[Treatment of 14 cases of Castlemans disease: the experience of one centre and an overview of literature]. / Lécba 14 prípadu Castlemanovy nemoci: zkusenosti jednoho centra a prehled literatury.

Castlemans disease is the term for reactive lymphocytary and plasmocytary proliferation which occurs in the unicentric (localized) form, usually without systemic symptoms, or in the generalized/multicentric form, typically with systemic symptoms (www.vzacne-diagnozy.cz). Over the past 25 years we diagnosed, treated and followed 14 histologically proven cases of Castlemans diseases. Seven patients had the localised form of the disease. In 5 of 7 cases the pathological lesion was located intrathoracically or intraabdominally and in only 2 cases it was on the surface of the body. No clinical symptoms were present in any of the patients with the unicentric form of the disease and surgical treatment led to the total removing of the disease in all of them. As opposed to that, all 7 patients with the multicentric form of Castlemans disease experienced febrile or subfebrile temperatures. Three of the 7 patients complained of severe troubling night sweats. Clinical expressions of vasculitis which was the cause of stroke, were present in 1 of 7 patients. Osteosclerotic changes on the skeleton were detected in 1 patient, who also suffered from fluid retention likely associated with this disease. Polyclonal propagation of immunoglobulins, predominantly immunoglobulin IgG type, was present in 5 of 7 patients with the multicentric form. In one case there was one complete molecule of monoclonal imunoglobuline present and in one case loose light chains κ were increased More than 1 sampling of material for histological examination of enlarged lymph nodes were needed in 6 of 7 patients for diagnosing the multicentric form of the disease. It has turned out beneficial with respect to diagnosing the disease to carry out surgical removal and histological examination of the nodes which accumulated the most fluorodeoxyglucose within PET-CT examination. The text describes experience of the treatment. In recent years the basis for the treatment has been the monoclonal antibody antiCD20 rituximab, or thalidomide and lenalidomide, or possibly their combination. The new medicine for these patients is interleukin-6 antibody called siltuximab (Sylvant), of which we have no own experience so far. Five of our seven patients with the multicentric form received treatment, 1 patient refused treatment and in one patient the signs of the disease activity are not expressed to such extent that would require treatment. The therapy containing rituximab reached complete remission in 2 patients and the therapy containing thalidomide and lenalidomide achieved the complete remission of the disease in 3 patients. In one of the above described cases the disease did not respond to the initial treatment with rituximab and remission was reached by thalidomide and lenalidomide and in one case the disease did not respond to the initial treatment with thalidomide and complete remission was reached with rituximab. Following the treatment, no patient with the multicentric form of Castlemans disease has had a relapse until now.

[PET-CT documented remission of multicentric Castleman disease after treatment with rituximab: case report and review]. / PET-CT dokumentovaná remise multicentrické formy Castlemanovy choroby po lécbe rituximabem Popis prípadu a prehled literatury.

We describe a case of multicentric Castleman disease with generalized lymphadenopathy and splenomegaly, accompanied by typical B symptoms - loss of 15 kg, fever of non-infectious origin, night sweats, symptoms of anemia. Histological examination of the nodes with the highest accumulation of fluorodeoxyglucose, taken from mediastinum by thoracoscopy, revealed plasmocellular type of Castleman disease. Tests for HIV and human herpesvirus 8 (HHV-8) were negative. Three recurrences of herpes zoster indicating an alteration of immunity preceded the dia-gnosis of disease. Treatment was initiated with combination of thalidomide, dexamethasone, and cyclophosphamide. The response after 2 months therapy was not clear and patient doesn't tolerated the therapy well. Therefore, this treatment was terminated and R-CHOP (Mabthera - rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone) was selected as a second-line therapy. Lymphadenopathy and splenomegaly were reduced during the 2 cycles of treatment, however, serious infectious complications accompanied the therapy. Therefore, only use of Mabthera monotherapy 375 mg /m2 was administered in 28-day intervals. This treatment has shown efficacy and tolerability. PET-CT scan has demonstrated disappearance of lymphadenopathy and splenomegaly, in addition, normalized accumulation of fluorodeoxyglucose. Monotherapy with Mabthera has proved to be effective and well tolerated drug in this case. Currently, there are more effective therapeutic alternatives in multicentric Castleman disease: treatment with monotherapy of rituximab or in combination therapy with immunomodulatory drugs (thalidomide or lenalidomide, treatment with anti-IL-6 (siltuximab) or against its receptor (tocilizumab). In the case of ineffectiveness of one treatment option must be tested other alternative. In this case the therapy based on thalidomide wasn't successful, whereas the treatment with Mabthera has achieved disappearance of disease symptoms.

Prognostic Significance of Immune-checkpoint Molecule PD-L1 in Classical Hodgkin Lymphoma: A Clinicopathologic Study of 120 Cases.

BACKGROUND/AIM: Classic Hodgkin lymphoma (cHL) is a common B-cell malignancy. Despite the good prognosis, in some patients the standard chemotherapy and radiotherapy-based approach does not lead to long-term remission, and these patients eventually relapse. Moreover, the primary refractory disease is of major concern regarding prognosis. PATIENTS AND METHODS: We performed a retrospective analysis to evaluate PD-L1 expression in 120 patients with classic Hodgkin lymphoma (cHL). RESULTS: The median follow-up of the entire group of patients was 90 months. After initial therapy, complete remission was achieved in 113 (94.2%) patients. During the follow-up, cHL relapse/refractory disease was reported in 23 (19.2%) cases. A total of five patients died during the follow-up period, all from cHL progression. When determining PD-L1 expression on Hodgkin-Reed-Sternberg (HRS) cells, 37 cases (30.8%) were evaluated as negative, and 83 cases (69.2%) as positive. In the negative PD-L1 group of patients, no cHL relapse/refractory disease was observed during the follow-up period. However, out of 83 patients with positive PD-L1 expression on HRS cells, 23 (28%) showed relapse/refractory cHL. CONCLUSION: A significantly higher relapse rate was observed in PD-L1-positive patients diagnosed with cHL.

Aberrant protein expression of Appl1, Sortilin and Syndecan-1 during the biological progression of prostate cancer.

Diagnosis and assessment of patients with prostate cancer is dependent on accurate interpretation and grading of histopathology. However, morphology does not necessarily reflect the complex biological changes occurring in prostate cancer disease progression, and current biomarkers have demonstrated limited clinical utility in patient assessment. This study aimed to develop biomarkers that accurately define prostate cancer biology by distinguishing specific pathological features that enable reliable interpretation of pathology for accurate Gleason grading of patients. Online gene expression databases were interrogated and a pathogenic pathway for prostate cancer was identified. The protein expression of key genes in the pathway, including adaptor protein containing a pleckstrin homology (PH) domain, phosphotyrosine-binding (PTB) domain, and leucine zipper motif 1 (Appl1), Sortilin and Syndecan-1, was examined by immunohistochemistry (IHC) in a pilot study of 29 patients with prostate cancer, using monoclonal antibodies designed against unique epitopes. Appl1, Sortilin, and Syndecan-1 expression was first assessed in a tissue microarray cohort of 112 patient samples, demonstrating that the monoclonal antibodies clearly illustrate gland morphologies. To determine the impact of a novel IHC-assisted interpretation (the utility of Appl1, Sortilin, and Syndecan-1 labelling as a panel) of Gleason grading, versus standard haematoxylin and eosin (H&E) Gleason grade assignment, a radical prostatectomy sample cohort comprising 114 patients was assessed. In comparison to H&E, the utility of the biomarker panel reduced subjectivity in interpretation of prostate cancer tissue morphology and improved the reliability of pathology assessment, resulting in Gleason grade redistribution for 41% of patient samples. Importantly, for equivocal IHC-assisted labelling and H&E staining results, the cancer morphology interpretation could be more accurately applied upon re-review of the H&E tissue sections. This study addresses a key issue in the field of prostate cancer pathology by presenting a novel combination of three biomarkers and has the potential to transform clinical pathology practice by standardising the interpretation of the tissue morphology.

HLA-E and HLA-F Are Overexpressed in Glioblastoma and HLA-E Increased After Exposure to Ionizing Radiation.

BACKGROUND/AIM: Glioblastoma (GBM) is one of the deadliest human cancers responding very poorly to therapy. Although the central nervous system has been traditionally considered an immunologically privileged site with an enhanced immune response, GBM appears to benefit from this immunosuppressive milieu. Immunomodulatory molecules play an important role in immune tumor-host interactions. Non-classical human leukocyte antigens (HLA) class Ib molecules HLA-E, HLA-F, and HLA-G have been previously described to be involved in protecting semi-allogeneic fetal allografts from the maternal immune response and in transplant tolerance as well as tumoral immune escape. Unfortunately, their role in GBM remains poorly understood. Our study, therefore, aimed to characterize the relationship between the expression of these molecules in GBM on the transcriptional level and clinicopathological and molecular features of GBM as well as the effect of ionizing radiation. MATERIALS AND METHODS: We performed the analysis of HLA-E, HLA-F, and HLA-G mRNA expression in 69 GBM tissue samples and 21 non-tumor brain tissue samples (controls) by reverse transcription polymerase chain reaction. Furthermore, two primary GBM cell cultures had been irradiated to identify the effect of ionizing radiation on the expression of non-classical HLA molecules. RESULTS: Analyses revealed that both HLA-E and HLA-F are significantly up-regulated in GBM samples. Subsequent survival analysis showed a significant association between low expression of HLA-E and shorter survival of GBM patients. The dysregulated expression of both molecules was also observed between patients with methylated and unmethylated O-6-methylguanine-DNA methyltransferase (MGMT) promoter. Finally, we showed that ionizing radiation increased HLA-E expression level in GBM cells in vitro. CONCLUSION: HLA-E and HLA-F play an important role in GBM biology and could be used as diagnostic biomarkers, and in the case of HLA-E also as a prognostic biomarker.