Figure 2.1. Benign vaginal mucosa with nonkeratinizing stratified squamous epithelium and underlying submucosal connective tissue containing elastic fibers and vascular channels.
Dyspareunia is a rare presenting symptom and may be associated with an abscessed Müllerian cyst.15 The cysts range from 1.4 to 7.0 cm and are lined by bland mucinous, endocervical, tubal, or endometrioid-type epithelium. The overwhelming majority have a benign prognosis; however, there is one report of an adenocarcinoma arising from a Müllerian cyst.9
TABLE 2.1: Clinicopathologic Characteristics of Vaginal Cysts
While rare, primary Bartholin gland adenocarcinoma can occur and is generally diagnosed in women over 40 years of age. Therefore, in this patient population, the cyst tissue should undergo careful macro- and microscopic review to rule out malignancy. The most frequent histologic subtypes include squamous cell carcinoma, adenocarcinoma, and adenoid cystic carcinoma (Figure 2.5A and B).18,19,20,21,22,23 The proposed criteria for a tumor arising in Bartholin glands include (1) the tumor should demonstrate areas of transition between the tumor cells and the normal gland, (2) the tumor should involve an area of the Bartholin gland, and (3) there should not be any evidence of another primary tumor.19 Refer to Table 2.1 and Chapter 1 for more details on Bartholin glands and associated pathologies.
Figure 2.3. Bartholin duct cyst. A-C, Images from the same case. A, A dilated cyst with mucinous glands are visible on low magnification (bottom of image). B and C, A mixture of ciliated and mucinous epithelium.
The overlying mucosa invaginates during the healing process and creates a cyst-like cavity filled with keratin debris and is lined by stratified squamous epithelium (Figures 2.9 and 2.10) and metaplasic changes may be seen (Figures 2.11 and 2.12). An EIC is generally small (mean, 1.6 cm) but may cause a mass effect resulting in urinary obstruction or stress incontinence and pain.12 If symptomatic or enlarging, squamous inclusion cysts can be locally excised.8
Figure 2.6. Skene duct cyst. The most common cause of a Skene cyst is infection. Note the extensive chronic inflammation surrounding the tangentially sectioned cyst.
postmenopausal women tend to develop in the upper vagina, are polypoid, and contain solid nests of metaplastic squamous epithelium with microcysts.28,29,30 The presence of sebaceous glands within the lesion has also been described.31 Tubulosquamous polyps are rare, and if suspected, immunohistochemical expression of CK7, prostate specific antigen, and/or NKX3.1 supports the diagnosis.27,29,30
Figure 2.8. Skene duct cyst. Columnar epithelium (bottom) and squamous epithelium (top) line the cyst.
Figure 2.9. Squamous inclusion cyst/epithelial inclusion cyst. Benign vaginal mucosa (top) with a squamous inclusion cyst in the underlying submucosa (bottom). Cysts typically form relatively close to the vaginal mucosal surface.
identified in the normal subepithelial connective tissue of the vagina comprise the central core of these polyps and occur in variable quantities to impart a hyper- or hypocellular stroma. The stromal cells give rise to this entity as a result of hormonal influence and will express immunohistochemical markers for desmin, estrogen receptor (ER), and progesterone receptor (PR).34,36 Rarely, FEPs may focally express myogenin.37 Local excision is generally curative. The FEPs that occur during pregnancy will generally regress in the postpartum period or are treated with local excision, if needed.34
Figure 2.11. Squamous inclusion cyst/epithelial inclusion cyst. Mucinous metaplasia of the cyst lining (right).
Figure 2.13. Cellular pseudosarcomatous FEP. The unremarkable squamous mucosa overlies a hypercellular stroma. The stroma of the polyp abuts the epithelial-stromal interface of the mucosa (a Grenz zone is absent).
Figure 2.15. Cellular pseudosarcomatous FEP. The stroma has a variable amount of collagen with mostly indistinct vessels and several bizarre, atypical stromal cells, including multinucleate forms.
Occurs in women of reproductive age
Recent endogenous or exogenous hormone exposure may increase cytologic atypia or mitotic activity
Benign overlying (+/- hyperplastic) vaginal squamous mucosa
The hypercellular stroma merges imperceptibly with the epithelial-stromal interface
The periphery of the lesion may become hypocellular in comparison with the central hypercellular stroma (a grenz zone is absent)
Multinucleated giant cells and atypical stellate stromal cells are invariably present
Increased mitotic activity (greater than 5 MFs per 10 HPFs); +/- atypical mitoses
No necrosis, cambium layer, rhabdomyoblasts, or smooth muscle differentiation
Rare local recurrences may occur following treatment by local excision
condyloma based on morphology alone can be challenging. A history of HPV infection or prior cervical dysplasia and high clinical suspicion may be helpful for favoring condyloma (see Pearls & Pitfalls). Additional details for approaching diagnostically challenging squamoproliferative lesions of the anogenital tract are further discussed in the vulvar chapter (see Benign squamous lesions of the vulva).
and age are also risk factors for developing VaIN, with the majority of VaIN 2-3 cases diagnosed in women over the age of 50 years.52 Clinically, it can be challenging to distinguish between low- and high-grade lesions on colposcopic examination, and therefore, biopsies of lesions are obtained for histologic examination to differentiate between VaIN 1 and VaIN 2-3.48,51
Figure 2.17. High-grade squamous intraepithelial lesion (VaIN3). The vaginal mucosa exhibits full-thickness cytologic atypia and lack of maturation.
Figure 2.18. High-grade squamous intraepithelial lesion (VaIN 3). The nuclear to cytoplasmic ratio is increased and there is full-thickness immaturity with cytologic atypia.
Low-grade lesions have koilocytosis with enlarged, wrinkled nuclei and perinuclear halos
Mitotic figures are limited to the lower one-third of the mucosa
Most VaIN 1 lesions exhibit patchy, focal, cytoplasmic, or negative expression of p16
High-grade lesions extend into the upper two-thirds (VaIN 2) or full thickness (VaIN 3) of the vaginal mucosa
Nuclei are enlarged and pleomorphic and mitotic figures are increased
Atypical mitoses may be present
p16 exhibits a strong, diffuse, “block-like” pattern
At least high-grade squamous intraepithelial lesion (VaIN 3).
Figure 2.19. Invasive squamous cell carcinoma. The squamous mucosa is acanthotic with hyperkeratosis and variably sized infiltrative nests visible at low-magnification.
Figure 2.20. Invasive squamous cell carcinoma. At the epithelialstromal interface, there are irregular invasive nests and individual cells of keratinizing squamous cell carcinoma with paradoxical maturation.
Figure 2.21. Invasive squamous cell carcinoma. Images from the same case. A, The surface epithelium is predominantly ulcerated with only focal VAIN at the edges (top left and right). B, Irregular nests of invasive squamous cell carcinoma infiltrate the vaginal stroma. There is an associated desmoplastic reaction with an extensive infiltrate of mixed inflammatory cells. C, Pleomorphic, hyperchromatic cells with keratin formation (top left).
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