Neodymium-yttrium aluminium garnet laser destruction of nonsensitized and hematoporphyrin derivative-sensitized tumors.

The injection of hematoporphyrin derivative (5 mg/kg i.v.) followed 24 hr later by a neodymium-yttrium aluminium garnet laser irradiation shows the destruction of CX1 tumors grafted on nude mice. This acidophilic necrosis occurred with a significantly increased frequency in tumors treated by hematoporphyrin derivative injection and irradiated with the neodymium-yttrium aluminium garnet laser as compared with noninjected but irradiated tumors or with injected tumors irradiated with sunlight. On the basis of our data, it seems difficult to maintain the hypothesis of singlet oxygen production as the only mechanism of the phenomenon. Further studies will be necessary to explain the necrosis that we observed.

Predictive factors for node involvement in papillary thyroid carcinoma. Univariate and multivariate analyses.

For patients with papillary thyroid carcinoma, lymph node involvement is a common complication, resulting in node dissection and its resulting morbidity. To determine means of limiting lymph node dissections, we attempted to define intra-operative criteria predictive of node metastasis and so identify the patients likely to benefit from this procedure. This retrospective study concerned 158 patients (118 female) treated between 1974 and 1996 for papillary thyroid carcinoma by total thyroidectomy associated with bilateral (central and lateral) (n = 119) or unilateral (n = 39) dissection. The following criteria were used to study the predictive value of node involvement: age, sex, tumour size, tumour site, uni- or multifocality, existence or not of a tumour capsule, existence or not of perithyroid involvement and presence or not of vascular invasion. 99 patients (63%) had node involvement. Four factors showed predictive value for node involvement in univariate analysis: vascular invasion (P = 0.02), male sex (P = 0.008), absence of a tumour capsule (P < 0.0001) and perithyroid involvement (P < 0.0001). Two factors were predictive in multivariate analysis: absence of a tumour capsule and perithyroid involvement. Our results enabled us to calculate the risk of node involvement for each patient as a function of the existence of a peritumoral capsule and/or perithyroid involvement and to determine the indication for dissection. When neither of these factors was present, the risk of node involvement was 38.3% and dissection was not considered essential. If both risk factors were found, the risk was 87.1% and dissection was considered necessary.

Experimental aspects of in vitro and in vivo photochemotherapy.

The selectivity of in vitro photodynamic reactions and the in vivo effects induced by PRT, whether the irradiation is applied interstitially or externally, still remains unclear. In vitro studies were performed using leukemic cell lines and syngeneic normal hemopoietic progenitors. For these, cells incubated with hematoporphyrin derivative (HPD) and non-incubated cells were irradiated with an argon laser. Data were obtained as the count of cell colonies found after a 7-day incubation period on semi-solid collagen gel medium. In vivo studies employed the HT 29 tumor model grafted into nude mice. Both animals injected with HPD and non-infected controls were irradiated with a dye laser pumped by an argon laser (Coherent) using a 400 micron optic fiber located either at a distance of 65 mm from the skin or inserted into the tumor. The temperature increase occurring during PRT was measured using non-absorbing thermocouples. In vitro, after HPD treatment and argon irradiation leukemic cells showed a greater phototoxicity (greater than 2 log10) than did the normal cells (0.25 log10). In vivo, when the heat rise is very similar (less than 4 degrees C) in both the tissues irradiated externally and those irradiated interstitially after HPD injection, histological examination of these did not reveal any quantitative differences (90% of tumor mass). These results are discussed.

Immunohistochemical study of 100 pancreatic tumors in 28 patients with multiple endocrine neoplasia, type I.

One hundred pancreatic tumors ranging in size from 0.3 to 7 cm were studied in 28 patients (17 male and 11 female patients; mean age 35 years) with multiple endocrine neoplasia, type I. An immunohistochemical study was performed on deparaffinized sections using the following antibodies: neuron-specific enolase, chromogranin A or synaptophysin, insulin, glucagon, somatostatin, pancreatic polypeptide (PP), vasoactive intestinal peptide (VIP), gastrin, adrenocorticotropic hormone, alpha-subunit of human chorionic gonadotropin, gonadotropin-releasing factor, serotonin, and calcitonin. Among the 100 tumors (all multiple), seven were unclassified, 10 were plurihormonal, and 83 produced a predominant hormonal secretion (with 50-90% of the same cell type), including 37 "A-cell tumors" (glucagon), 27 "B-cell tumors" (insulin), 11 PP-cell tumors, one G-cell tumor (gastrin) and one vasoactive intestinal peptide (VIP)-cell tumor. These multiple tumors had a different predominant hormonal secretion in the same patient in 23 of the 28 cases. There was a preferential association of A-cell tumor and B-cell tumor. Hyperplasia of the islets of Langerhans was not detected in adjacent pancreas. Nesidioblastosis was observed in 30% of cases.

Medullary thyroid carcinoma: search for histological predictors of survival (109 proband cases analysis).

A group of 13 pathologists belonging to the French Calcitonin Tumor Study Group (GETC: Groupe d'Etude des Tumeurs à Calcitonine) examined the histological slides and medical records of 109 proband cases of medullary thyroid carcinoma (MTC) diagnosed on clinical features. The cases belonged to the various forms of the disease (80 sporadic and 29 familial MTC). The aim of the study was to detect histological predictors for survival by comparing morphological data from patients killed by the disease versus the others. Twenty-seven histological parameters were considered, including cellular heterogeneity, shape of the cells, and cytoplasmic characteristics. Other parameters such as sex, age, and phenotype of the disease were also studied. First, predictive parameters of interest on survival function were selected by univariate analysis (Mantel-Cox test). Then, the extracted parameters were tested in a multifactorial analysis using the Cox's forward stepping proportional hazard model. Five parameters were significantly associated with a lower survival function: presence of necrosis in the tumor (P = .001), squamous pattern (P = .002), age over 45 years (P = .004), presence of oxyphil cells in the tumor and absence of cells with intermediate cytoplasm (P = .025), less than 50% of calcitonin immunoreactive cells in the tumor (P = .04).

Serotonin-producing pancreatic endocrine tumour. Histological, ultrastructural and immunohistochemical study of a case.

Serotonin-producing pancreatic endocrine tumours are rare neoplasms which in most cases exhibit malignant biological behaviour. These tumours, in the majority of the well-documented cases, are composed of argyrophil- and argentaffin-positive cells which contain large pleomorphic neurosecretory granules. In contrast, argyrophilic non-argentaffin pancreatic endocrine tumours with tumour cells containing round neurosecretory granules are exceptional. In this study we describe such a tumour not associated with clinical evidence of carcinoid syndrome in a 60-year-old woman. Histological examination revealed tumour extension in pancreatic lymphatic vessels and veins but no evidence of locoregional or distant metastases. Ten months after surgery the patient showed no recurrence of the disease. Immunohistochemistry revealed cytoplasmic serotonin production in the tumour cells which were negative for anti-gastrin, insulin, glucagon, somatostatin, pancreatic polypeptide (PP), vasoactive intestinal peptide (VIP) and ACTH. This study emphasizes the usefulness of combined ultrastructural and immunohistochemical investigations in order to identify and characterize the rare pancreatic endocrine tumours with serotonin production.

Histological, immunohistochemical, ultrastructural and biochemical study of human gastric composite tumor: expression of the serotonin-2B receptor by the neuroendocrine component.

We report a case of a human gastric composite tumor occurring seven years after a partial gastrectomy for a low grade B cell MALT lymphoma. Histological examination of the tumor revealed two intimately intermingled components: 1. A moderately to poorly differentiated tubulo-acinar adenocarcinoma with signet-ring cells; and 2. Isolated or clustered small neuroendocrine cells without atypia expressing chromogranin A, somatostatin and/or glucagon, serotonin (5-HT) and, the 5-HT2B receptors. In addition to immunohistochemical detection, the presence of 5-HT2B receptors was shown pharmacologically through [125I]-DOI binding. Since 5-HT2B receptors have been demonstrated to have autocrine functions and, mitogenic and transforming properties, these results suggest a role of 5-HT in neuroendocrine malignant transformation. On the other hand, the expression of somatostatin and the detection by reverse transcriptase polymerase chain reaction (RT-PCR) of somatostatin receptor subtypes 2, 3, and 5, which have been shown to be involved in tumor regression, might account for the long evolution of this case (> 5 yr). This case illustrates the importance of local humoral modulation in tumor growth. Moreover, ultrastructural results favor a unique origin of the tumor cells from one amphicrine cell type.

[Reproducibility of histological criteria of dysplasia in Barrett mucosa]. / Reproductibilité des critères histologiques de dysplasie sur muqueuse de Barrett.

Barrett's mucosa is a precancerous condition. The goal of endoscopic surveillance for patients with Barrett's esophagus is to grade dysplasia. The diagnosis of dysplasia is difficult. The aim of this study was to determine the observer variation in diagnosis of dysplasia. Thirty-seven biopsies selected from Barrett's mucosa reported as having dysplasia between 1987 and 1988 were reviewed by 4 pathologists. The biopsies were classified according to the method of Riddell, as no dysplasia, indefinite for dysplasia, low-grade dysplasia and high-grade dysplasia. Each pathologist reviewed the biopsies alone and then together. There was a total agreement between the 4 pathologists in 20 out of 37 biopsies (54%). The pair-wise agreement varied between 65 and 84%. It was 84% when the pathologists belonged to the same institution. Of 222 double reviews made by 6 pairs of pathologists (37 biopsies x 6 pairs of pathologists), there were 58 disagreements: 19 low grade/high grade dysplasia, 2 high grade/indefinite for dysplasia, 1 high grade/no dysplasia, 18 low grade/indefinite for dysplasia, 2 low grade/no dysplasia, 16 indefinite for dysplasia/no dysplasia. At the second review when the pathologists evaluated the biopsies together, the agreement was 92%; there were 3 biopsies on which there was total disagreement: twice between high grade and low grade dysplasia, once between low grade dysplasia, indefinite for dysplasia and no dysplasia. This retrospective study has shown that disagreement between pathologists was rarely found on the biopsies diagnosed as having high grade dysplasia, more often on those diagnosed as having low grade dysplasia or indefinite for dysplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

[Hormone immunocytochemical studies of 46 endocrine tumors of the pancreas in 24 patients]. / Etudes immunocytochimiques hormonales de quarante-six tumeurs endocrines du pancréas chez 24 malades.

The aim of this retrospective study was to correlate the results of hormonal immunocytochemistry of 46 endocrine tumors to the corresponding clinical syndromes in 24 patients. They were divided as following: 14 cases of insulinoma, 3 cases of Zollinger-Ellison syndrome, 1 case of glucagonoma, 1 case of carcinoid syndrome and 5 cases without any obvious endocrine manifestations. Each tumor was tested with anti-insulin, anti-glucagon, anti-pancreatic polypeptide, anti-vasoactive intestinal peptide, anti-gastrin immune sera according to the peroxidase-antiperoxidase method. The presence of insulin was proved in 13 of 14 cases of insulinomas and the presence of gastrin in 2 of 3 cases of Zollinger-Ellison syndrome. Among the 5 asymptomatic cases, a somatostatinoma and a vipoma were individualized. More than 50 p. 100 of the tumors showed plurihormonal secretion with one predominantly secreted hormone responsible for the clinical syndrome. This study demonstrated the diversity of the hormonal secretion by some tumors and their metastasis in the same patient. Malignant insulinomas correspond either to poorly secreting tumors or to plurihormonal tumors secreting gastrin and glucagon as well.

[Campylobacter pylori and gastric mucosa: histological and bacteriological study and preliminary results of an epidemiological survey in the area of Nantes]. / "Campylobacter pylori" et muqueuse gastrique: étude histologique, bactériologique et résultats préliminaires d'une enquête épidémiologique dans la région nantaise.

The aims of this study were to: a) evaluate the prevalence of Campylobacter pylori (CP) in patients referred to a gastroenterology unit for upper digestive tract endoscopy, b) compare the results of histologic (Warthin-Starry method) and bacteriologic (direct and culture) examinations, c) correlate the presence and abundance of CP with the "activity" of chronic gastritis as assessed by antral and fundic specimens, and d) report the preliminary results of an epidemiological survey in the area of Nantes, France. CP was observed in 30 of the 64 patients studied (46 p. 100 of cases), and was significantly associated with chronic gastritis of either the superficial or interstitial (87 vs. 12 p. 100 of patients positive and negative, respectively for CP studies, p less than 10(-9], and preatrophic and/or atrophic types (40 vs. 12 p. 100 of patients positive and negative, respectively, for CP studies, p less than 0.01). CP was also present in 7 of 10 patients with duodenal ulcers and in 4 to 6 with gastric ulcers. Histologic and bacteriologic studies gave concordant results in 94 p. 100 of cases, and had the same sensitivity for diagnosis. Patients positive for CP studies had a statistically significant increased incidence of epigastric burns, and, at endoscopic examination, their fundic area appeared congestive more frequently. CP were dictated in both the antrum and fundus, but lesions of chronic gastritis were more prominent in the former. There was a statistically significant correlation between the degree of inflammation observed in the lamina propria and the number of CP present in the same area (antrum and fundus).(ABSTRACT TRUNCATED AT 250 WORDS)

[Extension of an acinar cell pancreatic carcinoma with cystic changes invading the Wirsung canal]. / Carcinome à cellules acineuses pancréatique d'allure kystique, envahissant le canal de Wirsung.

We report a case of acinar cell carcinoma of the pancreas with misleading cystic changes. A 32-year-old woman presented with symptoms suggesting acute pancreatitis on chronic pancreatitis. The abdominal computed tomography and the endoscopic retrograde pancreatography demonstrated hypertrophy of the pancreatic head associated with global dilatation of main pancreatic duct and secondary canals and a 5 cm communicating cyst. A intraductal papillary-mucinous tumor was suggested. Microscopic findings showed a poorly differentiated adenocarcinoma. Six months later, a liver metastasis was detected. The microscopic appearance was different, suggesting acinar cell carcinoma, confirmed by immunohistochemistry. Only two other cases of acinar cell carcinoma with cystic component have been reported in the literature.

[Immunohistochemical study of 17 cases of rectal neuroendocrine tumors]. / Etude immunohistochimique de 17 cas de tumeurs neuro-endocrines rectales.

Seventeen rectal neuroendocrine tumors ("Rectal Carcinoids") were studied by immunohistochemistry using antibodies directed against neuroendocrine markers: chromogranin A, neuron-specific enolase, synaptophysin, neuroendocrine peptides (ACTH, glicentin, glucagon, pancreatic polypeptide, somatostatin, vasoactive intestinal peptide) and antibody against serotonin. All patients with tumors measuring 1 cm or less had no specific symptoms and survived between fifteen months and eight years. Only one patient with a 6 cm poorly differentiated neuroendocrine carcinoma died less than one year after diagnosis. Only five out of seventeen tumors secreted serotonin. Most tumors were derived from L cell secreting glucagon, glicentin or pancreatic polypeptide.

[Importance of using hematoporphyrine derivate in the destruction of adenocarcinomas with Nd Yag or argon lasers]. / Intérêt de l'utilisation de l'hématoporphyrine dérivée pour la destruction d'adénocarcinomes par le laser N.D. Yag ou le laser á argon.

As the hematoporphyrin derivate photochemical properties have been known for many years, this study tries to appreciate the laser beam effect on experimental tumors previously sensitized by H.P.D. Colic adenocarcinoma cells are grafted on mice. On the 10th day tumors are photocoagulated. Previously the mice were divided into 4 groups: G 1: H.P.D. intra-venous injection on the 9th day followed by a Nd Yag laser photocoagulation; G 2: Nd Yag laser only; G 3: H.P.D. intra-venous injection on the 9th day followed by an argon laser photocoagulation; G 4: argon laser only. The G 1 and G 2 study shows that, when Nd Yag laser is used, H.P.D. alters the type of necrosis obtained and the action depth. The G3 and G4 study shows that, when argon laser is used, H.P.D. does not alter the type of necrosis obtained but greatly increases the action depth.

[Neuroendocrine tumor of the larynx. Report of a case]. / Tumeur neuro-endocrine du larynx. A propos d'un cas.

Neuro-endocrine tumors of the larynx are uncommon. This paper reports a case of well differentiated neuro-endocrine carcinoma of the epiglottis of a 61-year-old man. Three years later, he developed a cervical larynx node and four years later, metastatic nodules on his scalp. The tumor produced calcitonin. Serotonin and metenkephalin were also secreted in skin metastases. Neuro-endocrine tumors of the larynx have a bad prognosis. Wenig proposed a classification adaptable to laryngeal neuroendocrine carcinoma based on histologic features and behavior.

[Diffuse sclerosing papillary carcinoma of the thyroid. Report of a case]. / Carcinome papillaire sclérosant diffus de la thyroide. Présentation d'un cas.

The authors report the case of a 12-year-old girl presenting with a diffuse sclerosing papillary carcinoma of the thyroid. The diagnosis was made on a total thyroidectomy specimen three months after thyroid enlargement was detected. This child had previously been treated medically for thyroiditis because of an enlarged thyroid gland with serum antithyroid autoantibodies. A few cases have been described in the literature. Six morphologic findings define this variant of papillary carcinoma: a diffuse growth pattern involving one or both lobes of the thyroid, prominent fibrosis, heavy lymphocytic infiltration with germinal centers, large numbers of psammoma bodies, squamous metaplasia and papillae within cleft-like tissue spaces. Some authors stated that this variant has a poorer prognosis than the usual papillary carcinoma of the thyroid. However, in some series a few patients survive without local recurrence or distant metastasis at a mean follow-up period of more than 10 years. Immunohistochemical studies have shown high accumulation of S-100 protein positive dendritic cells. Such an infiltration has been correlated with a better prognosis.

[Pancreatic epithelial tumors with double cellular components. Report of two cases with immunohistochemical study]. / Tumeurs épithéliales pancréatiques à double composante cellulaire. A propos de deux cas avec étude immunohistochimique.

Histopathological studies of pancreatic tumors can show two different cellular components: exocrine and endocrine. Histological and immunohistochemical staining is used to confirm the diagnosis and to appreciate the probable presence of an endocrine secretion. The hypothetical common embryological origin of the different pancreatic components is strengthened by the coexistence of these two cellular types; experimental studies in animals seem to confirm this view.

["Mixed' (follicular and parafollicular) carcinomas of the thyroid. Histological and immunocytological study of 5 cases]. / Les carcinomes "mixtes" (vésiculaires et paravésiculaires) de la thyroïde. Etude histologique et immunocytochimique de 5 cas.

We studied five cases of poorly differentiated follicular or papillary thyroid carcinomas. Immunohistochemical study revealed numerous ACE positive cells, also positive for calcitonin, ACTH, somatostatin or several of these peptides. These tumors containing both vesicular component and parafollicular cells are endocrine tumors of "mixed" or "intermediate" type. The diagnosis must be confirmed by immunohistochemistry but can be suggested by histological findings: abundant fibrous stroma, trabeculovesicular pattern, and swelled moderately acidophilic cells neighbouring vesicular cells. These facts argue in favor of a common-embryological origin of vesicular and parafollicular cells from ultimobranchial undifferentiated cells. Nevertheless such tumors must take place in thyroid neoplasia's classifications and an appropriate terminology remains to be precised.

[Neuroendocrine carcinoma of the larynx with secretion of calcitonin: primary tumor or metastasis of the medullary thyroid carcinoma?]. / Carcinome neuroendocrine laryngé avec sécrétion de calcitonine: cancer primitif ou métastase d'un cancer médullaire de la thyroïde?

Neuroendocrine carcinomas of the larynx are rare and their links with thyroid neoplastic lesions are not specified in most reported cases. We report such a case secondary to medullary thyroid carcinoma. In a 63-year-old man, a supra glottic laryngeal carcinoma confirmed by biopsy was initially treated by chemotherapy. A second biopsy of the laryngeal lesion after incomplete remission displayed a neuroendocrine carcinoma with calcitonin in neoplastic cells. Laryngectomy, cervical bilateral neck dissection and thyroid isthmic adenoma dissection were performed. Numerous neoplastic cells from these tissues contained calcitonin revealed by immunohistochemical method. Calcitoninemia was highly increased and multiple bone metastases were discovered. Secondary total thyroidectomy was not possible and the patient died 6 months after. In this case the neuroendocrine laryngeal carcinoma was probably secondary to a latent medullary thyroid carcinoma. Medullary thyroid carcinoma is most often unknown in similar previously reported cases of neuroendocrine laryngeal carcinoma. Thus a neuroendocrine tumour of the larynx should require search for extra thyroid and over all thyroid neuroendocrine carcinoma, even limited to a small and latent lesion.

[Immunohistochemical study of 6 multiple familial cervical paragangliomas with lymph node metastasis in one case]. / Etude immunohistochimique de six paragangliomes cervicaux multiples et familiaux avec métastase ganglionnaire dans un cas.

Cervical localizations of extra-adrenal paragangliomas are infrequently malignant, especially in their familial forms. An immunohistochemical study was performed on 6 cervical paragangliomas which were detected in 3 sisters at the age of 20 20. One had a lymph node metastasis. This study confirmed the diagnosis of paraganglioma with endocrine chief cells and supratentacular cells. It also enabled the hormonal contents of these cervical paraganglioma to be determined. In addition to catecholamine, these tumors may (like pheochromocytomas) produce serotonin and one or more other peptides.

[Immunohistochemical study of 4 cases of mucoid and argyrophilic carcinoma of the breast]. / Etude immunohistochimique de 4 cas de carcinomes mucoïdes et argyrophiles du sein.

Three to 5% of breast carcinomas are argyrophilic, including some which are mucinous and thus "composite", whereas there are no argyrophilic cells in normal breast nor in benign breast pathology. This raises the problem of the origin and type of these argyrophilic cells. We carried out a histologic and immunohistochemical study in 4 such cases of mucoid tumors containing at least 50% argyrophilic cells. Two of these tumors presenting node involvement were also studied immunohistochemically. The histologic study showed colloid and intragalactophoric proliferation areas in cell cases and some endocrine areas in 2 out of 4 cases. Argyrophilic cells were present in all of these areas. True mucoargyrophilic amphicrine cells were found primarily in colloid areas. None of these tumors were argentaffin. Immunohistochemical study was performed by the PAP method using antibody directed against VIP, ACTH, PP, somatostatin, bombesin, calcitonin, gastrin, prolactin and GH. Three out of four tumors were positive with VIP. Moreover one of them contained ACTH cells and a metastasis of this tumor contained bombesin cells. No tumor was positive with the other anti-sera tested. This study is related to the rare series in the literature which report secretion of ACTH, catecholamins, bombesin, gastrin, VIP, PP, somatostatin, prolactin, etc. The number of cases reported to date remains too low to show a significant prognostic difference between amphicrine tumors and other mammary carcinomas.