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Biomedical subjects

S A Pileri

Publications and source records attributed to S A Pileri.

At least 55 records · Page 3Linked to original sources

T-cell prolymphocytic leukaemia: does the expression of CD8+ phenotype justify the identification of a new subtype? Description of two cases and review of the literature.

T-cell chronic lymphocytic leukaemia (T-CLL) has recently been reclassified under the heading of T-cell prolymphocytic leukaemia (T-PLL) because of its unfavourable clinical course, independently of the morphologic features. This rare neoplasm usually shows CD4+/CD8- phenotype. Herein we report on two cases of T-PLL with CD8 expression that correspond to a possible variant of the disease first proposed by Hui et al. in 1987. These cases presented with malignant cells showing immunophenotypic features that can be easily identified and distinguished from other peripheral T-cell leukemias. However, the total number of cases studied is inadequate for defining a discrete clinico-pathologic entity with characteristic clinical features and cytogenetical abnormalities. An international collaboration in which tissue from similar cases is referred to a central pathologist for immunophenotyping and cytogenetical study, and clinical data are centrally compiled, may assist in defining this rare malady as a discrete clinico-pathologic entity.

Adult↗

The oncogenic 30 and 69 bp deletion variants of the EBV LMP-1 gene are common in HIV-negative lymphoproliferations, both malignant and benign.

BACKGROUND: In vitro studies have shown that the 30 and 69 base pair (bp) deletion variants of the latent membrane protein (LMP)-1 gene of the Epstein-Barr virus (EBV) have a higher transforming capacity than the wild-type variant. In recent years these studies have triggered an in vivo search for such potentially oncogenic variants in lymphoid tissues. PATIENTS AND METHODS: We used polymerase chain reaction (PCR) to investigate the prevalence of LMP-1 gene variants in EBV-positive lymph nodes from 60 HIV-negative Italian patients with benign and malignant lymphoid disorders. RESULTS: The 30 bp variant was detected in 10 of 39 (25.6%) malignant lymphomas but also in 4 of 13 (30%) reactive lymphadenitis with follicular hyperplasia. Of note is the fact that the 69 bp variant was detected in three cases of malignant lymphoproliferation but also in two cases of localized Castleman's disease of hyalin vascular type. CONCLUSIONS: The molecular detection of the oncogenic variants of the LMP-1 gene in a lymph node biopsy as an indicator of the aggressiveness of the EBV-associated lymphoproliferative disease must be considered with caution. The relatively high frequency of the 69 bp variant in our series compared with that reported in the literature probably reflects a different incidence of LMP-1 variants in healthy populations from different geographical areas.

Biopsy↗

Beta-HCG aberrant expression in primary mediastinal large B-cell lymphoma.

We report on a primary mediastinal large B-cell lymphoma with aberrant expression of beta-human chorionic gonadotropin (beta-hCG). The patient, a 33-year-old man, had cough, dyspnea, fever, superior vena cava syndrome, and a mediastinal bulky tumor. A biopsy showed that the latter was characterized by large cells, sclerosis, and compartmentalization. The neoplastic elements expressed CD45, CD20, CD79a and, partially, CD30, whereas they were negative for CD3, epithelial membrane antigen and cytokeratins. Surprisingly, they displayed a clear-cut positivity for beta-hCG. The remaining oncofetal markers applied (PLAP and alpha1-fetoprotein) were negative. Electron microscopy demonstrated the presence of numerous nuclear pockets and the lack of intercellular junctions. DNA analysis by polymerase chain reaction showed clonal rearrangement of Ig heavy-chain genes. The patient responded promptly to the administration of MACOP-B. To the best of our knowledge, this is the first example of B-cell lymphoma showing positivity for beta-hCG; a similar aberrant expression was previously observed only in three Japanese patients with human T-cell lymphotropic virus type I+ adult T-cell lymphoma/leukemia. Because primary mediastinal large B-cell lymphoma has in the past been frequently confused with germ cell tumors, pathologists should be aware of possible beta-hCG expression by lymphomatous cells to avoid the risk of misdiagnosis.

Adult↗

Acute leukaemia immunophenotyping in bone-marrow routine sections.

Immunohistochemistry of acute leukaemias in bone-marrow paraffin sections is commonly thought to be useless because of the poor preservation of many lineage-related markers. The recent development of antibodies against fixative-resistant epitopes and of new antigen retrieval techniques, however, has expanded the possibility of accurately testing routine samples. To assess the relevance of paraffin section phenotyping in lineage determination, 110 examples of acute leukaemia were studied by specific antibodies against CD1a, CD3, CD15, CD20, CD34, CD68, CD79a, TdT, myeloperoxidase, glycophorin A, and factor-VIII-related antigen. The cases included 59 acute myeloid leukaemias, classified according to the FAB cooperative group criteria, 39 precursor B-cell acute lymphoblastic leukaemias (ALLs), seven T-ALLs, and five mixed precursor B-cell/myeloid acute leukaemias. The combination of the markers employed always allowed the identification of the cell lineage (myeloid, lymphoid or mixed) and, in some instances, of phenotypic profiles characteristic of distinct acute leukaemia subtypes. According to the results obtained, bone-marrow biopsy may be regarded as a reliable tool for acute leukaemia diagnosis; this observation is of practical relevance especially for the classification of cases which lack circulating blasts in the peripheral blood or showing dry tap at bone-marrow aspiration.

Acute Disease↗

Anaplastic large cell lymphoma Hodgkin's-like: a randomized trial of ABVD versus MACOP-B with and without radiation therapy.

During the last few years, morphological, immunohistochemical, and genetic findings have placed anaplastic large cell lymphoma (ALCL) as a distinct clinicopathologic entity, and several reports have focused on the existence of different subtypes of the tumor. Particular attention has been paid to the ALCL-Hodgkin's-like (HL) subtype, which seems to be on the border between Hodgkin's disease (HD) and high-grade non-Hodgkin's lymphoma (HG-NHL). From September 1994 to July 1997, during the course of an Italian multicentric trial, 40 ALCL-HLs were randomized to receive as front-line chemotherapy MACOP-B (methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin-a third-generation HG-NHL regimen) or ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine-a scheme specific for HD). All patients with bulky disease in the mediastinum at diagnosis underwent local radiotherapy after the chemotherapeutic program. Complete response (CR) was achieved in 17 of the 19 (90%) patients who were treated with MACOP-B, and in 19 of the 21 (91%) patients who were administered ABVD. The probability of relapse-free survival, projected at 32 months, was 94% for the MACOP-B subset and 91% for the ABVD subset. The majority of patients with mediastinal bulky disease obtained CR (evaluated with 67Ga single photon emission computed tomography [SPECT]) after their radiotherapy. The present study suggests that ALCL-HL, in line with its borderline status, responds in an equivalent way to third-generation chemotherapy for HG-NHL and to conventional HD treatment in terms of both CR and relapse-free survival rates. However, as to the latter, a longer follow-up period may be needed before stating the absolute equivalence of the two regimens used.

Adolescent↗

ALK expression defines a distinct group of T/null lymphomas ("ALK lymphomas") with a wide morphological spectrum.

The t(2;5)(p23;q35) translocation associated with CD30-positive anaplastic large cell lymphoma results in the production of a NPM-ALK chimeric protein, consisting of the N-terminal portion of the NPM protein joined to the entire cytoplasmic domain of the neural receptor tyrosine kinase ALK. The ALK gene products were identified in paraffm sections by using a new anti-ALK (cytoplasmic portion) monoclonal antibody (ALKc) that tends to react more strongly than a previously described ALK1 antibody with the nuclei of ALK-expressing tumor cells after microwave heating in 1 mmol/L ethylenediaminetetraacetic acid buffer, pH 8.0. The ALKc monoclonal antibody reacted selectively with 60% of anaplastic large cell lymphoma cases (60 of 100), which occurred mainly in the first three decades of life and consistently displayed a T/null phenotype. This group of ALK-positive tumors showed a wide morphological spectrum including cases with features of anaplastic large cell lymphoma "common" type (75%), "lymphohistiocytic" (10%), "small cell" (8.3%), "giant cell" (3.3%), and "Hodgkin's like" (3.3%). CD30-positive large anaplastic cells expressing the ALK protein both in the cytoplasm and nucleus represented the dominant tumor population in the common, Hodgkin's-like and giant cell types, but they were present at a smaller percentage (often with a perivascular distribution) also in cases with lymphohistiocytic and small cell features. In this study, the ALKc antibody also allowed us to identify small neoplastic cells (usually CD30 negative) with nucleus-restricted ALK positivity that were, by definition, more evident in the small cell variant but were also found in cases with lymphohistiocytic, common, and "Hodgkin's-like" features. These findings, which have not been previously emphasized, strongly suggest that the neoplastic lesion (the NPM-ALK gene) must be present both in the large anaplastic and small tumor cells, and that ALK-positive lymphomas lie on a spectrum, their position being defined by the ratio of small to large neoplastic cells. Notably, about 15% of all ALK-positive lymphomas (usually of the common or giant cell variant) showed a cytoplasm-restricted ALK positivity, which suggests that the ALK gene may have fused with a partner(s) other than NPM. From a diagnostic point of view, detection of the ALK protein was useful in distinguishing anaplastic large cell lymphoma cases of lymphohistiocytic and small cell variants from reactive conditions and other peripheral T-cell lymphoma subtypes, as well as for detecting a small number of tumor cells in lymphohemopoietic tissues. In conclusion, ALK positivity appears to define a clinicopathological entity with a T/null phenotype ("ALK lymphomas"), but one that shows a wider spectrum of morphological patterns than has been appreciated in the past.

Anaplastic Lymphoma Kinase↗

Hodgkin's disease occurring in a child after liver transplantation.

Here we describe the case of a 14-year-old boy who underwent liver transplantation for post-Kasai biliary atresia when aged 4. Antirejection treatment consisted of prednisone and cyclosporine. At the age of 11 years the patient developed left cervical lymphadenopathy; the biopsy showed classical Hodgkin's disease(HD) of the mixed cellularity (MC) type. Neoplastic cells expressed CD30 and CD15, and were negative for CD45, CD20, CD3, CD43, and CD79a. Furthermore, they carried the EBV-related products LMP1 and EBER1/2. Treatment consisted of three cycles of adriamycin, bleomycin, vinblastine and DTIC (ABVD), followed by radiotherapy (2,000 cGys) on involved fields. At present, 42 months after the diagnosis of HD, the patient is still in complete remission. This is, to the best of our knowledge, the first reported case of classical HD following liver transplantation. The positivity of neoplastic cells for LMP1 and EBER1/2 indicates a possible role for immunosuppression in the development of the tumor, and whether a reduction in immunosuppression might have influenced the course of the disease is open to question.

Adolescent↗

Therapy with gemcitabine in pretreated peripheral T-cell lymphoma patients.

BACKGROUND: Gemcitabine is a novel nucleoside analogue which has shown promising results in most solid tumors; like the arabinosylcytosine analogue, gemcitabine may be an active drug in lymphoproliferative malignancies. We tested it in pretreated peripheral T-cell lymphoma patients with isolated skin involvement. PATIENTS AND METHODS: We performed a phase II study with the drug in 13 pretreated patients with peripheral T-cell lymphoma, five of whom had advanced-stage mycosis fungoides (MF), and eight peripheral T-cell lymphoma unspecified (PTCLU). Patients were treated on days 1, 8, and 15 of a 28-day schedule at the dosage of 1200 mg/m2 for a total of three courses. RESULTS: Of the 13 patients, one achieved complete response (CR) and eight achieved partial responses (PR); the remaining four showed no benefit from the treatment. Among the responders, one CR and four PR were documented in the PTCLU patients and four PR in MF patients. Treatment was well tolerated; hematologic toxicity was mild and no nausea/vomiting or organ toxicity was recorded. CONCLUSIONS: In view of its significant activity and its modest toxicity profile, the role of gemcitabine deserves further evaluation in the management of pretreated patients with peripheral T-cell lymphoma.

Adult↗

Localized amyloidosis and gastrointestinal lymphoma: a rare association.

AIMS: Five cases of primary gastrointestinal (GI) lymphoma (three in the stomach, one in the ileum (IPSID) and one in the colon) associated with localized AL amyloidosis were studied to identify morphological or immunohistochemical features which could explain the amyloid deposition. METHODS AND RESULTS: All the cases were low-grade marginal zone B-cell lymphomas; one case of gastric lymphoma and the IPSID also had a high-grade component. The lymphomas had a monoclonal plasma cell population, with different light and heavy-chain type expression in the five cases. Plasma cell differentiation was closely associated with the amyloid deposits. The latter were an incidental microscopic finding in one case, but produced tumoral masses in the other. CONCLUSIONS: The presence of amyloid in primary GI lymphoma is rare, but can have diagnostic value. In the present study, neither particular features of the lymphomatous proliferation nor specific agents are identified. Therefore, the factors predisposing to amyloid deposition require elucidation.

Aged↗

Retinoblastoma (RB1) gene product expression in breast carcinoma. Correlation with Ki-67 growth fraction and biopathological profile.

AIMS: To investigate the expression of retinoblastoma protein (pRb) in invasive breast tumours and compare its expression with the major biopathological prognostic indicators to identify more aggressive subgroups. MATERIAL: Archival paraffin embedded tissues from 153 consecutive primary breast carcinomas. METHODS: pRb, Ki-67, and oestrogen receptor/progesterone receptor proteins were identified by immunohistochemistry and score values were recorded by image cytometric analysis; p53 and EGFr expression was also evaluated. RESULTS: pRb scores correlated strongly with proliferation activity as determined by Ki-67 staining. Positive relations were also observed between pRb scores, tumour size, nuclear and histological grade, and oestrogen receptor/progesterone receptor content, while abnormal p53 accumulation was not associated with pRb expression. Among the high proliferating carcinomas it was possible to identify 13 cases with loss of pRb expression. CONCLUSIONS: pRb expression paralleled proliferative activity in the majority of breast carcinomas examined, suggesting that in these cases the protein behaves normally in regulating the cell cycle. Conversely in cases with loss of pRb immunostaining, the combined expression of specific highly aggressive factors (EGFr and p53 expression, oestrogen receptor/progesterone receptor negative status, and high K67) seems to characterise a more aggressive phenotype showing growth advantage and cellular "progression" rather than significant nodal involvement.

Biomarkers, Tumor↗

The EnVision++ system: a new immunohistochemical method for diagnostics and research. Critical comparison with the APAAP, ChemMate, CSA, LABC, and SABC techniques.

AIM: To assess a newly developed immunohistochemical detection system, the EnVision++. METHODS: A large series of differently processed normal and pathological samples and 53 relevant monoclonal antibodies were chosen. A chessboard titration assay was used to compare the results provided by the EnVision++ system with those of the APAAP, CSA, LSAB, SABC, and ChemMate methods, when applied either manually or in a TechMate 500 immunostainer. RESULTS: With the vast majority of the antibodies, EnVision++ allowed two- to fivefold higher dilutions than the APAAP, LSAB, SABC, and ChemMate techniques, the staining intensity and percentage of expected positive cells being the same. With some critical antibodies (such as the anti-CD5), it turned out to be superior in that it achieved consistently reproducible results with differently fixed or overfixed samples. Only the CSA method, which includes tyramide based enhancement, allowed the same dilutions as the EnVision++ system, and in one instance (with the anti-cyclin D1 antibody) represented the gold standard. CONCLUSIONS: The EnVision++ is an easy to use system, which avoids the possibility of disturbing endogenous biotin and lowers the cost per test by increasing the dilutions of the primary antibodies. Being a two step procedure, it reduces both the assay time and the workload.

Antibodies, Monoclonal↗

Concurrence of localized Castleman's disease and peripheral small B-Lymphocytic lymphoma within the same lymph node.

Castleman's disease, also known as benign giant lymph node hyperplasia, is a lymphoproliferative disorder which can occur either in a localized or multicentric form. The latter is characterized by the development of malignant lymphoma, Kaposi's sarcoma or carcinoma in 32% of cases. By contrast, localized Castleman's disease has exceptionally been reported in association with non-Hodgkin's lymphoma and - to the best of our knowledge - never at the same anatomic site. Here we describe the occurrence in the same lymph node of localized Castleman's disease (with monotypic plasma cell component) and an apparently unrelated peripheral small B-lymphocytic lymphoma.

Aged↗

Ultrasound-guided core-needle biopsy is effective in the initial diagnosis of lymphoma patients.

BACKGROUND AND OBJECTIVE: With the development and refinement of new guidance methods for percutaneous biopsies, many investigators have reported studies supporting a role for radiologically guided core-needle biopsy in the diagnosis of malignant lymphoma under certain clinical circumstances. The aims of this report are to evaluate the efficacy of findings at ultrasound (US)-guided core-needle biopsy of abdominal lymphoma on patient care and define the key determinants of clinical success. DESIGN AND METHODS: US-guided core needle biopsies were performed in 55 patients with abdominal lymphoma: 44 non-Hodgkin's lymphoma (NHL) and 11 Hodgkin's disease (HD); 41 had had no prior lymphoma and 14 had previously diagnosed lymphoma. All the biopsies were performed under US control using a 21-gauge modified Menghini needle. Overall, 53/55 (96%) patients were treated on the basis of biopsy findings only, including 14/14 (100%) patients with a history of lymphoma and 39/41 (93%) patients with no such history. RESULTS: In 46/53 (87%) patients it was possible to assess the specific histotype. No differences between the diagnostic rates of HD and high grade-NHL were recorded. There were no complications related to the biopsies. INTERPRETATION AND CONCLUSIONS: Our data indicate that abdominal US-guided core-needle biopsy should be considered as an effective and safe procedure in the diagnosis of patients with lymphoma offering the possibility of determining the tumor subtype and the subsequent specific treatment.

Abdominal Neoplasms↗

Antigen retrieval techniques in immunohistochemistry: comparison of different methods.

Routine sections of normal and pathological samples fixed in 10 per cent buffered formalin or B5, including EDTA-decalcified bone-marrow biopsies, were tested with 61 antibodies following heating in three different fluids: 0.01 M citrate buffer (pH 6.0), 0.1 M Tris-HCl (pH 8.0), and 1 mM EDTA-NaOH solution (pH 8.0). The sections underwent either three cycles of microwave treatment (5 min each) or pressure cooking for 1-2 min. The alkaline phosphatase/anti-alkaline phosphatase (APAAP) technique was used as the standard detection method; with 16 antibodies a slightly modified streptavidin-biotin complex (SABC)-immunoperoxidase technique was applied in parallel. The results obtained were compared with those observed without any antigen retrieval (AR), or following section digestion with 0.05 per cent protease XIV at 37 degrees C for 5 min. Chess-board titration tests showed that all antibodies but one profited by AR. Protease XIV digestion represented the gold standard for five antibodies, while 55 produced optimal results following the application of heat-based AR. By comparison with the other fluids, EDTA appeared to be superior in terms of both staining intensity and the number of marked cells. These results were independent of tissue processing, immunohistochemical approach, and heating device. Pressure cooking was found to be more convenient on practical grounds, as it allowed the simultaneous handling of a large number of slides and a time saving of 1 min 30 s, representing the proper time for the treatment.

Antigens↗

Peripheral T-cell lymphomas. Clinico-pathologic study of 168 cases diagnosed according to the R.E.A.L. Classification.

BACKGROUND: One hundred sixty-eight peripheral T-cell lymphomas (PTCLs) were reviewed according to the Revised European-American Lymphoma (R.E.A.L.) Classification. PATIENTS AND METHODS: The cases, originally diagnosed on the basis of the Updated Kiel Classification (UKC), were all provided with histological preparations, immunophenotype, clinical information, and follow-up data. The slides were reclassified by five observers, who integrated the R.E.A.L. criteria with cell size measurements. The prognostic value of clinical and pathologic findings was assessed by univariate and multivariate analysis. RESULTS: The R.E.A.L. Classification was reproducibly applied by all of the observers. Clinically, anaplastic large cell lymphomas (ALCLs) differed from the remaining PTCLs by mean age (29.5 vs. 52.9 years), bulky disease (52.3% vs. 11.3%; P = 0.000), mediastinal mass (52.7% vs. 32%; P = 0.004), and disease-free survival (68.0% vs. 38.2%; P = 0.0001). Although each histological type displayed specific clinical aspects, PTCLs other than ALCL were basically characterised by a poor clinical outcome which was not influenced by the UKC malignancy grade. At multivariate analysis, the risk of a lower complete remission rate was related to bulky disease (P = 0.001), histologic group (non-ALCL) (P = 0.01), and advanced stage (III-IV) (P = 0.0002). CONCLUSIONS: The present study supports the classification of T-cell lymphomas proposed by the R.E.A.L. scheme.

Adolescent↗

Pyothorax-associated lymphoma: description of the first two cases detected in Italy.

BACKGROUND: Pyothorax-associated lymphoma (PAL) is a rare, but distinct, clinico-pathologic entity which occurs most often in Japanese people; to the best of our knowledge, only six cases of it have been reported in Western countries. The tumour develops several decades following artificial pneumothorax or chronic pleuritis due to tuberculous infection, produces pleural effusion associated with extensive local lymphomatous infiltrates, and is sustained by a polymorphic large B-cell clonal proliferation showing EBV integration in the genoma of the neoplastic cells. PATIENTS AND METHODS: Herein we describe two cases of PAL observed in Italian patients, both extensively studied on the clinical, pathological, phenotypic, virological, and molecular levels. RESULTS: The two cases occurred, respectively, 45 and 50 years after therapeutic pneumothorax because of tuberculous pleuritis and were characterized by a pleural mass extending to the thoracic wall, which on histological examination were seen to consist of large elements with immunoblastic morphology. Immunohistochemistry show monotypic restriction of Ig light chains, as well as the expression of CD45, B-cell markers (CD20, CD79a, CD45RA), bcl-2 oncogene product, EBNA-2 and, partially, LMP-1. The ratio of cycling cells was extremely high as was the number of mitotic figures. In situ hybridization displayed the presence in the neoplastic cells of the EBV-related small RNAs EBER 1 and 2, which in turn, along with the positivity for EBNA-2 and LMP-1, further strengthened the close relationships between PAL and latent viral infection. Molecular studies revealed, on one hand, clonal rearrangement of the Ig heavy chain J region genes, and on the other, negativity for HHV8 in one case and positivity in the other. CONCLUSIONS: These cases of PAL are the first to be documented in Italy; they serve to direct attention to the fact that this condition is not confined to Japanese people, and that its occurrence in Western countries might be underestimated.

Aged↗