A 45-yr-old man presented with multiple subcutaneous masses in the left upper and lower extremities. At that time, neither lymph nodal involvement nor leukemia was detected. The patient received 6 cycles of CHOP (cyclophosphamide, adriamycin, vincristine, prednisolone) and IMVP-16 (ifosfamide, methotrexate, etoposide, prednisolone), but the disease progressed. Multiple subcutaneous masses and lymph nodal invasion developed in 10 and 21 months after the first visit. He received adjuvant radiation therapy, but leukemic transformation (blast, 34% in peripheral blood smear) and brain involvement also occurred in 23 and 27 months after initial presentation, respectively. In spite of further chemotherapy with daunorubicin, Ara-C (cytosine arabinoside), vincristine and prednisolone as well as intrathecal chemotherapy, he died of sepsis 28 months after the diagnosis.

A 17-yr-old girl presented with multiple bluish and purpuric maculopatches on the upper and lower extremities and back, and a deep subcutaneous nodule for 2 months. Initial hematological findings were within normal limit. The patient was transferred to another hospital and further follow-up results were not available.

An 18-yr-old man was admitted with left inguinal lymphadenopathy, night sweat and weight loss. A computed tomographic scan of the abdomen revealed splenomegaly and the enlarged left para-aortic lymph nodes. Peripheral blood findings were as follows: hemoglobin (Hb) 15.5 g/dL; white blood cells (WBC) 5.4×10³/µL; normal differential counts except increased monocytes (10.2%). The level of LDH (261 IU/L) and AST (144 U/L) increased. Bone marrow aspiration and biopsy showed no abnormal findings. He received 3 cycles of CHOP chemotherapy. Three months later, a cutaneous nodule in the left thigh developed. Subsequently he received additional 5 cycles of CHOP chemotherapy. Complete remission was achieved for 2 yr until he suffered from left mandibular pain. Extraction of a wisdom tooth followed by biopsy of the gum revealed atypical lymphoid infiltration. Two months later, he complained of headache and weight loss of 4 kg. On physical examination, protrusion of the right eyeball and enlargement of right neck lymph nodes were found. He was anemic (Hb 5.6 g/dL, Hct 15.7%, reticulocytes 0.08%) and had severe thrombocytopenia (93,000/µL) and leukopenia (480/µL). A computed tomographic scan of the head and neck showed a relatively well demarcated tumor in the right ethmoid sinus which extended into the right orbit, and the maxillary and frontal sinuses. Bone marrow biopsy was positive. Chemotherapy with IMVP-16 regimen was started. He died 60 months after the diagnosis.

A 22 yr-old male patient was admitted with the multiple lymphadenopathy of the inguinal, cervical, and preauricular lymph nodes, the largest of them measuring 4 cm in diameter. A computed tomographic scan of the abdomen revealed diffuse hepatosplenomegaly and the enlarged paraaortic, common iliac, and external iliac lymph nodes. Peripheral blood findings were as follows: Hb 15.3 g/dL; WBC 7.4×10³/µL; normal differential except increased monocytes (8.2%). The level of LDH (676 IU/L) increased. The bone marrow was positive. After biopsy of the cervical lymph node, he received one cycle of CHOP chemotherapy without response. Then high dose CHOP chemotherapy was given with achievement of complete remission. Subsequently the patient underwent peripheral blood stem cell transplantation, however, the tumor recurred in the bone marrow four months later.

Tumors of all four cases displayed similar appearance and were composed of diffuse infiltration of monotonous medium-to-large blastoid cells. Nuclei of three cases showed fine chromatin and inconspicuous nucleoli. Tumor cells of Case 4 exhibited prominent nucleoli simulating immunoblast. In skin biopsy, dense infiltration of tumor cells without necrosis or angiocentric growth was noted in the upper and mid-dermis and occasionally in the dermis to the subcutaneous tissue (Fig. 1). Mitoses were rather variable. The tumor cells exhibited no epidermotrophism. Biopsy of lymph nodes showed effacement of nodal architecture by diffuse proliferation of monomorphic lymphoid cells. Peculiarly, in Case 3, tumor cells were arranged around a central fibrillary core, which was very similar to Homer-Wright type pseudorosettes seen in neuroepithelial tumors (Fig. 2A). Touch imprint with Giemsa stain revealed no cytoplasmic azurophilic granules.

Immunohistochemial findings and main clinical information of these cases are summarized in Table 1. CD2 (Novocastra, U.K.), CD3 (Novocastra, U.K.), CD4 (Novocastra, U.K.), CD5 (Novocastra, U.K.), CD7 (Novocastra, U.K.), CD8 (Novocastra, U.K.), CD20 (Novocastra, U.K.), CD30 (Dako, Denmark), CD34 (Dako, Denmark), CD43 (Serotechs, Bethesda, MD), CD56 (Monosan, The Netherland), CD68 (Dako), CD79a (Dako), terminal deoxynucleotidyl transferase (TdT, Dako), myeloperoxidase (Dako), TIA-1 (Immunotech, Westbrook, ME), lysozyme (Zymed, U.S.A.) were used in the present study. All four tumors were CD4+/CD56+ (Fig. 3). Only Case 3 tumor displayed positive reactivity for TdT (Fig. 2B). All four tumors were negative for myeloperoxidase. As for CD68, three cases were positive, while Case 3 was negative. Flow cytometric analysis was performed in Case 3 and 4. Myeloid markers (CD13, CD33) were negative. EBV in situ hybridization was performed using the fluorescein-conjugated EBER1 and 2 oligonucleotides (Dako, Denmark). Briefly, paraffin sections were pretreated with xylene, followed by the treatment with proteinase K and finally hybridized with EBV oligonucleotides. As negative controls we used EBV-negative lymphoid tissues and the hybridization mixture without the EBV oligonucleotides. The results were all negative.

For polymerase chain reaction amplification of the T-cell receptor (TCR) gamma gene, DNA was prepared by standard proteinase K digestion and phenol/chloroform extraction. PCR followed by SSCP analysis was performed as described previously (5). No clonal rearrangement of TCR gene was demonstrated in all four cases.