DataSheet_1_Hemophagocytic lymphohistiocytosis in gastric cancer: A rare syndrome for the oncologist. Case report and brief review.pdf

Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition characterized by uncontrolled activation of the immune system. HLH is a reactive mononuclear phagocytic response that occurs in association with a constellation of conditions such as malignancies and infections. The clinical diagnosis of HLH remains challenging because HLH can present with symptoms that significantly overlap with other causes of cytopenia, such as sepsis, autoimmune diseases, hematological cancers, and multiorgan failure. A 50-year-old man went to the emergency room (ER) for hyperchromic urine, melena, gingivorrhagia, and spontaneous abdominal wall hematomas. The first blood tests showed severe thrombocytopenia, alteration of the INR, and consumption of fibrinogen, and therefore, a diagnosis of disseminated intravascular coagulation (DIC) was made. A bone marrow aspirate showed numerous images of hemophagocytosis. With the suspicion of immune-mediated cytopenia, oral etoposide, intravenous immunoglobulin, and intravenous methylprednisolone were administered. Then, a diagnosis of gastric carcinoma was performed with a lymph node biopsy and gastroscopy. On the 30th day, the patient was transferred to the oncology ward of another hospital. On admission, he had serious piastrinopenia, anemia, hypertriglyceridemia, and hyperferritinemia. He was supported with a platelet transfusion and underwent a bone biopsy that showed a picture compatible with myelophthisis from diffuse medullary localization of a carcinoma of gastric origin. A diagnosis of HLH secondary to solid neoplasm was formulated. The patient started chemotherapy with oxaliplatin, calcium levofolinate, 5-fluorouracil bolus, 5-fluorouracil for 48 h (mFOLFOX6), and methylprednisolone. Six days after the third cycle of mFOLFOX6, the patient was discharged with the stabilization of his piastrinopenia condition. The patient continued chemotherapy with an improvement in his clinical conditions and normalization of hematological values. After 12 cycles of mFOLFOX, it was decided to start maintenance chemotherapy with capecitabine but, unfortunately, after only one cycle, HLH reappeared. The oncologist has to keep in mind the existence of HLH when there is an unusual clinical presentation of cancer, such as cytopenia affecting ≥2 lineages and alterations of ferritin and triglycerides other than fibrinogen and coagulation. Increased attention and additional research as well as a close collaboration with hematologists are needed to benefit patients with solid tumors complicated by HLH.

噬血细胞性淋巴组织细胞增生症（Hemophagocytic lymphohistiocytosis, HLH）是一种罕见且危及生命的病症，以免疫系统失控激活为核心特征。HLH属于反应性单核巨噬细胞应答异常，常与恶性肿瘤、感染等一系列疾病相关联。由于HLH的临床表现与脓毒症、自身免疫性疾病、血液系统恶性肿瘤及多器官功能衰竭等可导致血细胞减少症的病因高度重叠，其临床诊断仍颇具挑战。一名50岁男性因浓茶色尿、黑便、牙龈出血及自发性腹壁血肿就诊于急诊室（Emergency Room, ER），首次血液检查提示重度血小板减少、国际标准化比值（International Normalized Ratio, INR）异常及纤维蛋白原消耗，遂诊断为弥散性血管内凝血（Disseminated intravascular coagulation, DIC）。骨髓穿刺涂片可见大量噬血现象，因怀疑为免疫介导性血细胞减少症，临床予口服依托泊苷、静脉注射免疫球蛋白及静脉注射甲泼尼龙治疗，随后通过淋巴结活检及胃镜检查确诊为胃癌。患者于就诊后第30日转至另一家医院的肿瘤科病房，入院时其存在严重血小板减少、贫血、高甘油三酯血症及高铁蛋白血症，予血小板输注支持治疗，并行骨髓活检，结果提示符合胃癌髓内弥漫浸润所致的骨髓病性改变，遂确诊为实体肿瘤继发HLH。患者随即接受奥沙利铂、亚叶酸钙、5-氟尿嘧啶推注联合48小时持续输注5-氟尿嘧啶（mFOLFOX6方案）及甲泼尼龙化疗，完成第3周期mFOLFOX6方案化疗后6日，患者血小板减少症状稳定，准予出院。后续化疗过程中患者临床症状逐步改善，血液学指标恢复正常，完成12周期mFOLFOX方案化疗后，临床决定予卡培他滨行维持治疗，但仅1周期后，HLH再次复发。肿瘤科医师需牢记：当癌症出现非典型临床表现时，如累及≥2个细胞系的血细胞减少症、铁蛋白及甘油三酯异常（需与纤维蛋白原及凝血功能异常相鉴别），需警惕HLH的发生。针对实体肿瘤合并HLH的患者，需进一步提升临床关注力度、开展更多研究，并与血液科医师密切协作，以改善此类患者的预后。