Fibrous/Myofibroblastic Proliferations of the Vulva

 

Age

Location

Clinical presentation

Gross

Microscopic features

Ancillary tests

Fibroepithelial stromal polyp

Reproductive age

Vulvovaginal region

Single mass

Flesh-colored mass covered with skin

Fibrous tissue and blood vessels

Positive immunohistochemistry for desmin, ER, PR

Multiple in pregnancy

Scattered multinucleated giant cells

Massive vulvar edema

Mean age: 46.5

Vulva, penis or scrotum

Usually in morbidly obese generalized genital enlargement present from 6 months to 6 years

Massive pedunculated masses

Edematous fibrous tissue with dilated lymphatics
 
Verrucous hyperplasia or papillomatosis of epidermis

Prepubertal vulvar fibroma

Prepubertal

Labia majora

Unilateral submucosal or subcutaneous mass

Tan-gray and ill delineated

Hypocellular fibrous tissue with bland fibroblast

Positive immunohistochemistry for CD34

Thick and wavy collagen fibers in stroma

Cellular angiofibroma

Mean age: 54

Labia majora and perineal region

Small, painless mass in the superficial soft tissues

Yellow to white firm mass

Well-circumscribed hypercellular spindle cell lesion

Positive immunohistochemistry for CD34, ER, PR

Hyalinized branching blood vessels

Angiomyofibroblastoma

Middle-aged women

Vulvovaginal region/labia majora

Painful mass that is usually misdiagnosed as Bartholin gland cyst or inguinal hernia

Gray to white, soft to rubbery, well-circumscribed mass

Well demarcated with hypo- and hypercellular areas

Positive immunohistochemistry for desmin

Wavy collagen fibers with spindle or stellate neoplastic cells

Aggressive angiomyxoma

Mean age: 40

Pelvis, perineum or vulva

Large asymptomatic lesion sometimes confused with a lipoma or leiomyoma

Tan-gray with rubbery consistence and gelatinous cut surface

Paucicellular tumor with myxoid stroma

Positive immunohistochemistry for desmin, SMA, ER, PR, and HMGIC t(8;12) (p12:q15)

Bland spindle and stellate cells

Medium-sized blood vessels

Superficial myofibroblastoma

Three to nine decades

Vulvovaginal region

Solitary nodular lesion < 3 cm

Tan-pink to white firm lesion covered by vulvar skin

Vague fascicles with lacelike collagen fibers

Positive immunohistochemistry for desmin, CD34, CD99 Variable ER, PR

Bland spindle to ovoid cells

Reactive fibroblastic and myofibroblastic proliferation of the vulva

55

Labia majora

Painful nodule perineal nodule exacerbated with physical activity (cycling, horseback riding)

Firm and fibrous with overlying skin

Adipose tissue with mildly cellular hyalinized stroma

Positive immunohistochemistry for ER, SMA

Haphazardly arranged vessels and nerves

Postoperative spindle cell nodule

Middle age

Lower genitourinary tract

Three to seven weeks after a surgical procedure

Poorly defined polypoid nodule with reddish-gray appearance

Plump spindle cells in intersecting fascicles

Positive immunohistochemistry for SMA, focally desmin Trisomy 7

Numerous mitosis





Fibroepithelial Stromal Polyp



Clinical Features


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.


Histopathology


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].

A313723_1_En_13_Fig1_HTML.jpg


Fig. 13.1
Fibroepithelial polyp is solid, unencapsulated, and tan-white


A313723_1_En_13_Fig2_HTML.jpg


Fig. 13.2
Core of fibroepithelial polyp is composed of fibrous tissue and blood vessels


A313723_1_En_13_Fig3_HTML.jpg


Fig. 13.3
The fibroepithelial polyp contains scattered multinucleated giant cells


A313723_1_En_13_Fig4_HTML.jpg


Fig. 13.4
Pseudosarcomatous fibroepithelial polyp is hypercellular and contains cells with enlarged pleomorphic nuclei that are mitotically active


A313723_1_En_13_Fig5_HTML.jpg


Fig. 13.5
The spindle and stellate cells of fibroepithelial polyps express desmin


Differential Diagnosis


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.


Summary





  • Clinical Presentation



    • Present in premenopausal women


    • Hormone related


    • Single mass, may be multiple in pregnancy


  • Histopathologic Features



    • Solid, unencapsulated, and tan-white.


    • Core composed of fibrous tissue and blood vessels.


    • Scattered multinucleated giant cells are characteristic.


  • Differential Diagnosis



    • Embryonal rhabdomyosarcoma


    • Condyloma acuminatum


Takeaway Essentials





  • Clinical Relevant Pearls



    • Lesions are hormone related and have been associated with hormone replacement therapy.


    • Should be considered in the differential diagnosis of vulvar polyps in premenopausal women.


  • Pathology Interpretation Pearls



    • Hypocellular and edematous stroma without a grenz zone, but can be hypercellular and with nuclear pleomorphism in pregnancy.


    • Squamous mucosa may demonstrate reactive hyperplasia that should not be confused with squamous cell carcinoma or viral changes.


Massive Vulvar Edema



Clinical Features


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 [1113]. The mean age at presentation is 46.5 years [14]. The enlargement is slowly progressive and the overlying skin may ulcerate.


Histopathology


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.

A313723_1_En_13_Fig6_HTML.jpg


Fig. 13.6
The dermis and fat septae are expanded by tan-gray tissue in massive lymphedema


A313723_1_En_13_Fig7_HTML.jpg


Fig. 13.7
The septae in the fat in massive lymphedema are expanded by edematous fibrous tissue that contains increased numbers of dilated lymphatics


A313723_1_En_13_Fig8_HTML.jpg


Fig. 13.8
In massive lymph edema, the subcutaneous tissue is replaced by bland fibro-myxoid tissue


Differential Diagnosis


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.


Summary





  • Clinical Presentation



    • Bilateral vulvar enlargement, may be massive


    • Slowly progressing, can lead to skin ulceration


  • Histopathologic Features



    • The septae of the subcutis are expanded by fibrous tissue.


    • Edematous fibrous tissue contains increased numbers of dilated lymphatics.


  • Differential Diagnosis



    • Aggressive angiomyxoma


Takeaway Essentials





  • Clinical Relevant Pearls



    • Bilateral lesion usually associated with morbid obesity and/or immobility, hyperthyroidism, and pregnancy


  • Pathology Interpretation Pearls



    • Pathologic findings are centered in the subcutis, an unusual location for liposarcoma.


    • Dilated lymphatics should not be confused with a primary lymphatic tumor.


Prepubertal Vulvar Fibroma



Clinical Features


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.


Histopathology


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.

A313723_1_En_13_Fig9_HTML.jpg


Fig. 13.9
Hypocellular fibrous tissue replacing fat in prepubertal fibroma


A313723_1_En_13_Fig10_HTML.jpg


Fig. 13.10
The fibroblasts in prepubertal fibroma have bland nuclei and are associated with varying amounts of collagen


Differential Diagnosis


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].


Summary





  • Clinical Presentation



    • Occurs in prepubertal females


    • Unilateral submucosal or subcutaneous mass in labia majora


  • Histopathologic Features



    • Hypocellular fibrous tissue with bland fibroblasts replacing fat.


    • Stroma has thick and wavy collagen fibers.


  • Differential Diagnosis



    • Aggressive angiomyxoma


    • Angiomyofibroblastoma


    • Fibroepithelial stromal polyp


Takeaway Essentials





  • Clinical Relevant Pearls



    • Mass in labia majora of prepubertal females with painless progressive swelling


    • Can cause emotional distress and should be addressed promptly


  • Pathology Interpretation Pearls



    • Bland fibroblasts admixed with variable amounts of thick and wavy collagen are good clues of the benign nature of the lesion.


    • Infiltrative growth into the surrounding tissues can cause confusion with more aggressive soft tissue tumors.


    • CD34 reactivity can be also seen in vulvar prepubertal fibromas and cellular angiofibroma; however, vulvar fibroma lacks hyalinized vessels and is not well circumscribed.


Cellular Angiofibroma



Clinical Features


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 [1719]. 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].


Histopathology


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).

A313723_1_En_13_Fig11_HTML.jpg


Fig. 13.11
Cellular angiofibroma has well-delineated margins

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].

A313723_1_En_13_Fig12_HTML.jpg


Fig. 13.12
Cellular angiofibroma is hypercellular and contains a staghorn-like vascular tree


A313723_1_En_13_Fig13_HTML.jpg


Fig. 13.13
The tumor cells in cellular angiofibroma are spindled with bland nuclei. The stroma contains wirelike bundles of collagen

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].


Differential Diagnosis


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].


Summary





  • Clinical Presentation



    • Arises in labia majora of the vulva and perineum


    • Unilateral subcutaneous mass


  • Histopathologic Features



    • Well-circumscribed hypercellular spindle cell lesion with fusiform or ovoid nuclei


    • Multiple hyalinized branching blood vessels


    • Wirelike collagen fibers in the stroma


    • Positive for CD34, nuclear positivity for ER and PR


    • Negative for muscle markers


  • Differential Diagnosis



    • Spindle cell lipoma


    • Myofibroblastoma


Takeaway Essentials





  • Clinical Relevant Pearls



    • Painless unilateral vulvar and perineal lesion, relatively small


    • Monoallelic deletion of RB1 and FOXO1 on 13q14-same derangement as spindle cell lipoma and myofibro-blastoma


  • Pathology Interpretation Pearls



    • Well-delineated margins support benign nature of the tumor.


    • Hypercellularity can cause confusion with more aggressive neoplasms.


Angiomyofibroblastoma



Clinical Features


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].


Histopathology


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.
Nov 11, 2017 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Fibrous/Myofibroblastic Proliferations of the Vulva
Premium Wordpress Themes by UFO Themes
%d bloggers like this: