.


  • Histologic Features



    • Large, dilated, blood-filled vessels lined by flattened endothelium


  • Differential Diagnosis



    • Vulvar varices


    • Lymphangioma


Takeaway Essentials





  • Clinical Relevant Pearls



    • Vulvar hemangiomas are multifocal in only 3 % of cases, while vulvar lymphangioma circumscriptum is bilateral or multifocal in 40 % of cases.


  • Immunohistochemical Findings



    • Hemangioma would be positive for CD34, while negative for D2-40 and Prox-1.


Infantile Hemangioma


There has been only a single description of an infantile hemangioma on the vulva of an 11-week female infant which was successfully treated with topical propranolol [41]. Infantile hemangiomas (IH) are benign tumors of the vascular endothelium with a unique natural history characterized by proliferative and involution phases. At birth, lesions appear as faint erythematous macules or areas of pallor with telangiectasia. Starting in the first weeks of life, lesions enlarge and become raised and bright red in color, usually reaching maximum size by 3–6 months. A brief plateau period ensues. Total or partial involution follows by 5–7 years of age, even in the absence of therapy [42]. The involution phase does not result in normal-appearing skin with about one half of lesions showing residual changes such as scarring, atrophy, redundant skin, discoloration, and telangiectasias.

The majority of infantile hemangiomas is self-limited and may be treated with “watchful waiting.” Five to twenty-one percent of lesions ulcerate and require active treatment due to a risk of bleeding, infection, and scarring. In the last few years, oral propranolol, a nonselective beta-blocker, has emerged as a potential first-line therapy with impressive efficacy and improved tolerance when compared with the significant side effects associated with steroids and chemotherapeutic agents such as vincristine and interferon [43]. Several case series and larger observational studies have shown oral propranolol to be an effective treatment for all types of IH, including periocular, airway, and cutaneous lesions [44].


Histopathology


The histopathologic composition of infantile hemangiomas varies with the age of the lesion. Early hemangiomas are highly cellular and are characterized by plump endothelial cells aligned to vascular spaces with small inconspicuous lumina (Figs. 14.6 and 14.7). As the lesions mature, blood flow increases, endothelium flattens, and the lumina of the vessels enlarge and become more obvious. During this interval the vessels convey a “cavernous” appearance that can be misinterpreted as a venous malformation. Regression is portrayed as progressive interstitial fibrosis and adipose metaplasia, a process without known stimulus.

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Figs. 14.6 and 14.7
Infantile hemangioma. A cellular vascular proliferation characterized by plump endothelial cells

Immunohistochemical studies have shown a complex expression profile including markers for endothelial cells (CD31 positive), pericytes (SMA positive), dendritic cells (factor XIIIa positive), and mast cells [42]. Of particular clinical importance, IH express high levels of erythrocyte-type glucose transporter protein, isotope 1 (GLUT-1), which is not expressed in the vasculature of normal skin nor in other tumors or vascular malformations, making it a highly selective and diagnostically useful marker (Fig. 14.8) [45]. GLUT-1 is also expressed in normal endothelium at sites of blood-tissue barriers, including the brain, eye, nerve, and placenta. North et al. [46] showed that of these tissues, IH’s expression profile is closest to that of fetal placental microvasculature, suggesting a possible origin of these tumors.

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Fig. 14.8
Infantile hemangioma. The vascular proliferation is positive for GLUT-1 immunostain


Differential Diagnosis


The differential diagnosis of IH includes vascular malformations and congenital hemangiomas. Fortunately, vascular malformations and congenital hemangiomas that affect the infant population usually do not stain for GLUT-1 (Table 14.3). Congenital hemangiomas differ from IH in that they are fully formed in utero. They can be detected by ultrasound as early as 12 weeks’ gestation [47]. Two types have been recognized based on their natural history: rapidly involuting congenital hemangioma (RICH) and non-involuting congenital hemangioma (NICH) [48, 49].


Table 14.3
Summary of GLUT-1 and D2-40 immunoreactivity in vascular tumors







































 
GLUT-1

D2-40

Infantile hemangioma

+


Congenital hemangioma


−/+

 Non-involuting congenital hemangioma

 Rapidly involuting congenital hemangioma

Kaposiform hemangioendothelioma


+

Tufted angioma


+/−

Pyogenic granuloma



Spindle cell hemangioma



RICHs are fully developed at birth, may be large and exophytic, and, as their name implies, involute rapidly during the first month of life. RICHs also rarely require treatment, although they may elicit clinical concern due to associated transient abnormalities (thrombocytopenia, low fibrinogen, and elevated fibrin degradation products). Histopathologically, RICHs are highly cellular with multiple well-defined lobules of proliferating capillaries that anastomose with each other to form ribbons within the dermis or subcutaneous tissue.

NICH grow proportionately with the child. Their vessel walls are often thicker than in IH, and their endothelium may be hobnail in appearance [50]. NICH do not regress as do the other infantile hemangiomas, while RICHs involute in a short period of time. NICH are characterized histopathologically by lobular collections of small, thin-walled vessels with large, often stellate, central lumina, separated by variable amounts of fibrous tissue richly supplied with normal and abnormal veins and arteries.


Summary





  • Clinical Presentation



    • Has a unique natural history characterized by proliferative and involution phases


  • Histologic Features



    • Proliferative stage: highly cellular and characterized by plump endothelial cells with small inconspicuous lumina


    • Involution stage: progressive interstitial fibrosis and adipose metaplasia


  • Differential Diagnosis



    • Congenital hemangioma including non-involuting congenital hemangioma (NICH) and rapidly involuting congenital hemangioma (RICH)


Takeaway Essentials





  • Clinical Relevant Pearls



    • Oral propranolol, a nonselective beta-blocker, has emerged as a potential first-line therapy.


  • Pathology Interpretation Pearls



    • Between the proliferative and involution phases, the vessels can have a “cavernous” appearance that can be misinterpreted as a venous malformation.


  • Immunohistochemical Findings



    • Expresses high levels of erythrocyte-type glucose transporter protein, isotope 1 (GLUT-1)


Lymphangioma


Lymphangioma circumscriptum can uncommonly present in the vulva [5154]. Congenital lymphangioma circumscriptum of the vulva typically affects females from 9 to 36 years [51]. Cutaneous lymphangiomas can be either superficial or deep. The superficial form or lymphangioma circumscriptum presents as multiple small vesicles over a localized skin area. Complications of lymphangioma circumscriptum include vulvar swelling, pain, and cellulitis [51]. Rarely lymphangiosarcoma can arise from a preexisting lymphangioma circumscriptum [51].

Treatment can include sclerotherapy, liquid nitrogen therapy, carbon dioxide laser therapy, radiotherapy, and surgical excision [52, 53]. Propranolol has been shown to be safe in infants and children with congenital lymphangiomatosis [55].


Histopathology


Dilated lymphatic channels are seen at the junction of papillary and reticular dermis in the superficial form or lymphangioma circumscriptum (Figs. 14.9a, b). Both the superficial and deep lymphatic channels are involved in the deep type.

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Fig. 14.9
(a, b) Lymphangioma. Dilated lymphatic vessels are seen in the superficial dermis associated with epidermal hyperplasia and also in the deep dermis


Differential Diagnosis


The clinical differential diagnosis of lymphangioma circumscriptum of the vulva includes molluscum contagiosum and genital warts [56]. The histologic differential diagnosis includes acquired lymphangiectasis, vulvar varices (venous lake), and angiokeratoma. Clinical history is essential to distinguish primary from acquired lymphangiomas, since lymphangiomas are present since birth or early childhood, while acquired lymphangiectasis is a secondary change associated with a number of causes.


Summary





  • Clinical Presentation



    • Lymphangioma circumscriptum presents as multiple small vesicles over a localized skin area.


  • Histologic Features



    • Dilated lymphatic channels are seen at the junction of papillary and reticular dermis.


  • Differential Diagnosis



    • Acquired lymphangiectasis


    • Vulvar varices (venous lake)


    • Angiokeratoma


Takeaway Essentials



Nov 11, 2017 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Vascular Lesions of the Vulva
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