Primary papillary epithelial tumour of the sella: expanding the spectrum of TTF-1-positive sellar lesions.

AIM: To describe four novel primary epithelial tumours of the sella with papillary architecture and Thyroid Transcription Factor 1 (TTF-1) expression. METHODS: Paraffin-embedded tissue from the four cases and recurrence of patient 1 was investigated with haematoxylin-eosin, special histochemical stains, immunohistochemistry with a broad panel of antibodies and next-generation sequencing. The ultrastructure of one tumour was studied in tissue retrieved from paraffin. RESULTS: The lesions occurred in three females aged 20, 26 and 42 years and a male aged 49 years. They presented with signs and symptoms secondary to pituitary stalk compression. Preoperative neuroimaging documented mixed solid and cystic, enhancing sellar masses with suprasellar extension. Histologically, the tumours showed thin papillae lined by a single layer of cytokeratin and TTF-1-positive cuboidal and cylindrical cells with mildly atypical nucleus. Next-generation sequencing performed in three cases did not identify any mutations. The main differential diagnosis included metastasis from lung or thyroid carcinoma, extraventricular choroid plexus papilloma and sellar ependymoma. CONCLUSION: We suggest the descriptive term of primary papillary epithelial tumour of the sella (PPETS) for this entity and propose that it could represent the intracranial equivalent of thyroid-like low-grade nasopharyngeal papillary adenocarcinoma. The cell of origin of PPETS remains undetermined although the intense and ubiquitous expression of TTF-1 may suggest a derivation from the infundibulum or ventricular recess. Our study expands the spectrum of sellar TTF-1-positive tumour and challenges the view that they all derive from pituicytes.

[Gastrointestinal stromal tumors: role of computed tomography before and after treatment]. / Tumeurs stromales digestives: rôle de la tomodensitometrie avant et apres traitement.

Gastrointestinal stromal tumors (GIST) are the most frequent mesenchymal tumors of the gastrointestinal tract. They are generally located in the stomach or the small bowel and the potential for becoming malignant varies. Due to their expression of c-kit protein, a positive diagnosis as well as a specific targeted treatment by molecular biology (imatinib) are available. Computed tomography is the best imaging method for diagnosis, staging and follow-up of GIST. They appear as a well-defined exophytic mass with heterogeneous enhancement after intravenous injection of iodinated contrast material. They may contain areas of necrosis and/or haemorrhage and enlarged lymph nodes are exceedingly rare. Most common metastatic sites are the liver and mesentery. Large tumour size and liver or mesenteric metastases are computed tomography criteria for a high malignant potential. After treatment, decrease in tumour size, number and density of lesions and the disappearance of enhancing nodules suggest a positive response to imatinib therapy, whereas a new enhancing nodule within a mass is the usual pattern of recurrence. Positron emission tomography may be useful in specific cases when clinical data are inconsistent with computed tomography criteria.

Role of plasma and platelet von Willebrand factor in arterial thrombogenesis and hemostasis in the pig.

To evaluate the relative role of plasma and platelet von Willebrand factor (vWF) pools in hemostasis and arterial thrombogenesis, pigs with vW disease (vWD) were injected with vWF concentrate and/or grafted with bone marrow from a normal pig. Hemostasis was assessed by measurement of ear immersion bleeding time, factor VIII (FVIII) activity, and plasma and platelet vWF antigen levels. The thrombotic process was explored at 650 s(-1) and 1600 s(-1) in an ex vivo cylindrical perfusion chamber. Pigs with vWD exhibited a prolonged bleeding time (>30 minutes) compared with normal pigs (<5 minutes); in addition, they showed normal platelet adhesion and thrombus formation at 650 s(-1) but profoundly reduced platelet adhesion and thrombus formation at 1600 s(-1). Each experiment was performed before and 3 and 24 hours after injection of vWF concentrate. In our bleeding time study, only plasma vWF restoration induced a partial but delayed correction (24 hours postinjection), which was correlated with the highest measured level of FVIII activity. In the perfusion chamber model, restoration of plasma or platelet vWF pools resulted in similar partial correction of platelet adhesion and average thrombus size. In the perfused pigs, the maximum correction occurred 3 hours postinjection. Platelet deposition reached normal values after vWF concentrate was injected into a grafted pig. The present results suggest that when both plasma and platelet vWF levels are restored in vWD pigs, bleeding time and the thrombotic process are normalized according to different kinetics and with differing degrees of effectiveness.

Dietary exposure in utero and during lactation to a mixture of genistein and an anti-androgen fungicide in a rat mammary carcinogenesis model.

Endocrine disruptors may play substantial roles in the high incidence of breast cancer. We previously described how early exposure to the mixture of phytoestrogen genistein (G) and the anti-androgen vinclozolin (V) affects peripubertal mammary development. This study evaluates the carcinogenic potential of exposure to V alone or associated with G from conception until weaning in Wistar rats. Dams were exposed to V, G or GV during pregnancy/lactation. At PND50 offspring were treated with DMBA[7,12-dimethylbenz(a)anthracene]. V or GV maternal exposure decreased number of DMBA-induced mammary tumors in the offspring, without significant modifications in tumor incidence, multiplicity and latency. G exposure decreased number of tumors, incidence and multiplicity. Unexpectedly, GV exposure increased tumor volume (p=0.04 vs controls) and epithelial proliferation (p=0.001 vs controls; p=0.005 vs G,V only). All tumors were in situ carcinomas. Concluding, maternal gestation/lactation exposure to a vinclozolin and genistein mixture significantly increases offspring tumor growth without changes in carcinogenesis susceptibility.

Thrombotic carotid megabulb: fibromuscular dysplasia, septae, and ischemic stroke.

The proximal internal carotid artery is most commonly spared in cerebral fibromuscular dysplasia. The authors report the cases of three young black patients with stroke and carotid megabulbs with fibrous components, two of whom had superimposed thrombi.

Bone marrow involvement by disseminated toxoplasmosis in acquired immunodeficiency syndrome: the value of bone marrow trephine biopsy and immunohistochemistry for the diagnosis.

A bone marrow biopsy was performed on four patients with acquired immune deficiency syndrome (AIDS) for a long-running course fever of unknown origin associated with a recent pancytopenia. In the four cases, striking histological similarities, such as interstitial edema, foci of necrosis and only few scattered or clustered histiocytes, were found. Near or in the foci of necrosis, free forms, and pseudocysts of Toxoplasma gondii were observed not only in the cytoplasm of macrophages and of some granulocytes, but also within megakaryocytes. No sign of other parasitic, bacterial, or fungus infection has been found. The diagnosis was confirmed by immunohistochemistry in the four cases and ultrastructural examination in one case. This case study stresses the importance of bone marrow histological changes for the diagnosis of severe toxoplasmosis in AIDS patients and particularly the localization of T gondii within the cytoplasm of megakaryocytes.

Macro and microheterogeneity in normal endothelial cells: differential composition of luminal glycocalyx and functional implications.

Endothelial cells (EC) are involved in various physiological and pathological processes through the expression of their surface glycoproteins. They are covered by the glycocalyx, composed of glucidic residues from cell surface membrane glycoproteins, glycoplipids and proteoglycans. Glucidic sequences can be specifically characterized by their binding to lectins. Eight lectins were used to investigate the distribution and regulation of EC surface glucidic residues in various blood vessels of adult and newborn pigs. EC lectin binding was compared to von Willebrand factor (vWF) expression as EC reference marker. Six out of eight lectins (BSI-B4, DBA, EEA, HP, MAL I and PNA) were helpful for this determination. Considering only the intensity of labelings, vWF and DBA gave the best stainings of adult pig ECs. In newborn pigs, the best labelings were obtained with EEA and MAL I. Furthermore, the distribution of lectin binding to ECs and EC vWF expression was heterogeneous depending on the EC location along vascular tree and age. Beside this macroheterogeneity this study highlights a microheterogeneity of EC lectin binding and vWF expression in situ, defined as a staining of equal intensity by individual ECs, scattered among negative ones, in a given vascular segment. EC surface sugar residues were differently modulated in newborn and adult pig ECs and differently according to EC vWF expression. The functional involvement of EC glycocalyx was reflected by EC lectin binding in the spleen and liver. This study emphasizes the high level of EC heterogeneity for various markers. The EC macro- and microheterogeneity reflect the "plasticity" or "unstability" of EC phenotypes and suggests that ECs are subject to several levels of regulation and are probably grouped in functional clusters to best adjust their functions to microenvironmental requirements. This concept must be considered in further investigations notably in in vitro studies where EC phenotype can be altered.

An experimental model of bulbar urethral stricture in rabbits using endoscopic radiofrequency coagulation.

OBJECTIVES: To develop an experimental model of endoscopic urethral stricture mimicking the human clinical situation. METHODS: Twenty-four New Zealand male rabbits were included. Eighteen animals (study group) underwent videourethroscopy with a pediatric resectoscope, and a 3 to 5-mm-long circumferential electrocoagulation of the bulbar urethra was performed, without postoperative urinary diversion. Six animals underwent the same procedure without application of electrocautery (control group). Each animal was assessed for urethral stricture on day 15 and day 30 by videourethroscopy and voiding cystogram. Among the study group, 8 animals were killed on day 15 and 10 on day 30 for histologic evaluation. All the control animals were killed on day 30 for histologic examination. RESULTS: Nine animals (50%) in the study group developed a significant bulbar stricture (reducing the lumen by more than 50%) at day 15. Histologic examination confirmed the presence of hyalin fibrosis mutilating the urethral wall. No spontaneous improvement of the stricture was observed on day 30. None of the controls developed urethral stricture, and histologic examination showed a normal urethra in each case. CONCLUSIONS: Endoscopic electrocoagulation of the urethral wall provides a reproducible model of stricture in the rabbit.

Popliteal lymph node response to procainamide and isoniazid. Role of beta-naphthoflavone, phenobarbitone and S9-mix pretreatment.

The popliteal lymph node assay (PLNA) was proposed for the preclinical prediction of xenobiotics-induced autoimmune reactions in humans. Among the substances so far tested in this model, procainamide and isoniazid gave negative PLNA responses despite reports of lupus syndromes in man. To confirm the hypothesis that a metabolite instead of the parent molecule is involved, rats were pretreated with phenobarbital or beta-naphthoflavone, then injected with procainamide or isoniazid. In additional groups of animals, procainamide or isoniazid were injected together with S9-mix following various incubation times. Pretreated rats had a positive PLNA response when injected with procainamide, whereas preincubation with S9-mix resulted in a positive response to isoniazid. These results further support the validity of the PLNA.

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.

Phenotypic and functional characteristics of porcine peritoneal mesothelial cells.

The objective of this study was to establish a technique to isolate porcine mesothelial cells (PMCs) from omental tissue and to compare them to human mesothelial cells (HMCs). The PMCs were dispersed by collagenase digestion and isolated on a Ficoll layer. Their morphologic and ultrastructural features were assessed at confluence by light and electronic microscopy, and they were characterized by immunohistochemistry using specific HMC markers. PMC proliferation was studied in the presence of growth factors platelet-derived growth factor (PDGF), epidermal growth factor (EGF) or transforming growth factors beta1, beta2, or beta3 (TGF). Fibrinolytic PMC activity was detected by zymography for tissue plasminogen activator (tPA) and by reverse zymography for plasminogen activator inhibitor-1 (PAI-1). The recalcification time of cell lysates was used to define PMC procoagulant activity, and gelatinase zymography was used to detect metalloproteinase production. At confluence, PMCs formed typical cobblestone monolayers and exhibited structural features characteristic of HMCs. Weibel Palade bodies were never seen. Specific HMC markers (HBME1, ME1, WT1) cross-reacted with PMCs. As HMCs and PMCs coexpressed cytokeratin and vimentin, and also expressed vinculin and alpha-actin. Addition of PDGF or EGF to the culture medium stimulated PMC proliferation. PMCs constitutively expressed fibrinolytic and procoagulant activity and secreted MMP9 and MMP2. The technique described in this study allows isolation of mesothelial cells from porcine omental tissue. These porcine cells exhibit a mesothelial phenotype and functional properties similar to those of HMCs. Our data warrant an evaluation of mesothelial cells as targets in several therapeutic strategies with porcine models.

Sinistroposition of the gallbladder and the common bile duct.

A left lateral bisegmentectomy was performed in a 29-year-old man presenting a primary lymphoma of the liver. Surgical exploration revealed a left-side gallbladder, located under the left lobe of the liver. During hepatic parenchyma dissection, performed strictly at the left of the round ligament and the umbilical portion of the left portal vein, common bile duct was injured. Complete separation of hepatic pedicle structures showed that the upper biliary convergence passed on the left side of the umbilical portion of the left portal vein before reaching the hepatoduodenal ligament. This case report discusses the embryological mechanism that could explain this uncommon bile duct abnormality, focusing on its consequences during left ruled lobectomy.

Comparison of popliteal lymph node responses in various strains of rats.

Outbred (namely Wistar and Sprague-Dawley) and inbred (Wistar-Furth, Lewis, Fisher 344 and Brown-Norway) strains of rats were screened for their responses to reference compounds in the popliteal lymph node (PLN) assay. Streptozotocin and diphenylhydantoin gave positive responses as evidenced by increased weight and cellularity indices in all strains used whereas procainamide, isoniazid and barbital consistently gave negative responses. Although these findings overall are in agreement with previous investigations involving these compounds, the lack of marked interstrain differences in PLN responses argues against a strong immunogenetically controlled mechanism as could be assumed in presumably auto-immune reactions. The question is raised whether drug-induced side-effects predicted by the PLN assay are basically non-autoimmune as suggested by clinical and immunological findings in man.

[Hepatic brucelloma: 2 cases and a review of the literature]. / Brucellome hépatique: deux nouveaux cas et revue de la littérature.

We report two new cases of hepatic brucelloma in addition to the 22 previously reported cases in the literature. Our analysis of these cases reveals certain characteristics. Hepatic brucelloma is a rare localization that follows previously undetected acute brucellosis. Brucelloma is a result of caseification of a granulomatous reaction induced by persistent Brucella in macrophages. Clinical manifestations can mimic malignant liver tumors or pyogenic, amebic liver abscess. Diagnosis is based on the association of characteristic imaging features (central calcification and peripheral necrotic areas), positive serology and hepatic granulomas. Brucella is rarely isolated in the blood or liver. Awareness of this clinical variant can prevent unnecessary laparotomy. Treatment should begin with rifampicine (900 mg per day) and doxycyclin (200 mg per day) for 3 months. If medical treatment is unsuccessful, percutaneous or surgical drainage should be performed. A cure should be achieved in all cases.

[Pseudo-myelomatous plasmacytosis of the bone marrow in a multicentric Castleman's disease]. / Plasmocytose médullaire pseudo-myélomateuse au cours d'une maladie de Castleman multicentrique. A propos d'une observation.

The authors report the case of a 35 year-old polynesian male admitted to hospital with a diagnosis of myeloma. Bone marrow study showed an intense plasmocytosis, mature, Marshalko type. A new physical examination disclosed polyadenopathies and the lymph node biopsy showed lymph node modifications typical of plasma cell type Castleman's disease. At the same time, the polytypic profile of the bone marrow plasmacytosis and of the hypergammaglobulinemia was demonstrated, thus confirming the reactive state of the plasmacytosis, due to Castleman's disease. Such massive, reactive plasmacytosis belong to one of the various pathological features of multicentric Castleman's disease. Thus, this disease should belong to the etiologic diagnosis of intense bone marrow plasmacytosis and be distinguished from multiple myeloma, sometimes associated to Castleman's disease, especially in case of POEMS syndrome.

[The intratesticular leiomyoma: an unusual location. Report of a case]. / Le léiomyome intratesticulaire: une localisation exceptionnelle. A propos d'un cas.

Intratesticular location of leiomyoma is unusual. A single case has been published in the literature. We report a case of what we consider to be an intratesticular leiomyoma, with a description of its pathology, a discussion of its differential diagnosis and histogenesis.

Systematic cavity shaving: modifications of breast cancer management and long-term local recurrence, a multicentre study.

BACKGROUND: The status of the surgical margins of lumpectomy is one of the most important determinants of local recurrence in breast cancer. Systematically practicing cavity margin resection is debated but may avoid surgical re-excision and allow the diagnosis of multifocality. METHODS: This multicentric retrospective study included 294 patients who underwent conservative management of breast cancer with 2-4 systematic cavity shavings. Clinico-biological characteristics of the patients were collected in order to establish whether surgical management was modified by systematic cavity shaving. Local recurrence rate with a long-term follow up of minimum 4 years was evaluated. RESULTS: Cavity shaving avoided the need for re-excision in 25% of cases and helped in the diagnosis of multifocality in 8% of cases. Resection volume was not associated with usefulness of the cavity shaving. No predictive factor of positive cavity shaving was found. The rate of local recurrence was 3.7% and appeared in a median time of 3 years and 8 month. Only one quarter of the patients with local recurrence had initially positive lumpectomy margins but negative cavity shaving. DISCUSSION: Systematic cavity shaving can change surgical management of conservative treatment. No specific target population for useful cavity shaving was found, such that we recommend utilising it systematically.

Lipomatous polyposis of the colon with multiple lipomas of peritoneal folds and giant diverticulosis: report of a case.

A case of multiple lipomatosis exclusively located in the colon is reported in a young male (33 years). It is characterized by a great number of lipomas with polyposis growth appearance, multiple lipomas of peritoneal folds, and giant diverticulosis probably caused by weakened areas of colonic wall induced by the lipomas.