Histomorfometria e índice proliferativo (Ki-67) no carcinoma escamocelular in situ de pregas vocais / Histomorphometry and proliferative index in squamous cell carcinoma in situ of the vocal cords

INTRODUÇÃO: As displasias da laringe são precursoras do carcinoma escamocelular invasivo e constituem lesões pouco comuns, pois a maior parte dos casos é detectada como carcinoma invasor. OBJETIVO: Caracterizar as displasias acentuadas/carcinoma in situ da prega vocal quanto a área do epitélio, diâmetro dos núcleos e índice proliferativo, comparando esses dados com os obtidos no epitélio escamoso normal e de transição. MATERIAL E MÉTODO: Entre as 1.400 biópsias e peças cirúrgicas de lesões intraepiteliais e carcinomas invasivos de laringe (1994-2006), foram selecionados cinco casos (0,35%) pareados com dois controles de epitélio normal e com a idade; todos foram submetidos a análise morfométrica e imuno--histoquímica (Ki-67). RESULTADOS: Comparando-se o epitélio displásico com o normal e de transição observou-se maior área e diâmetro nuclear no epitélio displásico; não houve diferenças significativas no diâmetro dos núcleos por camada entre o epitélio displásico e de transição; e o índice proliferativo foi maior no epitélio displásico com núcleos corados em todas camadas e menor com núcleos limitados a camada basal e parabasal no epitélio normal e de transição. CONCLUSÃO: verifica-se maior área no epitélio displásico. O diâmetro dos núcleos do epitélio displásico e do de transição são semelhantes, mas este apresenta núcleos uniformes em toda extensão em contraste com o pleomorfismo do epitélio displásico. O índice proliferativo (Ki-67) contribui para o diagnóstico diferencial das lesões escamosas da prega vocal, pois no carcinoma in situ/displasia acentuada observa-se maior número de núcleos marcados, os quais são vistos em todas as camadas no epitélio.

INTRODUCTION: Laryngeal dysplasias, precursors of squamous cell carcinomas, are uncommon lesions, inasmuch as most cases are diagnosed as invasive carcinomas. OBJECTIVE: To characterize severe dysplasia/in situ carcinoma of the vocal cords by comparing the area of involved epithelium, nuclear diameter, and proliferative index with transition and normal squamous epithelia. MATERIAL AND METHOD: Among 1,400 surgical and biopsy specimens of laryngeal lesions (1994-2006), five cases (0.35%) were selected and compared according to age with two controls with normal epithelium. Furthermore, all of them were identified and submitted to morphometric and immunohistochemical analysis (Ki-67). RESULTS: After comparing dysplastic with transition and normal squamous epithelia, it was observed an increased nuclear diameter in dysplastic epithelium. Additionally, there was no significant difference in nuclear diameter per layer between dysplastic and transition epithelia. Moreover, the proliferative index was higher in dysplastic epithelium with stained nuclei in all layers and lower in normal and transition epithelia with nuclei concentrated on the basal and parabasal layers. CONCLUSION: Dysplastic epithelium occupies larger areas. Nuclear diameter is similar in dysplastic and transition epithelia. However, the latter has uniform nuclei, in contrast with pleomorphism in dysplastic epithelium. The proliferative index (Ki-67) contributes to the differential diagnosis of intraepithelial lesions of the vocal cords, inasmuch as in severe dysplasia/in situ carcinoma there is a higher number of stained nuclei, which are seen in all epithelial layers.

Avaliação dos fatores preditivos de invasão neoplásica do complexo areolomamilar em pacientes com câncer de mama / Evaluation of the predictive factors involved in the neoplastic invasion of the nipple-areolar complex in patients with breast cancer

INTRODUÇÃO: A escolha pela mastectomia com preservação do complexo areolomamilar (CAM), de melhor resultado estético, depende da ausência de envolvimento neoplásico do CAM. OBJETIVO: Identificar os fatores preditivos de invasão neoplásica do CAM. MÉTODO: Foi realizado estudo analítico, retrospectivo, clínico-patológico de 48 peças de mastectomia de pacientes portadoras de carcinoma da mama, atendidas no Hospital de Câncer da Paraíba - Fundação Napoleão Laureano, durante o período de abril de 2007 a janeiro de 2008, com idade média de 52,69 ± 10,72 anos. O CAM foi seccionado separadamente mediante cortes perpendiculares e paralelos a partir da papila, estendendo-se a 2 cm de profundidade do tecido retroareolar (com o intuito de incluir seios lactíferos e ductos coletores e segmentares), seguidos de cortes transversais até a base. RESULTADOS: Identificou-se frequência de envolvimento do CAM por carcinoma invasivo em 14,58 por cento dos casos. Pacientes jovens (média 42,3 ± 4,7 anos), distância do tumor a mamilo/aréola < 2 cm, tamanho da aréola < 3 cm, tipo histológico (carcinoma ductal invasivo associado a carcinoma ductal in situ padrão comedônico), status dos linfonodos axilares (sobretudo com metástases em 10 ou mais linfonodos), presença de invasão angiolinfática ou perineural e existência de infiltrado inflamatório dos estromas intratumoral e peritumoral foram associados a maior risco de envolvimento do CAM (p < 0,05). O menor diâmetro da aréola foi relacionado significativamente com o menor peso da mama (p < 0,0016), mostrando que o tamanho da mama teve maior impacto no encontro de invasão do CAM que o diâmetro tumoral. CONCLUSÃO: Os resultados desta pesquisa permitiram identificar fatores associados a maior risco de invasão neoplásica areolopapilar.

INTRODUCTION: The choice for having mastectomy with preservation of the nipple-areolar complex (NAC), with better esthetic results, depends on the abscence of neoplastic invasion of the NAC. OBJECTIVE: To identify the predictive factors related to neoplastic NAC invasion. METHODS: We carried out a retrospective, analytical and clinical-pathologic study comprising 48 mastectomy specimens of breast carcinoma from patients treated at Cancer Institute of Paraíba - Napoleão Laureano Foundation (Hospital de Câncer da Paraíba - Fundação Napoleão Laureano) from April 2007 to January 2008. The mean age was 52.69 ± 10.72. The NAC complex was sectioned separately and perpendicular and parallel cuts were performed from the papilla extending 2 cm deep into the retroareolar tissue (including collecting ducts, lactiferous sinuses and segmental ducts), followed by transverse cuts toward the deep margin. RESULTS: The frequency of NAC involvement by invasive carcinoma was 14.58 percent. The following characteristics were associated with a higher risk of NAC involvement (p < 0.05): younger patients (mean age 42.3 ± 4.7 years), distance between the tumor and the areola/nipple < 2 cm, size of the areola < 3 cm, histological type (invasive ductal carcinoma associated with comedo type ductal carcinoma in situ), status of axillary lymph nodes (mainly with metastasis in 10 or more lymph nodes), presence of lymphovascular and perineural invasion, and inflammatory infiltrate of intra/peritumoral stroma. Smaller areolas correlated significantly with decreased breast weights (p < 0.0016), which demonstrated that the breast size had a greater impact on NAC involvement in comparison with the tumor diameter. CONCLUSION: The results of this study enabled us to identify factors associated with an increased risk of neoplastic NAC invasion.

Homozygous alpha-thalassemia with trisomy 7 mosaicism in a live-born infant.

The authors report a male infant born at 35 weeks gestational age with an atypical presentation of homozygous alpha-thalassemia. The live-born infant displayed abnormalities of the upper limbs and genitalia, which are vascular-type disruptive defects associated with this disease. Cardiomegaly and placentomegaly were the only evidence of fetal hydrops. Postnatal karyotype revealed mosaicism for trisomy 7, yet another rare finding in a live-born. The authors discuss their institutional experience with each of these rare conditions and the potential contribution of each to the overall unusual clinical presentation in this patient. This is the first report of these simultaneous diagnoses.

Core biopsy no diagnóstico das lesões mamárias impalpáveis na categoria mamográfica BI-RADS® 5 / Core biopsy in nonpalpable BI-RADS® 5 breast lesions

INTRODUÇÃO E OBJETIVOS: Determinar a associação entre alterações mamográficas classificadas na categoria BI-RADS® 5 (lesões altamente suspeitas de malignidade) e diagnóstico histopatológico em material obtido por core biopsy estereotáxica e estabelecer o valor preditivo positivo dessa categoria mamográfica para o diagnóstico de câncer. MÉTODOS: Por meio de estudo retrospectivo, transversal, analítico, de comparação entre métodos diagnósticos, foram analisadas 70 core biopsies de lesões mamárias impalpáveis, classificadas como BI-RADS® 5, de 70 pacientes, atendidas em serviços privados de Anatomia Patológica e Radiologia em Recife, Brasil, entre 2001 e 2006. RESULTADOS: Foram mais acometidos: sexo feminino (97,1 por cento), mama esquerda (60 por cento) e quadrante superior externo (62,9 por cento). Os nódulos irregulares espiculados constituíram 70 por cento da amostra e as microcalcificações estavam presentes em 44,3 por cento. O número médio de fragmentos obtidos foi 6 ± 2. Os diagnósticos histopatológicos foram: carcinoma (59 casos; 84,3 por cento); lesões benignas (sete casos; 10 por cento) e hiperplasia ductal atípica ou lesão suspeita de malignidade (quatro casos; 5,7 por cento). Os nódulos irregulares espiculados corresponderam significantemente a carcinoma invasivo (p = 0,005). O carcinoma ductal in situ (CDIS) padrão comedônico puro associou-se mais frequentemente às microcalcificações na histologia. Os valores preditivos positivos foram: 84,3 por cento para a categoria mamográfica BI-RADS® 5 como um todo; 100 por cento para nódulo irregular espiculado com microcalcificações; 87,8 por cento para nódulo irregular espiculado com ou sem microcalcificações; 84,2 por cento para nódulo irregular espiculado sem microcalcificações; e 75 por cento para microcalcificações sem nódulos. CONCLUSÃO: Lesões mamárias impalpáveis da categoria mamográfica BI-RADS® 5 são de alto valor preditivo para carcinoma, particularmente os nódulos irregulares ...

INTRODUCTION AND OBJECTIVES: To determine the association between mammographic alterations classified as BI-RADS® 5 category (lesions highly suggestive of malignancy) and the corresponding histopathological diagnoses of samples obtained by stereotactic core biopsy; to establish the positive predictive value of this mammographic category for the diagnosis of cancer. METHODS: By means of retrospective cross sectional analytical study comparing diagnostic methods, we investigated seventy stereotactic core biopsies of nonpalpable breast lesions classified as BI-RADS® 5 from 70 patients seen at private Anatomic Pathology and Radiology services in Recife (Pernambuco state, Brazil) from 2001 to 2006. RESULTS: Female patients (97.1 percent) were predominantly affected. The left breast (60 percent) and upper outer quadrant (62.9 percent) were more commonly involved. Irregular spiculated nodules corresponded to 70 percent of the cases, and microcalcifications to 44.3 percent. The mean number of core fragments was 6 ± 2. The histopathological diagnoses were: carcinoma (59 cases; 84.3 percent), benign lesions (seven cases; 10 percent) and atypical ductal hyperplasia or lesion suspected of malignancy (four cases; 5.7 percent). Invasive carcinoma was significantly associated with irregular spiculated nodules (p = 0.005). Pure comedo DCIS was more frequently associated with microcalcifications on histology. The positive predictive values were: 84.3 percent for BI-RADS® 5 category as a whole, 100 percent for irregular spiculated nodules with microcalcifications, 87.8 percent for irregular spiculated nodules with or without calcifications, 84.2 percent for irregular spiculated nodules without microcalcifications and 75 percent for microcalcifications without nodes. CONCLUSION: Breast lesions classified as BI-RADS® 5 have a high positive predictive value for carcinoma, particularly irregular spiculated nodules with microcalcifications.

Pathologic features of ulcerative colitis in patients with primary sclerosing cholangitis: a case-control study.

BACKGROUND: The pathologic features of ulcerative colitis (UC) in patients with primary sclerosing cholangitis (PSC) are, essentially, unknown. One previous clinical study suggested that UC-PSC patients reveal a high rate of rectal sparing and backwash ileitis. The purpose of this study was to systematically evaluate the pathologic characteristics and distribution of colonic disease in UC-PSC patients and to compare the results with a matched control group of UC patients without PSC. METHODS: Forty UC-PSC patients and 40 matched UC patients without PSC (controls) were identified from the files of 3 hospitals between the years 1989 and 2005. Clinical, endoscopic, and follow-up data (including incidence of pouchitis) were evaluated, and a detailed pathologic evaluation of biopsy and resection specimens (when available) was performed in a blinded fashion. The degree of activity and chronicity in mucosal biopsies and/or tissue from resection specimens was graded on a 5-point grading system (0 to 4), and each portion of the colon (cecum, ascending colon, transverse colon, descending colon, rectum) was assessed separately. Rectal sparing and patchiness of disease were evaluated, and scored as either absolute or relative depending on the complete absence of inflammatory disease in the former, or less inflammatory disease in the rectum compared with other parts of the colon in the latter. RESULTS: In this matched case-control study, UC-PSC patients presented at a significantly earlier age (24.5 y), had a higher prevalence rate of pancolitis (85%), and an overall significantly lower grade of inflammation in the colon (mean grade: 2.09+/-0.085) compared with UC controls (mean age: 33.8 y, pancolitis: 45%, inflammation grade: 2.59+/-0.92, P<0.05 for all comparisons). The incidence rate of absolute and relative rectal sparing (27.5%) and of patchy inflammatory disease proximal to the rectum (5.7%) was not significantly different between the UC-PSC cases and the UC controls (25% and 7.9%, respectively). UC-PSC patients had a higher prevalence rate of ileitis (35.7%) and pouchitis (42.8%), but the values were not significantly different from controls (26.9% and 26.6%, respectively). The incidence rate of dysplasia was similar between the 2 patient groups. CONCLUSIONS: UC patients with PSC show a propensity for more extensive, but less active, disease but are otherwise characterized by similar pathologic findings compared with UC patients without PSC. Rectal sparing and patchy disease activity is not characteristic of UC patients with PSC.

Carcinoma papilífero da tireoide associado à tireoidite de Hashimoto: frequência e aspectos histopatológicos / Papillary thyroid carcinoma associated to Hashimoto's thyroiditis: frequency and histopathological aspects

INTRODUÇÃO: O carcinoma papilífero é o tipo mais comum de câncer da tireoide e a tireoidite de Hashimoto é a causa mais frequente de hipotireoidismo em áreas onde os níveis de iodo são adequados. Vários investigadores detectaram incidência aumentada de carcinoma papilífero da tireoide em pacientes com tireoidite de Hashimoto. Na rotina de diagnósticos histopatológicos há uma aparente associação entre as duas patologias. OBJETIVO: Determinar a relação entre tireoidite de Hashimoto e carcinoma papilífero de tireoide, avaliando os aspectos histomorfológicos, quando concomitantes ou apresentando-se de forma isolada. MÉTODO: Foi realizado estudo retrospectivo a partir dos dados do arquivo do Serviço de Patologia do Hospital Barão de Lucena, afiliado ao Sistema Único de Saúde (SUS) (Recife-PE), incluindo 95 casos, entre 472 cirurgias de tireoide realizadas no período de janeiro de 1995 a janeiro de 2005. RESULTADOS: Houve 35 casos (7,4 por cento) de tireoidite de Hashimoto, 48 (10,2 por cento) de carcinoma papilífero e 12 (2,5 por cento) de associação significativa (p < 0,05) dessas patologias, representando 20 por cento dos casos de carcinoma papilífero. Não houve diferença significativa quanto a idade, sexo, existência de neoplasia benigna concomitante, maior diâmetro tumoral, invasão capsular, multifocalidade e variante histológica do carcinoma papilífero, quer ocorrendo isoladamente, quer em associação à tireoidite de Hashimoto. Houve associação significante com relação à maior frequência de cápsula nos carcinomas papilíferos isolados, quando em comparação com o grupo de carcinomas papilíferos associados à tireoidite de Hashimoto. CONCLUSÃO: A presença de tireoidite de Hashimoto deve alertar para o risco de desenvolvimento de carcinoma papilífero de tireoide, já que essas patologias estiveram significativamente associadas.

INTRODUCTION: Papillary carcinoma is the most common type of thyroid cancer and Hashimoto's thyroiditis is the most frequent cause of hypothyroidism in areas where iodine levels are adequate. Several investigators have detected an increased incidence of papillary thyroid carcinoma in patients with Hashimoto's thyroiditis. In histopathological diagnosis routine, there is an apparent association between these two pathologies. OBJECTIVE: To determine the association between Hashimoto's thyroiditis and papillary thyroid carcinoma, evaluating the histopathological aspects, when concomitantly present or isolated. METHODS: A retrospective study was carried out with data from the archives of the Pathology Service at hospital Barão de Lucena, SUS (Recife-PE, Brazil), which included 95 cases amongst 472 thyroid surgeries performed from January 1995 through January 2005. RESULTS: There were 35 cases (7.4 percent) of Hashimoto's thyroiditis, 48 cases (10.2 percent) of papillary carcinoma and 12 cases (2.5 percent) of significant association of these pathologies (p < 0.05), which corresponded to 20 percent of the papillary carcinoma cases. There was no significant difference as to age, gender, presence of concomitant benign neoplasia, larger tumor diameter, multifocality or histological variant of papillary carcinoma, between cases of isolated papillary carcinoma or carcinoma associated with Hashimoto's thyroiditis. There was a significant association concerning the higher frequency of a tumor capsule in isolated papillary carcinomas when compared with papillary carcinomas with concomitant Hashimoto's thyroiditis. CONCLUSION: The presence of Hashimoto's thyroiditis should alert to the risk of papillary thyroid carcinoma development, as these diseases were significantly associated.

Pre-operative estimation of esophageal tumor metabolic length in FDG-PET images with surgical pathology confirmation.

OBJECTIVE: The aim of this study was to evaluate a 3D tumor segmentation method for fluorodeoxyglucose positron emission tomography (FDG-PET) in the context of noninvasive estimation of tumor metabolic length (Lm), as it correlates with surgical pathology and phantom results. METHODS: Thirty-four patients (7 women, 27 men) with esophageal cancer were retrospectively evaluated. All patients underwent FDG-PET-computed tomography (CT) imaging following endoscopic ultrasound (EUS). Seventeen patients had esophagectomy after PET/CT, without prior neoadjuvant therapy. Tumor length was assessed by EUS (Le, n=31) and histopathology (Lp, n=17). Images were evaluated quantitatively with a 3D threshold-based region-growing program (Medical Image Processing Analysis and Visualization). Lm, total metabolic volume (Vm), maximum standardized uptake value (SUVmax), and average SUV (SUVa) over the entire tumor were obtained for several threshold values (mean activity in the liver plus 0-, 1-, 2-, 3-, and 4-SD of the activity in the liver). RESULTS: Lm showed a good correlation with Lp for all thresholds (best correlation for Lm(2-SD), r=0.74, P<0.001). A positive nonsignificant correlation was observed between Lp and Le (r=0.30, P=0.29). Lm(2-SD) correlated well with Le (r=0.71, P<0.001). Good correlations were also observed between Lm(2-SD) and Vm(2-SD) (r=0.89, P<0.001) and SUVa(2-SD) (r=0.38, P<0.05). Vm(2-SD) also had a significant correlation with Lp (r=0.61, P<0.05) and Le (r=0.57, P<0.001). CONCLUSIONS: FDG-PET-derived tumor metabolic length of untreated esophageal carcinomas correlates well with surgical pathology results, and provides preliminary evidence that noninvasive delineation of the superior and inferior extent of viable tumor involvement might be feasible using computer-generated metabolic length measurements.

FDG-PET/CT tumor segmentation-derived indices of metabolic activity to assess response to neoadjuvant therapy and progression-free survival in esophageal cancer: correlation with histopathology results.

PURPOSE: To evaluate the diagnostic and prognostic abilities of PET tumor segmentation-derived indices of metabolic activity for the assessment of response to neoadjuvant chemoradiotherapy and progression-free survival in patients with esophageal cancer. METHODS: Twenty-five patients with histologically confirmed esophageal cancer were retrospectively evaluated. The patients underwent PET-CT imaging before and after completion of neoadjuvant therapy. Images were evaluated visually and quantitatively with a three-dimensional threshold-based region-growing program, which calculates SUVm, SUVa of the entire tumor, metabolic tumor length (Lm) and volume (Vm) before and after therapy (SUVm1, SUVm2, SUVa1, SUVa2, Lm1, Lm2, Vm1, and Vm2, respectively). Percentage changes in these metabolic variables before and after therapy were also calculated (%SUVm, %SUVa, %Lm, %Vm, respectively). RESULTS: SUVm1 (P = 0.018), SUVa1 (P = 0.019), Lm1 (P = 0.016), and Vm1 (P = 0.016) correlated with T-status. Advanced stage tumors (T3 + T4) had significantly higher glucose metabolism, metabolic length, and volume. Moreover, Lm1 >47.4 mm and Vm1 >29 cm3 were the best predictors of the level of tumor invasiveness. SUVm1 >12.7 and SUVa1 >5.9 could differentiate patients with positive lymph nodes from those without at presentation. %SUVa >32.3% and the SUVa1 >5.5 proved to be reliable predictors of pathologic response. SUVa2 >3.55 and SUVm2 >4.35 were the best predictors of disease progression during follow-up, with the latter having the best prognostic value. CONCLUSIONS: This study showed that FDG-PET tumor segmentation-derived indices of metabolic activity play a definite role in the evaluation of response to neoadjuvant chemoradiotherapy and progression-free survival in patients with esophageal cancer.

Clusterin is a secreted marker for a hypoxia-inducible factor-independent function of the von Hippel-Lindau tumor suppressor protein.

Germline mutations in the von Hippel-Lindau (VHL) tumor suppressor gene predispose people to renal cancer, hemangioblastomas, and pheochromocytomas in an allele-specific manner. The best documented function of the VHL gene product (pVHL) relates to its ability to polyubiquitinate, and hence target for destruction, the alpha subunits of the heterodimeric transcription factor hypoxia-inducible factor (HIF). pVHL mutants linked to familial pheochromocyctoma (type 2C VHL disease), in contrast to classical VHL disease, appear to be normal with respect to HIF regulation. Using a simple method for identifying proteins that are differentially secreted by isogenic cell line pairs, we confirmed that the HIF targets IGBP3 and PAI-1 are overproduced by pVHL-defective renal carcinoma cells. In addition, cells lacking wild-type pVHL, including cells producing type 2C pVHL mutants, were defective with respect to expression and secretion of clusterin, which does not behave like a HIF target. Decreased clusterin secretion by pVHL-defective tumors was confirmed in vivo by immunohistochemistry. Therefore, clusterin is a secreted marker for a HIF-independent pVHL function that might be especially important in pheochromocytoma development.

Aumento da especificidade da mamografia no diagnóstico de lesöes näo-palpáveis: valor da core biopsy estereotática na exclusäo de malignidade / Increasing the specificity of mammography on the diagnosis of nonpalpable lesions: the value of stereotactic core-needley biopsy in excludes malignancy

A mamografia, no diagnóstico de lesöes näo-palpáveis, é considerada de alta sensibilidade e menor especificidade, levando a grande número de biópsias cirúrgicas para avaliaçäo de lesöes, na realidade, benignas. Dentre 700 biópsias estereotáticas de lesöes näo-palpáveis, utilizamos 567 para análise da freqüencia dos tipos de lesöes diagnosticadas. Os casos benignos tiveram acompanhamento clínico-manográfico (6-38 meses) para detecçäo de falsos negativos. Predominaram diagnósticos benignos em 433 (76,36 por cento) casos, sendo 354 (62,43 por cento) näo-neoplásicos e 79 (13,93 por cento) fibroadenomas. A diferença entre os benignos e a soma dos malignos e bordelines (134=23,63 por cento) foi significativa (p<0,0001). No seguimento dos benignos, nove (2,07 por cento) tiveram diagnóstico pós cirúrgico de carcinoma, dos quais sete foram operados ab initio, devido a a mamografias suspeitas. Os outros dois, após modificaçäo durante o acompanhamento clínico-mamográfico. A core biopsy estereotática é eficiente em excluir malignidade e subtipar condiçöes benignas, evitando muitas cirurgias para diagnóstico. Na core biopsy negativa, a biópsia cirúrgica é indicada, quando a a mamografia é sugestiva de malignidade