Nodular lymphocyte predominant Hodgkin's lymphoma in daily practice: A multicenter experience

Nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) is a rare subtype of Hodgkin's lymphoma. In this study, we aimed to investigate the clinical features and therapeutic outcomes of patients with NLPHL who were diagnosed at different institutes in Turkey. We retrospectively reviewed the records of the patients diagnosed with NLPHL. Adult patients who were diagnosed after 2005 with histological confirmation were selected for the study. Forty‐three patients were included in the study. Median age of patients was 37.5 years (18‐70) at the time of diagnosis. About 60.5% patients were diagnosed as stage I and II NLPHL, and remaining 39.5% had stage III and IV disease. Median follow‐up was 46 months. During follow‐up, none of the patients died. Seven patients relapsed or progressed after initial therapy at a median of 12 months. Five of 7 relapsed/refractory patients (71.4%) were salvaged with chemotherapy only (DHAP, ICE), and the remaining 2 (28.6%) were salvaged with chemoimmunotherapy. All of relapsed/refractory patients were able to achieve complete remission after salvage therapy. Lactate dehydrogenase levels were significantly higher in patients with progressive disease compared with nonprogressive disease. Our study showed an excellent outcome with all patients alive at last contact with a median follow up of 46 months despite a wide range of different therapeutic approaches. All relapsed and refractory patients were successfully salvaged despite a low frequency of patients received immunotherapy in conjunction with chemotherapy. Our results suggest that immunotherapy may be reserved for further relapses.     

Diffuse large B-cell lymphoma arising in nodular lymphocyte predominant Hodgkin lymphoma: a report of 21 cases from the Nebraska Lymphoma Study Group

We sought to investigate the clinical characteristics and pathologic features and survival outcome of patients with diffuse large B-cell lymphoma (DLBCL) arising in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), since controversy regarding their prognosis exists in the literature. Twenty-one patients with DLBCL arising either concurrently with (n = 7) or subsequent to (n = 14) a diagnosis of NLPHL were identified in the Nebraska Lymphoma Study Group Registry. The clinical and pathologic features of the cases were evaluated, and survival analysis was performed from the time of diagnosis of DLBCL. The median time to the development of DLBCL in those with prior NLPHL was only one year (range, 0.5 - 24 years). The median age of the patients at the time of diagnosis of DLBCL was 46 years (range, 18 - 72 years) and the male to female ratio was 17 : 4. Ten patients presented with nodal DLBCL only, 6 patients presented with both nodal and extranodal involvement, and 5 patients presented with only extranodal DLBCL. Eleven patients had limited stage (I/II) disease and 10 had advanced stage (III/IV) disease. The median overall survival (OS) and failure-free survival (FFS) of the entire group was 35 months and 11 months, respectively, and the predicted 5-year OS and FFS was 31% and 18%, respectively. There were no significant differences in the survival outcomes between patients with DLBCL arising in NLPHL and age- and sex- matched patients with de novo DLBCL. Our findings suggest that patients with DLBCL arising in NLPHL have a prognosis similar to those with de novo DLBCL and should be treated aggressively.     

Does “in situ lymphoma” occur as a distinct step in the development of nodular lymphocyte‐predominant Hodgkin lymphoma?

The concept of in situ neoplasia, already well acknowledged in epithelial tumors, has now been extended to lymphoid neoplasms. Among germinal center (GC)-derived lymphomas, a type of "in situ follicular lymphoma (FL)" has been described in which cells that strongly express BCL2 are observed in histologically abnormal follicles. In this commentary, the author suggests that another GC-derived lymphoma, ie, nodular lymphocyte-predominant Hodgkin lymphoma with a micronodular pattern in which small GCs or broken-up GCs are present within nodules, may be regarded as an early lesion limited to GC. Like "in situ FL," this is likely to be an in situ step that potentially leads to overt lymphoma.     

Resection alone in 58 children with limited stage, lymphocyte-predominant Hodgkin lymphoma-experience from the European network group on pediatric Hodgkin lymphoma

BACKGROUND: Lymphocyte-predominant Hodgkin lymphoma (LPHL) is a rare, CD20-positive, good prognostic lymphoma in children. Patients with early-stage LPHL who underwent successful surgical lymph node resection alone have been reported. To clarify the optimum treatment strategy in children, European study groups were asked to report their experience of surgery alone used in the treatment of pediatric LPHL. METHODS: Data from 58 patients were collected by the French Society for Pediatric Cancers, the German-Austrian Pediatric Study Group/German Society of Pediatric Oncology and Hematology (Germany), and the Children's Cancer and Leukaemia Group (United Kingdom). In total, there were 50 boys and 8 girls, and the median age was 11 years (age range, 4-17 years). Fifty-four patients had stage IA disease, 2 patients had stage IIA disease, and 2 patients had stage IIIA disease. RESULTS: With a median follow-up of 43 months (range, 2-202 months), the overall survival rate was 100%, and the progression-free survival (PFS) rate was 57%. Fifty-one of 58 patients achieved complete remission (CR) after surgery. In the CR group, the overall PFS rate was 67% (95% confidence interval, 51-82%). All seven patients who had residual disease after initial surgery developed recurrences (P = .003). Among 18 patients with stage IA LPHL who developed recurrent disease, 11 patients had local recurrences, and 7 patients recurred in stage IIA. One patient with stage IIIA disease presented with high-grade B-cell non-Hodgkin lymphoma at 10 years of follow-up. CONCLUSIONS: When complete resection was achieved, a substantial proportion of patients with surgically treated, early-stage LPHL experienced long-term remission and actually may have been cured.     

Nodular Lymphocyte Predominant Hodgkin Lymphoma

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare subtype of HL with unique clinicopathologic features. The hallmark histologic feature is the presence of malignant LP cells, unusual CD20⁺CD15^?CD30^? variants of Reed‐Sternberg cells, embedded within a nodular pattern of infiltrating lymphocytes. Compared with classical HL, NLPHL shows a slightly older median age at presentation (30–40 years), greater male predominance (3:1), less mediastinal involvement (<15%), and lower occurrence of classical HL risk factors. The differential diagnosis includes progressive transformation of germinal centers, lymphocyte‐rich classical HL, and T‐cell/histiocyte‐rich large B‐cell lymphoma, the latter of which may share a common biologic relationship. The vast majority of patients present with limited stage disease (70%–80%), the standard treatment for which is involved field radiotherapy at 30–36 Gy. Response rates to primary therapy exceed 90%, although relapses are common and may occur years after the initial diagnosis. Secondary malignancies, particularly non‐Hodgkin lymphoma, may also occur at a frequency similar to that of relapsed NLPHL. Patients with advanced stage disease may have lower response rates and overall survival times than those with limited stage disease. For relapsed disease, treatment options include the salvage therapies used in classical HL, and rituximab.     

Familial nodular lymphocyte predominant Hodgkin lymphoma: Successful treatment with CHOP plus rituximab

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare tumor type distinct from classical Hodgkin lymphoma and its familial form is unusual. The two cases (mother at age 48 and son at age 30 years) of NLPHL in advanced clinical stage are described. The patients were successfully treated with an immunochemotherapy schedule consisting CHOP plus rituximab (CHOP-R). This chemotherapy was well tolerated and the patients reached complete remission. These remissions were for 34 and 40 months for mother and son, respectively. In patients with NLPHL, CHOP-R regimen should be used as an alternative treatment regimen to obtain a good long-lasting response without any adverse events.     

Primary nodular lymphocyte predominant Hodgkin lymphoma of the palate: A rare incidence which was also associated with progressive transformation of germinal centres of cervical lymph node

Primary manifestation of nodular lymphocyte predominant Hodgkin lymphoma in oral cavity is very rare. We are describing such a case which was associated with progressive transformation of germinal centres in a cervical lymph node.     

Macrophages in T cell/histiocyte rich large B cell lymphoma strongly express metal‐binding proteins and show a bi‐activated phenotype

Abundant macrophage infiltration in tumors often correlates with a poor prognosis. T cell/histiocyte rich large B cell lymphoma (THRLBCL) is a distinct aggressive B cell lymphoma entity showing a high macrophage content. To further elucidate the role of tumor‐associated macrophages in THRLBCL, we performed gene expression profiling of microdissected histiocyte subsets of THRLBCL, nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), Piringer lymphadenitis, sarcoidosis, nonspecific lymphadenitis and monocytes from peripheral blood. In a supervised principal component analysis, histiocytes from THRLBCL were most closely related to epithelioid cells from NLPHL, with both types of cells expressing genes related to proinflammatory and regulatory macrophage activity. Moreover, histiocytes from THRLBCL strongly expressed metal‐binding proteins like MT2A, by which histiocytes of THRLBCL can be distinguished from the other histiocyte subsets investigated. Interestingly, the validation at the protein level showed a strong expression of TXN, CXCL9, MT2A and SOD2 not only in macrophages of THRLBCL but also in the tumor cells of NLPHL and classical Hodgkin lymphoma (cHL). Overall, the present findings indicate that macrophages in the microenvironment of THRLBCL have acquired a distinct gene expression pattern that is characterized by a mixed M1/M2 phenotype and a strong expression of several metal binding proteins. The microenvironments in NLPHL and THRLBCL appear to have a similar influence on the macrophage phenotype. The high expression of metal binding proteins in histiocytes of THRLBCL may be diagnostically useful, but a potential pathophysiological role remains to be identified.     

T-cell/histiocyte-rich B-cell lymphoma: Clinical presentation, management and prognostic factors: report on 61 patients and review of literature

T-cell/histiocyte-rich B-cell lymphoma (TC/HRBCL) is a rare subtype of diffuse large B-cell non-Hodgkin's lymphoma (DLBCL) with characteristic morphologic and immunophenotypic features, often misdiagnosed as Hodgkin's lymphoma and peripheral T-cell lymphoma. Few and conflicting clinical data are available in the literature addressing optimal treatment, prognosis and outcome. We retrospectively reviewed all patients diagnosed and managed at our institution between 1995 and 2004 diagnosed with T-cell-rich-B-cell lymphoma by WHO criteria. Sixty-one patients were identified. Initial pathology was incorrect in 82% of referred cases. The median age was 30 years. Seventy-one patients were males. Stage distribution was I - II in 21 patients, and III - IV in 40. Fifty-two percent of patients (32) had splenic involvement and thirty-seven patients (61%) presented with extranodal disease (22 ≥ 2 sites). The International Prognostic Index (IPI) score was ≥2 in 62% of patients. All 59 newly diagnosed TC/HRBCL patients were treated with CHOP or R-CHOP combination chemotherapy +/- radiation therapy. The overall response rate was 85% and nine patients progressed on therapy. Fourteen patients relapsed with a median time of relapse of 6 months (range, 2 - 28). At a median follow-up of 22 months (range 1 - 132); 32 patients (52%) are alive with no evidence of disease. The 5-year overall survival and event free survival rates were 46% and 39% respectively. To conclude, TC/HRBCL is difficult to recognize without immunohistochemistry. It has an aggressive course and poor outcome; with most of patients presenting with advanced disease stage together with high IPI score. Treatment outcome seems to be similar to IPI matched DLBCL counterpart.     

Pretransplantation [18‐F]fluorodeoxyglucose positron emission tomography scan predicts outcome in patients with recurrent Hodgkin lymphoma or aggressive non‐Hodgkin lymphoma undergoing reduced‐intensity conditioning followed by allogeneic stem cell transplantation

BACKGROUND:

The use of positron emission tomography (PET) scanning in Hodgkin lymphoma (HL) and aggressive non‐Hodgkin lymphoma (HG‐NHL) has recognized prognostic value in patients who are receiving chemotherapy or undergoing autologous stem cell transplantation (SCT). In contrast, the role of PET before reduced‐intensity conditioning (RIC) and followed by allogeneic SCT has not been investigated to date.

METHODS:

PET was used to assess 80 patients who had chemosensitive disease (34 patients with HG‐NHL and 46 patients with HL) before they underwent allogeneic SCT: 42 patients had negative PET studies, and 38 patients had positive PET studies. Patients underwent allograft from matched related siblings (n = 41) or alternative donors (n = 39).

RESULTS:

At the time of the last follow‐up, 48 patients were alive (60%), and 32 had died. The 3‐year cumulative incidence of nonrecurrence mortality and disease recurrence was 17% and 40%, respectively. The cumulative incidence of disease recurrence was significantly lower in the PET‐negative patients (25% vs 56%; P = .007), but there was no significant difference between the patients with or without chronic graft‐versus‐host disease (P = .400). The patients who had negative PET studies before undergoing allogenic SCT also had significantly better outcomes in terms of 3‐year overall survival (76% vs 33%; P = .001) and 3‐year progression‐free survival (73% vs 31%; P = .001). On multivariate analysis, overall survival was influenced by PET status (hazard ratio [HR], 3.35), performance status (HR, 5.15), and type of donor (HR, 6.26 for haploidentical vs sibling; HR, 1.94 for matched unrelated donor vs sibling).

CONCLUSIONS:

The current results indicated that PET scanning appears to be an accurate tool for assessing prognosis in patients who are eligible for RIC allografting. Cancer 2010. © 2010 American Cancer Society.     

Bendamustine is effective therapy in patients with rituximab‐refractory,indolent B‐cell non‐Hodgkin lymphoma

BACKGROUND:

Bendamustine hydrochloride is a novel alkylating agent. In this multicenter study, the authors evaluated the efficacy and toxicity of single‐agent bendamustine in patients with rituximab‐refractory, indolent B‐cell lymphoma.

METHODS:

Eligible patients (N = 100, ages 31‐84 years) received bendamustine at a dose of 120 mg/m² by intravenous infusion on Days 1 and 2 every 21 days for 6 to 8 cycles. Histologies included follicular (62%), small lymphocytic (21%), and marginal zone (16%) lymphomas. Patients had received a median of 2 previous regimens (range, 0‐6 previous regimens), and 36%were refractory to their most recent chemotherapy regimen. Primary endpoints included overall response rate (ORR) and duration of response (DOR). Secondary endpoints were safety and progression‐free survival (PFS).

RESULTS:

An ORR of 75% (a 14% complete response rate, a 3% unconfirmed complete response rate, and a 58% partial response rate) was observed. The median DOR was 9.2 months, and median PFS was 9.3 months. Six deaths were considered to be possibly treatment related. Grade 3 or 4 (determined using National Cancer Institute Common Toxicity Criteria [version 3.0.19]. reversible hematologic toxicities included neutropenia (61%), thrombocytopenia (25%), and anemia (10%). The most frequent nonhematologic adverse events (any grade) included nausea (77%), infection (69%), fatigue (64%), diarrhea (42%), vomiting (40%), pyrexia (36%), constipation (31%), and anorexia (24%).

CONCLUSIONS:

Single‐agent bendamustine produced a high rate of objective responses with acceptable toxicity in patients with recurrent, rituximab‐refractory indolent B‐cell lymphoma. Cancer 2010. © 2010 American Cancer Society.     

结节性淋巴细胞为主型霍奇金淋巴瘤和富于T细胞和(或)组织细胞的B细胞淋巴瘤的鉴别诊断

目的 探讨结节性淋巴细胞为主型霍奇金淋巴瘤（NLPHL）和富于T细胞和（或）组织细胞的B细胞淋巴瘤（TCRBCL）的鉴别诊断。方法 按照WHO淋巴瘤新分类法,对15例NLPHL和16例TCRBCL的组织学和免疫表型进行分析,并分别对其中3例NLPHL和4例TCRBCL进行了EBERl／2原位杂交和IgH基因重排检测。结果 组织学上,NLPHL和TCRBCL均表现为小淋巴细胞背景中散在分布的肿瘤性大细胞。NLPHL的肿瘤性大细胞形态特征以L＆H细胞（即爆米花细胞）为主,TCRBCL的肿瘤性大细胞以中心母细胞类型为主,两者都可伴有其他变异形态。免疫表型上,NLPHL和TCRBCL的肿瘤性大细胞都呈CD20、CD79a、bcl-6和EMA阳性,CD3、CD45RO、CDl5和CD30阴性,背景小淋巴细胞以T淋巴细胞为主。但在NLPHL中,CD57阳性细胞明显多于TIA-1阳性细胞,小B淋巴细胞呈小灶状或弥漫散在分布;而在TCRBCL中,TIA-1阳性细胞明显多于CD57阳性细胞,小B淋巴细胞非常稀少。CD21检测显示,NLPHL的结节呈CD21阳性滤泡树突细胞（FDC）网架结构,而TCRBCL以及NLPHL的弥漫类型或弥漫区域中,FDC网架缺乏。NLPHL和TCRBCL都呈EBER1／2阴性,IgH基因重排可检测到80～120bp的单克隆条带。结论 NLPHL和TCRBCL有组织学和免疫表型特征的相似性,诊断和鉴别诊断必须结合形态学和瘤细胞、背景细胞的免疫表型特征。