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ORIGINAL ARTICLE
Year : 2017  |  Volume : 54  |  Issue : 1  |  Page : 358-361
 

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


1 Division of Pathology, Regional Cancer Centre, Thiruvananthapuram, Kerala, India
2 Division of Medical Oncology, Regional Cancer Centre, Thiruvananthapuram, Kerala, India

Date of Web Publication1-Dec-2017

Correspondence Address:
Dr. R A Nair
Division of Pathology, Regional Cancer Centre, Thiruvananthapuram, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijc.IJC_89_17

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 » Abstract 

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.


Keywords: Classical Hodgkin lymphoma, composite lymphoma, follicular lymphoma


How to cite this article:
Vasudevan J A, Nair R A, Sukumaran R, Nair S G. Composite lymphomas: Experience from a tertiary cancer center in Kerala, South India. Indian J Cancer 2017;54:358-61

How to cite this URL:
Vasudevan J A, Nair R A, Sukumaran R, Nair S G. Composite lymphomas: Experience from a tertiary cancer center in Kerala, South India. Indian J Cancer [serial online] 2017 [cited 2020 Apr 5];54:358-61. Available from: http://www.indianjcancer.com/text.asp?2017/54/1/358/219604



 » Introduction Top


Composite lymphoma is defined as the occurrence of two or more distinct histological types of lymphoma in a single anatomic site.[1] Composite lymphoma with coexistent classical Hodgkin lymphoma (CHL) and non-Hodgkin lymphoma (NHL) is reported only rarely. Unlike NHLs in which both components presumably belong to the same clone, NHL and Hodgkin lymphoma (HL) represent mutually exclusive entities except nodular lymphocyte predominant HL (NLPHL) and diffuse large B-cell lymphoma (DLBCL) in which areas of transition between NLPHL and DLBCL were apparent.[2] Due to several overlapping features among lymphomas, the diagnosis of composite lymphoma requires unequivocal proof by ancillary techniques such as immunohistochemistry (IHC) and molecular techniques. Composite lymphoma must be distinguished from transformation in a lymphoma, differentiation in lymphoma of low grade, and discordant lymphomas composed of different histologic types of lymphomas presenting in different anatomic sites of the body.[3]


 » Materials and Methods Top


The present study included five cases diagnosed over a period of 5 years from November 1, 2011 to October 31, 2016. Clinical features and hematologic parameters including peripheral smear, bone marrow studies, histopathologic examination of lymph node along with immunoprofile, treatment, and follow-up details were noted. All the five cases were referred cases from other centers. Sections were cut at thickness of 4 μm, and evaluation of morphology was done in hematoxylin- and eosin-stained sections. A panel of antibodies were decided after the initial morphological examination and were then classified according to the 2016 revision of the World Health Organization classification of lymphoid neoplasms.


 » Results Top


We analyzed the five cases of composite lymphoma diagnosed at our center. Clinical features are summarized in [Table 1]. Age of the patients ranged from 44 to 72 years, with a median of 58 years. Four patients were males. No cases had any prior history of lymphoma. Three patients had limited stage disease and two patients had advanced stage disease. Bone marrow involvement was present in one patient and three patients had generalized lymph node enlargement. Four patients received treatment. NHL component in all cases was follicular lymphoma (FL) and CHL component was mixed cellularity CHL (MCCHL). Histopathological diagnosis and IHC data are summarized in [Table 2], and photomicrographs of each case are also shown in [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]. NHL component in all cases was positive for CD20, and B-cell lymphoma 6 (BCL6) and the CHL component were positive for CD30 and negative for leukocyte common antigen in all cases. CD15 was positive in two cases. Four patients were treated with chemotherapy and radiotherapy. Two patients were asymptomatic and the other two patients were lost to follow-up. One patient did not take any treatment and was lost to follow-up.
Figure 1: (a) Lymph node with effacement of architecture and composed of follicles and diffuse areas (H and E, ×40). (b) Follicle centers composed of centrocytes and centroblasts (H and E, ×400). (c) Several scattered Hodgkin and Reed–Sternberg cells admixed with small lymphocytes and histiocytes (H and E, ×400). (d) Follicle center cells are CD20 positive with interfollicular sheeting (IHC, ×400). (e) B-cell lymphoma 2 positive (IHC, ×400). (f) B-cell lymphoma 6 positive (IHC, ×400). (g) Hodgkin and Reed–Sternberg cells are CD30 positive (IHC, ×400). (h) Hodgkin and Reed–Sternberg cells are PAX5 positive (IHC, ×400)

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Figure 2: (a) Lymph node with effacement of architecture and composed of follicles and interfollicular area showing several scattered large atypical cells (H and E, ×40). (b) Follicle centers composed of centrocytes and centroblasts (H and E, ×400). (c) Reed–Sternberg cells admixed with several eosinophils (H and E, ×400). (d) Follicle center cells are CD20 positive (IHC, ×400). (e) B-cell lymphoma 2 positive (IHC, ×400). (f) B-cell lymphoma 6 positive (IHC, ×400). (g) Hodgkin and Reed–Sternberg cells are CD20 negative (IHC, ×400). (h) CD30 positive (IHC, ×400)

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Figure 3: (a) Lymph node with effacement of architecture and composed of follicles and diffuse areas (H and E, ×40). (b) Follicles composed of centrocytes and centroblasts (H and E, ×400). (c) Several scattered Reed–Sternberg cells in a polymorphous cell background (H and E, ×400). (d) Follicle center cells are CD20 positive with interfollicular sheeting (IHC, ×200). (e) B-cell lymphoma 2 positive (IHC, ×400). (f) B-cell lymphoma 6 positive (IHC, ×400). (g) Hodgkin and Reed–Sternberg cells are CD30 positive (inset showing CD20 negative Hodgkin and Reed–Sternberg cells) (IHC, ×400). (h) CD15 positive (IHC, ×400). (i) PAX5 positive (IHC, ×400)

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Figure 4: (a) Lymph node with effacement of architecture and composed of follicles (H and E, ×40). (b) Follicle centers composed of centrocytes and centroblasts (H and E, ×400). (c) Interfollicular area showing Reed–Sternberg cells admixed with several eosinophils (H and E, ×400). (d) Follicle center cells are CD20 positive (IHC, ×400). (e) B-cell lymphoma 2 positive (IHC, ×400). (f) CD10 positive (IHC, ×400). (g) Hodgkin and Reed–Sternberg cells are CD20 negative (IHC, ×400). (h) PAX5 positive (IHC, ×400). (i) CD30 positive (IHC, ×400)

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Figure 5: (a) Interfollicular area of lymph node showing several scattered large Hodgkin and Reed–Sternberg cells in a polymorphous background (H and E, ×200). (b) Follicle centers composed of centrocytes and centroblasts (H and E, ×400). (c) Reed–Sternberg cells (H and E, ×400). (d) Follicle center cells are CD20 positive (IHC, ×400). (e) B-cell lymphoma 2 positive (IHC, ×400). (f) B-cell lymphoma 6 positive (IHC, ×400). (g) Hodgkin and Reed–Sternberg cells are CD30 positive (IHC, ×400). (h) CD15 positive (IHC, ×400). (i) PAX5 positive (IHC, ×400)

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Table 1: Summary of clinical features of the five patients

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Table 2: Comparison of histopathology and immunoprofile of the five cases

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 » Discussion Top


We studied five cases of composite lymphoma in which both FL and MCCHL involved the same lymph node. FL and CHL had the required diagnostic IHC features. Composite CHL and NHL is a rare occurrence.[4] Composite lymphoma in Hodgkin disease (HD) occurs almost exclusively with BCL.[5] Clonal chromosomal abnormalities involving t(14,18) have been identified in tissues involved by HD also along with the amplification of BCL2 gene.[6],[7] All the five cases had CHL. Immunoglobulin gene rearrangements are also identified in many cases of CHL.[8] Clonal relationship has been suggested between CHL and FL.[6] Composite lymphoma was originally defined as the combination of more than one lymphoma in the same patient either at different anatomic sites or in the same location. This definition has evolved over time and now the accepted definition is the presence of two or more lymphoma types in the same lymph node or extranodal site.[1] Composite lymphomas are rare and mostly documented as case reports or as small case series.[5],[9] Their prevalence may also be underestimated as ancillary techniques for definitely proving them as composed of two or more lymphoma types may not be available in many centres. For documenting as composite lymphoma, all the cases morphologically consistent with composite lymphoma should be confirmed objectively by IHC or molecular techniques. The components of composite lymphoma can be NHL and another NHL, NHL and HL, BCL and T-cell lymphoma, and extremely rare complex composite lymphomas composed of B-cell, T-cell, and HL.[3],[10],[11],[12] Synchronous two or more types of NHL are described as more common than NHL and HD. Coexistent chronic lymphocytic leukemia and HD is also reported.[13] The etiology of composite lymphoma is variable, complex, and differs according to the components involved. Composite BCLs may be due to clonal selection with additional mutations and transformation into an aggressive neoplasm, genomic instability, and congenital predisposition or multideviant pathway in common precursor cells resulting in more than one type of BCL.[1],[14],[15],[16] Composite B-cell and CHL is also explained by common precursor cell theory.[14] T-cell and CHL/BCL may be due to Epstein–Barr virus infection which could result in some cooperative process between B- and T-lymphoid cells that favor neoplasia.[15],[16]


 » Conclusion Top


Composite lymphoma although rare is being increasingly reported in recent literature. Several combinations are possible and the individual components should be strictly proven by IHC and/or molecular techniques. Meticulous examination of lymph node by light microscopy is of utmost importance in the detection of salient morphological features of each tumor which when coupled with the appropriate panel of IHC markers will help us to arrive at the correct diagnosis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 » References Top

1.
Sanchez S, Holmes H, Katabi N, Newman J, Domiatti-Saad R, Stone M, et al. Composite lymphocyte-rich Hodgkin lymphoma and peripheral T-cell lymphoma associated with Epstein-Barr virus: A case report and review of the literature. Arch Pathol Lab Med 2006;130:107-12.  Back to cited text no. 1
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2.
Greiner TC, Gascoyne RD, Anderson ME, Kingma DW, Adomat SA, Said J, et al. Nodular lymphocyte-predominant Hodgkin's disease associated with large-cell lymphoma: Analysis of Ig gene rearrangements by V-J polymerase chain reaction. Blood 1996;88:657-66.  Back to cited text no. 2
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3.
Mokhtar NM. Review article composite lymphoma. J Egypt Natl Canc Inst 2007;19:171-5.  Back to cited text no. 3
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4.
Wei EX, Flamholz RB, Lowery-Nordberg M, Veillon DM, Behm W, Heldmann M, et al. Pathology case of the month. A mediastinal mass. Malignant lymphoma, composite (nodular sclerosis Hodgkin lymphoma and diffuse large B-cell lymphoma). J La State Med Soc 2004;156:294-7.  Back to cited text no. 4
    
5.
Gonzalez CL, Medeiros LJ, Jaffe ES. Composite lymphoma. A clinicopathologic analysis of nine patients with Hodgkin's disease and B-cell non-Hodgkin's lymphoma. Am J Clin Pathol 1991;96:81-9.  Back to cited text no. 5
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Cabanillas F, Pathak S, Trujillo J, Grant G, Cork A, Hagemeister FB, et al. Cytogenetic features of Hodgkin's disease suggest possible origin from a lymphocyte. Blood 1988;71:1615-7.  Back to cited text no. 6
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Poppema S, de Jong B, Atmosoerodjo J, Idenburg V, Visser L, de Ley L. Morphologic, immunologic, enzymohistochemical chromosomal analysis of a cell line derived from Hodgkin's disease. Evidence for a B-cell origin of Reed-Sternberg cells. Cancer 1985;55:683.  Back to cited text no. 7
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Rabiller F, Belaud-Rotureau MA, Fitoussi O, Dubus P, Merlio JP, de Mascarel A, et al. Composite lymphoma: Association of a follicular lymphoma and a chronic lymphocytic leukemia. Ann Pathol 2008;28:41-4.  Back to cited text no. 8
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Yun WK, Ko YH, Kim DS, Kim WS, Rhee PL, Kwak SY, et al. Composite marginal zone B cell lymphoma and enteropathy-type T cell lymphoma of the stomach: A case report. Eur J Gastroenterol Hepatol 2008;20:791-5.  Back to cited text no. 9
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Elmahy H, Hawley I, Beard J. Composite splenic marginal zone lymphoma and classic Hodgkin lymphoma – An unusual combination. Int J Lab Hematol 2007;29:461-3.  Back to cited text no. 10
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Steinhoff M, Assaf C, Anagnostopoulos I, Geilen CC, Stein H, Hummel M. Three coexisting lymphomas in one patient: Genetically related or only a coincidence? J Clin Pathol 2006;59:1312-5.  Back to cited text no. 11
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van den Berg A, Maggio E, Rust R, Kooistra K, Diepstra A, Poppema S. Clonal relation in a case of CLL, ALCL, and Hodgkin composite lymphoma. Blood 2002;100:1425-9.  Back to cited text no. 12
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Williams J, Schned A, Cotelingam JD, Jaffe ES. Chronic lymphocytic leukemia with coexistent Hodgkin's disease. Implications for the origin of the Reed-Sternberg cell. Am J Surg Pathol 1991;15:33-42.  Back to cited text no. 13
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Wang HY, Karandikar N, Payne D, Maleki A, Schultz BA, Collins R, et al. A 3-way collision tumor of the upper respiratory tract: A composite of 2 immunophenotypically distinct mantle cell lymphomas and a plasmacytoma. Hum Pathol 2008;39:781-7.  Back to cited text no. 14
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Jaffe ES, Zarate-Osorno A, Kingma DW, Raffeld M, Medeiros LJ. The interrelationship between Hodgkin's disease and non-Hodgkin's lymphomas. Ann Oncol 1994;5 Suppl 1:7-11.  Back to cited text no. 15
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16.
Hirose Y, Fukushima T, Masaki Y, Shimoyama K, Karasawa H, Ogawa N, et al. Epstein-Barr virus-associated composite lymphoma composed of peripheral T-cell lymphoma and an anaplastic variant of a diffuse large B-cell type of non-Hodgkin's lymphoma and strongly expressing p53 protein. Int J Hematol 2004;79:260-5.  Back to cited text no. 16
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2]



 

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