However days after he completed the
However, 10 days after he completed the last chemotherapy round with etoposide, the patient again visited our emergency department manifesting a fever. Lab data reported leukopenia, anemia, and elevated LDH (leukocyte:3600/μL, hemoglobin:10.9 g/dL, platelet:168 × 103/μL, and LDH:498 U/L). Thereafter, pneumocystis jirovecii pneumonia was strongly suspected due to the patient\'s chest X-ray and clinical presentation. After the antibiotic Sevatrim was administered (Trimethoprim 80 mg/Sulfamethoxazole 400 mg), the patient\'s fever subsided. At the same time, steroid medication was discontinued to avoid occult infection.
Six weeks later, the patient\'s fever recurred, and subsequent examination again noted progressive leukopenia, thrombocytopenia, and elevated LDH. Repeated bone marrow examination further revealed hypocellular marrow with hemophagocytosis. Therefore, the patient received two cycles of weekly etoposide. Follow-up lab data showed improved leukopenia and decreased LDH, after which he then received another five cycles of weekly etoposide. Unfortunately, induration over the bilateral cheek with skin erythematous change and progressive facial swelling was found. Lab data indicated recurred leukopenia (1700/μL) and elevated LDH (729 U/L). A CT scan of the nasopharynx reported an increased infiltration and swelling over the bilateral face, submandibular region and submental region. Furthermore, several neck FDA-approved Drug Library nodes were noted, and PET (positron emission tomography) scan revealed tumor involvement at the bilateral upper neck and posterior portion of the bilateral lower neck (Fig. 3). Thus, the patient received an incisional biopsy of the upper neck soft tissue, which showed panniculitis-like (Fig. 3) T-cell lymphoma and immunohistochemistry stain and showed CD3(+), CD20(−), CD56(−), CD4(−), CD8(+), TIA-1(+) and EBER(−) in-situ hybridization stain. Repeated bone marrow biopsy revealed no evidence of lymphoma bone marrow involvement. After treatment with chemotherapy using an ESHAP regimen (etoposide 40 mg/m2 BSA, cisplatin 25 mg/m2 BSA and methylprednisolone 500 mg at day 1 to day 4 and cytarabine 2000 mg/m2 at day 5), his symptoms and ferritin level improved (Fig. 4). However, the lymphoma response requires additional image evaluation at a later date.
Discussion Hemophagocytic lymphohistiocytosis (HLH) occurring as a primary or acquired disorder is a condition of uncontrolled immune system stimulation. Clinical manifestations include fever, organ enlargement, and weight loss. Additionally, laboratory tests customarily show bicytopenia or pancytopenia, cytolysis and cholestasis, serum ferritin elevation, and clotting disorders. Inherited forms of HLH produce symptoms in early childhood and can be fatal in the absence of specific treatment. In adults, the clinical spectrum ranges from mild and self-limited hemophagocytic lymphohistiocytosis to rapidly fatal multi-organ failure. However, many questions remain unresolved regarding the diagnosis and treatment in adults. Hematologic malignancies may be the main disease associated with hemophagocytic syndrome in adults. These patients have elevated early mortality, and the underlying diseases profoundly influenced the outcome. According to the HLH-2004 trial, HLH is diagnosed if five of the following eight findings are present: fever ≧38.5 °C, splenomegaly, peripheral blood cytopenia, hypertriglyceridemia and/or hypofibrinogenemia, hemophagocytosis in the bone marrow, spleen, lymph node, or liver, low or absent NK cell activity, elevated ferritin, and elevated soluble CD25 (soluble IL-2 receptor alpha). Our patient had fever, splenomegaly, cytopenia, hypertriglyceridemia and hypofibrinogenemia, hemophagocytosis in bone marrow, elevated ferritin and elevated soluble IL-2 receptor alpha. Initially, there was no evidence of malignancy according to both the lymphadenopathy and the initial bone marrow involvement. Thus, only HLH was diagnosed.