Anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma presenting in nasal cavity: a case report and review of literature

Anaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma (DLBCL) is a rare subtype of non-Hodgkin’s lymphoma (NHL) with distinct morphologic and immunohistochemical features. We reported a 57-year-old female with ALK-positive DLBCL in her left nasal cavity. Histologically, the tumor cells were characterized by plasmablastic morphology and tested positive for ALK in a cytoplasmic granular staining pattern. The neoplastic cells were positive for CD38, CD4, MUM1, CD138 and Vimentin. However, they failed to express CD56, CD30, as well as mature B cells markers, such as CD79a, CD20 and T cells markers such as CD2, CD3, CD5, CD7 and CD8. The patient achieved complete response after four cycles of CHOEP (cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide) treatment. Then she received radiotherapy of the originally involved area. This case represented a rare ALK-positive DLBCL in the nasal region.     

Intravascular large B-cell lymphoma secondary to lymphoplasmacytic lymphoma: a case report and review of literature with clonality analysis

Intravascular large B-cell lymphoma (IVLBCL) can be a fatal malignancy mainly because of difficulty in early detection. Due to the lack of specific clinical manifestations, early detection of IVLBCL remains a challenge, especially in the presence of comorbidities. Lymphoplasmacytic lymphoma (LPL) is an indolent B-cell lymphoma accompanied by monoclonal immunoglobulin M protein in most patients, and known to be associated with high risk of secondary hematological malignancies. Here, we report a patient who developed IVLBCL during treatment for LPL that presented a diagnostic challenge. Rearrangement analysis of the immunoglobulin heavy chain revealed the different clonal origins of two lymphomas, implying a predisposition of LPL to develop unrelated secondary lymphoma. Secondary lymphoma including IVLBCL during the treatment for LPL deserves consideration in order to facilitate early diagnosis and intervention.     

Development of angioimmunoblastic T-cell lymphoma after treatment of diffuse large B-cell lymphoma: a case report and review of literature

Cases of diffuse large B-cell lymphoma (DLBCL) arising after the initial diagnosis of angioimmunoblastic T-cell lymphoma (AITL) and DLBCL synchronous with AITL have been reported. To date, there is no report on the subsequent development of AITL in patients with DLBCL. Here we presented a rare case of AITL developing six months after the initial diagnosis of DLBCL. In order to investigate the clinical and molecular features of patients with AITL and DLBCL, we also reviewed the literature on AITL patients developing DLBCL, and patients with composite AITL and DLBCL.     

Extra-oral plasmablastic lymphoma: report of a case and review of literature

Plasmablastic lymphoma (PBL) of the oral cavity is classified as one subtype of diffuse large B-cell lymphoma that is most commonly seen in patients with human immunodeficiency virus infection. We report a rare case of PBL in the anal canal of a 33-year-old man with human immunodeficiency virus infection. The lymphoma cells were positive for CD138 and weakly positive for CD79a. In addition, these cells were also positive for CD10. The neoplastic cells were positive for Epstein-Barr virus and negative for human herpes virus 8. Review of the English medical literature revealed many more cases of extra-oral PBL. We propose that the term plasmablastic lymphoma of the oral cavity in World Health Organization classification be revised to simply plasmablastic lymphoma, which would include both oral and extra-oral PBLs, and the term to define the primary site of the lymphoma (ie, oral cavity) be dropped from the terminology used in World Health Organization classification.     

Clear cell variant of diffuse large B-cell lymphoma: a case report and review of the literature

Diffuse large B cell lymphoma (DLBCL) is a diffuse proliferation of large neoplastic B lymphoid cells with nuclear size equal to or exceeding that of normal macrophage nuclei. The DLBCL morphological variants are centroblastic, immunoblastic, T-cell- and histiocyte-rich, anaplastic, plasmablastic, anaplastic lymphoma kinase-positive, and primary mediastinal large B-cell lymphoma (PMBCL). These histopathologically-recognized morphological variants respond differently to treatment and have distinct prognoses. We report a case of a 43-year-old patient who presented pain in the lower abdomen that had begun four months prior. Ultrasound-guided biopsy revealed epithelial cell features and a partial alveolar growth pattern. We discovered large diffuse areas comprising large cells with slightly irregular nuclei and very clear cytoplasm. These features were similar to those of clear cell carcinoma in renal tissue, suggesting the possibility of an epithelial neoplasm. To test this possibility, immunohistochemistry for cluster designation markers was performed, but the diffuse areas were found to be positive only for CD45. Additional immunohistochemistry was performed, and the diffuse areas were found to be positive for CD20, CD79a, P53, and Mum-1. Based on these characteristics, a diagnosis of a clear cell variant of DLBCL was made, and the patient was treated with chemotherapy. Precise histological diagnosis is crucial for clinical management and ultimately for patient survival. There has been one additional report of a case of clear cell DLBCL, in outside the mediastinum. The features we identified can be used to define a new subtype of DLBCL. The expression of P53 and Mum-1 suggest a poor prognosis.     

Primary renal diffuse large B-cell lymphoma with central nervous system involvement: a rare case report and literature review

Primary renal lymphoma is a rare entity. Of these, diffuse large B-cell lymphoma is the most common pathological type and, R-CHOP regimen was the preferred chemotherapy for it. Here we present an adult case of primary renal diffuse large B-cell lymphoma.     

原发性肾上腺非霍奇金淋巴瘤3例并文献复习

目的探讨原发性肾上腺恶性淋巴瘤的临床病理特征。方法对3例原发性肾上腺恶性淋巴瘤进行临床、病理组织学和免疫组织化学观察,并结合文献探讨其临床表现、病理形态及鉴别诊断。结果本病临床上无特异性,组织学上瘤细胞呈弥漫片状分布,细胞体积较大,多呈圆形或卵圆形,核仁明显,核深染,异型性明显,核分裂象易见。免疫表型：瘤细胞CD45、CD20、CD79α阳性,CD3、CK、S-100蛋白、CEA、Syn及CgA阴性。结论原发性肾上腺恶性淋巴瘤是一种罕见的恶性度较高的肿瘤,预后差。病理诊断上应与继发性肾上腺恶性淋巴瘤鉴别。     

Diffuse large B-cell lymphoma of the uterus suspected of having transformed from a marginal zone B-cell lymphoma harboring trisomy 18: a case report and review of the literature

The patient was a 72-year-old female with the chief complaint of abdominal fullness. A giant primary myoma of the uterine cervix was suspected, and total hysterectomy was performed. Based on a postoperative histopathological examination of the tumor a diagnosis of diffuse large B-cell lymphoma (DLBCL) was made in the uterus and a mass in the greater omentum was diagnosed as a marginal zone B-cell lymphoma (MZBCL). No flow-cytometry studies or chromosome or gene examinations were performed on a fresh specimen. The results of an examination of a paraffin block histopathology specimen by fluorescence in-situ hybridization (FISH) showed no mucosa associated lymphoid tissue lymphoma translocation gene 1 (MALT1) (18q21.1), B-cell lymphoma 2 (BCL2) (18q21.3), or BCL6 (3q27) split signals in either the uterus or the greater omentum, however, trisomy 18 was detected in approximately 50%-70% of the tumor cells in both the uterus and the greater omentum. Trisomy 18 was present in around 15-33% of the DLBCL cells and MZBCL cells. These findings suggested a strong possibility that the tumor cells in the uterus and greater omentum were the same clone and that transformation from MZBCL to DLBCL had occurred. Since DLBCLs that result from a transformation usually have a worse outcome than de novo DLBCLs, even when a DLBCL seems to have originated in the uterus the surrounding tissue should always be examined, and caution should be exercised in regard to transformation from a low-grade B-cell lymphoma to a DLBCL.     

Diffuse large B-cell lymphoma in the spinal epidural space: A study of the Osaka Lymphoma Study Group

Diffuse large B-cell lymphoma (DLBCL) involving spinal epidural space (SEDLBCL) is relatively rare, constituting 1.8% of DLBCLs in Osaka, Japan. The aim of this study was to analyze SEDLBCL cases for their clinical and histopathologic findings, including an association with Epstein-Barr virus (EBV) and immunohistochemical characteristics.     

Composite primary breast diffuse large B-cell lymphoma and T lymphoblastic leukemia/lymphoma: report of a case and review of literature

We reported a rare case of composite diffuse large B-cell lymphoma and T lymphoblastic leukemia/lymphoma (T-LBL) in a 46-year-old woman with progressive enlargement of the breast lump. The patient initially sought care at a local hospital with a single left breast lump without any other physical examination findings. Histopathological analysis of which revealed a diffuse infiltration of tumor cells that were rich in cytoplasm with vesicular chromatin and prominent nucleoli. Further analysis of immunohistochemistry showed a cluster of neoplastic cells which express B-cell markers: CD19, CD20 (weak), CD79a, PAX5 and BCL-2, but negative for T-cell markers such as CD2, CD3, CD5 and CD7. PET-CT showed evidence of lymphadenopathy and splenomegaly, which may indicate lymphoma infiltration. Then a biopsy of bone marrow showed typical features of T-LBL. The aberrant terminal deoxynucleotidyl transferase (TDT) and cCD3 positive T-cell population that lack surface CD10 and CD19 were identified by flow cytometric immunophenotyping. Polymerase chain reaction analysis of the T-cell receptor gamma gene and IgH gene revealed a clonal rearrangement and confirming T-cell clonality. Fluorescence in-situ hybridization (FISH) revealed a deletion of the P53 gene in these T-neoplastic cells may indicate a bad outcome of such disease. Neither the large B-cells nor T-cells were positive for Epstein-Barr virus encoded RNA.     

CD56 positive diffuse large B-cell lymphoma: a case report and literature review

CD56 positive B-cell lymphoma is very rare. We experienced a case of CD56 positive diffuse large B-cell lymphoma, occurred in a young child. A 5-year-old girl complained with snoring and open mouth breathing. No any abnormality in laboratory or physical examination was present, except enlarged both tonsils. Bilateral tonsillectomy was performed. Cut sections of right tonsil showed a 2 cm size, solid mass. On microscopically, large monomorphic lymphoid cells were diffusely proliferated and showed positivity for CD20 and CD56 and negative for Epstein-Barr virus (EBV) polymerase chain reaction (PCR). Monoclonality was observed on immunoglobulin heavy chain gene rearrangement. This is a unique case with incidentally found and occurred in a young child.     

ALK-positive diffuse large B-cell lymphoma of the stomach associated with a clathrin-ALK rearrangement

ALK-positive diffuse large B-cell lymphoma is a rare, recently characterized lymphoma subtype that shows granular cytoplasmic ALK expression. This report describes a primary gastric ALK-positive B-lineage lymphoma in which a clathrin (CLTC)-ALK fusion was identified by RT-PCR and direct sequencing of the breakpoint. This confirmed the presence of t(2;17)(p23;q23) involving the CLTC gene and is only the 4th report of such a translocation in this lymphoma subtype and the first to describe this tumor within the stomach. As in previous reports, immunophenotyping showed the malignant cell to be a terminally differentiated B-lineage cell characterized by the absence of B-cell antigens and expression of antigens associated with plasma cell differentiation. This case confirms the existence of such a lymphoma subtype arising in extranodal locations and underscores the importance of detailed immunophenotyping and specialized molecular genetic investigations in confirming the diagnosis.     

原发性纵隔大B细胞淋巴瘤临床病理分析并文献复习

目的：探讨原发性纵隔大B细胞淋巴瘤(primary mediastinal large B-cell lymphoma,PMBL)的临床病理学特点及诊断要点。方法：收集2010年9月~2014年12月病理确诊为PMBL的病例,对其对PMBL进行临床特点、病理形态学及免疫组织化学观察分析,并复习相关文献。结果：3例PMBL2例为男性,1例为女性,3例均侵犯邻近器官,2例伴颈部或锁骨上淋巴结受累,1例椎体受累(C7-T4)。镜下见不同程度的纤维化,瘤细胞呈巢状或弥漫浸润,瘤细胞胞质空亮丰富,细胞核圆形或卵圆形,其中1例可见坏死。免疫组织化学均表达CD20、CD79a、CD23、bcl2、CD23,其中2例表达CD30,均不表达CD3、CD5。随访3例均生存,化疗后1例获得CR,2例获得PR。结论：纵隔原发弥漫大B细胞淋巴瘤很少见,形态变化多端,容易引起误诊。提高对PMBL的认识,对避免误诊是至关重要的。     

Primary platelet-derived growth factor-producing,spindle-shaped diffuse large B-cell lymphoma of the skull: a case report and literature review

A 39-year-old woman with a right frontal mass underwent a cranial bone tumor biopsy. Histopathologic examination of hematoxylin and eosin–stained slides showed spindle-shaped tumor cells in a storiform pattern, appearing somewhat like a sarcoma. However, the tumor cells were CD20-positive by immunohistochemical staining. Therefore, a diagnosis of spindle-shaped diffuse large B-cell lymphoma (Sp-DLBCL) was made. There have been at least 35 cases of Sp-DLBCL documented in the literature, and most were of the germinal center type, while the present case is the first report of a vimentin-positive primary Sp-DLBCL of the skull. The DLBCL in this case was immunohistochemically stained for six representative cytokines that might give rise to fibrosis, due to the evidence of fibroblastic proliferation. The DLBCL cells were positive for platelet-derived growth factor (PDGF), and some cells were also positive for tumor necrosis factor (TNF) α. Based on these findings, it was inferred that the PDGF and TNFα produced by DLBCL cells induced fibroblastic proliferation. The resultant conspicuous fibrosis caused interfibrous impingement on the DLBCL cells, which deformed them into a spindle shape. The present case is the first reported case of a PDGF-producing Sp-DLBCL.     

Comparative clinicopathological study of primary CNS diffuse large B-cell lymphoma and intravascular large B-cell lymphoma

Primary CNS diffuse large B-cell lymphoma (CNS DLBCL) is confined to the CNS, and constitutes a distinct entity. In the present study a series of 40 Japanese patients with CNS DLBCL who presented with neurological, but not systemic symptoms, was reviewed. Median survival was 18.7 months. CD5, CD10, Bcl-6, MUM-1, and Bcl-2 were positive in 30%, 10%, 84%, 100%, and 93% of patients, respectively. All CD10-negative patients had non-germinal center B-cell type. There was no significant difference in survival among the immunophenotypic subgroups. CNS DLBCL appeared to be homogenous as a group, which prompted the comparison with another distinct extranodal entity, intravascular large B-cell lymphoma (IVLBCL) in Japanese patients. CNS DLBCL patients did not differ in age, sex, or immunophenotype, including CD5 positivity, from IVLBCL patients, but were significantly less likely to have poor prognostic parameters than IVLBCL patients: the international prognostic index score was low or low–intermediate in 86% of CNS DLBCL patients and high or high–intermediate in 98% of IVLBCL patients. Notably, despite this difference, their survival curves almost overlapped. The present study highlights the issue of clinical distinctiveness of aggressive extranodal lymphomas, the peculiar migration and localization of which should be further clarified.     

Primary testicular diffuse large B-cell lymphoma shows an activated B-cell-like phenotype

The most common type of primary testicular lymphoma is diffuse large B-cell type, which has a poor prognosis relative to other extra-nodal diffuse large B-cell lymphomas (DLBCL). These constitute a heterogeneous group of lymphomas with germinal center B-cell-like and activated B-cell-like subtypes. Such a distinction theoretically utilizes the immunohistochemical expression of CD10, Bcl-6, and MUM1. The purpose of this study was that we could stratify primary testicular lymphoma of diffuse large B-cell type according to this scheme, and further elucidate the reason why primary testicular diffuse large B-cell lymphoma possesses a poor clinical outcome. Seventeen Chinese patients with primary testicular DLBCL were examined by means of a 3-antibody panel (CD10, Bcl-6, MUM1). Among these 17 cases, 16 were assigned to the activated B-cell-like subtypes. One case was classified as germinal center B-cell-like type. Twelve of these 17 cases expressed high proliferative activity (≥40% Ki-67 labeling). The majority of primary testicular DLBCLs have activated B-cell-like subtype characteristics and high proliferative activity. These features might be a significant factor; moreover, they are associated with poor prognosis.     

ALK-negative anaplastic large cell lymphoma primarily involving the bronchus: a case report and literature review

Anaplastic large cell lymphoma (ALCL) is a mature T cell lymphoma with characteristic morphologic, immunophenotypic and cytogenetic features. Current WHO classification includes anaplastic lymphoma kinase (ALK)-positive and ALK-negative variants. ALCL rarely presents with obstructive symptoms of the main airway. In addition to reporting a HIV-associated bronchial ALK-negative ALCL in a 44 year-old female, our literature review identified eight cases of bronchial ALCL with several interesting clinicopathological features, including: 1) a female predominance (67%); 2) two thirds of patients younger than 18 years old; 3) uniformly presented with respiratory symptoms and progressed to respiratory failure; 4) the tumor involving the main airways; 5) often with localized disease at the initial presentation. This unusual presentation of ALCL may pose as a diagnostic pitfall and delay the treatment.     

Intravascular large B-cell lymphoma with pontine involvement successfully treated with R-CHOP therapy and intrathecal administration: a case report and review of literature

A 46-year-old man developed a fever and cough, and computed tomography showed multiple, nodular infiltrative shadows in lungs. He was diagnosed as having intravascular large B-cell lymphoma (IVLBCL). Brain magnetic resonance imaging (MRI, T2W1) showed an abnormal signal area in the pons, which was IVLBCL involvement. R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) therapy and intrathecal (I.T.) injection of methotrexate, cytarabine and prednisolone were selected. Complete remission (CR) was achieved and pontine involvement disappeared. A total of 8 courses of R-CHOP therapy and 4 courses of I.T. were performed. CR has been maintained for 1 year and 2 months.