Secondary Hemophagocytic Lymphohistiocytosis Presenting As the Initial Manifestation of Diffuse Gastric Signet Ring Cell Adenocarcinoma: A Case Report.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome driven by uncontrolled immune activation, most commonly associated with hematologic malignancies. Its occurrence as the presenting manifestation of a solid tumor is rare and frequently underrecognized due to significant clinical overlap with severe infectious syndromes. We report the case of a 38-year-old male with no prior medical history who presented with persistent fever, severe lower back pain, and night sweats. These nonspecific constitutional symptoms, including fever, weight loss, and night sweats, initially raised suspicion for an infectious or inflammatory etiology. Laboratory evaluation revealed severe anemia, thrombocytopenia, marked hyperferritinemia, elevated lactate dehydrogenase, hepatic cytolysis, and hypertriglyceridemia. Peripheral blood smear demonstrated a leukoerythroblastic pattern with schistocytes and circulating erythroblasts, suggestive of bone marrow infiltration. An HScore indicated an 80-88% probability of HLH, supporting a high likelihood of reactive HLH in the adult setting. Extensive infectious workup was negative, including blood and urine cultures, which remained sterile throughout hospitalization. Imaging identified a left supraclavicular lymph node conglomerate consistent with Virchow's node and diffuse bone marrow infiltration throughout the spine, with anterior epidural extension at the D6 level. Initial computed tomography of the chest, abdomen, and pelvis did not reveal a clear primary intra-abdominal lesion but demonstrated hepatomegaly and lymphadenopathy, prompting further investigation. Upper gastrointestinal endoscopy revealed multiple large gastric ulcers, and histopathological analysis confirmed diffuse gastric adenocarcinoma with signet ring cell features. The tumor demonstrated proficient mismatch repair (pMMR), PD-L1 combined positive score (CPS) 5, HER2-negative status, and claudin 18 (CLDN18) positivity. A bone marrow biopsy was non-diagnostic due to extensive necrosis but showed immunohistochemical evidence suggestive of metastatic epithelial infiltration. Immunomodulatory therapy with anakinra was initiated; however, persistent severe thrombocytopenia precluded systemic oncologic therapy. The patient died 28 days after admission from multiorgan failure, highlighting the fulminant course and high mortality associated with malignancy-triggered HLH. This case highlights the importance of early consideration of malignancy in unexplained HLH and illustrates how hematologic compromise may preclude disease-modifying treatment.