Vulva

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This article addresses the basics of vulva, from a pathologic perspective.

Normal vulva

Microscopic

Features:

  • Stratified squamous epithelium with maturation.
  • No nuclear changes.
  • No inflammation.

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Mildly inflamed

VULVA, BIOPSY:
- SQUAMOUS MUCOSA WITH MILD CHRONIC INFLAMMATION AND REACTIVE CHANGES.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
Micro

The sections show squamous mucosa with a mild chronic inflammatory infiltrate that consists predominantly of lymphocytes. There is mild nuclear enlargement and intracellular edema. The nuclear membranes are regular. No nuclear hyperchromasia is apparent. No mitotic activity is readily apparent.

Benign disease

This is grab bag of non-neoplastic stuffs.

Condyloma acuminatum

General

  • Due to human papillomavirus (HPV).
    • Transmission: sexual, non-sexual, horizontal (mother to child).[1]
      • Should raise the suspicion of child abuse.

Note:

Clinical DDx:

Microscopic

Features:

  • Koilocytes.[4]
    • Cells with an enlarged nucleus and perinuclear clearing.
  • Papillomatosis.[5]
    • Papillomatosis = surface elevation due to dermal papillae enlargement.[6]
  • +/-Parakeratosis.

DDx:

Images

  • Condyloma acuminatum - low mag. (WC)

  • Condyloma acuminatum - very high mag. (WC)

  • Condyloma acuminatum - 2. (WC)

  • Condyloma acuminatum - 3. (WC)

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SKIN LESION ("VULVAR WART"), VULVA, EXCISION:
- CONDYLOMA ACUMINATUM (GENITAL WART).

LABIA MINORA, BIOPSY:
- CONDYLOMA/LOW-GRADE SQUAMOUS INTRAEPITHELIAL LESION (LSIL).
-- NEGATIVE FOR HIGH-GRADE DYSPLASIA.

Seborrheic keratosis-like

SKIN LESION, PERINEUM, BIOPSY:
- SEBORRHEIC KERATOSIS-LIKE CONDYLOMA ACUMINATUM (GENITAL WART).

Micro

The sections show a polypoid fragment of skin with epithelium on three sides, acanthosis, hyperkeratosis and parakeratosis. Koilocytic changes (mild nuclear enlargement, perinuclear clearing) are seen focally. There is mild basilar nuclear enlargement and hyperchromasia. The epithelium matures to the surface and a granular layer is present.

Seborrheic keratosis-like

The sections show skin with acanthosis with papillomatous features (round bulbous rete ridges, acanthosis with penetrating fibrovascular cores) pseudohorn cysts, parakeratosis and hyperkeratosis. There is no significant basal nuclear atypia. There are no mitoses and no melanocytic nests. There is mild dermal inflammation. There is no solar elastosis. Pigment incontinence is present focally.

Lichen sclerosus

Main article: Lichen sclerosus

Bartholin cyst

General

  • Common.
  • May become infected.

Treatment:

  • Drainage.
  • Marsupialization.

Microscopic

Features:

  • Cyst with squamous or urothelial epithelium.[7]

Images:

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Compatible with Bartholin cyst

VAGINA, CYST WALL, BIOPSY:
- SOFT TISSUE WITH A MIXED INFLAMMATORY INFILTRATE RICH IN NEUTROPHILS,
  NO EPITHELIUM APPARENT; COMPATIBLE WITH DENUDED CYST WALL.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.

Zoon vulvitis

  • AKA plasma cell vulvitis.
Main article: Zoon vulvitis

Neoplasms (non-malignant)

A short DDx:[8]

Hidradenoma papilliferum

General

Gross

  • Nodule.

Note:

  • Classically vulvar - reported in various locations.

Microscopic

Features:

  • Cystic spaces.
  • Epithelium with apocrine differentiation (as demonstrated by apocrine snouts).
  • Well-circumscribed.

Images:

Notes:

  • No attachment to epidermis.
  • No nuclear changes suggestive of malignancy.

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VULVAR LESION, EXCISION:
- PAPILLARY HIDRADENOMA.

Vulvar neoplasia

Classic vulvar intraepithelial neoplasia

  • Abbreviated classic VIN or cVIN.

General

Epidemiology:

  • Classic VIN, like CIN, is associated with HPV and seen in younger women.
  • May be multifocal, i.e. associated with cervical (CIN) or vaginal (VAIN) lesions;[15] multifocality has a strongly association with immunosuppression.[16]

Classic VIN is graded like cervical pre-cancerous lesions:

Microscopic

Features:

  • Increased NC ratio.
  • Multinucleation.
  • Lack of maturation to surface (not very useful -- unlike in the cervix).[18]
    • May have "vertical streaming" - the long axis of the cells are perpendicular to the free surface & basement membrane.
  • Apical mitoses.

DDx:

Images:

IHC

  • Classic VIN: p16 +ve, p53 -ve.
  • Differentiated VIN: p16 -ve, p53 +ve.[20]

Note:

  • p16 can be thought of as a poor man's HPV test.

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VIN I

VULVA, BIOPSY:
- CLASSIC VULVAR INTRAEPITHELIAL NEOPLASIA (VIN) I (MILD DYSPLASIA).
- NEGATIVE FOR INVASIVE MALIGNANCY.

VIN III

VULVA, EXCISION:
- CLASSIC VULVAR INTRAEPITHELIAL NEOPLASIA (VIN) III (SEVERE DYSPLASIA)
  WITH FOCAL ULCERATION.
- MARGIN FOCALLY POSITIVE FOR VIN III.
- NEGATIVE FOR INVASIVE MALIGNANCY.

Differentiated vulvar intraepithelial neoplasia

  • Abbreviated dVIN.
  • AKA VIN simplex.[21]

General

Epidemiology:

Note:

Microscopic

Features:[23]

  • Thickening of the stratum spinosum (acanthosis).
  • Elongation of rete ridges with bridging/anastomoses between rete ridges.
  • Nuclear atypia - esp. basal layer.
  • Nuclei in stratum corneum (parakeratosis).
  • +/-Atypical mitoses.

Notes:

  • Not graded like classic VIN.
  • Mnemonic BAD LAP: basal cell atypia, anastomosing rete ridges (bridging), dVIN, lichen sclerosus, acanthosis, parakeratosis.

DDx:

Images

  • Differentiated VIN - low mag. (WC)

  • Differentiated VIN - intermed. mag. (WC)

  • Differentiated VIN - deep - high mag. (WC)

www:

IHC

  • Differentiated VIN: p16 -ve, p53 +ve.[20]
  • Classic VIN: p16 +ve, p53 -ve.

Note:

  • p16 can be thought of as a poor man's HPV test.

Malignant neoplasms of the vulva

Overview

Most common malignancies of vulva:[24]

  1. Invasive squamous cell carcinoma.
  2. Malignant melanoma.

Vulvar squamous cell carcinoma

Main article: Squamous cell carcinoma

General

  • Most common vulvar malignancy.

Precursor lesions for SCC

  • Vulvar intraepithelial neoplasia (VIN).

VIN can be divided into:

  • Classic VIN, and
  • Differentiated VIN.
    • Differentiated VIN is mostly irrelevant as it is basically never seen alone, i.e. it usually accompanies cancer.

Low grade pre-cancerous lesions (VIN) are typically HPV positive, while high grade pre-cancerous lesions and cancer are less often HPV positive.[25]

Microscopic

Like SCC elsewhere.

  • Microinvasion: <=1 mm stromal invasion, tumour size <=2 cm (T1a).[26]
  • Depth from DE junction.

Note:

  • Tumour thickness != depth of invasion.
    • Thickness = granular layer or surface (no granular layer present) to deepest tumour.
    • Depth of invasion = epithelial-stromal junction in "valley" of papillae.

DDx:

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VULVA, LEFT SIDE, (INCISIONAL) BIOPSY:
- INVASIVE SQUAMOUS CELL CARCINOMA.
-- PLEASE SEE TUMOUR SUMMARY.

TUMOUR SUMMARY - VULVA
Specimen Size: multiple fragments - up to 2.5 cm in aggregate.
Tumour site: left vulva - around Bartholin's gland.
Tumour size: at least 10 mm, cannot be determined due to fragmentation.
Tumour focality: cannot be determined.
Histologic type: squamous cell carcinoma with focal keratinization.
Histologic Grade: G2 - moderately differentiated.
Microscopic tumour extension: greater than 2 mm, assessment limited by
 fragmentation and tissue orientation.
Tumour border: infiltrating.
Lymph-Vascular Invasion: present.
Additional findings:
 Vulvar intraepithelial neoplasia (VIN) 3 (severe dysplasia/carcinoma in situ).

See also

References

  1. ↑ Lefkowitch, Jay H. (2006). Anatomic Pathology Board Review (1st ed.). Saunders. pp. 280 Q29. ISBN 978-1416025887.
  2. ↑ Nucci, Marisa R.; Oliva, Esther (2009). Gynecologic Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 143. ISBN 978-0443069208.
  3. ↑ URL: http://emedicine.medscape.com/article/781735-differential. Accessed on: 5 July 2013.
  4. ↑ Huang, Z.; Yang, S.; Li, Q.; Yan, P.; Li, L. (Feb 2001). "[Evaluation the pathological diagnostic values of koilocyte in condyloma acuminatum].". Zhonghua Liu Xing Bing Xue Za Zhi 22 (1): 58-60. PMID 11860848.
  5. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 204. ISBN 978-0781765275.
  6. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 1230. ISBN 0-7216-0187-1.
  7. ↑ http://pathologyoutlines.com/vulva.html#bartholincyst
  8. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 456. ISBN 978-0781765275. }}
  9. ↑ Hidradenoma papilliferum. Stedman's Medical Dictionary. 27th Ed.
  10. ↑ URL: http://medical-dictionary.thefreedictionary.com/hidradenoma. Accessed on: 14 April 2011.
  11. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 1067. ISBN 0-7216-0187-1.
  12. ↑ 12.0 12.1 Duhan, N.; Kalra, R.; Singh, S.; Rajotia, N. (Oct 2011). "Hidradenoma papilliferum of the vulva: case report and review of literature.". Arch Gynecol Obstet 284 (4): 1015-7. doi:10.1007/s00404-010-1784-7. PMID 21132312.
  13. ↑ Daniel, F.; Mahmoudi, A.; de Parades, V.; Fléjou, JF.; Atienza, P. (Feb 2007). "An uncommon perianal nodule: hidradenoma papilliferum.". Gastroenterol Clin Biol 31 (2): 166-8. PMID 17347625.
  14. ↑ Morimura, S.; Kadono, T.; Sugaya, M.; Sato, S.. "Ectopic hidradenoma papilliferum on the abdomen.". Eur J Dermatol 21 (2): 278-9. doi:10.1684/ejd.2010.1236. PMID 21411413.
  15. ↑ Pai, K.; Pai, S.; Gupta, A.; Rao, P.; Renjhen, P. (Oct 2006). "Synchronous vulvar intraepithelial neoplasia (VIN) of warty type and cervical intraepithelial neoplasia (CIN): case report.". Indian J Pathol Microbiol 49 (4): 585-7. PMID 17183865.
  16. ↑ Ait Menguellet, S.; Collinet, P.; Houfflin Debarge, V.; Nayama, M.; Vinatier, D.; Leroy, JL. (May 2007). "Management of multicentric lesions of the lower genital tract.". Eur J Obstet Gynecol Reprod Biol 132 (1): 116-20. doi:10.1016/j.ejogrb.2006.04.011. PMID 16713062.
  17. ↑ Rufforny, I.; Wilkinson, EJ.; Liu, C.; Zhu, H.; Buteral, M.; Massoll, NA. (Apr 2005). "Human papillomavirus infection and p16(INK4a) protein expression in vulvar intraepithelial neoplasia and invasive squamous cell carcinoma.". J Low Genit Tract Dis 9 (2): 108-13. PMID 15870532.
  18. ↑ LAE. February 2009.
  19. ↑ 19.0 19.1 Kotsopoulos, IC.; Tampakoudis, GP.; Evaggelinos, DG.; Nikolaidou, AI.; Fytili, PA.; Kartsiounis, VC.; Gerasimidou, DK. (2011). "Implication of human papillomavirus-66 in vulvar carcinoma: a case report.". J Med Case Rep 5: 232. doi:10.1186/1752-1947-5-232. PMC 3150314. PMID 21702970. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3150314/.
  20. ↑ 20.0 20.1 20.2 Pinto, AP.; Miron, A.; Yassin, Y.; Monte, N.; Woo, TY.; Mehra, KK.; Medeiros, F.; Crum, CP. (Mar 2010). "Differentiated vulvar intraepithelial neoplasia contains Tp53 mutations and is genetically linked to vulvar squamous cell carcinoma.". Mod Pathol 23 (3): 404-12. doi:10.1038/modpathol.2009.179. PMID 20062014.
  21. ↑ Ruhul Quddus, M.; Xu, C.; Steinhoff, MM.; Zhang, C.; Lawrence, WD.; Sung, CJ. (Jun 2005). "Simplex (differentiated) type VIN: absence of p16INK4 supports its weak association with HPV and its probable precursor role in non-HPV related vulvar squamous cancers.". Histopathology 46 (6): 718-20. doi:10.1111/j.1365-2559.2005.02036.x. PMID 15910611.
  22. ↑ Yang, B.; Hart, WR. (Mar 2000). "Vulvar intraepithelial neoplasia of the simplex (differentiated) type: a clinicopathologic study including analysis of HPV and p53 expression.". Am J Surg Pathol 24 (3): 429-41. PMID 10716158.
  23. ↑ 23.0 23.1 van de Nieuwenhof, HP.; Bulten, J.; Hollema, H.; Dommerholt, RG.; Massuger, LF.; van der Zee, AG.; de Hullu, JA.; van Kempen, LC. (Feb 2011). "Differentiated vulvar intraepithelial neoplasia is often found in lesions, previously diagnosed as lichen sclerosus, which have progressed to vulvar squamous cell carcinoma.". Mod Pathol 24 (2): 297-305. doi:10.1038/modpathol.2010.192. PMID 21057461.
  24. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 459. ISBN 978-0781765275.
  25. ↑ De Vuyst H, Clifford GM, Nascimento MC, Madeleine MM, Franceschi S (April 2009). "Prevalence and type distribution of human papillomavirus in carcinoma and intraepithelial neoplasia of the vulva, vagina and anus: a meta-analysis". Int. J. Cancer 124 (7): 1626–36. doi:10.1002/ijc.24116. PMID 19115209.
  26. ↑ URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Vulva_11protocol.pdf. Accessed on: 9 March 2012.
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