Clinical overview
The vagina is an uncommon primary site for neoplasia, and that single fact dominates everything you say about vaginal tumours in the FCOG(SA) exam. Primary vaginal carcinoma accounts for only 1–2% of all gynaecological malignancies; the overwhelming majority of malignant tumours found in the vagina are secondary — direct extension from cervix, vulva, endometrium, bladder or rectum, or metastatic deposits. The diagnostic discipline that follows is strict: a malignancy is classified as primary vaginal only when the cervix and vulva are not involved, because if either is involved the lesion is classified as a cervical or vulvar primary by convention. This is not pedantry — it changes the staging system, the field of treatment, and the prognosis.
Benign vaginal tumours and tumour-like lesions are, by contrast, common and mostly inconsequential: epithelial inclusion cysts, Gartner duct (mesonephric) cysts, müllerian cysts, fibroepithelial polyps, and the occasional leiomyoma. The clinical art is separating a benign cyst or polyp that can be reassured or simply excised from the rare malignant lesion that demands biopsy and referral. In the South African context two further threads run through this topic and recur in the exam: the dominant role of HPV in vaginal squamous neoplasia in a population with very high HIV prevalence, and the historical but examinable association of clear cell adenocarcinoma with in-utero diethylstilboestrol (DES) exposure. This chapter is weighted, as the objective demands, toward pathological features — gross and microscopic — of both benign and malignant vaginal tumours, with the assessment and management sections kept to principles. It links closely to hpv-pathology, cervical-carcinogenesis, cervical-screening-sa, vulval-carcinoma and genital-tract-cysts.
Core knowledge
Anatomy and field considerations
The vagina is a fibromuscular tube lined by non-keratinised stratified squamous epithelium over a lamina propria, then a muscularis (inner circular, outer longitudinal smooth muscle) and an adventitia. There are no glands in the normal vaginal wall — mucus comes from the cervix and Bartholin glands — so a glandular lesion in the vagina is intrinsically abnormal and points to embryonic remnants (mesonephric/müllerian), adenosis, endometriosis, or adenocarcinoma. The upper two-thirds drains lymph to the pelvic (obturator, internal/external iliac) nodes and the lower third to the inguinofemoral nodes — a split that mirrors the embryological junction and explains the dual nodal spread of vaginal cancer depending on tumour level.
Benign tumours and tumour-like lesions
Figure D12.1 — Benign vaginal tumours and cysts: Gartner duct, Müllerian, squamous papilloma and fibroepithelial polyp — origin, appearance and the always-send-histology rule.
These are best learned as a short, gross-plus-microscopic list, because the exam tests recognition.
- Epithelial inclusion (epidermoid) cyst — the commonest vaginal cyst; usually in the lower posterior/lateral wall, often at a site of prior obstetric laceration or episiotomy repair where squamous epithelium is buried. Gross: small, firm, mobile. Micro: lined by stratified squamous epithelium with keratin debris. Benign; excise only if symptomatic.
- Gartner duct cyst — a mesonephric (Wolffian) remnant; characteristically along the anterolateral vaginal wall. Micro: lined by low cuboidal/columnar non-mucinous, non-ciliated epithelium. Usually asymptomatic; can rarely enlarge or become infected.
- Müllerian (paramesonephric) cyst — derived from müllerian remnants; lined by mucinous endocervical-type, tubal-type ciliated, or endometrioid epithelium. The presence of mucin/cilia distinguishes it from a Gartner cyst.
- Bartholin duct cyst/abscess — strictly at the introitus (vestibule), but classically examined alongside; lined by transitional/squamous epithelium.
- Fibroepithelial polyp — a benign stromal-epithelial polyp; soft, pedunculated. Micro: oedematous fibrovascular core covered by squamous epithelium, sometimes with bizarre but benign stromal cells (a recognised diagnostic pitfall — do not overcall as sarcoma).
- Vaginal leiomyoma — the commonest benign solid mesenchymal tumour of the vagina; arises from the muscularis. Gross: firm, whorled, well-circumscribed. Micro: interlacing fascicles of bland spindle smooth-muscle cells, low mitotic count, no atypia/necrosis.
- Vaginal adenosis — not a tumour but a key precursor concept: glandular (columnar müllerian) epithelium present in the vagina where there should be none. Strongly associated with in-utero DES exposure, and the soil from which clear cell adenocarcinoma can arise.
Pre-malignant squamous disease — VaIN (using WHO-2020 / LAST terminology)
Vaginal intraepithelial neoplasia is the squamous precursor and is HPV-associated, sharing biology with cervical and vulvar lesions. Under the WHO Classification of Tumours of the Female Genital Tract, 5th edition (2020) and LAST terminology, the two-tier system is used: LSIL (≈ VaIN 1, low-grade) and HSIL (≈ VaIN 2–3, high-grade), the latter the true precursor of invasive squamous carcinoma. Microscopically, HSIL shows full- or near-full-thickness loss of squamous maturation, nuclear crowding and pleomorphism, suprabasal mitoses and apoptotic bodies; block-positive p16 immunostaining marks transcriptionally active high-risk HPV (16/18 and others) and supports the diagnosis. VaIN is frequently multifocal and often coexists with cervical/vulvar HSIL as part of a field effect across the lower genital tract — a point of real importance in HIV-positive South African women, in whom HPV persistence, multifocal disease and progression are all more frequent.
Malignant tumours
Figure D12.2 — Primary vaginal malignancies: HPV-related squamous cell carcinoma, plus the exam traps — DES-related clear-cell adenocarcinoma and infantile sarcoma botryoides.
Primary squamous cell carcinoma — the dominant malignancy
Squamous cell carcinoma (SCC) accounts for roughly 85–90% of primary vaginal cancers. Most are HPV-associated (high-risk HPV, p16 block-positive), arising via HSIL; a smaller subset in older women is HPV-independent. The commonest site is the upper third of the posterior wall. Gross appearance ranges from an exophytic fungating mass to an ulcerated, indurated plaque or an annular constricting lesion. Microscopically it is a conventional keratinising or non-keratinising SCC: nests and sheets of malignant squamous cells with intercellular bridges, keratin pearls (in well-differentiated tumours), nuclear pleomorphism and infiltrative stromal invasion with a desmoplastic response. Spread is by direct local extension (into the paravaginal tissues, bladder anteriorly, rectum posteriorly), lymphatic spread (to pelvic nodes from the upper vagina, inguinofemoral nodes from the lower vagina), and late haematogenous dissemination.
Adenocarcinoma, including clear cell adenocarcinoma
Adenocarcinoma is far less common. The exam-critical entity is clear cell adenocarcinoma, the classic lesion of young women with in-utero DES exposure arising on a background of vaginal adenosis, typically on the anterior wall of the upper vagina. Microscopically it shows tubulocystic, papillary and solid patterns with clear (glycogen-rich) and characteristic hobnail cells — nuclei bulging into the lumen on scant apical cytoplasm. DES was withdrawn decades ago, so this is now historically rare, but it remains a favourite because of its precursor lesion and age profile. Other vaginal adenocarcinomas arise from müllerian remnants, adenosis, or endometriosis (endometrioid type).
Mesenchymal and other malignancies
- Embryonal rhabdomyosarcoma (sarcoma botryoides) — the most important malignant vaginal tumour of infancy and early childhood (typically <5 years). Gross: a soft, grape-like (botryoid) polypoid mass protruding from the vagina. Micro: small round/spindle malignant cells with a hypercellular cambium layer beneath the epithelium; cross-striated rhabdomyoblasts (strap cells) are diagnostic and stain for desmin and myogenin/MyoD1.
- Leiomyosarcoma — the commonest pure vaginal sarcoma of adults; distinguished from benign leiomyoma by coagulative tumour-cell necrosis, increased mitoses, and cytological atypia.
- Malignant melanoma — rare, aggressive, arises from mucosal melanocytes usually in the lower third/anterior wall; pigmented or amelanotic; S100/SOX10/HMB-45/Melan-A positive; poor prognosis (see melanoma).
- Metastatic / secondary tumours — remember these are the commonest malignant tumours encountered in the vagina overall: direct spread from cervix or vulva, and metastases from endometrium, choriocarcinoma/GTN deposits (vascular vaginal nodules — biopsy can bleed catastrophically), colorectum and bladder.
| Tumour | Typical patient / site | Key microscopic feature |
|---|---|---|
| Epithelial inclusion cyst | Lower wall, post-obstetric | Squamous lining + keratin |
| Gartner duct cyst | Anterolateral wall | Cuboidal/columnar, non-mucinous |
| Müllerian cyst | Variable | Mucinous/ciliated/endometrioid |
| Vaginal leiomyoma | Adult, muscularis | Bland spindle smooth muscle |
| HSIL (VaIN 2–3) | HPV+, often HIV+, multifocal | Full-thickness atypia, p16 block+ |
| Squamous cell carcinoma | Older, upper posterior wall | Invasive nests, keratin pearls |
| Clear cell adenocarcinoma | Young, DES/adenosis, anterior | Clear + hobnail cells |
| Sarcoma botryoides | Infant/child | Botryoid mass, cambium layer, strap cells |
| Melanoma | Lower/anterior wall | Atypical melanocytes, HMB-45/SOX10+ |
Assessment
Figure D12.3 — Secondary until proven primary: most vaginal malignancy spreads from cervix/endometrium/vulva; the rule before diagnosing a primary, with FIGO clinical staging.
Most vaginal tumours present with abnormal bleeding (postcoital, intermenstrual or postmenopausal), discharge, a palpable/protruding mass, or are found incidentally at speculum examination or during cervical screening. Because the posterior upper vagina is easily hidden by the speculum blades, a lesion is classically missed unless the speculum is slowly rotated and withdrawn while inspecting all four walls — a high-yield exam point. Any persistent vaginal lesion needs a biopsy for histological diagnosis; cytology alone is insufficient to characterise a mass.
In South Africa, vaginal HSIL is most often detected through the cervical screening pathway. Per the SASOG/BetterGyn cervical screening guideline (2024) and NDoH National Cervical Cancer Screening Policy, the public-sector programme screens women 30–50 with 3 smears 10-yearly historically, transitioning toward HPV-DNA primary screening (informed by the DiaVACCS trial) with triage by genotyping (16/18)/cytology/VIA and treatment by thermal ablation or LLETZ. HIV-positive women are screened at HIV diagnosis and approximately 3-yearly thereafter regardless of age — directly relevant because the same high-risk HPV that drives CIN drives VaIN, and the lower genital tract should be assessed as one field. An abnormal screen with no cervical lesion, or persistent abnormal cytology after hysterectomy for HSIL, should prompt colposcopy of the vaginal vault and walls with Lugol iodine (see colposcopy). Confirmed invasive disease is staged with examination under anaesthesia, biopsy, cystoscopy/proctoscopy as indicated, and cross-sectional imaging (MRI for local extent, PET-CT/CT for nodes and metastases). Vaginal cancer is staged with the FIGO clinical system for vaginal carcinoma; do not misapply the FIGO 2018 cervical or FIGO 2023 endometrial molecular systems, which belong to those primaries.
Management
Management is by principle for this pathology objective and should be delivered through a gynaecological-oncology multidisciplinary team.
- Benign lesions: reassure and observe asymptomatic cysts; excise symptomatic, enlarging, or diagnostically uncertain cysts, polyps and leiomyomas, always with histology to confirm benignity (and to avoid the fibroepithelial-polyp-overcalled-as-sarcoma trap).
- VaIN/HSIL: options include excision (partial vaginectomy or wide local excision), ablation (laser/thermal/electrofulguration), or topical imiquimod; multifocality and the field effect mean close follow-up is essential, particularly in HIV-positive women, in whom antiretroviral therapy with immune reconstitution improves control of HPV disease — South African first-line is TLD (tenofovir + lamivudine + dolutegravir).
- Invasive vaginal carcinoma: most cases are managed with definitive (chemo)radiation — external-beam radiotherapy with concurrent weekly cisplatin where appropriate, combined with image-guided brachytherapy to deliver tumoricidal dose while sparing bladder and rectum, following the modern EMBRACE-II / GEC-ESTRO image-guided adaptive brachytherapy principles extrapolated from cervical practice. Early, small lesions may be amenable to surgery. The proximity of bladder and rectum makes the therapeutic window narrow and brachytherapy expertise central.
- Sarcoma botryoides is treated with multimodal therapy — chemotherapy with conservative surgery ± radiotherapy — in a paediatric-oncology setting, with markedly improved survival under modern protocols.
- Vaginal melanoma is treated surgically where resectable, but prognosis remains poor.
- Prevention is the strategic answer in the SA exam: HPV vaccination prevents the high-risk-HPV disease that underlies most vaginal squamous neoplasia. The WHO Cervical Cancer Elimination Strategy (90-70-90 by 2030) frames this; South Africa has a school-based HPV programme since 2014 (girls 9–14), the single-dose schedule is WHO-endorsed (2022) and adopted across Africa, and the 9-valent (nonavalent) vaccine gives broadest cover.
Red flags / pitfalls
- A vaginal malignancy is secondary until proven primary. Always exclude cervical and vulvar involvement — if either is involved it is not a vaginal primary, and the staging/treatment field changes entirely.
- Don't miss the posterior upper vagina. Lesions hide behind the speculum; inspect all walls on slow rotation and withdrawal.
- A vascular vaginal nodule may be metastatic GTN — choriocarcinoma deposits are friable and bleed torrentially. In a woman of reproductive age with such a lesion, check βhCG and think trophoblastic disease before biopsying (see gtd-pathology).
- Fibroepithelial polyp with bizarre stromal cells is benign — over-diagnosing it as sarcoma is a classic histology trap; conversely, true leiomyosarcoma is defined by necrosis, mitoses and atypia.
- Vaginal adenosis / glandular epithelium in a young woman should trigger thoughts of DES exposure and clear cell adenocarcinoma surveillance.
- Persistent abnormal cytology after hysterectomy for HSIL is vaginal vault disease until excluded — examine and colposcope the vault, do not assume the problem was "removed".
- In HIV-positive women, expect multifocal, persistent and faster-progressing HPV disease; assess the cervix, vagina and vulva as one field and optimise ART.
Evidence anchors
- WHO Classification of Tumours of the Female Genital Tract, 5th edition (2020) — histological typing of all vaginal benign and malignant tumours; LAST/2014 LSIL–HSIL terminology (replacing VaIN 1–3) with HPV-associated vs HPV-independent distinction and p16 as the surrogate of high-risk HPV.
- SASOG / BetterGyn South African Cervical Cancer Screening Clinical Guideline (2024) and NDoH National Cervical Cancer Screening / Prevention & Control Policy — the SA source of truth for screening pathways (transition to HPV-DNA primary screening, DiaVACCS-informed; cytology 30–50, 3 smears 10-yearly historically; thermal ablation/LLETZ treatment) and the rule that HIV-positive women are screened at HIV diagnosis and ≈3-yearly regardless of age.
- WHO Cervical Cancer Elimination Strategy (2020) — 90-70-90 by 2030, single-dose HPV schedule (WHO 2022, adopted across Africa), 9-valent vaccine, and SA's school-based programme since 2014 — the preventive frame for HPV-associated vaginal squamous neoplasia.
- EMBRACE-II / GEC-ESTRO image-guided adaptive brachytherapy standards (ESTRO) — image-guided brachytherapy principles, extrapolated from locally advanced cervical practice, that underpin organ-sparing radiotherapy for invasive vaginal carcinoma.
- South African National HIV / ART Consolidated Guidelines (2023) — first-line TLD (tenofovir + lamivudine + dolutegravir); immune reconstitution improves control of HPV-related lower-genital-tract disease.