Dissection of DLBCL microenvironment provides a gene expression-based predictor of survival applicable to formalin-fixed paraffin-embedded tissue.

Background: Gene expression profiling (GEP) studies recognized a prognostic role for tumor microenvironment (TME) in diffuse large B-cell lymphoma (DLBCL), but the routinely adoption of prognostic stromal signatures remains limited. Patients and methods: Here, we applied the computational method CIBERSORT to generate a 1028-gene matrix incorporating signatures of 17 immune and stromal cytotypes. Then, we carried out a deconvolution on publicly available GEP data of 482 untreated DLBCLs to reveal associations between clinical outcomes and proportions of putative tumor-infiltrating cell types. Forty-five genes related to peculiar prognostic cytotypes were selected and their expression digitally quantified by NanoString technology on a validation set of 175 formalin-fixed, paraffin-embedded DLBCLs from two randomized trials. Data from an unsupervised clustering analysis were used to build a model of clustering assignment, whose prognostic value was also assessed on an independent cohort of 40 cases. All tissue samples consisted of pretreatment biopsies of advanced-stage DLBCLs treated by comparable R-CHOP/R-CHOP-like regimens. Results: In silico analysis demonstrated that higher proportion of myofibroblasts (MFs), dendritic cells, and CD4+ T cells correlated with better outcomes and the expression of genes in our panel is associated with a risk of overall and progression-free survival. In a multivariate Cox model, the microenvironment genes retained high prognostic performance independently of the cell-of-origin (COO), and integration of the two prognosticators (COO + TME) improved survival prediction in both validation set and independent cohort. Moreover, the major contribution of MF-related genes to the panel and Gene Set Enrichment Analysis suggested a strong influence of extracellular matrix determinants in DLBCL biology. Conclusions: Our study identified new prognostic categories of DLBCL, providing an easy-to-apply gene panel that powerfully predicts patients' survival. Moreover, owing to its relationship with specific stromal and immune components, the panel may acquire a predictive relevance in clinical trials exploring new drugs with known impact on TME.

Comparative genomic hybridisation in malignant deciduoid mesothelioma.

BACKGROUND: Malignant deciduoid mesothelioma is a rare variant of epithelioid mesothelioma. This tumour generally has poor prognosis, and can be asbestos related. AIM: To identify peculiar genetic changes responsible for critical phases in pathogenesis of malignant deciduoid mesothelioma and their prognostic relevance. METHODS: Comparative genomic hybridisation was carried out in six cases of malignant pleural deciduoid mesothelioma, four sporadic and two familial. All cases were found to be asbestos related. Four patients died during follow-up and the mean survival was 29.5 (SD 14.2, range 12-43) months. RESULTS: Genetic abnormalities were found in all the tumour tissues, the most frequent being chromosomal gains at 1p, 12q, 17, 8q, 19 and 20 and losses at 13q, 6q and 9p. Survival was found to be longer in those patients who presented a smaller number of losses (< or =2) in the tumorous chromosomes. CONCLUSIONS: Although numerous genetic changes are presented by deciduoid mesotheliomas, certain chromosomal regions are preferentially affected. The clinical outcome for this mesothelioma subtype is predicted by the number of losses.

Malignant deciduoid mesothelioma of the pleura: report of two cases with long survival.

AIMS: To present two rare cases of malignant mesotheliomas with deciduoid features arising in the pleura, both with long survival. METHODS AND RESULTS: These two cases of deciduoid mesotheliomas were observed in adult patients (one 73-year-old male and one 23-year-old female). Only the male had a history of occupational asbestos exposure, whereas the woman had a history of familial mesothelioma. A deciduoid morphology was predominant and focal areas with tubular-papillary features were noted. The tumour cells were positive for cytokeratins, HMBE-1, calretinin, EMA and mitochondrion antibodies. The follow-up data did not suggest a particularly poor prognosis; the mean survival observed was 23 months (17 and 39 months, respectively). CONCLUSIONS: This deciduoid mesothelioma histological subtype does not appear to represent an unfavourable prognostic category.

[Polycystic mesothelioma of the peritoneum. Description of 4 cases]. / Mesotelioma multicistico del peritoneo. Descrizione di quattro casi.

Cystic mesothelioma is a rare tumor of the peritoneal cavity arising from mesothelial cells. About 130 cases have been reported in the literature. The tumor is more frequent (85%) in adult women and rarely occurs in children. It is benign but recurrences are often described. The differential diagnosis with adenomatoid tumors, lymphangiomas, cystic malignant mesotheliomas and metastatic serous cystic tumors of the ovary is supported by immunohistochemistry. We describe four cases of cystic mesothelioma of the peritoneum; two of the cases occurred in pregnant women, one in a 45-year-old man and one in a 5-year-old boy. Asbestos exposure was not documented. The mesothelial origin of the neoplasms was supported by immunohistochemical analysis. Furthermore, tests for simian virus 40 (SV40 T antigen), to determine whether this virus was also present in the lesions, were negative.

A nodular pulmonary lesion due to Linguatula serrata in an HIV-positive man.

A coin-shaped pulmonary lesion was accidentally detected in a 42-year-old, HIV-seropositive man residing in Bari (Apulia, Southern Italy) during a routine X-ray examination. A lung cancer was suspected, obliging physicians to investigate surgically. After thoracotomy a lung nodule, 1.8 cm in diameter, was excised and submitted for histological examination. Histological analysis revealed a nodular infarctual lesion containing a larva of Pentastomida. Despite the poor state of preservation of the parasite it was possible to recognise some morphological characteristics which enabled the parasite to be identified as Linguatula serrata (Pentastomida, Porocephalida). This is the first case reported in Europe in the lung in a living man due to this parasite, the few others occurring in autopsy reports. No evident correlations were found in the present case between HIV-seropositivity and the development of the parasitosis. The importance of lung nodules caused by metazoan invertebrates is emphasised: even though they are rare in man, they are regularly mistaken for cancer at X-ray examination.