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HEMATOLOGY SECTION - BRIEF COMMUNICATION Table of Contents   
Year : 2008  |  Volume : 51  |  Issue : 1  |  Page : 121-124
Morphological spectrum of AIDS-related plasmablastic lymphomas


Department of Pathology, Tata Memorial Hospital, Mumbai, India

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   Abstract 

We have had a recent spurt in cases of AIDS-related lymphoma (ARL) at our centre. Most of these cases are aggressive mature B cell lymphomas, mainly plasmablastic lymphoma (PBL) and diffuse large B-cell lymphoma (DLBCL). Most of the PBL are extranodal in location and are mucosa-based. We reviewed the morphological features of 34 cases of PBL. Diagnosis was based on morphology, immunohistochemistry, proliferation index, HIV positive status and its preference to extranodal sites (mostly mucosa based). We classified PBL into three morphological subtypes (immunoblastic - 25, Burkitt's - 7, plasmacytic - 2). Tumor cells expressed as leucocyte common antigen (LCA) in 60%, CD138 in 100%, EMA in 45% and light chain restriction in 86% cases. CD20 was negative in all cases. Pathologists need to be aware of PBL and its various morphological subtypes as the identification of this entity from its close differentials carries major therapeutic implications.

Keywords: Morphology, plasmablastic lymphoma, AIDS related lymphoma

How to cite this article:
Gujral S, Shet T M, Kane S V. Morphological spectrum of AIDS-related plasmablastic lymphomas. Indian J Pathol Microbiol 2008;51:121-4

How to cite this URL:
Gujral S, Shet T M, Kane S V. Morphological spectrum of AIDS-related plasmablastic lymphomas. Indian J Pathol Microbiol [serial online] 2008 [cited 2020 Oct 21];51:121-4. Available from: https://www.ijpmonline.org/text.asp?2008/51/1/121/40423



   Introduction Top


AIDS-related lymphomas (ARL) constitute approximately 1.6% of all NHL at our centre. [1],[2] Common subtypes include plasmablastic lymphoma (PBL) and diffuse large B-cell lymphoma (DLBCL). We present the morphological features of 34 cases of PBL (both nodal and extranodal) diagnosed at our centre. The diagnostic criteria of PBL, as described elsewhere, are based on classical morphology and a characteristic IHC pattern (CD20−, LCA+/−, CD138+). [3] The morphology of PBL resembles immunoblastic lymphoma but the antigen profile is similar to that of plasmacytoma. Although DLBCL has been traditionally classified into various morphological subtypes, [4] there are no reports of morphological classification of PBL. The presentation at extranodal sites and its negativity for usual hematolymphoid markers (LCA, CD20 and CD3) makes its diagnosis more difficult. In this communication, we share morphological and immunophenotypic features of PBL.


   Materials and Methods Top


We could retrieve 77 cases of ARL from archives of our lymphoma registry in a 5-year period (2002-2006). Eighteen of these were referral cases with limited clinical details. Remaining 59 cases included PBL (34 cases), diffuse large B-cell lymphoma (DLBCL, 17 cases), Burkitt's lymphoma (4 cases), plasmacytoma (1 case), primary effusion lymphoma (2 cases) and Hodgkin's disease (1 case). These cases were further reviewed by two pathologists independently and the morphological features were recorded. The cases with inter-observer discrepancy were re-reviewed. The panel of IHC included LCA, CD3, CD20, CD10, CD30, EMA, CD138, kappa and lambda light chains, bcl-2, Mib1 proliferation marker, CD34 and Tdt. In addition, markers for epithelial (CK) and melanoma (S-100, HMB-45) differentiation were performed. HHV8 and EBER could be performed for a few cases only.


   Results Top


There were 24 males and 10 females with a median age of 39 years (range 12-70 years). Thirty-one cases (91%) were extranodal, out of which 30 (88%) were mucosa-based [25 in oral cavity and 5 in gastrointestinal tract (GIT)] and one case was in the soft tissues of the chest wall. Three cases were nodal PBL (cervical lymph nodes). Six cases (17%) showed bone marrow involvement by lymphoma. Anemia was observed in 29 cases. There was no M band on serum electrophoresis or any lytic lesions. Polyclonal hypergammaglobulinemia was observed in 11 cases. LDH was raised in 26 patients.

Histology revealed a high-grade malignant tumor with diffuse proliferation of tumor cells admixed with tingible body macrophages. It showed sheets of tumor cells with focal nesting pattern. High-power examination revealed a range of cytological features. Based on cytology, we classified our cases into three subtypes, namely, immunoblastic PBL, Burkitt's-like PBL and plasmacytic PBL.

Immunoblastic PBL revealed a cohesive growth pattern of large-sized polygonal tumor cells with squared borders. Tumor cells contained abundant basophilic cytoplasm and had an eccentrically placed large round nucleus with smooth but distinct nuclear borders, fine dusty chromatin and 1-2 prominent central eosinophilic nucleoli, which is observed in more than 90% of tumor cells as described [4] [Figure - 1]. Perinuclear hof was observed. Two cases of immunoblastic PBL had focal collection of anaplastic cells. The frozen section of one case was labeled as poorly differentiated carcinoma. Two other cases were labeled provisionally as a small round cell tumor.

Burkitt's-like PBL revealed a discohesive pattern of monomorphic intermediate-sized, round to oval tumor cells, with scanty to moderate cytoplasm (high nuclear-cytoplasmic ratio), irregular nuclear borders, small sized 1-2 nucleoli and no perinuclear hof [Figure - 2]. Fine needle aspirate of one case was labeled as Burkitt's lymphoma.

Tumor cells in plasmacytic PBL revealed mature-looking plasma cells, but showed brisk mitotic and apoptotic activity. Small-sized nucleoli were observed in less than 10% of tumor cells [Figure - 3].

Common features included a brisk mitotic and apoptotic activity, necrosis giving a "starry sky appearance." In the oral cavity and GIT, submucosa showed diffuse proliferation of tumor cells. Overlying mucosa showed ulceration and hyperplasia. Tumor infiltrated the surrounding soft tissues and muscles. Lymphoepithelial lesions were not observed in the GIT PBL. Background revealed mature looking plasma cells and lymphocytes in plasmacytic PBL. Binucleation and multinucleation was observed in both immunoblastic as well as plasmacytic subtypes. Russell bodies were not observed. Most cases of Burkitt's-like PBL revealed scanty tumor cells in a largely necrotic background.

ImmunohistochemIstry (IHC) profile did not show any variations in these different morphological subtypes. Tumor cells were negative for CD20, CD3, CD30 and CD10 in all cases, LCA was positive in 45% (weak positive), CD138 positive in 100% (week to strong expression) and EMA was positive in 45% cases. Kappa and lambda light chain restrictions were observed in 18 and 16 cases, respectively. Mib1 proliferation index ranged from 40 to 90%. Diffuse large B-cell lymphoma was ruled out as all these cases were CD20− and CD138+. Burkitt's lymphoma was ruled out as tumor cells were negative for CD10 and CD20 and the Mib1 proliferation index was less than 90% in all the cases. EBER-1 (in-situ hybridization) was positive in 5 out of 13 cases. LANA for KSHV8 (IHC) was performed in 2 negative cases only. The number of nucleolated cells was an important feature in distinguishing immunoblastic from plasmacytic variants. More than 90% of tumor cells revealed nucleoli in immunoblastic PBL. Less than 10% of tumor cells in both the cases of plasmacytic PBL showed the presence of inconspicuous nucleoli. Thus, we observed three major morphological variants of PBL, namely, immunoblastic (25), Burkitt's-like (7) and plasmacytic (2) PBLs. There was no correlation of stage with Mib1 proliferation index, while its relation with stage of HIV/AIDS could not be evaluated.


   Discussion Top


Plasmablastic lymphoma is presently listed in the WHO classification as a variant of DLBCL. [4],[5] It shares many morphologic and immunophenotypic features with plasmablastic plasma cell myeloma. [4] None of our cases had features of multiple myeloma as also observed by others. [4],[5] These patients had to be followed up to look for any subsequent development of M band or lytic lesions. There are various morphological and molecular classifications of myeloma in the bone marrow aspirate, including the plasmablastic variants of myeloma. [6],[7] PBL and its association with human immunodeficiency virus (HIV) was originally described in 1997 by Delecluse et al. [8] It has been reported that PBL represents a clinically heterogeneous spectrum. [9] with different morphological subtypes. However, there are no morphological classifications of PBL available in the literature. WHO 2000 classification divides DLBCL into various morphological subtypes: centroblastic, immunoblastic and plasmablastic. [4] The morphology of PBL resembles immunoblastic lymphoma but antigen profile is similar to that of plasmacytoma (LCA+/−, CD20− and CD138+). [4] IHC profile in our series of PBL was similar to as described elsewhere. [4],[5],[8],[9] There was no association of different morphological patterns with various sites (nodal and extranodal). One of the plasmacytic PBLs involved the chest wall. Five of the immunoblastic PBL and one of the BL-like PBL involved BM.

The term "PBL of the oral cavity" in the WHO classification of ARL [4] need to be revisited as PBLs are also observed in the GIT and rarely in the lymph nodes and also in HIV seronegative individuals, as seen in our series. [10],[11] The spectrum of morphological features of PBL have not been well defined. Awareness of this entity can prevent misdiagnosis with nonlymphoid malignancies, notably squamous carcinoma and malignant melanoma in the head and neck and anal canal region. PBL are negative for epithelial (CK, EMA), melanoma (S-100 protein and HMB-45) and conventional B-cell markers (CD20). Further, the plasmacytic PBL closely resembles plasmacytoma; however, it shows brisk mitotic and apoptotic activity. Mib1 proliferation index is an extremely useful stain in such cases to differentiate conventional plasmacytoma from plasmacytic PBL.

All three morphological subtypes show different differential diagnosis [Table - 1]. Thus, a judicious combination of morphology (tumor showing brisk mitotic and apoptotic activity) and IHC help in diagnosing PBL.


   Conclusion Top


Most of our ARL cases were aggressive mature B cell lymphomas, mainly PBL and DLBCL. Most of PBL are extranodal in location and are mucosa-based. Pathologists must be aware of PBL and its various morphological subtypes as identification of this entity from its close differentials carries major therapeutic implications. Plasmablastic lymphoma is a distinct entity and should be considered different from the PBL variant of DLBCL; it may occur at sites other than oral mucosa. This proposed morphologic classification will require validation by other centers studying AIDS-related lymphomas; further, its prognostic significance must be established.

 
   References Top

1.Sahni CS, Desai SB. Distribution and clinicopathologic characteristics of non-Hodgkin's lymphoma in India: A study of 935 cases using WHO classification of lymphoid neoplasms (2000). Leuk Lymphoma 2007;48:122-33.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Agarwal B, Ramanathan U, Lokeshwar N, Nair R, Gopal R, Bhatia K, et al . Lymphoid Neoplasms in HIV+ Individuals in India. J Acquir Immune Defic Syndr 2002;29:181-3.  Back to cited text no. 2    
3.Colomo L, Loong F, Rives S, Pittaluga S, Martνnez A, López-Guillermo A, et al . Diffuse large B-cell lymphomas with plasmablastic differentiation represent a heterogeneous group of disease entities. Am J Surg Pathol 2004;28:736-47.  Back to cited text no. 3    
4.Harris NL, Jaffe ES, Deibold J, Flandrin G, Muller-Hermelink HK, Vardiman J. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: Report of the clinical advisory committee meeting - Airlie House, Virginia, November 1997. J Clin Oncol 1999;17:3835-49.  Back to cited text no. 4    
5.Vega F, Chang CC, Medeiros LJ, Udden MM, Cho-Vega JH, Lau CC, et al . Plasmablastic lymphomas and plasmablastic plasma cell myelomas have nearly identical immunophenotypic profiles. Mod Pathol 2005;18:806-15.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Greipp PR, Raymond NM, Kyle RA, O'Fallon WM. Multiple myeloma: Significance of plasmablastic subtype in morphological classification. Blood 1985;65:305-10.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]
7.Bergsagel PL, Kuehl WM. Molecular pathogenesis and a consequent. Classification of multiple myeloma. J Clin Oncol 2005;23:6333-8.  Back to cited text no. 7    
8.Delecluse HJ, Anagnostopoulos I, Dallenbach F, Hummel M, Marafioti T, Schneider U, et al . Plasmablastic lymphomas of the oral cavity: A new entity associated with the human immunodeficiency virus infection. Blood 1997;89:1413-20.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]
9.Teruya-Feldstein J, Chiao E, Filippa DA, Lin O, Comenzo R, Coleman M, et al . CD20-negative large-cell lymphoma with plasmablastic features: A clinically heterogenous spectrum in both HIV-positive and negative patients. Ann Oncol 2004;15:1673-9.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]
10.Kravetz JD, Rose MG, Payne-Blackman S, Federman DG. Plasmablastic lymphoma presenting as an arm mass in an individual negative for human immunodeficiency virus: A case report. Clin Lymphoma Myeloma 2006;6:493-5.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]
11.Liu W, Lacouture ME, Jiang M, Dickstein J, Soltani K, Shea CR. KSHV/HHV8 associated primary cutaneous plasmablastic lymphoma in a patient with Castleman's disease and Kaposi's sarcoma. Cutan Pathol 2006;33:46-51.  Back to cited text no. 11    

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Correspondence Address:
S Gujral
Department of Pathology, Tata Memorial Hospital, Mumbai
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.40423

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    Figures

  [Figure - 1], [Figure - 2], [Figure - 3]
 
 
    Tables

  [Table - 1]

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