PubMed HealthSearch

Biomedical subjects

H R Harach

Publications and source records attributed to H R Harach.

At least 19 recordsLinked to original sources

Nodular goiter: a histo-cytological study with some emphasis on pitfalls of fine-needle aspiration cytology.

A comprehensive comparative histo-cytological study of 48 nodular goiters from an endemic goiter region was undertaken. Practically all features observed on the biopsies were identified, although with less frequency, on the smears. In agreement with previous observations, characteristic components of nodular goiter (NG) in aspirates included small to medium size epithelial cells with regular round nuclei, honeycomb pattern, large follicles, papillae showing the previously mentioned epithelial features, oxyphilic cells, and moderate to abundant background colloid material and thyroid phagocytes (macrophages). All eight features occurred together in only 2% of the studied cases, seven in 6 (12.5%), six in 4 (8%), five in 6 (12.5%), four in 12 (25%), three in 6 (12.5%), two in 11 (23%), and one in 2 (4%) cases, respectively. Regardless of the number and combination of features present, specific identification of NG on the smears may not always be possible and diagnostic pitfalls include thyroid cyst, Hashimoto's thyroiditis, granulomatous lesions, and, more frequently, follicular neoplasia. Our findings suggest that thyroid aspirates should be analysed with critical clinico-pathological approach and surgery considered only for nodules that are clinically suspicious or unresponsive to hormonotherapy when a diagnosis of follicular neoplasia is made.

Biopsy, Needle

Chromogranin A immunoreactivity compared with argyrophilia, calcitonin immunoreactivity, and amyloid as tumour markers in the histopathological diagnosis of medullary (C-cell) thyroid carcinoma.

Applying the WHO criteria for the histopathological diagnosis of medullary thyroid carcinoma (MTC)--as well as the criterion that a significant amount of argyrophil cells, amyloid deposits, or calcitonin (CT) immunoreactive cells shall be present--122 cases were identified from the files of the Swedish Cancer Registry. Both non-occult (n = 110) and "occult" (less than 1 cm in diameter) (n = 12) MTCs were included. Both primary tumours (n = 91) and metastatic lesions (n = 31) were investigated. The specimens available were all only conventionally formalin-fixed and paraffin-embedded. The presence of neoplastic cells immunoreactive with antisera against chromogranin A (Chr A) was compared with that of the other three MTC markers. Chr A immunoreactive cells were present in practically all the cases. Similar results were obtained when the argyrophil reaction alone and CT immunoreactivity alone were used as markers. When two of the three MTC markers were combined, it was found that virtually everyone of the 122 tumours could be identified as a MTC. In contrast, the presence of amyloid deposits was found to be a less constant MTC marker; whereas 94% of the primary tumours had amyloid deposits, they were present in only approximately 70% and 60% of the metastatic and "occult" tumours respectively. No differences in the staining reaction patterns were found between familial (n = 18) and the sporadic (n = 104) types of MTC.(ABSTRACT TRUNCATED AT 250 WORDS)

Amyloid

Necrotic debris in thyroid aspirates: a feature of follicular carcinoma of the thyroid.

Fine needle aspirates from 44 follicular thyroid tumours (30 adenomas, 14 carcinomas) have been studied. All aspirates contained neoplastic cells in follicular and trabecular arrangements. The individual tumour cells showed varying degrees of anisonucleosis and nuclear pleomorphism. Colloid was scanty or absent from all smears. Granular or filamentous necrotic material was observed in both biopsies and smears from one moderately and two poorly differentiated follicular carcinomas, but in none of the adenomas. This suggests that necrotic debris may be a feature of follicular carcinoma of the thyroid.

Adenocarcinoma

Parathyroid hyperplasia in tertiary hyperparathyroidism: a pathological and immunohistochemical reappraisal.

Thirty-one parathyroid glands from 11 patients with tertiary hyperparathyroidism were examined histologically and immunohistochemically to characterize better the nature of the accompanying parathyroid hyperplasia. The parathyroids showed varying degrees of nodular and diffuse hyperplastic involvement as well as apparently normal background tissue. The nodules were usually multiple within any one gland and, together with diffuse hyperplastic tissue, showed a varied cyto-architectural pattern. All glands studied showed both cellular argyrophilia and parathyroid hormone immunoreactivity. The staining pattern for parathyroid hormone ranged from negative or weak to strong, and from patchy to diffuse in hyperplastic tissue from different glands and within the same gland, regardless of the cell type. Apparently normal areas usually showed only patchy weak to moderately strong parathyroid hormone positivity. From the data obtained the most striking feature of the parathyroid glands in tertiary hyperparathyroidism is their extreme variability, both morphological and functional, as indicated by parathyroid hormone immunoreactivity. Furthermore, the generally lesser degree of parathyroid hormone immunoreaction observed in apparently normal parathyroid tissue may reflect suppression of hormone synthesis, with accompanying morphological regression to normal of pre-existent diffuse hyperplasia by autonomous hyperfunctioning nodules associated with tertiary hyperparathyroidism.

Adult

Parathyroid hyperplasia in multiple endocrine neoplasia type 1: a pathological and immunohistochemical reappraisal.

Twenty-nine parathyroid glands from nine patients with multiple endocrine neoplasia type 1 (MEN 1) syndrome were examined histopathologically and immunocytochemically to characterize better the nature of the accompanying parathyroid hyperplasia. The parathyroids showed varying degrees of nodular and diffuse (partial and total) hyperplastic involvement as well as apparently normal tissue. The nodules were usually multiple within any one gland and showed a varied cytoarchitectural pattern. All glands studied showed both cellular argyrophilia and parathyroid hormone immunoreactivity. The staining pattern for parathyroid hormone ranged from negative or weak to strong and from patchy to diffuse in hyperplastic tissue from different glands and within the same gland. Apparently normal areas usually showed the strongest positive reaction. Amyloid material was observed within glandular lumens from hyperplastic areas in over half of the studied cases and stained positively for parathyroid hormone. This suggests that the hormone could be the precursor molecule of parathyroid amyloid as occurs with hormone-derived amyloid from other endocrine tumours. The overall findings indicate that the most striking feature of the parathyroid glands in MEN 1 is their variability, both morphological and functional, as indicated by their parathyroid hormone immunoreactivity.

Adult

Parenchymatous thyroid nodules: a histocytological study of 31 cases from a goitrous area.

AIMS: To analyse the benefits and limitations of fine needle aspiration in the cytological differentiation of parenchymatous nodular goitres from follicular tumours in an endemic area. METHODS: Cytological smears of fine needle aspirates from 31 parenchymatous nodular goitres were studied. A sample from the punctured nodules was fixed in formalin and stained with haematoxylin and eosin for histological analysis. RESULTS: All nodules occurred in a multinodular gland, were well circumscribed, did not compress surrounding thyroid tissue, and for the most part, were unencapsulated. Two cases showed cytological features of nodular goitre, two of colloid cysts; the remaining 27 were cytologically indistinguishable from follicular lesions. CONCLUSIONS: Most of the parenchymatous nodules studied had features suggestive of follicular lesions or neoplasia, but surgical treatment should only be considered after hormone treatment has proved unsuccessful, and when they are not suspected as malignant clinically. Fine needle aspiration is useful as a diagnostic and screening aid, but the results should be interpreted with caution to prevent unnecessary surgery.

Biopsy, Needle

Thyroglobulin in human thyroid follicles with acid mucin.

The minority of human thyroid follicles that contain acid mucin are often grouped in the C-cell area of the gland, and are lined by abundant C cells. They are thought to be derived from the ultimobranchial contribution to the thyroid gland. This study demonstrates the presence of thyroglobulin reactive follicular cells and colloid as well as calcitonin and CGRP in these ultimobranchial-related thyroid follicles. These findings add further support to the belief that the ultimobranchial body is a source of at least some C cells and follicular cells, and support the view that thyroid mixed medullary follicular neoplasia may originate from an ultimobranchial stem cell line.

Animals

Cytopathology of follicular tumours of the thyroid with clear cell change.

A retrospective cytological study of nine follicular tumours of the thyroid with clear cell change was undertaken. In five clear cell adenomas and one moderately differentiated clear cell follicular carcinoma the epithelial cells occurred singly or in sheets and clusters; they sometimes assumed a trabecular or follicular pattern. The cells usually had pale diffusely vacuolated cytoplasm with ill-defined boundaries, a variable degree of anisonucleosis, nucleolar enlargement, and nuclear overlapping. Smears from a signet-ring cell adenoma contained in addition a few cells with large cytoplasmic vacuoles and compressed eccentric nuclei. In these cases a cytological diagnosis of 'follicular lesion' (or follicular neoplasia), clear cell type or signet-ring cell type, was given. A cytodiagnosis of 'carcinoma' was made only in the poorly differentiated follicular carcinoma-clear cell variant studied which showed unequivocal features of malignancy. Features suggestive of thyroid cyst, nodular goitre, Hashimoto's thyroiditis, and cell hyperactivity (marginal vacuoles, 'fire flare') were also found in the aspirated specimens of these cases of clear cell tumour of the thyroid.

Adenocarcinoma

Cytological features of non-small cell carcinomas of the lung in fine needle aspirates.

Fifty eight lung tumours were typed according to the second World Health Organization histological classification and compared with the cytological appearances obtained by fine needle aspiration in a total of 47 primary non-small cell carcinomas. The presence of glands, cell balls, branching or papillary structures, cylindrical cells and nuclear grooving were major diagnostic indicators for adenocarcinoma. Cytoplasmic macrovacuoles were more common in adenocarcinomas (69%) than in squamous (37%) and large cell (50%) carcinomas. Two or more of these features were combined in all well and moderately differentiated adenocarcinomas and in 67% of poorly differentiated adenocarcinoma. The major cytological indicators for squamous carcinomas were the presence of keratin and eosinophilic spindle cells with glassy or laminated cytoplasm. Granular cytoplasm was not specific for any histological type. A combination of the major features for both adeno- and squamous carcinoma was present in 58% of adeno-squamous carcinomas, including some poorly differentiated types. Correct typing could be obtained in almost all the well and moderately differentiated carcinomas and in about two thirds of the poorly differentiated tumours using FNA, provided that combinations and not individual variables are considered.

Adenocarcinoma

Occult papillary microcarcinoma of the thyroid--a potential pitfall of fine needle aspiration cytology?

The use of fine needle aspiration cytology detected papillary carcinoma in two patients with multinodular goitre measuring 0.7 cm and 0.9 cm in diameter, respectively. Like most of the cases from previous large series, the tumours progressed slowly as shown by absence of enlarged glands on surgical exploration and no clinical signs of metastasis after two and five years of follow up. This study shows that aspiration cytology can detect a virtually harmless occult papillary carcinoma that will oblige patients to have surgery. This very occasional "pitfall" of fine needle aspiration should not preclude this well known beneficial method from being used in the management of thyroid disease.

Adult

The pathology of granulomatous diseases of the thyroid gland.

In the present review we comment on granulomatous diseases of the thyroid gland based mainly on combined clinico-pathological criteria. Emphasis is given to diseases restricted to the thyroid (i.e., de Quervain's, palpation and interstitial giant cell thyroiditis), and those that may manifest as primary in the thyroid though they may be part of a generalized process (i.e., sarcoidal, tuberculous, fungal and syphilitic thyroiditis). Other disorders with minor variable granulomatous or pseudogranulomatous components affecting the thyroid are briefly described, and differential diagnoses analysed for granulomatous lesions both specific and non-specific to the thyroid.

Granuloma

The ultimobranchial gland and congenital thyroid abnormalities in man.

This study was carried out to investigate the fate of the ultimobranchial contribution to the thyroid in man when the thyroid lobe is not fully descended. Thyroid abnormalities were recorded in 41 of 29,000 autopsies at the London Hospital--a prevalence of 1.41/1000. The 18 major abnormalities included four cases of lingual thyroid, in two of which cystic structures were noted in the neck in the region of the upper parathyroid. Three further cases of lingual thyroid with upper parathyroid cysts were collected from other sources. The multilobulated cystic structures were up to 1.5 cm in diameter and showed a variety of histologic features. In four cases there were glandular nodules of up to 1 mm across lying in the intercystic connective tissue. These nodules showed solid areas of irregularly distributed cells that stained positively for calcitonin and calcitonin gene-related peptide, intermingled with, and sometimes apposed to, follicular structures that showed follicular cells and colloid that stained for thyroglobulin. This study has provided conclusive evidence that the ultimobranchial body contributes both C cells and follicular cells to the thyroid in man, has documented the prevalence of congenital defects of thyroid development, and has described the human ultimobranchial gland as showing a wide developmental potential which may have implications in the histogenesis of thyroid neoplasia.

Animals

Solid cell nests of the thyroid.

The ultimobranchial thyroid solid cell nests (SCN), irregular structures of about 1 mm in maximal diameter, are usually found in the middle third of the thyroid lateral lobes. SCN are basically composed of non-keratinizing epidermoid cells which lack intercellular bridges and are immunohistochemically positive for a panel of high and low molecular weight keratin proteins, as well as for carcinoembryonic antigen. In addition, SCN display isolated or grouped peripheral calcitonin-immunoreactive 'clear' (C) cells in up to 54 per cent of cases. The SCN central lumen, when present, is usually surrounded by mucinous cells; in addition, it may contain desquamated cells, cell debris, acid mucosubstances, characteristic PAS-positive granular material after diastase treatment, and colloid-like material. The so-called mixed follicles, structures lined by epidermoid cells of SCN and follicular epithelium, are often found as an additional component of the ultimobranchial remnants. The relationship of SCN to thyroid parenchymal cells and the probable implications of the thyroid 'ultimobranchial system' to tumour histogenesis are analysed. Pitfalls that may emerge with regard to SCN in practical pathological approaches are emphasized.

Humans

Thyroglobulin immunostaining in follicular thyroid carcinoma: relationship to the degree of differentiation and cell type.

A series of 47 primary and seven metastatic thyroid follicular carcinomas, including well, moderately and poorly differentiated, were tested for thyroglobulin (Tg) using immunohistology. In addition, three combined follicular undifferentiated carcinomas, 17 undifferentiated carcinomas and five renal cell carcinomas metastatic to the thyroid were examined. Only two follicular carcinomas did not stain for thyroglobulin. Some inter-tumour differences in Tg staining were found but there was no absolute correlation between this and the degree of tumour differentiation. The two tumours that failed to stain for Tg were poorly differentiated; thyroglobulin positive poorly differentiated tumours demonstrated a clearly weaker staining pattern for Tg. All but one of 15 oxyphilic follicular carcinomas stained positively for Tg but the staining intensity was often weak. Five of six clear cell follicular carcinomas were positive for Tg but the staining reaction was generally faint and there were often large areas devoid of positive cells. Positive staining was demonstrated in the differentiated areas of combined follicular undifferentiated carcinomas. Undifferentiated carcinomas and metastatic renal cell carcinomas gave negative results. Thyroglobulin is a reliable marker for thyroid follicular carcinoma but the patchy staining pattern, particularly in the less well-differentiated tumours may produce less reliable results in small biopsies.

Adenocarcinoma

Medullary (C cell) carcinoma of the thyroid with features of follicular oxyphilic cell tumours.

During the last few years the spectrum of histological features seen in tumours of C cell origin has broadened and, among other variants, papillary and glandular forms have been recognized. Seven cases are now reported of medullary carcinoma with features of oxyphilic follicular cell tumours. These cases were studied with routine techniques and an immunolocalization method using antibodies to calcitonin and thyroglobulin. The tumours were mainly composed of well-demarcated eosinophilic cells of variable size arranged in trabecular, solid and follicular structures. One of the cases was negative for calcitonin but displayed strong diffuse argyrophilia and amyloid deposits; two amyloid-free tumours revealed argyrophil granules and were positive for calcitonin, the immunoreaction being inconspicuous in one however. Apart from trapped normal thyroid follicles, thyroglobulin was absent in the tumours. It is concluded that medullary carcinoma should be considered in the differential diagnosis of thyroid oxyphilic cell tumours, even when showing glandular differentiation, and that immunolocalization techniques using calcitonin and thyroglobulin in combination with methods for demonstration of argyrophil granules and amyloid are essential for accurate diagnosis of this type of medullary carcinoma of the thyroid.

Carcinoma

Mixed follicles of the human thyroid gland.

Mixed follicles are structures composed of squamous-like and follicular epithelia. Little attention has been generally paid to these peculiar follicles of the human thyroid; thus the aim of the present study was to investigate their prevalence and biological properties by means of systematic autopsy, histochemical and immunohistochemical surveys. Mixed follicles were found to be present in 54% and 81% of the patients with solid cell nests, as well as in 50% and 77% of the total number of the ultimobranchial nests, when one or two histological samples from each solid cell nest were examined, respectively. The follicular lumen of mixed follicles usually contained an eosinophilic and PAS-positive colloid-like material, although in 22% of the cases acid mucins sometimes intermixed with PAS-positive granular material and cell debris were also present within lumina. Follicular cells lining mixed follicles basically did not stain positively for calcitonin. The results indicate that mixed follicles are not rarely found in the human thyroid. The presence of intraluminal mucins and cell debris and the absence of calcitonin-containing cells in the follicular epithelium lining these peculiar follicles suggest that at least some thyroid follicular cells could originate from ultimobranchial tissue.

Adolescent