Castleman病与淋巴瘤相关性研究进展

Castleman病是一种发病机制未明的淋巴组织增生性疾病。近年来有研究发现Castleman病可与淋巴瘤同时或先后诊断,部分淋巴瘤患者的淋巴结也可出现Castleman病样特征的改变,本文旨在对Castleman病与淋巴瘤的相关性及发病机制进行综述。     

Prognostic Significance of Bone Marrow Trephine and Peripheral Blood Smears in 55 Patients with Mantle Cell Lymphoma

Bone marrow trephine and peripheral blood smears taken at diagnosis of 55 cases of well-documented mantle cell lymphomas were reviewed in order to analyse the leukaemic involvement in this non-Hodgkin's lymphoma: its incidence, morphological characteristics and prognostic significance. A median survival of 36 months was found. The median age was 61 and the male to female ratio was 4:1. Morphologically 7 cases presented with a mantle zone pattern, all the others had a diffuse pattern. Involvement of the bone marrow was found in 58% and a trend for prolonged survival in patients with a negative trephine was seen. An absolute lymphocytosis above 10,000 μ1 was found at diagnosis in 5 cases (10%) and had a statistically significant impact on survival. An additional 5 cases developed frank leukaemia during the course of the disease and died within 1 to 6 months of this evolution, suggesting that marked lymphocytosis is more a terminal event associated with an extremely poor prognosis than a presenting symptom. Finally we identified an additional parameter with statistically prognostic significance, namely, the presence of atypical cells in the peripheral blood even in the absence of an increased lymphocytosis.     

Does Kaposi’s sarcoma predict multicentric Castleman disease in the presence of generalized lymphadenopathy?

Multisystemic Castleman disease (MCD) can be associated with HHV8 infection, which involves the mantle zone of follicles. This condition results in an increase number of HHV8-positive (HHV8+) plasmablasts that multiply and amalgamate to form plasmablastic B-cell lymphoma. All previously reported cases of HIV-positive patients with MCD were coinfected with HHV8. Twelve cases of HIV- MCD that are HHV8+ were encountered in the literature, three of them developed lymphoma, and none of those cases were reported to have Kaposi's sarcoma (KS). We report a unique case of HIV-negative elderly woman with preexisting KS that presented to the hospital with recurring nausea, vomiting, and fever, assessment revealed diffuse lymphadenopathy. Axillary lymph node biopsy showed HHV8+ MCD with foci of microlymphoma. Despite the treatment with high-dose steroids, she developed multisystem failure that lead to her death.     

Burkitt transformation of mantle cell lymphoma

The associated poor prognosis and potentially aggressive behavior of mantle cell lymphoma and its blastoid variants make differentiation from other non-Hodgkin B-cell lymphomas especially important. We present a case of mantle cell lymphoma with a marked leukemic component, which demonstrated both a typical nodular mantle cell pattern and Burkitt lymphoma within a single lymph node removed at the time of splenectomy. The presence of CD5, CD10, and Bcl-1 co-expression by immunohistochemistry and detectable t(11;14) and cMYC gene rearrangement by FISH analyses in the Burkitt region support a transformation of mantle cell lymphoma over a concomitant malignancy. A limited number of mantle cell lymphomas demonstrating dual t(11;14) and chromosome 8q24 cMYC gene rearrangements have been previously reported in the literature. They demonstrate an extremely aggressive course with a very poor prognosis. Although the accelerated terminal phase of this patient's clinical course mirrors these previous published cases; none have described the combined morphologic and immunophenotypic features of Burkitt lymphoma reported here. This case provides further support for the aggressive nature of these lymphomas and demonstrates the utility of flow cytometry, immunohistochemistry, and cytogenetic techniques in avoiding potential errors in their diagnosis, prognosis, and treatment.     

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma With Secondary Acquisition of t(11;14)(q13;q32)/CCND1-IGH: A Rare Variant Of Richter Transformation to Mantle Cell Lymphoma

IntroductionChronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) occasionally undergoes Richter transformation, mostly to diffuse large B-cell lymphoma, but its evolution to other types of B-cell lymphoma is rare. We report a CLL evolved to mantle cell lymphoma by acquiring t(11;14)(q13;q32); CCND1-IGH.MethodA Retrospective review of clinical and laboratory data.ResultsA 39-year-old male patient was diagnosed with CLL/SLL, and was initially followed without specific treatment, but subsequently received chlorambucil/fludarabine/rituximab due to exacerbated lymphocytosis. While his CLL/SLL waned and waxed, the immunophenotype and genotype of neoplastic B-cells remained unchanged, without cyclin D1 expression and CCND1-IGH fusion. Eleven years after the diagnosis, the patient's disease showed evidence of progression. Bone marrow examination demonstrated “CLL” with the morphology and immunophenotype similar to those seen in the previous biopsies. Unexpectedly, the neoplastic B-cells demonstrated cyclin D1 expression and harbored t(11;14)(q13;q32); CCND1-IGH, suggesting a clonal evolution to mantle cell lymphoma. He subsequently received cytoreductive chemotherapy followed by allogenic bone marrow transplant and remained in remission since then.ConclusionThe retention of immunophenotype suggests a clonal relationship between CLL/SLL and mantle cell lymphoma. While the acquisition of t(11;14)(q13;q32); CCND1-IGH likely alters the disease course, the pathogenesis of this illegitimate translocation in CLL remains to be studied.     

Mantle zone lymphoma with central nervous system involvement

A 68-year-old man with a 7-year history of lymphocytosis and lymphadenopathy is described. Accelerated disease, indicated by bilateral optic nerve and cerebrospinal fluid involvement, prompted thorough histologic and immunologic assessment. Although initially believed to have chronic lymphocytic leukemia (CLL), results showed mantle zone lymphoma (MZL) with central nervous system (CNS) involvement. The authors believe that this represents the first case of MZL with CNS involvement.     

Diffuse large B-cell lymphomas with plasmablastic differentiation

Recent evidence suggests that diffuse large B-cell lymphoma (DLBCL) with plasmablastic differentiation represents a clinically heterogeneous spectrum with different clinicopathologic characteristics representing distinct entities. Subtypes of DLBCL with plasmablastic features and terminal B-cell differentiation include plasmablastic lymphoma (PBL) of oral mucosa type; PBL with plasmacytic differentiation; primary effusion lymphoma (PEL); KSHV-positive solid lymphoma/extracavitary PEL/HHV-8 associated DLBCL; and DLBCL expressing ALK. In contrast, PBL associated with multicentric Castleman disease, DLBCL with secretory differentiation, pyothorax-associated lymphoma, and atypical Burkitt lymphoma with plasmacytoid differentiation have morphologic appearances of plasma cell differentiation but maintain a mature B-cell (CD20 positive) phenotype. These tumors as well as extramedullary plasmablastic tumors secondary to multiple myeloma or plasmacytomas are included in the differential diagnosis. In this review, we discuss recently described clinicopathologic insights, case observations, and recently reported molecules involved in terminal B-cell or plasma cell differentiation and their possible roles in disease pathogenesis.     

Unicentric Castleman Disease: A Rare Diagnosis of Radiological and Histological Correlation

Castleman disease is an uncommon nonneoplastic, lymphoproliferative disorder of that is associated with lymphadenopathy and nonclonal lymph nodes hyperplasia. It is further subdivided into two types: Unicentric Castleman disease and Multicentric Castleman disease. Unicentric Castleman disease is rare to be reported in patients having AIDS, because HIV infected patients most commonly presented with Multicentric Castleman disease and they mostly coinfected with HHV-8. Herein we reported a rare presentation of Unicentric Castleman disease with hyaline vascular variety evident Histopathologically as a preoperative diagnosis. The patient was initially managed conservatively and surgical excision (excisional biopsy) of the left cervical lymph node was than performed and sent for histopathology. The Immunohistochemistry findings were also consistent with the diagnosis of Castleman disease Hyaline vascular type as evident from left cervical lymph node excisional biopsy.     

CD10和Bcl-6在Castleman病中的表达及其意义

目的 探讨CD10和Bcl-6在Castleman病中的表达及其意义.方法 收集经病理诊断的Castleman病10例,反应性淋巴组织增生13例,滤泡性淋巴瘤13例,其中包括手术切除标本和活检穿刺标本,均应用免疫组织化学染色技术检测各组的CD10和Bcl-6的表达情况.结果 CD10免疫组化染色结果显示,Castleman病与反应性淋巴组织增生差异有统计学意义(P=0.003);Castleman病与滤泡性淋巴瘤差异有统计学意义(P<0.0001).Bcl-6免疫组化染色结果显示,Castleman病与反应性淋巴组织增生及滤泡性淋巴瘤差异均有统计学意义(P<0.0001).结论 CD10和Bcl-6可作为Castleman病的诊断及其与反应性淋巴组织增生和滤泡性淋巴瘤鉴别诊断的免疫学标志物.Castleman病的发病过程可能与Bcl-6基因异常有关;Bcl-6基因异常可能是Castleman病形态学改变的基础.     

An overlapping case of in situ mantle cell neoplasia and leukemic non-nodal mantle cell lymphoma

In situ mantle cell neoplasia (isMCN) and leukemic non-nodal mantle cell lymphoma (nnMCL) are classified as an indolent subtype of mantle cell lymphoma (MCL). The tumor cells of isMCN are restricted to the inner layer of the lymphoid tissue mantle zone, exhibiting an in situ pattern histologically. On the other hand, nnMCL is distributed in the peripheral blood, bone marrow and sometimes the spleen, but lymphadenopathy or systemic organ involvement is rare. We report a case of isMCN in a submandibular lymph node resected from a 65-year-old Japanese male. The tumor cells were positive for cyclin D1 (CCND1) and SOX11 expression, and were restricted to the mantle zone area of the lymph node. However, tumor cells were also detected in the stomach mucosa, bone marrow tissue and peripheral blood, suggesting nnMCL. isMCN and nnMCL may have a partly overlapping disease spectrum, although the correlation between these two subtypes has not been well described. This present case demonstrated characteristics overlapping between isMCN and nnMCL.     

Clinical outcome of incidental pelvic node malignant B-cell lymphomas discovered at the time of radical prostatectomy

Incidental pelvic node malignant B-cell lymphomas diagnosed at the time of radical prostatectomy are rare. Their clinical outcome has not been studied. We studied thirteen such cases with long-term clinical follow-up. Patients were followed between 9 and 94 months after surgery. Of 13 cases, 9 were chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), 3 marginal zone B-cell lymphoma (MZL) and 1 mantle cell lymphoma (MCL). All 13 patients did not receive radiation or chemotherapy; and five of 13 cases showed hematologic evidence of lymphoma progression between 1 and 5 months after radical prostatectomy. After progression, the mantle cell lymphoma patient received aggressive chemotherapy and had systemic dissemination. Two of 13 cases had recurrent prostate carcinoma. None of 13 patients had died from lymphoma or prostate carcinoma at the last follow-up. In conclusion, most incidental pelvic node lymphomas (8/13) showed no evidence of systemic dissemination to peripheral blood or bone marrow after a mean 42.8 weeks of follow-up despite the fact that no additional treatment was given. Strong consideration should be given to withholding further treatment in patients diagnosed with pelvic low-grade B-cell lymphoma at the time of radical prostatectomy until disease progression occurs.     

Mantle cell lymphoma in leukemic phase: characterization of its broad cytologic spectrum with emphasis on the importance of distinction from other chronic lymphoproliferative disorders.

BACKGROUND: Mantle cell lymphoma is a mature, virgin B-cell neoplasm characterized immunologically by a panB+, CD5+, CD23-, cyclin D1+ phenotype and genetically by t(11;14)(q13;q32) with overexpression of the cyclin D1 (bcl-1) gene. It usually presents as advanced stage disease, involving lymph nodes, spleen, bone marrow, and extranodal sites, particularly the gastrointestinal tract. However, frank leukemic presentation with high white cell counts is uncommon and can be difficult to distinguish from other chronic lymphoproliferative disorders. The aim of this study was to characterize the morphologic spectrum of leukemic mantle cell lymphoma. METHODS: During the period July 1994 through October 1998, 14 patients with mantle cell lymphoma in leukemic phase were diagnosed at the Department of Pathology, Queen Elizabeth Hospital, Hong Kong. The diagnosis of mantle cell lymphoma was based on histologic and immunocytochemical findings and was confirmed by cyclin D1 immunoreactivity in all cases. The clinical records and laboratory results were reviewed. Peripheral blood smears, bone marrow, and other tissue biopsies were examined, with particular attention to the cytologic features of the leukemic mantle cells. RESULTS: Mantle cell lymphoma in leukemic phase showed a very aggressive clinical course. Eight patients died at a mean of 13 months, and only 1 patient was disease free. Morphologically, the leukemic mantle cells exhibited a broad morphologic spectrum, with several cytologic patterns identified: 1) mixed small and medium-sized cells, 2) predominantly medium-sized cells, 3) predominantly large cells, and 4) giant cells. Despite variations in the size and nuclear shape, the leukemic mantle cells could usually be recognized by the nuclear irregularity and clefting, moderately dense but evenly distributed chromatin, small nucleoli, and scant cytoplasm. CONCLUSIONS: Recognition of the characteristic cytologic features of leukemic mantle cells can help to distinguish them from other chronic lymphoproliferative disorders. In contrast to the latter, the clinical course is aggressive and response to conventional chemotherapy is poor.     

A Japanese case of human herpes virus-8-associated multicentric castleman disease complicated by hemophagocytic syndrome

We report a Japanese case of human herpes virus-8 (HHV-8)-associated multicentric Castleman disease(MCD) complicated by hemophagocytic syndrome(HPS). A 60-year-old man presented with persistent fever and progressive pancytopenia in June 2004. On physical examination, anemia, icterus, hepatosplenomegaly, and generalized lymphadenopathy were detected. Laboratory findings showed elevated levels of serum ferritin and soluble interleukin-2 receptor. Anti-human immunodeficiency virus (HIV) antibody was negative. Bone marrow aspiration revealed a normocellular marrow with an increased number of hemophagocytic histiocytes. Biopsy of cervical lymph node disclosed pathological features compatible with the plasmablastic variant of Castleman disease. HHV-8 DNA was detected in the specimen from lymph node by polymerase chain reaction. Thus, the diagnosis of HHV-8-associated MCD complicated by HPS was made. The patient was treated with immunotherapy and subsequent chemotherapy. However, he died of bacterial sepsis after one-month therapy. This case report provides some evidence that HHV-8 may be a causative agent of MCD even in HIV-seronegative Japanese patients.     

CT and MRI findings with histopathologic correlation of a unique bilateral orbital mantle cell lymphoma in Graves’ disease: a case report and brief review of literature

Bilateral orbital mantle cell lymphoma is rare. We present an unusual case report of a patient with Graves’ disease and no previous history of lymphoma, who was found to have bilateral orbital mantle cell lymphoma on CT and MR imaging which was confirmed histopathologically. To our knowledge, there have been no previously described cases of bilateral mantle cell lymphoma in Graves’ disease. Of particular radiologic interest, the left orbital mass presented in a bicompartmental fashion with a discreet intraconal component separated by a fat plane from an extraconal component that extended intraconally. In our review of radiologic literature, this presentation has not been described previously.     

Simultaneous presentation of acute monoblastic leukemia and mantle cell lymphoma: case report and review of the literature

This paper reports a 73-year old woman with simultaneous presentation of acute monoblastic leukemia (acute myeloid leukemia (AML), French-American-British (FAB) type M5a) and mantle cell lymphoma. The patient presented with wasting, generalized lymphadenopathy, an extensive infiltrative rash and pancytopenia. Bone marrow and lymph node histopatholology showed extensive infiltration by leukemic monoblasts. Marrow cytogenetics revealed a complex karyotype, including t(8;16)(p11;p13). Flow cytometric immunophenotyping of peripheral blood, lymph node and bone marrow demonstrated two populations, expressing CD5, CD19, CD20 and CD22 and CD45, HLA-DR, CD13, CD33, CD14 and CD38, respectively. A focus of abnormal lymphocytes in the lymph node biopsy demonstrated BCL1 expression and t(11;14)(p11;p13) by fluorescence in situ hybridization and immunoglobulin heavy chain gene rearrangement by the polymerase chain reaction. The patient received infusional cytarabine, daunorubicin and etoposide chemotherapy, with complete remission of both the AML and the mantle cell leukemia. To the authors' knowledge, this is the first report of simultaneous presentations of AML, FAB M5a and mantle cell lymphoma. The case is discussed and the literature is reviewed.     

脾边缘区淋巴瘤伴自身免疫性溶血性贫血1例并文献复习

目的：提高对脾边缘区淋巴瘤(splenic marginal zone lymphoma,SMZL)的认识。方法：详细报告1例典型患者临床及实验室特征,并复习相关文献。结果：SMZL是一少见的原发于脾脏的低度恶性B细胞淋巴瘤。临床以脾脏明显肿大、淋巴细胞增多为特征,易浸润骨髓,可合并自身免疫疾患。肿瘤细胞表达成熟B细胞免疫表型,CD5^-、CD10^-、CD23^-、CD103^-,不表达T细胞相关分化抗原。结论：SMZL起病潜隐,进展缓慢,生存期长,容易漏诊。糖皮质激素和环孢菌素A治疗SMZL合并自身免疫性溶血性贫血(AIHA)近期疗效好,对SMZL本身也有一定治疗作用。     

Immunologic cell markers of peripheral blood and lymph node lymphocytes in chronic lymphocytic leukemia

The immunologic phenotype of the lymphocytes of 100 patients with chronic lymphocytic leukaemia (CLL) was investigated. Peripheral blood lymphocytes (PBL) were examined in all cases; in 46 patients with lymphadenopathy, a lymph node was biopsied and the histologic and immunologic patterns were assessed: 24 had a lymphocytic-lymphoplasmocytoid histology and 22 the follicular variant of lymphocytic lymphoma (mantle zone lymphoma, MZL). For comparison, lymph node suspensions from 19 patients with non-leukemic centrocytic lymphoma (CCL) were also studied. Significant differences in the PBL immunologic features were found between stage O and stage I patients. The phenotype of the lymphocytes of patients with lymphocytic histology was similar to that of stage 0 CLL patients, whereas major differences were found between these patients and those with mantle zone histology. This enables these patients to be recognized easily on immunologic grounds.     

A clinicopathologic study of primary small intestine lymphoma: prognostic significance of mucosa-associated lymphoid tissue-derived lymphoma

BACKGROUND: It remains unclear whether the presence of mucosa-associated lymphoid tissue (MALT) lymphoma has prognostic implications for patients with primary small intestine lymphoma. METHODS: The clinicopathologic features of 80 patients with primary small intestine lymphoma were examined retrospectively in relation to the presence of MALT lymphoma. Survival was compared univariately and multivariately among the groups divided by clinicopathologic findings. RESULTS: Twenty-one cases (26%) were diagnosed as low grade B-cell lymphoma (15 marginal zone B-cell lymphoma of MALT type, 2 mantle cell lymphoma, and 4 follicle center lymphoma), 46 cases (58%) were diagnosed as high grade B-cell lymphoma (19 secondary large cell lymphoma with a low grade MALT component, 17 diffuse large cell lymphoma without MALT features, 7 Burkitt lymphoma, and 3 lymphoblastic lymphoma), and 13 cases (16%) were diagnosed as T-cell lymphoma. A significantly better survival was noted for patients without colorectal and/or gastric involvement, diffuse infiltration under macroscopy, high grade histology, and perforation. Those patients with MALT type tumors, less advanced stage of disease, B-cell phenotype, benign lymphoid follicular hyperplasia, and radical tumor resectability appeared to have a better survival rate. Based on Cox multivariate analysis, early stage disease and MALT-derived tumors were determined to be independent prognostic factors (P < 0.05). CONCLUSIONS: The presence of MALT-derived lymphoma appears to have a favorable prognosis among patients with primary small intestinal lymphoma.     

The utility of interphase fluorescence in situ hybridization for the detection of the translocation t(11;14)(q13;q32) in the diagnosis of mantle cell lymphoma on fine-needle aspiration specimens

BACKGROUND: Mantle cell lymphoma can be difficult to differentiate cytologically from other small cell non-Hodgkin lymphomas. Nevertheless, the distinction is important, because mantle cell lymphoma is more aggressive than other small cell non-Hodgkin lymphomas. The purpose of this study was to determine whether fluorescence in situ hybridization (FISH) is helpful in diagnosing mantle cell lymphoma on fine-needle aspiration (FNA) specimens by detecting the t(11;14)(q13;q32) translocation that is characteristic of this tumor. METHODS: Fifty-five lymph node FNA specimens from 53 patients were analyzed using FISH. A 2-color FISH assay that employed probes at the 14q32 (immunoglobulin H) and 11q13 (dual-colored, directly labeled cyclin D1) loci was used. The number of single-fusion and double-fusion signals in 200 cells was counted. If > or = 14% single-fusion signals or > or = 1.5% double-fusion signals or both were present, then the sample was considered FISH positive. The findings were correlated with the cytologic, histologic, and immunophenotypic findings in each specimen. RESULTS: Of the 55 cytology specimens, 17 were mantle cell lymphomas, and 38 were nonmantle cell lymphomas, including 16 small lymphocytic lymphomas (9 of 16 in an accelerated phase), 5 large cell lymphomas, 5 follicular lymphomas, 7 transformed large cell lymphomas (Richter syndrome), 3 atypical lymphoid proliferations, and 2 low-grade B-cell lymphomas. All 17 mantle cell lymphomas were positive by FISH. In addition, there were six small lymphocytic lymphomas (two in accelerated phase), one transformed large cell lymphoma, and one large cell lymphoma of follicular origin positive by FISH. The mean number of single-fusion and double-fusion signals, respectively, was 36 and 33 in mantle cell lymphoma specimens and 19 and 3 in positive nonmantle cell lymphoma specimens. CONCLUSIONS: The detection of the t(11;14)(q13;q32) translocation by FISH analysis was helpful in diagnosing mantle cell lymphoma on FNA specimens. Double-fusion signals were more specific for mantle cell lymphoma than single-fusion signals. In rare instances, other non-Hodgkin lymphomas also showed increased numbers of single-fusion signals that were not necessarily indicative of the t(11;14)(q13;q32) translocation. Therefore, in an initial diagnosis of mantle cell lymphoma, significant numbers of double-fusion FISH signals should be identified and interpreted in conjunction with the cytologic and immunologic studies.     

Lymphocyte markers and clinical expression of lymphoproliferative disorders with moderate lymphocytosis

Lymphoproliferative syndrome with well differentiated lymphocytes and moderate lymphocytosis in the peripheral blood includes a heterogeneous group of disorders, that present often difficulties in classification. We have studied the lymphocyte markers (ER, EMR, sIg and T3, T4, T8 antigens) in 36 cases who had lymphocytic infiltration in the bone marrow and peripheral lymphocyte counts less than 15 X 10(9) l-1. Four cases (11.1%) had the characteristics of T8 lymphocytosis and 31 had a B cell monoclonal proliferation in the peripheral blood. Of these, four were sIg-, EMR+, 19 were sIg+, EMR+ and 8 were sIg+, EMR-. Most patients (17/32) had the clinical picture of stage 0 and I B-CLL. Six cases presented as pure splenomegalic form of CLL, three had the features of immunocytic lymphoma and five had the features of lymphocytic lymphoma. It is concluded that the majority of lymphoproliferative disorders presenting with moderate lymphocytosis represent early forms of B-CLL. Occasionally cases of lymphocytic or immunocytic lymphoma may present problems of differential diagnosis since there may be a dissociation of phenotypic characteristics of lymphocytes between tissues and peripheral blood.