S. Nakamura

Epstein–Barr virus-associated lymphoproliferative disease in non-immunocompromised hosts: a status report and summary of an international meeting, 8–9 September 2008

BACKGROUNDnRecently novel Epstein-Barr virus (EBV) lymphoproliferative diseases (LPDs) have been identified in non-immunocompromised hosts, both in Asia and Western countries. These include aggressive T-cell and NK-cell LPDs often subsumed under the heading of chronic active Epstein-Barr virus (CAEBV) infection and EBV-driven B-cell LPDs mainly affecting the elderly.nnnDESIGNnTo better define the pathogenesis, classification, and treatment of these disorders, participants from Asia, The Americas, Europe, and Australia presented clinical and experimental data at an international meeting.nnnRESULTSnThe term systemic EBV-positive T-cell LPD, as adopted by the WHO classification, is preferred as a pathological classification over CAEBV (the favored clinical term) for those cases that are clonal. The disease has an aggressive clinical course, but may arise in the background of CAEBV. Hydroa vacciniforme (HV) and HV-like lymphoma represent a spectrum of clonal EBV-positive T-cell LPDs, which have a more protracted clinical course; spontaneous regression may occur in adult life. Severe mosquito bite allergy is a related syndrome usually of NK cell origin. Immune senescence in the elderly is associated with both reactive and neoplastic EBV-driven LPDs, including EBV-positive diffuse large B-cell lymphomas.nnnCONCLUSIONnThe participants proposed an international consortium to facilitate further clinical and biological studies of novel EBV-driven LPDs.

Prognostic factors for mature natural killer (NK) cell neoplasms: aggressive NK cell leukemia and extranodal NK cell lymphoma, nasal type

BACKGROUNDnPatients with natural killer (NK) cell neoplasms, aggressive NK cell leukemia (ANKL) and extranodal NK cell lymphoma, nasal type (ENKL), have poor outcome. Both diseases show a spectrum and the boundary of them remains unclear. The purpose of this study is to draw a prognostic model of total NK cell neoplasms.nnnPATIENTS AND METHODSnWe retrospectively analyzed 172 patients (22 with ANKL and 150 with ENKL). The ENKLs consisted of 123 nasal and 27 extranasal (16 cutaneous, 9 hepatosplenic, 1 intestinal and 1 nodal) lymphomas.nnnRESULTSnComplete remission rate for ENKL was 73% in stage I, but 15% in stage IV, which was consistent with that for ANKL (18%). The prognosis of ENKL was better than that of ANKL (median survival 10 versus 1.9 months, P < 0.0001) but was comparable when restricted to stage IV cases (4.0 months, P = 0.16). Multivariate analysis showed that four factors (non-nasal type, stage, performance status and numbers of extranodal involvement) were significant prognostic factors. Using these four variables, an NK prognostic index was successfully constructed. Four-year overall survival of patients with zero, one, two and three or four adverse factors were 55%, 33%, 15% and 6%, respectively.nnnCONCLUSIONnThe current prognostic model successfully stratified patients with NK cell neoplasms with different outcomes.

CD5-positive diffuse large B-cell lymphoma: a retrospective study in 337 patients treated by chemotherapy with or without rituximab

BACKGROUNDnCD5-positive (CD5+) diffuse large B-cell lymphoma (DLBCL) shows poor prognosis and frequent central nervous system (CNS) relapses under anthracycline-containing chemotherapy. The aim of this study was to determine the prognosis and CNS relapse incidence of CD5+ DLBCL in the rituximab era.nnnPATIENTS AND METHODSnWe analyzed 337 patients with CD5+ DLBCL who received chemotherapy with (R-chemotherapy group; n = 184) or without (chemotherapy group; n = 153) rituximab.nnnRESULTSnNo significant difference was found in clinical background comparisons between the two groups. In the R-chemotherapy group, 60% of the patients were older than 65 years at diagnosis. Both the complete response rate and overall survival (OS) were significantly better in the R-chemotherapy group (P = 0.0003 and P = 0.002, respectively). Multivariate analysis confirmed that chemotherapy without rituximab was associated with unfavorable OS. However, the probability of CNS relapse did not differ between the two groups (P = 0.89). The CNS relapse was strongly associated with short OS (P < 0.0001). In the R-chemotherapy group, 83% of patients who experienced CNS relapse had parenchymal disease.nnnCONCLUSIONSnOur results indicate that rituximab improves the OS of patients with CD5+ DLBCL but does not decrease the CNS relapse rate. More effective treatments with CNS prophylaxis are needed for CD5+ DLBCL patients.

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

BACKGROUNDnCD5-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.nnnPATIENTS AND METHODSnThe 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.nnnRESULTSnIn 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%).nnnCONCLUSIONSnFor 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.

Chronic sclerosing pyelitis with an increased number of IgG4-positive plasma cells

IgG4-related disease has been recently described. This disease occurs in various anatomic locations including pancreas, biliary tract, liver, retroperitoneum, kidney, breast, lung, thyroid gland, prostate, salivary gland, lacrimal gland, and lymph node. In this article, we report the first case of IgG4-related disease arising in the renal pelvis. A 49-year-old Japanese woman was found to show left hydronephrosis by a medical checkup. Histological examination of the renal pelvic tumor showed IgG4-related disease. Her postoperative serum IgG4 was elevated, and this was compatible with IgG4-related disease. Systemic examination showed swelling of major and minor salivary glands and the lacrimal glands, and biopsy of the minor salivary gland revealed the finding of IgG4-related disease. Finally, pathologists and clinicians should be aware of the possibility that the renal pelvis may be involved in IgG4-related systemic disease.

Low-grade tubular-mucinous renal neoplasm with neuroendocrine differentiation: a histological, immunohistochemical and ultrastructural study.

Low‐grade tubular‐mucinous renal neoplasm (LGTMRN) was recently established as a distinct carcinoma classification. A 70‐year‐old, female traffic accident victim underwent a detailed examination that disclosed a huge mass in the lower pole of the left kidney. The patient underwent a nephrectomy based on a diagnosis of renal tumor. Macroscopically, the tumor was well demarcated and a whitish color with focal hemorrhage. Histological examination showed that tumor cells proliferated through tubular, trabecular, and solid growth patterns in the mucinous background. Focally, foci of clear cells or the proliferation of spindle cells was also observed. Nuclei were generally round and uniform in size. No abnormal mitotic figures were identified. Immunohistochemically, tumor cells were diffusely positive for AE1/AE3, vimentin and chromogranin A, and focally positive for cytokeratin (CK) 18, CK19, Ulex europaeus agglutinin‐1, epithelial membrane antigen, neuron‐specific enolase (NSE), CD9 and CD57. Ultrastructurally, tumor cells contained a moderate number of mitochondria, rough endoplasmic reticulum and dense‐core granules. No renin granules or glycogen were observed. Microvilli were focally seen. Our results render further evidence that LGTMRN is a distinct entity from the hitherto established renal neoplasms. Foci of clear cells and neuroendocrine differentiation should be added to the histological spectrum of LGTMRN.

Ki-67 is a strong predictor of central nervous system relapse in patients with mantle cell lymphoma (MCL)

BACKGROUNDnCentral nervous system (CNS) relapse is an uncommon but challenging complication in patients with mantle cell lymphoma (MCL). Survival after CNS relapse is extremely poor. Identification of high-risk populations is therefore critical in determining patients who might be candidates for a prophylactic approach.nnnPATIENTS AND METHODSnA total of 608 patients (median age, 67 years; range 22-92) with MCL newly diagnosed between 1994 and 2012 were evaluated. Pretreatment characteristics and treatment regimens were evaluated for their association with CNS relapse by competing risk regression analysis.nnnRESULTSnNone of the patients received intrathecal prophylaxis. Overall, 33 patients (5.4%) experienced CNS relapse during a median follow-up of 42.7 months. Median time from diagnosis to CNS relapse was 20.3 months (range: 2.2-141.3 months). Three-year cumulative incidence of CNS relapse was 5.6% [95% confidence interval (95% CI) 3.7% to 8.0%]. Univariate analysis revealed several risk factors including blastoid variant, leukemic presentation, high-risk MCL International Prognostic Index and high Ki-67 (proliferation marker). Multivariate analyses revealed that Ki-67 ≥ 30 was the only significant risk factor for CNS relapse (hazard ratio: 6.0, 95% CI 1.9-19.4, P = 0.003). Two-year cumulative incidence of CNS relapse in patients with Ki-67 ≥ 30 was 25.4% (95% CI 13.5-39.1), while that in the patients with Ki-67 < 30 was 1.6% (95% CI 0.4-4.2). None of the treatment modalities, including rituximab, high-dose cytarabine, high-dose methotrexate or consolidative autologous stem-cell transplant, were associated with a lower incidence of CNS relapse. Survival after CNS relapse was poor, with median survival time of 8.3 months. There was no significant difference in the survival by the site of CNS involvement.

Chromosomal abnormalities of clear cell renal cell carcinoma : Frequent gain of chromosome 7

Gain of chromosome 7 is well known to be a characteristic abnormality of papillary renal cell carcinoma (RCC). The purpose of the present study was to perform cytogenetic analysis of G‐band karyotype in 16 clear cell RCC obtained from nephrectomy. The age of patients ranged from 50 to 79u2003years and the tumor size in largest dimension ranged from 1.8 to 6.2u2003cm. As a result, the structural abnormality of chromosome 3 was most frequently observed (eight clones). Loss of chromosome 3 and gain of chromosome 7 followed (four clones). Among four clones showing gain of chromosome 7, two were associated with the abnormality of chromosome 3 and the remaining two were devoid of the abnormalities of chromosome 3. In addition, none of all four tumors showing gain of chromosome 7 demonstrated any foci of papillary growth pattern. The present study shows that gain of chromosome 7 is not exclusive to papillary RCC, but it can be found in clear cell RCC as well, and this finding may represent a diagnostic pitfall in distinguishing clear cell RCC from papillary RCC.

Comparison of outcomes between autologous and allogeneic hematopoietic stem cell transplantation for peripheral T-cell lymphomas with central review of pathology

Comparison of outcomes between autologous and allogeneic hematopoietic stem cell transplantation for peripheral T-cell lymphomas with central review of pathology

Immunohistochemical application of D2-40 as basal cell marker in evaluating atypical small acinar proliferation of initial routine prostatic needle biopsy materials.

D2-40 has been recently discovered as a lymphatic endothelial cell marker, and some investigators have found that D2-40 is also expressed in myoepithelial cells of salivary gland or breast. In this study, we evaluated D2-40 expression of basal cells and applied D2-40 immunohistochemistry in the combination of P504S, cytokeratin 5, and p63 for ten lesions with atypical small acinar proliferation (ASAP) in initial prostatic needle biopsy. As a result, D2-40 was expressed in basal cells, lymphatic endothelial cells, and some stromal fibroblasts of normal prostatic tissue. Among ten ASAP lesions, the final diagnosis of seven lesions was resolved by combination immunohistochemistry. D2-40 was comparable to cytokeratin 5 and p63 as a basal cell marker, and there were no lesions that failed to provide an accurate final diagnosis using only D2-40 immunohistochemistry without cytokeratin 5 or p63. However, we found some D2-40-positive stromal fibroblasts or D2-40-positive lumen-collapsed lymphatic vessels neighboring atypical glands. Pathologists should pay attention to avoid recognizing these cells as basal cells. In conclusion, the combination of immunohistochemistry of P504S, cytokeratin 5, p63, and D2-40 may contribute to the accurate diagnosis of ASAP in the initial prostatic needle biopsy.