Discordant molecular subtype classification in the basal-squamous subtype of bladder tumors and matched lymph-node metastases.

Molecular subtypes of muscle-invasive bladder tumors have emerged as a promising research tool with potential to stratify patients for neoadjuvant treatment. Prior to radical cystectomy, the utility of molecular classification and biomarkers depend on concordance between tissue from transurethrally resected specimens and disseminated disease. We assess the concordance of molecular subtypes and a large number of potential biomarkers in 67 pairs of muscle-invasive bladder tumors and synchronous lymph-node metastases. Tissue cores were stained for 29 immunohistochemistry markers and immunohistochemistry-based molecular subtype classification was performed. Molecular subtype was determined by mRNA profiling for 57 bladder tumors and 28 matched lymph-node metastases. Full section immunohistochemistry was performed to assess intra-tumor subtype heterogeneity in discordant cases, and exome sequencing was performed for 20 sample pairs. Discordant subtype classification between the bladder tumor and lymph-node metastasis was generally rare (12/67, 18%), but most (7/12, 58%) involved the Basal/Squamous-like subtype. Discordant Basal/Squamous-like tumors showed either Urothelial-like or Genomically Unstable, luminal-like phenotype in the lymph-node metastasis. Full section immunohistochemistry revealed intra-tumor subtype heterogeneity for six discordant cases including four involving the Basal/Squamous-like subtype. Subtype concordance for non- Basal/Squamous-like tumors was 91%. RNA-based classification agreed with immunohistochemistry classification but quantitative assessment is necessary to avoid false detection of subtype shifts. Most high confidence cancer mutations were shared between samples (n = 93, 78%), and bladder tumor private mutations (n = 20, 17%) were more frequent than those private to the lymph-node metastasis (n = 7, 6%). We conclude that bladder tumors and lymph-node metastases have overall similar molecular subtype, biomarker expression, and cancer mutations. The main exception was tumors of the Basal/Squamous-like subtype where most cases showed discordant classification, some with evidence of intra-tumor heterogeneity. The data are of relevance for neoadjuvant treatment stratification and raises questions on the dynamics of molecular subtypes during bladder cancer progression.

New pathologic entities in penile carcinomas: an update of the 2004 world health organization classification.

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.

Histologic classification of penile intraepithelial neoplasia.

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.

Carcinomas cutáneos: historia y clasificación / Cutaneous carcinomas: history and classification

Se efectua una apretada síntesis histórica desde los papiros egipcios hasta la actualidad. Luego se clasifica a los epiteliomas o carcinomas cutáneos en: 1- Carcinomas primitivos cutáneos. 2- Carcinomas intermediarios. 3- Carcinomas espinocelulares. 4- Carcinomas anexiales: sudoríparos, sebáceos, pilosos. 5- Carcinomas anexiales fundamentales. 6- Carcinomas "in situ" (intraepiteliales). Este sistema clasificatorio, basado en la histogénesis, ha demostrado ser de utilidad práctica a través del tiempo. Consideramos que se trata de un valioso trabajo de revisión y actualización producto de 5 décadas de experiencia. Se caracteriza por ser sintético, preciso y con criterio didáctico. Los conceptos están vertidos mediante 150 diapositivas demostrativas que expresan con certeza los caracteres clínicos e histológicos de las neoplasias cutáneas, salvo el melanoma. Uno de los autores (J.A) comienza el estudio en 1953 con su tesis de doctorado: "Epiteliomas cutáneos: ensayo de clasificación citogenética". Es un monumental ensayo ilustrado con numerosas microfotografías en blanco y negro, cuya consulta recomendamos en la Biblioteca de la Facultad de Ciencias Médicas de la UBA.

Basaloid squamous cell carcinoma of the hypopharynx.

In a retrospective study, clinical, histopathological and immunohistochemical findings of basaloid squamous cell carcinoma (BSCC) of the hypopharynx are analyzed and compared with the literature. Among 196 patients treated for hypopharyngeal carcinoma between January 1993 and December 2000, 6 patients fulfilled the morphological and immunohistochemical criteria of a BSCC. Three primary tumors were initially classified as T(3) and 3 as T(1), 3 presented with lymph node metastases. In no case was the BSCC associated with another primary neoplasm. Two patients developed distant metastases during the follow-up and died from the disease at 26 and 35 months. Four patients are alive with no evidence of disease at 27, 29, 61 and 87 months. We observed a contrast in the clinical behavior between the cases reported in the literature and our cases, as our BSCC of the hypopharynx were not detected at a more advanced stage than were the SCC and were in no case associated with another second primary tumor. However, the number of our cases is too small to draw reliable conclusions.

Karyometric study of basal cell carcinoma / Estudo da cariometria do carcinoma de células basais

The purpose of the present study was to determine different nuclear parameters of neoplastic cells in basal cell carcinomas. The results showed the absence of alterations in the size of the neoplastic cell nucleus, whereas the nuclear shape was significantly modified. According to the present study it is possible to claim that the parameters which estimate the nuclear shape are more sensitive that those reflecting the nuclear size to detect malignancy in basal cell carcinoma

beta-2-Microglobulin in primordial and differentiated basocellular carcinomas and basosquamous carcinomas.

27 cases of basocellular carcinomas and basosquamous carcinomas of the skin were classified into primordial and differentiated basocellular carcinomas and basosquamous carcinomas and stained for beta-2-microglobulin using the immunoperoxidase technique. All the differentiated basocellular carcinomas and some of the basosquamous carcinomas contained beta-2-microglobulin, but none was found in the primordial basocellular carcinomas. Staining of basal cell tumors for beta-2-microglobulin may be helpful in interpreting adnexoid and epidermoid differentiation in skin tumors.