Clinicopathologic characteristics and treatment outcome of the addition of rituximab to chemotherapy for CD5-positive in comparison with CD5-negative diffuse large B-cell lymphoma.

BACKGROUND: CD5-positive (CD5+) diffuse large B-cell lymphoma (DLBCL) comprises ∼10% of DLBCLs, and it is associated with poor prognosis. The clinicopathologic characteristics and prognosis of CD5-negative (CD5-) DLBCL and CD5+ DLBCL were compared. PATIENTS AND METHODS: The subjects were 607 DLBCL patients in whom cell surface markers could be analyzed, among 930 consecutive patients registered in the Adult Lymphoma Treatment Study Group between 1998 and 2008. RESULTS: In all, 102 patients (16.8%) had CD5+ DLBCL. Compared with CD5- DLBCL, CD5+ DLBCL was more closely associated with elevated serum lactate dehydrogenase level, advanced stage, poor performance status, extranodal sites, CD10-, BCL-2+, MUM1+, and nongerminal center B-cell type. The 5-year overall survival (OS) rates of CD5+ DLBCL (n = 102) and CD5- DLBCL (n = 505) were 55% and 65%, respectively (P = 0.032), with 5-year progression-free survival (PFS) rates of 52% and 61%, respectively (P = 0.041). In the CD5+ DLBCL patients, the addition of rituximab to chemotherapy significantly improved PFS (4-year PFS, 47.4% versus 62.5%), but not OS (4-year OS, 57.8% versus 63.5%). CONCLUSIONS: For CD5+ DLBCL, the addition of rituximab to chemotherapy significantly improved the PFS, but not OS. Therefore, it is thought that a new treatment strategy is necessary for CD5+ DLBCL.

A clinicopathological study of nm23-H1 expression in classical Hodgkin's lymphoma.

BACKGROUND: We carried out immunohistochemistry to examine the expression of nm23-H1 in Hodgkin and Reed-Sternberg cells in patients with classical Hodgkin's lymphoma (CHL). PATIENTS AND METHODS: We evaluated 128 patients with CHL [87 patients with nodular sclerosis (NS) and 41 patients with mixed cellularity (MC)] for CD15, CD20, Ki-67, EBER, TIA-1, and nm23-H1 by immunohistochemistry. RESULTS: CD15 was expressed in 79%, CD20 in 11%, Ki-67 in 93%, EBER in 34%, TIA-1 in 11%, and nm23-H1 in 60% of the CHL patients. NS patients showed a significantly higher rate of nm23-H1 expression than MC patients (P < 0.001). The serum nm23-H1 level was significantly higher in patients with positive nm23 expression. Univariate analysis showed that stage IV, poor performance status, low hemoglobin level, low serum albumin level, age of 45 years or older, TIA-1-positive status, and nm23-H1-positive status were associated with significantly shorter progression-free survival. Multivariate analysis with these factors showed TIA-1 and cytoplasmic nm23-H1 expression to be significant and independent prognostic factors. CONCLUSIONS: Our results indicate that nm23-H1 expression is a prognostic factor for CHL and that it is as important as serum nm23-H1, both of which are useful for planning the treatment strategy.

Clinicopathologic correlations of stage IE/IIE primary thyroid diffuse large B-cell lymphoma.

BACKGROUND: We studied the clinicopathological characteristics and prognoses of localized stage thyroid diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: This study included 32 patients with stage I/IIE thyroid DLBCL. Their median age was 66 years, the male/female ratio was 10/22. RESULTS: As to the cellular immunophenotype, CD20 was positive in 31/32, CD5 in 0/32, CD10 in 4/32, CD23 in 1/32, BCL2 in 14/30, and BCL6 in 24/32. Twelve cases showed abnormal karyotypes: two cases with t(8;14)(q24;q32), four cases with 3q27, two cases with 17p11, and four cases with other abnormal karyotypes. As for treatment, eight cases were treated with chemotherapy alone and 24 cases were treated with chemotherapy followed by radiotherapy. Complete response was achieved in 94%. The 5-year progression-free survival was 84% and the 5-year overall survival was 90% with a median follow-up period of 62 months. The germinal center B-cell (GCB) type had a significantly better prognosis than the non-GCB type. CONCLUSION: Localized stage thyroid DLBCL is a disease with a relatively good prognosis. It is, however, a heterogeneous disease with regard to histological type and pathological state. Localized stage thyroid DLBCL has a good prognosis and it is that there are more GCB-type DLBCL lymphomas.

Pathology review for paediatric non-Hodgkin's lymphoma patients in Japan; a report from the Japan association of childhood leukaemia study (JACLS).

A central pathology review system with an immunophenotyping laboratory was established in Japan to support the clinical trial, the Japan Association of Childhood Leukaemia Study (JACLS) NHL-98, for patients with paediatric non-Hodgkin's lymphoma (NHL). Pathology samples from 155 clinically-suspected NHL cases were evaluated centrally initially using the Revised European-American Lymphoma (REAL) classification in a rapid review (within 2 weeks after surgery/biopsy) and then later at the consensus review (once a year). The samples were subsequently re-classified according to the new World Health Organisation (WHO) classification. After the pathology review, 96 (62%) patients were eligible for the study, and 58 of them (60%) had extra-nodal primaries. These NHL cases included B-cell lymphomas (precursor B-cell, 11; Burkitt, 18; diffuse large B-cell, 18; not otherwise specified, 3) and T/Natural Killer (NK)-cell lymphomas (precursor T-cell, 23; anaplastic large cell, 20; others, 3). There was excellent concordance in making the diagnoses (95/96, 99%) and typing (93/96, 97%) of NHL between the rapid and consensus reviews. Five cases, initially diagnosed as diffuse large B-cell lymphoma by the review, were re-classified as Burkitt lymphoma according to the immunocytochemical criteria by the WHO classification. A total of 59 (38%) cases were excluded from the study: they were Hodgkin lymphoma (7), leukaemias (11), reactive lymphoid hyperplasia (20), necrotizing lymphadenitis (7), no consensus diagnosis (1), insufficient materials (2), and others (11). This is the first report of the central pathology review from the paediatric NHL group study in Japan. Because various diseases, either neoplastic or reactive, mimicked NHL, clinically and histopathologically, the central pathology review system was critical and essential for patient enrollment and protocol assignment in our clinical trial. Through the two-step review system, highly reliable data were generated to support this study.

Primary gastric T-cell lymphoma not associated with human T-lymphotropic virus type I: a case report and review of the literature.

Primary gastric T-cell lymphoma (PGTL) not associated with human T-lymphotropic virus type I (HTLV-I) is extremely rare and such a case is reported herein. The patient was a 58-year-old Japanese male presenting with submucosal tumor of the stomach identified on endoscopic examination. The lesion was diagnosed as non-Hodgkin's lymphoma by endoscopic biopsy and classified as peripheral T-cell lymphoma, unspecified, due to clonal rearrangement of the T-cell receptor beta (TCR) gene and expression of TCR beta protein in the absence of B-cell genotypes and phenotypes. Unlike previously reported cases of HTLV-I-unassociated PGTL, lymphoma in the current case was characterized histologically as "low grade" and phenotypically as CD4+, TIA-1+, granzyme B+, and CD103-. The lymphoma responded well to chemotherapy and radiation, and the patient was well with no detectable disease 10 months after initiation of therapy. A review of patients with PGTL in the literature revealed a few long-term survivors, and the investigation of therapeutic strategies for PGTL is, therefore, necessary.

Renal collecting duct carcinoma. Report of a case with cytologic findings on fine needle aspiration.

BACKGROUND: Collecting duct carcinoma (CDC) of the kidney is a rare type of renal cell carcinoma (RCC) of collecting duct origin. Cytologic differentiation of CDC from conventional RCC is important because CDC has a poorer prognosis than the latter. CASE: A 60-year-old male incidentally demonstrated a left renal mass that was hypovascular by angiography. Fine needle aspiration (FNA) revealed numerous clusters of cells arranged in a tubular structure. The cells consisted of highly atypical cells having large nuclei with coarse or vesicular chromatin, prominent nucleoli and lacy or granular cytoplasm. Based on these findings, which were indicative of high grade RCC, he underwent left radical nephrectomy and lymphadenectomy. Histologic and immunohistochemical findings, including anti-high-molecular-weight cytokeratin (HMCK) antibody, confirmed the diagnosis of CDC. CONCLUSION: CDC should be added to the differential diagnosis when the result of cytologic examination of a renal mass is suggestive of high grade RCC. These features of FNA smears, together with HMCK immunohistochemistry, can be useful for the cytologic differential diagnosis of renal tumors.

Usefulness of CT virtual endoscopy in imaging a large esophagorespiratory fistula.

A 73-year-old woman with a large esophagorespiratory fistula underwent bronchoscopy and computed tomographic (CT) virtual endoscopy before stenting. Noninvasive CT virtual endoscopy showed the large fistula, and the CT findings agreed with the bronchoscopic findings.

[Methodology and clinical implication of the identification of clonality in malignant lymphoma].

A variety of methods is now available to identify clonality of lymphoid neoplasia by recent progress in immunology and molecular biology. The target molecules for these include physiologically or pathologically altered genes/their products and virus-derived DNAs. Identification of clonality is important for more accurate diagnosis of lymphoma and, especially, related borderline lesions. It is also of considerable value in staging and follow-up study of the patients because higher sensitivity of polymerase-chain reaction made it possible to detect submicroscopic lesions including minimal residual disease after treatment. However, many lesions and phenomena which are clonal, but do not appear to be malignant, have been characterized. These may prompt an update of the conventional concept of "malignant lymphoma".

Middle ear adenoma with neuroendocrine differentiation.

The lining of the middle ear cleft is normally a thin modified respiratory type mucosa. Normal mucosa of the middle ear is devoid of salivary type seromucous glands. Middle ear adenoma is a rare tumor that seems to be derived from the middle ear mucosa. This tumor has been previously described under a variety of names because of its different nature and biological behavior. We herein report a case of middle ear tumor that shows adenomatous and neuroendocrine features. A 64-year-old woman presented with a history of hearing loss, tinnitus and stuffy feeling of the right ear. The patient was treated two times for ear polyp. She finally underwent a tympanomastoidectomy and there was no evidence of recurrence 18 months after the procedure. Histopathological examination displayed cuboidal and columnar cells, arranged as glands, trabeculae and solid sheets. Neuroendocrine differentiation was revealed by immunohistochemical staining with polyclonal antibodies against neuron specific enolase and chromogranin antigens.

Detection of t(14; 18)(q32;q21) in hyperdiploid cells by fluorescence in situ hybridization in a patient with Hodgkin disease.

The most frequent nonrandom chromosome rearrangements in B-cell non-Hodgkin lymphoma (NHL) is the t(14;18)(q32;q21) found in follicular lymphomas. The t(14;18) in Hodgkin disease (HD) was rarely observed using cytogenetic techniques. Although Southern blot analysis failed to demonstrate the t(14;18), there have been conflicting reports concerning the occurrence of the translocation using polymerase chain reaction (PCR) methods in HD. In some HD tissues, the translocation might be derived from background lymphocytes rather than Hodgkin and Reed-Sternberg (HRS) cells, because B-cells with t(14;18) are regularly generated in normal individuals. However, the cells bearing the translocation have remained unidentified. We describe a patient with HD who showed t(14;18) in hyperdiploid cells using fluorescence in situ hybridization (FISH) and HRS cells which were strongly positive for BCL2 by immunohistochemistry. These findings suggest that HRS cells may have a t(14;18).

[Present telemedicine and its problems in Wakayama Prefecture--from experiences of diagnosing by televised pathology].

The purpose of the telemedicine would be providing advanced medical information for diagnosis and therapy to everyone living in rural districts with proper medical expenses. Telepathology is one of the best solutions for the problem of absolute shortage of number in certified pathological doctors in Wakayama. We employed the computerized microscope (OLMICOSW, Olympus) equipped with remote control system via ISDN, which had a great advantage that pathologists could manipulate the remote microscope and select the appropriate diagnostic field of tissue samples. The telepathology system in Wakayama has produced following results: 1) The system has been well managed by the contract exchanged between the university hospital and a remote hospital. 2) The remote hospital does not need special pathology technician. 3) Official workers in the hospital have deep understanding for the importance of pathological diagnosis through the process on introduction of telepathology system. 4) The telepathology system has improved medical levels in the remote hospital, resulting good contribution to patients and to medical economy of the hospital.

Squamous cell carcinoma arising in a Warthin's tumor.

Warthin's tumor is a well-defined salivary gland neoplasm consisting of epithelial and lymphoid components. However, malignant transformation is extremely rare. Such a patient who developed squamous cell carcinoma within a Warthin's tumor of the parotid gland is described and possible pathogenesis is discussed.

gamma delta T-cell lymphoma: a clinicopathologic study of 6 cases including extrahepatosplenic type.

We report 6 cases of gamma delta T-cell lymphoma (GDTL) among 115 peripheral T-cell lymphomas over a 12-year period. All patients exhibited extranodal lymphomas, comprising 3 hepatosplenic, 1 cutaneous, 1 intestinal, and 1 thyroidal lymphoma. Despite therapies, all but 1 patient died of disease within 16 months of diagnosis. The cytologic features of lymphoma cells in 4 of 5 cases examined were very similar: coarsely reticulated nuclear chromatin, multiple small nucleoli, abundant faintly eosinophilic granular cytoplasm, and focal angiocentric proliferation. All 6 lymphomas showed Cd3+CD4-CD8-/+ phenotype. CD56 was positive in 3 cases, 1 of which was also CD16 positive. Perforin and T-cell intracellular antigen-1 were positive in all 5 cases examined. Southern blot analysis revealed clonal gene rearrangements of the T-cell receptor delta-chain gene in all 5 cases examined. Based on these findings, together with a review of the literature, GDTLs seem to have several common lineage-specific features, although clinical presentation and course of GDTL are heterogeneous.

Acute hepatic failure due to hepatosplenic B-cell non-Hodgkin's lymphoma in a patient infected with hepatitis C virus.

We report a 75-year-old Japanese man infected with hepatitis C virus (HCV) who died of acute hepatic failure due to the hepatic infiltration of B-cell non-Hodgkin's lymphoma (NHL) cells. He suddenly developed jaundice, fatigue, fever, and hepatosplenomegaly during the course of chronic infection with HCV. Postmortem liver necropsy revealed extensive infiltration of lymphoma cells into the liver. Although the association between HCV infection and NHL has recently become a matter of concern, we believe this to be the first reported case of acute hepatic failure caused by hepatic involvement of non-Hodgkin's lymphoma in an HCV-infected patient.

[Molecular genetic diagnostics and prognostic factors in lymphoma].

Recent advances in immunology and molecular biology have made considerable contribution to the diagnosis of lymphoma, which is a neoplasm of the immune system. Molecular diagnosis can be defined as "diagnostic testing directed at markers consisting of nucleotide sequences within DNA and RNA" (See reference 9.). The examination is now routinely applied to lymphoma diagnosis to identify the clonality, to estimate the cell of origin and normal counterpart, to investigate the etiology and pathogenesis including tumor progression, to detect minimal residual disease, and to evaluate the patient's prognosis. By this testing, oncologists and pathologists can obtain much important information for more objective diagnosis and appropriate management of patients with lymphomas. Although conventional examinations, such as histology, immunohistochemistry, and cytogenetics, are still required for selection of molecular genetic examinations and accurate interpretation of the results, they are undoubtedly a powerful tool for lymphoma diagnostics.

Detection of Epstein-Barr virus transcripts in anaplastic large-cell lymphomas by mRNA in situ hybridization.

Anaplastic large-cell lymphoma (ALCL) is a recently proposed subset of non-Hodgkin's lymphoma. To determine whether Epstein-Barr virus (EBV) is associated with this lymphoma, we performed mRNA in situ hybridization on seven cases of ALCL using a probe consisting of an RNA sequence complementary to the transcripts of BamHIW fragment of the EBV genome. We detected BamHIW transcripts of EBV in the majority of atypical large cells of all cases of ALCL, but in none of three cases of lymphoblastic and small lymphocytic lymphomas. Furthermore, we detected latent membrane protein-1 (LMP1) in two cases of ALCL by means of immunofluorescence and immunoperoxidase stainings. These findings suggest that EBV is involved in the neoplastic transformation for ALCL as in the case of Hodgkin's disease, which shares several clinicopathologic features with ALCL.

[Currently available classifications of lymphoid neoplasia and their clinical applicability].

Controversy and confusion in the classification of lymphoid neoplasia have long been sources of frustration as exemplifed by the statement of Rupert A. Willis in 1948, that "Nowhere in pathology has a chaos of names so clouded clear concept as in the subject of lymphoid tumors." Taxonomically, "Classifications are theories about the basis of natural order, not dull catalogues compiled only to avoid chaos." (Stephen J. Gould, 1989), but this definition can not always be applicable to the classifications of human diseases, even though they themselves are also biologic phenomena. The International Lymphoma Study Group has recently proposed "a revised European-American classification of lymphoid neoplasms", which has again resulted in the time of "the great debate". The major purpose of this article is, therefore, to assess the above classification.