Sarcoidosis. Retroperitoneal fibrosis, renal arterial involvement, and unilateral focal glomerulosclerosis.

In one patient with pulmonary sarcoidosis, hypertension occurred during the course of the disease. Aortography showed extensive narrowing of the right renal artery. Surgical exploration disclosed extensive periaortic and perirenal fibrosis. This fibrosis encircled the right renal artery and caused extrinsic compression. Pathological examination disclosed a large amount of histiocyte epithelioid infiltration in various samples of the fibrosis and particularly in the adventitia of the renal artery, highly suggestive of sarcoidal angiitis. Surgical biopsy was performed on both kidneys. The right kidney, protected by arterial stenosis, was little altered, while the left kidney showed extensive interstitial, tubular, and glomerular lesions. The glomerular lesions were focal and segmental hyalinosis.

True hermaphroditism: from female to male endocrine status.

True hermaphroditism was revealed by monthly intrascrotal bleeding in a 21-yr-old subject of male phenotype who had undergone surgical treatment for gonadal ectopy at the age of 7 yr. The presence of an ovary was demonstrated by the endocrine profile of an ovulatory menstrual cycle. Evidence for the presence of a testis was provided by a plasma testosterone increase after hCG administration (5000 IU/day for 3 days) and its spontaneous response to an endogenous preovulatory LH peak. Further endocrine studies revealed that both gonads were stimulated by endogenous gonadotropins. At surgery, a hemiuterus and an ovary with corpus luteum were found in the left hemiscrotum, and a testis and epididymis were found in the right hemiscrotum. After removal of the ovary, the subject passed from a predominantly female to a male endocrine status, which suggests that the endocrine secretion of the testis was inhibited by the negative feedback effect of ovarian steroids on gonadotropin secretion.

Nitrosoureas lomustine, carmustine and fotemustine induced hepatotoxic perturbations in rats: biochemical, morphological and flow cytometry studies.

Chloroethylnitrosoureas are reactive compounds that are highly effective against malignant neoplasms in humans and animals. The most widely used nitrosoureas, lomustine and carmustine, are known to be hepatotoxic and to induce pericholangitis and intrahepatic cholestasis, which in the long term lead to cholangiolysis and biliary cirrhosis. However, the nitrosourea fotemustine has proved to be non-hepatotoxic at 20 mg/kg and 50 mg/kg. We have studied the effect of these three nitrosoureas on the cytotoxicity and cellular kinetics of rat liver cells. Lomustine and carmustine modify the proliferation index of liver cells in vivo: flow cytofluorometry showed that DNA cell distribution is quite similar for lomustine and carmustine, with subsequent accumulation of cells in G2 + M phase. 3 months later regressive morphological and cell cycle perturbations are noted for the lower dose of lomustine and carmustine. The most severe lesions are noted with lomustine (50 mg/kg). Fotemustine is not hepatotoxic and preferentially induces S phase perturbations. The more toxic nitrosoureas, lomustine and carmustine, induce comparable hepatocyte cell cycle alterations which differ from those induced by the less hepatotoxic nitrosourea fotemustine.

Hepatosplenic gamma/delta T-cell lymphoma: a report of two cases in immunocompromised patients, associated with isochromosome 7q.

Two cases of peripheral T-cell lymphoma, characterized by hepatosplenic presentation and gamma/delta T-cell receptor phenotype on malignant cells, are reported. Little is known about the chromosomal changes in these peculiar lymphomas. We report the cytogenetic analysis of these two patients. Isochromosome 7q and trisomy 8 were observed. These abnormalities were reported previously in five cases of gamma/delta T-cell lymphoma. These two patients had lymphomatous infiltration of the spleen, liver, bone marrow, and (in one case) lymph nodes. These abnormalities occurred in immunocompromised patients (i.e., immunosuppressive therapy for kidney transplantation and chemotherapy for Hodgkin's disease), without Epstein-Barr virus infection stigmata in tumor cells.

Taenia crassiceps invasive cysticercosis: a new human pathogen in acquired immunodeficiency syndrome?

A fluctuant, painful, subcutaneous, and intermuscular tumor developed in a 38-year-old man with severe acquired immunodeficiency syndrome (AIDS) in which immunodeficiency was severe. Surgery revealed lesions that formed a multilocular pouch embedded in deep tissues in the forearm filled with tapiocalike material containing a viscous fluid, granules, and cysticercilike small vesicles. Pathologic and parasitologic evaluation showed cysticerci embedded in a fibrocollagen reaction with inflammatory granulomatous reaction. Each cysticercus contained an invaginated scolex with two rows of small (i.e., 80 microm) and large (i.e., 114 microm) rostellar hooks, identical to larva of Taenia crassiceps. All clinical, parasitologic, and pathologic features of these cysticerci were very different from those of all other larval cestode (i.e., Taenia solium cysticercosis, coenurosis, sparganosis, cysticercosis due to Taenia saginata [Cysticercus bovis], primary and secondary hydatidosis [Echinococcus species]). T crassiceps cysticerci usually develop in subcutis and pleuroperitoneal cavities of rodents, whereas the adult tapeworm is commonly found in the digestive tract of foxes. Biologic properties of T crassiceps cysticerci and epidemiologic characteristics of pandemic human immunodeficiency virus (HIV) could eventually indicate new potential cases of T crassiceps cysticercosis in humans.

Somatostatin does not affect multiplication of granule cells in the rat cerebellum.

Somatostatin receptor are transiently expressed by immature granule cells of rat cerebellum. The effects of somatostatin and octreotide on cell proliferation were studied in cultured cerebellar explants from 10-day-old rats. Cell multiplication was measured using [3H]thymidine incorporation and flow cytometric analysis of cell cycle parameters. [3H]Thymidine incorporation occurred exclusively in neuroblasts of the external granule cell layer in the presence of insulin (1 microM). The labeling index, the length of the S phase, and the potential doubling time were similar in vivo and in explants. Octreotide (10(-12) to 10(-6)M) had no effect on [3H]thymidine incorporation in cerebellar explants. In addition, somatostatin and octreotide did not modify the proportion of cells in the S, G0-G1, and G2-M phases. The present results demonstrate that somatostatin does not affect cell multiplication in neurons of the external granule cell layer.

An isochromosome 6p in a primary meningeal malignant melanoma.

The rearrangement of chromosome 6, particularly the deletion of 6q, has been observed in human malignant melanoma with or without brain metastases. The isochromosome 6p has also been described. In this study, we report the cytogenetic analysis of a primary malignant melanoma of the central nervous system. Its dominating karyotype was 47,XX,+i(6)(p10). Fluorescence in situ hybridization (FISH), using a 6p chromosome arm probe, confirmed the structure of the isochromosome. To our knowledge, this is the first report of this type of chromosomal aberration in an uncommon neoplasm of leptomeningeal melanocytic origin.

The hepatotoxicity of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) in rats. Ultrastructural evidence of a delayed microtubular toxicity.

A few cases of liver involvement have been reported in patients receiving treatment with the antineoplastic nitrosourea CCNU. A single oral dose of 20 or 50 mg/kg CCNU in female Wistar rats induced an important increase in transaminases between day 2 and day 6, followed by a second, moderate increase between day 21 and day 28. Alkaline phosphatases and conjugated hyperbilirubinemia (threefold-increase) were noted for the two doses and were greater for the highest dose. Histological and ultrastructural studies disclosed hepatic lesions of two types: during the first phase of transaminase increase, inflammation of the portal tracts; during the second phase marked dilation of bile canaliculi and numerous filamentous bundles distributed at random throughout the liver cell cytoplasm like normal microtubules. Thus, CCNU induced pericholangitis and intrahepatic cholestasis with microtubular abnormalities. The long-term evolution of hepatic alterations revealed that in the 3rd month after a single oral dose of 20 mg/kg CCNU, lesions were persistent but stable; no reversibility was observed in the 3rd month after 50 mg/kg CCNU, and evolution towards cholangiolysis and biliary cirrhosis was noted. We suggest that CCNU causes a bimodal hepatotoxicity in rats: an early and prolonged ductal injury and a delayed anti-liver cell microtubule toxicity.

Comparative effect of alpha-MSH and b-FGF on neurite extension of fetal rat spinal cord neurons in culture.

Basic fibroblast growth factor (b-FGF) and alpha melanocyte stimulating hormone (alpha-MSH) were tested for their ability to promote axonal elongation on E14 fetal rat spinal cord cell culture, and to support cell survival. A similar development of neurite was observed in alpha-MSH treated cultures or in control cultures, with an axonal length ranging from 87.50 microns to 195.60 microns on day 3. Complete cell death occurred after 6 days of incubation. Whatever the concentration of b-FGF used (0.312-2.5 ng/ml), a significant increase (1.2- to 1.4-fold) in neurite length was observed, with neuronal survival up to 9 days.

Experimental evaluation of bilayered human collagen as a dural substitute.

Many substances have been tried as possible dural substitutes, and different tissues and materials have been evaluated for use in dural repair; however, an entirely satisfactory solution still remains to be found. The authors report an experimental study involving the closure of dural defects in dogs with a new biomaterial, resorbable bilayered human placental collagen, using two types of collagen material. These include a collagen bilayered dural substitute made of oxidized type III + I collagen layer covered by a type IV oxidized collagen film (collagen dural substitute I) and a collagen bilayered dural substitute made of oxidized type III + I collagen layer covered by a type III + I collagen film (collagen dural substitute II). Macroscopic and histological examination, performed over a period of between 15 and 180 days after implantation, showed the resorption of collagen graft and formation of a neomembrane that looked like a neodura within 3 months. No infection and no cerebrospinal fluid fistulae were noticed. Nevertheless, one slight cerebromembranous adhesion was found with collagen dural substitute II. The authors suggest that human resorbable collagen biomaterial could be used as a very satisfactory dural substitute.

Pre-operative kinetic parameter determination of colorectal adenocarcinomas. Prognostic significance.

BACKGROUND: The aim of this study was to test the prognostic value of pre-operative assessment of tumour kinetics in colorectal adenocarcinoma. METHODS: The study of tumour kinetics was performed using an in vivo injection of bromodeoxyuridine. Endoscopic biopsies were obtained from the tumour and analysed using flow cytometry. This procedure enables calculation of the in vivo S-phase fraction labelling index (LI), the duration of S-phase (Ts) and the potential tumour doubling time (Tpot). Disease-free survival curves were calculated by a Kaplan-Meier method. The statistical significance between curves was tested by the log rank test. A multivariate analysis was performed using the Cox's proportional hazards model to determine the effect of pathological staging (lymph node involvement), ploidy and kinetic parameters. RESULTS: Thirty-eight colorectal carcinomas were studied without prior chemotherapy or radiation therapy. In univariate analysis, lymph node involvement, labelling index > 10% and Tpot < 5 days were associated with poor prognosis, with P= 0.0006, 0.049 and 0.029 respectively; no significant differences were found in Ts (P = 0.214), and ploidy (P= 0.095). In multivariate analysis, lymph node involvement, ploidy and Tpot were found to be independent factors of colorectal cancer prognosis (P= 0.028, 0.032 and 0.035 respectively) in all tumours. Tpot was considered a independent prognostic factor in diploid tumours (P= 0.047) but not in aneuploid tumours (P= 0.345). CONCLUSIONS: These results suggest that kinetic parameters determined by pre-operative biopsies of colorectal adenocarcinoma represent a prognosis factor, independent of pathological staging, particularly in diploid tumours.

Effect of radiation therapy on the potential doubling time of tumours in colorectal cancers.

OBJECTIVE: The aim of the present study was to investigate the effects of standard fractionated radiation therapy on the kinetic parameters of colorectal adenocarcinomas. METHODS: The study of tumour kinetics involved in vivo injection of bromodeoxyuridine. Endoscopic biopsies were obtained from the tumour and analysed with flow cytometry. This procedure provides a rapid calculation of qualitative parameters such as ploidy and quantitative parameters such as the in vivo S-phase fraction labelling index which indicates the percentage of cells that have entered into the cycle, the duration of S-phase (Ts) and the potential tumour doubling time (Tpot). RESULTS: Thirty-eight colorectal carcinomas were studied without prior chemotherapy or radiation therapy (group 1) and ten rectal carcinomas were studied following radiation therapy (group 2). In diploid tumours, the labelling index was significantly lower in the post-radiotherapy group than in the pre-radiotherapy group (2.7 +/- 1.1% versus 6.4 +/- 4.2%, respectively; P= 0.01), and the Tpot was significantly longer after radiotherapy (group 2) (22.0 +/- 7.0 days versus 8.6 +/- 6.0 days, P = 0.002). Standard fractionated radiation therapy also appears to result in a longer Tpot in diploid adenocarcinomas of the colon and rectum. This effect was not observed in aneuploid tumours. CONCLUSIONS: The effectiveness of hyperfractionated schedules of radiation therapy for aneuploid rectal tumours with short Tpot warrants further investigation in a larger patient population.

Antenatal exposure to atenolol and retroperitoneal fibromatosis.

We present a case of retroperitoneal fibromatosis in a fetus whose mother took atenolol during pregnancy. A 25-year-old obese woman was treated for hypertension with 100 mg atenolol daily from the second month until the end of pregnancy. At 29 weeks, echography disclosed a retroperitoneal mass and at 37 weeks, a boy was delivered. A biopsy of the tumor showed a fibromatosis with medullary compression, treated by antimitotics until 3 months of age. At the age of 4, the mass had disappeared but severe scoliosis was present. This in utero exposure to atenolol drew our attention because the retroperitoneal localization of the tumor is similar to that of fibroses reported in adults after exposure to atenolol and for other reasons: transplacental carcinogenesis has been demonstrated in humans, at least for diethylstilboestrol, atenolol crosses the placental barrier, the drug was taken during nearly the whole pregnancy, and retroperitoneal fibromatosis is exceptional as a neonatal tumour.

Cell proliferation in colorectal adenocarcinomas: comparison between Ki-67 immunostaining and bromodeoxyuridine uptake detected by immunohistochemistry and flow cytometry.

We compared three different means of assaying tumor proliferative activity in 30 human colorectal adenocarcinomas labeled in vivo with bromodeoxyuridine (BrdUrd). The labeling indices (LI) of BrdUrd obtained both by flow cytometry (FCM) and immunohistochemistry (IH) were also compared with the labeling index of Ki-67. These methods were then related to tumor ploidy and pathological features. Flow cytometry was performed in accordance with Begg's method after intravenous infusion of BrdUrd four hours before surgery. Immunohistology was carried out on paraffin-embedded sections with monoclonal antibodies against BrdUrd and Ki-67. A positive correlation was found between BrdUrd LI obtained by both FMC and IH (p<0.0001), a finding that complies with the literature. However, we report on a correlation between Ki-67 LI and BrdUrd LIs in colorectal tumors (p=0.012). The results were valid for all tumors when they were subdivided into diploid and aneuploid groups. The labeling indices were significantly higher in the aneuploid tumor group than in the diploid group (p=0.047). No relationship between proliferation parameters and tumor stage or grade was found. To our knowledge, this is the first report on a positive correlation between tumor proliferation indices in BrdUrd LIs and Ki-67 in colorectal carcinomas. This finding validates the value of Ki-67 immunostaining, which, however, should be confirmed in a larger series under the same technical conditions.

A European de facto standard for image folders applied to telepathology and teaching.

Since 1980, French pathologists at ADICAP (Association pour le Développement de l'Informatique en Cytologie et en Anatomie Pathologique) have created a common language code allowing the use of computers for routine applications. This code permitted the production of an associated exhaustive image bank of approximately 30,000 images. This task involved many specialists necessitating the definition of specific processes for security and simplicity of data handling. In particular, it has been necessary to develop image communication. To achieve that goal, it was necessary to define a folder, associating textual information to images. That was done through several industrial software providers contribution. Consequently, this folder, using a common packaging standard, allowed any pathologist access to images, codified data and clinical information. Accessing folders has been made easy by launching a Web server at CRIHAN under the supervision of ADICAP. An ADICAP software user may not only browse through the folder but may also import them into their own system and produce new folders. Today more than a hundred users in France and in foreign countries are able to provide diagnostic advice and also referential products useful for further education and quality control. The next challenge is the development of this preliminary de facto approach toward an internationally admitted standard suited for morphological image exchange.

Type 1-primary cutaneous meningioma of the scalp.

Type 1-primary cutaneous meningioma is a rare and often clinically unsuspected lesion of the scalp, forehead or paravertebral region which occurs at birth or during childhood. The pathogenesis of these lesions still remains uncertain. Several authors have emphasized that type 1-cutaneous meningiomas are not real tumors but sequestrated meningoceles or heterotopic meningeal nodules of the skin. Nevertheless, the search for an intracranial or intravertebral connection should be carried out. We describe the clinical and pathological features of a congenital type 1-meningioma of the vertex. No cranial defect or intracranial tumor was found. However, the cutaneous lesion was directly linked to a large cranial vein. The purpose of this study was to illustrate this rare lesion and to indicate the possible surgical risks and the pathological characteristics.

[Flow cytometry of polypoid neoplasms of the colon resected by endoscopy]. / Etude en cytométrie de flux des néoplasies polypoïdes du côlon réséquées par endoscopie.

Sixty-one neoplastic polypoid lesions of the large bowel and rectum, obtained by endoscopic resection, were submitted to cytofluorometric measurements. This study was performed on archival formalin fixed and paraffin embedded material using the method of Hedley. Coefficient of variation, DNA Index, DNA aneuploidy, proliferative activity were statistically correlated to histological grading (according to U.I.C.C.) and to the presence of trophic changes (epithelial displacement, hemorrhage, mucus discharge. Compared with morphological findings, cytofluorometric results revealed that DNA aneuploidy appeared only when intraepithelial carcinomatous changes were present, and was found in 50 percent of microinvasive carcinoma. The proliferative activity was significantly increased in intraepithelial carcinomas, with a significant enlargement of the coefficient of variation. This change may reflect initial disorders in DNA content of neoplastic cells. On the other hand, there was no significant difference between lesions with and without trophic alterations. These findings confirm that this increase is an independent phenomenon during tumor progression.

[Gallbladder involvement in Crohn disease]. / Atteinte vésiculaire au cours de la maladie de Crohn.

We report the case of a young woman with Crohn's disease involving the entire digestive tract and with associated lesions of the liver, pancreas and gallbladder. This latter lesion led to acute cholecystitis which required cholecystectomy. The histo-pathological examination showed granulomas with multinucleated giant cells in the lamina propria. This observation illustrates a severe and extended form of Crohn's disease involving the entire digestive tract as well as the liver, the pancreas and the gallbladder.

[Hemorrhagic rectocolitis and carcinoma of the colon. Contribution of flow cytometry. Report of 3 cases]. / Rectocolite hémorragique et carcinome colique. Données de la cytométrie en flux. A propos de trois observations.

Carcinoma complicating ulcerative colitis, although an uncommon event, is well known but follow-up of patients to detect high-grade dysplasia as a potential indicator for colectomy is very difficult. Retrospective morphological and cytometrical analysis of three resected colons harboring carcinoma coming from patients with ulcerative colitis were performed. It allowed to confirm the value of this technique. Histogram patterns varied between narrow unimodal in quiescent mucosa to broad unimodal with high IP (proliferation index) in regenerative mucosa and aneuploid in high dysplasic mucosa and carcinoma. In addition to histopathology and in spite of a patchy distribution of aneuploidy, different degrees of dysplasia in mucosa and technical sensibility DNA (desoxyribonucleic acid) analysis in long-standing ulcerative colitis seems to be helpful in the detection of potential malignancy.

[Anorectal stenosis caused by suppositories of dextropropoxyphene and paracetamol (Diantalvic)]. / Sténose anorectale par suppositoires de dextropropoxyphène et paracétamol (Diantalvic).

Occasionally, administration of medical substances per annum may result in serious local lesions. The authors report the case of a 58 year-old woman presenting ulcerative and stenosing lesions of the anal canal which led to abdominoperineal resection. History revealed the administration of two suppositories daily, each containing an association of dextropropoxyphene and paracetamol, during seven years because of a cervical pain. Fourteen similar cases have been found in the literature, underlining the difficulties in clinical and pathological diagnosis. The exact mechanism of these lesions remains unknown.