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Posttransplantation lymphoproliferative disease involving the pituitary gland
Human Pathology (2010) 41, 1641–1645
www.elsevier.com/locate/humpath
Case study
Posttransplantation lymphoproliferative disease involving the pituitary gland☆ Zina Meriden MD a , Grant C. Bullock MD, PhD a , Adam Bagg MD b , Hugo Bonatti MD c , John B. Cousar MD a , M. Beatriz Lopes MD, PhD a , Mark K. Robbins MD d , Helen P. Cathro MBChB a,⁎ a
Department of Pathology, University of Virginia Health System, PO Box 800214, Charlottesville, VA 22908, USA Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA c Department of Surgery, University of Virginia Health System, Charlottesville, VA 22908, USA d Department of Internal Medicine, University of Virginia Health System, Charlottesville, VA 22908, USA b
Received 27 October 2009; revised 29 January 2010; accepted 9 February 2010
Keywords: Posttransplantation lymphoproliferative disorder; T-cell lymphoma; B-cell lymphoma; EBV-negative; Pituitary
Summary Posttransplantation lymphoproliferative disorders (PTLD) are heterogeneous lesions with variable morphology, immunophenotype, and molecular characteristics. Multiple distinct primary lesions can occur in PTLD, rarely with both B-cell and T-cell characteristics. Lesions can involve both grafted organs and other sites; however, PTLD involving the pituitary gland has not been previously reported. We describe a patient who developed Epstein-Barr virus–negative PTLD 13 years posttransplantation involving the terminal ileum and pituitary, which was simultaneously involved by a pituitary adenoma. Immunohistochemistry of the pituitary lesion showed expression of CD79a, CD3, and CD7 with clonal rearrangements of both T-cell receptor gamma chain (TRG@) and immunoglobulin heavy chain (IGH@) genes. The terminal ileal lesion was immunophenotypically and molecularly distinct. This is the first report of pituitary PTLD and illustrates the potentially complex nature of PTLD. © 2010 Elsevier Inc. All rights reserved.
1. Introduction Posttransplantation lymphoproliferative disorders (PTLD) complicate solid organ transplantation and include polyclonal lymphoid hyperplasias as well as aggressive, high-grade lymphomas [1,2]. With an estimated mortality of up to 60% [3], PTLD is among the most significant risks of transplantation. Most monomorphic PTLD resemble Epstein-Barr ☆ Funding sources: Department of Pathology, University of Virginia Health System. ⁎ Corresponding author. E-mail address: [email protected] (H. P. Cathro).
0046-8177/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.humpath.2010.02.015
virus (EBV)-positive diffuse large B-cell lymphoma, whereas 15% resemble T-cell or natural killer cell lymphomas [1]. Multiple, molecularly unique primary lesions can occur in PTLD [4], and rare cases of PTLD with distinct lesions showing features of synchronous or metachronous B-cell and T-cell lymphoma have been documented [5-8]. PTLD commonly involves the lymph nodes, liver, lung, and bone marrow. Central nervous system PTLD is rare and typically involves the corpus callosum or basal ganglia. Although a few reports have described primary [9-11] and metastatic lymphomas to the pituitary [12], pituitary PTLD has not been reported. We describe a case of PTLD with multiple morphologically and molecularly
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Pituitary post-transplantation lymphoproliferative disorder distinct lesions involving the ileum and the pituitary gland, the latter containing a composite of 3 different lesions: a pituitary adenoma and clonal B-lymphocyte and Tlymphocyte proliferations.
2. Case report 2.1. Clinical findings A 43-year-old white female underwent unilateral lung transplantation for bronchiolitis obliterans and was subsequently placed on cyclosporine, prednisone taper, and azathioprine. She experienced no episodes of rejection or infections. Thirteen years posttransplantation, she presented with hypotension, fever, and altered mental status. The patient was presumed to be in septic shock, but an extensive infectious disease workup, including EBV serologies, was unrevealing. Head computed tomography demonstrated a diffusely enlarged pituitary gland. Chest x-ray and computed tomography revealed cystic bronchiectasis in the native right lung and bilateral pleural effusions. The patient died due to sepsis and respiratory failure 2 weeks later.
2.2. Autopsy findings The lower lobe of the transplanted lung was notable for acute bronchopneumonia. The terminal ileum had 2 discrete polyps, the larger being 5.4 cm. The brain was grossly and histologically normal apart from a moderately enlarged pituitary.
2.3. Histology, immunohistochemistry, and molecular analysis The terminal ileal lesions showed a relatively monomorphous population of moderate to large lymphoid cells with variably prominent nucleoli. Some of the moderately large cells were cleaved, and the large cells in one area of the lesion were markedly pleomorphic with wreath forms (Fig. 1A). The atypical cells were positive for CD79a (Fig. 1B), CD10, and PAX-5, but negative for CD3 (Fig. 1C), MUM1, CD20, Bcl-6, HHV-8, CD138, and TdT. In situ hybridization (ISH) for kappa and lambda light chains was polytypic, and EBER (Fig. 1D) was negative. Rare infiltrating T-cells were positive for CD4, CD5, CD7, and CD8. Ki-67 staining demonstrated 60% to 80% positivity of the tumor cells depending on the area examined. Given the morphology, immunohistochemical profile, and proliferation index of the lesion, it was classified as a monomorphic B-cell PTLD of
1643 diffuse large B-cell lymphoma type, with both centroblastic and anaplastic features. The pituitary was remarkable for an α subunit–positive pituitary adenoma. The adenoma was positive for chromogranin (Fig. 1E and F) and was involved by an atypical sinusoidal lymphoid infiltrate (Fig. 1E) composed mostly of smaller lymphoid cells than those of the terminal ileal lesion. These cells were degenerated, making nuclear features difficult to discern. A small population of intermediate to large cells displayed prominent nucleoli. Subclassification of this poorly preserved polymorphous population is problematic, but this is most likely a polymorphous PTLD. Ki-67 staining was not performed on this tissue because of the difficulty of interpreting poorly preserved material. The atypical cells were positive for CD79a (Fig. 1G), CD3 (Fig. 1H), and CD7, but were negative for CD20, PAX-5, CD4, CD5, TdT, and HHV-8. EBER ISH was negative. Dual staining was attempted but failed due to poor tissue preservation. Nonetheless, the strong diffuse staining with both B-cell and T-cell markers suggests both B-cell and T- cell populations at the very least. The loss of CD4, CD5, and CD8 expression suggests a neoplastic T-lymphocytic population. IGH@-polymerase chain reaction (PCR) of the pituitary showed a predominant IGH@ amplicon of 159 nucleotides (nt) consistent with a clonal B-cell proliferation (Fig. 2A). TRG@-PCR of the pituitary also showed a predominant TRG@ amplicon of 160 nt, consistent with a clonal T-cell proliferation (Fig. 2B). IGH@-PCR of the ileal lesion showed a predominant IGH@ amplicon that was detected by all 3 of the IGH@ V-J primer sets demonstrating a molecularly distinct clonal B-cell population (Fig. 2C-E). TRG@-PCR of the ileal lesion showed no evidence of clonality. The similarity in size of the IGH@ (159 nt) and TRG@ (160 nt) amplicons from the pituitary is coincidental, as these finding were reproducibly found on multiple repeat assessments done on different days, and all controls were as expected. These results suggest that the pituitary had clonal T-cells as well as clonal B-cells that are molecularly distinct from the clonal B-cells in the ileum.
3. Discussion PTLD involving the pituitary has not been previously reported. This case is a late-onset pituitary PTLD that formed a collision tumor with a pituitary adenoma. Furthermore, there appeared to be a separate, clonally unrelated lymphoma in the terminal ileum, highlighting the propensity for lymphoma in immunosuppressed patients. Both primary
Fig. 1 Terminal ileum and pituitary gland (×400). H&E of terminal ileum (A) shows cells with dispersed chromatin and small nucleoli. These cells are CD79a-positive (B) and CD3-negative (C). ISH for EBER was negative (D). H&E of pituitary (E) shows an adenoma with sinusoids containing atypical lymphoid cells. The cells composing the pituitary adenoma are chromogranin-positive (F), whereas the lymphoma cells stain positively for both CD79a (G) and CD3 (H).
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Fig. 2 Electropherograms demonstrate clonal B-cell and T-cell rearrangements in the pituitary that are distinct from the ileal lesion. The pituitary shows a clonal IGH@ D1-6→J rearrangement (A) and a clonal TRG@Vγ10→J1.3/2.3 rearrangement (B). The ileum shows a different clonal IGH@ rearrangement, with IGH@ VFR1→J at 337 nt (C), IGH@ VFR2→J at 272 nt (D), and IGH@ VFR3→J at 142 nt (E). The 3 clonal IGH@-PCR products seen in the small intestine at 337 nt, 272 nt, and 142 nt all represent the same clonal IGH@ gene rearrangement, which is molecularly distinct from that in the pituitary. Lymphocyte clonality was assessed using the BIOMED-2 IGH@ and TRG@ multiplex PCR primer sets [13] followed by capillary electrophoresis and GeneScan fragment analysis (Applied Biosystems). Clonal lymphoid proliferations result in 1 or 2 prominent, valid-sized peaks in the electropherogram. Prominent peaks have relative fluorescence intensity at least 3 times that of the polyclonal background peaks. In our laboratory, this method detects 94% of B-cell lymphomas and 89% of T-cell lymphomas.
and secondary pituitary lymphomas have been described in immunocompetent patients [9]. This case is the first report of pituitary PTLD. Early and late PTLD are thought to represent distinct clinicopathologic entities [14,15]. Early PTLD are commonly EBV-driven, have diverse clinical presentations, and display broader histologic patterns, ranging from polymorphic to monomorphic lesions. Early cases are more likely to involve the allograft, whereas late PTLD often occur in other sites, particularly the gastrointestinal tract [15]. Late PTLD are usually monoclonal, EBV-negative, and resist immunosuppressive modulation or chemotherapy, unlike early PTLD [14]. This case of pituitary PTLD demonstrates both B-cell and T-cell antigen expression. Several reports have described
synchronous or metachronous independent, mixed lineage lymphoid lesions in PTLD [5-8]. Based on these reports, one possible explanation for this case is that the pituitary lesion represents a mixed population of morphologically atypical clonal B-cells and clonal T-cells that persist due to chronic immunosuppression. An alternative explanation is that the pituitary lesion is involved by a lymphoma that expresses both B-cell and T-cell antigens and has both IGH@ and TRG@ gene rearrangements. The differing molecular genotype of the IGH@ clonal rearrangement detected in the enteric lymphoma suggests that it is a separate and clonally unrelated B-cell proliferation. PTLD may not always fit into distinct categories and the nature of the lesions comprising PTLD can be complex. This patient appears to have had a distinct monomorphic diffuse
Pituitary post-transplantation lymphoproliferative disorder large B-cell lymphoma, but a simultaneous molecularly distinct, clonal, mixed lineage lymphoid proliferation involving a pituitary adenoma. All lesions were EBVnegative and became clinically apparent 13 years posttransplantation. After transplantation, a sellar mass should raise the possibility of pituitary PTLD, as this site is not protected from involvement.
Acknowledgments The authors would like to thank Michael Cruise, Thomas Tillack, Mani Mahadevan, Lawrence Silverman, James Patterson, Nancy Mills, Regina Seaner, and Karen Siegrist for their assistance with this work.
References [1] Swerdlow SH, Campo E, Harris NL, et al. WHO classification of tumours of haematopoietic and lymphoid tissue. Albany (NY): World Health Organization; 2008. [2] Taylor AL, Marcus R, Bradley JA. Post-transplant lymphoproliferative disorders (PTLD) after solid organ transplantation. Crit Rev Oncol Hematol 2005;56:155-67. [3] Bakker NA, van Imhoff GW, Verschuuren EA, et al. Presentation and early detection of post-transplant lymphoproliferative disorder after solid organ transplantation. Transpl Int 2007;20:207-18. [4] Chadburn A, Cesarman E, Liu YF, et al. Molecular genetic analysis demonstrates that multiple posttransplantation lymphoproliferative disorders occurring in one anatomic site in a single patient represent distinct primary lymphoid neoplasms. Cancer 1995;75:2747-56.
1645 [5] Frankel AH, Thompson M, Vulliamy T, et al. A T cell clone in association with an Epstein-Barr virus–related B cell lymphoma. Transplantation 1991;52:1108-9. [6] Hollingsworth HC, Stetler-Stevenson M, Gagneten D, et al. Immunodeficiency-associated malignant lymphoma. Three cases showing genotypic evidence of both T- and B-cell lineages. Am J Surg Pathol 1994;18:1092-101. [7] Morovic A, Jaffe ES, Raffeld M, et al. Metachronous EBV-associated B-cell and T-cell posttransplant lymphoproliferative disorders in a heart transplant recipient. Am J Surg Pathol 2009;33:149-54. [8] Yin CC, Medeiros LJ, Abruzzo LV, et al. EBV-associated B- and Tcell posttransplant lymphoproliferative disorders following primary EBV infection in a kidney transplant recipient. Am J Clin Pathol 2005;123:222-8. [9] Landman RE, Wardlaw SL, McConnell RJ, et al. Pituitary lymphoma presenting as fever of unknown origin. J Clin Endocrinol Metab 2001;86:1470-6. [10] Liu JK, Sayama C, Chin SS, et al. Extranodal NK/T-cell lymphoma presenting as a pituitary mass: case report and review of the literature. J Neurosurg 2007;107:660-5. [11] Kaufmann TJ, Lopes MB, Laws Jr ER, et al. Primary sellar lymphoma: radiologic and pathologic findings in two patients. AJNR Am J Neuroradiol 2002;23:364-7. [12] Megan Ogilvie C, Payne S, Evanson J, et al. Lymphoma metastasizing to the pituitary: an unusual presentation of a treatable disease. Pituitary 2005;8:139-46. [13] van Dongen JJM, Langerak AW, Bruggemann M, et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia 2003;17:2257-317. [14] Dotti G, Fiocchi R, Motta T, et al. Lymphomas occurring late after solid-organ transplantation: influence of treatment on the clinical outcome. Transplantation 2002;74:1095-102. [15] Paranjothi S, Yusen RD, Kraus MD, et al. Lymphoproliferative disease after lung transplantation: comparison of presentation and outcome of early and late cases. J Heart Lung Transplant 2001;20:1054-63.
www.elsevier.com/locate/humpath
Case study
Posttransplantation lymphoproliferative disease involving the pituitary gland☆ Zina Meriden MD a , Grant C. Bullock MD, PhD a , Adam Bagg MD b , Hugo Bonatti MD c , John B. Cousar MD a , M. Beatriz Lopes MD, PhD a , Mark K. Robbins MD d , Helen P. Cathro MBChB a,⁎ a
Department of Pathology, University of Virginia Health System, PO Box 800214, Charlottesville, VA 22908, USA Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA c Department of Surgery, University of Virginia Health System, Charlottesville, VA 22908, USA d Department of Internal Medicine, University of Virginia Health System, Charlottesville, VA 22908, USA b
Received 27 October 2009; revised 29 January 2010; accepted 9 February 2010
Keywords: Posttransplantation lymphoproliferative disorder; T-cell lymphoma; B-cell lymphoma; EBV-negative; Pituitary
Summary Posttransplantation lymphoproliferative disorders (PTLD) are heterogeneous lesions with variable morphology, immunophenotype, and molecular characteristics. Multiple distinct primary lesions can occur in PTLD, rarely with both B-cell and T-cell characteristics. Lesions can involve both grafted organs and other sites; however, PTLD involving the pituitary gland has not been previously reported. We describe a patient who developed Epstein-Barr virus–negative PTLD 13 years posttransplantation involving the terminal ileum and pituitary, which was simultaneously involved by a pituitary adenoma. Immunohistochemistry of the pituitary lesion showed expression of CD79a, CD3, and CD7 with clonal rearrangements of both T-cell receptor gamma chain (TRG@) and immunoglobulin heavy chain (IGH@) genes. The terminal ileal lesion was immunophenotypically and molecularly distinct. This is the first report of pituitary PTLD and illustrates the potentially complex nature of PTLD. © 2010 Elsevier Inc. All rights reserved.
1. Introduction Posttransplantation lymphoproliferative disorders (PTLD) complicate solid organ transplantation and include polyclonal lymphoid hyperplasias as well as aggressive, high-grade lymphomas [1,2]. With an estimated mortality of up to 60% [3], PTLD is among the most significant risks of transplantation. Most monomorphic PTLD resemble Epstein-Barr ☆ Funding sources: Department of Pathology, University of Virginia Health System. ⁎ Corresponding author. E-mail address: [email protected] (H. P. Cathro).
0046-8177/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.humpath.2010.02.015
virus (EBV)-positive diffuse large B-cell lymphoma, whereas 15% resemble T-cell or natural killer cell lymphomas [1]. Multiple, molecularly unique primary lesions can occur in PTLD [4], and rare cases of PTLD with distinct lesions showing features of synchronous or metachronous B-cell and T-cell lymphoma have been documented [5-8]. PTLD commonly involves the lymph nodes, liver, lung, and bone marrow. Central nervous system PTLD is rare and typically involves the corpus callosum or basal ganglia. Although a few reports have described primary [9-11] and metastatic lymphomas to the pituitary [12], pituitary PTLD has not been reported. We describe a case of PTLD with multiple morphologically and molecularly
1642
Z. Meriden et al.
Pituitary post-transplantation lymphoproliferative disorder distinct lesions involving the ileum and the pituitary gland, the latter containing a composite of 3 different lesions: a pituitary adenoma and clonal B-lymphocyte and Tlymphocyte proliferations.
2. Case report 2.1. Clinical findings A 43-year-old white female underwent unilateral lung transplantation for bronchiolitis obliterans and was subsequently placed on cyclosporine, prednisone taper, and azathioprine. She experienced no episodes of rejection or infections. Thirteen years posttransplantation, she presented with hypotension, fever, and altered mental status. The patient was presumed to be in septic shock, but an extensive infectious disease workup, including EBV serologies, was unrevealing. Head computed tomography demonstrated a diffusely enlarged pituitary gland. Chest x-ray and computed tomography revealed cystic bronchiectasis in the native right lung and bilateral pleural effusions. The patient died due to sepsis and respiratory failure 2 weeks later.
2.2. Autopsy findings The lower lobe of the transplanted lung was notable for acute bronchopneumonia. The terminal ileum had 2 discrete polyps, the larger being 5.4 cm. The brain was grossly and histologically normal apart from a moderately enlarged pituitary.
2.3. Histology, immunohistochemistry, and molecular analysis The terminal ileal lesions showed a relatively monomorphous population of moderate to large lymphoid cells with variably prominent nucleoli. Some of the moderately large cells were cleaved, and the large cells in one area of the lesion were markedly pleomorphic with wreath forms (Fig. 1A). The atypical cells were positive for CD79a (Fig. 1B), CD10, and PAX-5, but negative for CD3 (Fig. 1C), MUM1, CD20, Bcl-6, HHV-8, CD138, and TdT. In situ hybridization (ISH) for kappa and lambda light chains was polytypic, and EBER (Fig. 1D) was negative. Rare infiltrating T-cells were positive for CD4, CD5, CD7, and CD8. Ki-67 staining demonstrated 60% to 80% positivity of the tumor cells depending on the area examined. Given the morphology, immunohistochemical profile, and proliferation index of the lesion, it was classified as a monomorphic B-cell PTLD of
1643 diffuse large B-cell lymphoma type, with both centroblastic and anaplastic features. The pituitary was remarkable for an α subunit–positive pituitary adenoma. The adenoma was positive for chromogranin (Fig. 1E and F) and was involved by an atypical sinusoidal lymphoid infiltrate (Fig. 1E) composed mostly of smaller lymphoid cells than those of the terminal ileal lesion. These cells were degenerated, making nuclear features difficult to discern. A small population of intermediate to large cells displayed prominent nucleoli. Subclassification of this poorly preserved polymorphous population is problematic, but this is most likely a polymorphous PTLD. Ki-67 staining was not performed on this tissue because of the difficulty of interpreting poorly preserved material. The atypical cells were positive for CD79a (Fig. 1G), CD3 (Fig. 1H), and CD7, but were negative for CD20, PAX-5, CD4, CD5, TdT, and HHV-8. EBER ISH was negative. Dual staining was attempted but failed due to poor tissue preservation. Nonetheless, the strong diffuse staining with both B-cell and T-cell markers suggests both B-cell and T- cell populations at the very least. The loss of CD4, CD5, and CD8 expression suggests a neoplastic T-lymphocytic population. IGH@-polymerase chain reaction (PCR) of the pituitary showed a predominant IGH@ amplicon of 159 nucleotides (nt) consistent with a clonal B-cell proliferation (Fig. 2A). TRG@-PCR of the pituitary also showed a predominant TRG@ amplicon of 160 nt, consistent with a clonal T-cell proliferation (Fig. 2B). IGH@-PCR of the ileal lesion showed a predominant IGH@ amplicon that was detected by all 3 of the IGH@ V-J primer sets demonstrating a molecularly distinct clonal B-cell population (Fig. 2C-E). TRG@-PCR of the ileal lesion showed no evidence of clonality. The similarity in size of the IGH@ (159 nt) and TRG@ (160 nt) amplicons from the pituitary is coincidental, as these finding were reproducibly found on multiple repeat assessments done on different days, and all controls were as expected. These results suggest that the pituitary had clonal T-cells as well as clonal B-cells that are molecularly distinct from the clonal B-cells in the ileum.
3. Discussion PTLD involving the pituitary has not been previously reported. This case is a late-onset pituitary PTLD that formed a collision tumor with a pituitary adenoma. Furthermore, there appeared to be a separate, clonally unrelated lymphoma in the terminal ileum, highlighting the propensity for lymphoma in immunosuppressed patients. Both primary
Fig. 1 Terminal ileum and pituitary gland (×400). H&E of terminal ileum (A) shows cells with dispersed chromatin and small nucleoli. These cells are CD79a-positive (B) and CD3-negative (C). ISH for EBER was negative (D). H&E of pituitary (E) shows an adenoma with sinusoids containing atypical lymphoid cells. The cells composing the pituitary adenoma are chromogranin-positive (F), whereas the lymphoma cells stain positively for both CD79a (G) and CD3 (H).
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Fig. 2 Electropherograms demonstrate clonal B-cell and T-cell rearrangements in the pituitary that are distinct from the ileal lesion. The pituitary shows a clonal IGH@ D1-6→J rearrangement (A) and a clonal TRG@Vγ10→J1.3/2.3 rearrangement (B). The ileum shows a different clonal IGH@ rearrangement, with IGH@ VFR1→J at 337 nt (C), IGH@ VFR2→J at 272 nt (D), and IGH@ VFR3→J at 142 nt (E). The 3 clonal IGH@-PCR products seen in the small intestine at 337 nt, 272 nt, and 142 nt all represent the same clonal IGH@ gene rearrangement, which is molecularly distinct from that in the pituitary. Lymphocyte clonality was assessed using the BIOMED-2 IGH@ and TRG@ multiplex PCR primer sets [13] followed by capillary electrophoresis and GeneScan fragment analysis (Applied Biosystems). Clonal lymphoid proliferations result in 1 or 2 prominent, valid-sized peaks in the electropherogram. Prominent peaks have relative fluorescence intensity at least 3 times that of the polyclonal background peaks. In our laboratory, this method detects 94% of B-cell lymphomas and 89% of T-cell lymphomas.
and secondary pituitary lymphomas have been described in immunocompetent patients [9]. This case is the first report of pituitary PTLD. Early and late PTLD are thought to represent distinct clinicopathologic entities [14,15]. Early PTLD are commonly EBV-driven, have diverse clinical presentations, and display broader histologic patterns, ranging from polymorphic to monomorphic lesions. Early cases are more likely to involve the allograft, whereas late PTLD often occur in other sites, particularly the gastrointestinal tract [15]. Late PTLD are usually monoclonal, EBV-negative, and resist immunosuppressive modulation or chemotherapy, unlike early PTLD [14]. This case of pituitary PTLD demonstrates both B-cell and T-cell antigen expression. Several reports have described
synchronous or metachronous independent, mixed lineage lymphoid lesions in PTLD [5-8]. Based on these reports, one possible explanation for this case is that the pituitary lesion represents a mixed population of morphologically atypical clonal B-cells and clonal T-cells that persist due to chronic immunosuppression. An alternative explanation is that the pituitary lesion is involved by a lymphoma that expresses both B-cell and T-cell antigens and has both IGH@ and TRG@ gene rearrangements. The differing molecular genotype of the IGH@ clonal rearrangement detected in the enteric lymphoma suggests that it is a separate and clonally unrelated B-cell proliferation. PTLD may not always fit into distinct categories and the nature of the lesions comprising PTLD can be complex. This patient appears to have had a distinct monomorphic diffuse
Pituitary post-transplantation lymphoproliferative disorder large B-cell lymphoma, but a simultaneous molecularly distinct, clonal, mixed lineage lymphoid proliferation involving a pituitary adenoma. All lesions were EBVnegative and became clinically apparent 13 years posttransplantation. After transplantation, a sellar mass should raise the possibility of pituitary PTLD, as this site is not protected from involvement.
Acknowledgments The authors would like to thank Michael Cruise, Thomas Tillack, Mani Mahadevan, Lawrence Silverman, James Patterson, Nancy Mills, Regina Seaner, and Karen Siegrist for their assistance with this work.
References [1] Swerdlow SH, Campo E, Harris NL, et al. WHO classification of tumours of haematopoietic and lymphoid tissue. Albany (NY): World Health Organization; 2008. [2] Taylor AL, Marcus R, Bradley JA. Post-transplant lymphoproliferative disorders (PTLD) after solid organ transplantation. Crit Rev Oncol Hematol 2005;56:155-67. [3] Bakker NA, van Imhoff GW, Verschuuren EA, et al. Presentation and early detection of post-transplant lymphoproliferative disorder after solid organ transplantation. Transpl Int 2007;20:207-18. [4] Chadburn A, Cesarman E, Liu YF, et al. Molecular genetic analysis demonstrates that multiple posttransplantation lymphoproliferative disorders occurring in one anatomic site in a single patient represent distinct primary lymphoid neoplasms. Cancer 1995;75:2747-56.
1645 [5] Frankel AH, Thompson M, Vulliamy T, et al. A T cell clone in association with an Epstein-Barr virus–related B cell lymphoma. Transplantation 1991;52:1108-9. [6] Hollingsworth HC, Stetler-Stevenson M, Gagneten D, et al. Immunodeficiency-associated malignant lymphoma. Three cases showing genotypic evidence of both T- and B-cell lineages. Am J Surg Pathol 1994;18:1092-101. [7] Morovic A, Jaffe ES, Raffeld M, et al. Metachronous EBV-associated B-cell and T-cell posttransplant lymphoproliferative disorders in a heart transplant recipient. Am J Surg Pathol 2009;33:149-54. [8] Yin CC, Medeiros LJ, Abruzzo LV, et al. EBV-associated B- and Tcell posttransplant lymphoproliferative disorders following primary EBV infection in a kidney transplant recipient. Am J Clin Pathol 2005;123:222-8. [9] Landman RE, Wardlaw SL, McConnell RJ, et al. Pituitary lymphoma presenting as fever of unknown origin. J Clin Endocrinol Metab 2001;86:1470-6. [10] Liu JK, Sayama C, Chin SS, et al. Extranodal NK/T-cell lymphoma presenting as a pituitary mass: case report and review of the literature. J Neurosurg 2007;107:660-5. [11] Kaufmann TJ, Lopes MB, Laws Jr ER, et al. Primary sellar lymphoma: radiologic and pathologic findings in two patients. AJNR Am J Neuroradiol 2002;23:364-7. [12] Megan Ogilvie C, Payne S, Evanson J, et al. Lymphoma metastasizing to the pituitary: an unusual presentation of a treatable disease. Pituitary 2005;8:139-46. [13] van Dongen JJM, Langerak AW, Bruggemann M, et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia 2003;17:2257-317. [14] Dotti G, Fiocchi R, Motta T, et al. Lymphomas occurring late after solid-organ transplantation: influence of treatment on the clinical outcome. Transplantation 2002;74:1095-102. [15] Paranjothi S, Yusen RD, Kraus MD, et al. Lymphoproliferative disease after lung transplantation: comparison of presentation and outcome of early and late cases. J Heart Lung Transplant 2001;20:1054-63.