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Composite lymphoma, defined as two or more distinct well-defined entities involving the same anatomic site, is rare. Here we report a 79-year-old woman with composite mantle cell lymphoma (MCL) and lymphoplasmacytic lymphoma (LPL) involving bone marrow at the time of initial diagnosis. The patient presented with splenomegaly and lymphadenopathy and laboratory studies showed an elevated serum IgM level and IgM kappa paraprotein. Bone marrow evaluation showed concurrent involvement by MCL and LPL, supported by immunophenotypic studies that revealed two distinct aberrant B-cell populations. Next-generation sequencing analysis identified concurrent MYD88 and CXCR4 mutations and fluorescence in-situ hybridization showed CCND1 translocation, supporting the diagnosis of concomitant MCL and LPL. In conclusion, composite lymphoma can present in the bone marrow. The use of ancillary studies was essential in reaching the diagnosis in this case, as the results excluded the possibility of MCL lymphoma with plasmacytic differentiation, as well as other CD5- and CD10-negative small B-cell lymphomas.

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Composite lymphoma (CL) is a rare cancer characterized by the concurrent occurrence of more than one type of lymphoma within the same organ or tissue in an individual. Its occurrence at extranodal sites is exceptional, with only a few cases documented in the literature. A 62-year-old gentleman presented with dystonia, dysphagia, and irregular enlargement of the right tonsil for the last three months. Based on a clinical suspicion of tonsillar malignancy, tonsillectomy was done. The histopathologic examination revealed effacement of the architecture by large irregular lymphoid nodules with interfollicular expansion. The nodules showed sheets of small atypical lymphoid cells, while the interfollicular areas showed large atypical lymphoid cells with scattered typical binucleate Reed-Sternberg cells. Immunohistochemistry confirmed mantle cell lymphoma (MCL) in the nodules and classical HL (cHL) in the interfollicular areas. Based on these features, a diagnosis of composite MCL with cHL was rendered. He was treated with bendamustine and rituximab chemotherapy and remained in complete remission for five years when he presented with significant right-sided neck swelling. Percutaneous fine needle aspiration and subsequent flow cytometry confirmed a relapse of the MCL component of the CL. The index report documents an exceptional case of CL, comprising MCL and cHL, presenting at an uncommon extranodal site. In addition, it also emphasizes the importance of adequate sampling and the simultaneous use of immunochemistry and/or flow cytometry to confirm the presence of more than a single type of lymphoma, which may be easily overlooked on microscopy alone.

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Lymphoid proliferations and lymphomas associated with immune deficiency and dysregulation (LP/L-IDD) are rare entities associated with the use of immunosuppressive drugs (ISD) for autoimmune conditions. Composite lymphomas, featuring both B-cell and T-cell lymphomas, are infrequent, and their occurrence as LP/L-IDD is rare. We herein report the case of a 70-year-old man with right pleural effusion and lymphadenopathy, who was treated with infliximab for sarcoidosis and ankylosing spondylitis. A biopsy revealed a composite lymphoma of DLBCL and PTCL-NOS. CHOP chemotherapy led to significant remission. This case report emphasizes the need to consider lymphoma in patients with autoimmune diseases such as sarcoidosis and ankylosing spondylitis, especially those treated with ISDs.

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Composite lymphoma is an uncommon type of lymphoid malignancy, and those consisting of concurrent diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) in the same organ are rare. Here, we report a case of a 75-year-old male patient admitted to our emergency department with intestinal obstruction presenting with abdominal pain and vomiting. He underwent partial resection of the small intestine under general anesthesia, and subsequent histopathology confirmed the mass to be composite DLBCL and PTCL-NOS. The patient received chemotherapy with a rituximab-based regimen and achieved complete remission (CR). However, the recurrent disease presented with obstruction again ten months after treatment. He refused a second surgery, but salvage treatment was not effective. The patient survived for 20 months after diagnosis. In addition, we did a literature review to understand the clinical features, pathology, treatment, and prognosis of this type of composite lymphoma.

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Diffuse large B-cell lymphoma (DLBCL) and angioimmunoblastic T-cell lymphoma (AITL) are two subtypes of non-Hodgkin lymphoma (NHL). The simultaneous occurrence of DLBCL and AITL in a composite lymphoma is very rare, and there are no established treatment regimens. We present the case of an 85-year-old male admitted to the intensive care unit with distributive shock, lymphocytosis, and lymphadenopathy, who was subsequently diagnosed with composite AITL and DLBCL, and treated with brentuximab vedotin (BV) and rituximab. To our knowledge, this is the first case of composite lymphoma presenting with distributive shock and treated with BV and rituximab, with successful resolution of shock.

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Composite/synchronous lymphoma is an uncommon condition that presents a challenge in histopathological diagnosis due to the simultaneous appearance of two or more lymphomas, including instances where they are intermixed within the same location. Performing a core needle tissue biopsy adds a challenge for pathologists when trying to diagnose a condition that requires excisional tissue for a thorough evaluation. This report highlights a distinctive instance of composite lymphoma in which classical Hodgkin lymphoma (cHL) is combined with diffuse large B-cell lymphoma (DLBCL). All pertinent information including clinical, histopathological, and immunohistochemical data for each of these composite lymphomas is provided. In addition, we conducted a literature review of the published data. The findings from these data further support the theory of a shared clonal origin and transdifferentiation occurrence in the process of lymphoma development.

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Session 3 of the 2021 European Association for Haematopathology/Society for Hematopathology Workshop focused on mediastinal large B cell lymphomas and surrounding gray areas. One half of the session was dedicated to primary mediastinal large B cell lymphoma (PMBL) and included cases with classic clinicopathologic features, as well as cases with either morphologic or immunophenotypic variation, and PMBL-like cases with primary extramediastinal disease. The role of additional immunophenotyping and/or molecular testing to aid in the diagnosis of PMBL was discussed. The second half of the session focused on mediastinal and non-mediastinal gray zone lymphomas (GZL) with features intermediate between diffuse large B cell lymphoma (DLBCL) and classic Hodgkin lymphoma (CHL). Several cases illustrating the current challenges in separating this entity from PMBL/DLBCL and CHL were presented. There was discussion regarding the clinical and genetic differences between mediastinal and non-mediastinal GZLs. Rare cases of PMBL and GZL associated with EBV or follicular lymphoma were reviewed. Finally, several cases included in the session highlighted composite or sequential CHL and PMBL/DLBCL and/or GZL, highlighting challenges in separating such cases from GZL.

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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.

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We report a case of an elderly male who presented with enlarged abdominal lymph nodes and was diagnosed as having Epstein-Barr virus-positive diffuse large B-cell lymphoma, not otherwise specified (EBV+ DLBCL, NOS). He was started on chemotherapy which had to be discontinued after three cycles due to the development of life-threatening pneumocystis carinii pneumonia and poor performance status. Within two years, the patient presented with features of relapse. A repeat histopathological examination of the lymph node showed features of peripheral T-cell lymphoma, NOS and the clonality was confirmed by T-cell receptor gamma chain rearrangement assay. More studies are needed to understand the association of EBV+ DLBCL, NOS with other lymphomas.

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Background: Compound lymphoma is an uncommon type of lymphoid malignancy, and those consisting of concurrent B- and T-cell tumors are relatively rare. Case Summary: A 41-year-old man was presented with a 1-month history of progressively worsening cough, chest tightness, and dyspnea after exercise, which could be relieved following rest. Contrast-enhanced computed tomography scan demonstrated a 7.4 × 4.9 cm2 heterogeneous mass in the anterior mediastinum, where a large area of cystic liquid existed, and multiple enlarged lymph nodes in the mediastinum. Since the biopsy failed to yield an exact diagnosis and there was no sign of metastasis, the tumor was surgically resectioned. Surgical findings included obscure boundaries and consistent tumor stiffness with pericardial and pleural invasion. Further pathological examination combined with immunophenotype and gene rearrangement test found the mass composite of angioimmunoblastic T-cell lymphoma (AITL) and B-cell lymphoma. The patient recovered well after R0 resection and received chemotherapy with four cycles of CHOP combined with chidamide 2 weeks after surgery. The patient has had a complete response for over 60 months. Conclusion: In conclusion, we reported a composite lymphoma of AITL combined with B-cell lymphomas. Our experience provides the first successful attempt to treat this rare disease with combined surgery and chemotherapy.

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Composite mantle cell lymphoma and classical Hodgkin lymphoma is very rare and the actual origin of it is still unclear. Here we reported a new case of composite mantle cell lymphoma and classical Hodgkin lymphoma and analyzed its molecular changes. Eight mutations were identified in its Hodgkin component through next-generation sequencing. In addition, we reviewed the published cases of composite mantle cell lymphoma and classical Hodgkin lymphoma and summarized the molecular changes of reported cases as well as the current case to explore the possible pathway of histogenesis.

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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.

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Background: Composite lymphomas involving B-cell and T-cell lymphomas is very rare. Case presentation: We reported a 63-year-old gentleman with composite chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL). The patient was admitted to our hospital due to abdominal pain, and was diagnosed with CLL/SLL after bone marrow (BM) biopsy, BM aspiration, and flow cytometry. Two weeks later, he was diagnosed with MEITL based on pathological analysis after intestine excision. Next gene sequencing (NGS) findings identified two hotspot mutation sites (STAT5B and DNMT3A) closely related with the pathogenesis of CLL/SLL and MEILT. Additionally, BCOR mutation was only detected in the CLL/SLL area. The likely pathogenic mutations of CLL were SETD2, NOTCH1, SF3B1, and PTPN11, while the likely pathogenic mutations related with the MEILT were TET2 and ZRSR2. Mutations of GATA3, PLCG2, and FAT1 were identified in both CLL/SLL and MEITL areas, but the clinical significance was unknown. Finally, the patient died in the 12-month follow-up after surgery. Conclusion: We report a rare case of composite CLL/SLL and MEITL that highlights the importance of careful inspection of hematologic neoplasms. We also present the results of NGS of different gene mutations in CLL and MEITL tissues.

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The co-occurrence of several lymphomas in a patient defines composite/synchronous lymphoma. A common cellular origin has been reported for both contingents of such entities. In the present review, we aimed to gather the available data on composite lymphomas associating a classical Hodgkin lymphoma (cHL) with another lymphoma, to better understand the plasticity of mature B and T-cells. This review highlights that >70% of patients with a composite lymphoma are ≥55 years old, with a male predominance. The most reported associations are cHL with follicular lymphoma or diffuse large B-cell lymphoma, with over 130 cases reported. The cHL contingent is often of mixed cellularity type, with a more frequent focal/weak CD20 expression (30% to 55.6%) compared to de novo cHL, suggesting a particular pathophysiology. Moreover, Hodgkin cells may express specific markers of the associated lymphoma (e.g., BCL2/BCL6 for follicular lymphoma and Cyclin D1 for mantle cell lymphoma), sometimes combined with common BCL2/BCL6 or CCND1 rearrangements, respectively. In addition, both contingents may share similar IgH/IgK rearrangements and identical pathogenic variants, reinforcing the hypothesis of a common clonal origin. Finally, cHL appears to be endowed with a greater plasticity than previously thought, supporting a common clonal origin and a transdifferentiation process during lymphomagenesis of composite lymphomas.

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Herein, we describe the clinicopathologic and genetic characteristics of the first report of simultaneous bone marrow involvement by classical hairy cell leukemia (HCL) and leukemic non-nodal variant of mantle cell lymphoma (L-NN-MCL) with t(11;14)(q13;q32) with BRAF mutation and deletion of TP53. A 40-year-old asymptomatic man was investigated for incidental neutropenia and thrombocytopenia. Flow cytometry showed two distinct monotypic B-cell populations: one expressed CD19 (bright), CD20 (bright), FMC7, CD103, CD25, CD11c, CD123, and IgD (bright) and showed kappa light chain restriction (bright), consistent with HCL and the other kappa-restricted CD5/CD10-negative B-cell population with distinctive immunophenotypic features. The bone marrow biopsy is infiltrated by an abnormal B-lymphoid infiltrate with different patterns of infiltration in different marrow areas. Fluorescence in situ hybridization (FISH) analysis revealed a CCND1/IGH rearrangement, t(11;14)(q13;q32), and deletion of TP53. The BRAF V600E missense mutation was detected by quantitative real-time polymerase chain reaction (PCR). The diagnosis of a composite B-cell neoplasm was composed of HCL together with a second CD5/CD10-negative monotypic B-cell population, with CCND1/IGH fusion, favoring the 2016 WHO new category of L-NN-MCL (CD5/SOX11-negative). Treatment with cladribine and rituximab normalized the blood counts within 6 weeks without significant side effects. L-NN-MCL is one of the smoldering MCL subtypes, recently listed in WHO 2016 as a separate variant, with a particular set of unique features and a less aggressive clinical course compared to classical MCL. To date, the clinicopathological features (including the bone marrow findings) of L-NN-MCL have not been sufficiently characterized in the literature. We describe the first report of synchronous presentation of HCL and L-NN-MCL. This case represents a real challenge from the biologic, diagnostic and therapeutic point of views, due to extremely rare combination of two distinct uncommon B-cell neoplasms. The study of composite lymphomas offers the opportunity to evaluate the etiology and the clonal interrelationship involved in the pathogenesis/evolution of lymphomas.

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Composite lymphoma represents 1-4% of lymphomas. Only 8 case reports concerned coexisting follicular lymphoma and mantle cell lymphoma. Here, we report the case of an 81 years old man who has been diagnosed with a composite follicular and in situ mantle cell lymphoma. The use of a large panel of immunohistochemical stains associated with the flow cytometry results have allowed us to make this particular diagnosis. We highlight here a common clonal origin of the composite lymphoma's two entities, as described in previous publications.

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Composite lymphoma is very rare and a combination of Hodgkin lymphoma and non-Hodgkin lymphoma and even histiocytic tumors can occur. Because of the unfamiliarity, not only can this cause diagnostic problems, but can also affect treatment plan. We report a case of composite lymphoma in a 40-year-old male. Initial biopsy showed a composite lymphoma of follicular lymphoma grade 1 and classic Hodgkin lymphoma. After chemotherapy, another lymph node was taken because of disease progression, which revealed follicular lymphoma, grade 3a without Hodgkin lymphoma component.

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A synchronous diagnosis of a plasma cell neoplasm (PCN) and a non-plasma cell hematologic malignancy is very rare. We report what we believe is the first instance of a synchronous PCN and B lymphoblastic leukemia/lymphoma (B-ALL) diagnosed at initial presentation. The patient underwent laboratory evaluation for an underlying plasma cell neoplasm, including immunology studies, bone marrow biopsy, and flow cytometry immunophenotyping. Serum lambda free light chain and serum IgG were elevated, with an IgG lambda M-protein identified by serum protein electrophoresis and immunofixation. The clinical working diagnosis was plasma cell myeloma. Bone marrow biopsy was positive for a composite PCN and B-ALL. The patient received treatment with VDT-PACE chemotherapy followed by autologous stem cell transplant and maintenance therapy with bortezomib/daratumumab and is in complete remission for both diseases 3.5 years after diagnosis. This case not only adds to the known repertoire of hematologic neoplasms that can occur in association to a PCN, but also demonstrates that patients presenting with this rare combination of hematopoietic neoplasms can be effectively treated simultaneously with excellent responses. Additional research is warranted to understand the pathophysiology, to identify potential prognostic factors, and to develop specific therapeutic plans for these patients.