Recent developments in vulvovaginal pathology

Abstract

This review discusses recent developments in vulvovaginal pathology. A variety of morphologically bland mesenchymal lesions occur at this site with considerable histological and immunohistochemical overlap. Aggressive angiomyxoma exhibits HMGA2 immunoreactivity in approximately 50% of cases, and this nuclear transcription factor is emerging as a useful and relatively specific marker for aggressive angiomyxoma, although occasional vulvovaginal smooth muscle neoplasms are positive. HMGA2 is useful in the diagnosis of aggressive angiomyxoma and its distinction from mimics, in the evaluation of resection margins and in the assessment of the presence or absence of residual disease in re-excisions. Aggressive angiomyxoma is almost invariably positive with oestrogen and progesterone receptors, and there have been several reports of a dramatic reduction in size following gonadotropin releasing hormone agonist therapy. Recent series of the relatively newly described entities cellular angiofibroma and superficial myofibroblastoma of the lower female genital tract have expanded upon the morphological spectrum of these neoplasms. Recently described mesenchymal lesions at this site include massive oedema and prepubertal vulval fibroma. Gastrointestinal stromal tumours have been described as primary neoplasms in the vagina, and rectovaginal septum and extragastrointestinal stromal tumour should be added to the differential diagnosis of a vulvovaginal mesenchymal lesion. Many mesenchymal lesions in the vulvovaginal region exhibit immunoreactivity with both CD34 and desmin, a somewhat unusual immunophenotype in mesenchymal lesions at other sites. It is now established that there are two distinct types of vulval intraepithelial neoplasia (VIN), most commonly termed classic and differentiated VIN, the former associated with human papillomavirus (HPV) infection. There are two corresponding types of vulval squamous carcinoma with HPV-associated and non-HPV-associated variants, the latter often arising in a vulval dystrophy and associated with p53 mutation. However, in some cases there is clinicopathological overlap between HPV-associated and non-HPV-associated squamous carcinomas, and immunohistochemistry with p16 is more reliable than morphology in predicting the presence of HPV. There have been new developments regarding Paget's disease of the vulva with the identification of markers that are useful in diagnosis and evidence that the neoplastic cells represent a proliferation of adnexal stem cells residing in sebaceous units. The newly described entity vaginal tubulo-squamous polyp typically exhibits immunopositivity with prostatic markers, possibly indicating derivation from displaced periurethral Skene's glands.

Differentiated vulvar intraepithelial neoplasia contains Tp53 mutations and is genetically linked to vulvar squamous cell carcinoma

“…[7][8][9] Clinicopathological overlap between HPV-associated and non-HPV-associated tumor may be observed in some cases, in which immunohistochemistry with p16 and HPV testing are more reliable than morphology for classification of both vulvar intraepithelial neoplasia and vulvar squamous cell carcinoma. 10,11 In the HPV-related pathway, classic VIN is generally accepted as a precursor of invasive carcinoma. Although differentiated vulvar intraepithelial neoplasia is a likely candidate for precursor of HPVnegative vulvar squamous cell carcinoma and has been implied by strong p53 immunohistochemical signal, the genetic relationship between these two entities is not well understood because of molecular heterogeneity in both cancers and precursors.…”

High-resolution genomic profiling of human papillomavirus-associated vulval neoplasia

“…It is now established that there are two distinct types of VSCCs, those associated with high-risk a human papillomavirus (hrHPV) and non-hrHPV-associated variants (McCluggage, 2009). HPV-positive tumours are frequently contiguous with classic vulval intraepithelial neoplasia (VIN) and usually arise in younger women.…”

Soft Tissue Lesions of Vulva: Histomorphology Vs Immunohistochemistry of These Rare Entities

“…The problem in accurately diagnosing is compounded by the very low incidence of these tumors which have till date been published only as case reports and few update articles (5) . The incidence is maximally reported in reproductive age group with a mean in the fourth decade (1)(2)(3) .…”

“…The overlapping clinical, morphological and immunehistochemical features of soft tissue lesions of the vulvovaginal area has been attributed to the common cell of origin -the mesenchymal stromal cells (5) . Table 1 shows the morphological and immunohistochemical profile in our cases.…”

“…Knowledge of the biological behaviour of these entities has been limited due to the rarity of the lesions. Nucci MR and Fletcher CD reviewed all the soft tissue lesions and updated the clinical aspects, biological behaviour and pathology in 2000 (1) followed by McCluggage in 2005 (2) and another one in 2009 (5) . However, since then there have been only case reports and few reviews or case series.…”