Prognostic value of POD18 combined with improved IELSG in primary central nervous system lymphoma

Purpose The International Extranodal Lymphoma Study Group (IELSG) score is widely used in clinical practice to stratify the risk of primary central nervous system lymphoma (PCNSL) patients. Our study aims to confirm and improve the IELSG score in PCNSL patients based on Chinese populations. Materials and methods A total of 79 PCNSL patients were retrospectively analyzed. All patients treated with high-dose methotrexate (HD-MTX)-based therapy collected clinical data. The receiver-operating characteristic (ROC) curve was used to determine the optimal cut-off values for the factors in IELSG score. Progression of disease (POD) at the most landmark time point was determine by Epanechnikov kernel and the area under the ROC curve (AUROC). Kaplan–Meier and multivariable regression methods were used to analyze survival data. Nomogram was generated for calculating the weight of each selected factor. Results The traditional IELSG score had no significant difference on OS and PFS except ECOG ≥ 2 and could not stratify the risk groups in PCNSL. The improved IELSG scoring system was established, which incorporated age ≥ 54 years, ECOG ≥ 2, deep brain structure, elevated CSF protein, and LDH/ULN > 0.75. On the other hand, POD18 was identified as a new powerful prognostic factor for PCNSL. In multivariate analysis, POD18 and the improved IELSG scoring system were independent prognostic factors for OS. Nomogram including the two significant variables showed the best performance (C-index = 0.828). Conclusions In this study, the IELSG score was improved and a new prognostic indicator POD18 was incorporated to construct a nomogram prognostic model, thereby further improving the predictive ability of the model (AU)

Angioimmunoblastic T-Cell Lymphoma and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Novel Form of Composite Lymphoma Potentially Mimicking Richter Syndrome.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is an indolent small B-cell neoplasm that may transform into a clinically aggressive disease, namely Richter syndrome, usually as diffuse large B-cell lymphoma. Besides, CLL/SLL encompasses an increased risk of developing other secondary cancers, including a variety of T-cell lymphomas, often of the anaplastic large-cell type or with a cytotoxic phenotype. Here, we report a small series of patients with composite lymphomas consisting of CLL/SLL and angioimmunoblastic T-cell lymphoma (AITL), a hitherto unrecognized association. The 3 patients (1 male/2 females, 68 to 83 y) presented with high-grade-type symptoms. One patient was clinically suspicious for Richter syndrome, in the others CLL/SLL and AITL were concomitant de novo diagnoses. CLL/SLL and AITL were admixed in the same lymph nodes (3/3 cases) and in the bone marrow (1/2 cases). In all cases, the AITL comprised prominent clear cells with a strong T follicular helper immunophenotype and similar mutations consisting of TET2 or DNMT3A alterations, IDH2 R172K/M, and RHOA G17V. The 3 patients received chemotherapy. One died of early AITL relapse. The other 2 remained in complete remission of AITL, 1 died with recurrent CLL, and 1 of acute myeloid leukemia. These observations expand the spectrum of T-cell lymphoma entities that occur in association with CLL/SLL, adding AITL to the rare variants of aggressive neoplasms manifesting as Richter syndrome. Given that disturbances of T-cell homeostasis in CLL/SLL affect not only cytotoxic but also helper T-cell subsets, these may contribute to the emergence of neoplasms of T follicular helper derivation.

Cutaneous composite lymphoma of mycosis fungoides and Hodgkin lymphoma: Response to sequential therapy.

Composite lymphoma is defined as two or more morphologically and immunophenotypically distinct lymphoma clones that occur in the same tissue site. The occurrence of cutaneous composite lymphoma (CCL) is extremely rare. Here we report a unique case of CCL consisting of Hodgkin lymphoma (HL) and mycosis fungoides (MF). Our patient presented with longstanding erythematous plaques on the skin and later developed axillary lymph node enlargement. Histopathologically, the skin lesions were characterized by a dense dermal lymphocytic infiltrate with prominent epidermotropism of pleomorphic T-cells, consistent with typical MF. Nonetheless, scattered large atypical cells resembling Reed-Sternberg (R-S) cells were interspersed among these atypical T-cells in the deep dermis. Immunophenotyping suggested a HL origin of these R-S cells. Monoclonality of T-cell receptor beta gene was detected in the skin, monoclonal immunoglobulin heavy chain gene rearrangement was identified in these R-S cells microdissected from the deep dermis, confirming the origin from HL. The lymph node biopsy showed nodular sclerosis classic Hodgkin lymphoma. Therefore, CCL of HL and MF, with lymph node HL was diagnosed. The lesions of this patient responded to a sequential treatment to HL and MF. Being aware of this rare CCL facilitates correct diagnosis and proper clinical management.

Methotrexate-associated lymphoproliferative disorder demonstrating composite lymphoma of EBV-negative diffuse large B-cell lymphoma and EBV-positive mucocutaneous ulcer.

Other iatrogenic immunodeficiency-associated lymphoproliferative disorders induced by immunosuppressive drugs, such as methotrexate (MTX-LPD), exhibit numerous pathological findings. We report the case of an 81-year-old Japanese woman diagnosed with MTX-LPD exhibiting two distinct pathological features from two different sites. Excisional biopsy of the left cervical lymph node revealed EBV-negative diffuse large B-cell lymphoma and biopsy of a pharyngeal ulcer revealed EBV-positive mucocutaneous ulcer. She was treated using an R-CHOP regimen and maintained complete remission for years. This case demonstrates the heterogeneous pathology of MTX-LPD and suggests the necessity of multiple biopsy.

Pegylated liposomal-encapsulated doxorubicin in cutaneous composite lymphoma: A case report.

BACKGROUND: Cutaneous composite lymphomas are very rare. Their treatment depends upon the different contributing lymphoma entities. Peripheral T-cell lymphoma, not otherwise specified, (PTCL-NOS) represents an aggressive lymphoma subtype. Follicular cutaneous B-cell lymphoma (FCBCL) runs an indolent course. Treatment with pegylated liposomal encapsulated doxorubicin (PLE-DOXO) has yet not been reported in this entity. CASE PRESENTATION: A 73-year-old male patient presented with 3 rapidly growing, painful nodules on his left leg. He was diagnosed as composite cutaneous lymphoma consisting of PTCL-NOS and FCBCL. All lesions had been surgically removed. Staging was unremarkable. After 4 months a relapse occurred with involvement of inguinal lymph nodes and systemic treatment with PEL-DOXO 20 mg/ m every 3 weeks was initiated. After 6 cycles PLE-DOXO, which were well tolerated without grade 3 or 4 toxicities, a mixed response was obtained with complete remission of cutaneous lesions.Lymph nodes were treated by radiotherapy. A second relapse occurred after 8 months and various polychemotherapy regimens were applied without remission. The overall survival was 28 months. CONCLUSION: PEL-DOXO is a possible initial systemic treatment in case of PCTL-NOS. Whether polychemotherapy offers an advantage for survival remains questionable but further investigations are needed.

[Composite lymphoma consisting of adult T-cell leukemia-lymphoma and diffuse large B-cell lymphoma].

A 68-year-old man was admitted to our hospital because of left back pain and systemic lymphadenopathy with hypercalcemia. Serum anti-HTLV-1 antibody was positive. Left cervical lymph node (LN) biopsy revealed proliferation of medium-sized to large CD4-positive atypical cells with modest infiltration of CD20 and Epstein-Barr virus (EBV)-encoded RNA dual-positive atypical large cells. Monoclonal integration of HTLV-1 proviral DNA, plus clonal rearrangement of the T-cell receptor chain gene and the immunoglobulin heavy chain gene, were detected in the same LN specimen. Composite lymphoma consisting of adult T-cell leukemia/lymphoma (ATL) and EBV positive diffuse large B-cell lymphoma (DLBCL) was diagnosed. He was successfully treated with aggressive chemotherapy including rituximab and attained remission. However, eight months later, he developed right shoulder pain due to multiple bone invasions with bilateral cervical lymphadenopathy. Biopsies of a bone lesion and cervical LN revealed recurrence of ATL alone. The patient died despite salvage chemoradiotherapy. These findings suggest that ATL-related immunodeficiency might induce EBV-associated DLBCL.

[Composite lymphoma cosisting of mantle cell lymphoma and follicular lymphoma].

Herein, we report the case of a 56-year-old man with composite lymphoma (CL) comprised of mantle cell lymphoma (MCL) and follicular lymphoma (FL). Six months after developing a right brachial tumor, he was diagnosed as having grade 3 FL with normal-size mantle zone. Simultaneously, advanced stage MCL with a diffuse growth pattern in a sigmoid colon tumor and abnormal lymphoid cells in bone marrow were observed. Thereafter, the right brachial tumor was re-examined and its mantle zone cells were immunophenotypically positive for cyclin D1 (CCND1) and cytogenetically positive for the IgH-CCND1 fusion gene. Consequently, he was diagnosed with composite lymphoma (CL) comprised of FL and MCL. As MCL and FL may form CL, the possible complication of MCL should be considered and steps taken to detect MCL.

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 ß 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.

Composite T lymphoblastic leukemia/lymphoma and diffuse large B-cell lymphoma: case report.

This report concerns a unique case of a composite lymphoma composed of T-lymphoblastic leukemia/lymphoma (T-LBL) and diffuse large B-cell lymphoma (DLBCL) in a 72-year-old woman with generalized lymphadenopathy, splenomegaly and ascites. Laboratory findings showed increased lactate dehydrogenase and soluble interleukin-2 receptor. The biopsy specimen showed replacement of the normal architecture of the lymph nodes by a tumor containing a dual cell population composed of large lymphocytes and medium-sized lymphocytes. Sheets of large lymphocytes often were punctuated by clusters of medium-sized lymphocytes. Flow cytometry and immunohistochemical analysis showed a composite lymphoma with both T-LBL and DLBCL. The T-LBL expressed CD1a, CD3, CD4, CD8, and terminal deoxynucleotidyl transferase. The DLBCL expressed CD19 and CD20, CD23, bcl-2, bcl-6, MUM1 and immunoglobulin κ light chain. Polymerase chain reaction detected a monoclonal pattern of T-cell receptor γ and immunoglobulin heavy chain rearrangements in the same specimen. She received eight cycles of R-CHOP (rituximab+cyclophosphamide, doxorubicin, vincristine, prednisone) therapy and achieved complete remission. She has shown no signs of recurrence 20 months after the diagnosis. We describe here a very unusual and, to the best of our knowledge, an as yet never reported case of a primary composite lymphoma of T-LBL and DLBCL.