High Ki67 index and bulky disease remain significant adverse prognostic factors in patients with diffuse large B cell lymphoma before and after the introduction of rituximab.

The aim of this study was to evaluate the impact of clinical variables and biologic features on response rate (RR), overall survival (OS) and progression-free survival (PFS) in 111 patients with de novo diffuse large B cell lymphoma (DLBCL). Fifty-three patients were treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) and 58 patients were treated with R-CHOP (rituximab + CHOP). The variables predictive of RR in the CHOP group were B symptoms, age, clinical stage, bone marrow involvement, bulky disease, International Prognostic Index (IPI) and Bcl-2; in the R-CHOP group, these variables were bulky disease, bone marrow involvement, IPI and Ki67 expression >80%. Multivariate analysis showed that in patients treated with CHOP, the independent prognostic factors associated with PFS were age, bulky disease, IPI and Bcl-2 and those associated with OS were performance status, clinical stage, IPI and bone marrow involvement. In contrast, in patients treated with R-CHOP, the variable shown by multivariate analysis to be an independent prognostic factor associated with PFS was bulky disease, whereas Ki67 expression >80% was associated with OS and PFS. Our data show that a high Ki67 expression and bulky disease could represent possible predictive factors of poor prognosis, which would help to identify a high-risk subgroup of newly diagnosed DLBCL.

Schnitzler's syndrome: monoclonal gammopathy associated with chronic urticaria.

Schnitzler's syndrome (SS) is defined by monoclonal gammopathy and chronic urticaria combined with at least two of the following features: fever, arthralgia or arthritis, bone pain, hepato- and/or splenomegaly, palpable lymph nodes, elevated ESR, and leukocytosis. We report a 49-year-old man with monoclonal IgM gammopathy and a 4-year history of recurrent urticarial rash, unexplained fever and arthralgias. The skin biopsy from an acute lesion revealed perivascular lymphocytic infiltrates consisting of CD4+ and CD8+ T lymphocytes. To our knowledge, this is the first report of an immunophenotypic characterization of skin infiltrates in SS. A lower CD4+/CD8+ ratio of circulating T lymphocytes was also detected. SS usually has a benign course, but in 15% of patients a lymphoproliferative disorder develops.

Common variable immunodeficiency patient with large granular lymphocytosis developing extranodal diffuse large B-cell lymphoma: a case report.

Here we describe a Common Variable Immunodeficiency (CVI) patient with large granular (LG) lymphocytosis and systemic non-malignant lymphadenopathy who developed diffuse large B-cell lymphoma of the stomach. This is the first report of gastric high-grade lymphoma with widespread lymphadenopathy in a patient with LG lymphocytosis associated with CVI.

Autoimmune myelofibrosis: report of three cases and review of the literature.

Autoimmune myelofibrosis is a distinct clinicopathological entity, recognizing immunopathogenetic mechanisms and occurring isolately or in association with systemic and/or organ-specific autoimmune diseases. It results in chronic cytopenias, and is defined by a pattern including bone marrow, peripheral blood, serological and clinical features. It has to be distinguished from other disorders having myelofibrosis. Among these, the most relevant differential diagnosis is with chronic idiopathic myelofibrosis, particularly when disclosing autoimmune clinical and/or laboratory features as epiphenomenon related to a secondary immune-dysregulation. Here we report on 3 patients admitted because of chronic cytopenias. In all of them, the clinicopathological evaluation essentially demonstrated myelofibrosis, not clustered megakaryocytes, reactive lymphoid infiltration in marrow biopsies, absence of significant tear-drop poikilocytosis and leukoerythroblastosis on peripheral blood smears, normal-sized spleen, positive autoimmune serology. The resulting patterns met the diagnosis of autoimmune myelofibrosis occurring isolately in a patient and associated with Sjögren's syndrome or concomitant Sjögren's syndrome and Hashimoto's thyroiditis in the other two, respectively. Transient improvements in cytopenias and unmodified myelofibrosis were observed following corticosteroid treatment. It is noteworthy the lack of a specific therapy, being the underlying pathophisiology of myelofibrosis still unclear. In conclusion, increased awareness of the clinicopathological pattern identifying autoimmune myelofibrosis is recommended in order to improve basic and clinical knowledge of this emerging entity.

Analytical and dimensional morphometry in early diagnosis cutaneous melanoma with dermoscopic images.

OBJECTIVE: To give to the clinician an objective numerical assessment tool to evaluate melanomas so that a diagnosis can be reached with the assistance of computerized procedures. STUDY DESIGN: The approach adopted for differential diagnosis of melanomas and nevi considers diverse morphologic characteristics intrinsic to the lesions, that is, shape, size, and symmetry in total independence of pigmentation, and proposes that this information can be evaluated quantitatively and separately by morphometric procedures with statistically valid independent numeric variables that guarantee objectivity and, from a method point of view, consistency. RESULTS: The results show that the differential diagnosis on malignant and benign lesions is made on five variables, which all describe the fine irregularities of the contour and have a high significance in comparing melanomas to nevi. CONCLUSION: The multivariate discriminant analysis demonstrates the ability of the analytic variables to discriminate 88% of the lesions, rising to 90% if two-dimensional variables are included.

Hepatitis B virus and Homo sapiens proteome-wide analysis: A profusion of viral peptide overlaps in neuron-specific human proteins.

The primary amino acid sequence of the hepatitis B virus (HBV) proteome was searched for identity spots in the human proteome by using the Protein Information Resource database. We find that the HBV polyprotein shares sixty-five heptapeptides, one octapeptide, and one nonapeptide with the human proteins. The viral matches are disseminated among fundamental human proteins such as adhesion molecules, leukocyte differentiation antigens, enzymes, proteins associated with spermatogenesis, and transcription factors. As a datum of special interest, a number of peptide motifs are shared between the virus- and brain-specific antigens involved in neuronal protection. This study may help to evaluate the potential cross reactions and side effects of HBV antigen-based vaccines.

Quantitative study of placental villi in trisomy by analytical morphometry.

OBJECTIVE: To assess the relationship between morphologic features of placental villi and the occurrence of trisomy. STUDY DESIGN: We selected 9 placentas with genetically diagnosed trisomy 21 and 6 normal placentas of matched gestational age. The 150 selected villi underwent a morphometric study using the Shape Analytical Morphometry system, availing itself of an ordinary section to study dimensions and of a specific section to study the shape. The analytic morphometric procedure for shape analysis consisted of 3 steps: upper degree polynomial equations, Fourier analysis and parabolic fitting. RESULTS: Trisomic villi showed bigger size and a more asymmetric and irregular shape than did normal villi. CONCLUSION: We believe that this method can provide valuable information and that further studies are needed to analyze more cohorts of pathologic villi, thus providing a complete pattern of morphologic aberrations related to each placental disease.

Abdominal lymphangioleiomyomatosis in a man with Klinefelter syndrome: the first reported case.

Lymphangioleiomyomatosis (LAM) is an uncommon progressive disease characterized by a hamartomatous tumor-like proliferation of smooth muscle cells that occurs most often in women. This disease commonly involves the lymph nodes, lungs, and mediastinum, and rarely the abdominal sites. We report a case of mesenteric LAM occurring in a 37-year-old man affected by Klinefelter syndrome with a 17-year history of androgen replacement therapy. Histology revealed a hamartomatous proliferation of spindle cells surrounding multiple ectatic lymphatic spaces intermixed with lymphatic follicles. When subjected to immunohistochemical studies, the tumor cells stained positive for muscular markers and negative for estrogen, progesterone, and androgen receptors. The occurrence of LAM in association with Klinefelter syndrome has never been reported in the literature and could represent a further clue in the still unclear pathogenesis of this disease.