Fibroepithelial stromal polyps often present as an incidental lesions that arise in the vulvovaginal region. Clinically, they may produce a mass sensation, bleeding, or discharge [1, 2].

They occur in premenopausal women and are hormone related; therefore, their development in postmenopausal women has been shown to be associated with hormone replacement therapy [3, 4]. The lesions are pedunculated, variable in size, and usually do not exceed 5 cm; rare examples of tumors as large as 20 cm have been described [5]. Fibroepithelial polyps are usually solitary lesions; however, multiple lesions can be seen during pregnancy [6, 7]. Treatment is simple excision and the risk of local recurrence is very low.

The gross appearance is that of a flesh-colored soft solid mass that is covered by squamous mucosa or skin (Fig. 13.1). The lesion has a fibrovascular core that contains spindled fibroblasts and scattered multinucleated stellate stromal cells that are often distributed close to the overlying epithelium without a grenz zone (Figs. 13.2 and 13.3). The stroma is usually hypocellular and edematous, but there can be areas of hypercellularity and limited nuclear pleomorphism. Importantly, a minority of polyps during pregnancy may show increased stromal cellularity, nuclear atypia, and numerous mitotic figures (Fig. 13.4) [8]. The overlying epithelium may demonstrate varying degrees of hyperplasia [4, 9, 10]. The stromal cells are often positive for desmin, estrogen receptor (ER), and progesterone receptor (PR), and in some cases they express CD34 and smooth muscle actin (SMA) (Fig. 13.5). The lesional cells are negative for keratin, S100, myogenin, and MyoD-1 [8].

The degree of hypercellularity and nuclear pleomorphism may mimic a malignant process, particularly embryonal rhabdomyosarcoma, and this explains why some lesions have been termed pseudosarcoma botryoides. In distinction from the botryoides variant of rhabdomyosarcoma, a cellular fibroepithelial polyp does not have a distinct cambium layer, nor does it demonstrate skeletal muscle differentiation by light microscopy or immunohistochemically [3]. (See Vignette 3 at the end of this chapter) The epithelial hyperplasia and fingerlike projections can mimic a condyloma acuminatum. The absence of viral changes such as koilocytes supports the diagnosis of fibroepithelial stromal polyp rather than human papillomavirus (HPV)-derived infection.

The tip of deep-seated aggressive angiomyxoma may present as a polypoid mass; however, it can be distinguished from fibroepithelial stromal polyp by virtue of its infiltrative growth pattern, deep location, presence of a prominent undulating vascular tree, and the hypocellular and myxoid nature of the tumor.

The lesion presents as enlargement of the vulva, most often bilateral, that may be massive and appear as confluent verrucous lesions. It usually affects morbidly obese individuals, and some patients may have a history of immobility, pregnancy, and hypothyroidism [11–13]. The mean age at presentation is 46.5 years [14]. The enlargement is slowly progressive and the overlying skin may ulcerate.

Grossly the lesion is tan-gray and poorly defined and ranges from a few to greater than 20 cm in dimension (Fig. 13.6). The epidermis may show verrucous hyperplasia or papillomatosis [14]. The accompanying adipose tissue shows thickening of the connective tissue septae that contain increased amounts of fibroblasts, collagen, myxoid stroma, lymphatics, and small- to medium-sized blood vessels (Figs. 13.7 and 13.8). The fibroblasts are spindle and stellate shaped and contain eosinophilic cytoplasm and nuclei that have fine chromatin. The fat may show foci of necrosis associated with macrophages, and the blood vessels can have a perivascular chronic inflammatory infiltrate.

The main lesion in the differential diagnosis is aggressive angiomyxoma. Distinguishing features are the presence of the tortuous and dilated lymphatics present in massive vulvar edema and the absence of broad fibromyxoid tissue. Because of the secondary changes that occur in the fat liposarcoma may be a consideration; however, lipoblasts and cells with enlarged hyperchromatic nuclei characteristic of liposarcoma are absent.

The lesion presents as painless progressive swelling that causes enlargement of the labia majora in prepubertal females. It usually appears as a unilateral submucosal or subcutaneous mass with ill-defined borders. Treatment is complete excision as the lesion can recur locally.

Grossly the lesion is tan-gray and poorly delineated from the surrounding tissues. Microscopically, it is hypocellular and composed of scattered spindle cells that are cytologically bland; there is no pleomorphism and mitoses are rare (Fig. 13.9). The stroma consists of collagen fibers that are thick and wavy and contains medium-sized blood vessels (Fig. 13.10). Histologically the lesion is poorly demarcated and infiltrates into the surrounding tissues. The spindle cells are strongly positive for CD34.

The infiltrative borders and hypocellularity can suggest the possibility of aggressive angiomyxoma; however, the collagenous stroma in aggressive angiomyxoma is composed of delicate fibrils, different from the thick, wavy fibers present in this entity, and the vessels in aggressive angiomyxoma are larger, more numerous, and undulating. Immunohistochemistry can also be helpful in the distinction in that the tumor cells in angiomyxoma express desmin, whereas the cells in prepubertal vulvar fibroma are typically negative for this antigen. Cytogenetics is also useful in separating these tumors from one another; however, the histological and immunohistochemical findings should allow for accurate identification [15].

Angiomyofibroblastoma should also be distinguished from prepubertal vulvar fibroma; however, the former is usually well circumscribed and shows a greater degree of cellularity. Additionally, the tumor cells are desmin positive. Fibroepithelial polyps can be included in the differential, as well, but they protrude from the surface and are more cytologically heterogeneous with multinucleation, nuclear pleomorphism, and mitotic activity [16].

The tumor arises in the vulva, particularly the labia majora and perineal regions of women who are middle aged (mean age, 54 years). Cellular angiofibroma is painless, relatively small (mean, 3.7 cm), and sometimes exophytic, that is, well circumscribed, and is centered in the superficial soft tissues [17–19]. Biologically, it is benign, rarely undergoes malignant transformation, and treatment is complete excision; recurrence rates are very low [20]. It harbors a monoallelic deletion of RB1 and FOXO1 located on 13q14 that also occurs in spindle cell lipoma and myofibroblastoma, and this finding suggests that these are very closely related to one another [21].

Grossly, cellular angiofibromas are yellow to white firm masses that are sometimes polypoid and infrequently gelatinous or cystic. They tend to be partially encapsulated but can have focally infiltrative borders [21] (Fig. 13.11).

Histologically the tumor is hypercellular and composed of haphazardly arranged spindle cells with fusiform or ovoid bland nuclei and pale indistinct eosinophilic cytoplasm. Interspersed in the tumor there are multiple small- to medium-sized blood vessels that usually have hyalinized walls and are arranged in a staghorn-like branching pattern (Fig. 13.12). The stroma contains wirelike collagen fibers, and scattered adipocytes and mast cells may be present (Fig. 13.13). The lesional cells are positive for CD34 and exhibit nuclear positivity staining for estrogen and androgen receptor and are often negative for all smooth muscle markers including SMA, desmin and h-caldesmon [22].

In a minority of cases the tumor may contain scattered cells with enlarged hyperchromatic nuclei that are reminiscent of those in symplastic leiomyoma and ancient schwannoma [19]. The mitotic rate for these tumors is usually low (< 1 mitosis per 10 high-power fields). Another very uncommon variant are cellular angiofibromas that have discrete areas of sarcomatous transformation. The sarcomatous component may exhibit the features of pleomorphic liposarcoma, atypical lipomatous tumor, or an undifferentiated pleomorphic spindle cell sarcoma. Immunohistochemistry has shown that the malignant component expresses p16, whereas the benign component is negative for this antigen. Despite the sarcomatous components, the affected patients have done well with no recurrences or metastases [19].

There are morphological and genetic similarities between cellular angiofibroma, spindle cell lipoma and myofibroblastoma, and these tumors likely represent a family of related lesions [21]. Myofibroblastoma has a fascicular arrangement of the tumor cells in contrast to the haphazard arrangement of cells in angiofibroma. Spindle cell lipoma has characteristic thick ropey collagen fibers that are typically absent in angiofibroma, and it also usually has a more prominent fatty component. Additionally, the hyalinized vessels are distinctive of cellular angiofibroma and not a feature of spindle cell lipoma [21].

This is an uncommon lesion that arises in the vulvovaginal area of middle-aged women, particularly in the labia majora [23]. It is often misdiagnosed clinically as a Bartholin gland cyst or inguinal hernia. Sometimes it presents as a pedunculated or painful mass. The treatment of choice is complete excision and local recurrence is infrequent [17, 18].

Angiomyofibroblastoma is a well-circumscribed tumor that has a soft to rubbery and gray-white to yellowish appearance (Fig. 13.14). Sometimes it can be shiny and gelatinous and rarely is cystic and hemorrhagic. They are usually small as they are usually less than 5 cm in greatest dimension.