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 7.4x103/microL; 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. No clonal rearrangement of TCR gene was demonstrated in all four cases.