Definition

A benign polypoid growth that arises from the distinctive subepithelial stroma of the distal female genital tract.

Clinical Features

Fibroepithelial–stromal polyps, which are hormonally sensitive, most commonly occur in the vulvovaginal region of reproductive age women, often during pregnancy. They may, however, also occur in postmenopausal women on hormonal replacement therapy. Often, the polyps are incidental findings discovered during routine gynecologic examination. Symptoms, when present, may include bleeding, discharge, or the sensation of a mass. These lesions are characteristically polypoid or pedunculated, varying in size but usually less than 5 cm, and are typically solitary, although multiple polyps may occur and are usually associated with pregnancy. Evidence supporting that these lesions are hormonally driven, benign, reactive proliferations include: (1) their occurrence during pregnancy, during which they can be multiple and after which they can spontaneously regress; (2) their association with hormonal replacement therapy in postmenopausal women; and (3) expression of estrogen and progesterone receptors by the constituent stromal cells. Incomplete excision or continued hormonal stimulation (e.g., pregnancy) may be associated with recurrence.1–6

Pathology

Gross examination typically reveals a polypoid mass with a central fibrovascular core covered by glistening squamous mucosa or skin (Figure 6.1). On occasion, multiple finger-like projections, which may clinically mimic a condyloma, are present. Histologically, these lesions exhibit: (1) a variably cellular spindle cell stroma most often located close to the surface epithelium with scattered stellate and multinucleate stromal cells; (2) a central fibrovascular core; and (3) overlying squamous epithelium or skin, which may exhibit varying degrees of hyperplasia (Figures 6.2 and 6.3).

The stromal component has no clearly defined margin and extends up to the epithelial–submucosal interface. Similar to non-neoplastic vulvar stroma, the stromal cells of these polyps may be reactive for desmin, actin, vimentin, and estrogen and progesterone receptors. The most variable component of these lesions is the stroma, which may exhibit a significant degree of cellularity, nuclear pleomorphism, and mitotic activity, thereby mimicking a malignant process (Figure 6.4).^7–10 These worrisome histologic features are particularly, but not invariably, present in polyps that occur during pregnancy (and account for the historical term ‘pseudosarcoma botryoides’).¹¹

Differential Diagnosis

Pseudosarcomatous stromal polyps can be distinguished from a malignant process by the presence of stellate and multinucleate stromal cells near the epithelial–stromal interface, which are characteristically present in these polyps even in the most floridly pseudosarcomatous examples, and by the lack of an identifiable lesional margin. Fibroepithelial–stromal polyps are also readily distinguished from botryoid embryonal rhabdomyosarcoma as they are rare before puberty and lack both the characteristic hypercellular subepithelial (cambium) layer of sarcoma botryoides and specific markers of skeletal muscle differentiation.¹²

Definition

A benign, self-limiting myofibroblastic neoplasm characterized by MYH9-USP6 gene fusion that shows rapid growth and spontaneous regression.13–16

Clinical Features

Nodular fasciitis typically occurs as a rapidly growing, painful, or tender subcutaneous mass in young adults. It most commonly involves the upper limbs, particularly the forearm; however, it occasionally occurs in the vulva. These lesions are benign and local marginal excision is adequate; if left untreated they will spontaneously regress over a period of months.

Pathology

Similar to its counterparts elsewhere, nodular fasciitis involving the vulva is usually a well-circumscribed, unencapsulated mass that typically measures less than 3 cm in size. Histologically, it is a relatively well-circumscribed cellular proliferation of loosely arranged spindle cells set within a variably edematous or myxoid matrix that may exhibit microcystic change (Figure 6.5). The spindle cells, which are arranged in short interconnecting fascicles, have bipolar eosinophilic cytoplasmic processes with indistinct borders and ovoid nuclei with occasional nucleoli, imparting an overall appearance to the cells that has been likened to tissue culture fibroblasts. Scattered inflammatory cells, particularly lymphocytes, and extravasated red blood cells are commonly present. Osteoclast-like giant cells are also quite common. Immunohistochemically, the spindle cells are typically reactive for smooth muscle actin and negative for desmin. Nodular fasciitis is distinguished from a sarcoma, particularly leiomyosarcoma at this site, by the following: (1) lack of nuclear hyperchromasia or pleomorphism, (2) lack of necrosis, and (3) characteristic reactive ‘tissue culture’-like myofibroblastic growth pattern.

Definition

A benign, nonrecurring tumor composed of myofibroblasts and thin-walled capillaries, which principally occurs in vulvovaginal soft tissue.

Clinical Features

Angiomyofibroblastoma is an uncommon tumor that occurs almost exclusively in the superficial soft tissue of the vulvovaginal region of reproductive age women; however, similar tumors also occur rarely in men in the inguinoscrotal region. Clinically, it is often mistaken for a cyst on examination, in particular a Bartholin gland cyst. Local excision is typically adequate treatment, as these tumors do not recur. Exceptionally, they undergo sarcomatous transformation. Rarely, they may have areas indistinguishable from aggressive angiomyxoma, suggesting that these two tumors may be related. In either of these unusual settings, excision with clear margins is recommended.

Pathology

Tumors are typically small (usually <5 cm), well demarcated, tan/white and may have a rubbery consistency (Figure 6.6). They are composed of plump, round to ovoid or spindle-shaped cells, set within a variably edematous to collagenous matrix with alternating zones of cellularity (Figure 6.7). These cells, which have moderate amounts of eosinophilic cytoplasm and round nuclei with fine chromatin and inconspicuous nucleoli, characteristically cluster around the prominent vascular component, which is composed of numerous delicate, thin-walled capillaries (Figure 6.8). Tumor cells may be binucleate or appear somewhat epithelioid. Mitotic activity is typically sparse and occasional cases may have an adipocytic component. The spindle cells are typically reactive for desmin and negative for actin. In postmenopausal patients, lesional cells may be desmin negative.^17–22

Differential Diagnosis

Angiomyofibroblastoma is distinguished from aggressive angiomyxoma by its well-circumscribed margin, its prominent vascular component (which is typically composed of smaller caliber vessels), and its alternating zones of cellularity. As both tumors share a similar immunophenotype, distinction is based on morphologic differences (Table 6.1).²³

Definition

A benign tumor of vulvar mesenchyme composed of a prominent vascular network admixed with bland spindle cells resembling those of spindle cell lipoma.

Clinical Features

Cellular angiofibroma is a rare benign stromal tumor that predominantly occurs in the vulva or perineum of middle-aged women (mean 54 years). Although initially described to occur exclusively at this site, they also occur in the inguinoscrotal region in men (so-called angiomyofibroblastoma-like tumor) and in extragenital sites (e.g., retroperitoneum, skin). In the vulva, they most commonly present as a relatively small (mean 2.7 cm) subcutaneous mass that is well circumscribed and painless. Cellular angiofibroma, if completely excised, behaves in a benign fashion with no recurrent potential. Incomplete excision may lead to regrowth of tumor; therefore, local excision with negative margins is adequate treatment. Very rare cases show sarcomatous transformation.24–29

Pathology

On gross examination, cellular angiofibroma typically is gray-white and has a firm, rubbery consistency (Figure 6.9). Histologically, it is usually well circumscribed; however, focal infiltration into surrounding soft tissue may be present. These tumors are characteristically cellular, composed of the following: (1) short, intersecting fascicles of bland, spindle-shaped cells with ovoid nuclei and scant palely eosinophilic cytoplasm; (2) numerous small to medium sized, thick-walled, and often hyalinized blood vessels; and (3) admixed wispy collagen bundles (Figure 6.10). In approximately 25% of cases, a usually minor component of adipose tissue is present. Mitotic activity, although brisk in some cases, is usually infrequent while necrosis and nuclear pleomorphism are typically absent. On occasion, atypia may be present, most commonly in the form of scattered hyperchromatic multinucleated cells (Figure 6.11). Rarely, abrupt transition to a discrete sarcomatous component can occur, which may exhibit features of atypical lipomatous tumor, pleomorphic liposarcoma or pleomorphic sarcoma, not otherwise specified.²⁹ The spindle cells of cellular angiofibroma are reactive for CD34 in 60% of cases, and less commonly reactive for smooth muscle actin (20%) and desmin (8%). Half of all cases show reactivity for estrogen and progesterone receptors. Keratin, epithelial membrane antigen, and S-100 protein are negative.

Differential Diagnosis

Cellular angiofibroma is distinguished from a smooth muscle tumor by its more prominent vascular component, shorter fascicular growth pattern, and relative lack of eosinophilic cytoplasm. Distinction from angiomyofibroblastoma is based on its uniform cellularity; larger, thick-walled, and hyalinized blood vessels; and spindle cells arranged in short intersecting fascicles (Table 6.1).³⁰ Mammary type myofibroblastoma and cellular angiofibroma are both well-circumscribed tumors composed of short intersecting fascicles of bland, CD34-positive spindle cells within a collagenous stroma; however, the vascular component of the former is typically not as prominent but can show a similar degree of hyalinization. These tumors both have similar genetic changes with loss of 13q14 (FOX1A1) and thus likely represent tumors along a spectrum exhibiting varied cellularity and vascularity.

Definition

A poorly circumscribed, hypocellular lesion composed of bland spindle cells within a variably edematous, myxoid, or collagenous matrix that usually occurs in prepubertal girls.31–32

Clinical Features

Prepubertal vulvar fibroma most commonly involves the labia majora of girls and usually presents as a painless, gradual vulvar swelling or enlargement. Lesions typically are under 5 cm in size, unilateral, and ill-defined submucosal or subcutaneous masses. While these lesions have been considered neoplastic due to their ability to recur, it has also been proposed that they represent growth of a hormonally responsive vulvar mesenchyme to changes in the hormonal environment at the time of puberty and thus represent a hyperplastic rather than a neoplastic process. Although only a limited number of cases have been studied, the lesions appear to be benign, except for quite frequent local recurrence when incompletely excised.

Pathology

Histologically, these tumors, which are located in submucosal or subcutaneous tissue, are poorly marginated with infiltration into surrounding tissue, including around adnexal structures and nerves, and into adipose tissue (Figure 6.12). In addition, there is no clear interface with the overlying epithelium. The lesion is hypocellular and composed of a patternless proliferation of bland, uniform spindle cells with ovoid nuclei and palely amphophilic cytoplasm set within a variably myxoid, edematous, or collagenous matrix (Figure 6.13). Small to medium sized vessels, some with mural thickening, are present. Mitotic activity is sparse and nuclear pleomorphism is absent. Lesional spindle cells are typically reactive for CD34 but are negative for smooth muscle actin, desmin, and S-100 protein.

Definition

A benign tumor of dermal connective tissue exhibiting a storiform growth pattern.

Clinical Features

Most commonly occurring on the limbs or trunk of adults, dermatofibroma occasionally involves vulvar skin. Although the clinical appearance is variable, most present as a flesh-colored papule, nodule, or plaque; however, some may be pigmented. The diagnosis may be suspected clinically by the presence of the so-called ‘dimpling’ sign; pinching of the tumor results in an inward dimpling of the lesion. Complete excision is usually not necessary unless the tumor shows unusual morphologic features (e.g., cellular, aneurysmal, plexiform, deeply infiltrative, or atypical variants) as these subtypes have locally recurrent potential. Following re-excision, very rare cases of these subtypes have been associated with regional lymph node or metastatic deposits in the lung; however, there are no morphologic indicators in the primary that would predict this biologic potential.33–43

Pathology

Dermatofibroma exhibits a storiform proliferation of bland spindle cells with varying degrees of hyalinization of the dermal collagen, which is birefringent under polarized light (Figure 6.14). The tumor is relatively well circumscribed; however, entrapment of hyalinized bundles of dermal collagen by the spindle cells at the periphery of the tumor imparts a characteristic pseudoinfiltrative pattern (Figure 6.15). Another characteristic feature is the presence of overlying epidermal hyperplasia, which is common. A number of histologic variants are recognized (although these occur principally outside of the vulva) and include hemosiderotic, lipidized, aneurysmal (angiomatoid), atypical, epithelioid, plexiform, cellular, and deeply penetrating types. The spindle cells are often focally reactive for smooth muscle actin and negative for CD34, although the cellular variant may be reactive for CD34 at the periphery of the tumor. These lesions are often factor XIIIa positive, but most staining is in reactive dermal dendritic cells toward the periphery.³³

Differential Diagnosis

Dermatofibroma can be distinguished from dermatofibrosarcoma protuberans, its main differential diagnostic consideration, by the following: (1) its lack of infiltration of adipose tissue (although this may be seen in the cellular and deeply penetrating variants), (2) presence of birefringent collagen under polarized light, (3) overlying epidermal hyperplasia, (4) tendency not to infiltrate around adnexal structures, and (5) lack of diffuse reactivity for CD34.⁴³

Definition

A tumor of neuroectodermal origin composed of cells that contain distinctive granular cytoplasm due to the accumulation of lysosomes.

Clinical Features

Granular cell tumor is an uncommon neoplasm that typically arises in the skin and subcutaneous tissue of middle-aged adults with a slightly increased frequency in women. Tumors typically involve the head, neck, and trunk region, but may occasionally occur in the vulva, most often the labium majus. Patients usually present with a solitary, slowly growing, asymptomatic nodule that is often discovered incidentally on clinical examination. If present, symptoms may include pain, increased growth, and pruritus. Complete excision with clear margins is standard treatment, although these tumors seldom recur, even if incompletely excised. Malignant examples are rare.44–49

Pathology

Granular cell tumors are composed of strands and nests of polygonal cells with abundant eosinophilic granular cytoplasm and small, centrally placed, hyperchromatic nuclei separated by thin fibrous septa (Figure 6.16). Although distinctive, the characteristic granular cytoplasmic change, which is due to the accumulation of lysosomes, is not specific for this tumor type and may be seen in other types of neoplasms, such as smooth muscle tumors. Although many granular cell tumors are relatively well circumscribed, nearly half may show poorly defined or infiltrative margins. Nests of tumor cells adjacent to or surrounding small nerves are common. In addition, the tumor is often associated with overlying pseudoepitheliomatous hyperplasia, which may be mistaken for a squamous neoplasm if the underlying granular cell tumor is overlooked. Granular cell tumors are reactive for S-100 protein, neuron-specific enolase, CD68, and NKI-C3.

Differential Diagnosis

The granular cell tumor is distinctive and few pose diagnostic difficulty. Exclusion of a smooth muscle tumor with granular cell change is the most likely differential diagnostic consideration, which can be accomplished by recognition of areas with typical smooth muscle morphology and architecture as well as coexpression of desmin, caldesmon, and smooth muscle actin.

Definition

A benign tumor of smooth muscle exhibiting intersecting fascicles of spindle cells with eosinophilic cytoplasm.

Clinical Features

Although genital smooth muscle tumors were initially considered within the category of superficial smooth muscle tumors, which includes pilar leiomyoma and angioleiomyoma, they are now classified separately based upon their differing clinical behavior, histologic features, and criteria for malignancy. Smooth muscle tumors of the distal female genitalia, unlike those of the uterus, are uncommon. They occur over a wide age range but are most common in the fourth and fifth decades and typically present as a painless, well-circumscribed mass usually <3 cm in size. Not uncommonly, the clinical impression is that of a cyst. Local excision for typical leiomyomas is adequate treatment. For tumors with unusual histologic features associated with recurrent potential (see the following sections), a margin of excision of at least 1 cm is recommended whenever possible, with close, long-term follow-up.50–55

Pathology

Similar to uterine smooth muscle tumors, vulvar leiomyomas usually exhibit the characteristic gross appearance of benign smooth muscle tumors of the myometrium but on occasion may have a more homogeneous appearance with less obvious whorling (Figure 6.17). In most instances, they are composed of intersecting fascicles of spindle-shaped cells with moderate amounts of eosinophilic cytoplasm and elongated, blunt-ended nuclei. However, an unusual morphologic pattern, which is commonly present in vulvar smooth muscle tumors, is the variable deposition of myxohyaline matrix, which imparts a plexiform or lacy appearance (Figure 6.18).

Due to the relative infrequency of vulvar smooth muscle tumors in combination with few published series with long-term follow-up, there is continued difficulty in reliably predicting which tumors are benign and which have recurrent potential. While a combination of size, circumscription, nuclear atypia, and mitotic thresholds has been proposed to identify those tumors with recurrent potential, in our experience any mitotic activity, nuclear pleomorphism, or infiltration of surrounding tissue may be associated with local recurrence, sometimes years after the initial excision. These observations suggest that smooth muscle tumors of the vagina and vulva fall along a biologic continuum with regard to their behavior and resist being rigidly classified into benign and malignant categories by currently definable histopathologic criteria.

From a practical standpoint, we advocate use of the term ‘atypical smooth muscle tumor’ for those cases having any of the following features: (1) mitotic activity, (2) nuclear pleomorphism, or (3) an infiltrative margin. Although published series have not included necrosis as a histologic criterion, leiomyosarcoma should be seriously considered in any smooth muscle neoplasm with coagulative tumor cell necrosis.

There are only case reports regarding the cytogenetic findings of vulvar smooth muscle tumors. In one case, a pericentric inversion (12)(p12q13–14) was described as the sole chromosomal abnormality, which resulted in activation of HMGA2, a gene that appears to be activated in smooth muscle tumors of genital, but not extragenital, origin. A clonal translocation, 46,XX,t(7;8)(p13;q11.2), has also been described in a periurethral smooth muscle tumor, an aberration not previously discovered in smooth muscle tumors from any site.

Definition

An abnormality of dermal lymphatic channels exhibiting numerous dilated and cystic lymphatic spaces.56–60

Clinical Features

Lymphangioma circumscriptum may be congenital, occurring during infancy and commonly associated with other lymphatic abnormalities such as cystic hygroma or cavernous lymphangioma, or it may be acquired (also termed ‘acquired lymphangiectasia’), which most commonly occurs in adults and is associated with secondary lymphatic damage such as that associated with radiotherapy or chronic lymphedema. It most commonly affects the skin and subcutaneous tissue of the trunk, thighs, and buttocks, but occasionally involves the vulva. Clinically, numerous small vesicles filled with clear fluid characterize this lesion. Symptoms typically include swelling, pain, and superimposed infection secondary to excoriation. Management of congenital lesions is local excision, including removal of any large feeding lymphatic channel, which may be deep seated, as incomplete removal is commonly associated with recurrence.

Pathology

Numerous dilated and cystic lymphatic channels are present, primarily within the papillary dermis, but also within the dermis and subcutaneous tissue. Those located in the papillary dermis are closely apposed to the overlying epithelium, which results in the clinical impression of a vesicle (Figure 6.19). Associated epidermal hyperplasia and a dermal lymphocytic infiltrate are common.

Definition

A lesion composed of superficial ectatic vascular channels associated with epidermal hyperplasia.

Clinical Features

Angiokeratoma involving the vulva occurs over a wide age range, but typically presents before the sixth decade as an asymptomatic, red to purple, papular lesion under 1 cm in size. It often has a warty appearance due to associated epidermal changes. When present, symptoms include bleeding, pain, or pruritus. The lesion may be solitary or multiple, and if multiple should raise the possibility of Fabry disease, a rare X-linked chromosomal disorder of lipid metabolism in which there is a deficiency of lysosomal α-galactosidase.61–62

Pathology

Angiokeratoma exhibits closely apposed, dilated, blood-filled vascular spaces within the papillary dermis, partially surrounded by the overlying epithelium (Figure 6.20). The epithelium typically shows acanthosis, hyperkeratosis, and occasionally papillomatosis, resulting in the clinical impression of a warty lesion.

Definition

A locally infiltrative, non-metastasizing, hypocellular myxoid tumor of the pelvicoperineal region with the potential for local, sometimes destructive, recurrence.

Clinical Features

Deep angiomyxoma occurs principally in the pelvicoperineal region of reproductive age women, with a median incidence in the fourth decade, but rarely also develops in the inguinoscrotal region of men, in whom the median age at presentation is in the sixth to seventh decade. Often the clinical impression is that of a labial cyst, most commonly a Bartholin gland cyst. Tumors vary in size, but are often relatively large (>10 cm) and poorly marginated (Figure 6.24). Although there is a 20–30% risk of local, sometimes destructive recurrence, more than one recurrence is unusual and most are cured by an additional surgical excision with negative margins. Hence the currently preferred terminology is deep angiomyxoma, as these tumors are not as ‘aggressive’ as originally thought. Besides positive surgical margins, there are no clinical or histopathologic features that predict recurrent potential. Wide local excision with 1 cm margins is considered optimal and adequate treatment.

Pathology

Tumors typically have a gelatinous or myxoid appearance (Figure 6.25), but occasionally may appear more fibrous in a recurrence, presumably due to previous surgical scar tissue. Histologically, deep angiomyxoma is a poorly marginated, paucicellular neoplasm composed of uniformly distributed bland spindle cells with round to ovoid nuclei and moderate amounts of palely eosinophilic cytoplasm, discernible as bipolar or multipolar cell processes (Figure 6.26). The cells are set within a copious myxoid matrix that contains variably sized, but often medium to large, thick-walled, often hyalinized, blood vessels. Condensation of delicate fibrillary collagen around the blood vessels is characteristic, as is the presence of bundles of brightly eosinophilic smooth muscle cells (Figure 6.27). The spindle cells are typically reactive for desmin, smooth muscle actin, and estrogen and progesterone receptors, similar to normal vulvar mesenchyme. The spindle cells also can be positive for CD34, HMGA2, and CDK4. The expression of the last two markers is related to the fact that structural rearrangements of 12q15 with involvement of HMGA2, which encodes a factor important in transcriptional regulation, is the most frequent chromosomal aberration observed in deep (aggressive) angiomyxoma. Rearrangements appear to occur in approximately 30% of cases and the 12q15 breakpoint can be either intragenic or extragenic. Consequently, immunohistochemical expression of HMGA2 may only be useful in confirming the diagnosis or assessing margin status in a subset of cases.^69–72

Differential Diagnosis

The differential diagnosis includes superficial angiomyxoma (see the following section), angiomyofibroblastoma, and an edematous fibroepithelial–stromal polyp (Table 6.1). Deep angiomyxoma is distinguished from angiomyofibroblastoma by its infiltrative margin, its vascular component (which is typically less prominent and composed of larger, thicker walled vessels), and its uniform paucicellularity. Deep angiomyxoma differs from edematous fibroepithelial–stromal polyps by its deep location, its infiltrative margin, its lack of polypoid superficial growth, and its uniformly bland cytomorphology with the lack of the characteristic stellate and multinucleate cells typical of stromal polyps.

Definition

A superficially located, multilobulated, myxoid neoplasm with a 20–30% risk of local, nondestructive recurrence.

Clinical Features

Superficial angiomyxoma usually involves the head, neck, and trunk region, but does occasionally occur in the vulva. It typically occurs in the fourth decade and patients usually present with a slowly growing, painless, polypoid mass that typically measures less than 5 cm in size. Although usually solitary, multiple lesions may be associated with Carney complex. Approximately one-third of these tumors recur locally if incompletely or marginally excised; therefore, complete excision with clear margins is recommended treatment.79–81

Pathology

Histologically, superficial angiomyxoma is a myxoid neoplasm with a distinctive multilobulated growth pattern that is centered in the dermis and superficial subcutaneous tissue (Figure 6.28). The relatively well-demarcated myxoid nodules contain slender spindle and stellate-shaped cells, delicate thin-walled capillaries, and scattered inflammatory cells, particularly polymorphonuclear leukocytes (Figure 6.29). The presence of acute inflammatory cells is not associated with necrosis or overlying epidermal ulceration and is presumably secondary to the production of a chemotactic factor by the tumor cells. In 10–20% of cases, an epithelial component—usually in the form of a squamous epithelial-lined cyst, buds of basaloid cells, or strands of squamous epithelium—is present, probably as a result of entrapped adnexal structures or stimulation of the overlying epithelium by the tumor. Immunohistochemically, the spindle cells are typically negative for actin, desmin, and S-100 protein.

Differential Diagnosis

Superficial angiomyxoma is distinguished from deep angiomyxoma by the following: (1) its superficial location, (2) well-demarcated margins, (3) lobulated growth pattern, (4) lack of thick-walled blood vessels, and (5) negativity of the lesional cells for desmin (Table 6.1).

Definition

A tumor of dermal connective tissue exhibiting a monomorphic storiform proliferation of fibroblastic spindle cells and infiltration of adipose tissue.

Clinical Features

Dermatofibrosarcoma protuberans most commonly occurs on the trunk, lower extremities, and groin area (although not commonly the vulva proper) of adults, principally between the third and sixth decades. Clinical presentation can vary from a flesh-colored to pigmented papule, plaque, nodule, or exophytic multinodular growth. Wide local excision with clear margins is necessary to prevent recurrence; rare cases (<0.1%) have metastasized, although this figure is higher (~15%) in cases that show higher grade fibrosarcomatous change.

Pathology

Histologically, the classic appearance of this tumor is that of a poorly circumscribed, storiform proliferation of uniform spindle cells involving the dermis and extending into subcutaneous adipose tissue in a characteristic lace-like or honeycomb pattern (Figure 6.30). A band of uninvolved dermis between the tumor and epidermis, which may be of normal thickness or atrophic, is typically present (Grenz zone). Entrapment of adnexal structures is common. In contrast to benign fibrous histiocytoma, polarizable collagen is typically absent. Some tumors, including those that occur in the vulva, may exhibit fibrosarcomatous change characterized by a herringbone, fascicular growth pattern with increased mitotic activity (Figure 6.31); tumors with this morphologic appearance have metastatic potential. Immunohistochemically, the neoplastic cells are typically diffusely reactive for CD34 and negative for factor XIIIa. Translocation between chromosomes 17 and 22, often in the form of supernumerary ring chromosomes, has been identified by cytogenetic analysis in this tumor type, including cases that have occurred in the vulva. This translocation results in the fusion of two genes, collagen type I α-1 (COL1A1) and platelet-derived growth factor β-chain (PDGFB).82–92

Differential Diagnosis

Dermatofibrosarcoma protuberans differs from dermatofibroma, its main differential diagnostic consideration, by the following: (1) its tendency to infiltrate subcutaneous adipose tissue in a characteristic honeycomb pattern (although extension into adipose tissue may be seen in some cases of fibrous histiocytoma), (2) entrapment of adnexal structures, (3) lack of birefringent collagen under polarized light, (4) lack of overlying epidermal hyperplasia, and (5) diffuse reactivity for CD34.

Definition

A rare sarcoma of vulvar soft tissue showing smooth muscle differentiation.

Clinical Features

Of all sarcomas of the vulva, which as a category are rare, leiomyosarcoma represents the most common subtype. Patients are typically in their fourth or fifth decade and present with symptoms related to a mass. Tumors may be of varying size but are typically under 5 cm. Treatment varies from wide local excision to radical vulvectomy.

Pathology

Histologically, most vulvar leiomyosarcomas have a similar morphologic appearance to those that occur more commonly elsewhere in the female genital tract that are of the spindle cell type (Figure 6.32). Due to the rarity of these lesions, defining criteria to predict those tumors with metastatic potential remains problematic yet of paramount importance due to potential differences in clinical management. Use of the criteria proposed by Tavassoli and Norris⁵⁵ is recommended, in which tumors with three or more of the following criteria should be diagnosed as leiomyosarcoma:

Although necrosis is excluded in this algorithm, its presence should strongly raise the possibility of malignancy.^{52–55,93–95}

Definition

Large cell variant of epithelioid sarcoma that has a predilection for the genital and perineal regions.

Clinical Features

Patients typically present in the fourth decade with symptoms related to a mass lesion. Tumor size in the genital area is usually under 6 cm but tumor size in general may range up to 20 cm (median, 4 cm). Clinically, the proximal subtype acts more aggressively than the usual (distal) epithelioid sarcoma, with earlier distant metastasis following excision of the primary.

Pathology

Histologically, this tumor exhibits a diffuse and often multinodular proliferation of relatively monomorphic large cells with abundant eosinophilic cytoplasm, imparting an epithelioid appearance. Rhabdoid inclusions are frequent (Figures 6.33 and 6.34). The tumor cells, which contain large vesicular nuclei and prominent nucleoli, commonly invade into subcutaneous or deeper soft tissue. Immunohistochemically, the tumor cells commonly react with keratin and epithelial membrane antigen. Approximately 50% express CD34 and may occasionally react for desmin and actin. The vast majority show loss of staining for INI1, the product of this ubiquitous chromatin remodeling gene located on chromosome 22q11.2, the expression of which is often lost in these tumors.96–100

Differential Diagnosis

In the genital region, the principal differential diagnosis is with carcinoma or melanoma. Proximal-type epithelioid sarcoma is distinguished from poorly differentiated carcinoma by its multinodular growth pattern, coexpression of CD34 and, occasionally, desmin, and lack of an intraepidermal in situ component. In addition, it differs from melanoma by the previous features as well as expression of epithelial markers and lack of S-100 protein reactivity.

Definition

Malignant mesenchymal neoplasm showing adipocytic differentiation.

Clinical Features

Liposarcoma usually arises in the limbs, trunks, and abdominal cavity, but uncommonly also in the vulva. It occurs predominantly in middle-aged women (median 52 years) on the labia majora and is of varying size but typically is under 8 cm. Many are thought clinically to represent a lipoma. Most are of the well-differentiated subtype and have a similar clinical behavior to those that occur outside the abdominal cavity, that is, complete excision with a clear margin is curative.

Pathology

Histologically, most tumors have the usual morphologic appearance of well-differentiated liposarcoma/atypical lipomatous tumor with variation in adipocyte size, adipocytic nuclear atypia, cellular fibrous septa (often with scattered hyperchromatic stromal cells), and occasional lipoblasts. Some, however, may have an unusual morphology that is unique to tumors that arise at this site. These tumors show an admixture of neoplastic bland spindle and round cells, variably sized adipocytes, and numerous bivacuolated lipoblasts (Figure 6.35). This unusual morphology is not associated with any difference in behavior.^101–104