Mini-symposium: Gynaecological pathologyVulvovaginal mesenchymal lesions: a review and update
Introduction
A wide variety of benign and malignant mesenchymal lesions, neoplastic and non-neoplastic, can involve the vulvovaginal region. These lesions not uncommonly result in diagnostic problems for pathologists because of their relative rarity and also because of overlapping morphological features.1, 2, 3, 4 Some of the lesions are relatively specific to or are characteristic of the vulvovaginal region while others may occur at any site with no predeliction for this area. Table 1 lists the site specific or characteristic vulvovaginal mesenchymal lesions. When faced with a mesenchymal lesion at this site, pathologists often consider the site specific or characteristic entities but fail to think of other lesions which have no predeliction for this area but which may potentially occur here. Morphologically bland mesenchymal lesions are a particular problem1, 2, 3, 4 and it is important to distinguish between the various entities since their behaviour may differ markedly. For example, aggressive (deep) angiomyxoma is a locally infiltrative neoplasm with a marked tendency to local recurrence following excision whereas most of the other lesions are well circumscribed with limited tendency to local recurrence. Many of the site specific vulvovaginal mesenchymal lesions are thought to arise from the specialized subepithelial stroma of the lower female genital tract which extends from the cervix to the vulva and which is highly vascular, often has a somewhat myxoid appearance and commonly contains atypical multinucleate fibroblast-like cells (Figure 1). The stromal cells of this region are hormone responsive and exhibit positive immunohistochemical staining with oestrogen receptor (ER) and progesterone receptor (PR). As a consequence, most of the mesenchymal lesions specific to this site are positive with ER and PR. This zone is also positive with desmin, CD34 and CD99 and immunoreactivity with these markers is common in vulvovaginal mesenchymal lesions (Figure 2); this constitutes an unusual immunophenotype since mesenchymal lesions at other sites are uncommonly positive with this combination of markers. In distinguishing between the various mesenchymal lesions, immunohistochemistry plays a relatively minor role because of immunophenotypic overlap, although there are some important exceptions which will be stressed in this review.
Given the overlapping morphology and immunophenotype and the relative rarity of the various mesenchymal lesions at this site, such that an individual pathologist is unlikely to see more than an occasional case in his or her practice, a specialist opinion should be considered; this has the added advantage of facilitating accrual of significant numbers of these uncommon lesions which can be incorporated into case series.
In this review, I concentrate mainly on the site specific or characteristic mesenchymal lesions but briefly review some other mesenchymal lesions which may occur at this site.
Section snippets
Aggressive (deep) angiomyxoma
Aggressive angiomyxoma, synonymously referred to as deep angiomyxoma by the World Health Organization,5 was first described in 1983 by Steeper and Rosai as “aggressive angiomyxoma of the female pelvis and perineum”.6 It is an uncommon and morphologically bland and infiltrative mesenchymal neoplasm with a propensity for local recurrence following excision.
Angiomyofibroblastoma
Angiomyofibroblastoma was first described in 1992 as a benign vulval mesenchymal neoplasm distinct from aggressive angiomyxoma.24
Fibroepithelial stromal polyp (FESP)
Fibroepithelial stromal polyp (FESP) is the most common mesenchymal lesion occurring on the vulva and vagina.
Smooth muscle neoplasms
Smooth muscle neoplasms are uncommon, but not rare, in the vulvovaginal region. Most are located in the vulva but vaginal examples also occur.
Cellular angiofibroma
Cellular angiofibroma is an uncommon mesenchymal neoplasm that usually occurs on the vulva. Since the original description in 1997,57 there have been several further reports.58, 59, 60, 61, 62, 63 These neoplasms may also occur in the inguinal region of males.64
Superficial myofibroblastoma of the lower female genital tract (superficial cervicovaginal myofibroblastoma)
In 2001, Laskin et al. described a mesenchymal tumour arising in the superficial lamina propria of the cervix and vagina.67 The term superficial cervicovaginal myofibroblastoma was used to encompass the superficial location in the cervix or vagina and presumed myofibroblastic differentiation. A subsequent series of cases involved the vagina and the vulva and the term superficial myofibroblastoma of the lower female genital tract was proposed since some neoplasms occur on the vulva.68
Prepubertal vulval fibroma
This lesion was initially described by two different groups in 2004 and 2005.70, 71 In the first publication, the lesion was designated “prepubertal vulval fibroma”70 and in the second “childhood asymmetric labium majus enlargement”.71 The term prepubertal vulval fibroma is preferred and is now in widespread use. In one of the papers, it was suggested that this might represent the childhood equivalent of aggressive angiomyxoma (although there is no justification for this) and in the other it
Superficial angiomyxoma
This is a benign myxoid mesenchymal neoplasm which has a wide distribution but which may occur on the vulva. A synonym is cutaneous myxoma.
Vulval oedema
While vulval oedema due to a variety of underlying conditions is not rare, it is usually clinically recognized as such and surgical excision or biopsy not undertaken.75, 76, 77 However, there are occasional reports of “massive” or localized vulval oedema resulting in a large vulval mass. The pathogenesis is likely to be lymphoedema secondary to chronic lymphatic obstruction. Similar cases have been described involving the upper and lower extremities of obese patients.78
Reactive fibroblastic and myofibroblastic proliferation of the vulva (“cyclist's nodule”)
This entity was reported in competitive female cyclists79 and is probably analogous to perineal nodules occurring in male cyclists, although the histologic features of the latter are not well documented.
Gastrointestinal stromal tumour of the vagina and rectovaginal septum
Occasional gastrointestinal stromal tumours (GISTs) arise in the vagina or rectovaginal septum without connection to the rectal wall and present as a vaginal mass.80 When occurring at this site, they are referred to as extragastrointestinal stromal tumours (eGISTs). Morphologically these are identical to GISTs arising at more usual locations but the pathologist may not think of the diagnosis. They are likely to be misdiagnosed as a smooth muscle neoplasm and there may be considerable
Rhabdomyoma and rhabdomyosarcoma
Occasional rhabdomyomas have been reported in the vulvovaginal region, usually in the vagina.82, 83 These are usually polypoid lesions in women of reproductive age group and are typically small. They are covered by unremarkable squamous epithelium and within the stroma there are cells exhibiting skeletal muscle differentiation with eosinophilic cytoplasm and cross striations. Cells with cross striations may be easily seen or few in number and are set within a loose somewhat vascular stroma.
Mesenchymal proliferations associated with prolapsed fallopian tube
Occasionally following vaginal or more uncommonly abdominal hysterectomy, the fallopian tube prolapses and presents as a nodule at the vaginal vault. Histology shows ciliated and non-ciliated tubal type epithelium and often an associated inflammatory reaction. Occasional examples of prolapsed fallopian tube associated with a florid mesenchymal proliferation have been reported. In one case, the mesenchymal proliferation mimicked angiomyofibroblastoma and in another aggressive angiomyxoma.87, 88
Postoperative spindle cell nodule
Postoperative spindle cell nodule (PSCN), similar to that described elsewhere within the genitourinary tract, may occur in the vulvovaginal region, especially the vagina.89, 90, 91, 92 This is a reactive but proliferative pseudosarcomatous lesion that develops following an operative procedure, usually after a period of 1–12 weeks but sometimes later. PSCN is a benign lesion that rarely recurs following surgical removal. The history of a recent operative procedure is crucial in establishing the
Miscellaneous lesions
A wide variety of other mesenchymal lesions may occasionally involve the vulvovaginal region and it is stressed that when dealing with a mesenchymal lesion at this site, the pathologist should think widely and consider other lesions rather than just the site specific ones discussed. Mesenchymal lesions that have been reported in the vulvovaginal region include nodular fasciitis, fibromatosis, spindle cell lipoma, liposarcoma, neural tumours (benign and malignant, including myxoid variants),
Conclusions
An extremely large array of mesenchymal lesions may involve the vulvovaginal region, some relatively specific to this site and others with a more widespread distribution. When faced with such a lesion, the pathologist may need to think widely and consider a wide range of diagnoses and not just those lesions specific to the vulvovaginal region. Distinguishing the various site specific lesions may be difficult because of overlapping morphological features. Histological examination is the mainstay
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