Case report: Chronic lymphocytic leukemia/small lymphocytic lymphoma and monomorphic epitheliotropic intestinal T-cell lymphoma: A composite lymphoma.

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.

[Composite lymphoma: Case report of a coexisting follicular and mantle cell lymphoma in situ in a cervical node]. / Lymphome composite : Case report d'un ganglion cervical siège d'un lymphome folliculaire et d'un lymphome à cellules du manteau in situ.

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.

Composite follicular lymphoma and "early" (in situ and mantle zone growth pattern) mantle cell neoplasia: A rare entity with peculiar cytogenetic and clinical features.

Composite follicular lymphoma (FL) and mantle cell lymphoma (MCL) is rare and not fully characterized from a genetic and clinicopathological point of view. We report a composite lymphoma (CL) in which a G1-2 FL was associated with an in situ mantle cell neoplasia (ISMCN) and a mantle zone growth pattern (MZGP) MCL, followed-up for six years after the first diagnosis, until the exitus of the patient. We performed a comprehensive immunohistochemical study and a detailed cytogenetic analysis, including conventional karyotyping, SKY FISH, FISH on metaphases and interphasic separated nuclei, and FISH on histological sections. The study was completed by the review of the 13 published composite FL and MCL. Our results show that this entity generally behaves like an indolent lymphoma, with the outcome of patients driven by the progression of the FL component. The MCL component generally does not evolve in an aggressive disease. Indeed, half of the cases present exclusively ISMCN. In our case, mantle cell neoplasia at diagnosis was represented by ISMCN and MZGP MCL and it was characterized by a simple karyotype, with t(11;14) as the sole cytogenetic abnormality. This cytogenetic aspect well correlates with the indolent behavior of the mantle cell component. Conversely, the complex karyotype of the FL component was associated with disseminated disease that influenced patient's outcome. Finally, we suggest that not only ISMCN, but also isolated MZGP MCL, may be considered as lesions with low potential of transformation in an aggressive MCL.

Composite Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Mantle Cell Lymphoma; Small Cell Variant: A Real Diagnostic Challenge. Case Presentation and Review of Literature.

BACKGROUND Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma (MCL) both have a common origin arising from mature CD5+ B-lymphocytes. Their distinction is crucial since MCL is a considerably more aggressive disease. Composite lymphoma consisting of CLL/SLL and MCL has been rarely reported. This type of composite lymphoma may be under-diagnosed as the 2 neoplasms have many features in common, both morphologically and immunophenotypically. CASE REPORT We report the case of a 57-year-old male patient who presented with a 4-month history of recurrent abdominal pain and distention with hepatosplenomegaly. Peripheral blood showed a high leukocytes count (46.7×10³/uL) with marked lymphocytosis of 35.0×10³/uL, mostly small mature-looking, with some showing nuclear irregularities, with approximately 3% prolymphocytes. Immunophenotyping by flow cytometry and immunohistochemistry revealed 2 immunophenotypically distinct abnormal CD5+monotypic B-cell populations. Fluorescence in situ hybridization (FISH) on peripheral blood demonstrated IGH/CCND1 rearrangement consistent with t(11;14) in 65% of cells analyzed. Accordingly, based on compilation of findings from morphology, flow cytometry, immunohistochemistry, and FISH, A diagnosis of composite lymphoma consisting of MCL; small cell variant and CLL/SLL was concluded. CONCLUSIONS We describe a case of composite lymphoma of MCL (small cell variant) and CLL/SLL that emphasizes the crucial role of the multiparametric approach, including vigilant cyto-histopathologic examination, immunophenotyping by flow cytometry and immunohistochemistry, as well as genetic testing, to achieve the correct diagnosis.

Orbital soft tissue composite lymphoma presenting as recurrence of a nodal lymphoma with mantle and follicular cell components: A case report, literature review and guideline for the treatment of patients.

Composite lymphoma with mantle and follicular cell components is a challenging diagnosis. Flow cytometry, immunohistochemistry and molecular genetics are required to distinguish the two components, as often the more aggressive one is predominant and masks the other. A 58-year-old man with history of nodal composite lymphoma presented with right exophthalmos and diplopia. A head CT scan showed an orbital tumor. A biopsy of the tumor revealed a mantle cell lymphoma predominating over a follicular lymphoma. Immunoglobulin heavy chain and light chain rearrangements analysis by PCR proved that both components of the orbital tumor were recurrences of the same nodal composite lymphoma diagnosed two years earlier. The nodal lymphoma was composed of a follicular lymphoma and an in situ mantle cell neoplasia. Consensus view is that dominant lymphoma should be treated when needed but taking into account if the mantle cell lymphoma is an in situ neoplasia and if it expresses CD5 and SOX11.

Coexistence of Hodgkin and Non-Hodgkin Lymphoma; Composite Lymphoma [CL] in a Patient Presenting with Waxing and Waning Lymphadenopathy.

BACKGROUND: The coexistence of two or more types of lymphoma within the same organ at the same time of diagnosis is defined as composite lymphoma, a rare disease that has recently been identified in the literature. Pointedly, the concurrence may be Hodgkin lymphoma with a Non-Hodgkin lymphoma [NHL], either B or T cells, or two different entities of NHLs. Furthermore, this condition has been described concurrently or sequentially. In order for the diagnosis to be established, two or more distinct clones should be proven by morphological and laboratory tests. CASE PRESENTATION: Herein, we cite a seventy-three-year old female patient with low-grade fever, waxing and waning cervical lymphadenopathy, whose biopsy of an axillary lymph node demonstrated the rare coexistence of Hodgkin and NHL, known as composite lymphoma. CONCLUSION: Composite lymphomas pose a particular diagnostic challenge, and currently, there are no agreed standards for treatment.

A Case of Composite Lymphoma with Extranodal NK/T-cell Lymphoma, Nasal-type and Diffuse Large B-cell Lymphoma.

Composite lymphoma (CL) is defined as the occurrence of two distinct types of lymphoma within the same patient. Most cases of CL involve Hodgkin and non-Hodgkin lymphomas or two distinct types of B-cell lymphomas; true CL is a composite B-cell and T-cell lymphoma, and is rare. We herein report a case involving concurrent extranodal NK/T-cell lymphoma, nasal-type and diffuse large B-cell lymphoma, which has not been previously reported. As the mechanisms and treatments of composite B-cell and T-cell lymphomas are unclear, further studies are required to improve the prognosis.

Primary Cutaneous Composite Lymphomas.

Composite lymphomas have been defined as 2 distinct subtypes of lymphoma occurring at a single anatomic site. Composite lymphomas limited to the skin are a rare occurrence and pose a unique challenge. Many reported cases within the skin are combined B-cell and T-cell lymphomas, typically mycosis fungoides and a low-grade B-cell lymphoma. These cases are challenging to recognize because lymphoid infiltrates within the skin often include a mixed population of B cells and T cells. In particular, reactive lymphoid proliferations (pseudolymphomas), primary cutaneous low-grade B-cell lymphomas, and primary cutaneous CD4+ T-cell lymphoproliferative disorder may show nearly equal numbers of B cells and T cells. In order to exclude these possibilities, overwhelming evidence in support of each lymphoma is helpful, including abnormal architecture, cytology, and immunophenotype, as well as molecular genetic evidence of clonality.

High-grade B-cell lymphoma with MYC and BCL2 rearrangements arising in a composite lymphoma.

BACKGROUND: We report the first case of composite lymphoma consisting of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), follicular lymphoma (FL) and high-grade B-cell lymphoma with MYC and BCL2 rearrangements within the same needle biopsy in which a clonal relationship between the FL and high-grade B-cell lymphoma components was demonstrated by molecular cytogenetics. CASE PRESENTATION: An 85-year-old man presented with masses in his neck and right groin. Cutting needle biopsy of the inguinal mass revealed the three lymphoma types which were morphologically, immunophenotypically and topographically distinct. Fluorescence in situ hybridization (FISH) identified an IGH-BCL2 rearrangement in both the FL and high-grade B-cell components while a MYC rearrangement was detected in the high-grade B-cell component alone. CONCLUSIONS: Our findings suggest that the high-grade lymphoma with MYC and BCL2 translocations evolved through transformation of the FL by a process that entailed acquisition of the MYC translocation. No clonal relationship between the FL and CLL/SLL components was evident since the IGH-BCL2 rearrangement was present in in the former but not the latter. This unique case of co-localized FL, CLL/SLL, and high-grade B-cell lymphoma contributes to our understanding of the clonal relationships that may exist between the components of composite lymphomas.

Composite lymphoma of follicular B-cell and peripheral T-cell types with distinct zone distribution in a 75-year-old male patient: a case study.

Composite lymphoma of T-/B-cell type is rare, and follicular lymphoma composite with peripheral T-cell lymphoma (PTCL) has not previously been reported. We report such a case with both neoplastic components displaying a unique zone of distribution. A 75-year-old male patient presented with generalized lymphadenopathy. Sections of axillary lymph node demonstrated potentially 2 clonal processes, PTCL with aberrant CD20 expression and follicular lymphoma. Interestingly, the 2 neoplastic components were confined to their respective classic distribution zones, with PTCL occupying the interfollicular areas and follicular lymphoma residing in follicles. Both populations were detected by flow cytometry, but their immunophenotypes were insufficient to define clonality. Nonetheless, biclonality was demonstrated by lymphoid receptor gene rearrangement analyses. Molecular cytogenetics showed IGH/BCL2 fusion in the follicular lymphoma and amplification of IGH gene or trisomy/tetrasomy 14 in the PTCL. The current case underscores the complexity of composite lymphoma and advocates a multimodal approach to establishing the diagnosis.

Composite lymphomas: Experience from a tertiary cancer center in Kerala, South India.

OBJECTIVES: Composite tumors are defined as tumors in which there are two different intermixed histologic types. Our objective was to study the clinical and pathologic features of five cases of composite lymphoma. MATERIALS AND METHODS: Our study included five patients of composite lymphoma diagnosed over a period of 5 years. Clinical presentation, hematological parameters including peripheral smear, bone marrow aspirate, and histopathological examination of lymph node including immunohistochemistry (IHC) were studied. Treatment and follow-up details were also noted. RESULTS: All the five cases were in the adult age group ranging from 44 to 72 years. All the cases were composite follicular lymphoma (FL) and mixed cellularity classical Hodgkin lymphoma (CHL). Diagnosis in all cases was suspected on morphology by identification of distinct neoplastic follicles in FL and classic Reed-Sternberg cells in CHL and confirmed by IHC. CONCLUSION: Although rare, composite lymphomas should be kept in mind. Careful histopathological examination of lymph node with identification of distinct morphological features along with IHC helps to arrive at the definitive diagnosis.

Composite lymphoma with coexistence of diffuse large B-cell lymphoma and anaplastic large cell lymphoma: Diagnostic pitfalls.

Composite lymphoma is a rare tumor composed of two or more distinct lymphomas in the same topographic site or tissue. Several combinations of B-cell non-Hodgkin lymphoma (NHL), T-cell NHL, and Hodgkin lymphoma can occur with different prognoses and treatments. The coexistence of a B-cell NHL and a T-cell NHL is unusual. The exact etiology of composite lymphoma is unknown; however, few mechanisms have been proposed to explain its pathogenesis. The chemotherapeutic protocols are heterogeneous but are essentially targeted against the high-grade component. Most of the cases show worse outcome with a median survival of 12 months. In this article, we report a case of composite lymphoma which was initially diagnosed as diffuse large B-cell lymphoma, and the presence of CD3-positive atypical cells in the bone marrow urged us to re-evaluate the lymph node biopsy following which a focus of Alk-1-positive anaplastic large cell lymphoma was identified.

Composite lymphoma of peripheral T-cell lymphoma and Hodgkin lymphoma, mixed cellularity type; pathological and molecular analysis.

Composite lymphomas (CLs) are defined as two unrelated lymphomas occurring at the same time within the same tissue. The incidence of these tumors is low. Of all possible combinations between lymphomas, the least frequent are the ones combining peripheral T-cell lymphoma (PTCL) and Hodgkin lymphoma (HL). We recently identified five cases of CL composed of PTCL and classical HL, mixed cellularity type. We investigated histological and clinical features of these cases. Immunostaining was performed on paraffin sections. PTCL cells were positive for CD8 and TIA-1 in four of the five cases. Hodgkin and Reed-Sternberg (HRS) cells were positive for CD30 and weakly positive for PAX5 in all cases, positive for CD15 in three of five cases, positive for CD20 in one of five cases, and negative for EBER. Monoclonal rearrangement of the T-cell receptor (TCR) and immunoglobulin heavy chain (IGH) genes was confirmed by polymerase chain reaction (PCR) using whole paraffin sections. We concluded more precisely the monoclonality of the IGH rearrangement of HRS cells based on single-cell PCR for IGH and DNA sequencing analysis after laser microdissection of single cells in one case. HL can occur in CD8-positive and TIA-1-positive PTCL. Clinicians should recognize the possibility of these CL.

Composite Blastoid Variant of Mantle Cell Lymphoma and Classical Hodgkin Lymphoma.

Composite lymphoma (CL) describes the rare occurrence of 2 or more distinct types of lymphoma in a single anatomical location. We present the case of a 78-year-old man presenting with a 3-month history of weakness, malaise, and increasing dyspnea. A lymph node excised from the posterior triangle of the neck revealed the coexistence of 2 morphologically and phenotypically distinct lymphoid neoplasms consistent with a blastoid variant of mantle cell lymphoma (MCL) occurring in composite with classical Hodgkin lymphoma (cHL), mixed cellularity subtype. A t(11;14)(q13;q32) translocation was demonstrated by fluorescence in situ hybridization in the MCL and Hodgkin Reed-Sternberg cells of the cHL. Multiplex polymerase chain reaction detected clonal Immunoglobulin heavy chain (VFR1-J, VFR2-J, and VFR3-J), clonal immunoglobulin light chain kappa (V-J and V/JC intron-kde) and clonal immunoglobulin light chain lambda (V-J) gene rearrangements in the MCL. This report represents the first case of a blastoid variant of MCL occurring in composite with cHL.

Four Lymphomas in 1 Patient: A Unique Case of Triple Composite Non-Hodgkin Lymphoma Followed by Classical Hodgkin Lymphoma.

Composite lymphomas consist of 2 or more distinct lymphomas occurring in a single anatomical site or simultaneously in different sites and can be composed of any combination of B-cell non-Hodgkin lymphoma (NHL), T-cell NHL, or Hodgkin lymphoma (HL). Cases of composite lymphomas with more than 2 lymphomas are extremely rare, with only 4 reports in the literature. We report the case of a 49-year-old man with a triple composite lymphoma in a single lymph node, consisting of small lymphocytic lymphoma, follicular lymphoma, and mantle cell lymphoma in situ. The patient received multiple courses of chemotherapy and an autologous stem cell transplant, which resulted in complete remission. Then, 6 years after the stem cell transplant, he developed classical HL. This unique case is, to our knowledge, the first report of a patient with triple composite lymphoma consisting of 3 small mature B-cell NHLs, who subsequently developed a fourth lymphoma.

Composite lymphoma with diffuse large B-cell lymphoma and classical Hodgkin lymphoma components: A case report and review of the literature.

Composite lymphoma (CL) is an infrequently diagnosed entity in which two or more distinct types of lymphomas occur synchronously in the same organ or anatomical site. Most commonly, CLs are composed of two non-Hodgkin B-cell lymphomas. We present a case of a composite lymphoma with diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS) and classical Hodgkin lymphoma (CHL) components involving the terminal ileum, colon and pericolic lymph nodes. Immunohistochemical evaluation for determination of cell of origin of the DLBCL-NOS component indicated a germinal center B-cell subtype. Immunoglobulin heavy chain fragment length analysis revealed identical dominant monoclonal peaks on the DH1-6-JH reaction, and also a dominant monoclonal peak observed only in the framework II reaction done on the CHL component, indicating a partial clonal relationship between the two components. Additionally, a review of the available literature reveals a total of 20 previously reported cases of CL with DLBCL-NOS and CHL components, and most of the tested cases showed clonal relationship between the two components. The overall findings indicate that in most cases, the two components of CL with DLBCL-NOS and CHL components are clonally related, and suggest a shared origin from a common B-cell precursor.

Multifocal mantle cell lymphoma in situ in the setting of a composite lymphoma.

OBJECTIVES: Mantle cell lymphoma in situ (MCLIS) consists of immunophenotypically defined but histologically inapparent neoplastic cells restricted to narrow mantle zones, without expansion or invasion beyond the mantle zone. We report a unique case of MCLIS associated with a much more manifest nodal marginal zone lymphoma (MZL) in an inguinal lymph node, porta hepatis lymph node, and bone marrow. METHODS: Biopsies from all three locations were evaluated using standard H&E-stained sections, immunohistochemistry, flow cytometry, metaphase cytogenetics, and/or fluorescence in situ hybridization (FISH). RESULTS: This case is unique for three reasons. First, the histologically covert mantle cell lymphoma was multifocal, detected in all three locations using one or more of flow cytometry, immunohistochemistry, cytogenetics, and FISH. Second, the MCLIS was always accompanied by a more histologically dominant MZL. Third, where evaluable, it did not grow in an appreciable mantle zone distribution, presumably due to destruction of the normal nodal architecture by the neoplastic MZL cells and the resulting absence of recognizable follicles and mantle zones. CONCLUSIONS: This unique case provides new insight into the pathogenesis of MCLIS.