The Natural History of Vulvar Intraepithelial Neoplasia, Differentiated Type: Evidence for Progression and Diagnostic Challenges

  title={The Natural History of Vulvar Intraepithelial Neoplasia, Differentiated Type: Evidence for Progression and Diagnostic Challenges},
  author={Susan M Bigby and Lois J. Eva and Kah Leng Fong and Ronald W. Jones},
  journal={International Journal of Gynecological Pathology},
Squamous cell carcinoma of the vulva (SCCV) develops through either human papillomavirus (HPV)-dependent or HPV-independent pathways. Approximately 60% of SCCV arise independently of HPV, commonly in a background of an inflammatory dermatosis, particularly lichen sclerosus. The likely direct precursor to most of these lesions is vulvar intraepithelial neoplasia (VIN), differentiated type (dVIN), although the evidence is largely circumstantial. There are few reports of progression to carcinoma… 

Clinical and molecular classification of vulvar squamous pre-cancers

It is suggested that HSIL and dVIN are characterized by different underlying molecular alterations that may have important implications for treatment and follow-up of women diagnosed with vulvar squamous cell cancer.

Role of Human Papillomavirus in Vulvar Cancer.

The prognostic role of HPV in VSCC is still contradictory, but increasing evidence suggests that HPV-associated tumors are less aggressive, and novel immunological strategies based on anti-HPV antigens are being evaluated in clinical trials.

Putative precancerous lesions of vulvar squamous cell carcinoma.

The available evidence and biologic basis for these HPV-independent precursor lesions of VSCC, among other speculated entities, are evaluated, and their clinical, diagnostic, and prognostic features are discussed.

Precursor lesions of vulvar squamous cell carcinoma - histology and biomarkers: A systematic review.

Differentiated Vulvar Intraepithelial Neoplasia-like and Lichen Sclerosus-like Lesions in HPV-associated Squamous Cell Carcinomas of the Vulva

A small subset of VSCCs conclusively associated with HPV may arise on intraepithelial lesions, mimicking precursors of HPV-independent VSCC.

Diagnostic Criteria for Differentiated Vulvar Intraepithelial Neoplasia and Vulvar Aberrant Maturation

Evaluation of women at risk for dVIN and VAM requires a collaborative approach by clinicians and pathologists experienced in vulvar disorders.

Somatic Mutation Profiling in Premalignant Lesions of Vulvar Squamous Cell Carcinoma

The preliminary data do not support a genetic background for the notion of LS as the VSCC premalignant lesion, and it appears that TP53 mutations are early events during VSCC carcinogenesis, being present in both HSIL and dVIN lesions.

Clinicopathologic Diagnosis of Differentiated Vulvar Intraepithelial Neoplasia and Vulvar Aberrant Maturation

The morphology of dVIN encompasses nonkeratinizing and keratinizing types, the latter subdivided into traditional, acantholytic, atrophic, hypertrophic, and subtle.

The Vulvar Cancer Risk in Differentiated Vulvar Intraepithelial Neoplasia: A Systematic Review

Patients with dVIN have a high risk of developing primary and recurrent VSCC with a short time to cancer progression, and the importance of clinical awareness and prompt identification of differentiated vulvar intraepithelial neoplasia, given its high malignant potential is highlighted.



Vulvar Squamous Cell Carcinoma is a Multifactorial Disease Following Two Separate and Independent Pathways

The results provide further evidence that vulvar squamous cell carcinoma is a multifactorial disease that develops from two different pathways, an HPV-dependent pathway with a remarkable resemblance to CIN lesions and cervical carcinoma and a HPV-independent pathway in which differentiated VIN III lesions that are hr-HPV-negative may be precursors.

Is Differentiated Vulval Intraepithelial Neoplasia the Precursor Lesion of Human Papillomavirus-Negative Vulval Squamous Cell Carcinoma?

The clinical and molecular evidence that implicates differentiated VIN (DVIN), rather than lichen sclerosus, as the most likely precursor lesion in HPV-negative vulval squamous cell carcinoma is discussed.

Early Vulvar Squamous Neoplasia: Advances in Classification, Diagnosis, and Differential Diagnosis

Five categories of early vulvar neoplasia are defined, based on the available literature, into (a) low-grade lesions with minimal cancer risk, (b) high- grade lesions associated with HPV, (c) high/low/high-grade lesions associated with other etiologies, (d) squamous atypias defined by abnormalities in differentiation rather than abnormalities in nuclear morphology, and (D) early carcinomas that do not exhibit conspicuous stromal invasion.

HPV-negative Vulvar Intraepithelial Neoplasia (VIN) With Basaloid Histologic Pattern: An Unrecognized Variant of Simplex (Differentiated) VIN

From a series of 110 invasive squamous cell carcinomas of the vulva negative for HPV by highly sensitive polymerase chain reaction, 51 had VIN lesions located at least 1 cm away from the tumor, and in 4 cases, the VIN had basaloid histologic features.

Vulvar squamous cell carcinoma development after diagnosis of VIN increases with age.

Differentiated Intraepithelial Neoplasia of the Vulva

  • N. MulvanyD. Allen
  • Medicine
    International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists
  • 2008
DVIN present diagnostic difficulty and considerable interobserver variation also exists, and it is suggested that Ki-67 and p16INK4A are useful for distinguishing DVIN and classical VIN 3, whereas p53 and CD1a are usefulFor distinguishing DVin and invasive squamous carcinoma.

TP53 mutations in vulval lichen sclerosus adjacent to squamous cell carcinoma of the vulva

Data suggest that TP53 mutations develop in NNEDV and are intrinsic to the clonal evolution that leads to SCC, and the type of mutation detected is more likely to occur due to endogenous cellular changes rather than exogenous carcinogen exposure.

Analysis of clonality and HPV infection in benign, hyperplastic, premalignant, and malignant lesions of the vulvar mucosa.

Monoclonal expansion triggered by high-risk type HPV integration is an early event for carcinogenesis of HPV-associated SCC, suggesting that a subset of cases of LS and SCH result from a neoplastic proliferation, similar to VINs but not related to infection with high- risk type HPV.

Vulval squamous cell carcinoma occurring on a background of differentiated vulval intraepithelial neoplasia is more likely to recur: a review of 154 cases.

VIN-related cancers arising on a background of dVIN appear more likely to recur than cancers arising from undifferentiated VIN; this is compounded by the concurrent presence of NNEDs.

Allelic imbalance in lichen sclerosus, hyperplasia, and intraepithelial neoplasia of the vulva.

The presence of allelic imbalance in vulvar hyperplasia and LS supports the hypothesis that these alterations are at greater risk for neoplasia despite the absence of conspicuous cellular atypia.