Progress in pathology
Advances in the pathology of penile carcinomas☆
Alcides Chaux MD a,b,c , Antonio L. Cubilla MD b,⁎
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA Instituto de Patología e Investigación, Martin Brizuela 325, Asunción, Paraguay 1617 c Universidaddel Norte School of Medicine, Gral. Santos 2409, Asunción, Paraguay 1614
Received 8 November 2011; revised 18 January 2012; accepted 25 January 2012
Penile cancer; Squamous cell carcinoma; HPV; Penile intraepithelial neoplasia; Prognosis
Summary The incidence of penile cancer varies from country to country, with the highest figures reported for countries in Africa, SouthAmerica, and Asia and lowest in the United States and Europe. Causes of this variation are not clear, but they are thought to be related to human papillomavirus infection, smoking, lack of circumcision, chronic inflammation, and poor genital hygiene. Most penile tumors are squamous cell carcinomas, and a variegated spectrum of distinct morphologies is currently recognized. Each one of these subtypeshas distinctive pathologic and clinical features. About half of penile carcinomas are usual squamous cell carcinomas, and the rest corresponds to verrucous, warty, basaloid, warty-basaloid, papillary, pseudohyperplastic, pseudoglandular, adenosquamous, sarcomatoid, and cuniculatum carcinomas. Previous studies have found a consistent association of tumor cell morphology and human papillomaviruspresence in penile carcinomas. Those tumors composed of small- to intermediate-sized, basaloid (“blue”) cells are often human papillomavirus positive, whereas human papillomavirus prevalence is lower in tumors showing large, keratinizing, maturing eosinophilic (“pink”) cells. Human papillomavirus–related tumors affect younger patients, whereas human papillomavirus–unrelated tumors are seen in olderpatients with phimosis, lichen sclerosus, or squamous hyperplasia. This morphologic distinctiveness is also observed in penile intraepithelial neoplasia. The specific aim of this review is to provide a detailed discussion on the macroscopic and microscopic features of all major subtypes of penile cancer. We also discuss the role of pathologic features in the prognosis of penile cancer, thecharacteristics of penile precursor lesions, and the use of immunohistochemistry for the diagnosis of invasive and precursor lesions. © 2012 Elsevier Inc. All rights reserved.
1. Epidemiology and geographical variation
☆ Disclosure: Dr Alcides Chaux was partially supported by an award granted by the Consejo Nacional de Ciencia y Tecnologia, Justo Prieto 223, Asunción, Paraguay 1836, CONACYT (NationalCouncil of Science and Technology), dependent of the Presidency of the Republic of Paraguay, as an Active Researcher of Level 1 (one) of the Programa Nacional de Incentivo a los Investigadores, PRONII (National Incentive Program for Researchers). ⁎ Corresponding author. E-mail address: firstname.lastname@example.org (A. L. Cubilla).
The incidence of penile cancer varies from country to country(Fig. 1), with the highest ﬁgures reported in Africa, South America, and Asia (2-4/100 000 inhabitants) and lowest in the United States and Europe (0.3-1/100 000 inhabitants) [1,2]. Causes of this variation are not clear, but they are thought to be related to various epidemiologic factors or conditions, some of which have been reported to be associated with high prevalence of penile cancer [3-6]. Ina
0046-8177/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.humpath.2012.01.014
Fig. 1 Worldwide distribution of penile cancer incidence. Colored areas represent age-standardized rates of incidence (reported rates in parenthesis): blue, high incidence; light green, moderate incidence; and dark green, low incidence.
A. Chaux, A. L. Cubilla