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1246 Part IX: Lymphocytes and Plasma Cells Chapter 81: Hematologic Manifestations of Acquired Immunodeficiency Syndrome 1247

HUMAN IMMUNODEFICIENCY the present era, but remains inferior to that of patients without HIV.
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VIRUS–ASSOCIATED PRIMARY CENTRAL The Center for AIDS Research database for 1996 to 2010 shows that the
2-year survival of HIV+ patients with primary CNS lymphoma was 24
NERVOUS SYSTEM LYMPHOMA percent, inferior to other major types of HIV-associated lymphoma (dif-
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Primary CNS lymphoma in HIV+ patients is an Epstein-Barr virus fuse large B-cell lymphoma, Burkitt lymphoma, Hodgkin lymphoma).
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(EBV)–related diffuse large B-cell lymphoma occurring in the brain, Prior CNS opportunistic infection and poor performance status 149,150
typically in patients with very advanced HIV: These patients usually confer an increased risk of death.
have a CD4 count of less than 50 cells/μL, and often of less than 20
cells/μL. 137,149–151 The epidemiology of primary CNS lymphoma illus- HUMAN IMMUNODEFICIENCY
trates the concept of specific types of lymphoma occurring at different VIRUS–ASSOCIATED PLASMABLASTIC
levels of immunodepletion. The incidence of primary CNS lymphoma
has declined markedly since the availability of ART (see Fig. 81–1). 150,152 LYMPHOMA
The pathophysiology of HIV-associated primary CNS lymphoma is Described in 1997, plasmablastic lymphoma is a rare and very aggres-
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related to EBV which is detectable in virtually all cases. Primary CNS sive B-cell NHL with plasmacytic differentiation that often involves the
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lymphoma should be considered in an HIV+ patient who presents with oral cavity, typically the gingiva and the palate. In the original report,
neurologic symptoms (confusion, cognitive decline, memory loss), 15 of the 16 cases were HIV+, and subsequent studies showed that plas-
headache, seizures, or ataxia. In one series, the most common symptom mablastic lymphoma comprises approximately 2 to 3 percent of NHL in
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was headache, followed by memory loss, ataxia, and seizure. Char- people living with HIV. A review of 112 cases of HIV-associated plas-
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acteristic features on magnetic resonance imaging (MRI) of the brain mablastic lymphoma showed that the median age of presentation was
include a single to several mass lesions in the subcortical white matter. approximately 40 years, and the median CD4 count was approximately
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Anatomic sites commonly involved are predominantly the cerebral cor- 180 cells/μL. Of the 112 patients, 58 percent had primary oral involve-
tex and periventricular area, but the basal ganglia can be involved in up ment. Other common sites of involvement were the gastrointestinal
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to one-third of cases. Cerebellar or brain stem involvement is rare. A track, the lymph nodes and skin, among other sites. In a recent series
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thorough physical exam for signs of systemic lymphoma is key, includ- of 50 cases of plasmablastic lymphoma, approximately 25 percent of
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ing a testicular exam as testicular lymphoma frequently involves the the patients had oral cavity involvement, and extraoral involvement was
CNS. A slit-lamp exam to assess for vitreous disease should be done; common. Diagnosis requires biopsy. The pathology shows a monomor-
this may assist in diagnoses of primary CNS lymphoma and may affect phic diffuse lymphoid infiltrate with cells resembling plasmablasts. The
therapy. Evaluation with a chest, abdomen, and pelvic CT and a marrow cells have a high proliferative rate with a Ki-67 often exceeding 90 per-
aspirate and biopsy should be performed. If a lumbar puncture can be cent, and are positive for plasma cell markers. CD20 is expressed in 2
safely done, cerebrospinal fluid (CSF) should be sent for cytology and percent or fewer of the cases and the majority of the cases (>80 percent)
flow cytometry to evaluate for leptomeningeal involvement with lym- are EBV+. The differential diagnosis of an oral cavity lesion in a person
phoma, and also for polymerase chain reaction (PCR) for EBV. Detec- with HIV includes odontogenic infection, squamous carcinoma, Kaposi
tion of EBV in the CSF supports, but does not confirm, the diagnosis sarcoma, and diffuse large B-cell lymphoma or Burkitt lymphoma.
of primary CNS lymphoma in these patients. PET-CT of the brain Many of the patients with plasmablastic lymphoma have been
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can also help distinguish primary CNS lymphoma from other com- treated with CHOP or with EPOCH, with poor outcome. In one retro-
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mon causes of focal brain lesions in profoundly immunosuppressed spective series, median overall survival was 11 months with no differ-
patients with HIV, namely, cerebral toxoplasmosis and other infec- ence in outcome between CHOP versus more intensive chemotherapy
tions. 156,157 Evaluation of HIV+ patients with CNS mass lesions should (EPOCH, hyperCVAD, or other regimens). Data from the German
include blood serology for toxoplasmosis, although a small percentage AIDS Related Lymphoma Cohort Study in the ART era confirmed the
of patients with CNS toxoplasmosis will have negative serologies. Ste- poor outcome of these patients, with a median survival of 5 months.
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reotactic brain biopsy should be performed if possible, but some lesions There are no prospective clinical trials to define optimal treatment for
are not readily accessible to biopsy; in these cases, the diagnosis of pri- patients with HIV-associated plasmablastic lymphoma. Case reports of
mary CNS lymphoma may rest on CSF cytology, detection of EBV in individual patients suggest that bortezomib may have activity in these
the CSF, and the results of PET-CT. Because of the rarity of primary patients, and this should be explored in future clinical trials. 165,166
CNS lymphoma in the ART era, there are no large prospective clinical
trial data to define optimal therapy. Case reports document long-term HUMAN IMMUNODEFICIENCY
responses to initiation of ART as a sole intervention in a small number VIRUS–ASSOCIATED PRIMARY
of patients who refused other therapy. All HIV+ patients with primary
CNS lymphoma should be on effective ART. Systemic glucocorticoid EFFUSION LYMPHOMA
treatment can temporarily ameliorate symptoms. Small retrospective Primary effusion lymphoma is an aggressive B-cell lymphoma character-
series report that whole-brain radiation therapy can result in improved ized by lymphomatous effusions in body cavities, most commonly pleu-
survival, but approximately one-third of these patients had detectable ral effusion, 167,168 followed by ascites and pericardial effusion or multiple
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leukoencephalopathy on followup. A large retrospective study found body cavities; lymph nodes, marrow, and skin can also be involved. A
that treatment with whole-brain radiation therapy and/or chemother- solid variant of primary effusion lymphoma presents without effusion,
apy was associated with a decreased risk of death, but this analysis but with lymph node, gastrointestinal, skin, or liver involvement has
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is confounded by lack of information on performance status. Small been reported. Primary effusion lymphoma comprises approximately
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numbers of patients have been treated with multiple cycles of high-dose 4 percent of HIV-associated NHL and occurs much more frequently
methotrexate with leucovorin rescue, without radiation therapy, with in men than in women (10:1 ratio), usually associated with low CD4
prolonged survival and no cognitive dysfunction, 158,159 and this may be counts (50 to 200 cells/μL). Of primary effusion lymphoma cases, 100
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a reasonable option in patients with good performance status. In the percent are human herpesvirus-8+ (HHV8+), and approximately 80
pre-ART era, median survival of the HIV+ patient with primary CNS percent are EBV+. HHV8 plays a key pathophysiologic role, possibly
lymphoma was approximately 2 months. The outcome has improved in by elaboration of a viral homologue of FLICE inhibitory protein and

Kaushansky_chapter 81_p1239-1260.indd 1246 9/21/15 11:19 AM