Unusual transformation of primary extranodal marginal zone B cell lymphoma of the uterus into a nodal follicular lymphoma grade IIIB

Abstract

Dear Editor, According to theWHO classification of non-Hodgkin lymphoma, extranodal marginal zone B cell lymphomas of mucosa-associated lymphatic tissue (MALT) is defined as a group of NHL (non-Hodgkin lymphoma) that account for approximately 7–8% of all B cell lymphomas [1]. The most common location of MALT is the gastrointestinal tract. A manifestation of the uterus is a rarity and to our best knowledge, fewer than 20 case reports of marginal zone B cell lymphoma of the uterus have been reported so far in literature [2, 3]. The histological transformation into an aggressive lymphoma occurs in approximately 4% and is associated with an inferior treatment outcome [4]. MALT lymphoma is characterized by recurrent chromosomal translocations, leading to the activation of the NF-ĸB signaling pathway. In 2011, a 60-year-old woman presented to our outpatient department with an extranodal marginal zone B cell lymphoma of the uterus. Morphologic examination of the specimen showed epithelium, which was partly invaded and destroyed by discrete aggregates of small lymphoma cells resulting in the so-called lymphoepithelial lesions. Tumor cells were CD20+, CD43+, and IgM+ and negative for CD5, CD10, CD23, and Cyclin D1 (Fig. 1b–d). An external staging CT scan revealed no other extranodal or nodal manifestation as examination of the bone marrow biopsy specimen showed no lymphoma infiltration. The lymphoma was classified as stage I according to the Ann Arbor classification. In the interdisciplinary tumor board, hysterectomy was recommended for a localized MALT lymphoma with a potential curative option. Two weeks after hysterectomy, a PET/CT scan showed a suspicious metabolic uptake in thoracic, axillary, and abdominal lymph nodes (Fig. 1a). Therefore, PET-CT led to an upstaging to stage III. Because the patient presented with asymptomatic disease, a watch and wait strategy was recommended. At the beginning of 2017, the patient presentedwith a disease progression with multifocal involvement of the liver, suspected manifestation of the spleen and both kidneys (Fig. 1e). A nodal biopsy of an inguinal lymph node of the left sidewas performed. The histology of the needle biopsy revealed a lymphoma, predominantly consisting of sheets of centroblasts with a follicular growth pattern. Immunohistochemically, the lymphoma was positive for CD19, CD20, and CD10. The proliferation rate (Ki67) was high with 60% (Fig. 1f–h); due to the follicular growth pattern and the immunohistological profile, a grade IIIB follicular lymphoma was diagnosed. Using consensus primers for the variable and joining segments of the Ig heavy chain (IgH), the resulting IgH gene rearrangement was identical for FR1, FR2, and FR3 in the lymphoma of the uterus and in the lymph node, proving a clonal relationship between the lymphomas. Correspondingly, a significantly increased LDH was found in the laboratory workup. Due to the transformation into a high-grade follicular lymphoma, the patient was included in a therapy study for aggressive B cell lymphomas (Optimal trial, NCT01478542). After 12 cycles of rituximab and 6 cycles of CHLIP-14 (cyclophosphamide, doxorubicin, liposomal vincristine, and prednisone), complete remission was achieved. At this time, the patient is in complete remission. * Christian Buske [email protected]