Prevalence of thyroiditis and immunohistochemistry study searching for a morphologic consensus in morphology of autoimmune thyroiditis in a 4613 autopsies series.

We sought to verify the prevalence of lymphocytic thyroiditis (LT) and Hashimoto's thyroiditis (HT) in autopsy materials. Cases examined between 2003 and 2007 at the Department of Pathology of Faculty of Medicine of São Paulo University were studied. Immunohistochemical analyses were conducted in selected cases to characterize the type of infiltrating mononuclear cells; in addition, we evaluated the frequency of apoptosis by TUNEL assay technique and caspase-3 immunostaining. Significant increase in overall thyroiditis frequency was observed in the present series when compared with the previous report (2.2978% vs. 0.0392%). Thyroiditis was more prevalent among older people. Selected cases of LT and HT (40 cases each) had their infiltrating lymphocytes characterized by immunohistochemical analyses. Both LT and HT showed similar immunostaining patterns for CD4, CD8, CD68, thus supporting a common pathophysiology mechanism and indicating that LT and HT should be considered different presentations of a same condition, that is, autoimmune thyroiditis. Moreover, apoptosis markers strongly evidenced that apoptosis was present in all studied cases. Our results demonstrated an impressive increase in the prevalence of thyroiditis during recent years and our data support that the terminology of autoimmune thyroiditis should be used to designate both LT and HT. This classification would facilitate comparison of prevalence data from different series and studies.

Iodine increases and predicts incidence of thyroiditis in NOD mice: Histopathological and ultrastructural study.

Prolonged intake of large amounts of iodine has been reported to increase the incidence of hypothyroidism in humans, as well as in animals which are prone to spontaneously developing autoimmune thyroiditis. We sought to investigate the histopathological consequences of large amounts of dietary iodine on the thyroid gland and observe the occurrence of lymphocytic infiltration associated with the time of exposure to iodine. An experimental model using non-obese diabetic (NOD) mice was analyzed. A potassium iodide intake of 0.2 mg/animal/day was administered via drinking water, in experimental groups of 60 and 90 days (EG60 and EG90). Distended rough endoplasmic reticulum, degenerated mitochondria, debris and amorphous spaces or 'ill-defined' spaces were observed with electron microscopy (EM). Lymphocyte infiltration was observed in the two groups and the time of exposure to iodine did not increase the appearance of lymphocyte infiltration but significantly associated with the development of necrosis. The results of the present study demonstrated that the NOD mouse is a feasible experimental model for thyroiditis induced by iodine administration and may represent an opportunity to analyze the steps and factors associated with genetic autoimmune thyroiditis. High doses of ingested iodine were observed to precdict and increase the incidence of the thyroiditis process.

[Ultrasonographic evaluation of thyroid nodules: comparison with cytologic and histologic diagnosis]. / Avaliação ultra-sonográfica dos nódulos tireóideos: comparação com exame citológico e histopatológico.

The purpose of this study was to evaluate our ultrasonographic classification of thyroid nodules, based on echo structure, echogenicity, calcification, margin and analysis of the surrounding parenchyma. From January 1998 to January 2002, 2,468 consecutive patients with thyroid nodules were referred for thyroid ultrasonography and ultrasound-guided fine needle aspiration biopsy (USFNAB) in our Thyroid Unit. Among 1,039 nodules classified as benign on ultrasound, 998 (96.1%) were also benign on cytology, 37 (3.6%) were suspicious and only 4 (0.4%) were malignant. On the other hand, among 153 nodules classified as suspicious on ultrasound, 20 (13.1%) were suspicious and 88 (57,5%) were malignant on cytology. Of the 71 nodules suspicious on ultrasound submitted to surgery, 67 (94.3%) were malignant and 56 (96.6%) of 58 nodules considered benign were benign on pathologic studies. In conclusion, we advocate USFNAB in nodules classified as indeterminate or suspicious. Nodules classified as benign may be followed up at periodic intervals.

Avaliação ultra-sonográfica dos nódulos tireóideos: comparação com exame citológico e histopatológico / Ultrasonographic evaluation of thyroid nodules: comparison with cytologic and histologic diagnosis

O objetivo deste estudo foi avaliar a nossa classificação ultra-sonográfica dos nódulos tireóideos, baseada na ecoestrutura, ecogenicidade, calcificação, contornos e análise do restante do parênquima. De janeiro de 1998 a janeiro de 2002, 2468 pacientes portadores de nódulos tireóideos foram encaminhados ao nosso serviço para realização de ultra-sonografia e punção aspirativa por agulha fina guiada pelo ultra-som (US-PAAF). De 1039 nódulos considerados benignos ao ultra-som, 998 (96,05 por cento) também apresentaram citologia benigna, 37 (3,6 por cento) tiveram citologia suspeita e somente 4 (0,4 por cento) tiveram citologia maligna. De 153 nódulos considerados suspeitos ao ultra-som, 20 (13,1 por cento) tiveram citologia suspeita e 88 (57,5 por cento) tiveram citologia maligna. Dos 71 nódulos suspeitos ao ultra-som submetidos à cirurgia, 67 (94,3 por cento) tiveram diagnóstico anatomopatológico maligno. Já, dos 58 nódulos considerados benignos, 56 (96,6 por cento) tiveram diagnóstico anatomopatológico benigno. Concluímos que a US-PAAF deve ser realizada em nódulos classificados como indeterminados ou suspeitos ao ultra-som. Nódulos classificados como benignos podem ser acompanhados periodicamente.

Identification of the primary site of metastatic adenocarcinoma in serous effusions. Value of an immunocytochemical panel added to the clinical arsenal.

OBJECTIVE: To use an immunocytochemical panel as ancillary method to identify the origin of adenocarcinomas in serous effusions. STUDY DESIGN: Serous effusion samples examined cytologically in the Department of Surgical Pathology, A. C. Camargo Hospital, between 1966 and 1990, were investigated. Of 4,297 cases, 2,317 were associated with adenocarcinoma, and 1,099 were positive for adenocarcinoma by cytologic examination. We selected a total of 248 cases of different origins to subject to immunoreactions. A panel composed of CA-125, CA-19.9, HBME-1, lactoferrin and BRST 2 was tested for the efficiency of these antibodies under two conditions: the panel alone and associated with clinical data, such as anatomic localization of the effusion (pleural or ascitic) and patient sex and age. RESULTS: BRST 2 and lactoferrin were both positive in 29.9% of cases of adenocarcinoma of breast origin; CA-125 and HBME-1 were 28.6% and 25.0% positive in cases of adenocarcinoma of the ovaries, respectively. These immunoreactivities were highly specific when compared to the others. The statistical significance of the results was improved by information on the anatomic location of the effusions and patient sex. CONCLUSION: Our data strongly indicate that BRST 2 and lactoferrin are important components of an immunocytochemical panel used to identify carcinomas of breast origin. Similarly, CA-125 and HBME-1 may be useful in suggesting the ovaries as possible primary sites.

Severe and mild neonatal hypothyroidism mediate opposite effects on Leydig cells of rats.

The effects of neonatal hypothyroidism on the number of Leydig cells were studied in neonatal Wistar rats. Moderate or severe hypothyroidism were induced during neonatal life by giving different amounts of methimazole (MMI; 0.05% or 0.1%) in the drinking water of pregnant and lactating dams. Rats were sacrificed on day 21 of postnatal life. Severely hypothyroid rats had approximately 45-fold higher serum thyrotropin (TSH) values and demonstrated approximately a 65% decrease in testes weight (p < 0.05) and the number of Leydig cells. However, in moderately hypothyroid rats, in which serum TSH was only approximately 16-fold higher, testicular weight was normal and the number of Leydig cells almost doubled (p < 0.01). There were no significant differences between the serum-free testosterone levels of the moderately and severely hypothyroid rats versus controls. Serum levels of 3alpha-androstanediol glucuronide, although decreased to less than 10% in severely hypothyroid rats (p < 0.01), were not changed by mild hypothyroidism. The number of Sertoli cells was increased in moderately hypothyroid rats versus controls (p < 0.05) and even further increased in severely hypothyroid rats (p < 0.05). We conclude that (1) severe neonatal hypothyroidism impairs the development and function of the testes and (2) moderate neonatal hypothyroidism stimulates the proliferation of Leydig cells.

Síndrome de Cushing associada à hiperplasia macronodular das adrenais: apresentaçäo de um caso e revisäo da literatura / Cushing's syndrome associated with macronodular adrenal hyperplasia: report of a case and literature review

O objetivo dessa apresentaçäo é discutir a Síndrome de Cushing secundária à hiperplasia macronodular primária das adrenais. Inicialmente, será apresentado um caso clínico e, em seguida, seräo discutidos a apresentaçäo clínica, laboratorial, radiológica e histológica, e os possíveis mecanismos patogenéticos envolvidos no desenvolvimento dessa patologia.

Morphological and immunohistochemical studies of normal adrenal gland

Morphologically and functionally distincts from each other, the two different types of endocrine tissue that constitute the adrenal gland, the medulla and the cortex, could have influence on the endocrine activity of each one, i.e., there might be regulatory mechanisms exercised by some products released from each of these two areas to the other one. Besides these findings, there are evidences of the presence of cells from the adrenal cortex within the medulla area and vice versa. Twenty-one cases without clinical evidence of endocrine disease were selected for morphological study of the adrenal tissue and to verify their immunoreactivity for hormones, intermediate filaments and neuroendocrine peptides. All cases were histologically classified as normal. Chromogranin was recognized in 20 cases only in medullary region. Synaptophysin was identified in the medullary area in 9 cases. S-100 protein was observed in all cases in both medullary and cortex areas. Immunoreactivity to cytokeratins was found in 14 cases. Vimentin showed focal positivity in 5 normal cortex areas and ACTH reactivity was present in only one case. Positivity for FSH was observed (one case in medulla and two in cortex), possibly due to antibody specificty. D-11 positivity was found in the cortex region in 18 cases. Further studies should be conducted in order to establish the utility of these findings, since presence of hormone or hormone-like sustance secreting cells could induce local paracrine stimulation.

Distribuiçäo de imunomarcadores em citologia de adenocarcinomas de mama ovário e endométrio metastáticos em derrames serosos / Distribution of markers in cytology of metastic adenocarcinomas of breast, ovary and endometrium in serous effusions

A discriminaçäo do sítio de origem de adenocarcinomas é importante para orientar a conduta clínico-cirúrgica de pacientes com metástases. A identificaçäo morfológica do sítio primário de um adenocarcinoma pela análise citológica de derrames cavitários nem sempre é precisa devido a similaridade de padröes. Por isso, o objetivo deste trabalho foi a identificaçäo de marcadores imunocitoquímicos que possam otimizar o desempenho laboratorial. Estudaram-se 143 casos de derrames cavitários positivos para malignidade: 68 de mama, 60 de ovário e 15 de endométrio. Foram realizadas reaçöes, amplificadas pelo sistema estreptavidinabiotina-peroxidase, com os marcadores: BRSt2, CAI19.9, CA125, CK7, CK20, HBMEI e lactoferrina , detacando-se as seguintes positividades: mama - BRST2 (20/68) e lactoferrina (21/68); ovário - CA125 (17/60) e CA 19.9 (12/60). Concluímos que os anticorpos BRST2 e lactoferrina, quando positivos, sugerem fortemente a origem mamária do adenocarcinoma. Os demais perfis podem sugerir determinado órgäo, mas apenas num contexto com outros dados

Sensibilidade do método citológico para o estudo de derrames cavitários: correlaçäo com o tipo histológico das neoplasias / Sensitivity of the cytologic method for the study of serous effusions: correlation with the histological type of neoplasm

O desempenho da citologia de derrames cavitários tem importância na avaliaçao de eventuais metástases, discriminando lesoes benignas e malignas. Pelas características morfológicas de algumas lesoes, esta discriminaçao poderá ser comprometida, resultando em falsos diagnósticos, positivos ou negativos. O interesse em otimizar os diagnósticos citológicos é na rotina citológica. O objetivo deste trabalho foi o de avaliar o diagnóstico da citologia de derrames, correlacionando o desempenho com o tipo histológico das neoplasias. Estudou-se retrospectivamente 3.551 casos de derrames malignos e 489 casos benignos, de pacientes atendidos no Hospital A.C. Camargo, de 1965 a 1999. Os tipos histológicos mais freqüentes de derrames malignos foram: 2.174 casos de adenocarcinomas: 386 de carcinomas espinocelulares: 361 de linfomas; 201 de carcinomas indiferenciados e 155 de sarcomas. A quantidade de falsos-negativos foi, de acordo com o tipo histológico: adenocarcinoma: 1.076 casos; carcinoma espinocelular: 279; linfoma: 118; sarcoma: 125 e Ca indiferenciado: 120. A sensibilidade da citologia para diagnóstico de câncer foi 50,50 por cento para adenocarcinoma; 47,92 por cento para linfoma; 40,30 por cento para carcinoma indiferenciado; 27,72 por cento para carcinoma espinocelular e 19,35 por cento para sarcoma. O Valor Preditivo Positivo (VP(+)) foi de 100 por cento para os cinco tipos histológicos mais freqüentes. Os casos histológicos nao-neoplásicos tiveram uma especificidade média de 96,70 por cento, e Valor Preditivo Negativo (VP(-)) de 100 por cento. Concluímos que a citologia apresenta uma alta capacidade resolutiva para neoplasias malignas que, quando diagnosticadas representam invariavelmente um resultado verdadeiro. Em contrapartida, a sensibilidade se mostrou baixa para os mais variados tipos histológicos.

Estudo morfológico de adenocarcinomas metatásticos em derrames cavitários / The morphologic study of metatastics adenocarcinomas in serous effusions

Estudou-se as características morfológicas de quatro tipos de adenocarcinomas metastáticos em derrames caviários com intuito de se observar parâmetros que auxiliassem na identificaçäo dos sítios primários das lesöes. Avaliou-se, em casos originários de mama, ovário, estômago e pulmäo, critérios com celularidade, textura de cromatina, mitoses, inclusöes intranucleares, nucléolos proeminentes, arranjos celulares, entre outros. Os resultados obtidos mostraram que a citologia, isoladamente, näo ofereceu a eficiência desejada para cumprir o objetivo proposto, sendo imperiosa a associaçäo com as informaçöes clínicas

Dyshormonogenetic goiter: A morphological and immunohistochemical study.

A retrospective morphological and immunohistochemical study of 21 cases of dyshormonogenetic goiter was carried out correlating patterns of hyperplasia and the atypias of the glandular tissues with specific defects in hormonal synthesis, including (1) thyroglobulin synthesis defect (Group I, n = 8); (2) defective organification of iodide (Group II, n = 11); and (3) iodide transport defect (Group III, n = 2). Microfollicular, trabecular, papillary, and oxyphilic cell patterns were more frequent in Group II compared with Group I (Group III was excluded because of the small number of cases). The combined microfollicular and trabecular patterns were more frequently seen in patients in Group II. Two cases of thyroglobulin synthesis defect demonstrated certain morphological specificity characterized by an alveolar pattern. Atypias were more frequent and severe in patients in Group II relative to patients in Group I, but features of malignancy were not found in any patients. Immunohistochemical study using thyroglobulin antiserum demonstrated correlation between morphology and positivity of follicular cells. Scarce C cells were verified in these cases by immunohistochemistry. Using two-paired samples, respectively, of 21 endemic and 21 dyshormonogenetic goiters, we distinguished 85.7% of the cases examined, presented in a double-blind fashion. Scarcity of colloid and prominent cellular atypia were highly suggestive of dyshormonogenetic goiter. Considering the relative rarity of dyshormonogenetic goiter, our studies point out the most common patterns of hyperplasia and atypias in this pathology to avoid misdiagnosis, principally when considering the possibility of malignancy.

Later complications on diabetic patients: nephropathies in necropsy material

The purpose of the present study was to analyze in detail the kidney lesions of diabetic patients. Revision of the histopathologic aspects of this nephropathy was performed, seeking to approach the pathophysiology of its formation. In 200 consecutive necropsies of cadavers of diabetic patients examined at the Pathology Department of the Medical School of the Säo Paulo University, some degree of nephropathy was found in 158 cases. The slides from parffin sections of these cases were reviewed according to a morphologic protocol previously established. Diffuse, nodular and mixed glomerulosclerosis were encountered in 42.2 per cent, 21.5 per cent and 5.7 per cent respectively. Subvcapsular drop and exudative lesion appeared in 12,7 per cent and 15.2 per cent of the cases. We also encoutered arteriosclerosis in 81.6 per cent, arteriolosclerosis in 88.6 per cent, necrotizing papillitis in 11.4 per cent and acute and chronic pyelonephritis in 23.4 per cent and 20.9 per cent respectively. We concluded that glomerular and vascular hyalin alterations were the most frequent findings in diabetic patients

Neoplasias malignas incomuns de regiäo tireoidiana diagnosticadas através de punçäo por agulha fina / Uncommon malignant neoplasias diagnosed by fine needle aspiration of the thyroid gland region

Entre outubro de 1979 e julho de 1990, 2000 casos de punçäo aspirativa com agulha fina (PAAF) da glândula tireóide foram realizadas no Hospital do Servidor Público Municipal. Dos números de casos positivos para malignidade, cinco apresentaram aspectos citológicos incomuns, em relaçäo aos padröes das neoplasias tireoidianas, como se segue: dois casos de linfomas, dois carcimonas de células escamosas e um carcimona papilífero com áreas indiferenciadas. Seguimentos clínico e/ou diagnóstico histopatológico confirmaram os achados citológicos das neoplasias: três casos foram corretamente interpretados como metástases para a tireóide; um caso mostrou tecido ganglionar neoplásico superposto à tireóide e em um caso observou-se carcinoma papilífero com metaplasia epideróide e corpos psamomatosos, ambos nas áreas papilíferas. Em nossa experênica, a PAAF é um método útil na avaliaçäo de nódulos tireoidianos, inclusive para diagnóstico de suspeita de câncer metastático

Study in necropsy material of "cause-specific mortality" in diabetics, in São Paulo-Brasil

Specific causes of death in diabetic patients was studied in retrospective work from necropsies performed at the Medicine School of the University of São Paulo from 1931 until 1989. From 145,043 necropsies, 813 indexed cases were found: 449 females (55.2) and 364 males (44.8). The race ratio of patients was: 584 (71.8) white, 208 (25.6) negro and 21 (2.6) asiatic. The predominant age of death incidence was between the fifth and sixth decades. The main causes reported were infections (42.68), coma (12.79), neurologic involvement (11.56) and cardiac diseases (11.07); indeterminate causes of death were related in 7.4 of cases. Our results differ from the others of literature mainly in two points: the high prevalence of infectious diseases and the proportional low incidence of cardiopathies. We concluded that, in our casuistic, infectious diseases in diabetic patients represent an important cause of death establishing important clinical parameters for their care.

Studies on functional and morphological aspects in human multinodular simple goiter tissues.

Samples from 2 different locations within the same euthyroid multinodular goiters (SMG) and normal (N) human thyroids were assayed for their content of DNA, thyroglobulin (Tg), and stable iodine (1271), and determined the response of adenosine 3',5'-cyclic monophosphate (cAMP) to TSH and NaF. Quantitative morphological estimation of histological components in the thyroid was performed and correlated with functional parameters. Regardless the zonal evaluation, in SMG the mean (± SD) DNA content (⧎g/mg tissue) (1.04 ± 0.86) was not statistically different from that in N (1.13 ± 0.21). The mean127I concentration (⧎g/⧎g DNA) in N tissues (0.357 ± 0.091) was greater than that in SMG (0.176 ± 0.074). In these tissues, the Tg mean level (± SD) (⧎g/⧎g DNA) was lower (28.3 ± 21.5) than that in N (75.6 ± 41.1). The mean relative proportion (Vv) of epithelial cells in SMG (range, 6.0-30.6%) was statistically different (p <0.00) from that observed in N tissues (range, 10.4-18.2%). The meanbasal (± SD) cAMP level (pmol/⧎g DNA) in these tissues (0.11 1 ± 0.036) was different (p < 0.05) from that in SMG (0.231 ± 0.026). In response to TSH (10 mU), both SMG and N increased their cAMP contents to 0.454 ± 0.045 and 0.572 ± 0.020, respectively. A further elevation in cAMP levels was observed in N (1.154 ± 0.210) after 75 mU TSH, whereas in SMG tissues, no consistent increase (0.609 ± 0.496) occurred. Goiter and normal thyroid slices were unable to increase their cAMP concentrations in response to NaF in vitro. No correlation was found between functional and morphological data in SMG samples. In contrast, this relation was quite uniform in normal thyroids. The results are concordant with the intrathyroidal pathogenic processes often cited for the heterogeneity in human goiter.

Citologia aspirativa da glândula tireóide com agulha fina em 1750 casos: análise crítica / Aspiration citology of the thyroid gland with fine needle in 1750 cases: critical analysis

Apresenta-se um estudo retrospectivo comparativo entre (i) citologia aspirativa por agulha fina (CAAF) da glândula tireóide, (ii) anatomia patológica, (iii) achados de "imprint" intraoperatório. Os autores estudaram 1750 casos de CAAF da glândula tireóide de pacientes do Hospital do Servidor Público Municipal de Säo Paulo atendidos entre outubro de 1979 e agosto de 1989. A acuidade dos diagnósticos da CAAF e sua fácil metodologia, indicam-na como excelente método para orientar a conduta de tratamento desta patologia.