Breast implant-associated anaplastic large cell lymphoma: two distinct clinicopathological variants with different outcomes.

BACKGROUND: ALK-negative anaplastic large cell lymphoma associated with breast implant (i-ALCL) has been recently recognized as a distinct entity. Among 43 830 lymphomas registered in the French Lymphopath network since 2010, 300 breast lymphomas comprising 25 peripheral T-cell lymphomas (PTCL) were reviewed. Among PTCL, ALK-negative ALCL was the most frequent and all of them were associated with breast implants. PATIENTS AND METHODS: Since 2010, all i-ALCL cases were collected from different institutions through Lymphopath. Immuno-morphologic features, molecular data and clinical outcome of 19 i-ALCLs have been retrospectively analyzed. RESULTS: The median age of the patients was 61 years and the median length between breast implant and i-ALCL was 9 years. Most implants were silicone-filled and textured. Implant removal was performed in 17 out of 19 patients with additional treatment based on mostly CHOP or CHOP-like chemotherapy regimens (n = 10/19) or irradiation (n = 1/19). CHOP alone or ABVD following radiation without implant removal have been given in two patients. The two clinical presentations, i.e. effusion and less frequently tumor mass correlated with distinct histopathologic features: in situ i-ALCL (anaplastic cell proliferation confined to the fibrous capsule) and infiltrative i-ALCL (pleomorphic cells massively infiltrating adjacent tissue with eosinophils and sometimes Reed-Sternberg-like cells mimicking Hodgkin lymphoma). Malignant cells were CD30-positive, showed a variable staining for EMA and were ALK negative. Most cases had a cytotoxic T-cell immunophenotype with variable T-cell antigen loss and pSTAT3 nuclear expression. T-cell receptor genes were clonally rearranged in 13 out of 13 tested cases. After 18 months of median follow-up, the 2-year overall survival for in situ and infiltrative i-ALCL was 100% and 52.5%, respectively. CONCLUSIONS: In situ i-ALCLs have an indolent clinical course and generally remain free of disease after implant removal. However, infiltrative i-ALCLs could have a more aggressive clinical course that might require additional therapy to implant removal.

Is a proliferation index of cancer cells a reliable prognostic factor after hepatectomy in patients with colorectal liver metastases?

BACKGROUND: In spite of many reports focusing on prognostic factors after hepatectomy in patients with colorectal liver metastases, few studies have investigated pathological factors, eg, fibrous pseudocapsulation, growth pattern at the tumor margin, and proliferation activity of cancer cells, other than histological type and surgical margin. The aim of the present study was to investigate whether absence of pseudocapsulation, infiltrative growth pattern of metastases, and higher proliferation of cancer cells shown by Ki-67 immunohistochemical reactivity were associated with poorer survival after hepatectomy among patients with colorectal liver metastases. METHODS: Between 1988 and 1998, 221 patients underwent hepatic resection of colorectal metastases with curative intent in our institution. Pathology analyses were focused on pseudocapsulation of liver metastases, growth pattern at the tumor edge, and Ki-67 labelling index (Ki-67 LI) of cancer cell nuclei. Univariate analyses of survival and of disease-free survival were performed for several clinicopathological factors, and multivariate analyses of survival and disease-free survival were also performed. RESULTS: The univariate survival analyses showed that pseudocapsulation, growth pattern, and Ki-67 LI were significant prognostic factors, besides synchronous versus metachronous occurrence of metastases, carcinoembryonic antigen level before hepatectomy, and number of metastases. A multivariate analysis showed that Ki-67 labeling index was the most reliable prognostic factor of survival. In addition, Ki-67 LI and microscopic growth pattern were multivariately predictive factors of disease-free survival. CONCLUSIONS: This large single-institution study showed that investigation of cancer cell proliferation and pathologic characteristics of the tumor margin are major prognostic factors.

Comparative evaluation of Celsior solution versus Viaspan in a pig liver transplantation model.

BACKGROUND: In a pig liver transplantation model, we compared the effects of Celsior solution (CS), an extracellular preservation solution, with Viaspan (University of Wisconsin solution, UW) on graft function and animal survival. METHODS: Pig livers were flushed with either CS or UW solution and cold-stored for 12 hr (group 1) or for 8 to 10 hr (group 2). Grafts were transplanted orthotopically. Intrahepatic reduced and oxidized glutathione and adenine nucleotides were evaluated 1 hr after reperfusion. Liver function of transplanted animals was monitored for up to 6 days by serum transaminases, total bilirubin, purine nucleoside phosphorylase, and prothrombin levels. RESULTS: In group 1, all animals died within 24 hr after reperfusion regardless of the preservation solution used. In group 2, no significant difference was seen in survival between the CS (72%) and the UW (67%) groups 6 days after transplantation, and there were no statistically significant differences in the biochemical data. There were no differences in histological evaluation of the livers at the time of death or killing of the animals between the CS and UW groups. CONCLUSION: Within the limits of this pilot study, CS is equivalent to UW in terms of graft function and animal survival.

Removal of primate xenoreactive natural antibodies by extracorporeal perfusion of pig kidneys and livers.

Organ perfusion is one of the possible strategies to attenuate rejection of discordant xenografts by reducing the levels of the recipient's xenoreactive natural antibodies (XNA). Its efficacy in terms of XNA removal was studied in models of primate blood or plasma perfusion through porcine kidneys or livers, with special attention to haematological consequences and potential side-effects. We first perfused the blood of rhesus monkeys through pig kidneys and livers, and demonstrated that the perfusion of a pig liver resulted in higher XNA adsorption (72 +/- 13%) than the perfusion of a pig kidney (51 +/- 25%). However, when we normalized for the weight of the perfused organs and for levels of natural antibodies in individual monkeys, livers adsorbed less antibody (1.4 +/- 0.9 U antibody/g) than kidneys (7.2 +/- 7 U antibody/g). Histological signs of rejection were observed in perfused kidneys, but not in perfused livers. A major drawback of the perfusion of blood through livers was a considerable decrease in the primates' haemoglobin and platelet levels. To avoid this, we developed a plasma liver perfusion device. This method allowed a significant improvement in the haemodynamic state of primates and was particularly effective in preventing anaemia. Moreover, plasma liver perfusion was as effective as blood liver perfusion to remove natural antibodies and, resulted in a marked decrease in their functional activity as assessed by complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). The level of other plasma proteins was not significantly affected, apart from a dilution effect. After xenoperfusion a strong antibody response was evidenced by ELISA, CDC and ADCC between days 7 and 14 and then decreased progressively. We conclude that the separation of blood to allow the perfusion of plasma through a pig organ is safer than the perfusion of unseparated blood and is associated with efficient natural antibody removal. However, organ perfusion is limited by a rebound in antibody levels after a few days, and thus will have to be associated with anti-B cell immunosuppressive therapy for long-term or repeated applications.

[Immunohistochemistry in the differential diagnosis of mesothelioma and adenocarcinoma. Evaluation of 5 new antibodies and 6 traditional antibodies]. / L'immunohistochimie dans le diagnostic différentiel entre mésothéliome et adénocarcinome. Evaluation de 5 nouveaux anticorps et réévaluation de 6 anticorps traditionnels.

The aim of this study was to evaluate three recently marketed putative mesothelioma-binding antibodies, calretinin, HBME-1 and thrombomodulin, and two putative adenocarcinoma-binding antibodies, AUA1 and MOC31, on paraffin sections from 28 mesotheliomas and 30 adenocarcinomas. Moreover, the expression of ACE, BerEP4, CA125, CA19.9, LeuM1 and vimentin was assessed. Calretinin, HBME-1 and thrombomodulin, which showed a 100%, 89% and 43% sensitivity, and a 50%, 70% and 87% specificity for mesothelioma respectively, were less efficient than vimentin (100% specificity and 67% sensitivity) for the positive identification of mesothelioma. AUA1, BerEP4 and MOC31 were 100% sensitive to adenocarcinoma, with BerEP4 and MOC31 having the highest specificity (86% each). The immunophenotype "vimentin-positive, ACE-negative, CA19.9-negative" yielded 100% sensitivity and 97% specificity for diagnosis of mesothelioma. We advocate the use of the four-marker panel of ACE, CA19.9, MOC31 (or BerEP4) and vimentin for differentiating mesothelioma from adenocarcinoma.

Production and characterization of monoclonal antibodies recognising defined regions of the human oestrogen receptor.

Mouse monoclonal antibodies were raised against the N-terminal (amino acids 151-165) and the very C-terminal (amino acids 578-595) regions of the human oestrogen receptor (hER). These antibodies recognise the hER by enzyme-linked immunosorbent assay, immunocytochemistry, immunoblotting, immunoprecipitation and gel retardation assays. The presence of hER is used prognostically in human breast cancer. We have tested the reactivity of our monoclonal antibodies on breast cancer sections, comparing with the commonly used Abbott rat monoclonal antibody H222. These studies show that the two monoclonal antibodies described here are highly versatile and will be useful tools for in vivo and in vitro studies of hER function. Furthermore, we show that the corresponding epitopes can be used as molecular "tags" for heterologous proteins and offer a powerful means of purifying and/or characterizing over-produced fusion proteins containing these regions.

[Malignant mesothelioma of the pleura. Analysis of its immunohistochemical aspects]. / Mésothéliomes malins de la plèvre. Analyse de leurs aspects immunohistochimiques.

To evaluate the usefulness of immunohistochemistry in the diagnostic distinction between pleural mesothelioma and metastatic adenocarcinoma to the pleura, the authors studied formalin-fixed paraffin-embedded tissue sections from 14 pleural mesotheliomas and 20 primary adenocarcinomas of the lung, stomach, ovary and breast by using 16 commercially available antibodies to cytokeratin (KL1), vimentin, EMA, CEA, CA19.9, CA125, Egp 34 (detected by HEA 125), secretory component, S100 protein, SP1-béta 1, Leu M1, alpha-1-AT, alpha-1-ACT, lysozyme, desmin and factor VIII. Keratin positivity was found in all mesotheliomas and adenocarcinomas. A coexpression of keratin and vimentin was present in 8/14 (57%) mesotheliomas but only in 2/20 (10%) adenocarcinomas. CEA and CA 19.9 were detected in 80% and 65% of the adenocarcinomas respectively, but not in any of the mesotheliomas. Interestingly, two adenocarcinomas (of the ovary and the stomach) that failed to stain for CEA, were immunoreactive to anti-CA 19.9 antibody. Thus, the combined use of anti-CEA and anti-CA 19.9 antibodies results in staining 90% of the adenocarcinomas. S100 protein, SP1-beta and Leu M1 were also absent in mesotheliomas but present only in less than half of the adenocarcinomas. Adenocarcinomas and mesotheliomas did not significantly vary in reaction to the remaining above mentioned antibodies. The authors conclude that the coexpression of keratin and vimentin and the absence of CEA and CA 19.9 might be the best criteria in the distinction of mesothelioma from metastatic non mucosecreting adenocarcinoma.

[Malignant peritoneal mesothelioma in a child. Diagnostic difficulties in a locally "non tumoral" form, revealed by cervical lymph node metastasis]. / Mésothéliome malin péritonéal chez un enfant. Difficultés diagnostiques devant une forme localement "non tumorale", à présentation métastatique ganglionnaire cervicale.

We report the unusual case-history of a ten-year-old girl who presented with enlarged cervical and supraclavicular lymph nodes apparently due to sinus histiocytosis upon initial histological evaluation. However, they were shown to be nodal metastases from an epithelial form of malignant mesothelioma coexpressing keratin, vimentin, and desmin. Exploratory laparotomy disclosed a diffuse "non tumoral" peritoneal mesothelioma. The neoplastic cells were so highly differentiated that analysis of peritoneal fluid pointed to reactive mesothelial hyperplasia. Intensive combination chemotherapy failed to achieve complete remission, but the child's condition was satisfactory after two and a half years follow-up. On the basis of data from the literature, we review the course, immunohistochemical features, and differential diagnosis of malignant peritoneal mesothelioma.