A novel thyroid hormone receptor-beta mutation, not anticipated to occur in resistance to thyroid hormone, causes variable phenotypes.

Resistance to thyroid hormones (RTH) is a syndrome characterized by a variable tissue hyposensitivity to thyroid hormones and is linked to mutations in the thyroid hormone receptor-beta (TRbeta) gene. We report here for the first time in vivo the mutation R429W (CCG-->TCG) located in the exon 10. The artificial mutant obtained in vitro displayed a normal T(3)-binding affinity and transactivation function. Therefore, it was thought to produce little, if any, clinical effect and to escape to clinical detection. The present report is at least in part discordant with this prediction since the propositus and his grandmother had an authentic hyperthyroidism with high FT(4) plasma level in the presence of inappropriate TSH. On the other hand, spontaneous variations of clinical features and - interestingly - of plasma FT(4) concentrations with time in the propositus, and the phenotype observed in his mother who never complained with thyrotoxic symptoms, confirmed the in vitro binding and functional predictions. The most intriguing is the clinical course of the grandmother as she first presented with predominant pituitary RTH and a diffuse goiter and finally with a toxic multinodular goiter with normal T(3) and T(4) plasma concentrations and suppressed TSH. In conclusion, we report a novel mutation in the gene encoding the thyroid hormone receptor responsible for predominant pituitary RTH already described in vitro but not in vivo. The fluctuant phenotype of the propositus suggests that other factors modulate the degree of tissue resistance that is under genetic control. Toxic multinodular goiter, possibly due to chronic TSH stimulation during RTH, in addition to the phenotype variability, increases the difficulty to diagnose this thyroid disorder.

[Transthoracic aspiration. Evaluation of cytologic and histologic diagnosis in a pulmonary nodule by retrospective comparison of 2 series of 267 cytoaspirations and 292 coaxial needle aspirations]. / La ponction trans-thoracique. Evaluation du diagnostic cytologique et histologique d'un nodule pulmonaire par comparaison rétrospective de 2 séries de 267 cytoponctions et de 292 ponctions à l'aiguille coaxiale.

Percutaneous fine-needle aspiration is a well established method for the diagnosis of peripheral lung lesion. In order to compare different methods of aspiration, we analyze retrospectively two different series: 267 fine needle aspirations (FNA) compared with the histological diagnosis on surgical specimens and 292 lung biopsies using a coaxial technique with comparison between cytological diagnosis--smears and imprints--and histological diagnosis simultaneously obtained on the same specimen. The sensitivity (91%), the specificity (90%) and the overall typing accuracy related to the histological types obtained by FNAB are equivalent to those of the literature. The low rate of pneumothorax in the series (6%) is related to the use of immediate interpretation of the specimen. Automated biopsy with a coaxial cutting needle provide cytological specimens--smears and imprint--with a high rate of sensibility (95.3%) and of sensibility (98%). The overall sensitivity of the cytological methods alone is better than biopsy (95.3% vs. 92.9%), but the typing accuracy is not as good as biopsy alone (98% vs. 100%). False-positive and false-negative diagnoses are the same in both series. In conclusion the percutaneous aspiration method choose to establish a morphological diagnosis in lung lesion depends now on the habits of the radiologist and the pathologist.

[Clear cell adenoma of the parathyroid gland: a rare and misleading lesion]. / Adénome parathyroïdien à cellules claires: une lésion rare et trompeuse.

Parathyroid adenomas are common lesions and are considered to be the cause of most of the primary hyperparathyroidism cases. We report the case of a 73 year-old man who presented with a primary hyperparathyroidism. Clinical and histological explorations revealed the presence of an isolated parathyroid tumor containing exclusively clear cells and devoid of malignancy. This is the second reported case of clear cell parathyroid adenoma. Thus, in spite of its low occurrence, this diagnosis must be considered after rejection of the most frequent parathyroid clear cell hyperplasia and parathyroid carcinoma, or depending of the location, clear cell thyroid tumor and clear cell renal carcinoma metastasis.

Familial non-medullary thyroid carcinoma: pathology review in 27 affected cases from 13 French families.

BACKGROUND AND OBJECTIVES: When familial non-medullary thyroid cancer (FNMTC) develops with no obvious associated pathogenetic factor, an inherited predisposition may underlie the process. The present study was conducted because detailed pathological findings are lacking in most series of FNMTC. PATIENTS AND METHODS: Thirteen families comprising 27 cases of FNMTC were included (1.8% of differentiated thyroid carcinoma). The family relationship (20 F, 7 M; age 46 +/- 16 years; mean +/- SD) was 'siblings' in eight families, 'parent and child' in four and 'aunt and niece' in one. Careful pathological review of the thyroid tumours (papillary/follicular: 25/2, size: 16 +/- 11 mm) was performed. RESULTS: Initial staging according to extension was as follows: grade I (n = 16), II (n = 2), III (n = 6), IV (n = 3). Fourteen tumours were papillary microcarcinomas (size: 8 +/- 2 mm). No tumour phenotype that may be considered specific for FNMTC was found when considering either age, pathological findings or tumour aggressiveness. Although rare events were found in both relatives of some families suggesting a putative 'familial' phenotype of FNMTC, this may be fortuitous. CONCLUSION: Micro familial non-medullary thyroid cancers are more common than previously reported and further studies are required to be able to distinguish this subgroup from sporadic papillary microcarcinomas. The careful pathological review of the familial non-medullary thyroid cancer in this study does not seem to point to a distinct subgroup of familial differentiated thyroid carcinoma although the data are intriguing. Genetic studies are now required to investigate this issue.

[Role of cytology and frozen sections in the intraoperative examination of the thyroid: comparison of two experiences]. / Place de la cytologie et de la congélation au cours de l'examen extemporané de la thyroïde: confrontation de deux expériences.

Two experiences of peroperative diagnosis in thyroid surgery are reported. In Bordeaux (France), frozen sections are supplemented by touch smears. Imprints alone give results similar to frozen but are not suitable in differentiating follicular adenoma from carcinoma; they appear more accurate for recognising the follicular presentation of papillary carcinoma. Touch smear is a rapid cost-effective alternative to frozen section. In Brussels (Belgium), a more conventional attitude results in 185 frozen. A false negative ends in a follicular carcinoma. Eleven follicular proliferations will be signed out adenoma (8 cases) or carcinoma (3 cases) and three papillary carcinomas will only be detected after embedding. Six false negative derive from frozen section, no false positive is noted. An immediate change in the surgical procedure is justified twice. These observations argue for the free choice by the pathologist of the best technical procedure in peroperative diagnosis.

[Borderline lesions of the thyroid: diagnostic strategy]. / Lésions frontières de la thyroïde: stratégie diagnostique.

Some thyroid neoplasms notoriously cause problems in the histologic diagnosis of their nature (follicular versus papillary for example) or their malignant potential (adenoma versus carcinoma) because of overlapping histologic features. Here, thyroid lesions are presented according to their histologic presentation (vesicular, papillary, trabecular, solid or cystic patterns, fibrosing thyroids and lymphoid infiltrate). For each entity, the most discriminant histologic features are described with emphasis on the diagnostic pitfalls and their histological clues.

Cytologic findings in a neovagina created with Vecchietti's technique for treating vaginal aplasia.

OBJECTIVE: To report long-term cytologic findings after treatment of congenital vaginal aplasia or Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) using progressive traction of the vulvar tissues, or Vecchietti's technique (VT). STUDY DESIGN: In eight women with MRKH, neovaginal smears stained by the Harris-Schorr technique were collected 2-12 years after VT. RESULTS: Eosinophilic superficial cells observed in all cases indicate that the neovaginal epithelium responds to hormonal variations. The presence of Döderlein bacilli (seven cases) suggests that the regional environment of the neovagina is almost the same as that of the normal vagina. Gardnerella vaginalis (one case) and human papilloma virus infection (low grade squamous intraepithelial lesions) (one case) were also observed. CONCLUSION: Neovaginal smears taken after the cicatrization period following construction of a neovagina by VT show a remarkable resemblance to those from normal vaginal mucosa and suggest that these neovaginas are almost the same as normal vaginas.

Telomerase activity in human thyroid carcinomas originating from the follicular cells.

Telomerase activity is known to be absent from most normal and well-differentiated tissues, although being detectable in the vast majority of malignant tumors. An increasing number of reports demonstrate that telomerase may be activated in benign tumors, such as adenomas. We have investigated a series of normal and neoplastic thyroid tissues for the presence of telomerase activity. As expected, all normal thyroid tissues (n = 20) had no display of telomerase activity. Amongst cancers, the incidence of telomerase activity varied with the histological subtypes. Telomerase activity was present in only 3/15 cases (20%) of papillary carcinomas. Telomerase activity was more frequently detected in follicular (4/6) and in undifferentiated (2/3) carcinomas. Unexpectedly, one case (1/12) of adenoma contained high levels of telomerase activity. Taken together, these results indicate that telomerase may play some role in the pathogenesis of thyroid tumors, in particular in follicular and undifferentiated carcinomas that are known to have the most aggressive behavior.

[A study of biological and histological criteria of thyroid autoimmunity in diffuse goiters with hyperthyroidism]. / Etude des paramètres biologiques et histologiques d'autoimmunité thyroïdienne dans les goitres diffus avec hyperthyroïdie.

Hyperthyroidism is usually classified as follows: with diffuse or with toxic plurinodular goiter, respectively considered as autoimmune and non-autoimmune thyroid disorders. This classification seems partially inadequate as signs of thyroid immunity may be found in some plurinodular toxic goiter and alternatively may by lacking in some cases of Graves' disease. These observations led us to study the intensity of intrathyroidal autoimmune process (IAP) and the levels of TBIAb, TPO- and Thyroglobulin-antibodies in 105 cases with diffuse goiter, hyperthyroidism and elevated RAIU (92 women and 13 men, age 34 +/- 11, mean +/- SD). The intensity of intrathyroidal autoimmune process (IAP) was determined by one pathologist (HT) by semi quantitative method applicable to routine clinical use. Subtotal thyroidectomy was performed because of a large goiter (n = 29), a concomitant cold nodule (n = 20), a recurrent disease (n = 18), intolerance to antithyroid drugs (n = 5) or because patients chose surgical treatment (n = 33). All cases were rendered euthyroid at the time of surgery using antithyroid drugs or iodine. The results show a lack of IAP and undetectable levels of TBIAb, TPO- and Thyroglobulin-antibodies in 10%, 11%, 25% and 47% respectively. The intensity of IAP was not different in case of first episode or recurrence of hyperthyroidism and was not related to type or duration of medical treatment. Comparison of patients with or without IAP show higher levels of TPO- and thyroglobulin-antibodies but not of TBIAb in the former group (P < 0.005). TBIAb were higher when ophthalmopathy and/or dermopathy were present vs absent (p < 0.05) and were correlated with FT4 levels (p < 0.05). The negative predictive value of TBIAb, TPO- and thyroglobulin-antibodies to predict the lack of significant IAP was 42%, 65% and 64%. The total absence of clinical, biological and histological signs of thyroid autoimmunity was found in only one case (female aged 35 with first episode of hyperthyroidism and no family history of thyroid disease) (0.9%). These results suggest that routine available criteria of thyroid immunity (including IAP) have a low specificity. It follows that they are probably inadequate to screen cases of hereditary toxic familial hyperplasia, a rare entity of still unknown prevalence.

[Appearance of hepatitis C virus replication and increase of aminotransferase activity after corticoid treatment of presumed autoimmune hepatitis. 2 cases]. / Apparition d'une réplication du virus de l'hépatite C et augmentation de l'activité des aminotransférases après traitement corticoïde d'une hépatite présumée auto-immune. Deux observations.

Autoimmune-related and hepatitis C virus-related chronic hepatitis are sometimes difficult to differentiate. We report two cases of chronic hepatitis with high levels of serum anti-smooth muscle antibodies, positive hepatitis C virus serology, and negative serum RNA, which were first treated with corticotherapy. Both patients responded with marked increases in aminotransferase levels, and positive RNA. The first case may have been type 1 autoimmune hepatitis with hepatitis C virus infection, and the second chronic hepatitis C with positive serum auto-antibodies. The increase in viral antigen expression on the surface of the hepatocytes following corticosteroid treatment may have favoured a direct cytopathogenic effect of hepatitis C virus.

Ontogeny of the striatal neurons expressing neuropeptide genes in the human fetus and neonate.

The distribution patterns of neurons expressing mRNAs for four neuropeptides in the human striatum were studied during ontogeny by the use of in situ hybridization. The results of our study demonstrate that somatostatin, enkephalin, dynorphin, and substance P mRNAs are present in striatal neuronal populations from week 12 of fetal life. Each neuronal population undergoes a specific differentiation. Neurons containing somatostatin mRNA are scattered throughout the caudate-putamen up until birth. Neurons containing enkephalin, dynorphin, or substance P mRNAs evolve throughout fetal life in relation to caudate-putamen and patch-matrix compartmentalization. Neurons containing enkephalin mRNA (distinct from those containing substance P or dynorphin mRNAs) are present in the matrix from week 12 of fetal life. These neurons are preferentially distributed in the matrix and, at birth, display higher enkephalin mRNA content in the matrix than in the patches. Dynorphin mRNA is found in the caudate and putamen, preferentially in the patch neurons; nevertheless, a low level of dynorphin mRNA is also present in neurons of the caudate matrix. Substance P mRNA is initially restricted to caudate neurons. At birth, both substance P and dynorphin mRNAs are expressed at high levels in the patches. These results demonstrate that each neuropeptide gene is expressed during human fetal life in neurons with a specific topology and pace of development in relation to caudate-putamen and patch-matrix differentiation. These results also contribute evidence that neurochemical evolution of the striatal neuronal populations is not complete at birth in humans.

[Papillary microcarcinoma of the thyroid]. / Microcarcinome papillaire de la thyroïde.

Treatment of thyroid differentiated carcinoma is controversial. In case of papillary microcarcinoma a low malignancy is usually considered and a limited surgical excision is currently used. We describe 49 cases with papillary tumor < 1 cm. Their high frequency (51% of all differentiated carcinoma discovered in the same period), current mode of their diagnosis (incidental histological findings: N = 48), and constant tumoral situation in extra nodular parenchyma are emphasised. In spite of median tumor size < 2 mm, 8% had extra thyroidal tumoral extent at diagnosis (node metastasis: N = 3; bone: N = 1). In one case with multifocal lesions in both lobes, an unilateral thyroidectomy would have missed contralateral periglandular metastatic nodes. Diagnosis of the case with asymptomatic bone metastasis was clearly attributable to radioiodine therapeutic use. These results suggest an heterogeneous prognosis of papillary microcarcinoma, with some cases requiring total bilateral thyroidectomy and radioiodine remnants ablation (e.g. Tumors invading peripheral thyroid tissue that seem at higher risk of extra glandular extension).

Malignant adenomyoepithelioma of the breast. An immunohistochemical, cytophotometric, and ultrastructural study of a case with lung metastases.

Adenomyoepithelioma of the breast is a rare tumor that, on the basis of histologic, immunohistochemical, and ultrastructural features, has a bicellular pattern of epithelial and myoepithelial cells regularly distributed in tubular structures. Until now, this tumor was thought to be a benign or low-grade malignant lesion because of possible local recurrences (7 recurrent cases of 60 in the literature). Only one of these cases had nodal involvement, thereby suggesting the possible malignancy of this lesion. This paper reports the first documented case of malignant adenomyoepithelioma with lung metastases presenting the same biphasic pattern as the primary tumor.