Balboni, M

Carli, M G

Castoldi, G

Cavazzini, P

Cuneo, A

Fagioli, F

Piva, N

English

Institutional Research Information System University of Turin

Lymphoblastic Lymphoma with Primary Splenic Involvement and the Classic 14;18 Translocation M. Gretel Carli, Antonio Cuneo, Nadia Piva, Massimo Balboni, Franca Fagioli, Pierluigi Cavazzini, and Gianluigi Castoldi ABSTRACT: Clinicopathologic features of a case of lymphoblastic lymphoma (LyLI with the classic 14;18 translocation are described in this article. The patient had prominent splenomegaly with numerous plenic nodules, exhibiting a homogeneous blast (:el/infiltrate and occasional cells with cleft nuclei, a picture suggestive of high-grade non-Hodgkin lymphama (NHL) possibly lymphoblastic, Early B-cell features were detected immunologically, thus confirming the diagno- s•s of LyL. The presence (ff primary splenic involvement and of the t(14;181fq32;q211 areun- usual in this histologic subset of B-cell Nt IL, these cytogenetic and clinicopathologic characteris- tics being typically associated with low- or intermediate-grade NHL of follicle center origin. These features, along with the presence of some centrocytelike cells in the biopsy sections, suggest that an unusual pattern of histologic evolution from u follicle center ('ell NIIL may have occurred in this case of LyL. INTRODUCTION Lymphoblastic lymphoma (LyL) is a morphologically distinct entity of non-Hodgkin lymphoma (NHL) [1] with aggressive clinical behavior. Both T-cell and B-cell pheno- types have been documented, the former immunologic subset frequently involving the mediastinum, the latter presenting with prevalent abdominal disease [2]. Cytogenetic studies were performed in a l imited number of patients, showing 14ql l  re- arrangements and other less frequent abnormalities, besides normal karyotypes [3, 4]. We recently observed a patient with typical B-cell LyL presenting with prominent splenomegaly and showing the classical t(14;18)(q32;q21) asthe sole aberration. These unusual cytogenetic and cl inicopathologic findings are here il lustrated and discussed with regard to their possible significance in terms of origin and evolution of this rare form of NHL. CASE HISTORY The patient, a 71-year-old man, was referred to our institution with fever, weight loss, and splenomegaly-related symptoms. Phy ical examination was unremarkable, except for marked spleen enlargement. A chest x-ray film was normal. A computed From the Chair of th;matology (M. G. C., A. C., N. P., M. B.. F. F., (;. C.) and the Department of Pathology (P. C.), University ofFerrara, Italy. Address reprint requests to: Dr. Antonio Cuneo, Department of Hematology, C.so Giovecca 203, 44100 Ferrara, Italy. Received December 20, 1990; accepted March 18, 1991. 47  © 1991 Elsevier Science Publishing Co., Inc. Cancer Genet Cylogenet 57:47-51 (1991) 655 Avenue of the Americas, New York, NY 10010 0165-4608/91/$03.50 48 M.G. Carli et al. Figure 1 Histologic: preparation showing diffuse infiltrate by lymphoblasts with some macro- phages. Some cells with cleft nuclei are arrowect. tomography (CT) scan of the abdomen revealed numerous plenic nodules, one of which involved the il ium structures. At laparotomy, omental infiltration was docu- mented, and multiple biopsies were obtained showing on frozen sections a monomor- phic blast cell infiltrate, a picture suggestive of high-grade NHL. Bone marrow (BM) smears, as well as trephine biopsy sections, documented the absenc:e of infiltration by lymphoma cells. Multiagent chemotherapy {cyclophosphamide, vincristine, daun- orubicine, and prednisone} was administered monthly, and partial reduction of the spleen size was obtained. The patient is alive after 6 months, but his clinic:al condition has deteriorated (Karnowsky score, 60). MATERIALS AND METHODS Histologic Studies A section of the biopsy specimen was sent to the pathologist for classification ac- cording to the Kiel system [5]. Histologic preparations were made from formalin-fixed material and were stained with hematoxylin-eosin, Giemsa, periodic acid-Schiff, and Gomori's silver impregnation. Immunophenotyping A piece of the diagnostic: tissue was minced into RPMI 1640 in sterile conditions immediately after surgical removal. An aliquot of the cell suspension, adjusted to the concentration of I × 106/ml was spun onto a cytocentrifuge, and slides were processed t(14;18) in Lymphoblastic Lymphoma 49 Table 1 hnmunophenotype of neoplastic cells a Monoclonal antibody % Positive cells B4/CD19 92 JS/CD10 87 Ig Mu Negative Kappa Negative Lambda Negative TdT 56 C3bR/CD35 6 Leul/CD5 Negative OKT16/CD7 Negative Kil/CD30 Negative OKT26a/CD25 Negative HPCA1/CD34 45 (weak) o Determined by APAAP technique (100 cells observed on cylospin preparations). Results were confirmed by immunohistochemical st inings showing positivity for the L26 associated B-cell antibody, positivity in a slight minority of cells for the I..N2 antibody and negativity for surface and cytoplasmic immunoglobulin chains. according to the APAAP technique [6]. The expression of the following markers was tested: CD19, CDIO, CD5, CD2, HLA-Dr, CD33, and surface and cytoplasmic immunoglobulins (Ig) (heavy and light chains). Immunohistologic stains were also performed on paraffin sections with the follow- ing murine antibodies: UCHL 1 (CD45), L26 (detecting a pan-B cell antigen) (Dako), LN1, LN2, LN3 (detecting antigens associated with germinal center cells) (Biotest Diagn.) and anti-kappa, anti-lambda, anti-mu, anti-gamma and anti-alpha immuno- globulin chains. The presence of intracytoplasmic immunoglobulin chains on histo- logic sections was tested with the peroxidase-antiperoxidase method [7]. Cytogenetic Analysis For cytogenetic analysis, 5 x 106 cells/ml were cultured in RPMI 1640 additioned with 10% fetal calf serum (Gibco), and 50-mi flasks were incubated at 37°C in 5% CO2 humidified atmosphere. Cells were harvested according to standard procedures [8] after 24 hours. RESULTS The typical morphologic features of LyL [9] were observed on histologic sections. The cells had a fine chromatin pattern, and cytoplasm was scanty. Cleft nuclei were only observed occasionally (Fig. 1). As shown in Table 1, immunophenotype was that of a very immature B cell with negative cytoplasmic and surface Ig chains. Cytogeneti- cally, the classical t(14;18)(q21 ;q32) was the sole aberration i  18/20 metaphases (Fig. 2). Two cells had a normal karyotype. DISCUSSION In this reported patient, morphologic features and immunophenotype of neoplastic cells were typical of B-cell LyL [10]. Unlike previously reported cases, however, the clinical presentation was consistent with the occurrence of primary splenic involve- 50 M.G. Carli et al. m --dtfi__ t J - -  "14 18 Figure 2 Partial karyotypes showing the classical t(14:18)(q32;q21) in our patient with LyL. No additional clonal aberrations were detected in this patient. ment. LyL with prominent splenomegaly has not been rei)orted in the largest pub- lished series [2, 10, 111, and the most frequent histological types encountered in primary splenic NHL are represented by low- and intermediate-grade NHL, including follicle center cell lymphomas, intermediate lymphocytic lymphoma (included among the centrocytic type in the Kiel system), and small lymphot:ytic lymphoma [12, 13]. The presence of the 14;18 translocation as the sole aberration in our patient is remarkable, since previous tudies have not detected this aberration in Lyl, [3, 4, 14]. However, some patients have recently been reported in which unusual evolution of low-grade follicle center cell NHL into high-grade Burkittlike histology were docu- mented [15, 16]. In one such case, immunophenotyping revealed, as in our patient, immature B-cell features, and cytogenetic analysis of BM lymphoma cells at the time of blastic conversion showed a 14;18 translacation variant as well as the classical t(8;14). While no residual nodular structures were observed in our biopsy sections, some cells had cleft nuclei, a feature suggestive of a possible follicle center cell origin. Thus, indirect evidence, based on the cytogenetic findings and on the clinical presentation, seems to suggest hat histologic evolution from a follicle center cell lymphoma may have occurred in our patient during the preclinical phase of the disease [17]. Addi- tional genetic events may be responsible for the clinicopathologic evolution of NHL with the t(14;18), irrespective of whether or not they may be detectable cytogeneti- cally. Interestingly, the activation of c-myc by a complex cytagenetic rearrangement has recently been detected in a cell line established from a patient with Lyl lacking the classical 8;14 translocation [18]. Taken together, these observations possibly indicate that B-cell LyL may represent a histologic subset deriving in same cases from NHL of follicle center cell origin. Because current trends tend to unify treatment of LyL and of acute lymphoblastic leukemia [19], based on the notion that they may be similar clinicobiologic entities, the recognition of a disease subset of LyL possibly representing an evolutive form of follicle center cell NHL may crucial for the choice in such cases of a classical "anti lymphoma" therapy. This work was supported by MPI funds grants no. 90-40-(}6-005 and no. 90-60-06-018 (Rome). t(14;18) in Lymphoblastic Lymphoma 51 REFERENCES 1. Nathawani BN, Kim H, Rappaport H {1976): Malignant lymphoma, lymphoblastic. Cancer 38:964-983. 2. Mazza P, Bertini M, Macchi S, Lauria F, Pileri S, Rivano MT, Baccarani M, Ricci P, Fiacchini M, Vitolo U, Canta M, Paolino W, Zinzani PL, Poletti G, Verlicchi F, (;herlinzoni F, Tufa S (1986): Lymphoblastic lymphoma in adolescent aml adults. Clinical, pathological nd prognostic evaluation. Eur J Cancer Clin Oncol 22:1503-1510. 3. Koduru PRK, Filippa DA, Richardson ME, Jhanwar SC, Chaganti SR, Koziner B, Clarkson BD, l,ieberman PH, Chaganti RSK (1987): Cytogenetic and histologic orrelations in malignant lymphoma. Blood 69:97-102. 4. 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Lymphoblastic lymphoma with primary splenic involvement and the classic 14;18 translocation

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Lymphoblastic lymphoma with primary splenic involvement and the classic 14;18 translocation

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