Peripheral T-cell Lymphoma-Unspecified (PTCL-U) Presenting with Hypereosinophilic Syndrome and Pleural Effusions
A 43-year-old woman was hospitalized in January 2004, with a 2-month history of a fever, a dry cough and a sore throat, which were refractory to antibiotic therapy. She had received supportive care for eosinophilia in another hospital. A physical examination demonstrated a 1×1 cm non-tender cervical lymph node, hepatosplenomegaly 3 cm below the costal border, peritonsillar exudates and pretibial pitting edema. Diffuse crackles were auscultated in the left lower lung field, and no heart murmur was detected. The peripheral blood counts were: hemoglobin, 11.3 mg/dL; platelets, 182,000/mm3; and white blood cells, 20,730/mm3 (neutrophils 46%, lymphocytes 13%, monocytes 3%, eosinophils 36%, basophils 1%, and plasma cell 10%). The absolute eosinophil count was 7,462/mm3. LDH was 1,529 IU/L, serum IgE 9.5 IU/mL and b2-microglobulin 2.70 mg/L. The sputum culture, blood culture, throat swab culture and pleural fluid culture provided negative results. Hepatitis B, hepatitis C, VDRL, and HIV diagnostic tests were negative. The EBV VCR IgG antibody was positive; while the IgA and IgM antibody tests were negative. Multiple examinations of stool specimens for ova and parasites were negative.\nClonorchis sinensis, paragonimus westermani skin test and cysticercus, paragonimus, sparganum, clonorchis, and toxocara specific IgG antibody tests gave negative result.\nAn electrocardiogram and an echocardiogram were normal. The CD3/CD4 lymphocyte percentage was 66.1%, and the CD3/CD8 lymphocyte percentage was 14.6%. The total CD3/CD4:CD3/CD8 (Helper:Suppressor) ratio was 4.53, which was increased compared to the normal reference range of 0.9-3.6.\nA chest X-ray revealed mild pulmonary congestion and a left pleural effusion (). Computed tomography of the chest and abdomen demonstrated diffuse hepatosplenomegaly, bilateral pleural effusions, and left paraaortic, subcarinal, and paratracheal lymphadenopathy (). Bone marrow aspiration and biopsy revealed a markedly increased number of eosinophils (24.8%), and a significant number of plasma cells and lymphocytes (). The patient's cytogenetic analysis demonstrated a normal karyotype, 46 XX. Despite treatment with empirical antibiotics, the fever and the sore throat persisted.\nPleural cytology demonstrated lymphocyte dominant exudates with a few atypical cells. These atypical lymphocytes were suspected to be malignant lymphoma cells, based on the results of immunocytochemistry (CD3, positive; CD20, negative; Ki-67, positive) (). A liver biopsy demonstrated a few atypical lymphoid cells and eosinophils in the sinusoids and the portal space, based on the results of immunocytochemistry (CD3, positive; CD20, negative; Ki-67, positive) ().\nBased on the results of the liver biopsy, the pleural cytology, and the bone marrow biopsy, a diagnosis was made of peripheral T-cell lymphoma with hypereosinophilic syndrome. The patient was treated with two courses of CHOP chemotherapy (cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2, and prednisolone 100 mg). During chemotherapy, the fever and the eosinophilia improved.\nHowever, the CT of the abdomen, performed on March 25, 2004, demonstrated that the hepatosplenomagaly and the lymphadenopathy, were unchanged. Peripheral blood counts were: hemoglobin, 9.4 mg/dL; platelets, 253,000/mm3; and white blood cells, 7,240/mm3 (neutrophils 41%, lymphocytes 20%, monocytes 10%, eosinophils 29%, basophils 1%, and plasma cell 2%). In addition, a high-grade fever persisted.\nThe chemotherapy regimen was then changed to IMVP-16 (ifosfamide 1,000 mg/m2, mesna 200 mg/m2, methotrexate 50 mg/m2, and ectoposide 100 mg/m2) plus prednisolone 100mg. After two courses of this chemotherapy, the eosinophilia, the fever and the pleural effusions improved. After the sixth course of chemotherapy, the CT of the abdomen, performed on July 29, 2004, demonstrated that the hepatosplenomagaly and lymphadenopathy had decreased by more than 50 percent (). After the eighth course of chemotherapy, 18F-fluorrodeoxyglucose positron emission tomography (FDG-PET), performed on September 15, 2004, demonstrated no hypermetabolic lesions.\nTwo months later, follow-up peripheral blood counts were: hemoglobin, 12.4 mg/dL; platelets, 165,000/mm3; and white blood cells, 8,870/mm3 (neutrophils 38%, lymphocytes 8%, monocytes 5%, eosinophils 49%, basophils 0.6%, and plasma cell 1.7%). However, a CT of the abdomen, performed on October 24, 2004, demonstrated that the lymphadenopathy had increased in both size and extent (). This was considered a relapse of the disease.\nAlthough the patient was subsequently treated with ESHAP chemotherapy (ectoposide 40 mg/m2, methylprednisolone 500 mg, cisplatin 25 mg/m2, and cytarabine 2000 mg/m2), her condition deteriorated. After completion of a course of this chemotherapy, 18F-fluorrodeoxyglucose positron emission tomography (FDG-PET), performed on November 24, 2004, demonstrated multiple metabolic lesions in the abdominal lymph nodes, the heart, the axillae, the mediastinal lymph nodes, and both lungs. High dose chemotherapy was then recommended, but the patient refused. Supportive care was provided for the continued eosinophilia, the uncontrolled fever, and the sore throat. Two months after the disease become refractory to treatment, the patient died of a cardiac tamponade.