Lymphoma & related disorders
General
Composite lymphoma
Last author update: 1 June 2017
Last staff update: 9 November 2020
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PubMed Search: Composite lymphoma [title]
Table of Contents
Definition / general | Essential features | Terminology | Epidemiology | Sites | Etiology | Clinical features | Diagnosis | Prognostic factors | Case reports | Treatment | Microscopic (histologic) images | Flow cytometry description | Differential diagnosisCite this page: Yang G, Abdelhalim F. Composite lymphoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lymphomacompositelymphoma.html. Accessed April 26th, 2024.
Definition / general
- Defined as two or more morphologically and immunophenotypically distinct lymphomas or lymphoid neoplasms that occur in the same organ or tissue site (Cancer 1977;40:959)
Essential features
- Two or more distinct lymphomas or lymphoid neoplasms in the same location
- 1 - 4.7% of all lymphomas
- One lymphoma component often overshadows the other component
- Ancillary studies very helpful
Terminology
- First introduced by Custer in 1954 as, "the occurrence of more than one histological pattern of lymphoma in a single patient" (Custer: Pitfalls in the Diagnosis of Lymphoma and Leukemia from the Pathologist's Point of View, Proceedings of the Second National Cancer Conference, Netherland Plaza Hotel, Cincinnati, Ohio, March 3,4,5, 1952)
- Refined by Kim et al. in 1977 (Cancer 1977;40:959)
Epidemiology
- Accounts for 1% to 4.7% of all lymphomas (J Clin Exp Hematop 2016;56:55)
- Combinations include (Am J Clin Pathol 2005;123:215):
- Hodgkin lymphoma (HL) with a B cell or a T cell non-Hodgkin lymphoma (NHL)
- B cell NHL with a T cell NHL
- 2 distinct B cell or T cell NHLs at the same anatomic site
- Most reported cases are B cell lymphoma composite with a Hodgkin lymphoma or two composite B cell lymphomas of different types (Hum Pathol 2014;45:768)
- Few cases of combined classic and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) also described (Ann Oncol 1994;5 Suppl 1:7)
Sites
- Lymph node is the most common involved anatomic site
- Also spleen or other extranodal sites including GI, respiratory system, salivary glands, bone, skin, liver and bone marrow (J Egypt Natl Canc Inst 2007;19:171)
Etiology
- For composite B cell lymphoma (J Egypt Natl Canc Inst 2007;19:171):
- Clonal selection
- Genomic instability and congenital predisposition
- Common precursor cell
- For composite B cell NHL and HL: common precursor cell origin (J Egypt Natl Canc Inst 2007;19:171)
- For composite T cell lymphoma with HL or B cell lymphoma:
- EBV infection in B cells or RS cells causes reactive T cell proliferation
- T cell neoplasm first provokes a B cell response with a pathogenic role for EBV; such B cells infected with EBV later transform to RS cells of Hodgkin lymphoma
- A state of immunosuppression associated with some cases of T cell lymphoma lead to a prominent EBV associated B cell proliferation
- Origin: (a) from a common EBV infected progenitor cell, (b) from the same clonal IgH gene rearrangement, (c) totally coincidental existence of two independent de novo neoplastic growth with two separate histogenic processes (J Egypt Natl Canc Inst 2007;19:171)
- For composite AITL and B cell lymphoma:
- The neoplastic cells in AITL produce B cell stimulatory factors leading to a continuous stimulation of B cells and promoting their malignant transformation
- EBV is known to be associated with AITL and this specific microenvironment might be associated with the increasing risk of development of an EBV positive B cell lymphoma
- TET2 mutations are commonly seen in AITL T cell tumor clones
- These mutations have been identified in some monocytes and hemopoietic precursor cells and might also be shared by the B cell clones
- As such, this genetic lesion might cause the simultaneous development of both T and B cell lymphomas (Lancet Oncol 2014;15:e435)
- Chronic exposure to common antigens or carcinogens simultaneously stimulates or transforms B and T cells lineages (Hum Pathol 2014;45:768)
Clinical features
- Seen in wide age range (26 - 88 years) but more common in elderly people with male predominance (2.5:1)
- Presents either as concurrent or sequential (metachronous) disease in the same organ
- In case of sequential disease, the second malignancy may be identified with recurrence of the primary type (J Egypt Natl Canc Inst 2007;19:171)
Diagnosis
- Biopsy (usually lymph nodes) investigated with morphological, immunohistochemical and molecular techniques
- The morphological criteria include cytological features of the tumor cells and the bystander cells and the growth pattern of the lymphoma (Lancet Oncol 2014;15:e435)
- Diagnosis can be challenging because one lymphoma component often overshadows the other component
- Ancillary studies, such as flow cytometry, immunohistochemistry, oncogenic virus tests, (such as EBV, cytogenetic study and molecular tests) can be very helpful in detection of masked neoplastic components (Hum Pathol 2014;45:768)
Prognostic factors
- The prognosis of CL patients is still not very clear and different literatures show conflicting conclusions (Hum Pathol 2014;45:768, Hum Pathol 2013;44:110, Am J Clin Pathol 2014;141:737)
- The overall prognosis usually depends on the more aggressive component of CL and should be treated accordingly
- The survival of CL patients is mainly defined by the response of the more aggressive component to chemotherapy (Eur J Haematol 2014;93:537)
Case reports
- 34 year old man with a distinctive composite FL and MCL with a mixed cell pattern (Am J Clin Pathol 2014;141:737)
- 35 year old man with composite diffuse large B cell lymphoma (DLBCL) and peripheral T cell non-Hodgkin lymphoma in the tibia (Am J Clin Pathol 2005;123:215)
- 43 year old man with composite peripheral T cell lymphoma, NOS and DLBCL in the larynx (Ann Clin Lab Sci 2012;42:73)
- 48 year old woman with composite AILT and diffuse large B cell lymphoma (Am J Clin Pathol 2002;118:848)
- 52 year old woman with composite peripheral T cell lymphoma, NOS and DLBCL in the bone marrow (Ann Lab Med 2015;35:152)
- 65 year old woman with composite classical and nodular lymphocyte predominant Hodgkin lymphoma with progression to DLBCL (Diagn Cytopathol 2017;45:262)
- 66 year old woman with composite DLBCL and CD20 positive PTCL NOS (Pathol Int 2011;61:662)
- 68 year old woman with a composite peripheral T cell lymphoma NOS and B cell SLL presenting with hemophagocytic lymphohistiocytosis (Int J Surg Pathol 2013;21:303)
- 69 year old man with composite MCL and "gray zone" lymphoma in two different anatomical locations (J Med Cases 2014;5:241)
- 69 year old white man with composite mantle cell lymphoma and diffuse large B cell lymphoma of the testis (Eur J Haematol 2014;93:537)
- 72 year old Japanese man with a composite FL and CD5 positive nodal marginal zone lymphoma (J Clin Exp Hematop 2016;56:55)
- 78 year old man with composite blastoid variant of mantle cell lymphoma (MCL) and classical Hodgkin lymphoma, mixed cellularity subtype (Int J Surg Pathol 2017;25:281)
- 80 year old woman and 61 year old man with composite peripheral T cell lymphoma unspecified and B cell small lymphocytic lymphoma (Hum Pathol 2007;38:787)
- 11 cases of composite MCL and CLL / SLL (Hum Pathol 2013;44:110)
- 14 cases of composite lymphoid neoplasm of B cell and T cell origins (Hum Pathol 2014;45:768)
- 21 cases of composite lymphoma containing both T and B cell lymphomas (Pathol Int 2012;62:690)
Treatment
- Overall therapeutic strategy needs to consider both disease components and the treatment goals vary dependent on the histological subtype for lymphomas (Lancet Oncol 2014;15:e435)
Microscopic (histologic) images
Images hosted on other servers:
Composite mantle cell lymphoma and CLL / SLL
Flow cytometry description
- Usefulness of multiparametric flow cytometry in detecting composite lymphoma: study of 17 cases in a 12 year period (Am J Clin Pathol 2011;135:541)
- Multiparameter flow cytometry is necessary for detection, characterization and diagnostics of composite mature B cell lymphoproliferative neoplasms (Int J Hematol 2013;98:589)
Differential diagnosis
- Anaplastic variant of diffuse large B cell lymphoma: large tumor cells with bizarre pleomorphic nuclei that may resemble Hodgkin or RS cells but with consistent immunological staining for B cell markers
- Classic HL (cHL) transformation to DLBCL: histological mixing zone exists
- Gray zone lymphoma: a lymphoma showing morphological or immunohistochemical aspects of another lymphoma entity, such as primary mediastinal B cell lymphoma with features of Hodgkin lymphoma (HL) (Lancet Oncol 2014;15:e435)
- T cell / histiocyte rich large B cell lymphoma: the large B cells may mimic Hodgkin and RS cells in cHL but express pan B cell markers with no expression of CD15 and CD30 (World J Gastroenterol 2013;19:6304)
