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Primary Dural Marginal Zone Lymphoma in a Woman With Inflammatory Breast Cancer

Division of Hematology/Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA

A 54-year-old woman presented to her physician with 4 days of left breast redness. She was treated for presumed mastitis with antibiotics without improvement. One month after initial presentation, physical exam revealed left breast peau d’orange, erythema, and warmth as well as a hard mass encompassing the upper hemisphere of the breast and palpable left axillary lymphadenopathy. Diagnostic mammography and ultrasound revealed a left breast upper hemisphere abnormality associated with pleomorphic calcifications, skin thickening and a left axillary lymph node. Shown in Figure 1 is the breast magnetic resonance imaging (MRI) with axial (Fig 1A) and coronal (Fig 1B) images revealing a large heterogeneously enhancing mass (Fig 1 arrows) in the left breast upper outer quadrant associated with diffuse skin and trabecular thickening as well as extensive, bulky left axillary and subpectoral lymphadenopathy, highly suggestive of inflammatory breast carcinoma. Core needle biopsy of the left breast revealed a moderately differentiated infiltrating ductal carcinoma. Estrogen and progesterone receptors were negative. HER-2/neu was positive by immunohistochemistry (3+) and FISH (red/green ratio, 7.38). Staging positron emission tomography (PET) and computed tomography (CT) scans were negative for evidence of metastatic disease. The patient began neoadjuvant systemic treatment with docetaxel, carboplatin, and trastuzumab (TCH). Following her second cycle of TCH, she was hospitalized and treated for febrile neutropenia associated with a severe perineal herpetic outbreak. After cycle five of chemotherapy, clinical exam revealed no residual breast abnormality. Figure 2 shows a preoperative breast MRI with no residual mass or enhancement indicating a radiographic complete response. She completed her sixth cycle of TCH and was scheduled to have mastectomy. However, 12 days before the scheduled mastectomy, her son found her confused and unable to speak. She was brought to the emergency room where she was noted to have expressive aphasia, altered mentation, and focal motor seizures in her right upper extremity. Figure 3 shows the contrast enhanced brain MRI with T2 (Fig 3A) and T1 (Fig 3B) weighted axial views as well as T2-weighted FLAIR coronal view (Fig 3C). Faint enhancement along the sulci of the left parietal lobe (Fig 3A and 3B arrows) with sulcal crowding (arrows panel A and B) and T2 flair hyperintensity (Fig 3C arrow) was noted, worrisome for carcinomatous or infectious meningitis. CSF cultures were negative and cytology was nondiagnostic. An electroencephalogram showed nonspecific left hemispheric slowing. She was empirically placed on intravenous acyclovir and dexamethasone without improvement in her neurological exam. Several days later, a repeat brain MRI was done showing persistent abnormal enhancement of the leptomeninges centered within the left parietal convexity and new extension into the posterior left temporal and superior left occipital regions. She underwent a second lumbar puncture for cytology and was given an empiric dose of intrathecal methotrexate. The cytology again was nondiagnostic. However, within 24 hours of receiving the intrathecal methotrexate, her expressive aphasia and confusion had resolved. A whole body PET scan showed no evidence of metastatic cancer. A diagnostic stereotactic cortical brain biopsy was done (Fig 4), showing a dense lymphocytic infiltrate involving the meninges and focally in the perivascular location within the parenchyma (Fig 4A, low power). The cells are small with slightly irregular nuclear membranes and coarse chromatin (Fig 4B, high power) and were found to be kappa light chain restricted and positive for CD45, CD20 and bcl-2, consistent with low grade B cell lymphoma, marginal zone/mucosa-associated lymphoid tissue (MALT) type (Fig 4C, immunostain). The proliferation index was low (Ki-67, 5% to 10%). Epstein-Barr early RNA–Epstein-Barr virus in situ stain was negative for Epstein-Barr virus.

View larger version (35K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 1.

View larger version (44K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 2.

View larger version (25K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 3.

View larger version (53K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 4.

Three days after the completion of whole brain radiotherapy, the patient underwent a left modified radical mastectomy and right simple mastectomy that showed a pathologic complete response in the breast and lymph nodes. Follow-up brain MRI was negative for leptomeningeal enhancement. At most recent follow-up, 4 months after mastectomy, she has completed radiation therapy to the chest wall and axilla and is without evidence of disease recurrence in the brain or breast. Her neurologic exam is normal.

Inflammatory breast cancer (IBC) is an aggressive malignancy that is clinically diagnosed in patients who present with a rapidly enlarging, tender, erythematous breast, often with peau d’orange skin changes. In many cases, there is no palpable underlying mass.¹ As a result of these nonspecific characteristics, IBC is often misdiagnosed as mastitis or breast abscess,¹ thus delaying appropriate therapy. IBC is relatively rare, comprising only two percent of all breast cancer cases in the United States.² It is associated with a lower overall survival rate than noninflammatory breast cancer and is more likely to be metastatic at presentation.² At least one study indicates that brain metastases occur more frequently in patients with IBC compared with non-IBC.³ Interestingly, HER-2/neu overexpression occurs more frequently in IBC (36%)⁴ compared to non-IBC (20% to 25%). A multimodal approach to treatment, including neoadjuvant combination chemotherapy, mastectomy, and radiation, reportedly offers a 10-year survival rate of approximately 33%.^5,6 The addition of anti-HER-2/neu targeted therapy to neoadjuvant chemotherapy for those tumors that overexpress HER-2/neu may improve treatment outcome.^7,8

Primary CNS non-Hodgkin's lymphomas in general are rare, accounting for only 0.1% to 1% of all non-Hodgkin's lymphomas.^9,10 They often present as large masses in hemispheric white or deep gray matter and are usually aggressive with a poor prognosis. In contrast, primary dural marginal zone/MALT lymphoma (PDML) is an extremely rare but indolent form of localized non-Hodgkin's lymphoma.¹¹ In our review of the literature, we found only 12 reported cases of PDML.^12-18 Like our patient, 11 of the 12 patients were women with an average age of 50 years. Five of the patients presented with seizure¹²-^14,18 while the remainder presented with other focal neurological symptoms, including headache, hemiparesis, visual or hearing changes, and facial weakness.^12,13,15,17 Unlike our patient, 10 out of 12 of the cases were misdiagnosed preoperatively as meningioma.^12-16 Four patients were treated with radiation alone with no evidence of disease recurrence at their last evaluation (range, 3 to 36 months).^12,15 Four patients were treated with radiation plus surgery and were without recurrence with follow-up ranging from 8 to 48 months.^13,14,16,18 Two patients were treated with resection alone and had no recurrence at 6 to 24 months follow-up.^13,17 One patient was treated with fludarabine alone (no recurrence at 2 months follow-up)¹² and one with radiation plus chemotherapy (no recurrence at 7 months follow-up).¹² It is not known what factors predispose patients to PDML, though it is notable that at the time of her diagnosis, our patient's immune system was suppressed from the systemic treatment for her breast cancer.

To our knowledge, this is the first reported case of a patient diagnosed with both IBC and PDML. Both diagnoses are rare but treatable malignancies, with durable remissions possible. This case demonstrates the importance of biopsy confirmation of the first suspected breast cancer metastasis. Had this patient been treated for presumed metastatic breast cancer, she would have received high-dose whole brain radiation, intrathecal chemotherapy, and prolonged systemic management, all of which would have been unnecessary. The patient continues to do well and shows no evidence of recurrence.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "Urdquo; are those for which no compensation was received; those relationships marked with a "C" were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

Employment or Leadership Position: None Consultant or Advisory Role: None Stock Ownership: None Honoraria: Sara A. Hurvitz, Genentech Research Funding: None Expert Testimony: None Other Remuneration: None

REFERENCES

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15. Goetz P, Lafuente J, Revesz T, et al: Primary low-grade B-cell lymphoma of mucosa-associated lymphoid tissue of the dura mimicking the presentation of an acute subdural hematoma. Case report and review of the literature. J Neurosurg 96:611-614, 2002[Medline]

16. Sanjeevi A, Krishnan J, Bailey PR, et al: Extranodal marginal zone B-cell lymphoma of malt type involving the cavernous sinus. Leuk Lymphoma 42:1133-1137, 2001[Medline]

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18. Altundag MK, Ozisik Y, Yalcin S, et al: Primary low grade B-cell lymphoma of the dura in an immunocompetent patient. J Exp Clin Cancer Res 19:249-251, 2000[Medline]

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ancheta, R. G. Articles by Hurvitz, S. A. Search for Related Content PubMed Articles by Ancheta, R. G. Articles by Hurvitz, S. A. Social Bookmarking                            What's this?