How to Diagnose and Treat CD5-Positive Lymphomas Involving the Spleen

Patients with CD5-expressing lymphomas presenting with splenomegaly are frequently diagnosed with chronic lymphocytic leukemia. The most important differential diagnosis is mantle cell lymphoma, both in its classical and leukemic, non-nodal forms, given its prognostic and therapeutic implications. Other small B-cell neoplasms that frequently involve the spleen and occasionally express CD5 include the splenic marginal zone lymphoma, hairy cell leukemia and, rarely, lymphoplasmacytic lymphoma. The frequency of CD5 positivity depends in part on the sensitivity of the detection methods employed. Usually, a combination of morphological, immunophenotypic and molecular findings allows for a precise sub-classification of CD5-positive, low-grade B-cell lymphomas of the spleen. Some of these tumors may display a mixture of small and larger B cells, raising the possibility of more aggressive lymphomas, such as diffuse large B-cell lymphomas (DLBCL). Approximately 5–10% of DLBCL are CD5-positive and some may manifest as primary splenic lesions. When available, the morphology of DLBCL in the splenic tissue is distinctive and a leukemic picture is very rare. In conclusion, the appropriate morphological and clinical context assisted by flow cytometry panels and/or immunohistochemistry allows the differential diagnosis of CD5-positive, non-Hodgkin, B-cell lymphomas involving the spleen.     

Flow cytometry in the diagnosis of mediastinal tumors with emphasis on differentiating thymocytes from precursor T-lymphoblastic lymphoma/leukemia

Flow cytometry (FC) has become the routine technique in the evaluation of hematopoietic neoplasms. Since the anterior mediastinum is a frequent site of involvement by both primary and secondary lymphoma/leukemia, flow cytometry plays an important role in the evaluation of mediastinal masses. The present study reviews 100 flow cytometry cases from patients presenting with mediastinal lesions. In 5 cases (5%) flow cytometry was not diagnostic due to either insufficient cell yield or low viability. In the remaining cases (95/100) cell suspensions were adequate for flow cytometry evaluation. Results showed that in 31/32 (96.8%), 2/3 (66.7%), 7/9 (77.8%), 7/8 (87.5%) and 11/11 (100%) cases of B-cell lymphoma, T-cell lymphoma, carcinoma, T-ALL/LBL and thymoma/thymic hyperplasia, respectively, the diagnosis could be reached by flow cytometry alone. Excluding HL, the general sensitivity of FC in diagnosing mediastinal tumors was ∼92%. Among the 100 cases, flow cytometry gave non-informative results in 3 cases of diffuse large B-cell lymphoma, 1 case of peripheral T-cell lymphoma, and 3 cases of carcinoma. No false positive results were encountered. The phenotypic pattern, especially surface CD3 expression versus forward scatter, reliably discriminated between immature thymocytes from thymoma/thymic hyperplasia from T-ALL/LBL. Flow methodology has the advantage of rapid turn-around time as well as high sensitivity, enabling patients with large anterior mediastinal masses and/or superior vena cava syndrome to begin treatment as promptly as possible. In experienced hands, flow cytometry plays a valuable and complementary role to histology and immunohistochemistry in diagnosing mediastinal tumors.     

Peripheral T-cell lymphoma

Since the discovery of human T-cell leukemia virus type 1 (HTLV-1) in patients with adult T-cell leukemia/lymphoma (ATLL), malignant neoplasms of mature (peripheral) T lymphocytes have attracted a great deal of attention. This type of neoplasm is more common in Japan than in Western countries, and may show distinct clinical pictures such as hypergammaglobulinemia, hypercalcemia, etc. T-cell lymphomas are more prone than B-cell lymphomas to become leukemic. Because of a marked intermingling of reactive cells (histiocytes, eosinophils, etc.), the histologic diagnosis of T-cell lymphoma is often difficult. Proliferation pattern and cellular size do not correlate with prognosis as in B-cell lymphoma. Since T-cell lymphomas often manifest with several distinct clinicopathologic settings, their categorization should be based on several parameters, such as the presence or absence of ATLL-associated antigen in serum, histology, phenotype of the neoplastic cell, and clinical features. Since a classification for T-cell lymphomas has not been established, a further multi-disciplinary approach is necessary for a better understanding of this interesting neoplasm.     

2008年版"世界卫生组织造血及淋巴组织肿瘤分类"指要

 2008年第4版"世界卫生组织造血及淋巴组织肿瘤分类"把该类肿瘤分列为12个项目,对分子生物学进展结合较多,基因、染色体改变均加入分类中。慢性骨髓增生性疾病改为骨髓增生性肿瘤,并将肥大细胞增多症（mastocytosis）归于此栏中。新增了伴有嗜酸细胞增多的髓系及淋巴细胞系恶性肿瘤及异常的PDDFRA、PDDFRB或FGFR1基因一栏。在骨髓增生异常综合征／骨髓增生性肿瘤（MDS／MPN）一栏中增加了伴环形铁粒幼细胞再生障碍性贫血并显著的血小板增多（RARS-T）（可能为一单独性疾病）。在骨髓增生异常综合征（MDS）一栏中分为一系或多系增生异常伴有一系或多系血细胞减少,并增添了儿童MDS。在急性髓系白血病及其有关前体细胞恶性肿瘤中,把髓系肉瘤（myeloid sarcoma）单独分类;新增加了唐氏综合征（Down syndrome）伴有的髓系增生疾病;新增加了母细胞性浆细胞样树突细胞肿瘤（blastic plasmacytoid dendretic cell neoplasm）。把系列不明的白血病（acute leukemia of ambiguous lineage）单列为一个项目,含6种白血病。在前体淋巴系肿瘤中分为B系及T系,淋巴母细胞性白血病／淋巴母细胞性淋巴瘤,其区别点在于骨髓中淋巴母细胞＞25 %,则诊断为淋巴细胞白血病[和急性髓系白血病（AML）不同,不设下限为20 %]。成熟B淋巴细胞系肿瘤分为39种,包括慢性淋巴细胞白血病、骨髓瘤、重链病、Burkitt淋巴瘤等,但不包括移植后淋巴细胞增生性疾病（PTLD）。成熟T淋巴细胞系和NK细胞系肿瘤栏目下列举了22种成熟T淋巴细胞系和NK细胞系恶性肿瘤。霍奇金淋巴瘤栏目下列举了6种霍奇金淋巴瘤。组织细胞和树突状细胞恶性肿瘤包括7种恶性肿瘤及播散性幼年型黄肉芽肿。移植后淋巴细胞增生性疾病（PTLD）被单独分类在一个栏目中,又分为５种类型。     

Targeted therapies in T-cell malignancies

The World Health Organization (WHO) has classified T-cell malignancies into mature T-cell and natural killer (NK)-cell neoplasms and precursor T-cell lymphoblastic lymphoma/leukemia. Mature T-cell lymphomas, alternatively known as peripheral T-cell lymphomas (PTCLs), are rare diseases with extremely heterogeneous clinicopathologic profiles. Treatment protocols for PTCL are mostly adapted from those used for B-cell lymphomas, but the prognosis is generally worse. More recently, monoclonal antibodies, including alemtuzumab (Campath-1H, anti-CD52) and denileukin diftitox (Ontak, anti-CD25), have been shown to be effective in the treatment of T-prolymphocytic leukemia (T-PLL) and cutaneous T-cell lymphoma. The unique association of human T-cell lymphotropic virus in adult T-cell lymphoma/leukemia has also led to the use of anti-viral agents in this disease with significant improvement in outcome. A number of novel monoclonal antibodies and histone deacetylase inhibitors are also being evaluated. The roles of these targeted therapies as first-line treatment or in combination with conventional chemotherapy and the roles of autologous and allogeneic hematopoietic stem cell transplantation in PTCL need further investigation.     

Molecular analysis of tumor suppressor genes, Rb, p53, p16INK4A, p15INK4B and p14ARF in natural killer cell neoplasms.

Natural killer (NK) cell neoplasms, which are derived from mature or precursor NK cells, are rare diseases and are observed predominantly in Asian countries. We analyzed the status of the Rb, p53, p15INK4B, p16INK4A and p14ARF genes in these diseases by Southern blot, polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and western blot analysis. We used 31 NK cell neoplasms, including four cell lines derived from NK cell neoplasms, 3 myeloid / NK cell precursor acute leukemias, 4 blastic NK cell lymphoma / leukemias, 4 aggressive NK cell leukemia / lymphomas, 4 nasal NK cell lymphomas, and 12 chronic NK lymphocytosis. We found gene amplification of the p53 gene in one nasal NK cell lymphoma, and point mutations of the p53 gene in one blastic NK cell lymphoma / leukemia and one chronic NK lymphocytosis. In addition, homozygous deletions of p15, p16 and p14 genes in 5 out of 31 samples were detected; 3 were from nasal NK cell lymphoma and 2 from blastic NK cell lymphoma / leukemia. Also hemizygous deletion of the Rb gene in one blastic NK cell lymphoma was detected. Rb proteins were highly expressed in one cell line as well as two myeloid / NK cell precursor acute leukemias. In other cell lines, complete loss and an aberrant migration pattern of Rb protein expression were observed. Comparative genomic hybridization suggested that the homozygous deletions of the p15, p16 and p14 were subtle chromosomal deletions and could not be identified by standard karyotyping in some cases. Although the number of cases we analyzed was not large, alterations identified in the Rb, p53, p16, p15 and p14 genes are of significance and might be associated with tumorigenesis in NK cell neoplasms.     

Heterogeneous CD52 expression among hematologic neoplasms: implications for the use of alemtuzumab (CAMPATH-1H).

PURPOSE: CD52 is a GPI-linked glycoprotein expressed by B cells, T cells, monocytes, and macrophages. The humanized monoclonal antibody alemtuzumab (CAMPATH-1H) is specific for CD52 and is Food and Drug Administration - approved for the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL). The utility of CAMPATH in the treatment of other hematologic neoplasms has been explored; however, a comprehensive survey of CD52 expression among a broad spectrum of WHO-defined tumor types has not been completed. EXPERIMENTAL DESIGN: We evaluated 294 hematologic neoplasms for the presence of CD52 using standard immunohistochemical techniques on paraffin-embedded biopsy specimens fixed with formalin, B-Plus, Zenker's acetic acid, or B5-formalin. RESULTS: The vast majority of low-grade B cell lymphoproliferative disorders (CLL/small lymphocytic leukemia, follicular lymphoma, lymphoplasmacytic lymphoma, hairy cell leukemia, and mucosa-associated lymphoid tissue lymphomas) express CD52. In addition, we found that the majority of precursor B cell acute lymphoblastic leukemia/lymphomas express this antigen. In contrast, there is surprising heterogeneity in CD52 expression among more aggressive B cell lymphomas, with 25% of cases of diffuse large B cell lymphoma and Burkitt lymphoma demonstrating no detectable CD52. In addition, the majority of neoplasms of the T cell lineage are negative for the antigen, including most cases of precursor T cell acute lymphoblastic leukemia/lymphoma, anaplastic large cell lymphoma, and peripheral T cell lymphoma, not otherwise specified. Finally, the vast majority of cases of acute myeloid leukemia, Hodgkin lymphoma, and multiple myeloma are negative for CD52 expression. CONCLUSION: In contrast with CLL, the variable expression of CD52 among other hematologic malignancies suggests that target validation on a case-by-case basis will likely be necessary to guide the rational analysis of CAMPATH therapy.     

Practical Utility of the Revised European-American Classification of Lymphoid Neoplasms for Japanese Non-Hodgkin's Lymphomas

A clinicopathological study of 515 non-Hodgkin's lymphoma (NHL) cases was performed using the revised European-American classification of lymphoid neoplasms (REAL classification) in an HTLV1-nonendemic area of Japan. The following characteristics were revealed: 1) frequency of extranodal lymphomas was high (59%) with 79% B-cell lymphomas in this series, while the overall ratio of B:T/NK lineage was 3.7:1; 2) the most common type was the diffuse large B-cell lymphoma (46%), follicle center lymphomas occurred at an incidence lower (15%) than that in European and American populations, and marginal zone B-cell lymphomas accounted for as much as 12%; 3) peripheral T-cell lymphomas were common (19%), with the unspecified type predominant (11%), while adult T-cell lymphomas were present at a level equivalent to that among European and American patients (1%). Clear segregation of survival curves was rated according to cell lineage and B-cell lymphomas had a better prognosis than T/NK-cell lymphomas. Furthermore, new subtypes in the REAL classification, such as marginal zone B-cell and mantle cell lymphomas, exhibited distinct curves. Taken altogether, the REAL classification demonstrated advantages for assessment of Japanese NHL cases.     

Practical utility of the revised European-American classification of lymphoid neoplasms for Japanese non-Hodgkin's lymphomas.

A clinicopathological study of 515 non-Hodgkin's lymphoma (NHL) cases was performed using the revised European-American classification of lymphoid neoplasms (REAL classification) in an HTLV1-nonendemic area of Japan. The following characteristics were revealed: 1) frequency of extranodal lymphomas was high (59%) with 79% B-cell lymphomas in this series, while the overall ratio of B:T/NK lineage was 3.7:1; 2) the most common type was the diffuse large B-cell lymphoma (46%), follicle center lymphomas occurred at an incidence lower (15%) than that in European and American populations, and marginal zone B-cell lymphomas accounted for as much as 12%; 3) peripheral T-cell lymphomas were common (19%), with the unspecified type predominant (11%), while adult T-cell lymphomas were present at a level equivalent to that among European and American patients (1%). Clear segregation of survival curves was rated according to cell lineage and B-cell lymphomas had a better prognosis than T / NK-cell lymphomas. Furthermore, new subtypes in the REAL classification, such as marginal zone B-cell and mantle cell lymphomas, exhibited distinct curves. Taken altogether, the REAL classification demonstrated advantages for assessment of Japanese NHL cases.     

Distribution and prognosis of WHO lymphoma subtypes in Taiwan reveals a low incidence of germinal-center derived tumors

To assess the distribution of lymphomas in Taiwan according to the WHO (World Health Organization) classification, 175 recently diagnosed cases of malignant lymphomas were studied and the clinicopathologic data were analyzed. B-cell lymphomas accounted for 57.1% of cases, T-cell lymphomas 38.9%, and Hodgkin's lymphoma 4%. Extranodal lymphomas predominated (55.4%). The most common subtype of B-cell lymphoma was diffuse large B-cell lymphoma (33.1%). All tumor types believed to be derived from germinal center (GC) B-cells including follicular lymphoma (4.6%), Burkitt lymphoma (1.7%), Hodgkin lymphoma (4.0%), and GC-like diffuse large B-cell lymphoma (as defined by combined expression of bcl-6 and CD10) were rather uncommon as compared to frequencies seen in series from Western countries. The common T-cell lymphomas included nasal and extranasal NK/T cell lymphoma (7.4%), mycosis fungoides (7.4%), and unspecified peripheral T-cell lymphoma (6.9%). Adult T-cell leukemia/lymphoma was very uncommon and accounts for only 0.6%. The proportional increase in T-cell lymphomas that were unrelated to type I human T-cell lymphotropic virus (HTLV-1) may be linked to differential Epstein-Barr virus (EBV) oncogenesis. The survival data revealed that mantle cell lymphoma, NK/T-cell lymphoma, unspecified peripheral T-cell lymphoma, and subcutaneous panniculitis-like T-cell lymphoma had an aggressive course. Our results confirm the utility of the WHO classification scheme for prognostic stratification and further highlight the distinctive distribution pattern of malignant lymphoma in Taiwan including the higher relative incidence of T cell lymphomas and the rarity of germinal center-derived B-cell tumors.     

Fine-needle aspiration biopsy of peripheral T-cell lymphomas. A cytologic and immunophenotypic study of 33 cases

INTRODUCTION: Peripheral T-cell lymphoma (PTCL) accounts for 10-20% of all non-Hodgkin lymphomas in the United States. In this study, the authors reviewed the cytologic and immunophenotypic findings of 33 fine-needle aspirations (FNAs) of PTCL. METHODS: Thirty-three FNAs from 26 patients (12 females and 14 males) with PTCL were identified during 1991-1999. The patients' age ranged from 19 to 96 years. Immunophenotyping was performed in 24 cases by using either flow cytometry (FC; 21 cases) or immunocytochemistry (IC; 3 cases). Follow-up included review of prior or current histology and clinical records. RESULTS: Nine cases were associated with mycosis fungoides, three cases were classified as T-cell chronic lymphocytic leukemia, and two were angioimmunoblastic adenopathy (AILD)-like T-cell lymphoma. The remaining 19 were classified as PTCL, not otherwise specified. The latter consisted of eight mixed cell variant, eight large cell variant, and three anaplastic variant. One of the mixed cell variant and one of the large cell variants contained numerous epithelioid histiocytes (Lennert lymphoma). Thirty (91%) cases had a definitive diagnosis of malignant lymphoma. Twenty-two cases (2 IC and 20 FC) showed a predominant population of T lymphocytes without a monoclonal B-cell population. In addition, FC revealed an aberrant expression of T-cell markers in 13 cases. Two cases were interpreted as "atypical lymphoid population"; one case was an AILD-like T-cell lymphoma, and the other case was PTCL, large cell type. One case initially was interpreted as granulomatous lymphadenitis; subsequent biopsy revealed PTCL, Lennert type. CONCLUSIONS: Peripheral T-cell lymphoma is a heterogeneous group of lesions with diverse cytomorphology. Cytologic analysis and immunophenotyping is an accurate method of diagnosing peripheral T-cell lymphoma.     

Molecular Analysis of Tumor Suppressor Genes, Rb, p53,pl6INK4A, pl5INK4B and p14ARF in Natural Killer Cell Neoplasms

Natural killer (NK) cell neoplasms, which are derived from mature or precursor NK cells, are rare diseases and are observed predominantly in Asian countries. We analyzed the status of the Rb, p53, p15INK4B, p16INK4A and p14ARF genes in these diseases by Southern blot, polymerase chain reaction–single strand conformational polymorphism (PCR–SSCP) and western blot analysis. We used 31 NK cell neoplasms, including four cell lines derived from NK cell neoplasms, 3 myeloid/ NK cell precursor acute leukemias, 4 blastic NK cell lymphoma/leukemias, 4 aggressive NK cell leukemia/lymphomas, 4 nasal NK cell lymphomas, and 12 chronic NK lymphocytosis. We found gene amplification of the p53 gene in one nasal NK cell lymphoma, and point mutations of the p53 gene in one blastic NK cell lymphoma/leukemia and one chronic NK lymphocytosis. In addition, homozygous deletions of pl5,p16 and p14 genes in 5 out of 31 samples were detected; 3 were from nasal NK cell lymphoma and 2 from blastic NK cell lymphoma/leukemia. Also hemizygous deletion of the Kb gene in one blastic NK cell lymphoma was detected. Rb proteins were highly expressed in one cell line as well as two myeloid/NK cell precursor acute leukemias. In other cell lines, complete loss and an aberrant migration pattern of Rb protein expression were observed. Comparative genomic hybridization suggested that the homozygous deletions of the p15, p16 and p14 were subtle chromosomal deletions and could not be identified by standard karyotyping in some cases. Although the number of cases we analyzed was not large, alterations identified in the Rb, p53, p16, p15 and p14 genes are of significance and might be associated with tumorigenesis in NK cell neoplasms     

Combined histologic and molecular features reveal previously unappreciated subsets of lymphoma in AKXD recombinant inbred mice

Hematopoietic neoplasms developing in AKXD recombinant inbred, NFS.V(+) and ICSBP knockout mice were assessed using morphologic, cytologic and molecular criteria that relate these disorders to human lymphoma and leukemia. Lymphoma types included precursor T-cell and B-cell lymphoblastic, small lymphocytic, splenic marginal zone, follicular, and diffuse large cell (DLCL). In addition to previously defined subtypes of DLCL composed of centroblasts or immunoblasts, two additional subtypes are defined here: lymphoblastic lymphoma like (LL) and lymphoma characterized by a histiocytic reaction (HS). DLCL(HS) were distinguished from true histiocytic lymphomas by the presence of clonal Ig gene rearrangements.     

112例淋巴系统恶性肿瘤骨髓免疫表型分析

背景与目的:淋巴细胞白血病和淋巴瘤骨髓侵犯的诊断以细胞形态学为基础,而免疫分型可通过获得肿瘤细胞分化和发育阶段的信息使淋巴系统恶性肿瘤的诊断更为准确,为临床合理治疗和预后判断提供重要的科学依据.本研究应用多参数流式细胞术(flow cytometry,FCM)探讨淋巴细胞白血病和非霍奇金淋巴瘤(non-Hodgkin's lymphoma,NHL)骨髓侵犯的免疫表型特点.方法:收集112例病理确诊NHL并伴骨髓侵犯和淋巴细胞白血病患者的骨髓标本.应用FCM检测肿瘤细胞的免疫表型.结果:45例前驱B淋巴母细胞白血病/淋巴瘤(precursor B lymphoblastic lymphoma/leukemia,B-ALL/LBL)主要表达CD19、CD10、TdT、CD34、HLA-DR和CD20;32例前驱T淋巴母细胞白血病/淋巴瘤(precursor T lymphoblastic lymphoma/leukemia,T-ALL/LBL)主要表达胞内CD3(cytoplasmic CD3,CyCD3)、CD7、CD5、TdT、膜表面CD3(surface CD3,sCD3)和HLA-DR.77例前驱淋巴细胞肿瘤中,28例(36%)有髓系抗原CD13、CD33的表达;9例(20%)B-ALL/LBL病例有CD20与CD34共同表达,28例(87.5%)T-ALL/LBL病例有CyCD3与TdT共同表达.成熟淋巴细胞肿瘤35例,其中17例慢性淋巴细胞白血病/小淋巴细胞淋巴瘤主要表达CD19、CD20、CD5和HLA-DR,并有CD19与CD5共同表达.4例弥漫大B细胞性淋巴瘤主要表达CD19、CD20、CD10和HLA-DR.3例伯基特淋巴瘤主要表达CD19、CD10、CD20、SIgM.1例套细胞淋巴瘤表达CD5、CD19、CD20、HLA-DR.5例外周T细胞淋巴瘤(PTCL)主要表达sCD3、CD5、CD7、CD4或CD8.1例间变性大细胞淋巴瘤主要表达sCD3、HLA-DR.4例NK/T细胞肿瘤表达CD56、HLA-DR,也表达CD7或CD4或CD8.成熟淋巴细胞肿瘤不表达早期抗原如CD34、TdT.成熟淋巴细胞肿瘤可伴有髓系抗原CD13、CD33的表达.结论:淋巴系统恶性肿瘤侵犯骨髓采用形态学结合FCM免疫学分型可获得T、B细胞来源、肿瘤细胞分化阶段和异常抗原表达等参数,有助于临床诊断和微小残留病灶的检测.     

316例淋巴组织肿瘤骨髓细胞形态学的WHO分型观察

目的：观察淋巴系肿瘤在骨髓细胞形态学中的表现,探讨WHO分型有关问题。方法：采用WHO分型方法,对316例伴有骨髓细胞形态学表现异常的淋巴组织肿瘤进行分析。结果：前体B、T淋巴母细胞急性白血病(ALL)占46．6％,外周B淋巴组织肿瘤中慢性淋巴细胞白血病/小淋巴细胞淋巴瘤(CLL／SLL)占18．4％,多发性骨髓瘤(MM)占14．6％,其他恶性淋巴瘤细胞骨髓浸润亦较多见,占12．2％,浸润程度不一。其余比例较少的疾病为Burkitt淋巴瘤／白血病、毛细胞白血病(HCL)、幼稚淋巴细胞白血病(PLL)、浆细胞白血病(PCL)、伴有绒毛淋巴细胞的脾淋巴瘤(SLVL)。B淋巴系肿瘤病例较T淋巴组织肿瘤明显增多。结论：WHO分型以细胞形态学和免疫分型为基础,确定主要分化类型和分化程度,并结合细胞遗传学异常以及特殊的病因学和临床特点综合分类,可能是目前国际上最为合理的分类法。     

Classification of malignant lymphoma

Over the past 30 years different lymphoma classifications were used world-wide. In Europe, the Kiel classification of K. Lennert dominated the scene, it was updated 1988 and 1992. In North America the Working Formulation, primarily designed to be an instrument for translation of one classification into the other, was predominantly used. Both classifications, however, showed little correspondence with each other, which made it difficult to compare the results of randomized clinical trials on both sides of the Atlantic Ocean. In 1994 the Revised European American Lymphoma (R.E.A.L.) classification was proposed by the International Lymphomas Study Group (ILSG). In contrast to the existing classifications it abandoned the grading of malignancies. The ILSG focused on diagnostic reproducibility and on the definition of distinct clinical-pathological lymphoma entities. Similar to the Kiel classification the new classification scheme was based on cell lineage (T- and B-cell origin) and cell differentiation (precursor and mature lymphomas) and included a number of distinct extranodal lymphomas. The new WHO classification is basically identical with the R.E.A.L. scheme and exhibits only minor changes. The WHO classification includes all hematopoietic and lymphoid neoplasms. It represents the first generally accepted classification, providing hematologists and oncologists with a solid diagnostic basis for therapeutic decisions.     

2016 US lymphoid malignancy statistics by World Health Organization subtypes

Collectively, lymphoid neoplasms are the fourth most common cancer and the sixth leading cause of cancer death in the United States. The authors provide contemporary lymphoid neoplasm statistics by subtype based on the 2008 World Health Organization classifications, including the most current US incidence and survival data. Presented for the first time are estimates of the total numbers of US lymphoid neoplasm cases by subtype as well as a detailed evaluation of incidence and survival statistics. In 2016, 136,960 new lymphoid neoplasms are expected. Overall lymphoma incidence rates have declined in recent years, but trends vary by subtype. Precursor lymphoid neoplasm incidence rates increased from 2001 to 2012, particularly for B‐cell neoplasms. Among the mature lymphoid neoplasms, the fastest increase was for plasma cell neoplasms. Rates also increased for mantle cell lymphoma (males), marginal zone lymphoma, hairy cell leukemia, and mycosis fungoides. Like incidence, survival for both mature T‐cell lymphomas and mature B‐cell lymphomas varied by subtype and by race. Patients with peripheral T‐cell lymphomas had among the worst 5‐year relative survival (36%‐56%, depending on race/sex), while those with mycosis fungoides had among the best survival (79%‐92%). For B‐cell lymphomas, 5‐year survival ranged from 83% to 91% for patients with marginal zone lymphoma and from 78% to 92% for those with hairy cell leukemia; but the rates were as low as 47% to 63% for patients with Burkitt lymphoma and 44% to 48% for those with plasma cell neoplasms. In general, black men had the lowest survival across lymphoid malignancy subtypes. These contemporary incidence and survival statistics are useful for developing management strategies for these cancers and can offer clues regarding their etiology. CA Cancer J Clin 2016;66:443–459. © 2016 American Cancer Society .     

Mature B-cell lymphoma/leukemia in children and adolescents: intergroup pathologist consensus with the revised European-American Lymphoma Classification.

Background:The Revised European–American Lymphoma(R.E.A.L.) Classification criteria were evaluated in the internationalprotocol FAB LMB 96 Treatment of Mature B-Cell Lymphoma/Leukemia: A SFOP LMB96/CCG-5961/UKCCSG NHL 9600 Cooperative Study. This includes B-lineagelymphomas: Burkitt's lymphoma (including ALL-L3); high-grade B-cell lymphoma,Burkitt-like; diffuse large B-cell lymphoma (excluding anaplastic large cellKi-1 lymphoma). Patients and methods:Cases were independently reviewed by eighthematopathologists from the three cooperative national groups (two SFOP, twoCCG, four UKCCSG), without prior discussion of classification criteria orguidelines for case rejection. Consensus diagnosis was determined by eachnational cooperative group, and final consensus diagnosis established when atleast two national consensus diagnoses were in agreement, or following groupagreement at a multiheaded microscope. Results:Two hundred eight cases were reviewed, with finalconsensus diagnosis established in two hundred three. The percent agreementof each group's national consensus diagnosis with final consensus diagnosiswas 86%, 86% and 71%. The percent agreement of thegroup's national consensus diagnosis with final consensus diagnosis forBurkitt's and diffuse large B-cell lymphoma were 88% and 80%,respectively, but only 42% for Burkitt-like lymphoma. Conclusions:International panel review of mature B-celllymphoma/leukemia in children and adolescents highlighted difficulties insubclassification, particularly with Burkitt-like, which is a 'provisionalentity' in the R.E.A.L. Classification. The absence of previous discussion ofclassification and guidelines for case rejection may in part explain thediscrepancy between pathologists. These results underline that morphology mayneed to be complemented by other studies, such as molecular genetics andcytogenetics, to discriminate between the mature B-cell lymphomas.     

Low-Grade Primary Splenic CD10-Positive Small B-Cell Lymphoma/Follicular Lymphoma

Primary splenic lymphoma (PSL) is a rare malignancy representing about 1% of all lymphoproliferative disorders, when using a strict definition that allows only involvement of spleen and hilar lymph nodes. In contrast, secondary low-grade B-cell lymphomas in the spleen, such as follicular lymphomas (FL), lymphoplasmacytic lymphoma and chronic lymphocytic leukemia/ small lymphocytic lymphoma, particularly as part of advanced stage disease, are more common. Indolent B cell lymphomas expressing CD10 almost always represent FL, which in its primary splenic form is the focus of this review. Primary splenic follicular lymphoma (PSFL) is exceedingly infrequent. This type of lymphoproliferative disorder is understudied and, in most cases, clinically characterized by splenomegaly or cytopenias related to hypersplenism. The diagnosis requires correlation of histopathology of spleen, blood and/or bone marrow with the correct immunophenotype (determined by flow cytometry and/or immunohistochemistry) and if necessary, additional molecular profiling. Management of this incurable disease is evolving, and splenectomy remains the mainstream treatment for stage I PSFL.