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histiocyte-rich large B-cell lymphoma
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Annals of Diagnostic Pathology 12 (2008) 290 – 292
Case Reports
Splenic micronodular T-cell/histiocyte-rich large B-cell lymphoma Elena Kan, MDa, Itai Levy, MDb, Daniel Benharroch, MDa,4 a
Departments of Pathology and Hematology, Soroka University Medical Center, PO Box 151, Beer-Sheva 84101, Israel b Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel
Abstract
A case showing the typical clinical and pathological features of splenic micronodular T-cell/ histiocyte-rich large B-cell lymphoma is presented. Since the series recorded by Dogan et al (Am J Surg Pathol 2003;27:903-911), there have been very few reports on this lymphoma variant. Our case presents minor variations on the recorded features. Possible reasons for the scarcity of reports and for the confirmation of this lymphoma as a variant of T-cell-rich large B-cell lymphoma are discussed. D 2008 Elsevier Inc. All rights reserved.
Keywords:
Large B-cell lymphoma; T-cell; Histiocyte
1. Introduction
2. Case report
In 2003, Dogan et al [1] described a series of 17 patients who presented with systemic symptoms, anemia, and splenomegaly and who underwent splenectomy. The splenic size varied from 850 to 2500 g. The spleen showed micronodularity, with the nodules set within a normal appearing splenic red pulp. Within the nodules, there was a heterogeneous reactive cellular population that included numerous CD3+ T-cells, histiocytes, some plasma cells, and a few eosinophilic granulocytes. Scattered among these cells, there were a few large CD20, Bcl-2, and Bcl-6 positive B-cells, which were negative for EBV and CD10 and variously positive for EMA and CD30. Four patients had mild lymphadenopathy at presentation. In the remainder, there was no evidence of lymphadenopathy. The histological and immunohistochemical features were consistent with T-cell/histiocyte-rich large B-cell lymphoma [1], and the lymphoma variant was designated as a splenic micronodular T-cell/histiocyte-rich large B-cell lymphoma. Most of the patients described by Dogan et al had died within 2 years of diagnosis [1]. Only a few patients with this variant lymphoma have been reported since the original description by Dogan et al [2-4]. We present an additional patient with splenic micronodular T-cell/histiocyte-rich large B-cell lymphoma who showed minor variations on the features described in the original cases.
A 63-year-old woman presented with fever, pruritus, weight loss, and fatigue. Anemia, elevated LDH, and hypogammaglobulinemia were found. The spleen was moderately enlarged, but there was no evidence of peripheral lymphadenopathy. Computed tomography (CT) scan confirmed the presence of isolated splenomegaly. A bone marrow biopsy showed predominantly paratrabecular infiltrates composed mainly of small lymphoid cells with irregular nuclei. The lymphoid cells were positive for CD20 and Bcl-2 and negative for CD3, CD43, and CD10. The interpretation of the marrow biopsy was difficult, but the possibility of follicular lymphoma was raised in view of the prominent paratrabecular infiltrates. A laparoscopic splenectomy was undertaken, and no other abdominal organs appeared to be involved. The spleen weighed 540 g, and the cut surface showed increased marking of the white pulp. Histological examination showed a micronodular pattern throughout the spleen with preservation of the red pulp between the nodules (Fig. 1). The nodules (Fig. 2) were composed of an admixture of small T-cells (CD3+; CD43+), histiocytes (CD68+), and eosinophils. Scattered among these cells were a few large, irregular lymphoid cells that were strongly CD20+ (Fig. 3), weakly CD30+, and focally positive for Bcl-2, Bcl-6, and epithelial membrane antigen (EMA). They were negative for CD23, CD15, CD10, and Epstein-Barr virus/latent membrain proteins (EBV/LMP). The diagnosis of splenic micronodular T-cell/histiocyterich large B-cell lymphoma was made on the basis of the histological and immunohistochemical findings.
4 Corresponding author. Tel.: +972 8 6400920; fax: +972 8 6232770. E-mail address: [email protected] (D. Benharroch). 1092-9134/$ – see front matter D 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.anndiagpath.2006.12.006
E. Kan et al. / Annals of Diagnostic Pathology 12 (2008) 290–292
291
Fig. 1. Micronodular involvement of spleen by the lymphoma with sparing of the red pulp (hematoxylin-eosin, 210).
Fig. 3. Large B-cells are prominent within a splenic nodule. Immunoperoxidase with CD20 antibody (diaminobenzidine, 430).
The patient was treated with 6 cycles of Rituximab, Cytoxan, Adriamycin, Vincristine, and Prednisone. The pruritus and fever subsided shortly after the beginning of treatment. CT and bone marrow examination at the conclusion of treatment confirmed evidence of complete remission. The patient remains well and in remission 12 months after diagnosis.
are scattered large B-cells in a background of numerous T-cells and histiocytes. The large B-cells stain with CD20 and Bcl-6; show a variable expression of EMA, Bcl-2, and CD30; and are negative for CD10 and EBV. No follicle dendritic meshwork is seen. Most of the patients in the initial series died within 2 years of diagnosis. In the same issue of the American Journal of Surgical Pathology, Mollejo et al [2] published a series of 33 cases of splenic large B-cell lymphoma. There were 9 of their cases that showed a micronodular pattern, including 3 who presented the features of micronodular T-cell-rich B-cell lymphoma, were diagnosed at an advanced stage, and had a poor prognosis. Li et al [3] have more recently described 3 cases of splenic T-cell-rich B-cell lymphoma that also showed a micronodular pattern but differed from the cases of Dogan et al [1] by the presence of florid extramedullary hematopoiesis. Wang et al [4] have reported a case of splenic marginal zone lymphoma associated with micronodular T-cell/histiocyte-rich large B-cell lymphoma located in the red pulp. They considered the possibility that the T-cell/histiocyterich component may have evolved as a transformation of the marginal zone B-cell lymphoma. Apart from the initial cases [1], only that described by Wang et al [4] depicted a splenic micronodular T-cell/histiocyte-rich large B-cell lymphoma, but it was combined with marginal zone lymphoma. Our patient presented with systemic symptoms, anemia, and splenomegaly, features which are most consistent with the diagnosis of splenic lymphoma, especially since the involvement seemed to be limited to the spleen and bone marrow. The fragmentation of the spleen that was removed by laparoscopic splenectomy may explain, in part, the relatively low splenic weight in our patient, which may also be related to an earlier diagnosis. Apart from the fact that Bcl-6 expression was weak and focal, all the other pathological and immunohistochemical findings in our patient are consistent with the diagnosis of splenic micronodular
3. Discussion Splenic micronodular T-cell/histiocyte rich large B-cell lymphoma was first described by Dogan et al [1]. It is found predominantly in males who present with anemia, systemic symptoms, and splenomegaly. Lymphadenopathy is usually absent and when present is minimal. The splenic weight in the reported cases ranges from 850 to 2500 g. The lymphoma involves the white pulp in a micronodular pattern and spares the red pulp. Within the nodules, there
Fig. 2. A nodule located in the white pulp shows a mixed cellular population with predominant histiocytes. Large lymphoid cells are not apparent (hematoxylin-eosin, 320).
292
E. Kan et al. / Annals of Diagnostic Pathology 12 (2008) 290–292
T-cell/histiocyte-rich large B-cell lymphoma. The diagnosis may be very difficult on the basis of the bone marrow biopsy alone, and the marrow findings may be misinterpreted as follicular lymphoma [1] as had occurred in our case. A number of conditions must be considered in the differential diagnosis of the splenic lesion seen in our patient. There was no evidence of granulomatous inflammation or follicular lymphoma. The possibility of T-cell lymphoma was suggested by the large number of T-cells present, but these were of small, uniform size, involved the white pulp only, and there was no significant necrosis. Nodular lymphocyte predominant Hodgkin disease was not a serious consideration because the large cells did not resemble lymphocytic and histiocytic cells and a follicular dendritic network was absent. Moreover, primary presentation of nodular lymphocyte predominant Hodgkin disease in the spleen is very rare. It was more difficult to exclude the possibility of classical Hodgkin disease. There were, however, no classical Reed-Sternberg cells, most of the large cells were strongly positive with CD20, CD30 expression was weak, and CD15 and EBV/LMP were negative. A micronodular pattern has, moreover, not been described in classical Hodgkin disease. The wide range of conditions that need to be considered in the differential diagnosis may account for the rare reports of splenic micronodular T-cell/histiocyte-rich large B-cell
lymphoma. Additional reports are needed to firmly establish this lymphoma variant. Recognition of micronodular T-cell/ histiocyte-rich large B-cell lymphoma of the spleen may contribute to the separation of T-cell/histiocyte-rich large B-cell lymphoma into several variants, accounting perhaps for the variable prognosis of this lymphoma [5,6]. References [1] Dogan A, Burke JS, Goteri G, et al. Micronodular T-cell/histiocyte-rich large B-cell lymphoma of the spleen: histology, immunophenotype, and differential diagnosis. Am J Surg Pathol 2003;27:903 - 11. [2] Mollejo M, Algara P, Mateo MS, et al. Large B-cell lymphoma presenting in the spleen: identification of different clinicopathological conditions. Am J Surg Pathol 2003;27:895 - 902. [3] Li S, Mann KP, Holden JT. T-cell-rich B-cell lymphoma presenting in the spleen: a clinicopathological analysis of 3 cases. Int J Surg Pathol 2004;12:31 - 7. [4] Wang SA, Olson N, Zukerberg L, et al. Splenic marginal zone lymphoma with micronodular T-cell-rich B-cell lymphoma. Am J Surg Pathol 2006;30:128 - 32. [5] Fraga M, Sanchez-Verde L, Forteza J, et al. T-cell/histiocyte-rich large B-cell lymphoma is a disseminated aggressive neoplasm: differential diagnosis from Hodgkin’s lymphoma. Histopathology 2002;41:216 - 29. [6] Bouabdallah R, Mounier N, Guettier C, et al. T-cell/histiocyte-rich large B-cell lymphoma and classical diffuse large B-cell lymphomas have similar outcome after chemotherapy: a matched-control analysis. J Clin Oncol 2003;21:1271 - 7.
Annals of Diagnostic Pathology 12 (2008) 290 – 292
Case Reports
Splenic micronodular T-cell/histiocyte-rich large B-cell lymphoma Elena Kan, MDa, Itai Levy, MDb, Daniel Benharroch, MDa,4 a
Departments of Pathology and Hematology, Soroka University Medical Center, PO Box 151, Beer-Sheva 84101, Israel b Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel
Abstract
A case showing the typical clinical and pathological features of splenic micronodular T-cell/ histiocyte-rich large B-cell lymphoma is presented. Since the series recorded by Dogan et al (Am J Surg Pathol 2003;27:903-911), there have been very few reports on this lymphoma variant. Our case presents minor variations on the recorded features. Possible reasons for the scarcity of reports and for the confirmation of this lymphoma as a variant of T-cell-rich large B-cell lymphoma are discussed. D 2008 Elsevier Inc. All rights reserved.
Keywords:
Large B-cell lymphoma; T-cell; Histiocyte
1. Introduction
2. Case report
In 2003, Dogan et al [1] described a series of 17 patients who presented with systemic symptoms, anemia, and splenomegaly and who underwent splenectomy. The splenic size varied from 850 to 2500 g. The spleen showed micronodularity, with the nodules set within a normal appearing splenic red pulp. Within the nodules, there was a heterogeneous reactive cellular population that included numerous CD3+ T-cells, histiocytes, some plasma cells, and a few eosinophilic granulocytes. Scattered among these cells, there were a few large CD20, Bcl-2, and Bcl-6 positive B-cells, which were negative for EBV and CD10 and variously positive for EMA and CD30. Four patients had mild lymphadenopathy at presentation. In the remainder, there was no evidence of lymphadenopathy. The histological and immunohistochemical features were consistent with T-cell/histiocyte-rich large B-cell lymphoma [1], and the lymphoma variant was designated as a splenic micronodular T-cell/histiocyte-rich large B-cell lymphoma. Most of the patients described by Dogan et al had died within 2 years of diagnosis [1]. Only a few patients with this variant lymphoma have been reported since the original description by Dogan et al [2-4]. We present an additional patient with splenic micronodular T-cell/histiocyte-rich large B-cell lymphoma who showed minor variations on the features described in the original cases.
A 63-year-old woman presented with fever, pruritus, weight loss, and fatigue. Anemia, elevated LDH, and hypogammaglobulinemia were found. The spleen was moderately enlarged, but there was no evidence of peripheral lymphadenopathy. Computed tomography (CT) scan confirmed the presence of isolated splenomegaly. A bone marrow biopsy showed predominantly paratrabecular infiltrates composed mainly of small lymphoid cells with irregular nuclei. The lymphoid cells were positive for CD20 and Bcl-2 and negative for CD3, CD43, and CD10. The interpretation of the marrow biopsy was difficult, but the possibility of follicular lymphoma was raised in view of the prominent paratrabecular infiltrates. A laparoscopic splenectomy was undertaken, and no other abdominal organs appeared to be involved. The spleen weighed 540 g, and the cut surface showed increased marking of the white pulp. Histological examination showed a micronodular pattern throughout the spleen with preservation of the red pulp between the nodules (Fig. 1). The nodules (Fig. 2) were composed of an admixture of small T-cells (CD3+; CD43+), histiocytes (CD68+), and eosinophils. Scattered among these cells were a few large, irregular lymphoid cells that were strongly CD20+ (Fig. 3), weakly CD30+, and focally positive for Bcl-2, Bcl-6, and epithelial membrane antigen (EMA). They were negative for CD23, CD15, CD10, and Epstein-Barr virus/latent membrain proteins (EBV/LMP). The diagnosis of splenic micronodular T-cell/histiocyterich large B-cell lymphoma was made on the basis of the histological and immunohistochemical findings.
4 Corresponding author. Tel.: +972 8 6400920; fax: +972 8 6232770. E-mail address: [email protected] (D. Benharroch). 1092-9134/$ – see front matter D 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.anndiagpath.2006.12.006
E. Kan et al. / Annals of Diagnostic Pathology 12 (2008) 290–292
291
Fig. 1. Micronodular involvement of spleen by the lymphoma with sparing of the red pulp (hematoxylin-eosin, 210).
Fig. 3. Large B-cells are prominent within a splenic nodule. Immunoperoxidase with CD20 antibody (diaminobenzidine, 430).
The patient was treated with 6 cycles of Rituximab, Cytoxan, Adriamycin, Vincristine, and Prednisone. The pruritus and fever subsided shortly after the beginning of treatment. CT and bone marrow examination at the conclusion of treatment confirmed evidence of complete remission. The patient remains well and in remission 12 months after diagnosis.
are scattered large B-cells in a background of numerous T-cells and histiocytes. The large B-cells stain with CD20 and Bcl-6; show a variable expression of EMA, Bcl-2, and CD30; and are negative for CD10 and EBV. No follicle dendritic meshwork is seen. Most of the patients in the initial series died within 2 years of diagnosis. In the same issue of the American Journal of Surgical Pathology, Mollejo et al [2] published a series of 33 cases of splenic large B-cell lymphoma. There were 9 of their cases that showed a micronodular pattern, including 3 who presented the features of micronodular T-cell-rich B-cell lymphoma, were diagnosed at an advanced stage, and had a poor prognosis. Li et al [3] have more recently described 3 cases of splenic T-cell-rich B-cell lymphoma that also showed a micronodular pattern but differed from the cases of Dogan et al [1] by the presence of florid extramedullary hematopoiesis. Wang et al [4] have reported a case of splenic marginal zone lymphoma associated with micronodular T-cell/histiocyte-rich large B-cell lymphoma located in the red pulp. They considered the possibility that the T-cell/histiocyterich component may have evolved as a transformation of the marginal zone B-cell lymphoma. Apart from the initial cases [1], only that described by Wang et al [4] depicted a splenic micronodular T-cell/histiocyte-rich large B-cell lymphoma, but it was combined with marginal zone lymphoma. Our patient presented with systemic symptoms, anemia, and splenomegaly, features which are most consistent with the diagnosis of splenic lymphoma, especially since the involvement seemed to be limited to the spleen and bone marrow. The fragmentation of the spleen that was removed by laparoscopic splenectomy may explain, in part, the relatively low splenic weight in our patient, which may also be related to an earlier diagnosis. Apart from the fact that Bcl-6 expression was weak and focal, all the other pathological and immunohistochemical findings in our patient are consistent with the diagnosis of splenic micronodular
3. Discussion Splenic micronodular T-cell/histiocyte rich large B-cell lymphoma was first described by Dogan et al [1]. It is found predominantly in males who present with anemia, systemic symptoms, and splenomegaly. Lymphadenopathy is usually absent and when present is minimal. The splenic weight in the reported cases ranges from 850 to 2500 g. The lymphoma involves the white pulp in a micronodular pattern and spares the red pulp. Within the nodules, there
Fig. 2. A nodule located in the white pulp shows a mixed cellular population with predominant histiocytes. Large lymphoid cells are not apparent (hematoxylin-eosin, 320).
292
E. Kan et al. / Annals of Diagnostic Pathology 12 (2008) 290–292
T-cell/histiocyte-rich large B-cell lymphoma. The diagnosis may be very difficult on the basis of the bone marrow biopsy alone, and the marrow findings may be misinterpreted as follicular lymphoma [1] as had occurred in our case. A number of conditions must be considered in the differential diagnosis of the splenic lesion seen in our patient. There was no evidence of granulomatous inflammation or follicular lymphoma. The possibility of T-cell lymphoma was suggested by the large number of T-cells present, but these were of small, uniform size, involved the white pulp only, and there was no significant necrosis. Nodular lymphocyte predominant Hodgkin disease was not a serious consideration because the large cells did not resemble lymphocytic and histiocytic cells and a follicular dendritic network was absent. Moreover, primary presentation of nodular lymphocyte predominant Hodgkin disease in the spleen is very rare. It was more difficult to exclude the possibility of classical Hodgkin disease. There were, however, no classical Reed-Sternberg cells, most of the large cells were strongly positive with CD20, CD30 expression was weak, and CD15 and EBV/LMP were negative. A micronodular pattern has, moreover, not been described in classical Hodgkin disease. The wide range of conditions that need to be considered in the differential diagnosis may account for the rare reports of splenic micronodular T-cell/histiocyte-rich large B-cell
lymphoma. Additional reports are needed to firmly establish this lymphoma variant. Recognition of micronodular T-cell/ histiocyte-rich large B-cell lymphoma of the spleen may contribute to the separation of T-cell/histiocyte-rich large B-cell lymphoma into several variants, accounting perhaps for the variable prognosis of this lymphoma [5,6]. References [1] Dogan A, Burke JS, Goteri G, et al. Micronodular T-cell/histiocyte-rich large B-cell lymphoma of the spleen: histology, immunophenotype, and differential diagnosis. Am J Surg Pathol 2003;27:903 - 11. [2] Mollejo M, Algara P, Mateo MS, et al. Large B-cell lymphoma presenting in the spleen: identification of different clinicopathological conditions. Am J Surg Pathol 2003;27:895 - 902. [3] Li S, Mann KP, Holden JT. T-cell-rich B-cell lymphoma presenting in the spleen: a clinicopathological analysis of 3 cases. Int J Surg Pathol 2004;12:31 - 7. [4] Wang SA, Olson N, Zukerberg L, et al. Splenic marginal zone lymphoma with micronodular T-cell-rich B-cell lymphoma. Am J Surg Pathol 2006;30:128 - 32. [5] Fraga M, Sanchez-Verde L, Forteza J, et al. T-cell/histiocyte-rich large B-cell lymphoma is a disseminated aggressive neoplasm: differential diagnosis from Hodgkin’s lymphoma. Histopathology 2002;41:216 - 29. [6] Bouabdallah R, Mounier N, Guettier C, et al. T-cell/histiocyte-rich large B-cell lymphoma and classical diffuse large B-cell lymphomas have similar outcome after chemotherapy: a matched-control analysis. J Clin Oncol 2003;21:1271 - 7.