Histol Histopath (1 989) 4: 271 -279 Histology and Histopathology IBL-like T cell lymphoma expressing monoclonal gammopathy (macroglobulinemia) in the serum Takeshi Kasajimal, Akihiro Masudal, Mikio Matsuda2,Yutaka Imai2 and Kensei Tobinai3 'Departrnent of Pathology, Tokyo Women's Medical College, Tokyo, 2TheSecond Department of Pathology, School of Medicine, Yamagata University, Yamagata and 31nternal Medicine Division, National Cancer Hospital, Tokyo, Japan Summary. A case of IBL-like T cell lymphoma with dysproteinemia (AILD) (Frizzera et al., 1975) and other serum monoclonal gammopathy was reported. A 58- related types lymphadenopathy (Castleman et al., 1956; year-old woman, who had suffered from heart failure. Lennert et al., 1968; Kojima, 1978). This disease was admitted because of asthma attack, fever and was characterized by polyclonal gammopathy of the lyrnphadenopathy. Leucopenia with a small amount of serum and systemic lyrnphadenopathy resembling IBL atypical lymphocytes was detected. Serum analysis and AILD. However, pathological characteristics showed monoclonal elevation of IgM-K (M-protein) and differing from IBL and AILD, included the appearance hv~erviscositv. Urinarv Bence-Jones urotein was of pale cells with large, clear cytoplasm and lacking diiected. Lymph &de biopsy rAealed the amorphous PAS-positive deposition in the lymph node disappearance of normal structure and proliferation of T (Suchi et al., 1987; Segami et al., 1988). In addition, cells with pale cells which characterized IBL-like T cell the nature of this disease was considered to be T cell lymphoma. Immunocytochemistry revealed the pale malignancy as opposed to B cell proliferation in IBL cells to bear T cell markers (MT-1, CD 5, CD 8 or CD 4) and AILD. and IgM-positive cell distribution. Tonsilar biopsy In this paper, we present a 58-year-old woman showed the infiltration of atypical lymphoids and pale who suffered from systemic lyrnphadenopathy and cells. Bone marrow biopsy showed moderate monoclonal gammopathy who was diagnosed as having lymphoplasmacytoid proliferation with lymph follicles. IBL-like T cell lymphoma by biopsy and macroglobuli- Clinical data and serum analysis suggested nemia by serum analysis. Immunocytochemical exami- macroglobulinemia. Additional lymph node biopsy was nation results and some points of interest are discussed. performed and revealed IBL-like T cell lymphoma. IBL- like T cell lymphoma is characterized by polyclonal Materials and methods hypergammaglobulinemia. The present case probably occurred initially as IBL-like T cell lymphoma and A 58-year-old woman had been well until the lymphoplasmacytoid cell proliferation might have age of 30. She suffered from pulmonary tuberculosis followed due to an excess of CD 4' cells. (1953-1974), glaucoma of the left eye (1960), retina1 bleeding of the right eye (1970), appendicitis with Key words: IBL-like T cell lymphoma, Monoclonal surgical removal (1977) and right ovarian cyst with gammopathy. Macroglobulinemia, Immunocytochemistry resulting surgical operation (1983). In 1983. she experienced palpitations and was treated under a diagnosis of paroxymal atrial tachycardia. In July 1987, lntroduction she was admitted to the Daini Hospital of the Tokyo Women's Medical College because of additional IBL-like T cell lymphoma was initially described by symptoms, including asthma attack, respiratory distress, Shimoyama et al. (1979, 1983) as a different entity from herpes zoster and weight loss with systemic lymphade- immunoblastic lyrnphadenopathy (IBL) (Lukes et al., nopathy. 1975), angioimmunoblastic lymphadenopathy with On admission, systemic lymph node swelling and tenderness. especially in the cervical and inguinal Offprint requests to: Prof. T. Kasajirna, Departrnent of Pathology, regions, up to 2 X 1 x 1 cm in size, was noted, but there Tokyo Wornen's Medical College, Kawadacho, 8-1, Shinjuku-ku, was no skin rash, swelling of liver or spleen, nor were Tokyo 162, Japan there any neurological abnormalities. 272 Monoclonal IBL-like T cell lymphoma Lyrnph nodes were exarnined by routine methods and T cell lymphoma. In September 1987, tonsillectomy was by immunocytochemical methods including the PAP also performed and specimen showed atypical neoplastic procedure by paraffin sections and directlindirect lymphoid cell infiltration with pale cells which were the immunoperoxidase staining of PLP-fixed frozen sections same kind of cells as in the lymph node. Additional including electron immunomicroscopy as previously lymph node biopsy were carried out in December 1987 reported (Kasajima et al., 1986, 1987). and also showed morphological features similar to the previously biopsied lymph node. Immunogenetical Results analysis was simultaneously performed and showed the rearrangement of the T cell receptor 13 chain constant Laboratory examinations showed a decrease of region with Southern blotting (Fig. 2). Based on the peripheral white cells, with 1-4% atypical lymphocytes. above mentioned clinical signs, and laboratory data. ESR was 67mmlhr and blood pressure was 140180mmHg. such as IBL-like T cell lymphoma accompanied by Biochemistry revealed a slight disturbance of liver macroglobulinemia (Tables 1.2) was diagnosed. function. Serum analysis showed a marked increase in IgM and of blood viscosity. Immunoelectrophoresis Pathological and immunocytochemical findings of biopsy disclosed M-protein which was monoclonal IgM kappa specimens light chain (Fig. 1) and also the urinary kappa type of Bence-Jones protein. Moreover, serum tests were 1. Lymph nodes. Lymph node biopsies were positive for cryoglobulin. However, there were no performed twice (July and December 1987). Both lymph antiautonuclear antibodies or anti-human T cell nodes disclosed similar histological features; i.e. leukemia virus type 1 antibodies (ATLA). After disappearance of normal architecture and proliferation admission, cardiac and respiratory symptoms were of atypical lymphoid cells with small arborizing blood slightly controlled with drug therapy, but weight loss, vessels. Lymph follicles were indistinct or had lymphadenopathy and the high level of serum IgM-Kstill disappeared at the light microscope level (Figs. 3, 4). continued. Bone marrow biopsy revealed increasing Medium and large lymphoid cells with round or slight lymphoplasmacytoid cells with formation of lymph convoluted nuclei. and large lymphoid cells with follicles. In addition. enlargement of liver and spleen prominent cytoplasm (so-called pale cells) were zonally were noticed. In July 1987, lymph node biopsy was or focally distributed (Fig. 5A). Moreover, performed. Pathological examination disclosed IBL-like lymphoplasmacytoid and plasma cells were 'located Irnrnunoelectro- 2ME; 2 mercaptoethanol treated patient serum phoresis of the WHS;whole human serum. serurn, showing reaction of the M-cornponent with Immunoelectrophoresis of the patient's serum anti-lgM and anti-K antisera (arrow). Monoclonal IBL-like T cell lymphoma DNA analysis (Southern blotting) JH with HindllI CTP with BamHI TQ3 with Bam HI :R/G faint H with Hind iii : G CTB; T cell receptor B-chain constant region gene Fig. 3. Lymph node from the first biopsy. Lymph follicles disappear JH ; Immunoglobulin heavy and atypical lymphoid cells distributed diffusely mingl with pale cells. chain joining region gene HE x 75 R ; rearrangement, G; germ line Fig. 2. DNA analysis of the second biopsied lymph node, showing rearragement of CTB (ai-row). site of lymph follicles (Table 3). 2. Tonsil. Lymph follicles disappeared and neoplastic irregularly or focally around the small vessels and large lymphoid cells with pale cells were distributed heneath the marginal sinus or medullary portion. throughout the entire part of submucosal area of tonsil. Depositioil of amorphous materials could not be Cytological features of these cells were similar to those of detected. the lymph nodes (Fig. 10). Immunocytochemically, neoplastic lymphoid cells and pale cells were positive for MT-1 on paraffin sections 3. Bone marrow. Bone marrow biopsy revealed no (Fig. 5B) and positive for CD 5 (Leu 1) in PLP-fixed lymphomatous condition. but somewhat lymphoplasma- frozen sections. but were negative for MB-1 and CD 20 cytoid cells increased and lymph follicles with germina1 (B 1). respectively. On the other hand, some lympho- centers were detected (Fig. 11). plasmocytoid cells and mature plasma cells contained Immunocytochemically, cells containing IgM were IgM more predominantly (Fig. 6) and K-light chain than more predominant than those containing IgA or IgG, but other heavy chains and A-light chain, but neoplastic cells monoclonal distribution of immunoglobulins was hardly never contained immmuiloglobulins. Immunoelectron- recognizable (Fig. 12). microscopically, both neoplastic cells reacted positively for CD 4 (Fig. 7) or CD 8 (Fig. 8) on each of their cell Discussion surfaces. IgM was recognized in the perinuclear spaces and rough endoplasmic reticulum (rER) of lymphoid and IBL-like T cell lymphoma was first reported by plasma cells (Fig. 9). In addition, some reticular areas Shimoyama et al. (1979). It resembles IBL, AILD and that reacted with DRC-1 and H107 coincided with the polyclonal immunoblastosis (Kojima, 1978). On the other 275 Monoclonal IBL-like T cell lymphoma Fig. 4. High power view of Fig. 3. Arborizing blood vessels increase Moreover, the prognosis of IBL-like T cell lymphoma and atypical lyrnphoids appear interrningling with srnall lyrnphocytes. was poorer than that of IBL. AILD and polyclonal