Search

Resumen Un adecuado conocimiento y comprension del concepto de planos conjugados es de capital importancia en la utilizacion del microscopio por cuanto que desde hace ya bastante tiempo el diseno de los microscopios se basa en la correcta situacion de sus dos conjuntos de planos conjugados. En 1893 August Kohler publico el trabajo «Un nuevo sistema de iluminacion en microfotografia» donde dio a conocer los fundamentos basicos de una tecnica de iluminacion que actualmente lleva su nombre. El conocimiento y aplicacion de los principios del sistema de iluminacion de Kohler constituye el elemento de mayor importancia en el correcto manejo de un microscopio. Dichos principios no siempre son bien conocidos y comprendidos por los usuarios del microscopio constituyendo una fuente frecuente de errores en microscopia, particularmente en microfotografia. En este articulo revisamos los principios basicos del concepto de planos conjugados y del sistema de iluminacion de Kohler.

Abnormal Wnt signaling and impaired cell–cell adhesion due to abnormal E-cadherin and b-catenin func tion have been implicated in many cancers, but have not been fully explored in nasopharyngeal carcinoma. The aim of this study was to analyze b-Catenin cellular location and E-cadherin expression levels in nasopharyngeal carcinoma. E-cadherin expression levels were also correlated with clinical data and underlying pathology. b-Catenin and E-cadherin expression were examined in 18 nasopharyn geal carcinoma and 7 non-tumoral inflammatory pharynx tissues using immunohistochemical methods. Patient clin ical data were collected, and histological evaluation was performed by hematoxylin/eosin staining. b-catenin was detected in membrane and cytoplasm in all cases of naso pharyngeal carcinoma, regardless of histological type; in non-tumoral tissues, however, b-catenin was observed only in the membrane. As for E-cadherin expression levels, strong staining was observed in most non-tumoral tissues, but staining was only moderate in nasopharyngeal carci noma tissues. E-cadherin expression was associated with b-catenin localization, study group, metastatic disease, and patient outcomes. Reduced levels of E-cadherin protein observed in nasopharyngeal carinoma may play an important role in invasion and metastasis. Cytoplasmic b-catenin in nasopharyngeal carcinoma may impair cell– cell adhesion, promoting invasive behavior and a metastatic tumor phenotype.

It It is widely held that solid cell nests (SCN) of the thyroid are ultimobranchial body remnants. SCNs are composed of main cells and C cells. It has been suggested that main cells might be pluripotent cells contributing to the histogenesis of C cells and follicular cells, as well as to the formation of certain thyroid tumors. The present study sought to analyze the immunohistochemical profile of SCN and to investigate the potential stem cell role of SCN main cells. Tissue sections from ten cases of nodular hyperplasia (non-tumor goiter) with SCNs were retrieved from the files of the Hospital Infanta Luisa (Seville, Spain). Parathormone (PTH), calcitonin (CT), thyroglobulin (TG), thyroid tran scription factor (TTF-1), galectin 3 (GAL3), cytokeratin 19 (CK 19), p63, bcl-2, OCT4, and SALL4 expression were evaluated by immunohistochemistry. Patient clinical data were collected, and tissue sections were stained with hematoxylin–eosin for histological examination. Most cells stained negative for PTH, CT, TG, and TTF-1. Some cells staining positive for TTF-1 and CT required discussion. However, bcl-2, p63, GAL3, and CK 19 protein expression was detected in main cells. OCT4 protein expression was detected in only two cases, and SALL4 expression in none. Positive staining for bcl-2 and p63, and negative staining for PTH, CT, and TG in SCN main cells are both consistent with the widely accepted minimalist definition of stem cells, thus supporting the hypothesis that they may play a stem cell role in the thyroid gland, although further research will be required into stem cell markers. Furthermore, p63 and GAL-3 staining provides a much more sensitive means of detecting SCNs than staining for carcinoembryonic antigen, calcitonin, or other markers; this may help to distinguish SCNs from their mimics.

WAG/Rij rat strain has been suggested as an animal model for the study of inherited human medullary thyroid carcinoma (MTC), due to its high incidence of spontaneous C-cell thyroid tumours. Although the role of the Ret proto-oncogene mutations, as responsible for human MTC, is well established, nothing has been published concerning this putative animal model. Based upon the previously reported rat Ret sequence, exons 10, 11, 13, 14, 15, and 16, known to carry activating mutations in humans, have been analysed in the WAG/Rij rat by PCR, single strand conformational polymorphism (SSCP) and direct sequencing. Neither the germline nor MTC samples showed any Ret sequence difference in the exons when analysed in comparison to a non-MTC-susceptible rat strain. Our results indicate that Ret exons relevant in humans are not involved in WAG/Rij rat MTC, as expected, and this questions the validity of this strain as a model for the human disease, and suggests there must be additional mechanisms for the genesis and progression of rat MTC.

The RET proto-oncogene, a member of the Receptor Tyrosine Kinase family, plays a crucial role during the development of the excretory system and the enteric nervous system, as demonstrated by in vivo animal studies and by its involvement in the pathogenesis of several human neurocristopathies like Hirschsprung disease and Multiple Endocrine Neoplasia type 2. Using a multistep RT-PCR approach we have isolated and sequenced the cDNA of the whole rat RET proto-oncogene, reporting the deduced amino acid sequence in comparison with the human and mouse counterparts. Moreover, two different isoforms (RET9 and RET51) have been confirmed in the rat, while a third RET isoform demonstrated in human (RET43) has not resulted to be conserved in this species. Finally, we have determined the genomic structure of the rat RET proto-oncogene comparing the exon-intron boundaries and intron sizes with the known structure of the human homologous gene. Our findings will facilitate the molecular study of appropriate rat models of RET related human diseases.

Aims c-erbB-2 expression has been found to be a potential marker of aggressive biological behaviour in some tumours, but the role played by this oncoprotein in the development and maintenance of thyroid tumours is still controversial. Therefore our objective was to determine whether c-erbB-2 was overexpressed in a large retrospective series of human thyroid tumours, including both from follicular and C-cell differentiation. Methods and results We have studied 67 thyroid tumours (10 follicular adenomas, 11 follicular carcinomas, three anaplastic carcinomas, 25 papillary carcinomas and 18 medullary carcinomas and 16 metastases) by immunohistochemistry using an antigen retrieval method for paraffin-embedded material and a specific polyclonal antibody against the intracytoplasmic part of c-erbB-2 oncoprotein. There are marked differences in the pattern of c-erbB-2 immunoreactivity depending on the type of thyroid tumour. Thus, no expression of the oncoprotein has been found in follicular adenomas, follicular carcinomas and anaplastic carcinomas, but 52% of papillary carcinomas (membranous and diffuse cytoplasmic patterns) and all medullary carcinomas (granular cytoplasmic pattern) are immunopositive. Conclusions Our results indicate that overexpression of c-erbB-2 oncoprotein is easily identifiable by immunohistochemistry in paraffin sections of certain thyroid tumours after applying an antigen retrieval method. This study suggests that c-erbB-2 oncoprotein may play some role in disease progression in papillary and medullary thyroid carcinomas, but the significance of the different immunohistochemical patterns merits further investigations.

Many papers have reported that chronic hypercalcemia induced either by large doses of vitamin D or by the administration of calcium or parathormone, produces hypertrophy and hyperplasia of C cells. However, more recent studies suggest that the effect of elevated calcium or 1.25(OH)2D3 concentration on the production of calcitonin may be more complex than previously suspected. To assess the validity of such a response an experimental model, where hypercalcemia was induced with vitamin D3 overdose, was designed. Male Wistar rats were administered vitamin D3 chronically (50,000 IU per 100 ml of drinking water with or without CaCl2). Serum calcium and calcitonin levels were determined. C cells were stained by immunohistochemistry using calcitonin and neuronal specific enolase (NSE) antibodies and their percentage was calculated by a morphometric analysis. We also investigated the ultrastructural characteristic of the C cells under experimental conditions. C cells did not have a proliferative response rather a decrease in their number was observed after 1 month of treatment with 25,000 IU of vitamin D3 (1.55 vs 2.43% in control animals) and 3 months with vitamin plus CaCl2 (2.27% vs 3.62% in control animals). In addition, no significant changes in serum calcitonin levels were observed during the experimental period. We conclude that rat C cells do not respond with hypertrophic and hyperplastic changes in a hypercalcemic state due to an intoxication with vitamin D3.

The use of FNA cytology to diagnose pathologic conditions of the thyroid has increased considerably in recent years, particularly since it has reduced by half the number of patients undergoing surgery. On the one hand, this diagnostic technique has attracted a certain amount of well justified criticism, but on the other, recent cytohistologic correlations and new scientific knowledge are continually improving its application. We shall discuss the latter aspect in more detail and deal with some simple but informative points which the pathologist may find useful in daily practice. Diagn. Cytopathol. 1997;17:422–428. © 1997 Wiley-Liss, Inc.

A study was conducted on histological patterns and biomolecular changes in Goitrogen-induced experimental rat thyroid tumors. The link between the histological types observed and N-ras, B-raf, and PI3KCA gene mutations widely reported in human thyroid cancers was explored.An analysis was done on paraffin-embedded tumor tissue sections from Wistar rats receiving 1% potassium perchlorate (KClO(4)) added to the ad libitum drinking-water supply over an 18-month period. Three experimental subgroups were formed, each comprising 10 thyroids: subgroup I (control) consisted of thyroids from untreated controls; subgroups II and III (experimental) consisted of thyroids from KClO(4)-treated rats, displaying capsular, vascular, or both invasion but no metastasis (II), or distant metastasis (III). DNA was extracted from paraffin-embedded tissues. To test for the genetic mutations most widely reported in human thyroid cancers, exon 1 of the N-ras gene, exons 9 and 20 of the PI3KCA gene, and exon 15 of the B-raf gene were amplified and sequenced.All tumors were of the follicular type. None of the 20 experimental rat thyroids displayed the expected gene mutations reported in humans. However, 90% of them contained four new B-raf gene mutations and all were silent and did not cause an amino acid substitution in the protein chain.Biomolecular analysis suggested that N-ras, PI3KCA, and B-raf gene mutations may not be involved in thyroid tumor formation using the experimental procedure applied in this study. But the four mutations in B-raf, though without functional repercussions, may be a specific marker for this tumor type.

To explore biomolecular characteristics of a group of patients with nasopharyngeal carcinoma from European (Spanish) hospitals, addressing the pathogenesis of the tumor and the response to treatment.Cyclin D1 and p16 expression were evaluated immunohistochemically in 33 tissue samples of nasopharyngeal carcinoma. CCDN1 gene amplification and p16 gene deletion were studied by fluorescence in situ hybridization. Patient clinical data were examined, and tissues were evaluated histologically using hematoxylin-eosin staining.Cyclin D1 overexpression was found in 19 cases, and p16 expression was undetected in 30 cases. An association was observed between impaired p16 expression and cyclin D1 overexpression (p = 0.034). Eleven patients displayed p16 gene deletion and CCDN1 gene amplification.Cyclin D1 overexpression and CCDN1 amplification, loss of p16 expression and p16 deletion may be among the genetic alterations involved in the pathogenesis of nasopharyngeal carcinoma.

In cortical adrenal gland tumours there are discrepancies between morphological criteria for malignancy and biological behaviour. This makes it difficult to select the appropriate treatment. We have studied morphometric and DNA densitometric features of 24 adrenal proliferative lesions (hyperplasia, adenoma, and carcinoma) by means of slide cytometry. All variables have been correlated with pathological diagnosis. The samples were selected from paraffin-embedded tissue, and representative lesions were Feulgen stained. Densitometric study showed aneuploid cell lines in every carcinoma, 5 of 8 adenomas, and 5 of 10 hyperplastic lesions. Both DNA nuclear content (mean ploidy of 2.11 c, 2.41 c, and 3.05 c) mean nuclear area (average of 31.26 microns 2, 35.92 microns 2, and 42.39 microns 2) showed progressive increase from hyperplasia to adenoma, and carcinoma. Mean shape factors were lowest in adenomas (1.69) and highest in carcinomas (1.82). Those karyometric variables which showed statistically significant differences (p < 0.05) among diagnostic groups were included in a stepwise three-way discriminant analysis. Only three parameters, shape factor (p = 0.0008), mean ploidy (p = 0.0012), and adrenal weight (p = 0.0055) persisted as independent predictive factors. Using the three variables selected by discriminant analysis on our cases, 100% of the adenomas were correctly classified, 83% of the carcinomas, and 80% of the hyperplasias. Tumour weight and nuclear shape factor differentiated adrenal cortex adenoma from carcinoma, while mean ploidy distinguished adrenal cortical hyperplasia from carcinoma. Nuclear pleomorphism (shape factor) and DNA-ploidy are the most important nuclear features in predicting the biological course of proliferative adrenal cortex lesions, although by themselves they are not bona-fide discriminators.

Blue nevus is an uncommon pigmented lesion of dermal melanocytes. By convention, two well defined histologic variants, designated as "common" and "cellular", have been recognised. In the last few years, these lesions have attracted much attention due to the recognition of news entities and to its confusion with malignant melanoma. In the present review, we point out the more striking features of new related entities (combined nevus, deep penetrating nevus, compound blue nevus) and establish the differential diagnosis with conflictive lesions such as atypical blue nevus, locally aggressive blue nevus, congenital giant melanocytic nevus with nodular growth and melanocytic dermal tumor of unpredictable outcome. We also review the concept of malignant blue nevus and the significance of lymph node metastases. The blue nevus is an uncommon pigmented lesion consisting of dermal melanocytes that can appear in diverse forms: dendritic, spindle-shaped, oval-shaped, or polyhedral. Although it usually occurs in skin, it has been reported in other locations, such as oral mucosa, sclera, uterine cervix, vagina, prostate, spermatic cord, pulmonary hilus, orbit, conjunctiva, maxillary sinus, breast, and lymph nodes 3,8,42,49. Generally, it occurs in adults as a single, acquired, intensely pigmented lesion, although familial and multiple nevi have been reported 7,39. By convention, there are two well-defined histologic variants, designated as "common" and "cellular", but lesions often manifest intermediate features. In the last few years, blue nevus has attracted much attention due to the recognition of new (clinical and histologic) entities and to its confusion with malignant melanoma.(ABSTRACT TRUNCATED AT 250 WORDS)

The development of calcitonin cells (C-cells) was investigated in rat thyroid glands from birth to 120 days, using an immunoperoxidase technique and a point-counting method. The proportion of C-cells to follicular cells was 4.5% on the day of birth and increased progressively to 10.4% by 120 days. The highest density of C-cells was noted in the mid-region of the lobes along a longitudinal axis. The caudal and cephalic regions of the lobes contained smaller numbers of C-cells. The C-cells tended to be more numerous in the posterior aspects of the lobes. Although the numbers of C-cells in 120-day-old animal were markedly increased as compared to animals at the time of birth, the cell distributions within the glands were similar at all ages.

Three pathologists evaluated a number of designated architectural features to assign grades to 41 cases of well- to moderately differentiated adenocarcinoma, and their opinions were compared. The consensus opinion was obtained and evaluated against objective measurements of glandular architecture that were obtained by morphometric techniques. The observers agreed on gland size, gland uniformity, and the number of glands per field in only 49%, 31%, and 39% of cases, respectively. There were significant differences in the Gleason grades assigned by observers. Paired matching of individual Gleason grades showed agreement among observers in 44% (18 of 41), 56% (23 of 41), and 75% (31 of 41) of cases, respectively. This level of interobserver disagreement occurred even though cases with predominant patterns were selected carefully and those with variable patterns were excluded. A direct relationship appears to exist between increasing Gleason grade and increasing glandular variability, and there is an inverse relationship between Gleason grade, gland lumen area, and the number of glandular nuclei, as assessed by a group of pathologists.

To analyze the presence of SDHD gene mutations in patients with sporadic head and neck paraganglioma.The presence of somatic and germline SDHD mutations was investigated in 10 patients by polymerase chain reaction and direct sequencing.Two patients displayed mutations: 259CT (P87S) in 1 case and 129GA (W43X) in the other. The first was considered a neutral polymorphism. The second was present in the germline of 1 of her sons, who had an apparently unrelated testicular seminoma and loss of heterozygosity (LOH) in the tumor cells.This is the first reported case of an SDHD mutation carrier showing LOH in a testicular seminoma.

The prognostic significance of objectively measured karyometric variables (ploidy pattern, nuclear roundness, area, elongation, chromatin texture, and nearest nucleus distance) was investigated in relation to clinical (stage and type of disease) and morphologic (histologic patterns) variables in 27 patients with the diagnosis of medullary thyroid carcinoma (MTC). The DNA and karyometric measurements of Feulgen-stained nuclei were made with a video cytometry system. The five-year and ten-year adjusted survival rates were 74.4 +/- 10.1% and 59.5 +/- 15.6%, respectively. Cox's survival analysis for mortality showed that only stage, age, sex, and 5N exceeding rate had predictive value (overall P = 0.0012) in decreasing order. Patients with the best prognosis were young females with clinical Stage I disease and low 5N exceeding rate tumors. When karyometric and histometric variables were considered by themselves survival correlates with the standard deviation (SD) of the nearest nuclear distance and nuclear elongation; that is, patients with crowded, high cellularity tumors and elongated cells had the worst prognosis. In univariate analyses only clinical stage correlated with adjusted survival rate. Multivariate survival analysis for morbidity showed that patients in Stages greater than or equal to II and high SD of ploidy values were free of symptoms for short intervals. When morphometric data were considered alone, patients with high variance in the chromatin texture and highly variable nuclear areas had shorter asymptomatic intervals.

The response of parathyroid cells to serum calcium is regulated by a calcium-sensing receptor protein (CaR). In patients with chronic renal failure, hypocalcemia contributes to the parathyroid hyperplasia and increased parathyroid hormone secretion characteristic of secondary hyperparathyroidism (sHPT). However, patients with uremia also display reduced sensitivity to extracellular calcium; this seems to be owing to an alteration of the receptor mechanism. This study examined calcium receptor expression in the parathyroid tissue of patients with sHPT, using immunohistochemical techniques and comparison with normal tissue and parathyroid glands of patients with primary hyperparathyroidism. In all the glands studied, immunostaining was more intense in chief cells than in oxyphilic, transitional, and clear cells. The parathyroid glands of patients with sHPT displayed significantly reduced expression of CaR with respect to morphologically normal ones; a very similar reduction is reported in adenomas. Furthermore, in glands displaying multinodular hyperplasia, expression was less marked in nodule-forming cells than in internodular areas. The decreased expression of calcium receptors in the parathyroid tissue of uremic patients was thought to be owing to the different cell populations present; these parathyroid glands contained predominantly transitional, oxyphilic, and clear cells, which normally express fewer receptors than chief cells, which are more abundant in normal glands.

We report 4 new cases of breast carcinoma in teenage girls diagnosed by use of histochemical and immunohistochemical methods. These cases of breast carcinoma in women under 20 years of age were found in the files of our department in the last 24 years (1976-2000). The patients had operable breast carcinomas corresponding to various histologic types (1 invasive ductal carcinoma associated with fibroadenoma, 2 secretory carcinomas, and 1 invasive lobular-type carcinoma). Simple mastectomy with low axillary lymph node dissection was performed in 2 postpubertal patients. Only 1 patient received adjuvant chemotherapy (case 4). After follow-up ranging from 76 to 126 months, 3 patients are alive and disease-free and 1 has disseminated metastatic disease. The correlations with prognosis-related risk factors (stage, age, previous benign lesions, family history, histologic types, hormonal receptors, and pregnancy) were examined.

Aims : Phaeochromocytomas may produce several neuropeptides as they are considered neuroendocrine tumours. Nevertheless, studies are scarce and no clear predictive biologic value has been stablished in the case of neuropeptides expression. Methods : We have investigated immunohistochemically the neuropeptides expression of a serie of 36 phaeochromocytomas: 25 sporadic, seven familial type MEN (multiple endocrine neoplasm) and four familial phaeochromocytomas not associated with MEN syndrome. The reactivity for neuron-specific enolase (NSE), synaptophysin, vasoactive intestinal peptide (VIP), chromogranin A, calcitonin, ACTH, somatostatin and HMB-45 was tested according to the avidin-biotin complex (ABC) method using polyclonal antibodies. Results : Phaeochromocytomas have a multiple synthetic activity as main neuroendocrine feature. Despite phaeochromocytoma tumour cells heterogeneity chromogranin and synaptophysin are the most common neuropeptides synthesised, as they are associated with the presence of neuroendocrine storage granules. We find a statistically significant higher synthesis of corticotrophin hormone in familial phaeochromocytomas than in sporadic forms, on the contrary the synthesis of VIP is statistically associated with sporadic forms of phaeochromocytomas. We also found a direct relation of ACTH and overexpression and malignant tumours and a positive relationship between NSE and benign forms of phaeochromocytomas.

In many rat strains, C-cell hyperplasia occurs in an age-dependent manner and is often associated with multifocal C-cell carcinoma. The purpose of this study was to investigate the spectrum of spontaneous, proliferative C-cell disorders by gender in Wistar rats throughout their lifespan. The incidence of C-cell hyperplasia shows a significant increase with age (P

Recently, the demonstration of DAP IV activity in thyroid cells aspirates has been proposed as an useful tool for the diagnosis of malignancy. We have studied the enzymatic activity of DAP IV, using the modified method of Lodja, in a series of 336 selected aspirates of the thyroid gland with the following cytologic diagnosis : 236 nodular hyperplasias, 60 follicular proliferations, eight Hashimoto's thyroiditis, eight Hurthle-cell proliferations, 20 papillary carcinomas, two anaplastic carcinomas, and two medullary carcinomas. The results were subjectively evaluated on the basis of staining intensity and extension in a minimum of 200 cells. Strong-to-moderate enzymatic activity with an extension of more than 40% of the cells were exclusively seen in follicular-cell derived carcinomas (papillary carcinoma, Hurthle-cell carcinoma, and follicular carcinoma). Medullary carcinoma, anaplastic carcinoma, and benign conditions were negative or weakly stained. Cytohistologic correlation in 88 patients operated on showed the following results : 26 nodular hyperplasia (18 nodular hyperplasia and eight follicular adenomas ), 36 follicular proliferation (24 nodular hyperplasia, six, adenomas, three papillary carcinomas, three follicular carcinomas), two Hurthle-cell proliferation (one Hurthle-cell adenoma and one Hurthle-cell carcinoma), ), 20 papillary carcinomas, two medullary carcinomas, and two anaplastic carcinomas. DAP IV staining was moderate to strong and extensive in all malignant tumors initially diagnosed as follicular or Hurthle-cell proliferations. We conclude that DAP IV activity is present in malignant differentiated thyroid tumors of follicular cells (papillary carcinoma, follicular carcinoma, Hurthle-cell carcinoma), but it is identified neither in medullary carcinoma nor in anaplastic carcinoma. Therefore, its usefulness is restricted to the diagnosis of follicular cell malignancies.

Recently tumors have been reported that have an architectural pattern and cellularity similar to hyalinizing trabecular adenoma and show either parafollicular differentiation or histological findings suggestive of malignant neoplasm of the follicular cells. This study describes two cases of thyroid carcinoma of follicular cells that displayed a hylinizing trabecular pattern. The first case was a 25-year-old euthyroid woman with a cold thyroid nodule in the right lobe. On fine needle aspiration a diagnosis of papillary carcinoma was rendered. The thyroidectomy disclosed a 2-cm, firm, brown, encapsulated tumor in the right lobe. The tumor had a growth pattern and cytologic features similar to those described in hyalinizing trabecular adenoma. The differences between these neoplasms were the presence of mitotic figures, prominence of the nucleolus, capsular blood vessel invasion, and microtubule groups in the endoplasmic reticulum. The second case was a 19-year-old euthyroid woman with a cold thyroid nodule in the left lobe. A cytologic diagnosis of follicular proliferation was rendered. A 4-cm, firm, whitish, encapsulated nodule was found in the left lobectomy. The tumor cells were arranged in two clear-cut patterns: a trabecular hyalinizing pattern with a small focus of papillary growth, and a follicular pattern. These findings confirm the existence of malignant thyroid tumors with a hyalinizing trabecular pattern and illustrate the nonspecificity of this peculiar pattern, since it may also be seen in papillary carcinomas of the thyroid. The relationship between hyalinizing trabecular adenoma and papillary carcinoma of the thyroid is commented on.

The heterogeneous distribution of thyroid C-cells has until now hindered an objective evaluation of changes caused by age or experimental stimuli. To overcome this, a rigorous methodology has been designed to detect variations in shape, size, and number of C-cells throughout development. Using this methodology, we have demonstrated that C-cells do not significantly alter their shape with age. However, their volume increases gradually from 472 microns3 in newborn rats to 1653 microns3 in 120-day-old animals. Over the same time period, the mean number of C-cells within the thyroid gland increased 9-fold (from 1.6 x 10(4) to 1.5 x 10(5), and the number of C-cells per unit area decreased (from 6.15 x 10(4)/mm3 to 2.6 x 10(4)/mm3). We conclude that there are marked variations in size, total number, and number of C-cells per unit area in the rat thyroid gland after birth.

Fifteen cases of anaplastic thyroid carcinoma, including eight cases with a differentiated component, were studied by DNA analysis. All areas of anaplastic carcinoma showed an aneuploid DNA content. The eight cases of anaplastic carcinoma with differentiated component (two follicular carcinomas, two papillary carcinomas, one Hürthle cell carcinoma and three poorly differentiated carcinomas) exhibited aneuploid DNA content in the differentiated area of the tumour. Karyometric parameters allowed a fairly clear separation between giant cell, spindle cell and differentiated components. The results support the hypothesis that patients with aneuploid differentiated carcinoma represent a higher risk group and are probably more prone to developing anaplastic carcinoma.

Seven cases of endometrial mucinous metaplasia and five of well-differentiated mucinous adenocarcinoma of the endometrium were studied. Cytologic specimens were obtained by Isaacs endometrial sampler, avoiding endocervical contamination. The histologic diagnosis between the intermediate type of mucinous metaplasia and the well-differentiated mucinous adenocarcinoma posed no problems. DNA analyses of the histologic samples showed a euploid pattern in benign and intermediate types of metaplasia, while well-differentiated mucinous adenocarcinoma showed a hyperdiploid pattern. The cytologic diagnosis of benign mucinous metaplasia should be suggested in the presence of abundant mucinous cells in endometrial samples in the absence of nuclear abnormalities.

The authors carried out a histochemical study with lectins (Ulex europaeus agglutinin-I [UEA-I], Triticum vulgaris [WGA], Glycine max [SBA], Dolichos biflorus [DBA], and Arachis hypogaea [PNA]) in different thyroid gland conditions (17 benign nodular goiters, three diffuse hyperplasias, five Hashimoto's thyroiditis, 20 follicular adenomas, 14 well-differentiated papillary carcinomas, five well-differentiated follicular carcinomas, and 30 normal thyroids) in order to determine if specific lectin patterns are developed during neoplastic transformation. The results showed that (1) in normal thyroid glands, the lectin, UEA-I, is able to discriminate between follicular cells and C-cells; (2) pathologic follicular epithelium had an increased expression of UEA-I, SBA, and WGA receptors; (3) no lectin or group of lectins allow a distinction between follicular carcinoma and papillary carcinoma; (4) when benign and malignant tumors are compared for UEA-I affinity there is a significantly greater frequency of malignant tumour with UEA-I receptor; and (5) although all investigated lectins have shown receptors in endothelial cells at least in one case, the most constant findings have been obtained with UEA-I and WGA. These findings suggest that lectins are not useful in routine diagnostic pathologic examination; however, in particular cases of follicular carcinoma, UEA-I may be a useful tool for the recognition of small vessels invaded by tumoral cells and the demonstration of fucose residues in malignant tumor cells.

A case of myxoid leiomyosarcoma located in the right pulmonary veins is presented. The patient complained of progressive dyspnea, orthopnea, sputum cruentum and right chest pain. Angiography revealed an obliteration of right pulmonary veins by a tumor mass that expanded into the left atrium. Histologically, the lesion contained densely packed fusiform cell areas that alternated with other much less cellular and richer in interstitial myxoid matrix. The tumor cells showed specific immunoreactivity to desmin antibodies and contained abundant thin filaments with focal densities and micropinocytic vesicles.

3 cases of cutaneous vegetant intravascular hemangioendothelioma are presented, 2 of them corresponded to a pure form, whilst the other arose in a pyogenic granuloma. All lesions behaved in a benign fashion. In some cases these may mimic an angiosarcoma (Masson’s pseudoangiosarcoma). The endothelial proliferation, which characterizes the lesion, is considered as a reactive phenomenon secondary to fibrin deposits originating from the destruction of the vascular walls of a hemangioma.

Abnormal Wnt signaling and impaired cell–cell adhesion due to abnormal E-cadherin and β-catenin function have been implicated in many cancers, but have not been fully explored in laryngeal squamous cell carcinoma. In this study, β-catenin cellular location and E-cadherin expression levels were analyzed in 16 laryngeal squamous cell carcinomas (LSCCs) (9 glottic and 7 supraglottic) and 11 samples of non-tumoral inflammatory larynx tissue, using immunohistochemical methods. All non-tumoral tissues showed equally strong membranous expression of β-catenin, while cytoplasmic expression was found in only 3 of the 11 samples. By contrast, whereas 8/9 glottic LSCCs exhibited only membranous expression of β-catenin, 6/7 supraglottic LSCCs displayed both membranous and cytoplasmic expression (p = 0.003). Strong E-cadherin staining was observed in 9/11 non-tumoral tissues and 7/9 glottic LSCCs, whereas 4/7 supraglottic LSCCs exhibited weak expression. Reduced membrane expression of E-cadherin and cytoplasmic retention of β-catenin in supraglottic LSCC seems to be related with more aggressive biological behavior which has been described in clinical studies. Further research is required to clarify the involvement of β-catenin in the mechanism associated with malignant transformation in laryngeal tissues.

The present histometric study is on thyroid glands of Wistar rats ranging in age from 0 to 120 days. The mean volume of one lobe of the thyroid in 4-month-old animals was some 22-, 10-, 5-, and 3-fold greater, respectively, than the volumes in the newborn, 5-, 10-, and 30-day-old rats. At 4 months of age the mean length of the lobe was 3 times greater than at birth. The volumetric fractions (Vv) of the different histological components (follicular cells, C-cells, colloid, and interstitial tissue) changed considerably in the course of development. The Vv of follicular cells diminished from 61.4% at birth to 37.2% at 4 months. C-cells increased from 2.9% in the newborn to 4% at 15 days, with no further significant change at 4 months. Colloid and stroma together represented 35.7% at birth, increasing to 58.5% at 120 days. In the course of the first 4 months of life, the absolute volumes occupied by follicular cells, C-cells, colloid, and stroma increased 13.25, 30.75, 38.6, and 33.7 times, respectively; these changes reflect the variations that occur in the volume of the gland and the Vv throughout postnatal development.

Two cases of non-Hodgkin's lymphoma that show a sarcomatoid pattern within the jaw are described. Their primary origin in bone was demonstrated by radiologic studies. In one case, diagnosis was delayed because the clinical picture suggested inflammatory periodontal disease. In both cases, the histologic picture was similar to that of a sarcomatoid neoplasm with intense stromal sclerosis; hemimandibulectomy was performed in one case. The tumor contained cells with large, irregular, sometimes lobulated nuclei and high mitotic activity, and perforated mandibular bone with infiltration into adjacent soft tissues. The lymphoid nature of these neoplasms was demonstrated by immunohistochemical and ultrastructural study.

This paper presents the results of investigations into the mitotic rates of thyroid endocrine cells in normal postnatal rats, aged 1-120 days. Our study revealed considerable age-dependent shifts in the mean mitotic activity of follicular cells and C-cells. The maximum indices of endocrine cell renewal were reached during the first 10 days of life, decreasing gradually and significantly until 25 days. At 1 month, there was a significant recuperation of the division rate for both cell types, which declined in the adult rat. These results mean that the proliferation of C-cells and follicular cells is inversely proportional to age. The preferential zone of localization of mitoses of both cell types is the central region of the thyroid lobe. The present paper provides new evidence for the postnatal origin of C-cells and follicular cells from the preexisting endocrine cells.

Although in both human and experimental pathology ras mutations have been related to the origin and progression of follicular-cell tumours, reports differ considerably with respect to the frequency of such mutations. The present paper reports, using direct sequencing, the incidence of Ki-ras mutations (codons 12 and 13) in follicular-cell carcinomas of the thyroid gland in Wistar rats induced by administration of radioactive iodine and potassium perchlorate. Direct sequencing revealed no mutations in the amplified gene segment of any of the 72 carcinoma samples studied. This absence of mutations agrees with some and is in sharp contrast with other previous reports in the literature, both for experimental animals and in studies of human thyroid follicular-cell carcinoma. Our results suggest that Ki-ras activation via mutations at codons 12 and 13 is neither a constant event nor an early event in the development of rat thyroid follicular-cell carcinoma.