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Year : 2016  |  Volume : 27  |  Issue : 3  |  Page : 334-338
Intraoral plasmablastic non-hodgkin's lymphoma associated with human immunodeficiency virus

Department of Oral Medicine and Radiology, Krishnadevaraya College of Dental Sciences, Bengaluru, Karnataka, India

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Date of Submission21-Feb-2016
Date of Decision11-Apr-2016
Date of Acceptance09-Jun-2016
Date of Web Publication13-Jul-2016


Plasmablastic Lymphoma of oral cavity is an aggressive rare form of Non Hodgkin's Lymphoma which is an Acquired Immuno Deficiency Syndrome defining condition. Head and neck region is the second most common area for extranodal NHL's primarily involving gingiva and palate, which often presents as a diagnostic problem. We report a case of PBL in a 19 year old female patient later diagnosed as Human Immunodeficiency Virus (HIV) positive. She presented with expanding painful ulceroproliferative lesion involving left mandible and gingiva of 20 days duration. Histopathological examination and immunohistochemical analysis confirmed the diagnosis. Uncommon discovery of multiple bony lesions in whole body CT and hypercalcemia raise a question about Multiple Myeloma (MM). Literature showed very few cases with osteolytic lesions and none of the cases reported multiple bone lesions in skull. Our case report stresses the importance of differentiating this extremely rare case of PBL with skull lesions from MM.

Keywords: Human immunodeficiency syndrome, multiple myeloma, non-hodgkin's lymphoma, plasmablastic lymphoma

How to cite this article:
Vasudevan V, Kumar YR, Chavva P, Naina S. Intraoral plasmablastic non-hodgkin's lymphoma associated with human immunodeficiency virus. Indian J Dent Res 2016;27:334-8

How to cite this URL:
Vasudevan V, Kumar YR, Chavva P, Naina S. Intraoral plasmablastic non-hodgkin's lymphoma associated with human immunodeficiency virus. Indian J Dent Res [serial online] 2016 [cited 2023 Mar 26];27:334-8. Available from:

Lymphomas arise as a result of somatic mutation in lymphocyte progenitor cells, either B-cell or T-cell or both. They are classified as Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma (NHL). Large B-cell Lymphoma (LBCL) is the most common type of NHL, accounting for about 30% of the cases reported. Plasmablastic Lymphoma (PBL), an aggressive Diffuse LBCL (DLBCL), was initially observed in the oral cavity of HIV-infected individuals and later reported in gastrointestinal tract, skin, nose, and anus. NHL being the second most common malignancy in HIV-positive patients shows an intraoral occurrence in about 58%.[1] It has also been reported in HIV-negative patients. The incidence of PBL is 2.6% of all the AIDS-associated NHLs,[2] with a possibility of Epstein–Barr Virus Human Herpes Virus-8-associated infection. It is known for its spectrum of presentation ranging from indolent to highly aggressive and potentially fatal with marked predilection for the oral cavity, the gingiva and palatal mucosa being the most common sites. Prevalence of disease-related deaths was 59.6% in oral NHL and the average mean survival is 14 months, indicating the aggressive nature of the disease, which thus entitles it to early detection and aggressive chemotherapy. We report a case of extranodal PBL in a young HIV-positive female patient substantiating it with biochemical, serological, radiologic, histopathological, and immunohistochemistry evidence.

   Case Report Top

A 19-year-old female presented to the outpatient department with a chief complaint of worsening swelling in the lower left back tooth region for the past 20 days. The swelling was preceded by severe, continuous, radiating tooth pain associated with a severe mobility. The swelling has been gradually increasing in size since its appearance from 3 months and it is associated with difficulty in mouth opening. No history of fever, loss of appetite, or weight loss was elicited. The patient did not find any pain relief after medication. No history of bleeding or discharge from the swelling was noted. The patient complained of paresthesia associated with the swelling for 2 weeks.

General physical examination revealed that the patient was moderately built, poorly nourished, asthenic, and showed pallor indicating anemia. The patient was febrile during examination. Extraoral examination revealed a solitary, unilateral, oval-shaped diffused swelling in the left lower one-third region of the face confined to the angle of mandible and submandibular region, extending anteriorly to the submental region with indistinct edges [Figure 1] and [Figure 2]. The skin overlying the swelling was stretched without any secondary changes. It is firm and tender on palpation without local rise in temperature. It is a nonreducible, noncompressible, nonfluctuant, and nonpulsatile swelling showing no evidence of translucency. The left submandibular lymph node is enlarged, hard, and movable on palpation.
Figure 1: Frontal extraoral photograph

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Figure 2: Profile extraoral photograph

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Intraoral examination revealed a solitary, oval-shaped ulcero-proliferative lesion in the lower gingivobuccal sulcus confined to the teeth 35, 36, and 37 measuring approximately 5 cm × 4 cm in size and extending anteriorly from the mesial aspect of 35 till the distal aspect of 37. On palpation, the edge of the ulcer was raised with the ulcer base resting on the attached and marginal gingiva in relation to 35, 36, and 37. The floor is covered by granulation tissue with inflammatory exudates [Figure 3]. It is soft and tender on palpation, without any induration of the edge and showed bleeding on touch. It caused obliteration of the vestibule. Involved teeth, i.e. 35, 36, and 37 showed grade III mobility. A provisional diagnosis of Kaposi's sarcoma was performed.
Figure 3: Intraoral picture showing the proliferative growth in the lower left vestibule

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The differential diagnosis, NHL, poorly differentiated squamous cell carcinoma, and Hand–Schuller–Christian disease was considered. On blood investigations, the patient was reactive to HIV I and II by enhanced chemiluminiscence ELFA and Tridot assay and negative for hepatitis B surface antigen. Orthopantomogram revealed an ill-defined radiolucency extending anteroposteriorly from the distal aspect of 34 till the distal aspect of 37 and superoinferiorly from the crest of mandible with complete destruction of the trabaculae causing thinning of the lower border of the mandible. Multiple punched out radiolucencies were seen in the mandible bilaterally extending throughout the length of the ramus and body [Figure 4]. Posterio-anterior skull, skull true lateral [Figure 5], and pelvic radiograph [Figure 6] also showed multiple radiolucencies, giving a typical appearance of multiple myeloma (MM).
Figure 4: Panoramic radiograph showing a huge periapical radiolucent lesion in relation to 36, 37, and 38 and multiple radiolucent lesions

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Figure 5: True lateral skull radiograph showing multiple osteolytic lesions

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Figure 6: Pelvic radiograph showing osteolytic lesions on the right side

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Whole body computed tomography scan revealed ill-defined radiolucency in relation to 35, 36, and 37 with lingual cortical erosion extending up to the lower border of the mandible. Multiple irregular lytic lesions were seen extending throughout the ramus and body of the mandible [Figure 7]. Such lesions were also seen in the left maxillary sinus, wall of the right orbit, and skull. Multiple lung nodules, soft tissue lesions in liver, and sigmoid colon were detected giving an impression of end-stage neoplasia. Owing to the presence of multiple bony lesions throughout the body, we further subjected the patient to additional investigations [Table 1].
Figure 7: Computed tomography coronal section shows proliferative growth with eroded lingual cortex of mandible

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Table 1: Heamatological investigations

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Serum creatinine, blood urea nitrogen, and uric acid levels were elevated indicating a significant renal failure. Elevated serum alkaline phosphatase level indicated altered liver function. Elevated serum calcium further raised a question about MM; although Bence Jones proteins were negative.

A fine-needle aspiration cytology and incisional biopsy of the lesion were advised. The histopathology report revealed monomorphic proliferation of round-to-ovoid cells with a plasmacytoid morphology, areas of mature small lymphocytes, and tangible body macrophages. Anisocytosis and nucleosis of the plasmacytoid cells with mitotic figures are seen [Figure 8]. A histopathological diagnosis of NHL of plasmablastic type was formulated. Immunohistochemistry was performed [Table 2]. It was positive for leukocyte common antigen (LCA), CD138 [Figure 10], and Kappa. Ki67 index was > 90%, thus confirming plasmablastic NHL [Figure 9].
Figure 8: Stereoscopic picture showing round-to-ovoid cells with plasmacytoid morphology and macrophages (H and E, ×40)

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Figure 9: Immunohistochemical staining: Tumor cells showing no staining to CD20 (Pathnsitu EP126)

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Table 2: Immunohistochemical investigations

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Figure 10: Immunohistochemical staining: Tumor cells strongly expressing staining to CD138 (Thermoscientific MI15)

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The patient was further subjected to bone marrow aspiration cytology followed by bone marrow biopsy. The bone marrow biopsy report revealed hypercellular marrow with focal areas showing infiltration by large cells with vesicular nucleus and prominent nucleoli. Residual hematopoeitic areas showed myeloid hyperplasia with an increase in neutrophil, eosinophilic series, and megakaryocytes, creating an impression of metastatic marrow.

Considering the status of the patient, she was referred to KIDWAI Memorial Institute of Oncology, a tertiary center, where she was started on Highly Active Anti Retroviral Therapy (HAART), and palliative pain relief was provided. She progressed into renal failure and expired within a span of 4 months.

   Discussion Top

PBL was first described by Delecluse et al. in 1997. The WHO has classified PBL as a Non-Hodgkin's B-cell Lymphoma, which occurs predominantly in HIV-positive patients.[3] AIDS-related lymphomas often occur extranodally and were seen as aggressive clinical course. PBL is characterized as a DLBCL, typically known for its aggressive nature and plasmacytic differentiation.

The sites of intraoral presentation are gingiva, palate, and tongue rarely. It usually presents as a nontender, soft-to-firm swelling of the area involved with overlying ulcerations; commonly causing gingival swelling associated with a tooth. It erodes the adjacent bone, causes the disappearance of lamina dura, presenting as solitary ill-defined radiolucency. In our case, the lesion involved the left posterior mandible and the gingivobuccal complex, causing lingual bone erosion and associated tooth mobility.

Kaneet al.[4] proposed minimum diagnostic criteria for PBL in developing countries with limited resources, the criteria were as follows:

  1. Predominant population of plasmablasts exhibiting high nuclear-to-cytoplasmic ratio, moderate amount of amphophilic cytoplasm, and round nucleus with prominent nucleolus
  2. High mitotic and/or apoptotic index
  3. Absence of neoplastic plasma cells in the background.

In addition to morphological criteria, they defined a diagnostic immunophenotype consisting of CD20 negativity, LCA (±), diffuse positivity for CD138/Vs38c, light chain restriction, and a high Ki-67 index (>60%). Considering Kane et al. criteria, the investigations done in our case fulfilled all the morphological and immunophenotypic criteria. Immunoglobulins are mostly of IgG type having κ or lambda light chains. Our case showed positivity for kappa light chains. Apart from the markers mentioned in the Kane's criteria, CD38 and MUM1 positivity and CD79a and PAX-5 negativity are characteristic of plasmablastic NHL.

PBL should be differentiated from other AIDS-related lymphomas. Immunoblastic DLBCL is positive for CD20, CD79a, and PAX-5, but rarely exhibits reactivity for CD138 or Vs38c, which are positive for PBL. Burkitt's lymphoma can be differentiated by the expression of B-cell antigens and IgM heavy chains, which are not expressed in PBL. MM can be differentiated by the presence of plasmacytic cells whereas plasmablastic NHL usually has a monotonous proliferation of plasmablasts and immunoblasts.[5]

Multiple punched out bone lesions, hypercalcemia, and renal failure did occur in our patient, which can often be misleading to the diagnosis of MM. However, the Bence Jones proteins were found negative. The possible explanation for hypercalcemia in lymphoma patients is because of parathyroid hormone-related peptide, Macrophage Inflammatory Protein 1α (MIP-1α), MIP-1β, and calcitriol increased levels.[6],[7] Dickkopf-1 is elevated in patients with MM that causes multiple lytic lesions of the bone.[8] It is found in the bone marrow of patients with DLBCL, which prevents the differentiation of mesenchymal stem cells into osteoblasts, thus leading to bone lesions of lymphoma.

Treatment of NHL is usually chemotherapy using Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisolone (CHOP) or CHOP-like regimens, radiotherapy, and a combination of chemo/radiotherapy. Current National Comprehensive Cancer Network guidelines advocate the use of cyclophosphamide, vincristine, doxorubicine, and methotrexate and then isofosphamide, mesna, etoposide, and cytrabine, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin or hyperfractionated chemotherapy cyclophosphamide, vincristine, doxorubicine, and dexamethasone, regardless of HIV status of an individual.[9] HAART to traditional chemotherapy significantly improved the prognosis of PBL with HIV infection.

According to Chao. Cet al., more than half of the HIV-positive patients with NHL died within 2 years of diagnosis, compared with 29% of the HIV-negative NHL patients, having HIV associated with a nearly 6-fold increase in 2-year mortality rate.[10] Patients with PBL and HIV infection have an overall survival rate of 14 months despite treatment, henceforth proving the aggressive and fatal nature of the disease. Authors of our case report conclude that multiple bone lesions result in unfavorable prognosis.

   Conclusion Top

Although the number of AIDS-affected individuals declined by one-third in Southeast Asian countries, there is a reported increase of NHL in India. NHL is the second most common malignancy with the plasmablastic variant being the most common histological subtype presented intraorally. Usually, it is a diagnostic problem because of the heterogeneous immunophenotype, genotypic presentation, and its close correlation with the clinical and radiological presentation of MM, which can be misleading. It has a poor outcome and so, accurate diagnosis followed by prompt chemotherapy would contribute to increase the survival rate.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed

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Conflicts of interest

There are no conflicts of interest.

   References Top

Hanna E, Wanamaker J, Adelstein D, Tubbs R, Lavertu P. Extranodal lymphomas of the head and neck. A 20-year experience. Arch Otolaryngol Head Neck Surg 1997;123:1318-23.  Back to cited text no. 1
Kaur T, Nayak R, Hosmani JV, Hugar D. Plasmablastic lymphoma, an oral manifestation of AIDS related complex in an HIV positive patient: A case report. Int J Contemp Dent 2010;1:64-7.  Back to cited text no. 2
Raphael H, Borisch B, Jaffe ES. Lymphomas associated with infection by the human immunodeficiency virus (HIV). In: Jaffe ES, Harais NL, Stein H, Vardiman JW, editors. World Health Organization Classification of Tumors of Hematopoietic and Lymphoid Tissues. 4th ed. Lyon: IARC Press; 2008. p. 260-3.  Back to cited text no. 3
Kane S, Khurana A, Parulkar G, Shet T, Prabhash K, Nair R, et al. Minimum diagnostic criteria for plasmablastic lymphoma of oral/sinonasal region encountered in a tertiary cancer hospital of developing country. J Oral Pathol Med 2009; 38: 138-144.  Back to cited text no. 4
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
Matsuhashi Y, Tasaka T, Uehara E, Fujimoto M, Fujita M, Tamura T, et al. Diffuse large B-cell lymphoma presenting with hypercalcemia and multiple osteolysis. Leuk Lymphoma 2004;45:397-400.  Back to cited text no. 6
Takasaki H, Kanamori H, Takabayashi M, Yamaji S, Koharazawa H, Taguchi J, et al. Non-Hodgkin's lymphoma presenting as multiple bone lesions and hypercalcemia. Am J Hematol 2006;81:439-42.  Back to cited text no. 7
Kaiser M, Mieth M, Liebisch P, Oberländer R, Rademacher J, Jakob C, et al. Serum concentrations of DKK-1 correlate with the extent of bone disease in patients with multiple myeloma. Eur J Haematol 2008;80:490-4.  Back to cited text no. 8
Ramírez-Amador V, Esquivel-Pedraza L, Lozada-Nur F, De la Rosa-García E, Volkow-Fernández P, Súchil-Bernal L, et al. Intralesional vinblastine vs 3% sodium tetradecyl sulfate for the treatment of oral Kaposi's sarcoma. A double blind, randomized clinical trial. Oral Oncol 2002;38:460-7.  Back to cited text no. 9
Chao C, Xu L, Abrams D, Leyden W, Horberg M, Towner W, et al. Survival of non hodgkin's lymphoma patients with and without HIV infection in the era of combined anti-retroviral therapy. AIDS 17, 24(11): 1765-70, 2010.  Back to cited text no. 10

Correspondence Address:
Vijeev Vasudevan
Department of Oral Medicine and Radiology, Krishnadevaraya College of Dental Sciences, Bengaluru, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0970-9290.186229

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10]

  [Table 1], [Table 2]

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