Mesenchymal Lesions of the Vulva and Vagina

Clinical Features

Fibroepithelial stromal polyps are common in women of reproductive age (most commonly during pregnancy) but may be seen in postmenopausal women on hormonal replacement therapy. They are often incidental findings discovered during routine gynecologic examination. Symptoms, when present, may include bleeding, discharge, or the sensation of a mass. Fibroepithelial polyps usually present as a solitary lesion; however, multiple polyps may occur during pregnancy, after which they typically regress.

Pathologic Features

Microscopic Findings

Fibroepithelial stromal polyps are exophytic lesions with a variably cellular stroma, central fibrovascular core, and overlying squamous epithelium. The most characteristic feature is the presence of stellate and multinucleate stromal cells, which are most commonly seen near the epithelial–stromal interface or adjacent to the prominent central vasculature ( Fig. 4.1 ). Sometimes the lesion displays high stromal cellularity, nuclear pleomorphism, and mitotic activity (including >10 mitoses/10 high power fields [HPFs] and atypical mitoses), thereby mimicking a sarcoma ( Fig. 4.2 ). Importantly, there is no clearly defined margin or sharp demarcation from the epithelial–stromal interface (absence of cambium layer).

Ancillary Studies

Differential Diagnosis

Fibroepithelial stromal polyps, particularly those with increased cellularity and atypical stromal cells, must be distinguished from a malignant process. Sarcomas typically have an identifiable lesional margin, show homogeneous cellularity throughout, and lack the stellate and multinucleate stromal cells near the epithelial–stromal interface. In contrast, even the most floridly pseudosarcomatous examples of fibroepithelial stromal polyps characteristically show stellate multinucleated cells and tend to exhibit a greater degree of cellularity in the center of the lesion. Fibroepithelial stromal polyps are readily distinguished from botryoid embryonal rhabdomyosarcoma , as fibroepithelial stromal polyps are rare before puberty and lack the characteristic hypercellular subepithelial (cambium) layer and specific markers of skeletal muscle differentiation. When stromal polyps are edematous, a deep (aggressive) angiomyxoma may be considered; however, the latter is typically more deeply located, is uniformly hypocellular, has myxoid instead of edematous stroma, and lacks stellate and multinucleate cells.

Prognosis and Therapy

These lesions have the potential to recur locally, particularly if incompletely excised or if there is continued hormonal stimulation (e.g., pregnancy).

Clinical Features

This is a benign neoplasm that occurs in the vulvovaginal region of reproductive-aged women but it may also occur in the inguinoscrotal region in males. It is often thought to represent a cyst on clinical examination.

Pathologic Features

Microscopic Findings

Angiomyofibroblastoma, although not encapsulated, is well demarcated from the surrounding vulvar soft tissues. It is composed of plump, ovoid (plasmacytoid) to spindle-shaped cells that may be multinucleated and tend to cluster around the numerous small- to medium-caliber blood vessels. The cell clusters are set within a variably edematous to collagenous matrix with alternating zones of cellularity ( Fig. 4.3 ). Mitotic activity is uncommon and occasionally intratumoral adipose tissue may be present.

Ancillary Studies

Prognosis and Therapy

Angiomyofibroblastoma is a benign tumor without recurrent potential; therefore, local excision with clear margins is adequate treatment. Rarely, this tumor may undergo sarcomatous transformation.

Clinical Features

Cellular angiofibroma is a benign tumor that occurs in the vulva or perineum of middle-aged women (mean 54 years), although it also occurs in the inguinoscrotal region in men and at extragenital sites. In the vulva, they most commonly present as a small, well-circumscribed, painless, subcutaneous mass.

Pathologic Features

Microscopic Findings

Most cellular angiofibromas have a well-demarcated border on low-power examination; however, a few may exhibit focal limited infiltration of surrounding soft tissues. It is a cellular neoplasm composed of short, intersecting fascicles of bland spindle-shaped cells with scant pale-staining cytoplasm and ovoid nuclei ( Fig. 4.4 ). Scattered atypical nuclei or multinucleate cells may sometimes be seen. Rare examples of cellular angiofibroma have discrete foci of cytologically atypical cells or a sarcoma-like component, the latter as an abrupt transition to a discrete sarcomatoid component which in a subset closely resembles atypical lipomatous tumor or pleomorphic liposarcoma; the prognostic significance of these findings is uncertain. Mitoses are typically infrequent, but some tumors may show brisk mitotic activity. The vascular component is prominent with numerous, relatively homogeneous small- to medium-sized, thick-walled (and often hyalinized) blood vessels. Interspersed wispy collagen bundles are also characteristic and mast cells are a common associated finding. In addition, most tumors also have a small component of adipose tissue, often located at the periphery. Entrapped small nerves may also be seen at the periphery of the tumor.

Ancillary Studies

Differential Diagnosis

Because of the presence of short intersecting fascicles, cellular angiofibroma may be confused with a benign smooth-muscle tumor. It is distinguished from a leiomyoma by its shorter fascicles, more prominent vascular component, less abundant eosinophilic cytoplasm, and lack of blunt-ended nuclei. Mammary-type myofibroblastoma and cellular angiofibroma show significant morphologic and immunohistochemical overlap (although the vessels of the former are not as prominent), and based on their shared molecular abnormality, may be related tumors on a morphologic spectrum. Less frequently, cellular angiofibroma may be confused with angiomyofibroblastoma (discussed previously), prepubertal vulvar fibroma, deep angiomyxoma, and solitary fibrous tumor. Prepubertal vulvar fibroma occurs more commonly in young girls, has ill-defined margins, a hypocellular appearance, and patternless proliferation of spindle cells. Deep angiomyxoma more commonly involves deep soft tissue and has an infiltrative margin. In addition, it is myxoid and hypocellular, and RB1 immunoexpression is intact. In contrast to cellular angiofibroma, solitary fibrous tumor is characterized by a “patternless” architecture, heterogeneous cellularity, hemangiopericytoma-like vasculature, and frequent presence of keloid-type collagen; it is also typically positive for STAT6.

Prognosis and Therapy

Cellular angiofibroma is a benign tumor. Incomplete excision may lead to regrowth of tumor; therefore, local (conservative) excision with negative margins appears to be adequate treatment.

Clinical Features

Mammary myofibroblastoma was first described in the breast with a predilection for older men; since its initial description, it is now known to occur in extramammary sites, particularly the inguinal/groin area and the term “mammary-type myofibroblastoma” is the designated terminology. In the largest series to date, this tumor more commonly affects males (66% vs. 34%) and anatomic locations include in order of frequency: inguinal/groin region, breast, chest wall/axilla, trunk, and extremities. The tumors occur in individuals over a wide age range (from first to tenth decade) with a mean age of 54 years. Most patients are asymptomatic but some present with a painless swelling or mass. Most tumors occurring in the groin are subcutaneous but it is important to note that outside this location, they may occasionally be deep-seated (intramuscular, pelvis, retroperitoneum, or abdomen).

Pathologic Features

Gross Findings

Mammary-type myofibroblastomas are usually pink or tan to brown, firm and well-circumscribed masses that often have a whorled, nodular, and occasionally mucoid cut section ( Fig. 4.5 ). Tumors can measure up to 22 cm with a mean size of 6.6 cm.

Microscopic Findings

These tumors histologically resemble mammary myofibroblastoma. They are well-circumscribed, unencapsulated tumors composed of haphazardly arranged variably sized fascicles or a patternless proliferation of bland spindle cells with oval nuclei, pale cytoplasm, and indistinct cell borders ( Fig. 4.6 ). A variable amount of adipose tissue is present ranging from little/none to predominant ( Fig. 4.6 ). Stromal collagen can sometimes have a ropy appearance reminiscent of that seen in spindle cell lipoma. Less commonly, focal cytologic atypia often seen as “bizarre” degenerative appearing nuclei, epithelioid morphology, or neurilemmoma-type nuclear palisading can be seen.

Ancillary Studies

Differential Diagnosis

The differential diagnosis includes cellular angiofibroma and angiomyofibroblastoma (discussed previously), prepubertal vulvar fibroma and deep (aggressive angiomyxoma). Prepubertal vulvar fibroma more commonly occurs at a younger age, is more infiltrative and less cellular, and lacks a fascicular growth. Deep (aggressive) angiomyxoma is uniformly myxoid and hypocellular, has infiltrative margins, lacks fascicular growth, and shows intact RB1 expression.

Prognosis and Therapy

Mammary-type myofibroblastoma is benign. There appears to be a very low risk of recurrence as there have been two documented recurrences 17 and 20 years after initial excision.

Clinical Features

Prepubertal vulvar fibroma typically occurs in young girls (range 4–12 years) as a gradual vulvar swelling; it is typically unilateral, painless, and most commonly involves the labium majus.