Tumor immunologic microenvironment is strongly involved in tumor progression and the presence of tumor infiltrating lymphocytes (TIL) with different phenotypes has been demonstrated to be of prognostic relevance in different malignancies. We investigated whether TIL infiltration of tumor tissues could also predict the outcome of prostate cancer patients. To this end, we carried out a retrospective analysis correlating the outcome of locally advanced prostate cancer patients undergone salvage radiotherapy upon relapse after radical surgery with the infiltration by different TIL populations. Twenty-two patients with resectable prostate cancer, with a mean age of 67 (C/¡3.93) years, who received salvage radiotherapy with a mean of 69.66 (C/¡ 3.178) Gy in 8 weeks, between June 1999 and January 2009 and with a median follow up of 123 (C/¡ 55.82) months, were enrolled in this study. We evaluated, by immunohistochemistry, the intratumoral ( t ) and peripheral stroma ( p ) infiltration by CD45, CD3, CD4, CD8, CCR7, FoxP3 or PD-1-positive cells on tumor samples taken at the diagnosis ( d ) and relapse times ( R ). We correlated these variables with patients' biochemical progression free survival (bPFS), post-radiotherapy progression free survival (PFS), and overall survival (OS). Substantial changes in the rate of TIL subsets were found between the first and the second biopsy with progressive increase in CD4, CCR7, FoxP3, PD-1 C cells. Our analysis revealed that higher CD8 p,RC and lower PD-1 RC TIL scores correlated to a longer bPFS. Higher CD8 p,RC and CCR7 t,RC TIL scores and lower CD45 p,RC and FoxP3 p,RC TIL scores correlated to a prolonged PFS and OS. These results suggest that the immunological microenvironment of primary tumor is strictly correlated with patient outcome and provide the rationale for immunological treatment of prostate cancer.
BackgroundPrimary lymphoepithelial-like carcinoma of the parotid gland is a rare tumour with an increased incidence among Eskimos and Orientals. In these populations, it is usually associated with Epstein-Barr virus. In Western countries, salivary gland lymphoepithelial-like carcinomas are uncommon and only 14 cases have been described so far; among these, only five cases showed Epstein-Barr virus positivity.Case reportA 45-year-old woman was admitted to Siena Hospital for evaluation of a pre-existent (2 years) painless and tender submandibular mass, rapidly enlarging since two months. On physical examination, a 2.5-cm mass was found in the right parotid. It was firm, mobile and non-tender. Laboratory data were within reference range. Nuclear magnetic resonance detected a 2,5×1,5×1-cm well-circumscribed mass in the deep lobe of the right parotid. A total right paroditectomy with dissection of a satellite lymph node was performed. On the basis of morphological, immunohistochemical and molecular biology findings, a diagnosis of stage II (according to TNM7) Epstein Barr-virus positive, undifferentiated lymphoepithelial-like carcinoma of the parotid gland was made. Twenty months after surgery the patient was free of disease.ConclusionsFurther studies seem to be necessary to completely elucidate the oncogenic role of Epstein Barr-virus in these tumors, which have identical morphology but different prognosis and variable presence of the virus.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1260381551000616
Objective. To prospectively evaluate if computed tomography perfusion (CTp) could be a useful tool in addition to multiphasic CT in renal lesion characterisation. Materials and Methods. Fifty-eight patients that were scheduled for surgical resection of a renal mass with a suspicion of renal cell carcinoma (RCC) were enrolled. Forty-one out of 58 patients underwent total or partial nephrectomy after CTp examination, and a pathological analysis was obtained for a total of 49 renal lesions. Perfusion parameters and attenuation values at multiphasic CT for both lesion and normal cortex were analysed. All the results were compared with the histological data obtained following surgery. Results. PS and MTT values were significantly lower in malignant lesions than in the normal cortex (P < 0.001 and P = 0.011, resp.); PS, MTT, and BF values were also statistically different between oncocytomas and malignant lesions. According to ROC analysis, the accuracy, sensitivity, and specificity to predict RCC were 95.92%, 100%, and 66.7%, respectively, for CTp whereas they were 89.80%, 93.35%, and 50%, respectively, for multiphasic CT. Conclusion. A significant difference between renal cortex and tumour CTp parameter values may suggest a malignant renal lesion. CTp could represent an added value to multiphasic CT in differentiating renal cells carcinoma from oncocytoma.
The concept of unidirectional differentiation of the haematopoietic stem cell has been challenged after recent findings that human B cell progenitors and even mature B cells can be reprogrammed into histiocytic/dendritic cells by altering expression of lineage-associated transcription factors. The conversion of mature B cell lymphomas to Langerhans cell neoplasms is not well documented. Three previous reports have described clonally related follicular lymphoma and Langerhans cell tumours, whereas no case has been published of clonally related marginal zone lymphoma and Langerhans cell sarcoma. We describe the case of a 77-year-old patient who developed a Langerhans cell sarcoma and 6 years later a nodal marginal zone lymphoma. Mutation status examination showed 100 % gene identity to the germline sequence, suggesting direct trans-differentiation or dedifferentiation of the nodal marginal zone lymphoma to the Langerhans cell sarcoma rather than a common progenitor. We found inactivation of paired box 5 (PAX-5) in the lymphoma cells by methylation, along with duplication of part of the long arm of chromosomes 16 and 17 in the sarcoma cells. The absence of PAX-5 could have triggered B cells to differentiate into macrophages and dendritic cells. On the other hand, chromosomal imbalances might have activated genes involved in myeloid lineage maturation, transcription activation and oncogenesis. We hypothesize that this occurred because of previous therapies for nodal marginal zone lymphoma. Better understanding of this phenomenon may help in unravelling the molecular interplay between transcription factors during haematopoietic lineage commitment and may expand the spectrum of clonally related mature B cell neoplasms and Langerhans cell tumours.
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