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CASE REPORT
Primary breast lymphoma and
HIV/AIDS
Pieter Barnardt, MB ChB, Dip Oncol
Medical Imaging and Clinical Oncology, Tygerberg Hospital, Tygerberg, W Cape
Dylan Narinesingh, MD, FC Rad Onc
Trinidad San Fernando General Hospital, Trinidad
Primary extranodal lymphoma of the breast is rare and accounts for
0.04 - 0.53% of all malignant tumours, less than 1% of
non-Hodgkin’s lymphomas (NHLs) and 1.7% of extranodal NHLs.1
Extranodal lymphoma arises from tissue other than lymph nodes and sites
that normally contain no lymphoid tissue. This case describes the
clinical and treatment dilemma posed by extranodal presentation in an
AIDS-NHL patient.
CASE REPORT
A 40-year-old woman presented with a history of a painful left
axillary mass that had progressively increased in size. She reported
symptoms of night sweats and weight loss. Physical examination revealed
a 17×13 cm left axillary nodal mass. Her left breast had the
clinical appearance of mastitis. Abnormal laboratory studies revealed
elevated serum uric acid (0.50 mmol/l, normal 0.15 - 0.35 mmol/l) and
lactate dehydrogenase (1 009 U/l, normal 100 - 190 U/l) levels. An
enzyme-linked immunosorbent assay was positive and the initial CD4+
count was 435 cells/μml. Microscopic examination of the
lymph node mass confirmed a diffuse large B-cell lymphoma (DLBCL). Bone
marrow aspiration and biopsy demonstrated no evidence of infiltration
by lymphoma. Cerebrospinal fluid (CSF) examination was negative for
lymphoma infiltration. Both the CSF cryptococcus Indian ink and latex
tests were negative, but a positive Varicella zoster polymerase chain reaction (PCR) test was reported.
A mammogram was not feasible owing to painful ulceration of the
breast mass. A computed tomography (CT) scan of the thorax and abdomen
revealed a 5 cm lymphoid nodal mass in the left axilla and a 3.4 cm
left supraclavicular lymph node. A gallium scan was consistent with
uptake in an area overlying the left breast, anterior chest wall and
markedly enlarged left axillary lymph nodes. Normal gallium
biodistribution was seen in the rest of the body (Fig. 1). The case was
considered to be a stage IIbE AIDS-NHL.
CHEMOTHERAPY
The standard CHOP regimen consisting of cyclophosphamide 750 mg/m2 , doxorubicin 50 mg/m2 and vincristine 1.4 mg/m2
on day 1 and prednisone 60 mg/day on days 1 - 5 every 3 weeks was
started. She completed 3 cycles without significant toxicity but then
presented with clinical progression. The left axillary lymph node and
breast mass had the appearance of breast cancer with erythema, oedema
and nipple retraction. A solid mass was palpable within the breast with
associated skin ulceration and multiple cutaneous nodules over the left
infra-clavicular region (Fig. 2).
However, an infection with varicella zoster virus (VZV) was
clinically apparent along dermatome T11 and 5 weeks later she reported
progressive bilateral lower limb pareses with associated weakening in
bladder control. Magnetic resonance imaging (MRI) of the vertebral
column showed degenerative changes with no focal spinal cord lesions.
The patient defaulted and returned 8 weeks later reporting that the
mass was more painful and larger with newly developed nodular cutaneous
lesions of the left breast region. She was given a 4th cycle of CHOP
and started concomitant antiretroviral therapy (lamivudine, stavudine
and efavirenz). Four weeks later there was no visible change in the
axillary and breast mass. The chemotherapeutic regimen was changed to
second-line CMV (cyclophosphamide 750 mg/m2 , methotrexate 60 mg/m2 and vincristine 1.2 mg/m2 ).
A follow-up review revealed overt clinical progression, as there was an
increase in both the size of the breast mass and the number of
cutaneous lesions. A clinical oncology consult offered palliative
radiotherapy, as she appeared resistant to first- and second-line
chemotherapy.
The clinical dilemma was as follows: was this (i) a systemic NHL with extranodal involvement of the left breast; (ii) an overlooked primary breast lymphoma (PBL); or (iii)
a misdiagnosed primary breast carcinoma? Before commencement of
radiotherapy histological examination therefore again confirmed
positivity for CD45 and CD20 lymphoma cells compatible with a DLBCL.
RADIOTHERAPY
Palliative external beam radiotherapy (EBRT) with cobalt-60,
consisting of 2 Gy × 18 fractions (36 Gy), was completed. The
clinical target volume was determined by CT scan (Fig. 3). This
included the left axillary nodal mass, the immediate lymphatic
drainage, the left breast, the remaining left anterior chest wall and
the left supra-clavicular region. Treatment was delivered using 8 MV
photons with a 1 cm daily bolus.
Before initiation of EBRT the patient started allopurinol 600 mg/d
to prevent tumour lysis syndrome. Her CD4+ count was 312 cells/μl, and trimetroprim-sulfamethoxazole as Pneumocystis jiroveci prophylaxis was added mid-course when the CD4+ count decreased to 56 cells/μl.
DISCUSSION
NHL is the second most common AIDS-associated malignancy and the
AIDS-defining diagnosis in an estimated 1.6 - 8% of HIV patients.2 PBL is rare, comprising 0.4 - 0.5% of all breast malignancies reported.3 Secondary breast lymphoma represents approximately 0.07%.4 When primary and secondary lymphoma cases are considered the most common sub-type is DLBCL (45 - 79%).5
Systemic AIDS-NHL treatment should include therapy for opportunistic
infections (OIs) and the underlying HIV and involves modifications of
conventional therapy. There appears to be a survival advantage for
patients receiving CHOP-ART therapy, suggesting that a decrease in OIs
was responsible for reduction in morbidity.6
Based on a 15 - 20% central nervous system involvement at presentation,
CNS prophylaxis is considered standard practice in AIDS-NHL. Series
with chemotherapy reported a 50% complete response and a median
survival of 18 months. An improved response rate does not significantly
add to survival owing to relapse and death from AIDS progression.7
Neurological manifestations of VZV have been described. Encephalitis
due to VZV infection results from small-vessel vasculitis, presenting
weeks after the original infection. An urgent MRI scan or myelography
is required to exclude extrinsic cord compression due to bacterial
abscess, tuberculous abscess or lymphoma. If these are excluded, CSF
should be sent for VZV PCR.8
The clinical and radiological features of PBL and carcinoma are
similar, as both are diseases of middle age with a median onset in the
6th decade. Symptoms include pain, fever, sweating and weight loss.
Contralateral involvement can be synchronous or metachronous up to 10
years after the primary lesion. Pathology remains the only way to
differentiate between these malignancies, as treatment differs
radically. Wiseman and Liao devised criteria to categorise breast
lymphoma into primary and secondary forms.9
There is no standard treatment for PBL, and for small localised tumours
adequate excision followed by radiotherapy may be effective. For
widespread tumours with axillary involvement the addition of
chemotherapy, surgery and radiotherapy may be required. The literature
suggests that the Ann Arbor stage and histological sub-type are
significant factors for survival.10
,
11 Reported 5-year survival rates vary from 9% to 85%. PBLs have a better outcome than primary breast carcinomas.12
Our patient presented with apparent systemic AIDS-NHL with
extranodal involvement of her breast, but review of her clinical
presentation and staging allows for reclassification as a PBL.
Unfortunately she was lost to follow-up and attempts to contact her
have failed. Close surveillance should be stressed, as contralateral
involvement can appear up to 10 years after the primary lesion. The era
of AIDS-related malignancies represents a challenge. There should be a
heightened clinical suspicion for extranodal lymphoma in AIDS-NHL
patients.
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Acknowledgement.
We acknowledge the assistance of Ms S Seier in the preparation of this
manuscript. Prior ethics approval was obtained. Part of the data were
used for a poster presentation at the Stellenbosch University 2010
Annual Academic Year Day. No conflict of interest is declared.
Fig. 1. Gallium-67 scans of lymphoma situated in the left breast and
axillary lymph nodes and extending into the left anterior chest wall.
Fig. 2. Clinical manifestation of an extranodal diffuse large B-cell
lymphoma (DLBCL) of the left breast in an HIV-positive patient.
Multiple cutaneous nodules, ulcerative skin lesions, erythema and
enlarged axillary lymph nodes are present.
Fig. 3. SOMA vision – virtual simulator
picture for the patient with breast lymphoma. The clinical target
volume (CTV) is outlined in red.