Follicular dendritic cell sarcomas (FDCS) are grouped with the histiocytic and dendritic cell neoplasms. The natural history and response to different treatments have not been well established. The cases of 14 patients with FDCS who were seen at M. D. Anderson between 1995 and 2005 were reviewed. Median patient age was 48 years (range, 25-69 years). Histologically, four cases showed low-grade features, three cases showed low-grade features with focal high-grade features, and five cases showed high-grade features. Tumors were positive for CD21, CD23, and CD35 in 83, 90, and 44% of cases, respectively. Twelve (92%) of 13 tumors were strongly positive for epidermal growth factor receptor. Information on initial treatment was available in 11 patients, which included surgery alone in one patient, surgery and radiation in two, surgery and chemotherapy in one, chemotherapy alone in three, chemotherapy and radiation in one, surgery followed by radiation and chemotherapy in three patients. In eight patients the initial chemotherapy regimen was cyclophosphamide, doxorubicin, vincristine, and prednisone. Complete remission was achieved in 7 (63%) of 11 patients. Ten patients were alive at a median follow up of 22 months, 3 (23%) of 13 had no evidence of disease, and 7 (53%) of 13 patients were alive with disease. Follicular sarcoma is an aggressive neoplasm. Although most of the patients initially responded to treatment, the majority of them (81%) relapsed. A better understanding of the biology of FDCS could guide our efforts in the development of new treatment modalities for this rare disease. Am. J. Hematol. 82:725-728, 2007. V

SummaryZAP-70 (zeta-chain-associated protein 70 kDa) expression is associated with poor prognosis in patients with chronic lymphocytic leukaemia (CLL). This study evaluated the efficacy of non-myeloablative allogeneic stem cell transplantation in patients with advanced CLL and assessed the impact of ZAP-70 expression on the outcome. Thirty-nine sequential patients were included. All had previously been treated with fludarabine. All patients received a preparative regimen of fludarabine (30 mg/m 2 /d for 3 d), intravenous cyclophosphamide (750 mg/m 2 /d for 3 d), and high-dose rituximab. Immunohistochemical techniques on marrow biopsy samples were used to determine that ZAP-70 was expressed in 25 patients, whereas 13 other patients were ZAP-70 negative, and one was of indeterminate status. With a median follow-up time of 27 months, the estimated overall survival and current progression-free survival (CPFS) rates at 4 years were 48% and 44% respectively. Patients who were ZAP-70 positive had 56% survival, and their CPFS rate increased from 30% to 53% after a donor lymphocyte infusion. Multivariate analysis indicated that chemorefractory disease and mixed T cell chimerism at day 90, but not ZAP-70 positivity, were associated with the risk of disease progression after transplantation. These results demonstrate a potent graft-versus-leukaemia effect that can overcome the adverse prognostic effect of ZAP-70 expression.Keywords: graft-versus-leukaemia, non-myeloablative transplantation, ZAP-70, chronic lymphocytic leukaemia. 70 kDa) expression is an important prognostic factor in CLL (Rosenwald et al, 2001;Crespo et al, 2003;Orchard et al, 2004;Rassenti et al, 2004). Using immunoblot assays, investigators found that ZAP-70 expression was associated with the absence of somatic hypermutations in IgHV genes (Chen et al, 2002;Wiestner et al, 2003). In 107 patients with CLL, ZAP-70 expression was associated with the unmutated IgVH mutation phenotype, correctly predicting it in 93% of patients (Wiestner et al, 2003). The ability of ZAP-70 to predict a shorter time to treatment and poorer survival was also similar to that of IgVH mutation status.Recent articles suggested that allogeneic transplantation may overcome the adverse prognosis of unmutated IgVH (Ritgen et al, 2004;Caballero et al, 2005;Moreno et al, 2005). However, these studies involved high-dose or reduced-intensity ablative preparative regimens, associated with substantial toxicity. To date, however, it is unknown whether truly nonmyeloablative allogeneic transplantation relying on GVM effects can overcome the therapeutic resistance due to unfavourable biological features. We report here on the efficacy of the graft-versus-leukaemia effect after a complete non-myeloablative transplantation in a group of 39 B-CLL patients, with adverse clinical and/or biological prognostic factors. Patients and methods Patient selectionThis phase II trial of non-myeloablative stem-cell transplantation included patients aged 18-70 years with CLL that was refractory to fludarabine o...

Using immunohistochemical methods, we evaluated zeta-associated protein (ZAP)-70 expression in 341 cases of non-Hodgkin and Hodgkin lymphoma. In B-cell NHL, ZAP-70 was positive in five of six (83%) precursor B-lymphoblastic lymphoma, 11 of 37 (30%) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/ SLL), five of 39 (13%) mantle cell lymphoma, one of 12 (8%) Burkitt lymphoma, and one of 12 (8%) nodal marginal zone B-cell lymphoma. In 22 cases of CLL/SLL, seven of nine (78%) with unmutated IgV H genes expressed ZAP-70, compared with one of 13 (8%) with mutated IgV H genes (P ¼ 0.0015 Fisher's exact test). ZAP-70 expression was not detected in diffuse large B-cell lymphoma (n ¼ 26), extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (n ¼ 24), follicular lymphoma (n ¼ 21), plasma cell myeloma/ plasmacytoma (n ¼ 10), lymphoplasmacytic lymphoma (n ¼ 10), or splenic marginal zone lymphoma (n ¼ 6). In T/NK-cell NHL, ZAP-70 was positive in all extranodal natural killer (NK) / T-cell lymphoma, nasal-type (n ¼ 6) and enteropathy-type T-cell lymphoma (n ¼ 4), four of five (80%) subcutaneous panniculitis-like T-cell lymphoma, six of eight (75%) mycosis fungoides, three of five (60%) precursor T-lymphoblastic lymphoma, 10 of 17 (59%) peripheral T-cell lymphoma, two of four (50%) blastic NK-cell lymphoma, one of three (33%) T-cell prolymphocytic leukemia, 13 of 52 (25%) anaplastic large cell lymphoma, and one of six (17%) angioimmunoblastic T-cell lymphoma. Seven of 12 (58%) cutaneous CD30-positive lymphoproliferative disorders were also ZAP-70-positive. In Hodgkin lymphoma, ZAP-70 was negative in neoplastic cells in all cases tested. ZAP-70 staining in B-cell lymphomas and reactive T cells was predominantly nuclear with variable cytoplasmic staining. By contrast, ZAP-70 staining in T/NK-cell lymphomas was heterogeneous, and a shift from predominantly nuclear to predominantly cytoplasmic staining was observed, particularly in those neoplasms with high-grade morphology. In summary, ZAP-70 is expressed by many lymphoma types, correlates with immunoglobulin heavy-chain variable region gene mutational status in CLL/SLL, and can be detected reliably using immunohistochemical methods.

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The bcl-3 gene at chromosome 19q13 encodes a member of the IjB family involved in regulating the NFjB pathway. Originally identified by its involvement in the rare t(14:19)(q32;q13), BCL-3 expression has never been analyzed in a wide variety of lymphomas. We assessed BCL-3 expression in 353 cases of non-Hodgkin lymphoma and Hodgkin lymphoma using formalin-fixed, paraffin-embedded tissue specimens, a monoclonal antibody specific for BCL-3, and immunohistochemical methods. Of 172 B-cell lymphomas, 10 (6%) were positive for BCL-3, including six of 23 (26%) diffuse large B-cell lymphoma, one of 17 (6%) small lymphocytic lymphoma, one of 26 (4%) follicular lymphoma, and two of 49 (4%) mantle cell lymphoma. All other B-cell neoplasms were negative, including marginal zone lymphoma (n ¼ 24, 11 extranodal, nine nodal, four splenic), Burkitt lymphoma (n ¼ 10), lymphoplasmacytic lymphoma (n ¼ 10), lymphoblastic lymphoma (n ¼ 8), and plasmacytoma (n ¼ 5). Of 111 T/NK-cell lymphomas, 25 (23%) were positive for BCL-3, including 13 of 40 (32%) anaplastic large-cell lymphoma, three of 10 (30%) angioimmunoblastic T-cell lymphoma, two of eight (25%) extranodal NK/T-cell lymphoma of nasal type, three of 12 (25%) mycosis fungoides, one of five (20%) enteropathy-type T-cell lymphoma, and two of 21 (10%) peripheral T-cell lymphoma unspecified. All other T-cell neoplasms were negative, including lymphoblastic lymphoma (n ¼ 6), prolymphocytic leukemia (n ¼ 6), and subcutaneous panniculitis-like T-cell lymphoma (n ¼ 3). Of 70 Hodgkin lymphomas, of all types, 29 (41%) were positive for BCL-3. The relatively high frequency of BCL-3 expression in some non-Hodgkin and Hodgkin lymphoma types raises the possibility that BCL-3 is involved in the pathogenesis of these tumors, and may be a target of new therapies.

We report 22 cases of Hodgkin lymphoma involving Waldeyer ring seen at our institution during a 31-year interval. There were 16 males (73%) and 6 females (27%) with a median age of 48 years (range, 5-81 years), and 15 (68%) patients had airway obstruction or tonsillar enlargement. For 19 patients, the clinical stage was as follows: I, 7 (32%); II, 11 (50%); and III, 1 (5%). The 3 patients (14%) whose disease was unstaged had concurrent or a history of non-Hodgkin lymphoma. Histologically, the neoplasms were classified as follows: lymphocyte-rich classical, 8 (36%); nodular sclerosis, 7 (32%); mixed cellularity, 4 (18%); unclassified, 2 (9%); and lymphocyte depletion, 1 (5%). Of 7 stage I cases, 4 (57%) were the lymphocyte-rich classical type. Reed-Sternberg and Hodgkin cells were positive for CD15 and CD30 in 20 cases assessed. Epstein-Barr virus latent membrane protein type 1 was positive in 12 (67%) of 18 cases assessed. We conclude that Hodgkin lymphoma rarely involves Waldeyer ring, with the lymphocyte-rich classical type being common at this location.

Myeloid sarcoma is a neoplasm of immature granulocytes, monocytes, or both involving any extramedullary site. Myeloid sarcoma involving the testis, however, is uncommon and very rarely occurs as an isolated mass. We describe 4 patients with myeloid sarcoma involving the testis, including 2 patients in whom the neoplasm was isolated to the testis (1 unilateral and 1 bilateral). Histologically, 4 neoplasms were poorly differentiated and 1 was blastic. Each neoplasm was shown to be of myeloid lineage, and negative for T- and B-cell specific antigens using immunohistochemical methods. One case was also positive for chloroacetate esterase. In the literature, most cases of myeloid sarcoma involving the testis represent relapse or the initial presentation of acute myeloid leukemia. Including the 2 cases we report here, only 7 cases of myeloid sarcoma isolated to the testis have been reported.

We studied the clinicopathologic, immunophenotypic, and cytogenetic features of 26 patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) associated with serum IgM paraprotein. The study group (16 men; 10 women; median age, 64 years; range, 40-82 years) represents approximately 2.5% of CLL/SLL cases at our institution. The paraprotein level ranged from 1 to 14 g/L (median, 4 g/L). Neoplasms in bone marrow were composed of small round lymphocytes arranged in nodular (n = 6), diffuse (n = 5), interstitial (n = 5), or mixed (n = 10) patterns. All cases were positive for monotypic surface immunoglobulin light chain, IgM/IgD, CD5, CD19, CD20, and CD23. CD11c (14/20 [70%]), CD79b (11/19 [58%]), FMC-7 (11/26 [42%]), CD22 (8/20 [40%]), and ZAP-70 (6/19 [32%]) were expressed in subsets of cases. Of 17 bone marrow specimens assessed by conventional cytogenetics, 6 were abnormal and 11 were diploid. The overall survival of this group (median follow-up, 24 months) was not significantly different from that for an age-, sex-and stage-matched group of 52 CLL/SLL patients without IgM paraprotein (P = .60). We conclude that CLL/SLL cases with serum IgM paraprotein are similar to other CLL/SLL cases in their clinicopathologic and immunophenotypic features.