Abstract

A 52-year-old male patient presented in the emergency department with fatigue and persistent back and flank pain. Computed tomography revealed lymphadenopathy and disseminated osseous lesions. Staging was completed and a low differentiated signet ring cell carcinoma of the distal esophagus (AEG I), UICC stage IV [1], was diagnosed. Immunohistochemistry showed expression of human epidermal growth factor receptor 2 (HER2)/neu and E-cadherin without expression of programmed death-ligand [1]. No microsatellite instability was detected. Palliative polychemotherapy with 5-fluorouracil, folinic acid, oxaliplatin and docetaxel (FLOT) was initiated. Due to progressive pancytopenia with transfusion-dependent thrombocytopenia, abnormal renal function tests, fever and rapid clinical deterioration, we suspected malignancy-associated Thrombotic Microangiopathy (TMA), and therefore promptly initiated daily plasmapheresis. However, no objective response upon plasmapheresis was observed, while extended laboratory tests revealed elevated levels of lactate dehydrogenase (1477U/l, range: 135-250U/l), ferritin (4410μg/l, range 30- 400μg/l), triglycerides (366mg/dl, range >200mg/dl) and soluble interleukin 1 receptor (1807IU/ml, range: <710IU/ml). Abdominal ultrasonography revealed splenomegaly. Notably, bone marrow biopsy revealed extensive carcinomatosis and activation of stromal macrophages (Figure 1). According to those findings and a calculated H-score (reference: http://saintantoine.aphp.fr/score/), malignancy associated Secondary Hemophagocytic Lymphohistiocytosis (sHLH) was diagnosed.