Abstract

We analyzed the clinicopathologic features of 10 cases of vulvovaginal myofibroblastoma to widen its morphological and immunohistochemical spectrum. Most tumors (8/10 cases) were located in the vagina. The patients' age ranged from 44 to 77 years, and tumor size ranged from 0.4 to 3 cm. Histologically, 5 tumors had the characteristics of vulvovaginal myofibroblastoma. In addition, we identified 3 cases composed of spindle-shaped cells arranged in short fascicles with intervening thick collagen bands, closely reminiscent of mammary myofibroblastoma. Notably, 1 case resembled Sertoli cell tumor, sclerosing type, because of its predominant cord-like arrangement. In another case, there were highly cellular areas composed of uniform-packed, rounded cells that, at low magnification, looked like a malignant "small round blue cell tumor." A variably thick band of native connective tissue separated tumors from the overlying squamous epithelium even if, in 3 cases, tumor cells extended up to the epithelium. In 7 cases, a variable number of vessels showed perivascular hyalinization. Only rare mitotic figures were identified. All tumors were diffusely positive for vimentin, desmin, and CD99. A variable staining intensity was observed for CD34, Bcl-2, B-cell lymphoma 2 (Bcl-2) CD10, estrogen receptor, and progesterone receptor in most cases, but none expressed α-smooth muscle actin. We emphasize that vulvovaginal myofibroblastoma encompasses a morphological spectrum wider than previously described. The overlapping morphological and immunohistochemical features of vulvovaginal and mammary myofibroblastomas led us to speculate that these are related entities with morphological variations on a common basic theme likely dependent on anatomical location.

A wide variety of mesenchymal lesions occur in the lower female genital tract.^5,6 Broadly, these mesenchymal lesions can be separated into two groups. The first group includes several well-characterized tumors that show a marked tendency to occur in the lower female genital tract, such as aggressive angiomyxoma, angiomyo- fibroblastoma, and cellular angiofibroma.^7-9 These tumors can also be called as relatively site-specific. The second group embraces a wide range of heterogeneous lesions that frequently occur in this region, but arise in other anatomic sites as well, with examples as fibroepithelial stromal polyp, superficial angiomyxoma and leiomyoma.

SCVM represents a new member of the first group. SCVM appears underrecognized. To our knowledge, only 31 cases of SCVM have been reported so far in the literature.^1-4 The current four cases raise the number to 35. These 35 cases occurred in 34 patients ranging in age from 23 to 80 years with mean of 57 years. To date, 32 patients (94%) were in their peri- or post-menopausal years. Eleven (32%) patients had received Tamoxifen or hormone- replacement therapy. Clinically, the most common presentation was an asymptomatic polypoid nodule or mass, with cysts or polyps being the most preoperative diagnosis. Thirty patients presented with solitary nodular mass, whereas 4 patients had two separated lesions. Thirty tumors were located in the vagina or vaginal fornix, 3 in the cervix and 2 in the vulva. Because the tumor also occurred in the vulva, Ganesan et al² suggested the term superficial myofibroblastoma of the lower female genital tract to replace SCVM.

Overall, most SCVM were described as polyps or had a polypoid outline, measuring 1.0 cm to 8.0 cm (mean, 2.5 cm) in diameter. Histologically, SCVM was characterized by its superficial subepithelial location and uniform spindle and stellate cells arranged in diverse growth patterns within a myxoid to collagenous stroma. Tumor cells in SCVM typically expressed vimentin, desmin, CD34, ER and PR, with desmin and CD34 accentuating the dendritic processes of the cytoplasm, whereas actins was consistently negative.

Due to some histological and immunohistochemical overlapping features, SCVM can be confused with other mesenchymal lesions of the lower female genital tract. The principal differential diagnosis is FSP, especially the cellular variant.⁹ As described in the original paper, 4 cases had been primarily diagnosed as FSP. The younger population of FSP, absence of distinct Grenz zone in FSP, lack of heterogeneous cellularity and diverse growth patterns, are crucial features to distinguish SCVM from FSP.⁹ The other tumor enters the differential diagnosis is angiomyofibroblastoma (AMF). AMF is also characterized by alternating hypercellular and hypocellular areas. However, unlike SCVM, AMF contains abundant small to medium sized blood vessels. The tumor cells in AMF also have a propensity to grow around the vessels. Furthermore, SCVM is frequently negative for α-smooth muscle actin. In contrast, AMF is usually positive for actins.⁸ Cellular angiofibroma (CA) is another site-specific mesenchymal tumor that should be considered in the differential diagnosis. CA usually involves the vulva and the inguinoscrotal region. CA differs from SCVM by its numerous small- to medium-sized thick-walled vessels and negative stainging for desmin. Other lesions that may be confused with SCVM include leiomyoma, solitary fibrous tumor (SFT) and mammary-type myofibroblastoma.¹⁰ Vulvovaginal leiomyoma often shows a hyalinized or myxoid stroma, so called myxohyaline pattern. In addition to desmin, ER and PR, the tumor cells in leiomyoma are also positive for actins. SFT is another tumor which may display alternating cellularity. In contrast to SCVM, SFT is typically positive for CD34 and negative for desmin. Mammary-type myofibroblastoma is a spindle cell tumor with morphological and immunophenotypic features identical to myofibroblastoma of breast. Mammary-type myofibroblastoma shows a predilection for the inguinal area of older men. Only one case has been reported in the vaginal wall.¹¹ In our opinion, this case is possibly a lesion of SCVM.

The pathogenesis of SCVM is not well understood. However, nearly one third of SCVM patients had a history of Tamoxifen or hormone-replacement therapy, suggesting that hormones may possibly have a role in the development of the tumor. It has been postulated that the subepithelial mesenchymal cells of the lower female genital tract, which are normally estrogen and progesterone positive, tend to be the origin of most site-specific mesenchymal tumors that arising in this site.¹

Follow-up information was available in 30 cases of SCVM. Twenty-nine cases pursued a benign outcome with no evidence of recurrence or metastasis. Only one patient experienced local recurrence 9 years after initial excision biopsy.³ As there is limited potential for local recurrence, complete local excision is curable for SCVM. Nevertheless, long-term follow-up is recommended.

In conclusion, SCVM represents a distinctive entity which shows a marked predilection for the superficial aspect of the lower female genital tract, predominantly the vagina. Hormones may be involved in the growth of the tumor. Although this new entity is of little relevance to the gynecologist for therapeutic decisions, awareness of its unique clinical and histological features is helpful for the pathologists at differential diagnosis.