Differential reactivity for galectin-3 in Hürthle cell adenomas and carcinomas.

Hürthle cell carcinomas behave as the most aggressive variant of differentiated thyroid carcinoma of follicular origin, with frequent recurrences and higher morbidity. Its differential diagnosis with Hürthle cell adenoma remains a problem for the clinician and for the pathologist. The vertebrate lectins, galectin-1 and galectin-3 have been implicated in the regulation of cellular growth, differentiation, and malignant transformation in thyroid neoplasms. Galectin-3, a beta-galactoside binding protein, has been recently found to be highly expressed in papillary and follicular carcinomas. The current study was undertaken to investigate immunohistochemical reactivity for galectin-3 of thyroid specimen tissues with Hürthle cell adenomas (n = 14) and carcinomas (n = 17), follicular (n = 14) and papillary (n = 11) carcinomas, colloid goiter (n = 30), Hashimoto's thyroiditis (n = 11), follicular adenoma (n = 9), and normal thyroid tissues (n = 18). Follicular (78.5%) and papillary (82.0%) carcinomas were frequently reactive for galectin-3, more often when some H rthle cells were present. There was no galectin-3 immunostaining in any of the specimens from Hashimoto's thyroiditis, colloid goiters or normal thyroid samples, whereas only one case of follicular adenoma was found positive (11.1%). By contrast, galectin-3 immunostaining in Hürthle cell carcinomas was significantly higher (59%) than in H rthle cell adenomas (7.1), p < 0.05). These results suggest that galectin-3 may potentially serve as a marker in difficult differential diagnosis cases involving Hürthle cell adenomas and Hürthle cell carcinomas.

Frequência de adenocarcinomas em derrames cavitários / Frequency of adenocarcinomas in serious effusions

Objetivo. Identificação de freqüência de adenocarcinomas de diferentes sítios primários em derrames cavitários. Material e Métodos. Foram estudados 2.317 casos: 1.146 de derrame pleural (943 mulheres e 203 homens), 1.168 de ascite (727 mulheres e 441 homens) e três pericárdio (duas mulheres e um homem) e realizada análise retrospectiva dos prontuários dos pacientes e correlação dos achados clínico-laboratoriais. Resultados. Os sítios primários mais freqüentes em derrames pleurais foram: mama (N=586 - 51,1 por cento), pulmão (N=185 - 16,1 por cento: 102 homens e 83 mulheres), ovário (N=124 - 10,8 por cento); em ascites: estômago (N=473 - 40,5 por cento: 300 homens e 173 mulheres), ovário (N=306 - 26,2 por cento) e mama (N=83 - 7,1 por cento). Desses, 555 casos foram citologicamente positivos para malignidade em derrames pleurais, 541 em ascite e dois em pericárdio. Os sítios primários mais freqüentes em derrames pleurais citologicamente positivos foram: mama (N=288 - 51,9 por cento), pulmão (N=92, 16,6 por cento: 45 homens e 47 mulheres) e ovário (N=54, 9,7 por cento); e, em ascites: ovário (N=205 - 37,9 por cento), estômago (N=202, 37,3 por cento: 119 homens e 83 mulheres) e mama (N=31 - 6,8 por cento). Em 47 derrames pleurais (8,5 por cento) e 37 ascites (6,8 por cento), a origem dos adenocarcinomas persistiu indeterminada. Conclusão. As freqüências estabelecidas poderão, em associação e dados clínicos, orientar a investigação dos sítios primários de adenocarcinomas metastáticos.

Combined ultrasonographic and cytological studies in the diagnosis of thyroid nodules.

Many aspects of thyroid nodule evaluation and management remain controversial. Widespread application of ultrasonography has resulted in frequent discovery of incidental nodules in the general population which has created a management dilemma for physicians. In this paper we have introduced a novel approach for evaluation of solid nodules, using an index derived from ultrasonographic and cytologic studies. Briefly thyroid nodules were classified ultrasonographically into four grades, with increasing score numbers (1-4) as progression to malignantly suspicious lesions was present. Similarly, four grades of a cytologic classification of fine needle biopsy aspirates were introduced with scores of 1-6 (benign to malignant diagnosis). The sum of the ultrasonographic and cytologic scores were the basis of a diagnostic index: benign (2-4), doubtful (5), suspicious (6) and malignant (7-10). Sixty patients with an index equal or higher than 6 were submitted to thyroidectomy and the prevalence of thyroid cancer (n = 46) in the excised nodules was 76.6%. Most series report a 10% to 30% incidence of malignancy in excised nodules with suspicious diagnosis. We concluded that using an index derived from combined ultrasonographic and cytologic studies will result in a better patient selection for surgery.

[Frequency of adenocarcinomas in serous effusions]. / Freqüência de adenocarcinomas em derrames cavitários.

BACKGROUND: Metastatic adenocarcinomas in effusions are frequently observed. Cytologic diagnosis of adenocarcinoma is often precise; unfortunately, the classification of the primary site is not possible in a great number of cases. The scope of this study was to report the frequency of adenocarcinomas in effusions according to the primary site. MATERIAL: We studied 2317 sequential cases: 1146 pleural effusions (943 women and 203 men), 1168 ascitic (727 women and 441 men), and 3 pericardial (2 women and 1 men). METHOD: Retrospective analysis of the records of the patients and correlations of the data of clinical follow up and morphological findings. RESULTS: The primary sites more frequently seen in pleural cavity were: breast (N = 586--51.1%), lung (N = 185--16.1%: 102 men and 83 women), and ovary (N = 124--10.8%); in ascites: stomach (N = 473--40.5%: 300 men and 173 women), ovary (N = 306--26.2%) and breast (N = 83--7.1%). Regarding only the samples of malignant effusions we observed 555 in pleural cavity: breast (N = 288--51.9%), lung (N = 92, 16.6%: 45 men and 47 women) and ovary (N = 54, 9.7%). In ascites we reported: ovary (N = 205--37.9%), stomach (N = 202--37.3%: 119 men and 83 women) and breast (N = 31--6.8%). In 47 pleural effusions (8.5%) and 37 ascites (6.8%), the original site of the neoplasia remained undetermined. CONCLUSION: The knowledge of the relative frequencies, associated with clinical information, can be helpful in the selection of further investigation for the metastatic adenocarcinomas.

Neoplastic and non-neoplastic thyroid lesions in autopsy material: historical review of six decades in São Paulo, Brazil.

AIMS AND BACKGROUND: The aim of the study was to report and discuss a historical series of neoplastic and non-neoplastic lesions of the thyroid gland obtained at autopsy that were examined between 1931 and 1989 at the Pathology Department of the Medical School of the University of São Paulo. METHODS: Records of 145,043 cases were reviewed to select those affecting the thyroid gland. The slides of these selected cases were analyzed and classified according to the current terminology. RESULTS: Non-neoplastic lesions comprised 91.62% of the cases (n = 4647), and most of them were adenomatous goiter (n = 3014). Neoplastic lesions were divided into two groups: primary and metastatic. Of the 282 primary tumors, 135 were benign and 147 were malignant. Among the malignant neoplasms, the most frequent types were follicular, papillary and undifferentiated (n = 39, 36 and 29, respectively). The most frequent tumor types among the metastatic neoplasms were lymphoproliferative processes and carcinomas (n = 67 and 34, respectively). CONCLUSIONS: We conclude that, because of the high frequency of neoplastic lesions (8.38%), 68.24% of which were malignant, detailed examination of the thyroid by pathological methods should be carefully and systematically performed for the accurate detection of thyroid lesions, especially carcinomas.

Adenocarcinoma in females detected in serous effusions. Cytomorphologic aspects and immunocytochemical reactivity to cytokeratins 7 and 20.

OBJECTIVE: To investigate the usefulness of assessing the immunoreactivity of cytokeratins 7 (CK7) and 20 (CK20) as well as several cytomorphologic parameters in effusions with metastatic adenocarcinomas in the search for the primary site of the tumor. STUDY DESIGN: From the files of the Pathology Department, A. C. Camargo Hospital, we studied cytologic smears from 73 metastatic adenocarcinomas originally from the breast, 63 from the ovary, 40 from the lung and 32 from the stomach, looking for morphologic parameters that could have discriminant potential in suggesting the primary site in a routine situation, including intranuclear inclusions, prominent nucleoli, mitosis, signet-ring cells, psammoma bodies, nuclear crease, binucleation and multinucleation, papillary features, acinar profile (including ball cells) and single cells. Immunoreactions were performed with monoclonal antibodies to CK7 (OV-TL 12/30) and CK20 (Ks 20.8) and included morphologic analysis. Both analyses were studied in a blind fashion regarding the primary site of the tumors. RESULTS: Positivity ratios for breast, ovary, stomach and lung cases were 67.6%, 63.5%, 29.7% and 45.5%, respectively, for CK7 and 17.2%, 15.8%, 13.5% and 32.2%, respectively, for CK20. Discriminant analysis of morphologic and immunocytochemical parameters had an error rate of 42.9% in recognizing the primary site and a Wilk's lambda of .7290. CONCLUSION: The more efficient parameter with discriminant function was the papillary appearance showed by CK7, which should be used in further studies with a similar scope. The set of parameters used in this study were insufficient to discriminate the primary site of female adenocarcinomas in effusions with significant accuracy.

Lactoferrin in thyroid lesions: immunoreactivity in fine needle aspiration biopsy samples.

OBJECTIVE: Lactoferrin is an iron-binding protein that has been used for distinguishing normal from neoplastic conditions in many different tissues. In order to improve evaluation of thyroid lesions, we studied the lactoferrin immunoreaction in cytologic smears obtained by fine needle aspiration and in biopsy samples from primary neoplasms and from adenomatous goiter. STUDY DESIGN: A retrospective study on fine needle aspiration cytology samples and corresponding available biopsies from thyroid lesions in patients examined at São Paulo County Hospital between 1982 and 1992, performed in order to evaluate lactoferrin immunoreactivity in morphologically well characterized samples from neoplastic and nonneoplastic lesions. Immunoperoxidase procedures were performed using monospecific polyclonal rabbit antihuman lactoferrin as a primary antibody and biotinylated goat antirabbit IgG as a secondary antibody. Amplification was performed with the avidin-biotin-peroxidase complex, and the color sign of the positive reactions was developed using a diaminobenzidine solution. RESULTS: Lactoferrin was not detected in cytologic smears from goiters, whereas only one biopsy was slightly positive (1/21, or 4.76%). One smear from adenoma showed low positive staining (1/19, or 5.26%), which was present in 4 of 13 biopsies (30.77%) from adenoma. Papillary carcinomas were positive in 19 of 33 smears (57.58%) and in 100% of biopsies, whereas 31.25% (5/16) of follicular carcinoma smears were positive for lactoferrin, detected in all the biopsy samples. CONCLUSION: Lactoferrin immunoreactivity was strongly associated with neoplastic proliferation and may be used as a useful auxiliary marker to distinguish malignant from benign thyroid lesions in cytologic smears and biopsy samples.

Cytological diagnosis of serous effusions in a cancer hospital in Brazil.

The performance of cytological diagnosis in serous effusions was evaluated through a historical large series study which was carried out at Department of Surgical Pathology of Hospital A.C. Camargo. Files from the period of 1966 to 1990 were reviewed. Out of 4297 serous effusions samples (from 3379 patients), 2520 were pleural, 1763 ascitic and 14 pericardiac, with cytological report of malignancy in 917, 688 and 4 cases, respectively. Cytological diagnoses were confirmed true or false after correlation with the final diagnosis of the patients (clinical follow-up and/or histological evaluation). The results observed were 1982 false-negative, 21 false-positive, 1588 true-positive and 468 true-negative cases. Suspicious (161 or 3.75%) and inconclusive (77 or 1.79%) cases were not considered for statistical evaluation. Sensitivity, specificity, efficiency, as well as positive and negative predictive values were 44.5%, 95.7%, 50.1%, 98.7% and 20%, respectively. These values in pleural and ascitic effusions, separately showed similar performance, which was not observed in pericardiac samples due to small casistics. These data show low sensitivity and negative predictive values which contrast with the high specificity and positive predictive values that can be partially explained by the methodological limitations and invasive features of neoplasias.

Neoplastic and non-neoplastic thyroid lesions in surgical material: historical review of five decades in São Paulo, Brazil.

AIMS AND BACKGROUND: The goal of the study was to report and discuss the neoplastic and non-neoplastic diseases of the thyroid gland present in a historical series of surgical material examined during the period 1945 to 1989 at the Pathology Department of the São Paulo University Medical School. METHODS: Records of 281,175 cases were reviewed to select those which affected the thyroid gland. The slides of these selected cases were analyzed and classified according to current terminology. RESULTS: Non-neoplastic lesions comprised 86.68% of the cases (n = 7024), and most of them were nodular goiter (n = 6458). Neoplastic lesions were divided into two groups: primary and metastatic. Of 1072 primary neoplasms, 530 were benign and 542 were malignant. Of the malignant neoplasms, papillary and follicular were the most frequent types (n = 201 and 187, respectively), followed by undifferentiated (n = 86), Hürthle (n = 46), medullary (n = 16) and others (n = 6). Of 8 metastatic neoplasms, 4 were from and undetermined primary epidermoid carcinoma. CONCLUSIONS: We concluded that owing to the high incidence of neoplastic lesions (13.32%), half of which were malignant, examination of the thyroid gland should be done with strict criteria in view of the therapeutic and prognostic implications.

Thyroid papillary carcinoma lipomatous type: report of two cases.

The authors present two cases of a new variant of papillary carcinoma of the thyroid gland with an unusual lipomatous component. The first case occurred in a 50-year-old woman: the thyroid gland showed lipomatous foci in the stroma of the papillary carcinoma. The second case occurred in a 38-year-old man with the same lipomatous component appearing in small foci. In both cases, the lipomatous tissue was found within the stroma. As far as we known, there are only tree other reports of this type of thyroid gland carcinoma in the literature.

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 São Paulo University, some degree of nephropathy was found in 158 cases. The slides from paraffin sections of these cases were reviewed according to a morphologic protocol previously established. Diffuse, nodular and mixed glomerulosclerosis were encountered in 42.2%, 21.5% and 5.7% respectively. Subcapsular drop and exudative lesion appeared in 12.7% and 15.2% of the cases. We also encountered arteriosclerosis in 81.6%, arteriolosclerosis in 88.6%, necrotizing papillitis in 11.4% and acute and chronic pyelonephritis in 23.4% and 20.9% respectively. We concluded that glomerular and vascular hyalin alterations were the most frequent findings in diabetic patients.

Immunohistochemistry of medullary thyroid carcinoma and C-cell hyperplasia by an affinity-purified anti-human calcitonin antiserum.

BACKGROUND: The diagnosis of medullary thyroid carcinoma (MTC) depends on the calcitonin immunohistochemistry. Familial MTC is associated with C-cell hyperplasia (CCH), whereas sporadic MTC is not. A specific and sensitive calcitonin immunohistochemistry is necessary for the diagnosis of MTC and CCH. METHODS: An affinity-purified anti-calcitonin antiserum (APxCT) was used for immunohistochemistry of the thyroids of 15 patients with MTC. The thyroids of five patients with familial MTC were studied in detail, with each gland sectioned in 48 areas. RESULTS: Between three and ten independent MTC were found in each thyroid, and CCH was found in all five patients (24.2%, varying from 8.4-56.3% of the 48 areas from each thyroid). MTC and CCH were localized mainly in the middle third and in the central axis of the thyroid lobes. They often were found together in the same area (in a total of 21 areas for the five thyroids sectioned in 48 areas) but ten areas with MTC did not have CCH, and 37 areas with CCH did not have MTC. In ten thyroids partially studied, CCH was indicated in three patients thought to have sporadic MTC. In two thyroids, with follicular and papillary carcinoma, a higher density of C-cells was found around the tumors, but disease was not characterized as CCH. CONCLUSIONS: APxCT antiserum increased the immunohistochemical specificity and sensitivity. The distinction of the familial from the sporadic MTC requires a careful and extensive search of CCH. C-cells in high density may be found around follicular cell carcinomas, being a potential source of diagnostic error.

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.

[Incidence of adrenalitis in necropsy material]. / Incidência de adrenalites em material de necropsia.

In the necropsy material of the Medical School of the University of São Paulo, collected between 1931 and 1981, consisting of 131,466 post-mortem examinations, there were 254 (0.2%) cases of adrenalitis, 185 male and 69 female. In 161 of these cases the affection was bilateral, in 46 it was unilateral and in 47 cases this information is lacking. In 111 cases (43.7%), the adrenalitis was caused by tuberculosis, in 86 cases (33.8%), by South American blastomycosis, in three cases (1.2%) by histoplasmosis, in two (0.8%) by Salmonellosis, in two (0.8%) by cytomegalovirus infection and in one (0.4%) by leishmaniasis. The high number of cases with tuberculosis and paracoccidioidomycosis of adrenal glands is due to high incidence of these infections in Brazil.

[Early detection of medullary thyroid carcinoma in multiple endocrine neoplasia type II]. / Detecção precoce do carcinoma medular de tireóide na neoplasia endócrina múltipla tipo II.

The early diagnosis of medullary thyroid carcinoma was made in two among six examined siblings belonging to two sibships that were offsprings of multiple endocrine neoplasia type II parents. The calcitonin secretory reserve was determined by a combined test using Ca++ (2 mg/kg) and pentagastrin (0.5 mcg/kg), intravenously. Two abnormal tests made on different days supported the diagnosis. Basal calcitonin levels were moderately high (90-500 pg/ml; NL = 15-85 pg/ml) and peak levels were also abnormal (480-1500 pg/ml; NL less than 320 pg/ml), in both cases. Total thyroidectomy associated to prophylactic resection of lymph nodes from central neck region were performed in both. A small nodule (3-5 mm) was found in each lobe in both cases. Pathological and immunocytochemical data supported the diagnosis of medullary thyroid carcinoma. C-cell hyperplasia was present in the peritumoral zones. Pheochromocytoma and definite hyperparathyroidism were not detected in these cases. Two years after surgery, basal and stimulated serum calcitonin levels remained normal. Carcinoembryonic antigen levels were and continue to be normal, in both. These seem to be the first cases published in this country in which this early diagnosis was made.

[Retrospective analysis of the incidence of midline supratentorial neoplasms in children and young patients: craniopharyngiomas, hypophyseal and pineal neoplasms]. / Análise retrospectiva da incidência de neoplasias supratentoriais da linha mediana em crianças e jovens: craniofaringeomas, neoplasias da hipófise e pineal.

The authors analyzed, in a retrospective study made at the Pathology Department of the Medical School of the University of São Paulo, 1632 cases of intracranial neoplasms in a period of 50 years (1931-1981). The investigation concentrated on 592 cases (36.2%) of patients with age ranging from 0 to 20 years. The overall number of craniopharyngiomas in this group was 21 (3.5%); 8 cases (1.35%) of hypophyseal neoplasms, and 4 cases (6%) of pineal neoplasms. Neoplastic infiltration of the hypophysis and pineal was present in 24 cases (4.0%). No metastases were observed. The description and importance of these findings, and their correlation with data from other authors are presented.

The prevalence of unsuspected thyroid pathology in 300 sequential autopsies, with special reference to the incidental carcinoma.

Three-hundred whole thyroid glands were collected at autopsy from patients who had no known clinical history of thyroid disease, and who varied from 13 to 82 years of age; 200 were male and 100 female. Thyroid glands were weighed, measured, and examined after previous formalin fixation. Histologic examination was done in 16 areas from both lobes and isthmus, and divided into three levels, anterior, medial, and posterior. All areas suspected of neoplasia macroscopically were identified and studied microscopically; other areas were collected randomly for microscopic examination in the proportion of one fragment per 5 grams of tissue. In all cases both benign and malignant neoplasias were an incidental finding, seen in 6.6% of the cases and with no relation to the patient's main disease. Overall, there were malignant neoplasias in 2.33% but occult carcinoma comprised 1% of the cases. The incidence of other thyroid pathologies, all of them unrelated to the main disease of the patient, are also reported.

[Progressive systemic sclerosis, B-cell malignant lymphoma of the ileum and thyroid adenocarcinoma]. / Esclerose sistêmica progressiva, linfoma maligno de células B em íleo e adenocarcinoma de tireóide.

A patient with progressive systemic sclerosis with rapid evolution to death is presented. The post-morten examination revealed besides the typical changes of the progressive systemic sclerosis in the skin, kidneys, heart and blood vessels a B-cell ileal malignant lymphoma with generalized metastases, and an adenocarcinoma of the thyroid gland. A possible mechanism involved in the association of these diseases might be the action of the oncogenes modifying the cellular hormostasis and the immunological tolerance.

Normal expression of the serologically defined H-Y antigen in Leydig cell hypoplasia.

H-Y antigen, the proposed inducer of testicular organogenesis, was determined serologically in 3 patients with male pseudohermaphroditism due to Leydig cell hypoplasia, a pathological model with lack of Leydig cell differentiation but normal seminiferous tubule embryogenesis. One patient was the offspring of consanguineous parents and 2 siblings presented as women with a lack of breast development and primary amenorrhea. Gonads were palpable in the inguinal canal, except for the right intra-abdominal testis in 1 patient. Two patients had female external genitalia and 1 had partial labial fusion. Karyotypes were 46XY. Gonadotropin levels were elevated, and testosterone was low and failed to increase after stimulation with human chorionic gonadotropin. Testosterone precursors were not elevated. Testicular histology showed absence of mature Leydig cells but relatively preserved seminiferous tubules. Family history was consistent for autosomal recessive inheritance. H-Y antigen expression measured by an enzyme-linked immunosorbent assay was normal, indicating that lack of other inductive factors for Leydig cell differentiation are responsible for Leydig cell hypoplasia.