C A S E R E P O R T

Presentation of a plasmablastic lymphoma in a humanimmunodeficiency virus-positive patient after administration of aninferior alveolar dental blockGerald McKenna & Sarah Manton

Restorative Dentistry, Dundee Dental Hospital, Dundee, UK

Abstract

Human immunodeficiency virus (HIV) is a serious worldwide healthcareproblem with implications for all healthcare workers. The reported oralmanifestations of the disease are numerous and have been categorisedaccording to the strength of their association with HIV infection. Oral non-Hodgkin’s lymphoma is strongly associated with HIV infection, and anincreased incidence of such neoplasms is widely reported. This case reportdetails the presentation of a rare subcategory of plasmablastic lymphoma inan HIV-positive patient after administration of an inferior alveolar dentalblock to facilitate extraction of mandibular teeth. This highly aggressiveneoplasm is a large B-cell lymphoma with a predilection for the oral cavity.Unfortunately, the prognosis for such a tumour is poor as detailed inthis case.

Key words:inferior alveolar, local anaesthetic, neoplasia

Correspondence to:Dr G McKenna

Restorative Dentistry

Dundee Dental Hospital

Park Place

Dundee

Tayside

DD1 4HN

UK

Tel.: +44 1382 635976

Fax: +44 1382 225163

email: g.mckenna@ucc.ie

Accepted: 28 May 2008

doi:10.1111/j.1752-248X.2008.00024.x

Introduction

Non-Hodgkin’s lymphoma (NHL) is the second mostcommonly observed human immunodeficiency virus(HIV)-related tumour after Kaposi’s sarcoma1. Theincidence of NHL in HIV-positive individuals hasdeclined since the introduction of highly active anti-retroviral therapy (HAART) but remains 60–200 timesmore common than in the general population2,3. Bur-kitt’s lymphoma and diffuse immunoblastic B-celllymphoma are the most common NHLs to be associatedwith HIV disease, although a variety of other lympho-mas may develop. Plasmablastic lymphoma is a raresubcategory of NHL associated with HIV. It has themorphologic features of a large B-cell lymphoma, withminimal or no expression of the leukocyte commonantigen or of the B-cell antigen CD20.

Most commonly identified in adults, plasmablasticlymphoma has a marked predilection for the oralmucosa and jaws4. Plasmablastic lymphoma is com-monly associated with Epstein–Barr virus (EBV) and

also, more recently, human herpes virus 8 (HHV8)1.The tumours are usually very aggressive, with rapidgrowth and expansion resulting in a mean reportedsurvival time of 6 months4. This case report details thepresentation of a plasmablastic lymphoma arising atthe site of an inferior alveolar dental nerve block givenfor the extraction of carious and symptomatic teeth inthe lower arch of an HIV-positive patient.

Case report

A 29-year-old woman presented to a dental emergencyservice complaining of pain from the upper left, lowerright and lower left quadrants. Medically, the patienthad been diagnosed as HIV positive, asthmatic andtaking the following medications as prescribed: pred-nisolone, co-proxamol, fluconazole, aciclovir, nystatin,salbutamol and diazepam. Later, consultation with thepatient’s supervising physician revealed a history ofpneumonia, candidal infection and a CD4 count of<200 cells/mL, thus indicating that she had full blown

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acquired immunodeficiency syndrome (AIDS). Thepatient had previously received HAART but had devel-oped drug-resistant strains of the virus. After an oralexamination supported by an orthopantomogramradiograph, a treatment plan was established whichinitially included extraction of 26, 38, 46, 47 and 48under local anaesthetic and steroid cover, with moreextractions planned to follow.

Firstly, 26, 38 and 46 were extracted to relieve thepatient’s pain. The patient returned 4 days after theextractions with localised alveolar osteitis (dry socket)associated with the 46 socket. The socket was irrigatedwith sterile saline and was packed with a medicateddressing. Six weeks later, 47 and 48 were removed as asurgical procedure. A 5 day course of antimicrobials wasprescribed to reduce the possibility of post-operativeinfection insuchanimmunocompromisedpatient.

One week after the extractions, the patient wasreviewed. She reported some minor discomfort in thelower right quadrant and, clinically, the socketsappeared inflamed and packed with food debris. As aresult, the area was irrigated with sterile saline anddilute chlorhexidine mouthwash. Six weeks later, thepatient presented with a swelling at the back of themouth on the right side. The swelling had beenincreasing in size for 1 week and was causing pain onswallowing and eating. On examination, an isolatedindurated, raised lump of 1 cm diameter was presenton the right fauces at the site of administration ofprevious inferior alveolar dental nerve block injections(Fig. 1). The lesion had a necrotic surface, but therewas no discharge or associated soft tissue swelling. Anextra-oral survey revealed no regional lymphaden-opathy. An orthopantomogram was made of thepatient but this revealed no obvious hard tissuepathology associated with the area.

Because of the suspicious clinical appearance of thelesion, an incisional biopsy was taken under localanaesthetic. A differential diagnosis of a non-specificnon-healing ulcer associated with HIV disease (Fig. 2),tuberculosis, squamous cell carcinoma or anotherneoplasm was made. The patient missed two subse-quent appointments and was seen 10 days later. Theswelling had now increased significantly in size andthere was obvious alveolar bony involvement (Fig. 3).The exposed bone appeared necrotic. The lesion wasstill indurated and tender to palpation. Again, therewas no associated soft tissue swelling or clinicalinvolvement of the regional lymph nodes.

The biopsy report returned a histopathological diag-nosis of a high-grade malignant B-cell lymphoma. Thespecimen was positive for VS38c, EBV and virus latentmembrane protein marker. The EBV was amplified inthe tumour tissue by polymerase chain reaction. Allother lymphocytic markers were negative including

Figure 1 Initial lesion 6 weeks after inferior alveolar nerve block.

Figure 2 An example of a non-specific traumatic ulcer in HIV positive

patient.

Figure 3 Lesion 10 days after initial presentation.

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154 Oral Surgery 1 (2008) 153–157. © 2008 The Authors

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leukocyte common antigen, CD20, CD3 and CD10.HHV8 infection was also negative. From these findings,a diagnosis of plasmablastic lymphoma was made.After liaison with the patient’s medical staff, anappointment was made for her to see her supervisingconsultant physician the following afternoon accom-panied by her social support worker. After discussionwith the patient and considering the advanced natureof the neoplasm, a palliative approach was adoptedinvolving radiotherapy and opiate analgesia.

Prior to the beginning of radiotherapy to the jaws,the patient’s mouth was examined once again (Fig. 4).The patient was complaining of generalised dentalpain from most of the remaining molar teeth and wasexperiencing trismus. It was decided that all cariousteeth should be removed to prevent further symptomsand before the side effects of radiotherapy, particularlythe developing severity of the trismus, made furthertreatment impossible.

Discussion

Since the institution of HAART for treatment of HIVinfection, a dramatic regression of oral lesions hasbeen observed5. However, NHL still presents in 3% ofHIV-positive patients6 and is the second most commonHIV-related tumour1. NHL is recognised as an AIDS-defining condition and in contrast to the lymphomasthat occur in immunocompetent individuals, HIV-related lymphomas often occur extranodally and runan aggressive clinical course7. Oral NHL may manifestas swelling, ulceration, exophytic masses, mobility orearly loss of teeth, trigeminal neuropathy or delayedhealing of extraction sites8–12. The case presenteddetails the first report of oral NHL presenting at the

site of an inferior alveolar dental nerve block injec-tion. The gingivae and palate are the sites most com-monly affected, although lesions may occur in othersites including the tongue and the maxillarysinuses13,14. Oral NHL may be the first clinical mani-festation of HIV disease15.

Most NHLs are high-grade small non-cleaved celllymphomas of B-cell origin with two associated condi-tions identified: primary effusion lymphoma and oralplasmablastic lymphoma5. In 2001, the World HealthOrganization classified plasmablastic lymphoma as anNHL16. Plasmablastic lymphoma is a variant of diffuselarge B-cell lymphoma with a unique phenotype and astrong predilection for the oral cavity4. The microscopicappearance of plasmablastic lymphoma mimics otherhigh-grade blastic NHLs with brisk mitotic activityand a ‘starry-sky pattern’. Distinguishing plasmablasticlymphoma from AIDS-related immunoblastic lym-phomas and from Burkitt’s lymphoma purely on thebasis of morphologic features is difficult. The significantphenotype appears to be VS38c, which is the onlymarker to be expressed by all plasmablastic lympho-mas4. This protein is a 64 kD intracellular type IItransmembrane protein localised to the endoplasmicreticulum and reacts strongly with both benign andmalignant plasma cells17.

There is a strong association between plasmablasticlymphoma and the presence of the EBV, which can befound in up to 75% of reported cases1. EBV is known toinfect B lymphocytes and to convert them into immortallymphoblasts by altering p53 gene expression andprotein regulation. EBV has also been intimately asso-ciated with the development of a number of cancers,namely, African Burkitt’s lymphoma, B-cell lymphop-roliferative disorders in immunodefiency states andnasopharyngeal carcinoma18. In addition, recent evi-dence has also indicated the presence of a dual infectionwith EBV and HHV8 in tumour cells of HIV-positiveindividuals with oral plasmablastic lymphoma3. In thiscase, polymerase chain reaction indicated evidence ofinfectionwithEBVbutnotwithHHV8.

Patients with HIV-associated NHL have poor prog-nosis19. The tumour can metastasise to involve thecentral nervous system and the gastrointestinal tract,and often fails to respond to conventional anti-NHLtherapies. The literature describes the use of chemo-therapy, radiotherapy or a combination of the two,but recognises there is no established treatment planfor such cases20. However, significantly improved out-comes of HIV-associated plasmablastic lymphoma havebeen reported with the use of HAART21,22. Unfortu-nately, the patient described here was unable to betreated in this way as she had previously developed

Figure 4 Lesion prior to commencement of radiotherapy.

McKenna & Manton Presentation of a plasmablastic lymphoma

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resistant strains of HIV. She survived only 4 monthsafter initial presentation and responded poorly toradiotherapy.

Conclusions

The sudden and rapid development of a plasmablasticlymphoma at the site of a recently administered infe-rior alveolar dental nerve block injection illustrates theneed for vigilance when treating patients with HIVdisease or AIDS. The initiation of a tumour after a nor-mally innocuous dental trauma indicates the need toreview immunocompromised patients after invasivetreatment. Unfortunately, plasmablastic lymphoma isan aggressive tumour and confirms the presence of anHIV-associated malignancy. Sometimes, this can be thefirst clinical presentation of the underlying disease.Awareness of plasmablastic lymphoma can preventmisdiagnosis with odontogenic cellulitis, non-specificHIV-associated ulceration and non-lymphoid malig-nancies such as Kaposi’s sarcoma. The prognosis forplasmablastic lymphoma remains poor, but there issome evidence to suggest that HAART may improveoutcomes for HIV-positive patients. Further research isrequired on this recently categorised neoplasm in orderto establish a recognised treatment strategy for affectedpatients.

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