CD30阳性的大B细胞淋巴瘤临床病理分析

目的探讨CD30阳性的弥漫性LBCL的组织病理形态、免疫表型及临床预后的意义。方法参照WHO2001年恶性淋巴瘤分类,对8例同时表达B细胞抗原及CD30抗原的弥漫性LBCL进行形态学观察、免疫组化标记及临床随访。结果8例弥漫性LBCL免疫组化CD30阳性,阳性反应定位于胞膜,其中2例伴有核旁高尔基区点状阳性,1例合并ALK呈粗大颗粒状胞质阳性,全部表达B系列抗原CD20、CD79α及CD138,2例EBV阴性,2例TIA-1阴性。组织学特征：3例呈窦性生长,2例呈明显的T／null间变性大细胞淋巴瘤的核型改变,3例以普通的中心母细胞性为主。临床以老年患者多见,4例随访4—28个月,1例仍在化疗,3例情况良好,4例失访。结论CD30阳性的弥漫性LBCL具有嗜窦性,间变性或为普通性非间变性的组织细胞形态特征,可合并ALK阳性。     

CD56阳性弥漫性大B细胞淋巴瘤一例

患者男,35岁.2007年3月因颈部肿胀,CT提示胸腺占位考虑恶性淋巴瘤压迫上腔静脉在外院治疗.术前化疗2个周期后行胸腺部位肿瘤切除,术后病理诊断:纵隔肿瘤化疗后大片坏死,残留极少量变性肿瘤组织.手术后又进行瘤床放疗,治疗结束B超及CT检查均未见明显异常.同年9月患者出现腰背部疼痛,CT检查发现后腹膜多发淋巴结肿大,于2007年10月来本院治疗.根据病史考虑纵隔肿瘤术后、放化疗后,后腹膜淋巴结受累,行姑息性放化疗.4个疗程治疗结束后肿瘤明显缩小.2008年3月患者于后腹膜胰头上方出现结节灶(3.4 cm×3.0 cm×3.0 cm),经治疗后无明显改变;同期左下颈部发现直径3.0 cm大小肿块,至2008年9月左颈肿块达6 cm×5 cm×5 cm,行左颈部肿块切取活检.     

Composite diffuse large B-cell lymphoma and CD20-positive peripheral T-cell lymphoma

Composite lymphoma is defined as two or more distinct types of lymphoma in a single anatomical site. Among various combinations, composite B-cell and T-cell non-Hodgkin's lymphomas (CBTL) are very infrequent. Herein we describe a 66-year-old female with CBTL presenting with lymphadenopathy, multiple bone lesions and an epidural tumor. Light microscopic examination of a biopsied cervical node revealed a dual population of lymphoid cells: sheets of large cells admixed with medium-sized cells. The large cells expressed B-cell markers and showed immunoglobulin light chain restriction, consistent with diffuse large B-cell lymphoma (DLBCL). The medium-sized cells were positive for CD20 as well as T-cell markers. Because polymerase chain reaction amplification showed monoclonal rearrangement of the T-cell receptor β chain gene, this population was compatible with peripheral T-cell lymphoma not otherwise specified (PTCL-NOS). We therefore made a diagnosis of composite DLBCL and CD20-positive PTCL-NOS. Complete remission was achieved after six cycles of R-CHOP regimen (rituximab, doxorubicin, vincristine, cyclophosphamide and prednisolone). This is the first report of CD20-positive PTCL-NOS associated with composite lymphoma. Moreover, a literature review of composite DLBCL and PTCL-NOS indicates that this rare clinical entity may be featured by efficacy of systemic chemotherapy in spite of prevalent extranodal lesions.     

ALK阳性的弥漫性大B细胞淋巴瘤

目的 探讨间变性淋巴瘤激酶(ALK)阳性的弥漫性大B细胞淋巴瘤的组织病理形态和免疫组化表达的意义。方法 参照WHO2001年恶性淋巴瘤分类,对222例弥漫性大B细胞淋巴瘤进行形态学观察和免疫组化Polymer两步法标记。结果 6例弥漫性大B细胞淋巴瘤免疫组化ALK阳性表达,阳性反应物质定位于细胞质内,成粗大的颗粒状,1例合并CD30阳性表达,全部表达B系列抗原CD20、CD79α和CD138,4例不表达CD45。组织病理形态：3例为浆母细胞性,2例为免疫母细胞性伴浆细胞样分化,1例为间变性。结论 ALK阳性的弥漫性大B细胞淋巴瘤是组织形态和免疫表型独特的变异类型,与CLTC—ALK基因易位和NPM—ALK融合基因易位有关,其分子遗传学的异质性不同于以往的认识。     

De novo CD5-positive and Richter's syndrome-associated diffuse large B cell lymphomas are genotypically distinct.

Diffuse large B cell lymphomas (DLBLs) represent a heterogeneous collection of aggressive non-Hodgkin's lymphomas that can arise either de novo or as a result of transformation from chronic lymphocytic leukemia, small lymphocytic lymphoma, follicular lymphomas, or lymphomas of mucosa-associated lymphoid tissue. A small percentage of DLBLs express the CD5 antigen. The majority of these cases have evolved from a pre-existing low grade non-Hodgkin's lymphoma (Richter's syndrome). However, we identified and characterized nine CD5-positive DLBLs in which the patients did not have a previous history or concomitant evidence of chronic lymphocytic leukemia, small lymphocytic lymphoma, follicular lymphoma, or mucosa-associated lymphoid tissue-associated non-Hodgkin's lymphoma, suggesting that they arose de novo. All nine cases expressed CD20 and monotypic immunoglobulin, all eight cases examined expressed CD19, CD22 and CD43, eight of the nine cases expressed HLA-DR, and two of eight cases expressed CD11c. None of the cases expressed CD3, CD10, CD11b, CD21, CD23 or CD30. CD5 expression by these cells was found to be identical to that of CD5-positive B cell chronic lymphocytic leukemia by quantitative polymerase chain reaction analysis of CD5 mRNA. These nine de novo CD5-positive DLBLs exhibited clonal immunoglobulin heavy and light chain gene rearrangements but lacked integration of the Epstein-Barr virus genome and structural alterations of the bcl-1, bcl-2, c-myc, H-ras, K-ras, and N-ras proto-oncogenes and the p53 tumor suppressor gene. However, bcl-6 proto-oncogene rearrangement, which is involved in chromosome band 3q27 aberrations, was found in four cases (44.4%). This is comparable with the frequency of bcl-6 gene rearrangement in CD5-negative DLBL. In contrast, bcl-6 gene rearrangement was absent in six cases of DLBL associated with Richter's syndrome. These findings suggest that de novo CD5-positive DLBLs are genotypically similar to CD5-negative DLBLs and may be pathogenetically distinct from the DLBLs associated with Richter's syndrome.     

皮肤原发性CD30阳性间变性大细胞淋巴瘤

目的 探讨皮肤原发性CD30阳性间变性大细胞淋巴瘤（ALCL）的临床及组织病理学特征,为病理诊断和鉴别诊断提供依据。方法 采用组织病理学及免疫组织化学SP法的白细胞共同抗原、CD20、CD30、CD45RO、CD68、上皮膜抗原、细胞角蛋白和HMB45染色对9例皮肤原发性CD30阳性ALCL进行观察。结果 患者年龄31-84岁（平均58.2岁）,男女之比2：1,均以皮肤丘疹或皮下包块就诊。组织形态;瘤细胞体积大,呈多形性、圆形或椭圆形,胞质丰富。核大,核仁明显,核分型象多,常见R-S样细胞和多核巨细胞,CD30阳性,其中6例同时表达CD45RO,非T非B型3例表达,随访：2例因肿瘤转移而死亡,2例肿瘤复发,5例无复发,健在。结论 皮肤原发性CD30阳性ALCL是具有独特形态特点及预后较好的肿瘤,根组织病理特征及CD30阳性,可与其他恶性肿瘤鉴别。     

Analysis of immunoglobulin VH genes in CD10-positive diffuse large B-cell lymphoma

CD10, a proteolytic enzyme seen in germinal center cells and in the majority of follicular lymphomas, is occasionally expressed in diffuse large B-cell lymphomas (DLBCL). To clarify the origin and cellular characteristics of CD10-positive DLBCL, we analyzed 36 de novo cases of DLBCL for somatic mutations of the immunoglobulin heavy chain variable region (VH) genes and for their immunophenotypes. Expression greater than that of grade 2 Bcl-6 was observed in 11 of the 30 CD10-negative cases (37%) and in all six CD10-positive cases (100%; P < 0.05) without expression of CD5, CD23, cyclin D1, CD30 or CD138. The average mutation frequencies of the six CD10-positive and 30 CD10-negative DLBCL were 12.9 and 9.8%, respectively. The range of SM frequencies in CD10-positive DLBCL (9.52-18.06) was distinctly narrower than that observed for CD10-negative DLBCL (0.69-26.89). These findings seem to indicate that CD10-positive DLBCL, originating from germinal center B cells, is a genetically and immunophenotypically more homogeneous group than CD10-negative DLBCL. Furthermore, three extranodal lymphomas, in five of the six CD10-positive DLBCL, showed ongoing mutation, indicating that antigen-driven, high-affinity somatic mutation may play an important role in clonal expansion in CD10-positive DLBCL. All four extranodal cases of the six CD10-positive DLBCL showed ongoing mutation and/or bcl-2/JH rearrangement. This result suggests that the cell origin of extranodal CD10-positive DLBCL may be the same as that of follicular lymphomas.     

Sinusoidal CD30-positive large B-cell lymphoma: a morphologic mimic of anaplastic large cell lymphoma.

Anaplastic large cell lymphoma (ALCL) has been recognized recently as a distinct clinicopathologic entity, restricted to a subset of CD30-positive diffuse large cell lymphomas of T/null lineage. Some of the characteristic features of ALCL, such as CD30 antigen expression and the presence of large pleomorphic lymphoid cells infiltrating lymph node sinuses, can be found rarely in diffuse large B-cell lymphomas. We collected 11 such cases, and their clinical, morphologic, and immunophenotypic features are reviewed. The age of the patients ranged from 36 to 82 years (mean, 63.2 years) with a male to female ratio of 1:1.2. All neoplasms were nodal with a sinusoidal infiltrative pattern, although four neoplasms also had foci of confluent growth. Eight tumors were composed predominantly of large pleomorphic cells with occasional Reed-Sternberg-like cells. The other three tumors had a higher proportion of large monomorphic lymphoid cells. Necrosis and admixed granulocytes were other common features. Immunophenotypically, all cases were positive for CD30 and CD20 or CD79a. All eight cases examined for anaplastic lymphoma kinase-1 immunoreactivity were negative. In situ hybridization for Epstein-Barr virus RNA was performed in eight cases; two were positive. Excluding one consultation case with no available clinical follow-up data, six patients died of the disease within 3 years and one had disease relapse within 1 year. We conclude that an unusual variant of diffuse large B-cell lymphoma can closely mimic ALCL. However, these neoplasms can be distinguished from ALCL by virtue of their B-lineage and lack of anaplastic lymphoma kinase-1 expression. Evidence of Epstein-Barr virus infection can be found in a small subset of these neoplasms.     

A case of diffuse large B‐cell lymphoma transformed from primary duodenal follicular lymphoma

Primary intestinal follicular lymphoma (FL) is a variant of FL characterized by frequent duodenal involvement and a very indolent clinical behavior without therapy. Unlike nodal FL, there have been no reports of histologic transformation (HT) or death attributable to primary intestinal FL. Here, we report the first case of primary duodenal FL showing HT. A Grade 1 FL in the duodenum was incidentally detected in a 73‐year‐old man. A watch‐and‐wait strategy was adopted because the disease was stage IE. Six months later, bone marrow involvement was suspected. The intestinal lesions had not changed during the first year since the initial diagnosis. Sixty‐two months after the initial diagnosis, a biopsy specimen showed diffuse large B‐cell lymphoma (DLBCL). A perforation of the intestine occurred before chemotherapy was started. Partial resection was performed and subsequent chemotherapy was administered. The clone of the initial FL and DLBCL were identical according to PCR analysis, indicating that the primary intestinal FL had transformed into DLBCL. Although HT is rare, it could occur in some patients with primary intestinal FL. Based on this case, it may be necessary to re‐evaluate the clinical watch‐and‐wait strategy for primary intestinal FL in some patients.     

Analysis of the immunoglobulin heavy chain gene variable region of CD5-positive diffuse large B-cell lymphoma.

To clarify the cell origin of CD5+ diffuse large B-cell lymphoma (DLBCL), we analyzed and compared the variable region of the immunoglobulin heavy chain gene (VH gene) in eight cases of CD5+ DLBCL and 23 cases of other CD5+ B-cell neoplasms; 10 cases of chronic lymphocytic leukemia (CLL), one case of small lymphocytic lymphoma, one case of hairy cell leukemia, and 11 cases of mantle cell lymphoma. CD5+ DLBCL were comprised of two cases of de novo lymphoma of nodal origin, five cases of de novo lymphoma of extranodal origin, and one case of Richter transformation. Whereas all cases of mantle cell lymphoma except one showed a germ line or low mutation frequency of the rearranged VH gene, the rearranged VH genes in both CD5+ CLL and CD5+ DLBCL were heterogeneous. The degree of somatic mutation of CD5+ CLL and CD5+ DLBCL ranged between approximately 0 to 15.0% and 0.7 to 12.9%, respectively. High frequency of expression of the VH4 family in both CD5+ CLL and CD5+ DLBCL was found. Moreover, none of the three cases of CD5+ DLBCL examined exhibited intraclonal diversity. These findings may be common characteristics of the rearranged VH gene of CD5+ CLL and CD5+ DLBCL and suggested that the cell origin of CD5+ DLBCL was the same as that of CD5+ CLL.     

CD56-positive large B-cell lymphoma.

CD56 (NCAM), a neural adhesion molecule, is normally expressed on natural killer cells and subsets of T cells and is commonly seen on hematolymphoid neoplasms such as plasma cell myeloma and acute myelogenous leukemia. It is uncommon in B-cell lymphoma. From 2001 to 2003 a cohort of 20 cases of CD56 B-cell lymphomas was identified by flow cytometry (<0.5% of all B-cell lymphomas studied) during a 2-year period. Most (90%) expressed CD10 and 5/5 tested cases were BCL6, suggesting a follicular origin. An extranodal disease presentation was seen in 45% and may be related to CD56 expression. These CD56 B-cell lymphomas may represent a new subset of large B-cell lymphoma. The relationship of cells with this antigenic profile to normal B-cell differentiation is explored.     

Genomic imbalances during transformation from follicular lymphoma to diffuse large B-cell lymphoma.

Follicular lymphoma is commonly transformed to a more aggressive diffuse large B-cell lymphoma (DLBCL). In order to provide molecular characterization of this histological and clinical transformation, comparative genomic hybridization was applied to 23 follicular lymphoma and 35 transformed DLBCL tumors from a total of 30 patients. The results were also compared with our published findings in de novo DLBCL. Copy number changes were detected in 70% of follicular lymphoma and in 97% of transformed DLBCL. In follicular lymphoma, the most common alterations were +18q21 (33%), +Xq25-26 (28%), +1q31-32 (23%), and -17p (23%), whereas transformed DLBCL most frequently exhibited +Xq25-26 (36%), +12q15 (29%), +7pter-q22 (25%), +8q21 (21%), and -6q16-21(25%). Transformed DLBCL showed significantly more alterations as compared to follicular lymphoma (P=0.0001), and the alterations -6q16-21 and +7pter-q22 were only found in transformed DLBCL but not in follicular lymphoma (P=0.02). Alterations involving +13q22 were significantly less frequent, whereas -4q13-21 was more common in transformed as compared to de novo DLBCL (P=0.01 and P=0.02, respectively). Clinical progression from follicular lymphoma to transformed DLBCL is on the genetic level associated with acquisition of increasing number of genomic copy number changes, with non-random involvement of specific target regions. The findings support diverse genetic background between transformed and de novo DLBCL.     

CD138 mRNA expression from peripheral blood of patients with follicular and diffuse large B cell lymphoma: relation to disease progression and treatment response

Syndecans are among those transmembrane PGs which act via their heparan sulphate chains as receptors for different matrix elements (e.g. collagen I–III, fibronectin, thrombospondin, tenascin) and co-receptors for growth factors (e.g. bFGF, aFGF, GM-CSF, IL-3, IFNg). We hypothesized that there is a positive relationship between the expression of syndecan-1 (CD138) and treatment response in non-Hodgkin’s lymphoma. To identify the expression of syndecan-1 (CD138) in cases of non-Hodgkin’s lymphoma and to correlate its expression with treatment response and disease stage, this study was carried out as a cross-sectional study and included 30 patients with non-Hodgkin’s lymphomas attending Suez Canal University Hospital; diagnosis of patients was made by routine histological and immunohistochemical examination. CD138 mRNA expression was assessed by TaqMan technique using real-time PCR method. There was increased expression of CD138 mRNA in patients with follicular lymphoma than in patients with diffuse large B cell lymphoma (6.25 versus 3.46, respectively) (p?≤?0.05). Syndecan-1 (CD138) mRNA expression from peripheral blood may be a useful marker for follicular lymphoma and can be used as a marker of treatment response in patients with follicular and diffuse large B cell lymphoma.     

CD3-positive diffuse large B-cell lymphoma relapses as CD3-negative large B-cell lymphoma: Loss of aberrant antigen expression in B-cell lymphoma after chemotherapy

Aberrant expression of CD3 on diffuse large B-cell lymphoma (DLBCL) is rare, and its mechanism and biological significance are currently unclear. Herein we report a case of Epstein-Barr virus-negative, CD3-positive DLBCL in a 53?year-old male, who had a remote history of renal transplantation. After standard chemotherapy, the patient was in clinical remission. He relapsed three years later, but at this time with apparent loss of CD3 expression. PCR-based IGK gene rearrangement studies demonstrated clonal amplicons with an identical nucleotide size between the primary and secondary DLBCL, confirming the clonal relationship despite their phenotypic differences. To our knowledge, this is the first case of CD3-positive DLBCL that demonstrated a loss of aberrant CD3 on relapse. The chronologic change in phenotype seen in this case suggests that the source of the patient’s lymphoma relapse may arise from either a quiescent subclone without CD3 expression, or from an upstream neoplastic precursor cell.