Tumor-Like and Inflammatory Lesions
Condyloma Acuminatum
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These resemble their vulvar counterparts ( Chapter 1 ) except for a more frequent occurrence of flat condylomas and those with a ‘spiked’ surface due to asperities or minute surface projections that contain capillaries and scanty stroma. Diffuse vaginal involvement may occur.
Adenosis ( Figs. 3.1–3.9 )
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Prior to the use of diethylstilbestrol (DES) in pregnant women, vaginal adenosis was a rare finding in the reproductive and postmenopausal age groups. In contrast, adenosis was subsequently found in a third of asymptomatic young females exposed in utero to DES. Adenosis has also been associated with Stevens–Johnson syndrome and CO2 laser vaporization or topical 5-fluorouracil treatment of condylomas.
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Clinically, the mucosa is red and granular and fails to stain with iodine. The upper third of the vagina is almost always affected, whereas the middle and lower thirds are involved in 10% and 2% of cases, respectively.
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In 20% of DES-exposed females, congenital cervicovaginal malformations accompany the adenosis. Rare patients with diffuse vaginal adenosis unrelated to DES exposure have had an imperforate hymen.
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Microscopically, benign columnar epithelium of endocervical or tubo-endometrioid type replaces the normal squamous epithelium or forms glands within the superficial stroma. Tubo-endometrioid epithelium is particularly common in the lower vagina.
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Rare findings in adenosis include:
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Papillae (papillary adenosis); microglandular hyperplasia secondary to oral contraceptive use or pregnancy; Arias-Stella reaction in pregnancy; and intestinal metaplasia.
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Dysplastic changes (including adenocarcinoma in situ), usually within tuboendometrioid adenosis adjacent to clear cell carcinomas (CCCs), suggesting that they are premalignant in some cases. Similar dysplastic changes may be associated with adenosis associated with an imperforate hymen.
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The glands typically undergo replacement by metaplastic squamous epithelium with the formation of squamous pegs. Striking examples of this process may be misconstrued as squamous cell carcinoma.
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The pegs and small mucin-filled spaces (mucin droplets) within the pegs or surface squamous epithelium may be the only clues to adenosis.
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The glycogen-poor metaplastic squamous epithelium is gradually converted to normal glycogen-rich squamous epithelium.
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As alluded to above, adenosis is rarely complicated by the development of a vaginal or cervical adenocarcinoma (usually CCC) or by intraepithelial neoplasia (VaIN) (see corresponding headings).
Cysts ( Figs. 3.10 – 3.11 )
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These uncommon lesions are often an incidental finding in the reproductive or postmenopausal era but may be a symptomatic mass.
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They are of the following types:
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Müllerian-type cysts located anywhere in the vagina but most common anterolaterally. They are lined by endocervical-type, tubal, or endometrioid epithelium; focal metaplastic squamous epithelium may be present. Most of them probably arise from adenosis.
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Epithelial inclusion cysts, lined by squamous epithelium and containing keratin; most of these arise in sites of a previous episiotomy or laceration.
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Mesonephric (Gartner’s duct) cysts, lined by cuboidal to attenuated, nonciliated epithelial cells that lack cytoplasmic mucin and would be expected to be GATA3+. These arise from mesonephric remnants within the lateral vaginal walls.
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Endometriotic cysts ( Chapter 19 ) and Bartholin’s duct cysts ( Chapter 1 ).
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Rare cysts of urethral, paraurethral, or Skene’s origin lined by transitional, squamous, or columnar epithelium.
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Prolapsed Fallopian Tube ( Fig. 3.12 )
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This process is a rare complication of hysterectomy, usually of vaginal type. Tissue grossly resembling granulation tissue is usually seen at the vaginal apex. Rarely the appearance can mimic a cervical polyp.
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A misdiagnosis of papillary adenocarcinoma may occur if there is reactive atypia of the tubal epithelial cells. The presence of plicae and ciliated epithelial cells with a mostly benign appearance and a history of vaginal hysterectomy facilitate the diagnosis.
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Rarely a prolapsed tube has exhibited focal features resembling angiomyofibroblastoma ( Chapter 1 ) or aggressive angiomyxoma ( Chapter 1 ), potentially leading to misdiagnosis.
Postoperative Spindle Cell Nodule ( Fig. 3.13 )
Clinical features
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This lesion (PSCN) is a pseudosarcomatous spindle cell lesion that typically occurs within a surgical site in the lower genitourinary tract 1–12 weeks postoperatively.
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Upper vaginal examples usually follow a vaginal hysterectomy, whereas those in the lower vagina or vulva usually follow an episiotomy.
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Rare local recurrences have been successfully treated by re-excision.
Pathologic features
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Soft polypoid masses, usually <4 cm in size, are composed of spindle cells arranged in intersecting fascicles, often with a network of small blood vessels. The cells have plump, vesicular nuclei with prominent nucleoli but lack significant cytologic atypia. Mitotic figures are often numerous.
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Other features may include overlying ulceration, a deeper acute and chronic inflammatory infiltrate, focal hemorrhage and edema, and limited local infiltration.
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PSCNs are usually immunoreactive for vimentin, desmin, SMA, and surprisingly, cytokeratin.
Differential diagnosis with well-differentiated leiomyosarcoma
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This distinction may be difficult as some leiomyosarcomas (LMSs) may have only mild cytologic atypia and mitotic rates similar to or less than that of PSCNs. However, most LMSs exhibit at least focal severe nuclear atypia and usually lack the prominent vascular network of PSCNs.
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A history of a recent operation in the lesional site strongly favors a diagnosis of PSCN over that of LMS.
Fibroepithelial Polyp ( Figs. 3.14–3.17 )
Clinical features
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The vagina is the commonest site of fibroepithelial polyps (FEPs) in the female genital tract (FGT); less common sites include the vulva, or rarely, the cervix. FEPs usually occur in the reproductive and postmenopausal age groups (rarely, in infants) who may be asymptomatic or have postcoital bleeding or a mass.
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In ~20% of cases the patients are pregnant and 10% have received hormonal treatment (estrogen, oral contraceptives, tamoxifen, or an unspecified hormone), suggesting a hormonal etiology in some cases.
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Local excision is almost always curative; re-excision is successful in the rare instance of recurrence. Postpartum regression may occur.
Pathologic features
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Most FEPs are <4 cm in size but occasionally are as large as 12 cm. They are usually single but can be multiple and numerous, especially in pregnancy, and are sessile to pedunculated to villiform, soft to rubbery, and gray-pink; occasionally they have a botryoid appearance.
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FEPs are usually covered by unremarkable squamous epithelium, but occasionally it is koilocytotic or dysplastic. The stroma is fibrous to edematous and usually sparsely cellular. The vessels are thin- to thick-walled, the latter type usually located more centrally within the lesion.
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There is usually no distinct margin with the underlying normal tissue and the lesional stromal cells usually extend to the overlying squamous epithelium, without a Grenz zone.
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The polygonal to spindle to stellate stromal cells usually have scanty pale cytoplasm and tapering cytoplasmic processes with typically bland, mitotically inactive nuclei. Cells with multiple (or multilobed) nuclei are common, often in a wreath-like arrangement.
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Occasional FEPs, especially during pregnancy, exhibit features that can raise concern for malignancy (‘pseudosarcoma botryoides’): striking cellularity, which is often greater in the center of the lesion; bizarre, hyperchromatic, multiple or multilobed nuclei with prominent nucleoli; and mitotic figures (usually <3 but rarely >5 mf/10 hpf) that may be abnormal.
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The stromal cells typically stain for vimentin, desmin, and ER and PR, and have ultrastructural features of fibroblasts and myofibroblasts. Occasional FEPs contain myogenin+ stromal cells.
Differential diagnosis
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Aggressive angiomyxoma ( Chapter 1 ). These tumors are much less likely to be polypoid, are typically bulky and deep, contain numerous blood vessels of various sizes (including thick-walled vessels), often exhibit smooth muscle differentiation, have infiltrative borders and only rare multinucleated cells. This differential, however, may be difficult in a superficial biopsy specimen.
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Sarcoma botryoides. Features favoring this diagnosis vs a FEP with stromal atypia include an age <5 years; a history of rapid growth; a cambium layer containing small mitotically active cells with scanty cytoplasm and hyperchromatic nuclei (or similar cells elsewhere in the lesion); invasion of the squamous epithelium; cells with cytoplasmic cross striations; and staining for skeletal muscle markers.
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Superficial myofibroblastoma ( Chapter 1 ).
Tubulosquamous Polyp ( Fig. 3.18 )
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These lesions (TSPs) occur in postmenopausal, or less commonly, late reproductive, age groups. They are usually found in the upper vagina and are <3 cm in size.
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Microscopically, well-circumscribed nests of bland epithelial cells lie within a hypocellular fibrous stroma.
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Most nests are composed of glycogenated or nonglycogenated squamous cells, often with central necrosis, calcification, keratinization, or combinations thereof.
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Small tubules are also present, usually at the periphery of the squamous nests, and are lined by cuboidal cells with pale cytoplasm, sometimes with intracellular mucin.
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Uncommon findings include prominent basaloid epithelial differentiation, sebaceous glands, and mucinous and goblet cell differentiation.
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The epithelial elements are positive for cytokeratins, ER, and in some cases, PAP and/or PSA. Roma found diffuse positivity for GATA3 in the squamous component and focal positivity for NKX3.1 in the glandular component.
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Kelly et al. suggest that TSPs, as well as rare vaginal cases of ectopic prostate tissue, are derived from eutopic or ectopic Skene’s glands. Roma suggests that TSPs are synonymous with vaginal Brenner tumors.
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Aside from ectopic prostate tissue, the differential diagnosis includes vaginal Brenner tumor and benign mixed tumor. Contrasting features of the latter include a location near the hymenal ring and a predominant cellular spindle cell component.
Endometriosis ( Figs. 3.19–3.22 )
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Superficial vaginal endometriosis, which typically involves the vault, is rarer than its cervical counterpart, but is similar microscopically and for its predilection for involving sites of prior trauma and lack of associated pelvic endometriosis.
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Deep vaginal endometriosis is more common and is typically associated with pelvic endometriosis and involvement of the cul-de-sac and rectovaginal septum. When extensive this process may form nodular or polypoid mucosal masses (polypoid endometriosis) on the posterior vaginal wall.
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The differential diagnosis of vaginal endometriosis, particularly the superficial type, includes vaginal adenosis of the tuboendometrial variety; the latter, however, lacks endometrial stroma and the other features of endometriosis.
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The presence of endometriosis adjacent to a vaginal tumor favors a primary rather than a metastatic tumor. The former include endometrioid or clear cell adenocarcinoma (see corresponding headings in this chapter), endometrial stromal sarcoma, and adenosarcoma. Endometriosis-associated tumors are considered in Chapter 19 .
Nephrogenic Adenoma ( Figs. 3.23 – 3.24 )
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A nephrogenic adenoma arising in a urethral diverticulum may present as a vaginal mass and exhibit histologic features that can raise concern for a clear cell adenocarcinoma (CCC) which can also arise in a urethral diverticulum.
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Most of the patients studied by Medeiros and Young were <40 years of age. Microscopic examination showed the typical tubular, cystic, and papillary patterns of nephrogenic adenoma, as well as hobnail and clear cells in some cases.
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Awareness of this lesion and the absence of deep invasion, a diffuse growth of clear cells, nuclear atypia, and mitotic figures militate against CCC. GATA3 positivity favors nephrogenic adenoma, although only 40% of the latter are GATA3+.
Ectopias and Metaplasias ( Fig. 3.25 )
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Transitional cell metaplasia, similar to that occurring more commonly in the cervix ( Chapter 4 ), occasionally occurs in the vagina, sometimes in association with a transitional cell neoplasm.
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Mucinous epithelium other than that seen in adenosis (see Adenosis ) may occur in the vagina:
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Rare cases of vaginal endocervicosis and müllerianosis ( Chapter 19 ) have been reported. In one of the former cases, typical benign endocervical-like glands merged with an adenocarcinoma.
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Replacement of the vaginal epithelium by metaplastic mucinous epithelium occurred in a woman with cervical agenesis. The mucinous epithelium, which was focally atypical, involved the entire genital tract.
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One vaginal intestinal-type polyp has been reported.
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Rare vaginal examples of ectopic skin (with cutaneous appendages) or isolated ectodermal structures (sebaceous glands, hair follicle-like structures) have been reported. Single cases of thyroid/parathyroid tissue and prostatic tissue have also been described, the latter with features similar to this finding in the uterine cervix ( Chapter 4 ).
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Ectopic decidua within the vagina in pregnancy has clinically mimicked carcinoma in some cases. The histologic features are similar to those of eutopic and ectopic decidua in other sites.
Inflammatory and Infectious Lesions ( Figs. 3.26 – 3.27 )
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Lichen sclerosus ( Chapter 1 ) and Darier’s disease rarely involve the vagina. The latter can result in an abnormal Pap smear.
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Tuberculosis, mycoses (cryptococcosis, histoplasmosis), schistosomiasis, malacoplakia, xanthogranulomatous inflammation, a tumorous granulomatous reaction to keratin, mucicarminophilic histiocytosis ( Chapter 19 ), and ligneous inflammation ( Chapter 4 ) have occurred in the vagina.
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Emphysematous vaginitis is a self-limiting lesion in the reproductive and postmenopausal age groups. Subepithelial gas-filled cystic spaces are lined by foreign-body giant cells and chronic inflammatory cells. The cervix and/or vulva can also be involved. The pathogenesis is obscure; some cases appear to be caused by gas-forming bacteria.
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Desquamative inflammatory vaginitis can occasionally be due to vaginal toxic shock reaction caused by toxin 1 (TSST-1)-producing Staphylococcus aureus infection.
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Polypoid granulation-type tissue may be encountered, most commonly post procedure or in the postpartum setting.
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In patients who undergo surgical construction or re-construction of the vagina utilizing an intestinal segment, changes similar to diversion colitis may be seen and have been termed diversion neovaginitis. These changes include acute and chronic inflammation, increased lymphoid aggregates, crypt distortion, and Paneth cell metaplasia.
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Tumor-like masses due to a foreign-body reaction.
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Snover et al. described a vaginal fibrohistiocytic reaction with a storiform pattern that mimicked fibrous histiocytoma except for a foreign-body reaction to polarizable material.
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Russell et al. described a 3.5 cm vaginal mass due to the filler substance polyacrylamide hydrogel (Aquamid). Pools of homogeneous basophilic, alcianophilic, and mucicarminophilic material associated with a foreign-body reaction were found in hyalinized tissue and vascular spaces.
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Other Tumor-Like Lesions
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Multinucleated stromal giant cells, identical to those within FEPs (see corresponding heading), were found in the vagina in 12% of cases in one autopsy study.
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Mesonephric remnants and/or mesonephric hyperplasia ( Chapter 4 ) occur in the vagina and can be associated with an abnormal Pap smear.
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Benign pigmented lesions of the vaginal mucosa include melanosis, blue nevus of usual and cellular type, atypical melanocytic hyperplasia, and ochronosis.
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Fadare has described ‘vaginal stromal sclerosis’ in women 50–62 years of age who had dyspareunia, vaginal atrophy, and a vaginal nodule or plaques. The lesions consisted of subepithelial zones of sparse fibroblastic stromal cells separated by collagen and elastic fibers.
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Rare examples of vaginal involvement by retroperitoneal fibrosis have been documented.
Benign Tumors
Epithelial Tumors ( Figs. 3.28 – 3.29 )
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Most benign papillary squamous lesions of the vagina are condylomas, noncondylomatous vaginal squamous papillomas being rare and resembling those of the cervix. Vestibular squamous papillomatosis is considered in Chapter 1 .
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Rare vaginal mucosa papillomas, usually in children, resemble müllerian papillomas of the cervix ( Chapter 4 ), and may clinically suggest embryonal rhabdomyosarcoma.
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Two otherwise similar papillomas that were mural (nonmucosal) consisted of papillae, glands, and solid areas; the lesional cells had eosinophilic cytoplasm and bland nuclei.
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One müllerian papilloma recurred many times over a 40-year period, eventually progressing to a clear cell carcinoma.
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Rare vaginal tubulovillous adenomas of colonic type have contained goblet cells (with enteric mucin) and Paneth cells. Some have showed focal high-grade dysplasia or merged with an adenocarcinoma (see Mucinous Adenocarcinomas ).
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‘Seborrheic-keratosis-like’ lesion of the vagina and cervix (see Chapter 4 ).
Epithelial-Stromal Tumors
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Ovarian-type benign epithelial stromal tumors occurring in the vagina have included rare Brenner tumors (some of which were probably examples of tubulosquamous polyp; see corresponding heading) and endometrioid papillary cystadenofibroma.
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Lesions resembling mammary fibroadenomas that involved the upper vagina were described by Moore et al. The glands were lined by a double epithelial layer (luminal and basal with focal squamous differentiation in one case). The cells were PAX8+/GATA3+; the basal cells were also p63+/CK5/6+. The stroma was comprised of bland fibroblastic cells.
Mixed Tumor (Spindle Cell Epithelioma) ( Figs. 3.30–3.34 )
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These rare tumors of uncertain histogenesis occur near the hymenal ring in the reproductive and postmenopausal age groups. They are typically an incidental clinical finding or the patient notices a slowly enlarging, painless mass. Occasional tumors have recurred after local excision.
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The tumors are usually superficial, <5 cm in size, and well circumscribed. The cut surface is usually solid, gray to white, and sometimes focally myxoid.
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The characteristic microscopic appearance is a predominant to exclusive component of usually closely packed spindle cells in intersecting fascicles; vague whorls, cords, nests, and hyaline spherules may be seen. Obvious epithelial elements in the form of nests of mature squamous epithelium (sometimes with keratin) and glands lined by mucinous or nonspecific epithelium are usually present, but may be scanty.
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The spindle cells have scanty cytoplasm, round to spindled nuclei, fine chromatin, indistinct nucleoli, and rare to absent mitoses. The cellularity varies with the amount of intercellular alcianophilic material and collagen.
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The spindle cells typically stain for epithelial markers (AE1/3, CK7), mesenchymal markers (SMA, desmin, h-caldesmon), CD10, PR, and WT-1 (Berdugo et al.).
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Ultrastructural findings suggest that these tumors are purely epithelial rather than mixed epithelial stromal tumors.
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The differential diagnosis includes smooth muscle and endometrial stromal tumors, the immunoprofiles of which partly overlap with that of the mixed tumor. The typical location of the tumor and the usual admixture of well-differentiated epithelial elements with the spindle cells facilitate the diagnosis. A metastatic tumor may rarely be a consideration but many differences, including clinical findings, aid in reaching the correct diagnosis.
Aggressive Angiomyxoma, Angiomyofibroblastoma, Cellular Angiofibroma, Myofibroblastoma
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See Chapter 1 .
Leiomyoma ( Figs. 3.35 – 3.36 )
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Leiomyomas are the most common vaginal mesenchymal tumor and typically occur in the reproductive and postmenopausal age groups. Larger tumors may cause pain, dyspareunia, bleeding, dystocia, or urinary tract symptoms. The tumors arise anywhere in the vagina.
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The gross and microscopic features are similar to their uterine counterparts ( Chapter 9 ). They are usually submucosal and composed of spindle cells or occasionally epithelioid cells. About 10% of tumors have myxoid foci and rare tumors have bizarre nuclei.
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Tumors in pregnancy may show increased mitotic activity. Rare tumors may recur in one or more pregnancies, suggesting hormone dependency.
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The differential diagnosis is usually with leiomyosarcoma (see separate section later in Chapter 3).
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Extragastrointestinal stromal tumors are also in the differential diagnosis (see separate section later in Chapter 3).
Rhabdomyoma ( Figs. 3.37 – 3.38 )
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These rare FGT tumors are most common in the vagina (occasionally in the vulva and cervix), typically occurring in the reproductive or postmenopausal age groups as a small (<3 cm) smooth, solitary, submucosal mass cured by local excision.
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Most tumors are covered by intact squamous epithelium and are composed of variable numbers of benign, amitotic, skeletal muscle cells (eosinophilic cytoplasm, cross striations, positivity for myogenin and myoD) that appear round or strap-shaped depending on the plane of section. There is a variable amount of vascular fibromyxoid stroma.
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The tumors should be thoroughly sampled as rare tumors contain an admixed component of rhabdomyosarcoma or an appearance intermediate between the two lesions.
Differential diagnosis
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Fibroepithelial polyps. These lesions lack skeletal muscle differentiation.
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Fetal rhabdomyomas. These have some morphologic resemblance to genital rhabdomyomas but typically occur in the head and neck of children.
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Embryonal rhabdomyosarcoma. These tumors, in contrast to rhabdomyomas, occur in infants or children, exhibit rapid growth, and have a cambium layer, mitotic activity, and an infiltrative border.
Miscellaneous Benign Tumors
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Rare vaginal examples of dermoid cyst, adenomatoid tumor, myxoma, solitary fibrous tumor, angiomyolipoma, hemangioma, glomus tumor, glomangioma, glomangiomyoma, mesenchymoma (containing skeletal and smooth muscle and fat), neurofibroma (including one with rhabdomyomatous differentiation [‘Triton’ tumor]), schwannoma (typical and cellular), granular cell tumor, and paraganglioma have been reported.
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Two vaginal myoepitheliomas (both in women in their fifth decade) were circumscribed nodules subjacent to the squamous epithelium and composed of spindle and/or epithelioid cells with bland nuclear features. The lesional cells stained with both epithelial and myoid markers.
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Moore et al. reported two fibroadenoma-like lesions in the upper vagina. The glands had a double lining of luminal and basal cells with focal squamous differentiation in one case. The stroma was comprised of bland fibroblastic cells with occasional atypical symplastic cells in one tumor. The luminal and basal cells were PAX8+/GATA3+ and largely ER−/PR−; the basal cells were also p63+/CK5/6+.
Malignant Tumors
Vaginal Intraepithelial Neoplasia (VaIN) ( Fig. 3.39 )
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VaIN is only 1% as common as its cervical counterpart and tends to occur in an older age group, although its frequency is increasing in younger women. The usual presentation is an abnormal Pap smear.
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There is usually a prior or synchronous preinvasive or invasive squamous neoplasm of the cervix or vulva, in some cases possibly representing multicentric clonal lesions (Vinokurova et al.). Other risk factors include immunosuppression, smoking, prior pelvic irradiation, and adenosis.
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The upper third of the vagina is usually involved. The lesion may be clinically visible as a raised, roughened, white to pink lesion or only visible colposcopically. About 50% of lesions are multifocal.
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The microscopic and immunohistochemical features are as for cervical SILs ( Chapter 5 ).
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LSIL is synonymous with VaIN1 and HSIL collectively denotes VaIN2 and VaIN3.
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Sopracordevele et al. found occult invasion in 10% of their cases.
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HPV DNA is detected in the tumor cells in at least 80% of cases; even VaIN1 lesions can contain high-risk HPV (Srodon et al.).
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Local recurrence is more likely with nonextirpative treatment. Patients with VaIN2/VaIN3 are at high risk for recurrence or invasive SqCC. Progression may be more likely in patients who have received pelvic irradiation for an unrelated lesion.
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Ki-67 and p16 staining can facilitate the differential diagnosis of VaIN with reactive atypia, postradiation atypia, atrophy, transitional cell metaplasia, and immature squamous metaplasia within adenosis. Hampl et al., however, found that only 62% of vaginal HSILs were p16+ (vs 85% for vulvar HSILs and 90% of cervical HSILs).
Squamous Cell Carcinoma ( Figs. 3.40 – 3.41 )
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SqCCs account for about 90% of primary vaginal cancers and 1% of FGT cancers. The ratio of vaginal:cervical SqCCs is ~1 : 50.
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The risk factors are those for VaIN as well as multiple sexual partners, early age at first intercourse, and antibodies to HPV16. About 80% of vaginal SqCCs contain HPV DNA, most commonly HRHPV 16/18. Up to half the patients have a history of hysterectomy for benign disease or cervical squamous neoplasia.
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The patients are usually in the late reproductive or postmenopausal age groups; 10% are <40 years of age. The presenting features include vaginal bleeding or discharge, urinary symptoms, abnormal cytology, a mass, or combinations thereof.
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Most tumors arise in the upper third of the vagina, vary from polypoid to ulcerating, and microscopically resemble typical keratinizing or nonkeratinizing cervical SqCCs ( Chapter 5 ).
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Uncommon variants include verrucous ( Chapter 2 ), warty ( Chapter 5 ), papillary ( Chapter 5 ), sarcomatoid ( Chapter 5 ), lymphoepithelioma-like ( Chapter 5 ), and squamotransitional (see next section).
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Almost all HPV+ tumors are diffusely p16+ and are usually nonkeratinizing, warty, or basaloid subtypes (Fuste et al.).
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The most important prognostic factor is stage (see Table 3.1 ). Survival figures from a Stanford study of patients treated with radiation were 94% (stage I), 80% (stage II), 50% (stage III), and 0% (stage IV).
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Hellman et al. found that older age and tumors ≥4 cm were adverse prognostic factors whereas Wolfson et al. using multivariant analyses found that the risk of death for stage I and II tumors >2 cm was doubled.
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Low histologic grade, tumor size of <2 cm (or <3 cm in other studies), and an absence of lymphatic invasion have been favorable prognostic factors in some studies.
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The term ‘microinvasive SqCC’ has been proposed for tumors that invade <2.5 mm but this term has not been uniformly adopted, as such tumors are occasionally fatal.
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The LAST standardization project for HPV-associated lesions recommends the use of the term ‘superficially invasive squamous cell carcinoma (SISCCA)’ for a minimally invasive SqCC of the lower anogenital tract that has been completely excised and potentially amendable to conservative surgical therapy. However, no recommendation was provided regarding tumors primary to the vagina as there was insufficient data to define early invasion at this site.
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Larsson et al. found that women with HPV+ tumors, especially if HPV16+, had a better survival than those with HPV− tumors. Similarly, Feldbaum et al. found that p16+ tumors had a better survival than p16− tumors (~49 m vs ~25 m).
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The AJCC 8th edition staging system for vaginal carcinomas added substaging to the pT1 category. pT1a tumors are confined to the vagina and ≤2.0 cm in size, whereas pT1b tumors are confined to the vagina but >2.0 cm in size.
Table 3.1
FIGO staging of carcinoma of the vagina
Stage I
The carcinoma is limited to the vaginal wall
Stage II
The carcinoma has involved the subvaginal tissue but tumor has not extended to the pelvic wall
Stage III
The carcinoma has extended to the pelvic wall or pelvic or inguinal lymph node metastasis
Stage IV
The carcinoma has extended beyond the true pelvis or has involved the mucosa of the bladder or rectum
IVA
Tumor invades bladder and/or rectal mucosa and/or direct extension beyond the true pelvis
IVB
Spread to distant organs
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Transitional and Squamotransitional Cell Carcinomas ( Fig. 3.42 )
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Rare vaginal carcinomas with transitional cell differentiation have been either pure transitional cell carcinomas (TCCs) or squamotransitional cell carcinomas (STCCs).
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Pure vaginal TCCs resemble urinary tract TCCs. Some have been associated with the latter and/or vaginal transitional cell metaplasia. One tumor had a CK7+/CK20+ phenotype. Most of the reported tumors were noninvasive and indolent; rare invasive tumors have had nodal metastases.
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Vaginal STCCs have clinical and morphologic features that overlap with papillary SqCCs. In some cases, there is a synchronous or metachronous HSIL and/or an invasive SqCC of the vagina or cervix. A CK7+/CK20- phenotype is typical; HPV16 was found in one tumor.
Clear Cell Adenocarcinoma ( Figs. 3.43–3.48 )
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Vaginal clear cell carcinomas (CCCs) were very rare prior to the use of diethlystilbestrol (DES) in the early 1950s; most occurred in postmenopausal women. Some arose from vaginal endometriosis.
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Subsequently, about 400 vaginal CCCs were reported by 1994, mostly in adolescents and young adults (median age, 19 years). Approximately 80% of these patients were exposed in utero to DES or another type of synthetic estrogen. The ratio of vaginal to cervical DES-related CCCs ( Chapter 6 ) is 2 : 1.
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In a recent study with 40-year follow-up from the CCC Registry, Huo et al. found that 80% of DES-related vaginal (and cervical CCCs) occurred in those 15–31 years of age (the oldest being 55 years old); a small second peak occurred around the age of 42. The risk was highest in the 1951–1956 birth cohort. By age 50, the cumulative risk of CCC was 1 per 750 exposed women.
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Larger CCCs may cause bleeding; asymptomatic small tumors are often found on examination prompted by a DES history. The upper third of the anterior vaginal wall (the most common site of adenosis) is usually involved; rare tumors are multicentric.
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CCCs range from microscopic to large polypoid, nodular, flat, or ulcerated tumors. Small tumors may not be seen colposcopically if covered by intact mucosa, but may be palpable.
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The microscopic features are identical to CCCs in other FGT sites ( Chapter 6 , Chapter 8 , Chapter 14 ). Adenosis (see corresponding heading), which may be atypical, usually abuts the tumor.
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The differential diagnosis includes microglandular hyperplasia and Arias-Stella reaction, both of which may occur in vaginal adenosis (see Differential Diagnosis under these headings in Chapter 4 ).
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About 15% of stage I tumors and 40% of stage II tumors have nodal spread at presentation. About a third of the recurrences are extra-abdominal (vs 10% for vaginal SqCCs).
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The survival rates are 90% for stage I tumors and almost 100% for small incidentally discovered tumors. DES-related CCCs have a better prognosis than sporadic CCCs, a difference that appears to be unrelated to tumor stage or size.
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