- Human pathology

Home > E. Pathology by systems > Reproductive system > Female genital system > Vulva > vulvar squamous cell carcinoma

vulvar squamous cell carcinoma

Tuesday 27 April 2004

vulvar SCC, vulvar SCCs

Definition: Vulvar squamous cell carcinoma (VSCC) accounts for >90% of the malignant tumours of the vulva. Most VSCCs originate in vulvar intraepithelial neoplasia (VIN), that precede the development of VSCC by a variable period of time.

Strong evidence has accumulated showing that there are two different aetiopathogenic pathways for the development of VSCC and VIN, one associated with infection by human papillomavirus (HPV), and a second independent of HPV infection.

These two different types of VSCC have different epidemiological, pathological and clinical characteristics, and should therefore be considered as two separate entities.


- Vulvar intraepithelial neoplasia (VIN)


Squamous precancerous lesions and invasive squamous cell carcinomas (SCCs) of the lower female genital tract are etiologically linked to human papillomavirus (HPV) infection and appertain to the complex of the multicentric lower genital tract squamous neoplasia.

Unlike in uterine cervix, the majority of vulvar SCCs are HPV DNA negative with TP53 gene mutations emerging in the environment of vulvar dermatoses such as lichen sclerosus (LS) and lichen simplex chronicus (LSC) as the probable main etiologic factor.

Histologically, HPV-associated VSCCs are of the basaloid or warty type, and arise from VIN of the usual type.

Inactivation of p53 and the retinoblastoma tumour suppressor gene product by the viral gene products E6 and E7 is involved in the process of malignant transformation.

HPV-independent VSCCs are histologically keratinizing, are associated with differentiated VIN and lichen sclerosus, and frequently show mutations of p53. p16(INK4a) and p53 immunostaining can be useful for classifying VSCC into HPV-associated or HPV-independent.

Although large, multicentre studies are needed to definitively assess the involvement of HPV in the prognosis of VSCC, most studies have not found clear differences in survival between HPV-associated and HPV-independent tumours.

- Stage 1a (24076774)

  • Invasive squamous cell carcinoma of the vulva with ≤1 mm stromal invasion is classified as stage 1A.
  • Cancer staging systems state that the depth of invasion should be measured from the epithelial-stromal junction of the adjacent most superficial dermal papilla to the deepest point of the invasive tumor.
  • Measurement of the depth of invasion guides patient management.
  • Even though this measurement is critical, no studies have reported the reliability among pathologists for determining the cutoff point of ≤1 mm stromal invasion in vulvar cancer.


- vulvar verrucous carcinoma

  • Vulvar verrucous carcinoma is a rare variant of squamous cell carcinoma of the vulva that afflicts older women and is characterized by a well-differentiated morphology with minimal nuclear atypia.


- PNI is an independent indicator of risk for recurrence in vSCC.

  • The association of PNI with increased risk for recurrence, independent of DOI, nodal involvement, lymphovascular invasion, or stage, should encourage practicing pathologists to thoroughly search for and report the presence of PNI in vSCC. (25786085).

Paywall References

- Interobserver Agreement for Assessing Invasion in Stage 1A Vulvar Squamous Cell Carcinoma. Abdel-Mesih A, Daya D, Onuma K, Sur M, Tang S, Akhtar-Danesh N, Boutross-Tadross O, Ceballos KM, Chapman W, Colgan T, Deb P, Nucci MR, Oliva E, Lytwyn A. Am J Surg Pathol. 2013 Sep;37(9):1336-41. doi : 10.1097/PAS.0b013e31829f306a PMID: 24076774

- Perineural Invasion Is an Independent Pathologic Indicator of Recurrence in Vulvar Squamous Cell Carcinoma. Holthoff ER, Jeffus SK, Gehlot A, Stone R, Erickson SW, Kelly T, Quick CM, Post SR. Am J Surg Pathol. 2015 Mar 16. PMID: 25786085

- Pathways of vulvar intraepithelial neoplasia and squamous cell carcinoma. Del Pino M, Rodriguez-Carunchio L, Ordi J. Histopathology. 2012 Sep 18. PMID: 23190170

- Skapa P, Zamecnik J, Hamsikova E, Salakova M, Smahelova J, Jandova K, Robova H, Rob L, Tachezy R. Human papillomavirus (HPV) profiles of vulvar lesions: possible implications for the classification of vulvar squamous cell carcinoma precursors and for the efficacy of prophylactic HPV vaccination. Am J Surg Pathol. 2007 Dec;31(12):1834-43. PMID: 18043037

- Nascimento AF, Granter SR, Cviko A, Yuan L, Hecht JL, Crum CP. Vulvar Acanthosis With Altered Differentiation: A Precursor to Verrucous Carcinoma? Am J Surg Pathol. 2004 May;28(5):638-643. PMID: 15105653