PVSG and WHO bone marrow evaluation in 90 essential thrombocythaemia (ET) patients treated with Peg interferon A2b. Preliminary results

Splenectomy influences bone marrow infiltration in patients with splenic marginal zone cell lymphoma with or without villous lymphocytes.

BACKGROUND Splenic marginal zone cell lymphoma (SMZL) is a low grade B-cell lymphoma in which patients can have circulating villous lymphocytes and can show a peculiar intrasinusoidal bone marrow (BM) infiltration. Splenectomy is the reported treatment of choice for these patients. The objective of this study was to evaluate the effects of splenectomy on patients with BM lymphomatous infiltration. METHODS BM biopsies of 16 patients with SMZL were studied morphologically and immunohistochemically. In 12 patients, BM biopsies were taken before and after splenectomy. Four patients did not undergo splenectomy, and their BM biopsies were performed with an approximately 1 year interval. RESULTS B…

Immunophenotypical comparison of Gaucher's and pseudo-Gaucher cells.

An immunohistochemical study on bone marrow biopsies and spleens of patients with Gaucher's disease and chronic myeloid leukemia was performed to investigate the immunophenotype of Gaucher's cells and pseudo-Gaucher cells. A panel of antibodies was used which were reactive on paraffin-embedded tissues and directed against different hematopoietic lineage cells. Gaucher's cells and pseudo-Gaucher cells expressed a very similar immunophenotype and displayed an intense reaction for the monocytic antibodies tested, thus confirming their common origin and that they belong to the same system. The expression of HLA-DR antigens was much stronger in Gaucher's than in pseudo-Gaucher cells. This last f…

Does Exist A Correlation Between BMI and Gleason Patterns 4 and 5 At Prostate Biopsy?

Background: Obesity has been related with higher Gleason grade and worse prognosis. Increasing proportion of Gleason pattern 4 or 5 is a critical factor for biochemical recurrence, progression and mortality. The endocrine activity of visceral fat could be responsible of the differentation of the prostatic malignant cell towards a more aggressive fenotype. The aim of our study was to correlate Body Mass Index with the presence of Gleason pattern 4 or higher at biopsy. Materials and Methods: Consecutive patients with positive prostate biopsy were included. A transrectal prostate biopsy procedure with 12 cores, was performed. All tissue samples were reviewed. Results: Out of 135 patients diagn…

Targeting CD162 for Multiple Myeloma immunotherapy.

Primary Plasma Cell Leukemia Associated with Adult Fanconi Syndrome

Abstract Primary plasma cell leukemia (PCL) is a rare variant of multiple myeloma that occurs de novo in patients without a history of plasma cell disorder. We describe a case of λ PCL that showed a prolonged survival of 2 years and 6 months associated with a generalized dysfunction of the proximal renal tubule. On presentation, the patient had anemia (hemoglobin level, 11 g/dL), thrombocytopenia (platelet count, 102,000/μL), and renal insufficiency (creatinine level, 2.75 mg/dL; creatinine clearance, 19 mL per minute; urea, 71 mg/dL). In addition to the common clinical picture, our case showed proteinuria (30 mg/dL), glycosuria (150 mg/dL) with normal glycemia, low uric acid concentration …

Challenges and new prospects in hepatosplenic γδ T-cell lymphoma.

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of lymphoid neoplasms characterized by aggressive clinical behavior and dismal prognosis. Hepatosplenic γδ T-cell lymphoma (γδ-HSTL) is a particular form of PTCL that arises from a small subset of γ/δ T-cell receptor-expressing lymphocytes. γδ-HSTL has a rapidly progressive course and poor outcome due also to its refractoriness to conventional chemotherapy regimens. The very low incidence of γδ-HSTL, along with its propensity to mimic different pathological entities, makes this lymphoma a true diagnostic challenge. In this review, we highlight the biological and clinical features of γδ-HSTL that contribute to making this lymphoma…

Essential thrombocythemia or chronic idiopathic myelofibrosis? A single-center study based on hematopoietic bone marrow histology.

Reported here is the case of a 6-week-old female infant with a severe Bordetella pertussis infection requiring supportive pressure-positive ventilation in the intensive care unit. After being discharged from the intensive care unit, she developed hemolytic anemia, thrombocytopenia and acute renal failure, which suggested a diagnosis of hemolytic uremic syndrome. The clinical outcome was favorable with no renal consequences. This case suggests there may be a direct cause-effect relationship between B. pertussis infection and hemolytic uremic syndrome.

Splenic marginal zone lymphoma with or without villous lymphocytes

The Integruppo Italiano Linfomi (IIL) carried out a study to assess the outcomes of splenic marginal zone lymphoma and to identify prognostic factors in 309 patients. The 5-year cause-specific survival (CSS) rate was 76%. In univariate analysis, the parameters predictive of shorter CSS were hemoglobin levels below 12 g/dL (P < .001), albumin levels below 3.5 g/dL (P = .001), International Prognostic Index (IPI) scores of 2 to 3 (P < .001), lactate dehydrogenase (LDH) levels above normal (P < .001), age older than 60 years (P = .01), platelet counts below 100,000/microL (P = .04), HbsAg-positivity (P = .01), and no splenectomy at diagnosis (P = .006). Values that maintained a negative influe…

Associations between Notch-2, Akt-1 and HER2/neu expression in invasive human breast cancer: a tissue microarray immunophenotypic analysis on 98 patients.

&lt;i&gt;Objective:&lt;/i&gt; We aimed to investigate the existence of associations between well-established and newly recognized biological and phenotypic features of breast cancer involved in tumor progression and prognosis. &lt;i&gt;Methods:&lt;/i&gt; Ninety-eight cases of invasive breast cancer were assessed for the immunohistochemical expression of estrogen and progesterone receptors, Ki-67, HER2, Akt-1, and Notch-2, using the tissue microarray technique. Data regarding tumor histotype, histological grade, tumor size and lymph node status were collected for each patient and included in the analysis. &lt;i&gt;Results:&lt;/i&gt; Several significant associations between histological and/o…

Thyroid maltoma: report of a case without coexistent Hashimoto's thyroiditis

The "gray zone" of the Ph-negative myeloproliferative neoplasm; proposal of a decision tree useful in the differential diagnosis

Sea urchin sns chromatin insulator prebents silencing and positional effect variegation of oncoretroviral vectors transgene expression in murine erythroid cell line

Long-lasting remission of primary hepatic lymphoma and hepatitis C virus infection achieved by the alpha-interferon treatment

Primary hepatic lymphoma is a rare but well-defined lymphoma entity that often pursues an aggressive clinical course. Most cases have been described in hepatitis C virus (HCV)-related chronic liver disease patients. Although anthracycline-based chemotherapy has been reported to be highly effective, the best therapeutic strategy has not been defined yet. The prognosis is dismal especially in patients treated with chemotherapy alone or when an advanced liver disease is present. Herein, we describe a case of primary hepatic large B-cell non-Hodgkin’s lymphoma, in a patient with HCV chronic infection. After a minor response with eight cycles of CHOP chemotherapy, a complete and sustained remiss…

Variant "Pyogenic granuloma-like" of Kaposi's Sarcoma in ACRAL location: our experience.

C1q Production by Bone Marrow Stromal Cells

Reply to Pich et al.: intrasinusoidal bone marrow infiltration and splenic marginal zone lymphoma: a quantitative study

Circulating intercellular adhesion molecule-1 in chronic hepatitis C patients with normal or elevated aminotransferase before and after alpha-interferon treatment

&lt;i&gt;Objectives:&lt;/i&gt; Intercellular adhesion molecule-1 (ICAM-1) plays a fundamental role during liver inflammation. In fact, weak ICAM-1 expression is physiologically restricted to the endothelium of portal vessels and to sinusoidal lining cells, but it becomes markedly evident on sinusoidal lining cells and at the surface of hepatocytes during inflammatory liver diseases. The aim of this study was to evaluate the behaviour of soluble ICAM-1 (sICAM-1) in chronic hepatitis C (CH-C) patients with persistently normal aminotransferase in comparison with patients with CH-C and elevated aminotransferase, and its changes during α-interferon (IFN) therapy. Immunohistochemical localization…

Assessment of the frequency of additional cancers in patients with splenic marginal zone lymphoma

Abstract: Objectives: Solid second primary cancers (SPC) have become an issue of extensive research. The purpose of the present study was to estimate the standardised incidence ratio (SIR) and the absolute excess risk (AER) of SPC in patients with splenic marginal zone lymphoma (SMZL). Methods: We investigated the incidence of additional cancers in 129 patients consecutively diagnosed with SMZL in three Italian haematological centres, asking the cooperating doctors for additional information on initial and subsequent therapies and on the onset and type of second cancers. Results: Twelve SPC were recorded (9.3%); the 3- and 5-yr cumulative incidence rates were 5.5% and 18.3% respectively, wi…

Report of a case of localized Castleman's disease with progression to malignant lymphoma.

Nationwide interobserver variation in the diagnosis of follicular lymphoma. A study of the pathologists of GISL (Gruppo Italiano Studi Linfomi).

Immunophenotypic profile and role of adhesion molecules in splenic marginal zone lymphoma with bone marrow involvement

Abstract Splenic Marginal Zone Lymphoma (SMZL), with or without villous lymphocytes (VL+/-), is a low-grade lymphoproliferative disorder with constant involvement of the bone marrow (BM). Different BM infiltration patterns, mainly intra-sinusoidal, interstitial and nodular, have been described. Adhesion molecules (AMs) constitute a heterogeneous group of antigenic receptors playing a major role in leukocyte recruitment, in lymphocyte homing and in cellular-mediated immune response. Evolution and pattern of the BM infiltrate could be influenced by a variable expression of AM on SMZL lymphocytes. The degree and pattern of BM infiltration and the immunohistochemical expression of AM (H-CAM, BL…

Bone marrow granulomas in hairy cell leukaemia following 2-chlorodeoxyadenosine therapy

Morphometric Study of the Bone Marrow in Polycythemia Vera Following Interferon-Alpha Therapy

Bone marrow cellularity and extent of fibrotic change were determined in nineteen patients with polycythemia vera, treated with interferon-alpha (IFN) for 1 year. The cellularity was evaluated with an interactive semiautomatic method using Leitz TAS plus microscope: in particular, number and size of megakaryocytes were evaluated after immunostaining with Y2/51 (CD 61); reticulin content was studied by light microscope with a semiquantitative method. Before IFN therapy mean cellularity was 80.5% (+/- 13.7). After 6 and 12 months mean cellularity was 75.4% and 68.4% respectively. Six months after cessation of IFN therapy the cellularity was 69.1%. A decrease of the number, density and morphom…

Pattern of lymphoproliferations in the bone marrow

High risk Gleason patterns at prostate biopsy and body mass index.

Hepatosplenic T-cell lymphoma

Manifestations of Hodgkin Lymphoma in the Bone Marrow

Expression of cell cycle markers and human papillomavirus infection in oral squamous cell carcinoma: use of fuzzy neural networks.

Our aim was to evaluate in oral squamous cell carcinoma (OSCC) the relationship between some cell cycle markers and HPV infection, conditionally to age, gender and certain habits of patients, and to assess the ability of fuzzy neural networks (FNNs) in building up an adequate predictive model based on logic inference rules. Eighteen cases of OSCC were examined by immunohistochemistry for MIB-1, PCNA and survivin expression; presence of HPV DNA was investigated in exfoliated oral mucosa cells by nested PCR (nPCR, MY09-MY11/GP5-GP6), and HPV genotype was determined by direct DNA sequencing. Data were analyzed by traditional statistics (TS) and FNNs. HPV DNA was found in 9/18 OSCCs (50.0 %) wi…

Assessment of the Frequency of Additional Malignancies in Patients with Splenic Marginal Zone Lymphoma (SMZL)

Constant detection of cyclooxygenase 2 in terminal stages of myeloid maturation.

Immunophenotypic profile and role of adhesion molecules in splenic marginal zone lymphoma with bone marrow involvement

CONGENITAL UNILATERAL URETEROPELVIC JUNCTION OBSTRUCTION:RENAL DAMAGE EVALUATION AND CORRELATION BETWEEN RENAL BIOPSY AND PRE-POSTOPERATIVE RADIONUCLIDE SCAN

PURPOSE to correlate severity of UPJO with immunohistochemical findings and radionuclide renal scan split function (SF), to obtain indications and timing of surgical correction of congenital UPJO. MATERIAL AND METHODS 21 patients, 57-105 days old, were studied. UPJO was assessed by MAG 3 diuretic renography. Patients underwent biopsy at pyeloplasty. Histological and himmunoistochemical analysis for Bcl-KL, Bcl2, AKT-1, BAD, Bax, AIF, FAS FAS-L, H-TERT, Mib-1 and Nocth2 was performed. TUNEL technique was used to detect apoptotic nuclei. Severity of UPJO was assessed intraoperatively and histologically. Renography was repeated one year after surgery. RESULTS All patients showed half-time wash…

Bone marrow stroma CD40 expression correlates with inflammatory mast cell infiltration and disease progression in splenic marginal zone lymphoma

Splenic marginal zone lymphoma (SMZL) is a mature B-cell neoplasm characterized by rather indolent clinical course. However, nearly one third of patients experience a rapidly progressive disease with a dismal outcome. Despite the characterization of clone geneticsandthe recognition of deregulated immunologic stimulation in the pathogenesis of SMZL, little is known about microenvironment dynamics and their potential biological influence on disease outcome. Here we investigate the effect of stroma-intrinsic features on SMZL disease progression by focusing on the microenvironment of the bone marrow (BM), which represents an elective disease localization endorsing diagnostic and prognostic rele…

Functional characterization and use in the retrovirus vectors of the sea urchin SNS chromatin insulator in erythroid cells

Bone Marrow Biopsy Revision According to WHO Criteria in 272 Patients of the Registro Italiano Trombocitemia (RIT): Preliminary Report On Clinical and Histopathological Implications.

Abstract Abstract 4974 Background The bone marrow trephine biopsy (BMB) has a crucial role for the diagnosis of essential thrombocythemia (ET), both according to the PVSG and the WHO criteria. The WHO 2001 criteria enhanced the role of BMB also by distinguishing the true-ET (ET) from the prefibrotic and the early fibrotic chronic idiopathic myelofibrosis. The WHO 2008 criteria, in the JAK2 era, confirmed the diagnostic and prognostic relevance of the histopathological features in ET as well as in the other Ph-neg myeloproliferative neoplasms (MPN). Otherwise, only few validated data are presently available, and the reproducibility in the evaluation of some morphological details is still con…

Identification of CD162 in plasma-cell dyscrasia.

The Sea Urchin sns5 Insulator Protects Retroviral Vectors From Chromosomal Position Effects by Maintaining Active Chromatin Structure

Silencing and position-effect (PE) variegation (PEV), which is due to integration of viral vectors in heterochromatin regions, are considered significant obstacles to obtaining a consistent level of transgene expression in gene therapy. The inclusion of chromatin insulators into vectors has been proposed to counteract this position-dependent variegation of transgene expression. Here, we show that the sea urchin chromatin insulator, sns5, protects a recombinant gamma-retroviral vector from the negative influence of chromatin in erythroid milieu. This element increases the probability of vector expression at different chromosomal integration sites, which reduces both silencing and PEV. By chr…

Splenic marginal zone lymphoma.

Splenic marginal zone lymphoma (SMZL) is a specific low-grade small B-cell lymphoma that is incorporated in the World Health Organization classification. Characteristic features are splenomegaly, moderate lymphocytosis with villous morphology, intrasinusoidal pattern of involvement of various organs, especially bone marrow, and relative indolent course. Tumor progression with increase of blastic forms and aggressive behavior are observed in a minority of patients. Molecular and cytogenetic studies have shown heterogeneous results probably because of the lack of standardized diagnostic criteria. To date, no definitive therapy has been established. Therapeutic options include treatment absten…

Differential diagnostic features of bone marrow biopsies in essential thrombocythemia

Essential Thrombocythemia (ET) is a chronic myeloproliferative disorder (CMPD) characterized by a high platelet count and originating from a multipotent stem cell. For a long time, according to Polycythaemia Vera Study Group (PVSG) criteria, ET diagnosis has not included histopathological data. Bone Marrow (BM) histology was used only to exclude previous or other subtypes of Ph-CMD or Myelodysplastic syndromes (MDS). In addition, the lack of any cytogenetic or molecular-biological marker has made the discrimination between ET and cases of Reactive Thrombocytosys (RT) without a well known cause quite problematic. Analogously, the distinction of ET from the other Ph- CMPDs with similar clinic…

Immunohistochemical evaluation of bone marrow lymphoid nodules in chronic myeloproliferative disorders

One hundred and seventy bone marrow biopsies from patients with chronic myeloproliferative disorders (CMPDs) were evaluated for the presence of lymphoid nodules (LNs) and were immunostained using a panel of monoclonal antibodies (UCHL1, 4KB5 and L26) recognizing different lymphocyte antigens. LNs were found in 35% of cases of idiopathic thrombocythaemia, 24.6% of myelofibrosis/osteomyelosclerosis, 18.2% of polycythaemia vera 12.1% of chronic myeloid leukaemia and 19.2% of borderline cases. Varying degrees of immunohistochemical positivity for the three antibodies tested were found. LNs were always made up of variable proportions of both T- and B-lymphocytes with a prevalence of T-cells. Thi…

Linfomi T maturi e biopsia osteomidollARE

Clinical implications of a rare renal entity: Pleomorphic Hyalinizing Angiectatic Tumor (PHAT)

Abstract Pleomorphic Hyalinizing Angiectatic Tumor (PHAT) is a rare benign lesion characterized by slow growth, infiltrative behavior and high rate of local recurrences. Only one case has been described in retroperitoneum, at renal hilum, but not involving pelvis or parenchyma. Here we present the first case of PHAT arising in the renal parenchyma. A nodular lesion in right kidney lower pole was diagnosed to a 61 year old woman. The patient underwent right nephrectomy. Microscopically, the lesion showed solid and pseudo-cystic components with hemorrhagic areas characterized by aggregates of ectatic blood vessels. Pleomorphic cells were characterized by large eosinophilic cytoplasm with irre…

Oral lichenoid drug reaction by lithium in a patient with bipolar disorder

Bipolar disorder (BD) is a psychiatric disease characterized by recurrent and alternated episodes of depression and mania. For the treatment of BD, anticonvulsants drugs as lithium, carbamazepine and oxcarbazepine can be used. These drugs can be associated with potential adverse effects: weight gain, tremors, thyroid abnormalities, and cognitive, gastrointestinal, cardiac or dermatological problems. We describe a case of BD with oral lichenoid drug reaction probably because of the mood stabilizers.

321. Sea Urchin sns Chromatin Insulator Prevents Silencing and Positional Effect Variegation of Oncoretroviral Vectors Transgene Expression in Murine Erythroid Cell Line

Silencing and position effect are considered significant obstacles to obtain a consistent level of transgene expression in viral gene therapy. Furthermore recent studies had shown that retroviruses tend to land on active genes with the potential consequence of insertional mutagenesis. The inclusion of elements, such as chromatin insulators, capable to insulate a gene from the surrounding chromatin effects at the integration site should improve both efficacy and safety of gene therapy vectors. We have previously characterized a 265 bp insulator element, termed sns, localized at the 3’ end of the early histone H2A gene of the sea urchin Paracentrotus lividus. This sequence contains three cis-…

R-CVP versus R-CHOP versus R-FM for the initial treatment of patients with advanced-stage follicular lymphoma: results of the FOLL05 trial conducted by the Fondazione Italiana Linfomi.

Purpose Although rituximab (R) is commonly used for patients with advanced follicular lymphoma (FL) requiring treatment, the optimal associated chemotherapy regimen has yet to be clarified. Patients and Methods We conducted an open-label, multicenter, randomized trial among adult patients with previously untreated stages II to IV FL to compare efficacy of eight doses of R associated with eight cycles of cyclophosphamide, vincristine, and prednisone (CVP) or six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or six cycles of fludarabine and mitoxantrone (FM). The principal end point of the study was time to treatment failure (TTF). Results There were 534 patients…

Morphological and biomolecular charachteristics of subcentimetric invasive breast carcinomas: a sicilian multicentric retrospective analysis

Nationwide interobserver variation in the diagnosis of follicular lymphoma: a report from the pathologists of GISL (Gruppo Italiano Studio Linfomi)

Interobserver variability may occur in FL diagnosis, even when the diagnosis is performed by expert haematopathologists. Very limited informations are currently available on the reliability of FL diagnosis performed in laboratories on a national scale, where the lymphoma diagnosis is not always carried on by expert haematopathologists. In this study, the reproducibility of the FL diagnosis and related grading system was tested by a group of pathologists members of the Gruppo Italiano Studio Linfomi (GISL).

Bone marrow fibrosis and diagnosis of essential thrombocythemia

However, there are serious issues to beraisedconcerningtheauthors’analysisoftheclinicaldata,thecriteriausedtodiagnoseET,andthequantificationoffibrosis.Altogethertheauthors compared a heterogenous patient database, which included311 patients evaluated for presenting features, 299 for response totherapy,361forcomplicationrates,97forprogressionoffibrosis,andfour for reversal of BM fibrosis, so no single cohort with consistentfeatures was described throughout the study of 361 patients. Forexample, for the analysis of progression of fibrosis, only 97 (12%) oftheoriginal809patientsenteredintheUK-PT1trial

Uncommon Presentations of Non-Hodgkin’s Lymphoma

D2-40 negative pyogenic granuloma-like Kaposi's sarcoma: Diagnostic features and histogenetic hypothesis of an uncommon skin tumor in HIV-negative patients

Locate full-text(opens in a new window)|View at Publisher| Export | Download | Add to List | More... Pathology Research and Practice Volume 211, Issue 7, July 01, 2015, Pages 528-532 D2-40 negative pyogenic granuloma-like Kaposi's sarcoma: Diagnostic features and histogenetic hypothesis of an uncommon skin tumor in HIV-negative patients (Article) Cabibi, D.a, Giannone, A.G.a , Guarnotta, C.a, Schillaci, O.b, Franco, V.a a Department of Sciences for Promotion of Health and Mother and Child Care, University of Palermo, Palermo, Italy b Servizio di Anatomia Patologica, Dipartimento Oncologico di III livello, La Maddalena Casa di Cura di Alta Specialità, Palermo, Italy View references (20) Abst…

Rituximab with cyclophosphamide, vincristine, non-pegylated liposomal doxorubicin and prednisone as first-line treatment for splenic marginal zone lymphoma: a Fondazione Italiana Linfomi phase II study

Rituximab ® provides high response rates and effective disease palliation in patients with splenic marginal zone lymphoma (SMZL). We conducted a phase II trial in patients with SMZL who were either untreated or were splenectomized but had shown disease progression within 1 year after splenectomy. Treatment consisted of six courses of Rituximab with cyclophosphamide, vincristine, non-pegylated liposomal doxorubicin and prednisone (R-COMP). Fifty-one patients were eligible for the analysis. The overall response rate was 84%. The 6-year progression-free survival and overall survival were 54% and 72%, respectively. Toxicity was substantial (grade ≥ 3 neutropenia: 26%; grade ≥ 3 infections: 8%).…

The sea urchin chromatin insulator, sns-5 protect retrovirus vector from chromosomal position effects

Breast and chest wall metastatic seeding of adenocarcinoma of the colon with bone metaplasia: immunohistochemical study and differential diagnosis

CD27 distinguishes two phases in bone marrow infiltration of splenic marginal zone lymphoma.

Aims:  To investigate CD27 expression in splenic marginal zone lymphoma (SMZL), an indolent low-grade B-cell lymphoma with constant involvement of the bone marrow, especially with an intrasinusoidal pattern. It is not clear if the neoplastic clone is composed of virgin or somatically mutated B cells. CD27 is reported to be a hallmark of memory B cells. Methods and results:  We evaluated 64 bone marrow biopsy specimens (BMBs) from 36 patients with SMZL for the expression of CD27. For comparison, splenectomy specimens of patients with traumatic splenic rupture or with SMZL were used. All BMBs showed lymphomatous infiltration. When located in the marrow sinusoids, neoplastic cells were CD27– i…

Splenic marginal zone lymphoma proposals for a revision of diagnostic, staging and therapeutic criteria

Since the initial description of splenic marginal zone lymphoma (SMZL) in 1992, an increasing number of publications have dealt with multiple aspects of SMZL diagnosis, molecular pathogenesis and treatment. This process has identified multiple inconsistencies in the diagnostic criteria and lack of clear guidelines for the staging and treatment. The authors of this review have held several meetings and exchanged series of cases with the objective of agreeing on the main diagnostic, staging and therapeutic guidelines for patients with this condition. Specific working groups were created for diagnostic criteria, immunophenotype, staging and treatment. As results of this work, guidelines are pr…

P-Selectin Glycoprotein Ligand-1 as a Potential Target for Humoral Immunotherapy of Multiple Myeloma (Supplementry Material)

Monoclonal antibodies (mAbs), successfully adopted in the treatment of several haematological malignancies, have proved almost ineffective in multiple myeloma (MM), because of the lack of an appropriate antigen for targeting and killing MM cells. Here, we demonstrate that PSGL1, the major ligand of P-Selectin, a marker of plasmacytic differentiation expressed at high levels on normal and neoplastic plasma cells, may represent a novel target for mAb-mediated MM immunotherapy. The primary effectors of mAb-induced cell-death, complement-mediated lysis (CDC) and antibody-dependent cellmediated cytotoxicity (ADCC), were investigated using U266B1 and LP1 cell-lines as models. Along with immunolog…

TRA ORRORE E SCIENZA: LA NASCITA DEL GABINETTO DI ANATOMIA PATOLOGICA DELL'UNIVERSITÀ' DI PALERMO

This paper outlines the history of the Cabinet of Pathological Anathomy at the University of Palermo, describes rapidly its current status and analyzes the composition of its displays in 1859. It aims to highlight the analogies with other collections of a similar kind and to pinpoint potential actions to endorse and develop this important scientific asset.

Essential thrombocythemia or chronic idiopathic myelofibrosis? A single-center study based on hematopoietic bone marrow histology.

We reviewed a large series of patients with essential thrombocythemia diagnosed on the basis of the Polycythemia Vera Study Group criteria, and reclassified them by evaluating their major morphologic features and clinical course using the World Health Organization classification. The morphologic review of the bone marrow biopsies of 116 patients (44 males and 72 females; aged 19 - 83 years, median 55 years; median follow-up 121 months) led to 22 cases (19%) being classified as essential thrombocythemia (ET), 24 (21%) as chronic idiopathic myelofibrosis (CIMF)-0, 44 (37%) as CIMF-1, 13 (12%) as CIMF-2, 9 (8%) as latent phase polycythemia vera, and four (3%) as chronic myeloproliferative diso…

An automated image analysis methodology for classifying megakaryocytes in chronic myeloproliferative disorders

This work describes an automatic method for discrimination in microphotographs between normal and pathological human megakaryocytes and between two kinds of disorders of these cells. A segmentation procedure has been developed, mainly based on mathematical morphology and wavelet transform, to isolate the cells. The features of each megakaryocyte (e.g. area, perimeter and tortuosity of the cell and its nucleus, and shape complexity via elliptic Fourier transform) are used by a regression tree procedure applied twice: the first time to find the set of normal megakaryocytes and the second to distinguish between the pathologies. The output of our classifier has been compared to the interpretati…

P-selectin glycoprotein ligand-1 as a potential target for humoral immunotherapy of multiple myeloma.

Monoclonal antibodies (mAbs), successfully adopted in the treatment of several haematological malignancies, have proved almost ineffective in multiple myeloma (MM), because of the lack of an appropriate antigen for targeting and killing MM cells. Here, we demonstrate that PSGL1, the major ligand of P-Selectin, a marker of plasmacytic differentiation expressed at high levels on normal and neoplastic plasma cells, may represent a novel target for mAb-mediated MM immunotherapy. The primary effectors of mAb-induced cell-death, complement-mediated lysis (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC), were investigated using U266B1 and LP1 cell-lines as models. Along with immunolo…

Pathophysiology of age-related diseases

Abstract A Symposium regarding the Pathophysiology of Successful and Unsuccessful Ageing was held in Palermo, Italy on 7-8 April 2009. Three lectures from that Symposium by G. Campisi, L. Ginaldi and F. Licastro are here summarized. Ageing is a complex process which negatively impacts on the development of various bodily systems and its ability to function. A long life in a healthy, vigorous, youthful body has always been one of humanity's greatest dreams. Thus, a better understanding of the pathophysiology of age-related diseases is urgently required to improve our understanding of maintaining good health in the elderly and to program possible therapeutic intervention.

Morphological and biomolecular characteristics of subcentimetric invasive breast carcinomas in Sicily: A multicentre retrospective study in relation to trastuzumab treatment

Little information from clinical trials is available regarding the efficacy of trastuzumab treatment in subcentimetric breast carcinomas (BCs). The aim of this study was to verify the existence of correlations between HER2 and hormone receptor status, Ki67 values, grade, histotype and node involvement in a cohort of pT1a,b BCs from an area not widely covered by screening campaigns. A total of 410 pT1a,b BC formalin-fixed paraffin-embedded samples collected from eight Sicilian Anatomo-Pathological Units (APUs) were classified according to the WHO classification and tumour grading was established. Estrogen and progesterone receptor status, Ki67 labelling index and HER2 status were available. …

European Bone Marrow Working Group trial on reproducibility of World Health Organization criteria to discriminate essential thrombocythemia from prefibrotic primary myelofibrosis: Haematologica 2012;97(3):360-5 - Comment

Any study of myeloproliferative neoplasms (MPNs) that lacks adequate clinical input is doomed to cause diagnostic uncertainty and increased controversy. In the paper by Buhr et al. published in Haematologica,[1][1] the authors studied 102 cases of essential thrombocythemia (ET) and early primary

R-CVP versus R-CHOP versus R-FM as first-line therapy for advanced-stage follicular lymphoma: Final results of FOLL05 trial from the Fondazione Italiana Linfomi (FIL)

8006 Background: The optimal chemotherapy regimen for patients with advanced, active follicular lymphoma (FL) has not been established yet. We conducted a randomized trial comparing R-CVP with R-CHOP and R-FM. Methods: Previously untreated patients with advanced FL were randomly assigned to receive 8 doses of rituximab associated to 8 cycles of CVP, or 6 cycles of CHOP or FM (fludarabine 25 mg/m2 day 1-3, mitoxantrone 10 mg/m2 day 1). No maintenance therapy was allowed. The principal study end point was Time to Treatment Failure (TTF). Events in TTF were failure of induction therapy, progressive or relapse disease and death from any causes. In order to show a hazard ratio between each expe…

Linfomi T maturi e biopsie osteomidollari

Intrasinusoidal bone marrow infiltration: a possible hallmark of splenic lymphoma.

A particular type of lymphomatous bone marrow infiltration defined as intrasinusoidal and occuring in seven patients with splenomegaly and mild to moderate thrombocytopenia is reported. Immunocytochemistry highlighted the intrasinusoidal pattern and showed a mature B-cell phenotype. Four patients underwent splenectomy and a diagnosis of splenic marginal cell lymphoma was made. The disease course seems to be chronic and quite indolent. All patients are alive and well ; follow-up ranges from 2 to 42 months. The value of bone marrow biopsy as a primary diagnostic tool in splenic marginal zone lymphomas is discussed.

Discordance rate of HER2 status in primary breast carcinomas versus synchronous axillary lymph node metastases: a multicenter retrospective investigation.

Antonio Ieni,1 Valeria Barresi,1 Rosario Caltabiano,2 Anna Maria Cascone,3 Rachele Del Sordo,4 Daniela Cabibi,5 Pio Zeppa,3 Salvatore Lanzafame,2 Angelo Sidoni,4 Vito Franco,5 Giovanni Tuccari1 1Department of Human Pathology Gaetano Barresi, Section of Anatomic Pathology, University of Messina, Messina, 2Department GF Ingrassia, Section of Anatomic Pathology, University of Catania, Catania, 3Department of Medicine and Surgery, University of Salerno, Salerno, 4Institute of Pathologic Anatomy and Histology, Division of Cancer Research, University of Perugia, Perugia, 5Department of Human Pathology, Section of Anatomic Pathology, University of Palermo, Palermo, Italy Background: Human epiderma…

Interactive computerized morphometric analysis for the differential diagnosis between dysplasia and well differentiated adenocarcinoma of the prostate

To distinguish prostatic dysplasia (or adenosis) from well differentiated adenocarcinoma on transrectal needle biopsy, a morphometric study was conducted on 20 cases of adenosis and 20 cases of well differentiated adenocarcinoma of the prostate. About 100 cells for each patient were analyzed by means of a computerized image analyzer, and mean nuclear diameter, mean nuclear area, mean form factor and number of cells in eight classes of nuclear diameter were studied. The best predictors of malignancy (evaluated by means of Receiver Operating Characteristics curves) were mean nuclear area greater than 28 mu2, presence of more than 5% of cells with nuclear diameter greater than 6.15 mu, and mea…

Xanthogranulomatous Cholecystitis

Summary Xanthogranulomatous cholecystitis (XC) is a chronic inflammatory lesion of the gallbladder histologically characterized by the presence of varying amounts of foamy histiocytes in the inflammatory infiltrate. In this study a review of 63 cases selected from 1207 surgically removed gallbladders is presented; the percentage found (5.2%) is slightly higher than that of previous reports showing that XC is less uncommon than generally believed. A detailed microscopic study is performed: the authors observed according to the histological features particularly the different patterns of distribution of the inflammatory infiltrate and postulate the existence of three subtypes of XC: multinodu…

Splenic marginal zone lymphoma with or without villous lymphocytes

BACKGROUND Splenic marginal zone lymphoma (SMZL) is a well defined pathologic entity. However, questions regarding the bone marrow infiltration rate, the minimal diagnostic data set, and therapy remain unanswered. METHODS Clinical-pathologic features and outcomes of 57 consecutive patients who had splenomegaly with no clinically significant lymphadenomegaly and who were diagnosed with SMZL with or without (±) villous lymphocytes (VL) were reviewed. RESULTS SMVL ± VL occurred mostly in elderly males (median age, 62 years ± 10 years; male-to-female ratio, (1.85). Anemia was recorded in 49% of patients, and 30% of patients had moderate thrombocytopenia. Leukocytosis and leukopenia were found i…

PLEOMORPHIC HYALINIZING ANGIOECTATIC TUMOR (PHAT) OF RENAL PARENCHYMA. FIRST CASE REPORTED IN LITERATURE

Microenvironment-centred dynamics in aggressive B-cell lymphomas.

Aggressive B-cell lymphomas share high proliferative and invasive attitudes and dismal prognosis despite heterogeneous biological features. In the interchained sequence of events leading to cancer progression, neoplastic clone-intrinsic molecular events play a major role. Nevertheless, microenvironment-related cues have progressively come into focus as true determinants for this process. The cancer-associated microenvironment is a complex network of nonneoplastic immune and stromal cells embedded in extracellular components, giving rise to a multifarious crosstalk with neoplastic cells towards the induction of a supportive milieu. The immunological and stromal microenvironments have been cl…

Refertazione istopatologica e fattori prognostici del carcinoma mammario: requisiti minimi

Bone marrow biopsy in Hodgkin's lymphoma

In the study of patients with Hodgkin's lymphoma (HL) the evaluation of bone marrow biopsy (BMB) can be difficult. In this review we analyze the main diagnostic features and the clinical risk factors of BM involvement. Although the role of BMB is criticized by some authors, its value is irreplaceable in the staging of HL and in the diagnosis of primary medullary HL. The Ann Arbor staging committee criteria should be revised and updated in the light of the current immunohistochemical studies that give a fundamental help in the diagnostic process. A single BMB should be adequate for diagnosis in most instances. In cases of suspicious involvement a controlateral BMB could be performed.

Impact of liver steatosis on the antiviral response in the hepatitis C virus-associated chronic hepatitis.

: Background/Aim: Liver steatosis (LS) has been variably associated with chronic hepatitis C (CHC) but whether it affects sustained virological response to antiviral treatment and by what mechanisms is a question still under debate, at least for some genotypes. The aim of this work was to assess the frequency of LS, its relationship with host and viral factors and to what extent it can influence the response to antiviral combination therapy with pegylated interferon (INF)+ribavirin in a group of patients with CHC from a single center. Patients: One hundred and twelve patients with histologically proven CHC were treated with Peg INF-α 2a 180 μg a week subcutaneously for 48 weeks plus ribavir…

False versus true ET. Morphologic, immunophenotypic and molecular features

Concomitant inflammatory pseudotumor of the liver and spleen.

We report the case of a 53-year-old man with inflammatory pseudotumor (IPT) of the liver and spleen. This concomitant association has rarely been reported. The patient presented with a hypoechoic mass in the liver and a clinical picture of recurrent sepsis; hematochemical exams and imaging data were nonspecific. Antibiotic therapy improved the clinical course, but did not resolve it definitively. After 50 days of therapy, as the hepatic mass decreased a similar lesion appeared in the spleen. The final diagnosis was made on splenectomy and an intra-operative biopsy of the residual liver lesion. The diagnostic problems encountered in this very rare association of IPT of the liver and spleen w…

Bone marrow evaluation according to the PVSG and WHO criteria in 90 essential thrombocythemia (ET) patients treated with PEG interferon alpha-2b. Preliminary results

Abstract Ninety ET patients diagnosed according to the PVSG criteria were enrolled in a phase II study (sponsored by the Schering-Plough Company) designed to evaluate the efficacy, safety and tolerability of a two years treatment with PEG Interferon alpha-2 b (PEG Intron). The patients, observed in 16 Italian Centres belonging to the GIMEMA Cooperative Group and judged at high risk, had been previously treated with cytoreductive (97%) and antiplatelet (91%) drugs. At the study start the patients, 60 F and 30 M, mean age 45 years, showed splenomegaly in 22% of cases. The Hematological Response (HR: PLT&amp;lt;500 x109/L) was observed in 64/81 (79%) and 48/55 (87%) of the patients on PEG Intr…

Gamma-delta T-cell lymphomas.

Peripheral T-cell lymphomas (TCLs) are uncommon neoplasms, accounting for about 12% of all lymphoid tumors worldwide. TCLs in which gammadelta T-cell receptors are expressed (gammadelta TCLs) are extremely aggressive and rare (<1% of lymphoid neoplasms). gammadelta TCLs originate from gammadelta T cells, a small subset of peripheral T cells with direct antigen recognition capability acting at the interface between innate and adaptive immunity. Two distinct gammadelta TCL entities are recognized: hepatosplenic T-cell lymphoma (HSTL) and primary cutaneous gammadelta T-cell lymphoma (PCGD-TCL). HSTL is a well-characterized extranodal lymphoma that has a disguised onset, secondary to intrasinus…

Prognostic features of splenic lymphoma with villous lymphocytes

Intravesical chemotherapy for intermediate risk non-muscle invasive bladder cancer recurring after a first cycle of intravesical adjuvant therapy

Context: The therapeutic strategy in intermediate risk (IR) non-muscle invasive bladder cancer (NMIBC) recurring after intravesical therapy (IT) is not well defined. Most patients are usually retreated by Bacillus Calmette-Guerin (BCG). Aims: To evaluate the efficacy of intravesical chemotherapy (ICH) given at recurrence after the first cycle of ICH in IR-NMIBC recurring 6 months or later. Settings and Design: Retrospective analysis of the efficacy of ICH given after previous IT. Materials and Methods: The clinical files of IR-NMIBC patients recurring later than 6 months after transurethral resection (TUR) and IT and retreated by IT were reviewed. The patients should be at intermediate risk…

Gastric and gingival localization of mucosa-associated lymphoid tissue (MALT) lymphoma. An immunohistochemical, virological and clinical case report.

Non-Hodgkin's lymphomas (NHL) of the mucosa-associated lymphoid tissue (MALT) are characterized by their mucosal and glandular tissue localization. The case described here falls into the European-American classification of a low-grade B-cell lymphoma of the MALT type, with a gingival lesion 2 years after a gastric lesion. The pathogenetic mechanisms of NHL in oral MALT and the diagnosis and treatment are discussed.

Concomitant inflammatory pseudotumor of the liver and spleen

We report the case of a 53-year-old man with inflammatory pseudotumor (IPT) of the liver and spleen. This concomitant association has rarely been reported. The patient presented with a hypoechoic mass in the liver and a clinical picture of recurrent sepsis; hematochemical exams and imaging data were nonspecific. Antibiotic therapy improved the clinical course, but did not resolve it definitively. After 50 days of therapy, as the hepatic mass decreased a similar lesion appeared in the spleen. The final diagnosis was made on splenectomy and an intra-operative biopsy of the residual liver lesion. The diagnostic problems encountered in this very rare association of IPT of the liver and spleen w…

Myeloid sarcoma: clinico-pathologic, phenotypic and cytogenetic analysis of 92 adult patients.

Myeloid sarcoma ( MS) is a rare neoplasm whose knowledge is largely based on case reports and/or technically dated contributions. Ninety-two MSs in adulthood with clinical data available were evaluated both morphologically and immunohistochemically. Seventy-four cases were also studied by fluorescent in situ hybridization on tissue sections and/or conventional karyotyping on bone marrow or peripheral blood. Histologically, 50% of the tumors were of the blastic type, 43.5% either monoblastic or myelomonocytic and 6.5% corresponded to different histotypes. CD68/KP1 was the most commonly expressed marker (100%), followed by myeloperoxidase (83.6%), CD117 (80.4%), CD99 (54.3%), CD68/PG-M1 (51%)…

Different immunophenotypical apoptotic profiles characterise megakaryocytes of essential thrombocythaemia and primary myelofibrosis.

Aims: Essential thrombocythaemia (ET) and primary myelofibrosis (PMF) share some clinical and pathological features, but show different biological behaviour and prognosis. The latest contributions to understanding the nature of these disorders have focused on bone marrow microenvironment remodelling and proliferative stress, recognising megakaryocytes (MKCs) as “key-cells”. The aim of this study was to investigate the apoptotic profile of ET and PMF MKCs in order to further characterise the biology of these disorders. Methods: Bone marrow biopsy samples from 30 patients with ET, and 30 patients with PMF, were immunophenotypically studied for the expression of pro-apoptotic (Fas, Fas-L, Bax,…

Re: ?Splenic marginal zone B-cell lymphoma associated with primary Sj�gren?s syndrome?

We describe a 67-year-old woman with primary Sjögren's syndrome who developed a splenic marginal zone B-cell lymphoma, and complained of a dry mouth and Raynaud's phenomenon. She had splenomegaly, swollen lymph nodes and monoclonal IgM-kappa cryoglobulin. After splenectomy, Raynaud's phenomenon had improved with the decrease of cryoglobulin. This is the first case of primary Sjögren's syndrome with splenic marginal zone B-cell lymphoma to be reported.

Bone marrow biopsy in hemophagocytic syndrome.

Abstract Aims. Hemophagocytic syndrome (HPS) is a severe and acute clinical event occurring with fever, hepatosplenomegaly, and pancytopenia due to uncontrolled phagocytosis of blood cells and precursors. Although HPS represents a secondary phenomenon, it can mask the underlying condition, generally a neoplastic or infective disease, thus making the patient management rather difficult. The aims of this study were to point out the main pathological features useful to highlight the primary disease and show the eventual discrepancies among the different cases. Methods and results. Bone-marrow biopsies (BMBs) of 26 patients with HPS were morphologically and immunophenotypically evaluated; the p…

Bone marrow biopsy in Hodgkin's lymphoma.

In the study of patients with Hodgkin's lymphoma (HL) the evaluation of bone marrow biopsy (BMB) can be difficult. In this review we analyze the main diagnostic features and the clinical risk factors of BM involvement. Although the role of BMB is criticized by some authors, its value is irreplaceable in the staging of HL and in the diagnosis of primary medullary HL. The Ann Arbor staging committee criteria should be revised and updated in the light of the current immunohistochemical studies that give a fundamental help in the diagnostic process. A single BMB should be adequate for diagnosis in most instances. In cases of suspicious involvement a controlateral BMB could be performed.

Reproducibility of the WHO histological criteria for the diagnosis of Philadelphia chromosome-negative myeloproliferative neoplasms

This study, performed on behalf of the Italian Registry of Thrombocythaemias (Registro Italiano Trombocitemie), aimed to test the inter-observer reproducibility of the histological parameters proposed by the WHO classification for the diagnosis of the Philadelphia chromosome-negative myeloproliferative neoplasms. A series of 103 bone marrow biopsy samples of Philadelphia chromosome-negative myeloproliferative neoplasms consecutively collected in 2004 were classified according to the WHO criteria as follows: essential thrombocythaemia (n=34), primary myelofibrosis (n=44) and polycythaemia vera (n=25). Two independent groups of pathologists reviewed the bone marrow biopsies. The first group w…

CD38/CD31, the CCL3 and CCL4 chemokines, and CD49d/vascular cell adhesion molecule-1 are interchained by sequential events sustaining chronic lymphocytic leukemia cell survival.

AbstractCD38 and CD49d are associated negative prognosticators in chronic lymphocytic leukemia (CLL). Despite evidence that both molecules are involved in interactions occurring between CLL and normal cells in the context of CLL-involved tissues, a functional link is still missing. Using gene expression profiles comparing CD38+CD49d+ versus CD38−CD49d− CLL cells, we showed overexpression of the CCL3 and CCL4 chemokines in cells from the former group. These chemokines were also up-regulated by CD38 signals in CLL; moreover, CCL3 was expressed by CLL cells from bone marrow biopsies (BMB) of CD38+CD49d+ but not CD38−CD49d− cases. High levels of CCR1 and, to a lesser extent, CCR5, the receptors…