Seminars in Diagnostic Pathology RSS feed: Current Issue. Each issue of Seminars in Diagnostic Pathology offers current, authoritative reviews of topics in diagnostic anatomic pathology. The Seminars is of interest to pathologists, clinical investigators and physicians in practice. 2011 Topics, Volume 28 February POrthopedic Pathology Alan Schiller, MD May Lymphomas Stefano A. Pileri, MD http://www.semdiagpath.com/?rss=yesElsevier Inc.en © 2012 Published by Elsevier Inc. All rights reserved. Seminars in Diagnostic Pathology0740-2570292May 2012 © 2012 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.semdiagpath.com/article/PIIS0740257012000159/abstract?rss=yesCover10.1053/S0740-2570(12)00015-9Seminars in Diagnostic Pathology 29, 2 (2012)2012-05-01Seminars in Diagnostic Pathology2012-05-01292S0740-2570(11)X0007-2OFCOFChttp://www.semdiagpath.com/article/PIIS0740257012000160/abstract?rss=yesMasthead10.1053/S0740-2570(12)00016-0Seminars in Diagnostic Pathology 29, 2 (2012)2012-05-01Seminars in Diagnostic Pathology2012-05-01292S0740-2570(11)X0007-2IFCIFChttp://www.semdiagpath.com/article/PIIS0740257012000172/abstract?rss=yesEditorial Board10.1053/S0740-2570(12)00017-2Seminars in Diagnostic Pathology 29, 2 (2012)2012-05-01Seminars in Diagnostic Pathology2012-05-01292S0740-2570(11)X0007-2iihttp://www.semdiagpath.com/article/PIIS0740257012000196/abstract?rss=yesTopics10.1053/S0740-2570(12)00019-6Seminars in Diagnostic Pathology 29, 2 (2012)2012-05-01Seminars in Diagnostic Pathology2012-05-01292S0740-2570(11)X0007-2iiiihttp://www.semdiagpath.com/article/PIIS0740257012000184/abstract?rss=yesContents10.1053/S0740-2570(12)00018-4Seminars in Diagnostic Pathology 29, 2 (2012)2012-05-01Seminars in Diagnostic Pathology2012-05-01292S0740-2570(11)X0007-2iiiiiihttp://www.semdiagpath.com/article/PIIS0740257011001109/abstract?rss=yesTraditional knowledge is that penile carcinomas are mostly squamous cell carcinomas (SCCs) and that pathologic classification is not problematic. In reality, only half of penile epithelial tumors are of the usual or conventional histology. The other half is represented by a variegated spectrum of clinicopathological and etiologic entities, some of them difficult to classify, especially the rare ones. Morphologic clues are provided in this publication to aid in the differential diagnosis. The role of human papillomavirus (HPV) infection, present in near half of the tumors, will be discussed in detail. Other topics will include the stratification of patients in prognostic risk groups using pathologic variables and the value of the dynamic sentinel lymph node biopsy to detect early metastasis in penile cancer. A recent work on precancerous lesions will be presented in detail.IntroductionAlcides Chaux, Antonio L. Cubilla10.1053/j.semdp.2011.09.002Seminars in Diagnostic Pathology 29, 2 (2012)2012-05-01Seminars in Diagnostic Pathology2012-05-01292S0740-2570(11)X0007-25758http://www.semdiagpath.com/article/PIIS0740257011000712/abstract?rss=yes Most primary malignant tumors of the penis are squamous cell carcinomas (SCC) of the usual type. In recent years several variants, each with distinctive clinicopathologic features, have been described. Pseudohyperplastic carcinoma and carcinoma cuniculatum are both low-grade, extremely well-differentiated SCC variants characterized by an indolent clinical course and good prognosis. The former, which may be confused with pseudoepitheliomatous hyperplasia, preferentially affects the inner foreskin mucosa of elderly men and the latter is a verruciform tumor with an endophytic, burrow-like pattern of growth. Pseudoglandular carcinoma (featuring solid tumor nests with extensive central acantholysis simulating glandular lumina) and clear cell carcinoma (human papillomavirus [HPV]-related tumors composed of periodic acid–Schiff positive clear cells) are aggressive tumors with a high incidence of inguinal nodal metastases. Papillary carcinomas are HPV-unrelated verruciform tumors composed of complex papillae with acanthosis, hyper- and parakeratosis, absence of koilocytes, irregular fibrovascular cores, and jagged tumor base. Finally, in warty–basaloid carcinomas areas of warty (condylomatous) and basaloid carcinomas coexist in the same tumor, either separated or intermingled, giving the tumor a variegated appearance. In this review special emphasis is given to the differential diagnosis of these special variants with a discussion of the possible implications for clinical management. New pathologic entities in penile carcinomas: an update of the 2004 World Health Organization ClassificationAlcides Chaux, Elsa F. Velazquez, José E. Barreto, Enrique Ayala, Antonio L. Cubilla10.1053/j.semdp.2011.06.001Seminars in Diagnostic Pathology 29, 2 (2012)2012-05-01Seminars in Diagnostic Pathology2012-05-01292S0740-2570(11)X0007-25966http://www.semdiagpath.com/article/PIIS0740257011001092/abstract?rss=yes Emerging evidence suggests that penile cancer follows 2 etiologic pathways, 1 related to human papillomavirus (HPV) infection and the other related to other factors including phimosis, chronic inflammation, and lichen sclerosus. HPV DNA is found in 47% to 48% of all penile tumors, and most of these cases correspond to high-risk genotypes, preferentially HPV-16. HPV status is associated with histologic subtype, with higher detection ratios in warty–basaloid carcinomas and lower detection ratios in keratinizing variants (ie, verrucous, papillary, and usual squamous cell carcinomas). It is the cell type, rather than a distinctive architecture, that is more strongly associated with HPV presence. The detection ratio is higher in tumors composed entirely or partially of cells with basaloid features. In addition, a few studies have evaluated the impact of HPV infection on the prognosis of patients with penile cancer. However, results are controversial, and more data are needed to clarify this matter. A proper understanding of the role of HPV in penile carcinogenesis might help in planning intervention strategies such as vaccination against HPV infection. The role of human papillomavirus infection in the pathogenesis of penile squamous cell carcinomasAlcides Chaux, Antonio L. Cubilla10.1053/j.semdp.2011.09.001Seminars in Diagnostic Pathology 29, 2 (2012)2012-05-01Seminars in Diagnostic Pathology2012-05-01292S0740-2570(11)X0007-26771http://www.semdiagpath.com/article/PIIS0740257011001018/abstract?rss=yes Penile precancerous and invasive lesions exhibit a variegated morphology. Although the diagnosis and classification of penile tumors is straightforward in most cases, a few entities are problematic, especially to pathologists from countries in which penile cancer is rarely encountered. The differential diagnosis of squamous hyperplasias from differentiated penile intraepithelial neoplasia or from extremely low-grade invasive neoplasms (eg, pseudohyperplastic and verrucous carcinomas) may be particularly difficult. Similarly, given the morphologic features shared by all verruciform tumors (ie, verrucous, warty, papillary, and cuniculatum carcinomas, along with giant condylomas), it is challenging at times to distinguish one from another. At the other end of the spectrum, because of their lack of differentiation, it is sometimes difficult to classify high-grade carcinomas, such as basaloid and sarcomatoid, which may have etiologic/prognostic implications. Penile mixed tumors, harboring more than 1 histologic subtype and grade, constitute a frequent finding in routine pathology. The recognition of distinctive morphologic patterns and histologic grades in these tumors is important because these features could be related to etiologic factors, such as human papillomavirus infection, or they could influence outcome. Penile tumors with glandular features (eg, adenosquamous and mucoepidermoid carcinomas), although rare, may be confused with the more common pseudoglandular (adenoid, acantholytic) variant of squamous cell carcinomas, their main mimicker. In this review we provide clues that may help in the differential diagnosis of these lesions. Diagnostic problems in precancerous lesions and invasive carcinomas of the penisAlcides Chaux, Antonio L. Cubilla10.1053/j.semdp.2011.08.002Seminars in Diagnostic Pathology 29, 2 (2012)2012-05-01Seminars in Diagnostic Pathology2012-05-01292S0740-2570(11)X0007-27282http://www.semdiagpath.com/article/PIIS0740257011001055/abstract?rss=yes Inguinal lymph node metastasis is the single most important factor for predicting survival in patients with penile squamous cell carcinomas. To estimate the likelihood of this event, investigators have combined pathologic features of the primary tumor in the form of stratification systems. In this article we review 3 such systems (Solsona et al, J Urol 2001;165:1506; Hungerhuber et al, Urology 68:621, 2006; and Chaux et al, Am J Surg Pathol 2009;33:1049) built upon histologic grade, extent and depth of tumor invasion, and perineural invasion. We evaluate their usefulness, limitations, and possible implications for the management of patients with penile cancer. We also provide clues for the proper identification and interpretation of these pathologic features. Inguinal metastases were observed in 64% to 83% of patients in high-risk groups, 20% to 33% of intermediate groups, and 0% to 8% of low-risk groups. The results of these studies suggest that patients in high-risk groups could benefit from prophylactic bilateral groin dissection. In addition, patients in low-risk groups might be managed by surveillance alone. Finally, the authors suggest that additional approaches, such as sentinel lymph node biopsy, should be used for the intermediate-risk group. The identification of other pathologic features, such as vascular and perineural invasion, could tip the scales in problematic or paradoxical cases. The fate of these risk groups would be better defined by the identification of molecular biomarkers and genetic profiling. Stratification systems as prognostic tools for defining risk of lymph node metastasis in penile squamous cell carcinomasAlcides Chaux, Antonio L. Cubilla10.1053/j.semdp.2011.08.006Seminars in Diagnostic Pathology 29, 2 (2012)2012-05-01Seminars in Diagnostic Pathology2012-05-01292S0740-2570(11)X0007-28389http://www.semdiagpath.com/article/PIIS0740257011001006/abstract?rss=yes Sentinel lymph node (SLN) biopsy is a fairly new technique that is becoming the standard of care for regional lymph node staging of many solid tumors. This technique is based on the hypothesis of stepwise distribution of malignant cells in the lymphatic system. The absence of tumor cells in the first lymph node(s) in the lymphatic drainage of a tumor would indicate the absence of further spread in the regional lymph node basin(s). Therefore, this first lymph node is the guardian (sentinel) of the regional lymph node basin. To localize the sentinel node preoperatively, lymphoscintigraphy is usually performed after intradermal peritumoral injections of colloid particles labeled with technetium-99m. The tracer is transported through the lymphatic channels to the first draining nodes in the groins and is visible on the lymphoscintigram as hot spots. The main advantage of SLN biopsy in penile cancer is to decrease the treatment-related morbidity without compromising the survival benefit for the patient. Recent figures indicate a false-negative rate of 7%, with a complication rate of less than 5% for SLN biopsy. In conclusion, sentinel node biopsy of patients with penile cancer has evolved into a highly reliable procedure enabling the detection of lymph node invasion at the earliest possible time with minimal morbidity. With this technology at hand, which minimizes the treatment-related morbidity, there is hardly any place for standard lymphadenectomy in penile cancer patients. Sentinel lymph node biopsy in penile carcinomaSimon Horenblas10.1053/j.semdp.2011.08.001Seminars in Diagnostic Pathology 29, 2 (2012)2012-05-01Seminars in Diagnostic Pathology2012-05-01292S0740-2570(11)X0007-29095http://www.semdiagpath.com/article/PIIS0740257011001080/abstract?rss=yes Penile squamous cell carcinomas (SCCs) and their corresponding precancerous lesions can be classified in 2 major groups: human papillomavirus (HPV) related and HPV unrelated. In the former (warty and basaloid SCC), there is a predominance of undifferentiated basaloid cells. In the latter (eg, usual, papillary, and verrucous SCC), the predominant cell is larger with abundant eosinophilic cytoplasm. Based on these morphologic features, a new term, “penile intraepithelial neoplasia” (PeIN), was proposed. PeIN was further subclassified into differentiated and undifferentiated, with the latter being subdivided into basaloid, warty, and warty–basaloid subtypes. Macroscopically, PeIN subtypes are indistinguishable. Microscopically, differentiated PeIN is characterized by acanthosis, parakeratosis, enlarged keratinocytes with abundant “pink” cytoplasm (abnormal maturation), and hyperchromatic cells in the basal layer. In basaloid PeIN the epithelium is replaced by a monotonous population of uniform, small, round, and basophilic cells. Warty PeIN is characterized by a spiky surface, prominent atypical parakeratosis, and pleomorphic koilocytosis. Warty–basaloid PeIN show features of both warty and basaloid PeIN. There is a significant association of subtypes of PeIN with specific variants of invasive SCCs. This is a simple and reproducible nomenclature for penile precancerous lesions based on cell type and differentiation. It takes into account the similarities between vulvar and penile pathology and the hypothesis of a bimodal pathway of penile cancer progression. Histologic classification of penile intraepithelial neoplasiaElsa F. Velazquez, Alcides Chaux, Antonio L. Cubilla10.1053/j.semdp.2011.08.009Seminars in Diagnostic Pathology 29, 2 (2012)2012-05-01Seminars in Diagnostic Pathology2012-05-01292S0740-2570(11)X0007-296102