Composite lymphoma (CL) involving B-cell lymphoma and T-cell lymphoma is extremely rare. Herein, we report three such cases using immunohistochemistry, flow cytometry, and the next-generation sequencing (NGS) to identify the pathological and molecular characteristics of CL. In the first case, the patient was admitted to hospital for generalized pruritic maculopapular rash over the whole body. An excisional biopsy of the skin lesions showed T-cell lymphoma. At the same time, the staging bone marrow (BM) biopsy revealed a diffuse large B-cell lymphoma (DLBCL). After R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapies, the patient produced a good response with substantial dissipation of the rashes and relief of skin. The other two patients were admitted to hospital due to lymphadenopathy and were diagnosed with DLBCL and follicular lymphoma (FL) after core needle biopsy of lymph nodes, BM biopsy, BM aspiration, and flow cytometry. Following R-CHOP and R-COP (rituximab, cyclophosphamide, vincristine, and prednisone) therapies, they achieved complete remission unconfirmed (CRu) and complete remission (CR). However, one or two years later, they suffered a relapse of lymphadenopathy. The shocking fact was that re-biopsy of lymphadenopathy revealed peripheral T-cell lymphoma (PTCL) and angioimmunoblastic T-cell lymphoma (AITL). NGS findings identified DNA methyltransferase 3a (DNMT3a), isocitrate dehydrogenase 2 (IDH2), Ras homolog gene family, member A (RHOA), splicing factor 3B subunit 1 (SF3B1), and tumor protein p53 (TP53) mutations. After immunochemotherapy, these patients achieved CRu and CR again. Nevertheless, they suffered a second relapse of T-cell lymphoma. Finally, they died due to progression of disease. We found that the occurrence of CL is associated with Epstein-Barr virus infection and DNMT3a, IDH2, and TP53 mutations, and the prognosis of the disease is closely related to the T-cell lymphoma components.
Humans ; Rituximab/therapeutic use* ; Vincristine/therapeutic use* ; Prednisone/therapeutic use* ; Epstein-Barr Virus Infections/drug therapy* ; Herpesvirus 4, Human ; Neoplasm Recurrence, Local ; Lymphoma, T-Cell/drug therapy* ; Cyclophosphamide/therapeutic use* ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Doxorubicin/therapeutic use* ; Lymphadenopathy/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Chimeric antigen receptor (CAR) is a recombinant immunoreceptor combining an antibody-derived targeting fragment with signaling domains capable of activating cells, which endows T cells with the ability to recognize tumor-associated surface antigens independent of the expression of major histocompatibility complex (MHC) molecules. Recent early-phase clinical trials of CAR-modified T (CAR-T) cells for relapsed or refractory B cell malignancies have demonstrated promising results (that is, anti-CD19 CAR-T in B cell acute lymphoblastic leukemia (B-ALL)). Given this success, broadening the clinical experience of CAR-T cell therapy beyond hematological malignancies has been actively investigated. Here we discuss the basic design of CAR and review the clinical results from the studies of CAR-T cells in B cell leukemia and lymphoma, and several solid tumors. We additionally discuss the major challenges in the further development and strategies for increasing anti-tumor activity and safety, as well as for successful commercial translation.
Animals ; Humans ; Immunity, Cellular ; Immunotherapy ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; immunology ; pathology ; therapy ; Receptors, Antigen, T-Cell ; immunology ; Recombinant Fusion Proteins ; immunology ; T-Lymphocytes ; immunology ; transplantation

Peripheral T cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with poor prognosis. Elderly (age ≥ 65years) patients generally have impaired bone marrow function, altered drug metabolism, comorbidities, and poor functional status. Thus, treatment of elderly patients with relapsed or refractory PTCL remains a challenge for clinicians. A recent study disclosed that pralatrexate has a synergistic effect in combination with bortezomib. Weekly pralatrexate and bortezomib were administered intravenously for 3 weeks in a 4-week cycle. Of 5 patients, one achieved complete response after 4 cycles which has lasted 12 months until now. Another patient attained partial response after 2 cycles. Only 1 patient experienced grade 3 thrombocytopenia and neutropenia. Two patients suffered from grade 3 mucositis. Combination therapy with pralatrexate and bortezomib may be used as a salvage therapy for relapsed or refractory PTCL in the elderly with a favorable safety profile.
Aged ; Aminopterin/adverse effects/*analogs & derivatives/therapeutic use ; Antineoplastic Agents/adverse effects/*therapeutic use ; Bortezomib/adverse effects/*therapeutic use ; Drug Administration Schedule ; Drug Therapy, Combination ; Humans ; Lymphoma, T-Cell, Peripheral/diagnostic imaging/*drug therapy/pathology ; Male ; Neoplasm Recurrence, Local ; Neutropenia/etiology ; Positron Emission Tomography Computed Tomography

No abstract available.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biopsy ; Chemoradiotherapy, Adjuvant ; Diagnostic Errors ; Dupuytren Contracture/diagnosis ; *Fingers/pathology/ultrasonography/virology ; Hematopoietic Stem Cell Transplantation ; Herpesvirus 4, Human/genetics ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; *Lymphoma, Extranodal NK-T-Cell/diagnosis/therapy/virology ; Male ; Middle Aged ; Neoadjuvant Therapy ; Predictive Value of Tests ; RNA, Viral/genetics ; *Tendons/chemistry/pathology/ultrasonography/virology ; Treatment Outcome ; Tumor Markers, Biological/analysis ; Ultrasonography, Doppler, Color

No abstract available.
Antibodies, Monoclonal, Murine-Derived/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; B-Cell-Specific Activator Protein/metabolism ; Bone Marrow/metabolism/*pathology ; Cyclophosphamide/therapeutic use ; Doxorubicin/therapeutic use ; Endoscopy, Digestive System ; Female ; Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor ; Genetic Loci ; Humans ; Liver/metabolism/pathology ; Lymphocytes/cytology/immunology ; Lymphoma, Large B-Cell, Diffuse/complications/*diagnosis/drug therapy ; Lymphoma, T-Cell, Peripheral/complications/*diagnosis/drug therapy ; Middle Aged ; Prednisone/therapeutic use ; Receptors, Antigen, T-Cell, gamma-delta/genetics ; Tomography, X-Ray Computed ; Vincristine/therapeutic use

OBJECTIVETo investigate the clinical and pathological characteristics of patients with primary Waldeyer's ring lymphomas (PWRL), and to analyze its therapeutic efficacy and prognostic factors.

METHODSA total of 112 patients with PWRL confirmed by pathological and immunohistochemical methods between January 2009 and January 2014 were studied. Clinical data were collected and analyzed retrospectively.

RESULTSPWRL accounted for 3.9% of lymphoma over the same period. Median age of patients with PWRL was 51.5 years old. The affected areas were tonsil, nasopharynx, tongue base and oropharynx, which accounted for 63.4% (71/112), 22.3% (25/112), 5.3% (6/112) and 4.5% (5/112) respectively. The most common pathological types of these four areas were diffused large B-cell lymphoma (DLBCL) and extranodal NK/T cell lymphoma (NKTCL) which accounted for 58% and 15.2%. The overall response rate (CR/CRu = 51.4%; PR = 30.8%) in all patients was 82.2%, the estimated 5-year overall survival (OS) rate were 71.6%. The 5-year OS rate were 94.7% in the group used Rituximab. Meanwhile, chemotherapy combined with radiotherapy could improve the outcome of T-cell PWRL patients and the 5-year OS rate were 88.9%. Age, disease stages, pathological types, IPI scores, LDH level, β2-MG level and the efficacy of initial therapy were prognostic factors with statistical significance. Cox multivariate analysis showed that age of more than 60 years, LDH level, pathological types and the efficacy of the initial therapy were independently associated with OS.

CONCLUSIONPWRL has a relatively good prognosis. The pathological types affect the prognosis directly and guide treatment. Combined modality therapy should be chosen for patients with PWRL. Patients with T-cell PWRL should accept chemotherapy combined with radiotherapy, while rituximab may be better for B-cell PWRL. The efficacy of initial therapy is crucial for the outcome of patients. Age and LDH level are also important prognostic factors.

Combined Modality Therapy ; Humans ; Lymphoma, Extranodal NK-T-Cell ; diagnosis ; pathology ; Lymphoma, Large B-Cell, Diffuse ; diagnosis ; pathology ; Middle Aged ; Multivariate Analysis ; Prognosis ; Retrospective Studies ; Rituximab ; Survival Rate

A seven months old male infant visited Severance Children's Hospital for evaluation of anterior mediastinal mass. With chest computed tomography (CT) image and biopsy, precursor T-cell lymphoblastic lymphoma was suspected but the ultrasonography guided biopsy specimen was insufficient to confirm the disease. Because there was a life-threatening risk to perform open biopsy to the small infant, we started chemotherapy empirically. The mass decreased, however, the lesion increased again and did not respond to the drugs. Finally we decided to resect the anterior mass with sternostomy and the pathology report finally resulted in thymoma.
Biopsy ; Drug Therapy ; Humans ; Infant ; Male ; Pathology ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Thorax ; Thymoma ; Ultrasonography

OBJECTIVETo determine the efficacy of palliative radiotherapy in treating tumor-stage cutaneous T-cell lymphoma/mycosis fungoides (MF).

METHODSFrom January 2008 to January 2013, a total of 11 patients with tumor-stage MF were treated with local radiation therapy in Peking Union Medical College Hospital. The median age of these patients was 53.36 ± 14.45 years. Female-male ratio was 1:1.2. The average course of disease was 10.82 ± 3.37 years. All the patients were treated with local electronic beam irradiation with a total median dosage of 48.55 ± 9.51 (40-74) Gy in an average of 24.55 ± 5.57 (20-40) fractions, 5 fractions per week.

RESULTSThe median follow-up time was 55.27 ± 29.3 (13-103) months. No severe acute or chronic side effects of irradiation were observed. Complete clinical response (CR) rate of the radiated sites was 54.5% (6/11), partial response (PR) rate was 36.4% (4/11), and the overall response rate (CR+PR) was 90.9%. One patient showed no response.

CONCLUSIONLocal radiotherapy with psolaren plus ultraviolet A and/or interferon maintaining treatment is an effective palliative therapy in the treatment of tumor-stage MF patients.

Adult ; Aged ; Antineoplastic Agents ; administration & dosage ; therapeutic use ; Chemoradiotherapy, Adjuvant ; methods ; Disease-Free Survival ; Female ; Humans ; Interferons ; administration & dosage ; therapeutic use ; Lymphoma, T-Cell, Cutaneous ; drug therapy ; pathology ; radiotherapy ; Male ; Middle Aged ; Mycosis Fungoides ; drug therapy ; pathology ; radiotherapy ; Neoplasm Staging ; PUVA Therapy ; methods ; Palliative Care ; methods ; Radiotherapy Dosage ; Skin Neoplasms ; drug therapy ; pathology ; radiotherapy ; Treatment Outcome

BACKGROUND/AIMS: In Asia, the incidence of non-Hodgkin lymphoma (NHL) has increased in recent decades. Waldeyer's ring (WR) is the most common site of NHL involving the head and neck. In this study, the pathological distribution of WR-NHL and its clinical features were analyzed retrospectively. METHODS: From January 2000 through December 2010, we analyzed the medical records of 328 patients from nine Korean institutions who were diagnosed with WR-NHL. RESULTS: The study group comprised 197 male and 131 female patients with a median age of 58 years (range, 14 to 89). The rate of localized disease (stage I/II) was 64.9%, and that of low-risk disease (low/low-intermediate, as defined by the International Prognostic Index) was 76.8%. Diffuse large B-cell lymphoma (DLBCL; 240 patients, 73.2%) was the most common pathologic subtype, followed by peripheral T-cell lymphoma (14 patients, 4.3%) and nasal NK/T-cell lymphoma (14 patients, 4.3%). WR-NHL occurred most frequently in the tonsils (199 patients, 60.6%). Extranodal involvement was greater with the T-cell subtype (20 patients, 42.5%) compared with the B-cell subtype (69 patients, 24.5%). Multivariate analyses showed that age > or = 62 years, T-cell subtype, and failure to achieve complete remission were significant risk factors for overall survival. CONCLUSIONS: DLBCL was found to have a higher incidence in Korea than those incidences reported by other WR-NHL studies. T-cell lymphoma occurred more frequently than did follicular lymphoma. T-cell subtype, age > or = 62 years, and complete remission failure after first-line treatment were significant poor prognostic factors for overall survival according to the multivariate analysis.
Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Disease-Free Survival ; Female ; Head and Neck Neoplasms/mortality/*pathology/therapy ; Humans ; Incidence ; Kaplan-Meier Estimate ; Lymphoma, Extranodal NK-T-Cell/pathology ; Lymphoma, Large B-Cell, Diffuse/pathology ; Lymphoma, Non-Hodgkin/mortality/*pathology/therapy ; Lymphoma, T-Cell, Peripheral/pathology ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Proportional Hazards Models ; Recurrence ; Remission Induction ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Time Factors ; Treatment Outcome ; Young Adult

Intravascular lymphoma (IVL) is a rare disorder characterized by the presence of large neoplastic lymphoid cells restricted to the lumens of small vessels with a predilection for the skin and the central nervous system. While the vast majority of cases involving IVL are of B-cell lineage, the disease rarely affects the T-cell, the histiocytes, and the natural killer cells. We report a case of intravascular T-cell lymphoma (IVTL) associated with Epstein-Barr virus (EBV). A 23-year-old healthy woman presented with tender indurated erythematous patches with overlying telangiectasia on her right breast, abdomen, both the upper and the lower extremities and the back for 3 months. The pathology revealed an infiltration of dermal and subcutaneous vessels by large and atypical lymphoid cells with immunohistochemical features of the T-cell lineage with a cytotoxic phenotype (CD3+, CD8+, granzyme B+, TIA-1+, CD4-, CD5-, CD20-, CD56-). Interestingly, the DNA extracted from the skin biopsies demonstrated evidence of a monoclonal immunoglobulin heavy chain gene rearrangement, but no T-cell receptor gene rearrangement was found. In situ hybridization study for EBV-encoded RNA was positive. She was diagnosed with an EBV-associated IVTL. The patient's skin lesions were refractory to the combination of chemotherapy and autologous stem cell transplant, and she expired. The findings in the present case may highlight the unique clinicopathologic aspects of EBV-associated cytotoxic IVTL that occurred in a young, immunocompetent woman.
Abdomen ; B-Lymphocytes ; Biopsy ; Breast ; Central Nervous System ; DNA ; Drug Therapy ; Female ; Gene Rearrangement ; Genes, T-Cell Receptor ; Granzymes ; Herpesvirus 4, Human ; Histiocytes ; Humans ; Immunoglobulin Heavy Chains ; In Situ Hybridization ; Killer Cells, Natural ; Lower Extremity ; Lymphocytes ; Lymphoma ; Lymphoma, T-Cell* ; Pathology ; Phenotype ; RNA ; Skin ; Stem Cells ; T-Lymphocytes ; Telangiectasis ; Young Adult