Enfermedad granulomatosa hepática / Hepatic granulomatous disease

Resumen Los granulomas son lesiones circunscritas compuestas principalmente por células mononucleares que surgen en respuesta a estímulos antigénicos pobremente degradables. Se encuentran en 2 a 15 % de las biopsias hepáticas; su hallazgo puede significar desde un fenómeno incidental, hasta la manifestación de una enfermedad sistémica de origen infeccioso, autoinmune o neoplásico. El cuadro clínico suele apuntar a la patología subyacente, sin embargo, la lista de condiciones asociadas es amplia y difiere con base en los antecedentes epidemiológicos y a las características basales del paciente. El elemento de mayor utilidad para su estudio es la historia clínica exhaustiva, con énfasis en viajes recientes, exposición de riesgo y consumo de fármacos o alimentos crudos o exóticos. El análisis histopatológico detallado puede auxiliar en la identificación de la etiología, por ejemplo, la presencia de granulomas epitelioides con necrosis caseosa indica tuberculosis y su ausencia, sarcoidosis; la abundancia de eosinófilos es señal de reacciones farmacológicas o infecciones parasitarias; la presencia de cuerpos extraños puede ser la causa de la enfermedad granulomatosa hepática. En este artículo describimos los aspectos clínico-patológicos básicos de esta enfermedad y proveemos un breve resumen de las etiologías más comunes, principalmente en la región de Latinoamérica.

Abstract Granulomas are circumscribed lesions mainly composed of mononuclear cells that arise in response to poorly degradable antigenic stimuli. They are found in 2-15 % of liver biopsies and the meaning of their finding can range from an incidental phenomenon to the manifestation of a systemic disease of infectious, autoimmune or neoplastic origin. Clinical presentation usually points at the underlying pathology; however, the list of associated conditions is extensive, and differs based on patient epidemiological history and baseline characteristics. The most useful element for their study is a thorough medical history, with an emphasis on recent trips, exposures and consumption of drugs or raw or exotic foods. Detailed histopathological analysis may help identify the etiology. For example, the presence of epithelioid granulomas with caseous necrosis indicates tuberculosis and, its absence, sarcoidosis; eosinophil abundance can be associated with drug reactions or parasitic infections; and the presence of foreign bodies can be the cause of granulomatous liver disease (GLD). In this article, we describe the basic clinical-pathological aspects of GLD, and provide a brief summary of the most common etiologies, with an emphasis on the Latin-American region.

Ursodeoxycholic Acid Therapy in Patients with Primary Biliary Cholangitis with Limited Liver Transplantation Availability

ABSTRACT Introduction. There is little information on survival rates of patients with primary biliary cholangtis (PBC) in developing countries. This is particularly true in Latin America, where the number of liver transplants performed remains extremely low for patients with advanced liver disease who fulfill criteria for liver transplantation. The goal of this study was to compare survival rate of patients with PBC in developing countries who were treated with ursodeoxycholic acid (UDCA) versus survival of patients who received other treatments (OT) without UDCA, prescribed before the UDCA era. Material and methods. A retrospective study was performed, including records of 78 patients with PBC in the liver unit in a third level referral hospital in Mexico City. Patients were followed for five years from initial diagnosis until death related to liver disease or to the end of the study. Patients received UDCA (15 mg/kg/per day) (n = 41) or OT (n = 37) before introduction of UDCA in Mexico. Results. Response to treatment was higher in the group that received UDCA. In the five years of follow-up, survival rates were significantly higher in the UDCA group than in the OT group. The hazard ratio of death was higher in the OT group vs. UDCA group, HR 8.78 (95% Cl, 2.52-30.61); Mayo Risk Score and gender were independently associated with the risk of death. Conclusions. The study confirms that the use of UDCA in countries with a limited liver transplant program increases survival in comparison to other treatments used before the introduction of UDCA.(AU)

Low grade urothelial carcinoma mimicking basal cell hyperplasia and transitional metaplasia in needle prostate biopsy

ABSTRACT Purpose The vast majority of urothelial carcinomas infiltrating the bladder are consistent with high-grade tumors that can be easily recognized as malignant in needle prostatic biopsies. In contrast, the histological changes of low-grade urothelial carcinomas in this kind of biopsy have not been studied. Materials and Methods We describe the clinicopathologic features of two patients with low-grade bladder carcinomas infiltrating the prostate. They reported dysuria and hematuria. Both had a slight elevation of the prostate specific antigen and induration of the prostatic lobes. Needle biopsies were performed. At endoscopy bladder tumors were found in both cases. Results Both biopsies showed nests of basophilic cells and cells with perinuclear clearing and slight atypia infiltrating acini and small prostatic ducts. The stroma exhibited extensive desmoplasia and chronic inflammation. The original diagnosis was basal cell hyperplasia and transitional metaplasia. The bladder tumors also showed low-grade urothelial carcinoma. In one case, the neoplasm infiltrated the lamina propria, and in another, the muscle layer. In both, a transurethral resection was performed for obstructive urinary symptoms. The neoplasms were positive for high molecular weight keratin (34BetaE12) and thrombomodulin. No metastases were found in either of the patients, and one of them has survived for five years. Conclusions The diagnosis of low-grade urothelial carcinoma in prostate needle biopsies is difficult and may simulate benign prostate lesions including basal cell hyperplasia and urothelial metaplasia. It is crucial to recognize low-grade urothelial carcinoma in needle biopsies because only an early diagnosis and aggressive treatment can improve the prognosis for these patients.

Diferenciación neuroendocrina y marcadores de proliferación celular en adenocarcinoma de próstata en un grupo de casos con antígeno prostático específico normal vs elevado / Neuroendocrine differentiation and markers of cell proliferation in a group of patients with prostate adenocarcinoma and normal or high serum prostate-specific antigen levels

Objetivo. Investigar la población de células neuroendocrinas y sus características morfológicas en pacientes con cáncer de próstata y antígeno sérico normal versus antígeno sérico elevado. Material y métodos. En 13 años se identificaron 372 casos de cáncer de próstata de los cuales 19 (5.1%) con antígeno sérico normal (Grupo I). Se seleccionaron 16 grupos controles con antígeno sérico elevado y características histopatológicas similares (Grupo II). Se evaluaron porcentaje de necrosis tumoral, invasión vascular y perineural, inmunohistoquímica: sinaptofisina, enolasa neuroespecífica, antígeno prostático específico, Ki-67 y p53. Resultados. En el grupo I, se obtuvieron 61 % de casos positivos para antígeno tisular, 28.6 % sinaptofisina, 7.1 % para enolasa neuroespecífica, 50 % para p53 y 78.6 % para Ki-67. En el grupo II, los resultados fueron: sinaptofisina 13.3%, enolasa-neuroespecífica 26.6%, antígeno tisular 93%, p53 46.6% y Ki-67 66.7%. Con punto de corte de antígeno tisular expresado en < 80% de células neoplásicas, en el grupo I se encontraron 69.2% de casos, y en el grupo II 21.4% (p = 0.02). Conclusiones. El único dato histológico que mostró diferencia significativa fue la expresión tisular de antígeno prostático específico en < 80% de las células neoplásicas en el grupo I. Se asoció el incremento de las células neuroendocrinas con el menor número de células productoras de antígeno tisular; esta situación podría ser más visible al estudiar un mayor número de pacientes con características semejantes.

OBJECTIVE: Study the morphologic characteristics of neuroendocrine cells in prostate cancer with normal versus elevated prostate specific antigen (PSA). MATERIALS AND METHODS: 372 cases of prostate cancer were identified during a 13 year period, of which 19 displayed normal PSA (group I). Sixteen controls with elevated PSA and similar histopathological characteristics (group II) were included. We studied the degree of tumor necrosis, vascular and perineural invasion. Synaptophysin (SP), neuron specific enolase (NSE), PSA, Ki-67 and p53 inmunoreactivity were also analyzed. RESULTS: Group I positive findings were 61% PSA, 28.6% SP. 7.1% NSE, 50%p53, and 78.6% Ki-67. Group II positive findings were 93% PSA, 13.3% SP, 26.6% NSE 46.6% p53, and 66.7% Ki-67. When we used a <80% cut off point for PSA immunoreactivity in tumor cells, 69.2% of group I and 21.4% of group II were found. CONCLUSIONS: The sole histopathological finding that showed statistical significance was the tissular expression of the specific prostatic antigen in 80% of neoplasic cells in group I. The increase of neuroendocrine cells was associated with a smaller number of tissular antigen producing cells, a finding that could be more apparent if we were to study a larger sample size.

Hallazgos patológicos en 100 biopsias prostáticas por punción y diagnóstico original de benignidad / Histological findings in 100 NEEDLE prostatic biopsies and original diagnosis of benignity

Introduction. Detailed revision of prostate biopsies with benign alterations may show potentially malignant lesions limited to isolated fields, which may be overviewed in routine analysis. Aim. To exam the morphological alterations in patients with suspicious of prostatic carcinoma and benign diagnosis in needle biopsies. Materials and methods. During 2000-2001, one hundred consecutive patients with first prostate biopsy diagnosed as benign were included. Biopsies were performed by sextants or modified sextants technique. Slides were reviewed by two observers with knowledge of original diagnosis and this was accepted or modified in accordance to the findings found during the review. Results. Patients age ranged between 57 and 79 years old. Nine per cent of biopsies originally diagnosed as benign revealed different potentially malignant lesions, which should be noted due to possible association with carcinoma. In this group, there were five biopsies with atypical small acinar proliferation, three with few isolated glands with xanthomatous cytoplasm, and one with scarce atypical cells in the prostatic stroma. In contrast with Caucasian and Afro-American population, frequency of high grade intraepithelial neoplasia in needle biopsy seems to be very low and this lesion was not found in any of the 100 biopsies reviewed. Some lesions that simulate carcinoma, as atypical basal cell hyperplasia, post-atrophic hyperplasia, and adenosis were diagnosed as benign, and there was none false positive result. Conclusions. A small but significant group of the biopsies originally diagnosed as benign lesions, showed atypical lesions in isolated fields that were overlooked in the routine analysis. It is necessary the urologist to ask for a directed review of the biopsies if clinical and laboratory data strongly suggest prostatic carcinoma. Additional histological cuts, immunohistochemical studies and more than one observer may increase the frequency of detection of potentially malignant lesions.

Introducción. La revisión detallada de las biopsias prostáticas consideradas benignas, en ocasiones puede mostrar cambios histológicos con potencial maligno limitadas a campos aislados, que pueden ser pasadas por alto en la interpretación rutinaria. Objetivo. Examinar las alteraciones morfológicas en pacientes con sospecha de carcinoma prostático con diagnóstico de benignidad en biopsias prostáticas por punción. Material y métodos. En el periodo 2000-2001 se incluyeron 100 pacientes consecutivos cuya primera biopsia se interpretó como benigna. Las biopsias fueron por sextantes, o sextantes modificadas. Se revisaron las laminillas por dos observadores con el conocimiento del diagnóstico original y éste se aceptó o modificó de acuerdo con los hallazgos encontrados. Resultados. La edad varió de 57 a 79 años. Nueve de las 100 biopsias diagnosticadas como benignas revelaron alteraciones histológicas potencialmente malignas que debieron anotarse en el reporte de patología por su posible asociación con carcinoma. Éstas incluyeron cinco biopsias con proliferaciones acinares atípicas, tres con glándulas de aspecto xantomatoso en campos aislados y una con escasas células atípicas en el estroma prostático. En contraste con la población caucásica y afroamericana, la frecuencia de neoplasia intraepitelial prostática en biopsias por punción en nuestra población parece ser muy baja y ninguna de las 100 biopsias mostró esta alteración. Algunas lesiones que simulan carcinoma como la hiperplasia atípica de células básales, la hiperplasia postatrófica y la adenosis fueron reconocidas como benignas, y no hubo ningún resultado falso positivo. Conclusiones. Un porcentaje significativo de las biopsias con el diagnóstico original de patología benigna, mostraron en la revisión dirigida lesiones focales que fueron pasadas por alto en la práctica cotidiana, incluidas algunas con potencial maligno. El urólogo debe solicitar una revisión dirigida en búsqueda de lesiones sugestivas de malignidad si los datos clínicos y de laboratorio sugieren fuertemente la posibilidad de carcinoma. En estos casos, los niveles histológicos adicionales, los estudios inmunohistoquímicos y la revisión por más de un observador podrían incrementar la detección de lesiones potencialmente malignas.