Clinical overview
"Vulvar epithelial hyperplasia" is an old clinico-pathological label that the FCOG(SA) registrar must handle carefully, because the term has been retired, redefined and partly re-absorbed into other entities over the last three decades. In the historical (pre-2004) ISSVD scheme, the chronic white vulvar plaques were lumped together as "vulvar dystrophies" and split into hyperplastic dystrophy (now called squamous cell hyperplasia), lichen sclerosus, and mixed dystrophy. "Squamous cell hyperplasia" was the diagnosis given to a thickened, hyperkeratotic vulvar epithelium showing acanthosis and hyperkeratosis but no atypia and no identifiable dermatosis — in practice, the histological footprint of chronic rubbing and scratching, i.e. lichen simplex chronicus. The clinical complaint is almost always vulvar pruritus with a palpable, leathery, white or grey thickened plaque, and the central clinical anxiety is whether this lesion is a benign reactive change, a precursor of squamous carcinoma, or an already-malignant lesion masquerading as a benign one.
The reason this objective is weighted as higher-order thinking (HOTS) rather than rote recall is that the registrar must integrate terminology (old "hyperplasia" vs current WHO-2020 categories), the two divergent pathways to vulvar squamous carcinoma (HPV-associated vs HPV-independent), and a low threshold for biopsy in a South African population with high HIV prevalence and therefore high HPV-driven disease burden. Getting the pathology right drives the entire management chain: reassurance and topical steroid for benign hyperplasia, versus excision and oncological work-up for differentiated VIN or invasive cancer. Distinguishing these on a small white plaque is genuinely difficult, which is precisely why histology — not clinical inspection — is the arbiter. Cross-reference the precursor and invasive ends of this spectrum at lichen-sclerosus and vulval-carcinoma.
Core knowledge
Terminology: what "epithelial hyperplasia" means now
The single most important exam point is that the WHO Classification of Tumours of the Female Genital Tract, 5th ed (2020) no longer recognises "vulvar dystrophy" or "hyperplastic dystrophy" as diagnoses. The vulvar epithelial disorders are now sorted into:
- Non-neoplastic / inflammatory dermatoses — lichen sclerosus, lichen planus, and lichen simplex chronicus (the lesion the old term "squamous cell hyperplasia" mostly described). These show no epithelial atypia.
- Squamous intraepithelial neoplasia — divided by aetiology:
- HPV-associated (usual-type) VIN, graded in WHO-2020/LAST terminology as LSIL (flat condyloma / VIN 1 equivalent) and HSIL (VIN 2–3 / usual-type VIN equivalent).
- HPV-independent VIN, of which differentiated VIN (dVIN) is the prototype, plus the newer entities differentiated exophytic vulvar intraepithelial lesion (DEVIL) and vulvar acanthosis with altered differentiation (VAAD).
- Invasive squamous cell carcinoma and its variants.
So when a referral says "squamous cell hyperplasia" or "vulvar epithelial hyperplasia", the registrar's job is to decide which modern bucket the biopsy actually belongs in. The crucial intellectual move is recognising that acanthosis (epithelial thickening) is the shared morphological theme across benign lichen simplex chronicus, the reactive epithelium adjacent to lichen sclerosus, and the deceptively bland-looking dVIN. The presence or absence of atypia, and where that atypia sits in the epithelium, is what separates benign from premalignant.
Gross / macroscopic features
Benign vulvar squamous (epithelial) hyperplasia — lichen simplex chronicus — presents as a localised, well-demarcated, raised, leathery plaque, usually on the labia majora, mons, or lateral labia. The surface is often white (a clinically "leukoplakic" plaque from hyperkeratosis and surface maceration), sometimes grey or dull pink, with accentuated skin markings (lichenification) and excoriation marks from scratching. It is typically firm and thickened to palpation but not indurated in the way an invasive cancer is, and there is no ulceration, no fixed nodularity and no friable bleeding surface — those features mandate biopsy to exclude malignancy. Lesions may be solitary or multiple and are frequently symmetrical when the underlying driver is generalised itch.
The diagnostic difficulty is that all of these macroscopic descriptors overlap with early dVIN and with HPV-associated HSIL, and with lichen sclerosus (which is classically porcelain-white, atrophic, "cigarette-paper" wrinkled, with loss of architecture, agglutination of the labia minora and clitoral burying). Mixed pictures are common: lichen sclerosus and squamous hyperplasia frequently coexist, and that combination historically carried the highest malignant-transformation worry.
Microscopic features — benign squamous hyperplasia (lichen simplex chronicus)
Figure D14.1 — Benign vulvar white plaques: lichen simplex chronicus (itch-scratch cycle, acanthosis, no atypia) vs lichen sclerosus (the substrate for dVIN).
The defining microscopy of benign vulvar epithelial hyperplasia:
- Acanthosis — thickening of the epithelium with elongation and broadening of the rete ridges.
- Hyperkeratosis (thickened, compact orthokeratotic surface keratin) and often hypergranulosis (a thickened, prominent granular layer).
- Preserved, orderly maturation — basal layer to surface keratin progresses normally; no loss of polarity.
- No nuclear atypia, no abnormal mitoses, no dyskeratosis.
- A superficial dermal chronic inflammatory infiltrate (lymphocytes, sometimes with dermal fibrosis from chronic rubbing).
The take-home is proliferation without atypia. This is the pathological signature of a reactive, benign process. Because it is reactive, identifying and treating the underlying itch-driver (a dermatosis, candidiasis, contact irritant, or lichen sclerosus) is part of "treating the hyperplasia".
Microscopic features — the premalignant mimics the registrar must not miss
Figure D14.2 — The VIN spectrum: HPV-associated usual-type HSIL (p16 block-positive) vs HPV-independent differentiated VIN (p53-aberrant, higher/faster cancer risk).
The HOTS challenge is that two premalignant lesions can look superficially like benign hyperplasia.
Differentiated VIN (dVIN) is the dangerous one. It is HPV-independent, typically arises in older, post-menopausal women on a background of lichen sclerosus or lichen planus, and is the precursor of the majority of vulvar squamous carcinomas worldwide. Its histology is treacherously subtle and "well-differentiated": there is parakeratosis and acanthosis, elongated and anastomosing rete ridges, abnormal keratinocyte maturation with premature/abnormal keratinisation (dyskeratosis) and keratin pearls deep in the rete, and — the key feature — atypia confined to the BASAL and parabasal layers (enlarged nuclei, prominent nucleoli, increased basal mitoses) while the upper epithelium looks deceptively mature. Because the atypia is basal and the surface matures, dVIN is easily under-called as "hyperplasia" or "lichen simplex" on a superficial biopsy. p53 immunohistochemistry typically shows an abnormal/mutant-pattern stain (basal overexpression or null pattern) and p16 is negative (reflecting its HPV-independence). dVIN has a short latency and high progression risk to invasive carcinoma — far higher and faster than HPV-associated HSIL — which is why over-calling benign hyperplasia is a real harm.
HPV-associated squamous lesions (LSIL/HSIL) are the other precursor pathway, driven by high-risk HPV (chiefly 16). In WHO-2020/LAST terms:
| WHO-2020 / LAST | Older VIN term | Histology |
|---|---|---|
| LSIL | VIN 1 / flat condyloma | Koilocytosis, mild basal atypia confined to lower third; productive HPV change |
| HSIL | VIN 2–3 / usual-type VIN | Full-thickness loss of maturation, atypia through upper two-thirds/full thickness, numerous and abnormal mitoses |
HPV-associated HSIL is diffusely p16-positive (block positivity) and p53 wild-type pattern — the immunohistochemical mirror-image of dVIN. It tends to occur in younger women, is often multifocal, may be pigmented, and is strongly associated with smoking, immunosuppression and HIV. This is highly relevant in South Africa, where the HIV epidemic substantially increases the prevalence and persistence of high-risk HPV and therefore of HPV-driven HSIL of the cervix, vulva and the rest of the lower genital tract (the "field effect" of anogenital HPV). See hpv-pathology and cin-pathophysiology for the shared carcinogenic mechanism.
Molecular and aetiological framework
The unifying modern concept — and the answer to "discuss the pathological features" at HOTS level — is the two-pathway model of vulvar squamous neoplasia:
- HPV-independent pathway: chronic inflammatory dermatosis (lichen sclerosus / lichen planus) → squamous hyperplasia / dVIN with TP53 mutation, p53-aberrant IHC, p16-negative → keratinising SCC. Older women; the dominant pathway numerically; worse-prognosis cancers.
- HPV-associated pathway: persistent high-risk HPV → LSIL → HSIL (p16 block-positive, p53 wild-type) → basaloid/warty SCC. Younger women; smoking and HIV-amplified; better stage-for-stage prognosis.
"Vulvar epithelial hyperplasia" sits at the benign reactive end of the HPV-independent axis — but it must be interpreted as a clue that the patient has the inflammatory/dermatosis substrate from which dVIN and keratinising carcinoma arise. That is why it is not simply dismissed.
Assessment
Figure D14.3 — Biopsy the boundary: distinguishing benign from premalignant (VIN) and malignant vulvar lesions, and which lesions must be biopsied.
Assessment is built around histological diagnosis, because clinical inspection cannot reliably separate benign hyperplasia from dVIN or early invasion.
History: duration and character of itch (chronic pruritus driving scratch–lichenify cycles favours lichen simplex chronicus); pain, bleeding, a non-healing ulcer or a growing lump (red flags for malignancy); prior or current lichen sclerosus/lichen planus; HPV-associated disease elsewhere (cervical HSIL, warts); HIV status and ART adherence; smoking; immunosuppression; menopausal status; topical treatments already tried and the response.
Examination: systematic inspection of the whole anogenital field under good light, documenting site, size, colour, surface (keratotic/eroded/ulcerated), borders, and palpable induration or nodularity. Examine the cervix and vagina (multifocal HPV disease) and palpate the inguinal nodes. A magnified/colposcopic view of the vulva with application of acetic acid (and consideration of toluidine blue) can map abnormal areas to guide biopsy, but the vulva's keratinised skin makes acetowhitening less reliable than on the cervix — see colposcopy.
Investigation — the biopsy is the test. Any persistent white, raised, pigmented, ulcerated, indurated, or treatment-refractory vulvar lesion must be biopsied. A representative punch or wedge/keyhole biopsy taken from the thickest/most atypical area, including the dermo-epithelial junction and some dermis, is essential — a superficial shave can miss the basal atypia of dVIN and any early invasion. Multiple biopsies are appropriate for a large or heterogeneous field. Request p16 and p53 immunohistochemistry explicitly when distinguishing benign hyperplasia from dVIN/HSIL: the p16-block-positive (HPV-associated HSIL) vs p53-aberrant/p16-negative (dVIN) dichotomy is the practical discriminator. In South Africa, vulvar histology and IHC are processed through the NHLS, and turnaround and IHC availability should inform the urgency of follow-up. HIV testing should be offered to every patient with HPV-associated vulvar disease, with linkage to ART.
Management
Management follows directly from the histological category, which is why getting the pathology right is the whole game.
Confirmed benign squamous (epithelial) hyperplasia / lichen simplex chronicus, no atypia. Treat the itch–scratch cycle and any underlying dermatosis. First-line is a potent topical corticosteroid (e.g. clobetasol propionate 0.05% ointment) to break the inflammation and lichenification, plus rigorous skin-care/emollient and irritant-avoidance advice and treatment of any coexisting candidiasis or contact dermatitis. Where lichen sclerosus coexists, treat it on its own pathway (see lichen-sclerosus). Crucially, re-biopsy any area that fails to respond to adequate topical steroid, because non-response is a classic way that an unrecognised dVIN or early carcinoma declares itself.
Confirmed HSIL (HPV-associated, p16-positive). This is a recognised precursor requiring treatment and surveillance: options include surgical excision (preferred where invasion cannot be excluded or in older women), laser ablation, or topical imiquimod, with the modality chosen by lesion size, multifocality, site and concern for occult invasion. Optimise immune status — in South Africa that means ensuring effective ART for HIV-positive women, smoking cessation, and screening the rest of the lower genital tract because the HPV field effect makes synchronous cervical/vaginal disease common (link this to the SA cervical-screening pathway, cervical-screening-sa).
Confirmed dVIN. Because of its high and rapid progression risk and the difficulty of excluding occult invasion, dVIN is managed with complete surgical excision with clear margins and close lifelong follow-up of the underlying dermatosis, not topical therapy or ablation. Treat the background lichen sclerosus aggressively and review regularly, since long-term control of the dermatosis is the only modifiable lever on cancer risk.
Any invasive squamous carcinoma found on biopsy is staged and managed on the vulvar-cancer pathway (FIGO staging, wide local excision, sentinel lymph node biopsy for unifocal tumours <4 cm with clinically negative groins, and groin management per the ESGO vulvar cancer guideline 2023 / GROINSS-V II) — covered in vulval-carcinoma.
Prevention context (SA). Primary prevention of the HPV-associated pathway rests on HPV vaccination: South Africa has run a school-based HPV programme for girls 9–14 since 2014, now moving to a single-dose schedule in line with WHO/SAGE, and the WHO Cervical Cancer Elimination 90-70-90 strategy (90% of girls vaccinated by 15, 70% screened with a high-performance test, 90% treated) shapes national policy. The nonavalent vaccine gives the broadest cover. These measures reduce HPV-driven HSIL across the whole anogenital field, vulva included.
Red flags / pitfalls
- The biggest pitfall is accepting "squamous/epithelial hyperplasia" as a final reassuring diagnosis without excluding dVIN. dVIN is bland, well-differentiated, basal-only in its atypia, and is the precursor of most vulvar carcinomas — it is the single most under-diagnosed premalignant vulvar lesion. If the clinical lesion is worrying or steroid-unresponsive, re-biopsy and request p53/p16 IHC.
- A treatment-refractory white plaque is cancer until proven otherwise. "We've been treating leukoplakia with steroid for months" is a classic missed-carcinoma narrative.
- Don't take a superficial shave biopsy — it can decapitate the diagnostic basal atypia of dVIN and miss early invasion. Take a deep, representative punch/wedge including dermis.
- Don't forget the field. HPV-associated vulvar HSIL travels with cervical/vaginal HSIL; examine and screen the whole lower genital tract, and always address HIV status in the SA setting — uncontrolled HIV drives HPV persistence and progression.
- Don't conflate lichen sclerosus with benign hyperplasia and stop there. They coexist, and lichen sclerosus is itself the substrate for dVIN — both need ongoing dermatosis control and surveillance, not one-off treatment.
- Pigmented, ulcerated, indurated, rapidly growing, or fixed-node lesions demand urgent biopsy and oncology referral — never a trial of topical steroid.
- Terminology trap (exam): know that "hyperplastic dystrophy" and "squamous cell hyperplasia" are obsolete, that the current framework is WHO-2020, and be ready to translate LSIL/HSIL to VIN 1 / VIN 2–3.
Evidence anchors
- WHO Classification of Tumours of the Female Genital Tract, 5th ed (2020) — the authoritative histological framework: retirement of "vulvar dystrophy", the LAST/WHO LSIL–HSIL terminology (with CIN/VIN equivalence), and the HPV-associated vs HPV-independent classification of vulvar squamous lesions, including differentiated VIN.
- ESGO Guidelines for vulvar cancer — Update 2023 (Int J Gynecol Cancer) — management of the invasive end of the spectrum: sentinel lymph node biopsy for unifocal tumours <4 cm with clinically negative groins, groin treatment for lesions beyond T1a, and GROINSS-V II (groin radiotherapy may replace inguinofemoral lymphadenectomy for sentinel-node micrometastasis ≤2 mm; macrometastasis >2 mm still needs lymphadenectomy ± RT).
- WHO Cervical Cancer Elimination Strategy (2020) — 90-70-90 by 2030, single-dose HPV schedule (WHO 2022; SAGE/RITAG Nov 2023), nonavalent vaccine — primary prevention of the HPV-associated vulvar pathway; SA school-based HPV programme since 2014.
- South African cervical cancer screening — SASOG / BetterGyn Clinical Guideline (2024) + NDoH National Cervical Cancer Screening / Prevention & Control Policy — the SA framework for HPV-driven lower-genital-tract disease and the basis for screening the field (including in HIV-positive women, screened at HIV diagnosis and more frequently regardless of age).
- South African National HIV / ART Consolidated Guidelines (2023) (TLD: TDF + 3TC + DTG) — effective ART is the key modifiable factor in HPV persistence/progression in the high-HIV-prevalence SA population; relevant to every patient with HPV-associated vulvar disease.
Note on uncertainty: docs/VERIFIED-SOURCES.md does not list a dedicated guideline for benign vulvar dermatoses/lichen simplex chronicus management; RCOG GTG 58 (vulval skin disorders) is archived, with the verified substitute being BSSVD + BAD Lichen Sclerosus (2018) + ISSVD terminology (cited in this list for lichen-sclerosus). The specific drug named (clobetasol propionate 0.05%) reflects standard dermatological practice for lichen simplex chronicus/lichen sclerosus and is not a quoted dose from a VERIFIED-SOURCES entry — verify against the current SA EML / dermatosis guidance before quoting an exact regimen. Histological and IHC descriptors above are drawn from the WHO-2020 framework.