An Asian variant of intravascular large B-cell lymphoma: clinical, pathological and cytogenetic approaches to diffuse large B-cell lymphoma associated with haemophagocytic syndrome

Diffuse large B-cell lymphoma with haemophagocytic syndrome (BCL-HS) has been reported mainly in Asia and is regarded as a distinct variant of intravascular lymphoma (IVL). However, it is unclear whether all cases of BCL-HS fall within the framework of IVL and available clinical information is limited. We analysed 25 cases with BCL-HS, including 11 autopsied cases (median, 66 years; male-female ratio, 1.1:1). The patients presented with fever, anaemia, thrombocytopenia, hepatosplenomegaly, haemophagocytosis, bone marrow invasion, respiratory disturbance and disseminated intravascular coagulopathy, but usually lacked lymphadenopathy, mass formation, neurological abnormalities and skin lesions. The clinical course was aggressive with a median survival of 7 months. The morphological findings were uniform: large lymphoid cells infiltrated vessels and/or sinusoids of the liver, marrow, lung, kidney and other organs. They were positive for CD19, CD20, CD79a and HLA-DR, but negative for CD10, CD23 and CD30. CD5 was positive in five out of 17 cases. Our critical review indicates that BCL-HS is the equivalent of the Asian variant of IVL.     

The addition of rituximab to anthracycline-based chemotherapy significantly improves outcome in 'Western' patients with intravascular large B-cell lymphoma

Some case reports and a Japanese series suggest benefit from the use of rituximab in patients with intravascular large B-cell lymphoma (IVL). Rituximab efficacy was evaluated in Western patients with IVL, comparing outcome of 10 patients treated with rituximab + chemotherapy (R-CT) and of 20 patients treated with chemotherapy alone (CT). There were no significant differences in patients' characteristics between the two subgroups. The addition of rituximab was associated with improved complete remission rate (90% vs. 50%; P = 0.04), event-free survival (3-year: 89% vs. 35%; P = 0.003) and overall survival (3-year: 89% vs. 38%; P = 0.01). In conclusion, rituximab may substantially change the dismal prognosis of IVL.     

A clinicopathological study of 13 cases of intravascular lymphoma: experience in a single institution over a 9-yr period

Intravascular lymphoma (IVL) is a rare type of extranodal lymphoma in which the lymphoma cells proliferate exclusively in lumina of small vessels. Here, we report a clinicopathological study of 13 cases IVL diagnosed at our institution between March 1999 and July 2007, and evaluated the clinical characteristics, usefulness of random skin biopsy and response to chemotherapy containing rituximab. Three of 13 patients were diagnosed at autopsy. The most common clinical features were unexplained fever, neurological deterioration, respiratory failure, and poor performance status. Thrombocytopenia, high serum lactate dehydrogenase and soluble interleukin2 receptor levels were the most common laboratory abnormalities. Adrenal tumor was detected in four cases and pituitary involvement was seen in all three autopsied cases and in two surviving patient by brain magnetic resonance imaging. Bone marrow invasion was seen in all 13 cases by bone marrow smear, and it was subtle in trephine biopsy. Immunohistochemical analyses revealed that CD5 was positive in one-third of the cases. Most of the cases were positive for MUM1/IRF, Bcl-2 and negative for CD10 and BCL-6 indicating the postgerminal center cell origin of this peculiar type of lymphoma. On random skin biopsy, the most recent seven patients were diagnosed promptly and chemotherapy containing rituximab was successfully administered. Patients with IVL exhibit the characteristic clinical and immunophenotypic features cited above and the use of random skin biopsy facilitates prompt diagnosis. Early commencement of chemotherapy containing rituximab appears promising for this peculiar lymphoma. As the recent seven patients were diagnosed by random skin biopsy over the past 13 months, the incidence of IVL is thought to be much higher than generally accepted.     

Intravascular T-cell lymphoma with bowel involvement: case report and literature review

Intravascular lymphoma (IVL) is a rare form of non-Hodgkin lymphoma characterized by massive proliferation of large, neoplastic cells in small- and medium-sized blood vessels. Most cases of IVL are of B-cell immunophenotype; fewer than 15 cases of T-cell IVL have been reported. A 23-year-old male presented with acute abdominal pain, fever, and tender lower abdomen. Pathology at laparotomy revealed infiltration of colonic vessels with large lymphoid cells compatible with IVL. We reviewed all cases of IVL diagnosed at the Queen Elizabeth II Health Sciences Centre in Halifax, Nova Scotia, from August 1992 to August 2002. A literature review was also performed. Five additional cases of IVL were identified at this institution during a 10-year period. Three patients presented with neurological symptoms, and two with abdominal pain. In 4 of 5 cases, patients died of lymphoma within 3 months of presentation; one patient experienced a 10-month remission. While visceral involvement with IVL is common at autopsy, IVL presenting as an acute abdomen in an immunocompetent patient has not previously been described. Among the 15 cases of T-cell IVL reported in the literature, only two occurred in people under age 30. Given the rarity of T-cell IVL, it is remarkable that three cases of T-cell IVL have been diagnosed at our institution during a 10-year period.     

Composite and sequential lymphoma between classical Hodgkin lymphoma and primary mediastinal lymphoma/diffuse large B-cell lymphoma,a clinico-pathological series of 25 cases

Composite and sequential lymphomas involving both classical Hodgkin lymphoma (CHL) and primary mediastinal B-cell lymphoma (PMBCL) are rare phenomena. Beyond the relevant biological interest raised by these cases, treatments and outcome data are poorly covered in the recent literature. This retrospective analysis describes the pathological and clinical characteristics of 10 composite and 15 sequential cases included after a central pathological review. At diagnosis, 70% of the composite lymphomas presented a disseminated and extranodal disease. Among the 15 sequential lymphomas, 12 were CHL at first occurrence and three were PMBCL. Based on their clinical evolution, these sequential lymphomas could be divided into early (i.e., diagnosis of second lymphoma within a year) and late [(i.e., a second lymphoma occurrence occurring after a long period of complete remission]). All composite cases were alive in complete remission after a median follow-up of 34 months. If the early sequential lymphoma presented a particularly poor outcome with a median overall survival shorter than one year, the late cases were efficiently salvaged. Further molecular studies are needed to describe the underlying biology of these rare diseases, possibly representing the extreme of tumour cell plasticity found in grey-zone lymphoma.     

Random skin biopsy and bone marrow biopsy for diagnosis of intravascular large B cell lymphoma

Intravascular lymphoma (IVL) is a rare type of extranodal lymphoma in which the lymphoma cells proliferate exclusively in the lumina of small vessels. The diagnosis of IVL requires histological confirmation. Although random skin biopsy from healthy-appearing skin in patients with suspected IVL appeared to be useful, the sensitivity of this method for the diagnosis of IVL remains unknown. We performed a random skin biopsy from 12 consecutive cases of IVL diagnosed at our institution over the past 4 years and evaluate its relevance of clinical and laboratory characteristics, presence or absence of skin lesions, and bone marrow involvement. All 12 patients were diagnosed antemortem by either random skin biopsy or bone marrow biopsy and treated with rituximab-containing chemotherapy. Random skin biopsy was performed in all 12 patients, and the results were positive in ten patients (83.3%). Erythematous skin lesions were seen in 3 of 12 patients, but biopsy was positive for lymphoma lesion in two patients. Bone marrow invasion was seen in 11 of the 12 patients (91.6%) by bone marrow smear and/or flow cytometric analysis, but was detected in only half of the patients by trephine biopsy. We concluded that random skin biopsy from normal-appearing skin is highly sensitive in the diagnosis of IVL comparable to bone marrow trephine biopsy. It should be performed irrespective of the presence or absence of skin lesions in patients who were suspicious of IVL.     

Presenting features,natural history,and prognostic factors in localized non-Hodgkin's lymphomas: analysis of 117 cases from a single institution

Abstract: Clinical features and prognostic factors were analyzed in a series of 117 patients with localized non-Hodgkin's lymphoma (stage I-II). Median age of the patients was 53 years and 52% were men; 22% had a lymphoma of low-grade histology and one-third presented with extranodal involvement. Eighty percent of the patients achieved a complete response (CR); stage of disease and histology were revealed as the most important factors for response. When analysis was restricted to intermediate/high-grade cases, stage showed a predictive value for response. With a median follow-up of 4.5 years, median overall survival was 12.0 years, with 73% and 62.5% of patients being alive at 5 and 10 years, respectively. Main initial parameters significantly related to a shorter survival were intermediate/high-grade histology, stage II, poor performance status, bulky disease, high serum LDH levels, increased ESR, and advanced International Index. In the multivariate analysis, stage, histology and performance status (PS) were statistically significant. Among intermediate/high-grade lymphoma patients, stage and PS provided prognostic value for survival. Twenty-six patients relapsed after CR; median survival after relapse was 2.7 years. Stage (I vs II) was the only predictive variable for relapse in both the whole series and the intermediate/high-grade subset.     

Extranodal NK/T‐cell lymphoma,nasal type: Clinical features,outcome, and prognostic factors in 101 cases

Objectives

We aimed to define the clinical features, outcome, and prognostic factors for extranodal NK/T‐cell lymphoma (ENKTL) patients in Taiwan.

Methods

We retrospectively reviewed 101 ENKTL patients diagnosed between February 1998 and October 2015.

Results

The median age of 101 patients was 52 years old (range 22‐85); 76.2% of patients were Ann Arbor stage I/II disease. The 5‐year progression‐free survival (PFS) and overall survival (OS) were 49.9% and 54.8%, respectively. Patients with log[EBV‐DNA] ≥ 3.8 and bone marrow hemophagocytosis at diagnosis had inferior PFS and OS. Most stage I/II patients received combined chemoradiotherapy with anthracycline‐containing regimen, with overall response rate of 96.7%, complete response rate 86.9%, 5‐year PFS 65%, and OS 72%. The relapse rate was 29.3% with a short median disease‐free survival of 6.2 months. In advanced stage patients, overall response rate was only 13.6%, with median PFS 2.3 months, and OS 4.8 months. Age ≥ 60 (HR 3.773, 95% CI 1.733‐8.215, P = 0.001) and stage III/IV (HR 7.785, 95% CI 2.312‐26.213, P = 0.001) were unfavorable prognostic factors for PFS and OS by multivariate analyses.

Conclusions

Age ≥ 60 and stage III/IV are independent poor prognostic factors for PFS and OS. Early‐stage ENKTL patients had good response to combined chemoradiotherapy with anthracycline‐containing regimen but with a high relapse rate and short disease‐free survival. Anthracycline‐containing regimen in advanced stage had poor response and dismal outcome.

     

Primary Bone Lymphoma: A 13 Year Retrospective Institutional Analysis in the Chemo-Immunotherapy Era

Primary Lymphoma of bone (PBL) is an uncommon extranodal tumor accounting for 1% of all malignant lymphomas. The incidence of PBL is so rare that many of its aspects remain unknown. We retrospectively analysed our data in order to know clinical characteristics and treatment outcome in Indian population in chemo-immunotherapy era. We identified 49 patients [2007–2019] (median age 52 years) of which, 35 (71.4%) were males. Nearly one-third patients (n = 18; 36.8%) were elderly (Age > 60). The most common histological subtype was DLBCL. Local pain /swelling (n = 23; 47%) and B symptoms (n = 20; 44.4%) was the most common presentation. Spine was the most frequently involved site (n = 25; 51%) followed by pelvis (n = 17; 34.7%). One third patients had poor ECOG-PS ≥ 2, (n = 16; 32.6). More than 50% of the population presented with IPI score ≥ 2 (n = 25; 55.5%). Majority of the patients presented with Ann-Arbor stage IV disease (n = 31; 63.2%). (n = 32; 71.1%) cases received chemotherapy alone and (n = 13; 28.9%) patients were treated in combination with local radiotherapy. R-CHOP was the most common treatment regimen given to patients (n = 43; 95.5%). Overall, three-fourth patients (n = 36; 80%) achieved a complete response. At a median follow-up of 45 ± 2 (range 3–144) months, 4-year OS (Overall Survival) and PFS (Progression free survival) was 83.1% and 74.5%, respectively, using Kaplan–Meier survival curves. Prognostic factors for OS on multivariate analysis were ECOG-PS 0–1 [p = 0.05], age < 60 [p = 0.03] and achievement of CR [p = 0.001]. PBL in India is usually of DLBCL subtype, with spine as the most common site. It has an excellent prognosis in the R-CHOP era. Chemo-immunotherapy with 6 R-CHOP followed by addition of Radiotherapy if partial response appears to provide good outcomes. However, the exact role of radiation still needs to be confirmed.     

老年弥漫性大B细胞淋巴瘤预后因素及治疗分析

目的探讨老年弥漫性大B细胞淋巴瘤（DLBCL）预后因素,不同治疗方案对其生存的影响。方法回顾性分析72例初发老年DLBCL的性别、年龄、临床分期、B症状、ECOG-PS评分、结外病灶、血清LDH水平、血红蛋白水平、IPI评分与预后的相关性,其中可评价的为64例。比较接受3周CHOP方案34例和接受3周R-CHOP方案30例的生存情况。结果老年DLBCL患者中位生存期40．3个月,2年OS率67．43％,3年OS率49．89％。多因素分析显示年龄、ECOG-PS、临床分期、IPI评分是影响老年DLBCL患者预后的独立危险因素（P〈0．05）。CHOP组和R-CHOP组2年及3年OS率差异均有统计学意义,2年OS率（53．3％VS72．1％,P〈0．05）,3年OS率（39．2％VS60．8％,P〈0．05）。结论年龄、ECOG-PS、临床分期、IPI评分是老年DLBCL患者的预后相关因素,R-CHOP方案疗效优于CHOP方案。     

Intravascular large B cell lymphoma: proposed of the strategy for early diagnosis and treatment of patients with rapid deteriorating condition

We summarize our experience and propose methods for early diagnosis and treatment of intravascular large B cell lymphoma (IVL). A total of 16 patients with IVL between 1994 and 2007 were included and analyzed in this study. Predicted survival durations were short until September 2003. However, there have been marked improvement since the introduction of rituximab, and all patients responded to treatment and survived for more than 1 year following diagnosis of IVL. We propose an early clinical diagnostic strategy for starting treatment for IVL patients with quite poor performance status (PS) and in whom time is a limiting factor: (1) age >40 years, (2) fever above 38°C with poor PS (ECOG 2-4), (3) lactate dehydrogenase (LDH) more than twice the upper limit of the normal level and/or sIL2R >5,000 IU/ml in serum, (4) worsening PS and/or elevation of serum LDH on a daily basis, and (5) confirmation of pathological lymphoid cells in peripheral blood or bone marrow smear and/or flow cytometry. Although accurate pathological diagnosis is quite important, time is a limiting factor for most of IVL patients. In such cases, we can start chemotherapy based on early clinical diagnostic strategy with high sensitivity and obtain good clinical outcome.     

Prevalence of Intravascolar Large B-Cell Lymphoma with Bone Marrow Involvement at Initial Presentation

We used immunohistochemical analysis to investigate 146 bone marrow (BM) clot specimens from patients with fever of unknown origin (FUO) (n = 124) or hemophagocytic syndrome (HPS) (n = 22). Intravascular lymphoma (IVL) primarily involving BM was detected in 12 (8.2%) of the 146 patients. Diagnosis was based on the presence of CD20+ and CD79a+ tumor cells confined within the lumina of sinuses and surrounded by CD34+ endothelial cells. Of the 12 IVL cases, 6 were CD5+; of these 6 CD5+ cases, 5 were positive for vimentin. The finding of a considerably high prevalence of IVL tumor cells in BM from patients with FUO or HPS suggests that immunohistochemical examination of BM may be helpful in the diagnosis of IVL in these patients. Vimentin coexpression in CD5+ IVL might be evidence of origin from a subset of prefollicular B-cells.     

Primary early-stage intestinal and colonic non-Hodgkin＇s lymphoma： Clinical features, management, and outcome of 37 patients

AIM: To analyze the clinical features, management, and outcome of treatment of patients with primary intestinal and colonic non-Hodgkin's lymphoma (PICL). METHODS: A retrospective study was performed in 37 patients with early-stage PICL who were treated in our hospital from 1958 to 1998. Their clinical features, management, and outcome were assessed. Prognostic factors for survival were analyzed by univariate analysis using the Kaplan-Meier product-limit method and log-rank test. RESULTS: Twenty-five patients presented with Ann Arbor stage I PICL and 12 with Ann Arbor stage II PICL. Thirty-five patients underwent surgery (including 31 with complete resection), 22 received postoperative chemotherapy or radiotherapy or both. Two patients with rectal tumors underwent biopsy and chemotherapy with or without radiotherapy. The 5- and 10-year overall survival (OS) rates were 51.9% and 44.5%. The corresponding disease-free survival (DFS) rates were 42.4% and 37.7%. In univariate analysis, multiple-modality treatment was associated with a better DFS rate compared to single treatment (P=0.001). While age, tumor size, tumor site, stage, histology, or extent of surgery were not associated with OS and DFS, use of adjuvant chemotherapy significantly improved DFS (P=0.031) for the 31 patients who underwent complete resection. Additional radiotherapy combined with chemotherapy led to a longer survival than chemotherapy alone in six patients with gross residual disease after surgery or biopsy. CONCLUSION: Combined surgery and chemotherapy is recommended for treatment of patients with PICL. Additional radiotherapy is needed to improve the outcome of patients who have gross residual disease after surgery.     

Intravascular large B cell lymphoma diagnosed by senile angioma biopsy

An 82-year-old man without notable medical history was admitted to our hospital following subacute deterioration of apettite, disorientation and strange behavior. There was spasticity of the right extremities without weakness. LDH and serum soluble IL2 receptor antibody levels were elevated, and as well as the protein level and IgG levels in the cerebrospinal fluid. CT scanning of the brain revealed a lesion at the left corona radiata. The patient's level of consciousness was worsening, and follow-up study of the brain showed a new lesion in the left occipital lobe. Intravascular lymphomatosis was therefore suspected. We performed a skin biopsy from two typical senile angiomas. In one of these biopsy specimens, a capillary hemangioma was present in the mid-reticular dermis and it was filled with abnormal B cells. The diagnosis of intravascular B cell lymphoma (IVL) was thus established. IVL is a rare subtype of extranodal diffuse large B cell lymphoma with a poor outcome. However, it is recently thought that if the diagnosis is established early, aggressive chemotherapy increases survival. Senile angioma is a skin eruption that is considered prevalent for the most part in elderly people. If a patient is suspected to have IVL, and there is no appropriate site of biopsy, it might be beneficial to try a skin biopsy aiming at senile angiomas for early diagnosis.     

35岁以下肺癌患者基因突变状态及生存分析

目的 分析35岁以下肺癌患者基因突变状态与预后的关系.方法 对52例<35岁肺癌患者临床资料(年龄、性别、吸烟状态、初发临床表现、影像特点、疾病分期、治疗方案)、表皮生长因子受体(EGFR)突变、棘皮动物微管结合蛋白4-间变性淋巴瘤激酶(EML4-ALK)融合基因突变状态和生存状态进行回顾性分析.结果 52例患者中,女性较多(59.6%),腺癌最为常见(78.8%).47例为非小细胞肺癌,0~ⅢA期17例,ⅢB~Ⅳ30例,其中Ⅳ期27例.22例非小细胞肺癌患者行EGFR和EML4-ALK基因检测,7例(31.8%)EGFR突变阳性,6例(27.3%)EML4-ALK融合基因阳性.ALK阳性患者胸部CT影像表现为单发实质性肿块或结节的患者比例达83.3%,EGFR突变患者初诊即为Ⅳ期的比例达71.4%.50例随访患者的中位生存时间为24.6个月;分期早晚、手术与否、是否有基因突变是影响中位生存时间的主要因素.结论 年龄<35岁的肺癌患者以女性、腺癌、晚期居多;其EGFR、ALK基因突变检出率高于一般肺癌人群,ALK阳性患者胸部CT影像表现以单发实质性肿块或结节多见,EGFR突变患者初诊时大部分已达Ⅳ期;分期较早、行手术治疗、有基因突变等因素提示有较好预后.     

Clinicopathologic features of intravascular large B-cell lymphoma in Japan: review of the special reference to the Asian variant

The Asian variant of intravascular large B-cell lymphoma (IVL) is characterized by hemophagocytic syndrome, i.e. the clinical features include pancytopenia, hepatosplenomegaly, and rarely mass formation. It usually lacks any neurological abnormality or skin lesions, which are typical features of classical IVL. Sixty-seven cases of IVL reported in Japan since 1990 were classified into two groups, and their clinicopathologic features were compared. Forty-five cases of IVL that met the clinical and laboratory criteria for the Asian variant were classified into Group A (average: 66 yr; male: 62%), and 22 cases that did not meet the criteria were classified into Group C (average: 65 yr; male: 73%). Hemophagocytosis was described only in Group A. The positivity rates for bone marrow invasion, fever, hyperbilirubinemia and elevated levels of LDH and CRP were significantly (p = 0.0037, p < 0.0001, p = 0.0428, p = 0.0108 and p = 0.0008, respectively) higher in Group A than in Group C. On the other hand, the positivity rates for neurological abnormality and skin lesions were significantly (p < 0.0001 and p = 0.0011, respectively) higher in Group C than in Group A. Our reassessment of the reported cases of IVL in Japan identified two major categories of IVL: the classical form and the Asian variant.     

Primary gastric non-Hodgkin's lymphoma: a clinicopathological study of 41 patients

Pathological findings in 41 patients (male/female ratio: 1.3/1) with primary localized gastric non-Hodgkin's lymphoma (NHL) were retrospectively studied and correlated with survival. The median observation period after diagnosis was 32 (0–189) months. Nineteen patients were low-grade NHL, all but one B-cell lymphomas of the mucosa-associated lymphoid tissue (MALT) type. Twenty-two patients had primary (n-7) or secondary (n=15) high-grade lymphomas; Musshoff stage IE was found in 29 and II E in 12 cases. The median age at diagnosis was 61 years (range, 26–88 years), and proliferation, measured by the number of mitosis and Ki-67 antigen positivity (MIB-1), was high or moderately high in 24 cases and low in 17 cases. Follicular lymphatic hyperplasia could be found in 25 of 34 evaluable cases, more often in low-grade than in high-grade NHL. Most of the patients were treated by resective surgery and additional ratio- or chemotherapy. Thirteen patients (31%) died (median survival: 10 months), 5 of them within 3 months after surgery owing to postoperative complications. Survival was superior, though not statistically significant, in low-grade lymphomas. Our retrospective anlysis of heterogeneously treated gastric lymphomas reveals that gastric lymphomas, especially of the low-grade MALT type, often remain a localized disease with a good long-term prognosis. Our study confirms previous reports indicating that lymphomas of the MALT type represent a specific clinicopathological entity.     

Infection with Nocardia species: clinical spectrum of disease and species distribution in Madrid,Spain, 1978-2001

Background: Clinical experience with nocardiosis is very limited in European countries. We describe 34 cases of nocardial infection seen at one Spanish teaching hospital. Patients and Methods: A retrospective review of the clinical features and outcome of nocardial infections was conducted during a 24-year period (1978–2001). All cases were confirmed by culture. Results: Predisposing factors included immunosuppression and/or pulmonary disease in 85% of patients; eight cases were related to HIV infection. Most isolates were initially identified as Nocardia asteroides complex (97%). The most common clinical form was pulmonary disease (41%), followed by disseminated (15%), cutaneous (12%), cerebral (9%) and articular disease (3%). A high proportion of patients (20%) had pulmonary colonization. Therapy with sulfonamides, imipenem or amikacin was given to 26 patients and a clinical response was observed in 65%. Overall mortality among patients with nocardial disease was 48% (13/27) but only seven patients (26%) died from nocardiosis. Conclusion: Nocardiosis remains a rare opportunistic infection that appears in immunosuppressed patients. HIV infection has become a common predisposing condition. The species distribution and disease spectrum are similar to those described in other European countries. Although most patients develop active disease, pulmonary colonization might not be as rare as has generally been assumed. Treatment with sulfonamides is usually efffective and many patients may remain free of nocardial disease for a prolonged period. Received: September 15, 2001 · Revision accepted: July 25, 2002 V. Pintado (corresponding author)     

Malignant histiocytosis-like B-cell lymphoma, a distinct pathologic variant of intravascular lymphomatosis: a report of five cases and review of the literature

Malignant histiocytosis (MH)-like B-cell lymphoma (BCL) is a neoplastic proliferation of large B cells clinically characterized by fever, hepatosplenomegaly, haemophagocytosis and abnormal laboratory data, without lymphadenopathy or skin lesions. Interestingly, most cases have been reported in Asian patients, and it is unclear whether MH-like BCL is biologically distinct from conventional large B-cell lymphomas. We report five Japanese patients with MH-like BCL. Biopsied specimens of bone marrow, liver and/or spleen showed infiltration of neoplastic B cells accompanied by haemophagocytosing histiocytes. Lymphoma cells were positive for CD19, CD20 and HLA-DR surface antigens, and negative for CD5 and CD10. In four cases elevated serum levels of interleukin (IL)-6 and the soluble IL-2 receptor isoform were noted, but not IL-1β, IL-2 or tumour necrosis factor-α. Autopsies of two cases were pathologically diagnosed as intravascular lymphomatosis (IVL). Based on these observations, the current and nine previous cases reported as MH-like BCL in Japan were re-evaluated. They appear to form a peculiar variant of IVL, characterized by bone marrow involvement at presentation, haemophagocytic syndrome, and a rapidly aggressive clinical course, but rarely neurological complications or skin lesions. This variant may merit separate consideration because of the problems posed in the initial diagnosis and therapeutic approaches.     

Combined chemotherapy including high-dose methotrexate in KSHV/HHV8-associated primary effusion lymphoma

Primary effusion lymphoma (PEL) is a rare KSHV/HHV8-associated high-grade non-Hodgkin's lymphoma (NHL) of B-cell origin, characterized by serous effusions in body cavities. Most patients are HIV-infected homosexual men with severe immunosuppression and other KSHV/HHV8-associated diseases such as Kaposi's sarcoma (KS). The prognosis is poor with a median survival of less than 6 months in most cohorts. The achievement of a sustained complete remission is rare. High-dose chemotherapy regimens are warranted to improve complete remission rate and survival. Seven patients with AIDS-associated PEL were treated with a combined chemotherapy including high-dose methotrexate followed by leucovorin rescue. In all cases, KSHV/HHV8 sequences were detected in the effusion samples using quantitative PCR assays. Five patients had a pre-existing KS, associated in three cases with multicentric Castleman's disease (MCD). Upon diagnosis, 6 patients received antiretroviral therapy, which was maintained during chemotherapy in 5 of them. At time of analysis, 3 out of 7 patients were in complete remission 18, 26, and 78 months after PEL diagnosis. Three patients died with a progressive PEL at 22, 67, and 153 days after diagnosis, and 1 patient died 9 months after PEL diagnosis with a MCD-associated plasmablastic NHL. Complete remission was obtained in 3 out of 7 patients treated for AIDS-associated PEL with combined chemotherapy containing high-dose methotrexate.