Miyuki Yoshii

Primary bone marrow diffuse large B‑cell lymphoma accompanying cold agglutinin disease: A case report with review of the literature

Cold agglutinin disease (CAD) is a well-recognized complication of lymphoproliferative disorders. It has been previously recognized that cases of primary CAD frequently exhibit underlying malignant lymphoma in the bone marrow. Lymphoplasmacytic lymphoma is the most common subtype of malignant lymphoma; however, diffuse large B-cell lymphoma (DLBCL) has also been documented, albeit extremely rare. The current report presents a case of primary bone marrow DLBCL accompanying CAD. A 76-year-old male presented with fever and fatigue. Laboratory tests revealed anemia and elevated bilirubin and cold agglutinins with a titer of 8,192 at 4°C. Bone marrow biopsy demonstrated DLBCL and systemic surveillance failed to detect tumorous lesions or lymphadenopathy. Following R-THP-COP therapy, cold agglutinins titer was markedly decreased (by <4); however, malignant lymphoma relapsed and cold agglutinin levels increased again (4,096). This is the second documented case of primary bone marrow DLBCL accompanying CAD. Previously, malignant lymphoma exclusively involving the bone marrow, namely primary bone marrow lymphoma (PBML), has been recognized as a rare and aggressive subtype. The analyses of the present study revealed that the incidence of hemolytic anemia in primary bone marrow DLBCL may be high compared with conventional DLBCL. Therefore, additional analyses are required to clarify the clinicopathological features of PBML.

Pulmonary marginal zone B-cell lymphoma of MALT type: a cytological report with emphasis on the usefulness of detection of lymphoepithelial lesion.

Dear Dr. Bedrossian, Primary pulmonary marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissues (MALT) type (MZBL of MALT type) is a rare extranodal lymphoma, which accounts for 0.5% of all primary lung neoplasms and 70–90% of primary pulmonary lymphomas. The cytodiagnosis of MZBL of MALT type may be missed because of the rarity of this disease, as well as minimal cellular atypia and “polymorphous” appearance of lymphoma cells in the cytological specimen. Herein, we describe a case of primary pulmonary MZBL of MALT type successfully diagnosed by a brush cytological specimen, and discuss the usefulness of detection of lymphoepithelial lesion (LEL) and its cytological differential diagnostic considerations. A 71-year-old Japanese female presented with persistent chest pain. Computed tomography demonstrated a relatively well-circumscribed nodular lesion, measuring 65 mm 3 30 mm in diameter, in the left lower lung (S8) (Fig. 1). Bronchoscopy was performed under the clinical diagnosis of lung cancer or malignant lymphoma, followed by brush cytological examination and bronchial biopsy. Subsequently, the patient underwent lobectomy of the left lower lung. Her postoperative course was uneventful, and no tumor recurrence has been observed 5 months after the surgery. Papanicolaou smear of the brush cytological specimen demonstrated single or small-clustered ciliated epithelium and an abundance of lymphoid cells as well as a few macrophages (Fig. 2a). The lymphoid cells consisted of predominantly centrocyte-like cells, which were characterized by smallto medium-sized lymphocytes with slightly irregular-shaped nuclei containing small nucleoli (Fig. 2b). Careful observation revealed infiltration of centrocyte-like cells into the cluster of ciliated epithelium, which corresponded to the histopathological features of LEL (Fig. 2b, inset). Plasma cells and monocytoid B-cells were rare on Papanicolaou stained slides, but were more numerous among centrocyte-like cells on May– Gr€unwald–Giemsa stained slides (Fig. 2c). Monocytoid B-cells were characterized by medium-sized lymphoid cells with rich cytoplasm occasionally containing vacuolation in the cytoplasm and reniform nuclei harboring aggregated chromatin and smallto medium-sized nucleoli. Immunocytochemical analysis showed positive immunoreactivity for CD20 in the lymphoid cells (Fig. 2c, inset). Histopathological study of the bronchial biopsy revealed infiltration of many smallto medium-sized lymphoid cells with slightly irregular nuclei under the bronchial epithelium and lymphocytic infiltration into the ciliated epithelium (typical features of LEL) (Fig. 3). Immunohistochemical analyses showed that these lymphoid cells were positive for CD20, bcl-2, and MUM1, but negative for CD5, CD10, bcl-6, and cyclin D1 (Fig. 3, inset). Therefore, a pathological diagnosis of MZBL of MALT type was made. The histopathological features of the resected lung specimen were fundamentally the same as those of the bronchial biopsy specimen. Flow cytometric analyses of the resected lung specimen showed that CD19/CD20-positive cells were predominant (75%), and kappa-chain positive cells were also predominant (the ratio of kappa/lambda-positive cells was 22.3) (Fig. 4). In addition, fluorescence in situ hybridization demonstrated translocation of the MALT1 (18q21) gene (Fig. 4). These findings confirmed a diagnosis of MZBL of MALT type. These two authors contributed equally to this work. *Correspondence to: Mitsuaki Ishida, M.D., Ph.D., Department of Clinical Laboratory Medicine and Division of Diagnostic Pathology, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu, 520-2192, Japan. E-mail: mitsuaki@belle.shiga-med.ac.jp Received 7 February 2013; revised 26 May 2013; Accepted 27 August 2013 DOI: 10.1002/dc.23039 Published online 25 October 2013 in Wiley Online Library (wileyonlinelibrary.com).