Case report – patient 1:
A 58-year-old male patient (ex-smoker, abstinent since 30 years) was admitted in May 2020 to our institution due to very severe thrombocytopenia with platelet counts of 1 x 109/L (range, 140-360 x 109/L). The patient reported progressive petechia at the lower legs and large hematomas after minor trauma. A few days prior to admission a dental operation was performed with increased bleeding. Thus, complete blood count was taken. With the exception of extremely low platelets, blood count was unremarkable. No B-symptoms were present.
In suspicion of an idiopathic thromobocytopenic purpura (ITP) therapy with corticosteroids (dexamethasone 40 mg/kg/body weight for four days) and immunoglobulins 30g per day for five days was initiated. Since severe thrombocytopenia was persistent despite combined therapy the thrombopoetin-receptor agonist eltrombopag 50mg/day for 7 days was added. However, there was still no response to therapy.
Flow cytometry analysis of the peripheral blood showed no evidence of a T-cell lymphoma, but a shifted kappa/lambda ratio (0.2) with no reliable differentiation of a monoclonal subpopulation. Bone marrow evaluation displayed a hyperplastic, slightly dysplastic medullary pattern after administration of corticosteroids, but no clear lymphocytic infiltration. Flow cytometry of the bone marrow detected a small monoclonal B-cell population (0.8%), most compatible with marginal zone lymphoma, which could not be confirmed by immunohistochemistry staining. Cytogenetics was normal in 20 metaphases. In fluorescence in-situ hybridization analysis no MALT1-rearrangement was present. In addition, a computer tomography-scan (CT) was performed, which showed large, centrally located focal infiltrates in both sides of the lung (Figure 1, Panels A and C) as well as a splenomegaly of 16 cm. Histopathology evaluation after bronchoscopic biopsy revealed a BALT-Lymphoma (Figure 2). Further staging with esophageal-gastro-duodenoscopy detected a gastric infiltration of a MALT-lymphoma without Helicobacter pylori infection resulting in an Ann Arbor stadium IIIA.
A combined immunochemotherapy with rituximab (375mg/m2, day 0) and bendamustine (90mg/m2, day 1-2) was initiated. Already in response to rituximab the platelet count increased to 121 x 109/L. Thus, the patient was discharged and the therapy was continued on an outpatient basis for a total of six cycles, repeated every four weeks. Contrast-enhanced CT stagings were performed after three and six cycles showing no evidence of the disease after six cycles (Figure 1, Panels B and D). Platelets were within normal range during treatment without additional supportive medication or transfusions. In addition, a gastroscopy was performed without any further detection of suspicious results. Thus, complete remission (CR) of the BALT lymphoma was achieved.