[112 cases of sporadic and genetically determined pheochromocytoma: a comparative pathologic study]. / 112 cas de phéochromocytomes sporadiques et génétiquement déterminés: Etude anatomo-pathologique comparative.

The aim of this study was to compare 64 genetically determined pheochromocytomas (PH) (49 MEN IIa, 3 MEN IIb, 6 Von Recklinghausen diseases, 1 von Hippel-Lindau disease, 5 familial pheochromocytomas) and 48 sporadic PH. Genetically determined PH were more often observed among men and more frequently bilateral and multicentric than sporadic PH. Sporadic tumors had more often adrenal capsular invasion, necrosis and pseudocysts. Genetically determined PH were more differentiated with an insular pattern, hyaline globules and a higher percentage of polyhedric cells. Sporadic tumors were less differentiated with more frequently a diffuse pattern and small cells. Adrenal medullar hyperplasia was significantly associated with genetically determined PH. Adrenal cortical hyperplasia was not associated with a particular type of PH. The PS100 and chromogranin immunodetection was equivalent in both groups.

[Papillary microcarcinoma of the thyroid. 179 cases reported since 1973]. / Le micro-carcinome papillaire du corps thyroïde. 179 cas observés depuis 1973.

OBJECTIVES: Defined as a tumor measuring < or = 1 cm, the prognosis and treatment of occult papillary thyroid carcinoma has been the topic of some controversy. The aim of this study was to report experience with a series of 179 cases observed since 1973. PATIENTS AND METHODS: Occult papillary thyroid carcinoma was discovered in 179 patients aged 12 to 81 years (151 women and 28 men) at cervicotomy prescribed for Graves' disease (n = 9), toxic adenoma (n = 16), isolated nodule (n = 71), multinodular goiter (n = 74) or cervical node enlargement (n = 9). The surgical procedures were lobo-isthmectomy (n = 79), subtotal thyroidectomy (n = 74), or total thyroidectomy (n = 26) with node dissection in case of enlargement. Thyroxin was prescribed in all cases and annual follow-up was programmed. Five patients were lost to follow-up. RESULTS: Two cervical recurrences were observed warranting reoperation. None of the patients died from cancer-related causes. CONCLUSION: Minute papillary carcinomas of the thyroid are frequently discovered, but prognosis is generally excellent. Systematic total thyroidectomy and node dissection are not warranted. Only those lesions with an extrathyroid extension, associated node enlargement or inaugural metastasis require wide resection. These results are in agreement with a critical analysis of data reported in the literature demonstrating the exceptional nature, and in half of the cases, cure of metastatic occult papillary thyroid carcinoma.

[Treatment of differentiated thyroid cancers of nodular type]. / Traitement des cancers thyroïdiens différenciés à forme nodulaire.

Papillary and follicular carcinomas are the most frequent thyroid cancers. The choice of the treatment is dependent on the prognostic scoring systems. A good prognosis is linked to the small size of the nodule (especially) microcarcinoma) the age of the patient (less than 40), the lack of extra-thyroid (for papillary cancer) or extra capsular (for follicular carcinoma) extension. Total thyroidectomy decreases the number of recurrences but does not modify the mortality. The risk of laryngeal nerve palsy and hypoparathyroidism is not negligible. Lobo-isthmectomy thus can be used in the low risk tumors. Radioactive iodine administration is rational after total thyroidectomy but its efficacy is questioned. Thyroxine treatment is always prescribed. Taking into account the risk of osteopenia and cardiovascular disturbances induced by iatrogenic thyrotoxicosis, the desirable serum TSH level is debated.

[Multiple endocrine neoplasia type I. Review and presentation of the study group of multiple endocrine neoplasia type I (GENEM I)]. / Les néoplasies endocriniennes multiples de type I. Mise au point et présentation du groupe d'étude des néoplasies endocriniennes multiples de type I (GENEM I).

Multiple endocrine neoplasia type I, also known as Wermer's syndrome, is characterized by the presence of functioning or nonfunctioning tumors or hyperplasia of the parathyroid glands, pancreatic islet cells and pituitary gland. MEN I syndrome may be either familial or sporadic. MEN I locus has recently been mapped to chromosome 11, and further characterization of the abnormal gene appears imminent. The GENEM I, a multidisciplinary study group is in the process of formation. Pathologists have to specify the morphological criteria of hyperplasia vs tumor. Further characterization of the gene and its product requires the application of molecular biology methods to the pathologic tissues of these patients.

Studies of monoclonal antibody BL2-10D1 as a marker for the detection of the urothelial origin of tumors.

BACKGROUND: In previous studies, the authors demonstrated the value of the monoclonal antibody (MoAb) BL2-10D1 in identifying malignant transitional cells. In this study, the authors evaluate the possible diagnostic value of a murine MoAb, BL2-10D1, raised against human bladder cancer in the determination of the urothelial origin of metastases in a series of 29 patients with metastatic bladder or prostatic carcinoma. METHODS: Using an immunoperoxidase method, BL2-10D1 and anti-prostate-specific antigen (anti-PSA) reactivity were studied, using histologic sections from 18 pelvic lymph nodes and 4 other anatomic sites invaded by transitional cell cancer, and from 7 pelvic lymph nodes containing prostatic cancer. RESULTS: All lymph nodes containing metastases of transitional cell carcinoma were positive with BL2-10D1, whereas all metastases of prostatic cancer were negative; the four instances of distant urothelial metastases were positive with BL2-10D1 MoAb. Conversely, anti-PSA reacted only with prostatic metastases. CONCLUSION: Thus, MoAb BL2-10D1 and anti-PSA complement each other in the separation of cancers of prostatic and urothelial origin, and the BL2-10D1 MoAb has potential usefulness in differentiating between urothelial carcinoma and prostate adenocarcinoma. In patients with bladder tumors of uncertain origin, BL2-10D1 may be helpful in confirming that a tumor is a transitional cell carcinoma.

A useful monoclonal antibody (BL2-10D1) to identify tumor cells in urine cytology.

The monoclonal antibody (MoAb) BL2-10D1 directed against a tumor-associated antigen of human bladder cancer was used to identify tumor cells obtained by bladder washing or voided urine. The reactivity of BL2-10D1 MoAb was detected by an immunoperoxidase method and evaluated in ten healthy donors and in a series of 65 patients. The 65 patients studied were divided into three groups: ten with nontumor bladder disease (group A); 36 with bladder carcinoma (group B); and 19 with a history of bladder neoplasia but no visible tumor at the time of cytologic sampling (group C). The results were compared with the standard cytologic diagnosis on Papanicolaou-stained preparations. Conventional cytologic study showed a high false-negative rate in low-grade tumors (transitional cell carcinomas [TCC] Grades 1 and 2, 1/4 and 4/17, respectively). All urine from patients with a histologically proved TCC Grade 1 were stained with BL2-10D1 MoAb. Cytologic findings from patients with TCC Grade 2 (17 cases) contained positive cells in 14 cases and failed to react in three cases. Furthermore, whereas urine from patients with TCC Grade 2 or 3 was not always stained with BL2-10D1 MoAb, all patients with dysplastic lesions (three cases) or carcinoma in situ (5 cases) showed a positive reactivity. Such results suggest that BL2-10D1 MoAb may be considered as a valuable adjunct to the classical methods of early detection and follow-up of bladder cancer. However, a larger scale study is needed for MoAb BL2-10D1 to be proposed as an aid to improve the diagnostic sensitivity of urine cytologic investigation in the follow-up of patients treated for recurring bladder cancer, and for the screening of workers exposed to potent bladder carcinogens.

A monoclonal antibody (BL2-10D1) reacting with a bladder-cancer-associated antigen.

A hybridoma cell line secreting an IgM monoclonal antibody (MAb) was produced after immunizing a mouse with RT4 cells and a crude suspension of human bladder carcinoma cells (WHO grades II and III TCC). This MAb reacted with RT4 target cells derived from a human transitional bladder cancer but failed to react with a majority of non-bladder cancer cell lines. Immunohistological studies indicate that this MAb reacts inconstantly with normal bladder: in positive cases only a few superficial cells (5% to 10% umbrella cells) are stained but not intermediate or basal cells of the urothelium. This MAb was evaluated on 118 tumors: it reacted with tumor tissue in a majority of grade I (79.5%) and grade II papillary TCC (77.3%), less with grade III papillary TCC (45%) and very rarely with invasive non-papillary TCC (14%). In cases of flat lesions a strong reactivity of superficial, intermediate and/or basal layer cells was observed in 50% of moderate and severe dysplasia and in all cell layers of carcinomas in situ (CIS)(9/9).

[Cushing's syndrome caused by ectopic production of CRF by a medullary carcinoma of the thyroid body]. / Syndrome de Cushing secondaire à la production ectopique de CRF par un carcinome médullaire du corps thyroïde.

A 58-yr-old man presented a Cushing's syndrome gradually developed for two years, and a cervical tumor. Urinary free cortisol and 17-hydroxy-corticosteroids were elevated and non suppressible under high dose dexamethasone (8 mg a day X 2 days). Plasma calcitonin (7,200 pg/ml), CEA (803 ng/l), beta LPH (624 pg/ml), and CRF (29 pg/ml) were elevated. Total thyroidectomy revealed a medullary carcinoma of the thyroid. Postoperatively the Cushing's syndrome disappeared and plasma CRF became undetectable although plasma calcitonin remained elevated. One out of 3 CRF antisera tested for immunocytology was positive in 10 to 30% of the cells. In tumor extract, CRF (RIA) concentration was 4.75 ng/g. There was no detectable ACTH in the tumor by biochemical as well as immunocytochemical method. In the present report, the next evidences are--for the first time--simultaneously present to demonstrate an ectopic secretion of CRF by a medullary thyroid carcinoma: presence of CRF in systemic blood being undetectable after surgery; cure of the clinical and biological features of Cushing's syndrome after thyroidectomy; characterization of CRF immunoreactivity in tumor. Taken together, the radioimmunological and the immunocytochemical data suggest the production of several molecular forms of CRF.

Electron microscope localisation of insulin-like immunoreactivity of conventionally processed human insulinomas.

Localisation of insulin-like immunoreactivity has been studied using the immunogold staining procedure on thin sections of 6 human insulinomas, conventionally processed for electron microscopy. The labelling was restricted to the secretory granules. Depending on their morphology, these either resembled B-cell granules of human adult pancreas or belonged to the atypical (non-diagnostic) group. Within the former group, those with a crystalloid core or an amorphous dense or moderately dense core were strongly immunoreactive, whereas others, filled with a pale material, were poorly labelled. Most granules of this type were stored together within the heavily granulated cells of 3 insulinomas, presenting the classical features of clinical and biological behaviour and a typical light microscopic staining pattern. In contrast, the non-diagnostic granules, characterized by their smaller size, a very dense core and a thin halo, were mainly found within the poorly granulated cells making up the other tumours, and showed a very uneven labelling. Strongly labelled granules were found in one insulinoma that also belonged to the classical type; these were stored together with a few diagnostic granules within the same cells. Only poorly labelled atypical granules were present in two cases revealing a number of unusual features; these included moderate elevation of insulinaemia, uncertain tumour histology, as well as weak immunostaining for insulin/proinsulin and variable argyrophilia of the tumour in paraffin sections. These findings suggest that human insulinomas differ not only in storage capacity but also in their degree of granule maturation. This may involve some deficiency of either the prohormone conversion or the subsequent processing of the cleavage products.

[Auto-immunity and ovarian failure (author's transl)]. / Hypogonadisme d'origine auto-immune.

The authors report the case of a 17 year-old girl presenting with primary amenorrhea. Investigations showed that it was due to auto-immune hypogonadism. Such an etiology is rarely found in ovarian insufficiencies. In the reported case, there was no other associated auto-immune disorder. Two types of anti-ovarian antibodies are known: antibodies to steroid-producing cells and antibodies to germ-cells. The first ones are found in patients presenting with auto-immune Addison's disease, and are directed against antigens common to ovary and adrenal glands and their presence does not imply ovarian dysfunction. The second ones are more specific and found chiefly in patients with sterility and amenorrhea; they are divided into 2 subgroups: antibodies against the cytoplasm of the ovacyte antibodies and antibodies against zona pellucida. In patients with primary ovarian insufficiency, the presence of such antibodies should always be investigated.

[Malignant syndrome in burned children. Nosologic and therapeutic approach]. / Le syndrome malin de l'enfant brûlé. Approche nosologique et thérapeutique.

A malignant syndrome was observed in 7 children less than 3 years old; the extent of burn was between 5 and 25 p. cent. This syndrome appeared between the second and the fifth days. It was characterized by fever, autonomic disorders and finally coma. The clinical, biological and anatomical features look like the syndrome of Reye. The use of dopamine before coma allowed healing.

Ribosomal and transfer RNA contents of the normal and pathologic human thyroid gland.

One hundred and seventy seven pieces of normal or pathologic thyroid tissue from 17 patients were assayed for rRNA, tRNA and DNA content. The tRNA/DNA and rRNA/DNA ratios in pathologic tissue were statistically compared with the same ratios in normal tissue. In toxic adenoma (5 cases) and anoplastic cancer (2 cases), both ratios were increased. In cold nodules (9 cases), there was in increase of the tRNA/DNA ratio only in 1 case, of the rRNA/DNA ratio only in 4 cases, and of both ratios in 3 cases. In one case of a cold nodule in a Basedow's disease gland, there was no modification of these ratios. In Basedow's disease (3 cases), there was an increase of rRNA/DNA ratio only in one case.