Vulvar cancer pathophysiology

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Overview

Vulvar cancer, a malignant invasive growth in the vulva, accounts for about 4 % of all gynecological cancers and typically affects women in later life. It is estimated that in the United States in 2006 about 3,740 new cases will be diagnosed and about 880 women will die as a result of vulvar cancer.[1] Vulvar carcinoma is separated from vulvar intraepithelial neoplasia (VIN), a non-invasive lesion of the epithelium that can progress via carcinoma-in-situ to squamous cell cancer, and from Paget disease of the vulva.

Types

Table 31-1. Histologic Subtypes of Vulvar Cancer

1. Vulvar carcinomas

  • Squamous cell carcinoma
  • Basal cell carcinoma
  • Vulvar Paget disease
  • Adenocarcinoma
  • Transitional cell carcinoma
  • Verrucous carcinoma
  • Merkel cell tumors
  • Verrucous carcinoma

2. Vulvar malignant melanoma

3. Vulvar sarcoma

  • Leiomyosarcoma
  • Malignant fibrous histiocytoma
  • Epithelial sarcoma


Melanoma

About 5% of vulvar malignancy is caused by melanoma of the vulva. Such melanoma behaves like melanoma in other locations and may affect a much younger population. Contrary to squamous carcinoma, melanoma has a high risk of metastasis.

Basal cell carcinoma

Basal cell carcinoma affects about 1-2% of vulvar cancer is a slowly growing lesion and affects the elderly. Its behavior is similar to basal cell carcinoma in other locations that is it tends to grow locally with a low potential of deep invasion or metastasis.

Other lesions

Vulvar cancer can be caused by other lesions such as adenocarcinoma or sarcoma.

Vulvar carcinomas Subtype Features on Gross Pathology Features on Histopathological Microscopic Analysis
Squamous cell carcinoma of vulva
  • Most lesions originate in the labia, primarily the labia majora. Other areas affected are the clitoris, and fourchette, and the local glands.
  • unifocal
  • Eosinophilia.
  • Extra large nuclei/bizarre nuclei.
  • Inflammation (lymphocytes, plasma cells).
  • Long rete ridges.
  • Numerous beeds/blobs of epithelial cells that seem unlikely to be rete ridges.
  • Tan/reddish brown color
  • Sharp borders
  • Well-demarcated, dome-shaped papular/verruccous lesion
  • Sharp border differentiating malignant vs. normal tissue due to absence of intraepidermal lateral spread / no radial growth plate (most characteristic feature)
  • Appearance of epithelioid cells with occasional spindle cells
  • Melanocytes may have absent/minimal pigmentation
Acral lentiginous melanoma
  • Brown/black color, but may include reddish brown or white
  • Hyperkeratotic, diffused borders with no distinct demarcation
  • Irregular and elevated
  • Epidermal acanthosis and hyperkeratosis (most characteristic feature)
  • Malignant melanocytes spread along the basal layer
  • Cells arranged in lentiginous and dycohesive pattern along the dermoepidermal junction
  • May be any of round, epithelioid, spindle, or oval cells
  • May have perineural or endoneural invasion
Lentigo maligna melanoma
  • Brown/black color, but may include reddish brown or white
  • Hyperkeratotic, diffused borders with no distinct demarcation
  • Irregular and elevated
  • Epidermal atrophy and flattening and prominent dermal invasion (most charactersitic feature)
  • Large, pleomorphic cells
  • Cells arranged in lentiginous and dycohesive pattern along the dermoepidermal junction
  • Preservation of retiform epidermis
  • May be any of round, epithelioid, spindle, or oval cells
  • Evidence of actinic damage of the dermal matrix
  • May have perineural or endoneural invasion
  • Positivity for CD133+ and CD34+
Non-cutaneous melanoma
  • Variable morphology depending on location of melanoma
  • Histopathologically similar to other subtypes of melanoma
Desmoplastic/Spindle cell melanoma
  • Skin colored and morphologically resembles scar tissue
  • Dermal, fibrotic nodule
  • Ill-defined, variable spindle cells with irregular contours and stromal desmoplasia
  • Highly infiltrative pattern
  • Appearance of sclerotic collagen fibers
  • Nuclear hyperchromasia
  • Appearance of lymphoid aggregates
  • Solar elastosis
  • Involvement of endoneurium and perineurium (neurotropism)
  • Possibly evidence of other melanoma subtypes (co-existing tumors, especially lentiginous melanoma)"
Nevoid melanoma
  • Morphologically similar to a melanocytic nevus
  • Dermal mitosis
  • Hypercellular and monomorphous-appearing dermal melanocytes that have a characteristic sheet-like appearance
  • Evidence of cytologic atypia (nuclear enlargement, pleomorphism, irregular nuclear membrane, hyperchromasia)
  • Irregular basal infiltration
  • Evidence of angiotropism
Spitzoid melanocytic neoplasm
  • Morphologically similar to a Spitz nevus
  • Appearance of melanocytic proliferation along with features of Spitz tumors (small diametes, well-demarcated, symmetric lesion with no ulceration, epidermal effacement, dermal mitosis, or involvement of the subcutaneous fat)
  • May have features that are not typically characteristic of Spitz tumors (ulceration, poor demarcation)
  • Vertically oriented spindled melanocytes
  • Clefts between junctional melanocytes
Angiotropic melanoma
  • No gross morphological features that distinguish angiotropic melanoma from other subtypes of melanoma
  • Melanoma cells in close proximity to abluminal surfaces of blood and/or lymphatic channels
  • No invasion within the vascular lamina itself
Blue nevus-like melanoma
  • Morphologically similar to a blue nevus
  • Asymmetric nodular/multinodular appearance
  • Aggregates of melaninized, atpical spindle cells
Composite melanoma

Features of more than one subtype on gross pathology

  • Features of more than one subtype on microscopic analysis
  • May be characterized by one of the following:
  • Collision tumor: Collision of melanoma and another nearby malignant tumor
  • Colonization: Colonization of melanocytes in a tumor
  • Combined: Two distinct tumors appear to have mixed features of the melanoma and the other tumor
  • Biphenotypic: One tumor that has features of melanoma and another epithelial malignancy

References

  1. American Cancer Society (2006). "Cancer facts and Figures 2006" (PDF). Retrieved 2006-10-13.