Carcinoma of the penis pathophysiology

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Editor(s)-in-Chief: C. Michael Gibson, M.S., M.D. [1] Phone:617-632-7753; Joel Gelman, M.D. [2], Director of the Center for Reconstructive Urology and Associate Clinical Professor in the Department of Urology at the University of California,Irvine

Overview

On gross pathology, scaly patches or nodules, erythematous, and ulceration are characteristic findings of carcinoma of the penis. On microscopic histopathological analysis, keratinization and intercellular bridges are characteristic findings of carcinoma of the penis.

Pathogenesis

  • Penile cancers traditionally begin as small lesions, most commonly on the glans or prepuce.
  • About 95% of penile cancers develop from flat, scale-like cells called squamous cells. squamous cell carcinoma (SCC) can develop anywhere on the penis, but most develop on the foreskin (in uncircumcised men) or the glans. This type of cancer is typically slow growing. When found early, it is often curable.
  • Penile cancer arises from precursor lesions, which generally progress from low-grade to high-grade lesions.
  • Penile malignant lesions and tumors, can be divided into HPV-related and non–HPV-related groups.
  • For HPV related penile cancers this sequence is as follows:[1]
  • Non-HPV related penile squamous cell cancers include:
  • SCC usual type/Not Otherwise Specified (NOS)
  • Pseudohyperplastic carcinoma
  • Pseudoglandular carcinoma
  • Verrucous carcinoma
  • Carcinoma cuniculatum
  • Papillary carcinoma NOS
  • Adenosquamous carcinoma
  • Sarcomatoid carcinoma
  • Tumors with basal and/or warty morphology display HPV more frequently.

Gross & Microscopic Pathology

HPV-related Penile Carcinoma

  • Basaloid SCC
    • Occurs most frequently the glans or the foreskin
    • Flat ulcerated masses, which are deeply invasive and sometimes necrotic
    • Metastasis is seen in about 50% of cases; lymph nodes most common
    • Closely packed small basophilic cells; mitosis is frequent with central keratinization
    • “Starry sky” like features; displays close features to neuroendocrine tumors
    • p16 positive
    • Hyalinization of the stroma is frequent
    • Local recurrence is high; mortality is high, depends on the extension at time of treatment
  • Papillary basaloid carcinoma
    • Rare and affect the glans
    • Hyperparakeratosis and kondylomatous features are frequent
    • p16 positive
    • Resemble urothelial carcinomas
  • Warty carcinoma
    • Look like condylomas
    • Account for 5–10% of the penile carcinomas
    • Macronodular cauliflower-like appearance
    • Papillae have a dark fibrovascular core that the tumor surrounds with a whitish aspect
    • Pleomorphic koilocytes, hyper and parakeratosis, nuclear pleomorphism, and cellular clarification
    • Individual cell necrosis
    • Carcinomas invading corpus cavernosum and dartos, usually do not display intravascular or perineural invasion
    • Nodal metastasis is seen in <20%
    • The mortality rate is low
  • Warty–basaloid carcinoma
    • Shows both warty and basaloid features
    • Present as voluminous masses growing from the glans and foreskin
    • Histologically, these tumors are mixed with a papillomatous warty-like surface and a solid basaloid invasive component
    • p16 is strongly expressed
    • Invasion into deeper structures is frequent, vascular and perineural invasions are frequent
    • More aggressive than their warty counterpart
    • Around 50% will develop lymph node metastasis; 30% will die of disease
  • Clear-cell carcinoma
    • aggressive
    • occurs as a large mass of the glans and foreskin
    • tumor develops in sheets
    • necrosis is frequent
    • Staining of the clear cells is positive for p16
    • vascular and perineural invasion is frequent
    • tumor-related mortality is around 20%

Microscopic Pathology

  • On microscopic histopathological analysis, keratinization and intercellular bridges are characteristic findings of carcinoma of the penis.[2]

Grades of penile cancer

  • Grading is a way of classifying penile cancer cells based on their appearance and behaviour when viewed under a microscope.[3]
  • The grade of penile cancer is based on the degree of differentiation of cells and their rate of growth.
Grade Definition
GX Grade of differentiation cannot be assessed
G1 Well differentiated or low grade
G2 Moderately well differentiated or moderate grade
G3 Poorly differentiated or high grade
G4 Undifferentiated or high grade

References

  1. Bleeker MC, Heideman DA, Snijders PJ, Horenblas S, Dillner J, Meijer CJ (2009). "Penile cancer: epidemiology, pathogenesis and prevention". World J Urol. 27 (2): 141–50. doi:10.1007/s00345-008-0302-z. PMID 18607597.
  2. Accessed on Septermber, 30 2015 "Squamous cell carcinoma of the penis.Libre Pathology 2015" Check |url= value (help).
  3. Accessed on Septermber, 30 2015 "Grades of penile cancer.Canadian Cancer Society 2015" Check |url= value (help).


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