An Atypical relapsing follicular lymphoma to composite Hodgkin's lymphoma.

Composite lymphoma is defined as two or more lymphomas with distinct morphological and immunophenotypical characteristics synchronously diagnosed at the same anatomical site. Composite lymphoma is rare, and the most common combination is follicular lymphoma (FL) associated with diffuse large B cell lymphoma, followed by FL associated with classic Hodgkin's lymphoma (HL). Histologically, composite lymphomas display a mixed pattern or distinct zonal distribution of each lymphoma component. Composite lymphoma poses a diagnostic challenge, especially when two lymphoma components are mixed in the same lymph node. Here, we report a case of composite HL and FL 11 years after initial and repeat biopsies consistent with FL in a man in his 70s emphasising the importance of repeat biopsy in lymphoma diagnosis.

[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.

Pathological and molecular analysis of a composite lymphoma of mantle cell lymphoma and Epstein-Barr virus-positive follicular lymphoma.

Composite lymphoma (CL) is a very rare clinical entity defined by the presence of two or more different subtypes of lymphoma in the same lymph node. We report a case of CL in a 78-year-old male presenting with leukocytosis and swelling of multiple lymph nodes. A left axillary node biopsy showed atypical lymphocytes in both the interfollicular and follicular areas. Immunohistochemistry revealed that mantle cell lymphoma (MCL) was mainly present in the interfollicular area and follicular lymphoma (FL) was present in the follicular area. Polymerase chain reaction analysis of immunoglobulin heavy chain gene rearrangements confirmed that they were clonally related neoplasms. However, Epstein-Barr virus (EBV) DNA was detected in only FL cells, suggesting that MCL and FL had split into two clones in the early steps of pathogenesis. This is the first reported case of CL with EBV-negative B-cell non-Hodgkin lymphoma (NHL) and EBV-positive B-cell NHL with a clonal relationship. We discuss the developmental processes of these two lymphomas.

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.

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.

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.

Diagnostic utility of programmed cell death ligand 1 (clone SP142) in mediastinal composite lymphoma: A report of two cases.

Composite lymphoma is a well-known diagnostic entity exhibiting the synchronous occurrence of two or more distinct types of lymphomas in the same specimen. Here we report two patients, a 14-year-old female (Case 1) and a 45-year-old male (Case 2), with mediastinal composite lymphoma, comprising nodular sclerosis classic Hodgkin lymphoma (NSCHL) and primary mediastinal large B-cell lymphoma (PMBL). Both patients had a mediastinal mass, and manifested two different histologic components in the same biopsy, one characteristic of NSCHL and the other PMBL. The NSCHL areas included Hodgkin and Reed-Sternberg (HRS) cells with typical immunophenotypic features (CD30-positive and CD20-negative), whereas the sheets of large tumor cells characteristic of PMBL were strongly and uniformly CD20-positive. Interestingly, although both cases showed neoplastic PD-L1 (nPD-L1) positivity on the HRS cells of NSCHL, they differed regarding nPD-L1 expression on the PMBL tumor cells. In Case 1, the nPD-L1-negative PMBL component was anatomically situated outside the NSCHL lesion. On the other hand, in Case 2, the nPD-L1-positive PMBL component was characterized by transitional or continuous areas with the NSCHL component. These findings suggested that nPD-L1 expression may define two subtypes of PMBL that are more similar to or distinct from classic Hodgkin lymphoma.

Composite Lymphoma Containing Mantle Cell and Peripheral T-cell Lymphoma, Not Otherwise Specified: A Report of 2 Cases Treated With Up-front Autologous Stem Cell Transplantation.

We report 2 cases of composite lymphoma comprising mantle cell lymphoma and peripheral T-cell lymphoma, not otherwise specified, a rare association that has only been reported twice in the literature. In case 1, a 64-year-old woman presented with massive splenomegaly and lymphadenopathy. Immunohistochemical studies of the lymph node biopsy suggested the presence of 2 lymphomas, a predominant component of a peripheral T-cell lymphoma, not otherwise specified and an in situ mantle cell neoplasia. These suspicions were confirmed with polymerase chain reaction and fluorescence in situ hybridization studies. In case 2, a 45-year-old man presented with an enlarged right tonsil. Contrary to case 1, the biopsy suggested a predominant infiltration of a classical mantle cell lymphoma and an atypical proliferation of T cells. Biclonality was also confirmed with fluorescence in situ hybridization and molecular techniques. Both cases were treated with an up-front autologous stem cell transplantation after achieving first complete remission, and they remained free of disease for a long period of time.

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.

The Conundrum of Diagnosing Cutaneous Composite Lymphoma in the Molecular Age.

INTRODUCTION: Cutaneous composite lymphoma (CCL) is extremely rare. When 2 potentially distinct lymphoid lesions occur at one skin site, distinguishing between one neoplastic clone and a secondary reactionary lymphoid response versus a second neoplasm is difficult. In this study, we describe a unique case of CCL along with a review of reported cases in literature to identify clues and discuss issues that are relevant to the diagnosis of CCL. DESIGN: Review of a CCL case from our institution and a systematic review of reported cases of CCL in the literature. RESULTS: A total of 18 studies describing 22 cases and a case report from our institution are included. The mean age at diagnosis was 68 years. Most cases herein presented with multiple skin lesions (67%) and reported a history of immune suppression (76%). Nineteen cases (83%) had a combination of T-cell and B-cell neoplasms, whereas the remaining cases had 2 distinct B-cell clones. Clonal differentiation was confirmed based on morphology and immunohistochemistry in all cases, and by polymerase chain reaction studies in 19 cases. Complete remission was achieved in only one quarter of reported cases. CONCLUSION: Diagnosing CCL can be challenging because accurate differentiation of 2 or more clonal populations at 1 site is tedious. A stepwise approach and integration of clinical, morphologic, immunohistochemistry, and molecular data along with an understanding of the prognosis of the lymphomas in question is essential for an accurate diagnosis and necessary because of therapeutic and prognostic implications.

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.

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: Simultaneous development of three different lymphomas in a single patient: A clinical case].

In the past decades, there has been an increase in the incidence of malignancies, including polyneoplasms. Composite synchronous lymphoma characterized by the simultaneous development of several lymphoproliferative diseases occurs very rarely. This paper describes a case of development of 3 different lymphomas in the same patient. Aggressive T-cell lymphoma and indolent B-cell lymphoma are diagnosed during lifetime; primary central nervous system lymphoma is verified only by examination of autopsy material. Three different lymphomas could be identified by an integrated assessment of their clinical picture and by current diagnostic techniques, such as histology, immunohistochemistry, and molecular genetics.

Pathogenesis, diagnosis, and treatment of composite lymphomas.

In rare instances, two distinct lymphomas concurrently occur in a patient. Such composite lymphomas can be combinations of two non-Hodgkin lymphomas or a combination of a non-Hodgkin lymphoma and a Hodgkin's lymphoma. Composite lymphomas pose a particular diagnostic challenge, and there are currently no agreed standards for treatment. Combined B-cell non-Hodgkin lymphomas are often clonally unrelated. However, in many composite non-Hodgkin lymphomas and Hodgkin's lymphomas, the tumours are clonally related. In most of these instances, the malignant clones developed separately from a common precursor, usually a germinal centre B cell. This finding suggests a scenario in which the common premalignant precursor had acquired shared transforming events, and the two distinct lymphomas developed from descendants of that precursor after acquiring additional separate transforming events. Findings from molecular studies support this notion. Hence, clonally related composite lymphomas are elegant models to study the multistep transformation process in lymphomagenesis.