PATHOLOGY

The role of pathologic prognostic factors in squamous cell carcinoma of the penis
Cubilla AL
Department of Pathology, Facultad de Ciencias Medicas, Instituto de Patología e Investigación, Universidad Nacional de Asunción, Asunción, Paraguay
World J Urol. 2008; 3. [Epub ahead of print]

• Purpose: The aim of this review was to identify prognostic pathologic factors which are independent from other clinical or molecular variables.
• Methods: We reviewed the literature on morphological prognostic factors emphasizing our personal experience.
• Results: We found that for a proper evaluation of prognostic factors a familiarity with penile complex anatomy is required. A biopsy of the primary tumor is not useful for a complete evaluation of prognostic factors other than malignancy and a resected specimen should be utilized. Penile carcinomas have a fairly predictable pattern of local, regional and systemic spread. Pathologic factors affecting patients outcome are multiple but it is difficult from the available studies using heterogeneous pathologic methodologies, different therapeutic approaches and ecologically variable patient populations to ascertain the independent validity of these factors. Invasion of perineural spaces by tumor, lymphatic-venous embolization and histological grade appear to be the most important pathologic predictors of nodal spread and cancer mortality. Other commonly cited factors influencing prognosis are tumor depth or thickness, anatomical site and size of the primary tumor, patterns of growth, irregular front of invasion, pathologic subtypes of the SCC, positive margins of resection and urethral invasion. A combination of two factors, histological grade and depth has been reported as significant predictor of cancer regional spread. After a preselection of significant factors, nomograms have been constructed to collectively evaluate the predictive power of various clinical and pathological indicators.
• Conclusions: Among various factors perineurial invasion, vascular invasion and high histological grade appear to be the most important adverse pathological prognostic factors.
  
  
• Editorial Comment
  This is a very comprehensive review on a tumor that is very important in Brazil. A very recent article in Int Braz J Urol has shown the epidemiologic characteristics of penile cancer in this country (1). It is a very frequent tumor, predominantly affecting low income, non-neonatal circumcised males, Caucasian patients living in North and Northeast regions of Brazil where there may be a delay in obtaining specialized medical assistance.
  Dr. Cubilla is an expert on penile carcinoma living in a country (Paraguay) also with a very high frequency of this tumor. He reviews the prognostic factors in squamous cell carcinoma. Among various factors, perineural invasion, vascular invasion and high histological grade appear to be the most important adverse pathological prognostic factors and should be reported by the pathologist. He also emphasizes the importance of the gross examination of the surgical specimen.
  The grading of squamous cell carcinoma of the penis is based on the production of keratin. Abundant keratin production characterizes well differentiated tumors; keratinization of isolated cells moderately differentiated tumors; and, no production of keratin undifferentiated tumors.
  The histopathologic subtypes are also important in prognosis. Verrucous carcinoma is a very well differentiated variant, the base is broad in all cases with pushing, regular borders composed of broad bulbous projections, which are usually restricted to the lamina propria but may extend deeper. They are slowly growing, locally infiltrative but do not metastasize. In some reports in the literature, this tumor is erroneously called giant condyloma. Verrucous carcinomas lack the HPV-related cellular changes characteristically seen in giant condyloma, and are not causally related to HPV, unlike giant condyloma (2).

References
1. Favorito LA, Nardi AC, Ronalsa M, Zequi SC, Sampaio FJ, Glina S: Epidemiologic study on penile cancer in Brazil. Int Braz J Urol. 2008; 34: 587-91; discussion 591-3.
2. Cubilla AL: The penis. In: Young RH, Srigley JR, Amin MB, Ulbright TM, Cubilla AL (eds.), Tumors of the prostate gland, seminal vesicles, male urethra, and penis, Atlas of Tumor Pathology. Washington DC, Armed Forces Institute of Pathology, Washington, DC, 2000.

Dr. Athanase Billis
Full-Professor of Pathology
State University of Campinas, Unicamp
Campinas, São Paulo, Brazil
E-mail: athanase@fcm.unicamp.br