Final Diagnosis -- A 65-year-old woman with malignant lymphoma


Malignant lymphoma, small B-cell type with plasmacytic differentiation and crystal-storing histiocytosis.


Primary non-Hodgkin lymphomas (NHLs) of the breast are rare, accounting for about 2% of extranodal NHL cases and about 0.5% of all NHLs.13 The diagnosis should be limited to patients without evidence of systemic lymphoma or leukemia at the time that the breast lesion is detected.14 The majority of patients are women, with ages ranging from 13 to 90 years of age at diagnosis 1, with an often reported bimodal age distribution of 30-35 years and 55-60 years.15 In contrast to breast carcinoma, primary lymphoma of the breast more often occurs on the right side, with a ratio of approximately 60:40.10 Mammographically, the tumor may be well circumscribed or irregular, simulating a carcinoma. Diffuse infiltration and multiple ill-defined lesions are radiological clues to the diagnosis of lymphoma, and in contrast to the majority of carcinomas, lymphomas are usually hypoechoic on ultrasound.2

The most common NHL of the breast is diffuse large B-cell lymphoma (DLBCL), with frequencies ranging from 45 - 55%. Burkitt lymphoma, more common in younger patients, and extranodal marginal zone lymphoma of mucosa associated lymphoid tissue (MALT) type, are the next most common. Lymphoplasmacytic lymphoma (LPL), follicular lymphoma, and T-cell lymphoma have also been reported with frequencies less than 10%.1,3,13,14

In the case presented, the lymphoma was characterized by a lymphoplasmacytic infiltrate with only rare apparent lymphoepithelial lesions and associated with crystal-storing histiocytosis. The differential diagnosis includes MALT lymphoma with plasmacytic differentiation and lymphoplasmacytic lymphoma. The presence of lymphoepithelial lesions strongly favors the former diagnosis. Immunophenotyping does not aid in this differential as there are no specific markers for either type of lymphoma: the majority of both are CD5 and CD10 negative, with variable CD43 positivity, and the majority express IgM.5 The molecular pathogenesis of MALT lymphomas arising in the breast is not well established. However, a recent report found that, unlike extra-mammary sites, translocations involving the MALT1 gene, including t(11;18) and t(14;18), are absent.11 Thus, FISH for MALT1 gene rearrangements may not aid in the distinction between primary MALT and lymphoplasmacytic lymphoma of the breast. As demonstrated immunohistologically, the plasma cells and crystal-containing histiocytes were strongly positive for IgM. Whether the patient has a monoclonal serum paraprotein and whether there is bone marrow involvement would thus be of great interest. The distinction between these two types of lymphomas in this setting, fortunately, is less critical, as both are indolent tumors.

A prominent feature of the case presented was the presence of crystal-storing histiocytosis (CSH) in association with the lymphoma. The crystal-storing cells were histiocytes, as demonstrated by CD68 immunoreactivity, and the immunoglobulin origin of the crystalline inclusions was shown by their reactivity with IgM and kappa light chain. Rare cases of crystal deposition have been reported in the literature in patients with plasma cell dyscrasias, mostly in multiple myeloma but also in lymphoplasmacytic lymphoma and extranodal marginal zone lymphoma.4,6 In the only previously published report of it involving the breast, CSH was associated with an IgA-lambda multiple myeloma in a patient with massive bone marrow CSH and extensive systemic disease.16 The crystalline material in CSH is thought to be paraprotein components, and may belong to any immunoglobulin class or type of light chain. It is thought to be related to phagocytosis of immunoglobulin possibly secreted by the neoplastic plasma cells and subsequent storage in lysosomes.7 Furthermore, although rare, the association of cryoprecipitible immunoglobulins with plasma cell dyscrasias is well documented.6

Finally, it is pertinent to mention, given the patient's history of diabetes, the clinical and pathologic differential diagnosis of diabetic mastopathy, or sclerosing lymphocytic lobulitis. Sclerosing lymphocytic lobulitis has been described in patients with both types 1 and 2 diabetes, as well as in patients with other autoimmune diseases such as Hashimoto's thyroiditis, Sjogren syndrome, Grave's disease, and in patients without known autoimmune disease.12 It is characterized histologically by the tetrad of circumscribed lymphoid infiltrates with associated atrophic lobules, a perivascular infiltrate of lymphocytes, epithelioid myofibroblasts and dense keloid-like collagen.8 There may be numerous B-cells. Our case did not show any of these features; nevertheless, this differential should be kept in mind as it may mimic more typical cases of primary breast MALT lymphoma.

Acknowledgement We would like to acknowledge Dr. Valerie Holst of St. Luke's Regional Medical Center for contributing this case.


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Contributed by Nicole Nicosia Esposito, MD and Steven H. Swerdlow, MD

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