At the age of 17 years, the patient was diagnosed with a lymphoblastic T-cell lymphoma (stage III), manifesting as mediastinal mass and mesenteric lymph nodes. Until the diagnosis, the patient had always been healthy. There were no indications of an increased susceptibility to infections. He was treated with poly-chemotherapy according to treatment guidelines NHL BFM 2012. Serology of EBV and CMV was consistent with prior infection. The tumor masses rapidly responded to chemotherapy, but prolonged myelosuppression prompted testing of TPMT pharmacogenomics which revealed a homozygous polymorphism (*3A/*3C). As a consequence, maintenance therapy per protocol with oral 6-MP was reduced to 10% of the maximum 6-MP dose (50 mg/m2) and regularly adjusted according to blood cell counts. MRI, 1 year after diagnosis, showed complete remission. At his own request, the patient then emigrated abroad while still taking oral maintenance chemotherapy (6-MP and MTX). The last documented blood cell counts were low, but within the target range defined by the study protocol (leukocytes, granulocytes, lymphocytes, thrombocytes).
Five months later, he returned in reduced general condition, presenting with diffuse abdominal pain and massive weight loss (30 kg in ~5 weeks, equivalent to 25% of his body weight). Two weeks prior to his return, he had been admitted to a general hospital abroad for suspected pneumonia with symptoms of coughing and high fever. The chest x-ray showed multiple round pulmonary lesions. He reported having regularly taken the prescribed medication in the recommended dose (6-MP, methotrexate, cotrimoxazole for PCJ prophylaxis).
His markers of inflammation were elevated (CRP 116 mg/l, ESR 98 mm/h), LDH was increased (520 U/l) and pancytopenia with distinct lymphopenia (leucocytes 2.900/mul, Hb 9.1 g/dl, thrombocytes 90.000/mul, granulocytes 2.450/mul, lymphocytes 116/mul) was noted. Flow cytometry (fluorescence-activated cell sorting) did not show a relevant B-/T- or NK-cell gap. The immunoglobulin levels were within normal range [IgG 763 mg/dl (reference range 700-1,550 mg/dl)]. Low-level reactivation of EBV (EBV-DNA PCR 610 copies/ml) and CMV (CMV-DNA-PCR positive, <300 copies/ml) was detected. Work-up for other infections (including HIV, TBC, fungi) was negative. Bone marrow biopsy showed a representative bone marrow cytology without blasts. Except for the described lymphopenia, there was no further evidence of an underlying immunodeficiency. Imaging of chest, abdomen and pelvis confirmed the presence of multiple round lung foci and revealed an extensive abdominal tumor with suspected ileal perforation. Explorative laparotomy was performed, which revealed tumor masses within the ileum, infiltrating the bladder wall. En-bloc resection of the ileal segment including the bladder wall and termino-terminal ileo-ileostomy was executed. Somewhat unexpectedly, pathology revealed an EBV-associated, diffuse large B cell lymphoma, strongly expressing CD20, CD79a, CD30, and co-expression of CD45. EBV early RNA (EBER) in situ hybridization was markedly positive and the proliferation activity (Ki- 67) was above 70%.