Continuous Spatial Sequences of Lichen Sclerosus, Penile Intraepithelial Neoplasia, and Invasive Carcinomas: A Study of 109 Cases.

Lichen sclerosus (LSc) with penile cancer is found in about two thirds of specimens. It has been hypothesized that LSc represents a precancerous condition. To qualify as such, in addition to cytological atypia and similarity with the invasive tumor, a spatial correlation between LSc and neoplastic lesions needs to be demonstrated. The purpose of this study was to evaluate such a spatial relationship. Circumcision (28 cases) and penectomy (81 cases) specimens were evaluated. All cases had LSc, penile intraepithelial neoplasia (PeIN), and/or invasive squamous cell carcinomas. We examined LSc in relation to invasive carcinoma, PeIN, and normal epithelia. Invasive squamous cell carcinomas, classified according to the World Health Organization criteria as non-human papillomavirus (HPV)-related and HPV-related PeIN, were present in 100 cases. Non-HPV-related (differentiated) PeIN was the most common subtype associated with LSc (89%). There were 5 spatial patterns identified: (1) LSc adjacent to PeIN (23%), (2) LSc adjacent and comprising PeIN (42%), (3) LSc next to and within invasive carcinomas (8%), (4) LSc throughout the sequence PeIN-invasive carcinoma (24%), and (5) LSc was separate (with normal tissue between the lesions) from PeIN and/or invasive carcinomas in a minority of cases (3%). LSc within the cancer was not previously described. In this series, we found 35 cases with LSc within invasive carcinomas. The striking continuous spatial relationship among LSc, PeIN, and/or invasive carcinoma as shown in this study may be a necessary (but not sufficient) condition for the hypothesis postulating LSc as a penile precancerous lesion.

International journal of surgical pathology. 2019 Jan 07 [Epub ahead of print]

Sofía Cañete-Portillo, Diego F Sanchez, María José Fernández-Nestosa, Adriano Piris, Patricia Zarza, Sabrina Oneto, Lorena Gonzalez Stark, Cecilia Lezcano, Gustavo Ayala, Ingrid Rodriguez, Mai P Hoang, Martin C Mihm, Antonio L Cubilla

1 Instituto de Patología e Investigación, Asunción, Paraguay., 5 Brigham and Women's Hospital, Boston, MA, USA., 7 Memorial Sloan Kettering Center, New York, NY, USA., 8 University of Texas Health Science Center at Houston, TX, USA., 3 Universidad Nacional de Asunción, Facultad de Ciencias Médicas, Asunción, Paraguay., 6 Harvard Medical School, Boston, MA, USA.