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Posttransplant lymphoproliferative disorder presenting as a cutaneous forehead mass
Posttransplant lymphoproliferative disorder presenting as a cutaneous forehead mass MATTHEW M. HANASONO,
MD,
BRIAN M. PARRETT,
BA,
and ARNOLD S. BREITBART,
Posttransplant lymphoproliferative disorder (PTLD) is defined as the presence of an abnormal proliferation of lymphoid cells in the setting of posttransplant immunosuppression.1 PTLD has been described in patients receiving solid organ and bone marrow transplants. Although most often seen in the gastrointestinal tract, PTLD has been described as occurring in several other organ systems including the head and neck. PTLD presenting as nodules of the skin or superficial soft tissue is rare, with, to our knowledge, only 2 cases reported in the literature, one of which presented on the face.2,3 We report the case of a kidney-transplant recipient who presented with PTLD manifested as a rapidly growing forehead mass. CASE REPORT A 22-year-old man 8 years status post livingrelated donor kidney transplantation was referred to us for evaluation of a forehead mass that had rapidly grown over the past 2 months. On physical examination, the patient was observed to have a fleshy, lobulated mass measuring 6 ⫻ 5 cm protruding from his left forehead (Fig 1). His immunosuppressive medications included azathioprine and prednisone, and he had previously been treated with cyclosporine. A head computed tomography scan demonstrated a large, lobulated soft-tissue mass arising from the left frontal scalp without evidence for adjacent bone involvement or intracranial extension. A 10 ⫻ 5-mm biopsy sample of the mass was taken in wedge fashion. The biopsy demonstrated nodular and dense lymphoid proliferation present From the Division of Plastic and Reconstructive Surgery, Columbia Presbyterian Medical Center. Reprint requests: Arnold S. Breitbart, MD, Division of Plastic and Reconstructive Surgery, Columbia Presbyterian Medical Center, 161 Fort Washington Ave, New York, NY 10032-3784; e-mail, [email protected]. Otolaryngol Head Neck Surg 2004;130:372-4. 0194-5998/$30.00 Copyright © 2004 by the American Academy of Otolaryngology–Head and Neck Surgery Foundation, Inc. 10.1016/j.otohns.2003.08.019 372
MD,
New York, New York
in the subcutaneous tissue with extension into the dermis (Fig 2). Mitotic activity was brisk and apoptotic cells were numerous. Based on these features, a diagnosis of PTLD was made. The patient’s immunosuppressive medications were stopped, and he was treated with cyclophosphamide, rituximab, and solumedrol, but the forehead mass persisted with no decrease in size. The patient was taken to the operating room for excision of the mass and primary closure after relaxing incisions were made in the galea aponeurotica. Final pathologic examination demonstrated a dense lymphoid proliferation in the dermis and subcutaneous tissue. Immunohistochemical marker analysis of these cells was positive for the CD45 antigen and the CD138 antigen and negative for the CD20, CD79a, and Bcl-6 protein. CD20 negativity was attributed to the patient’s treatment with anti-CD20 antibody (rituximab). The diagnosis was PTLD of the skin and subcutaneous tissue, favoring a monomorphic type with immunoblastic and plasmacytoid features. DISCUSSION The use of immunosuppressive agents in solid organ transplantation is associated with a 20- to 50-fold increased risk of lymphoma.1 PTLD occurs in 2% to 5% of all transplant recipients and is associated with Epstein-Barr virus (EBV) infection in nearly all cases.1 Younger age and EBV seronegativity appear to increase the risk for developing PTLD. It is believed that PTLD is more common in children because many children are EBV naive at the time of transplantation. Although PTLD may occur at any time, the majority of cases arise within the first 2 posttransplantation years. It is believed that PTLD occurs due to the immunosuppression, limiting the cytotoxic T-lymphocyte response that normally controls EBV-infected B-cell proliferation. The diagnosis of PTLD is made by pathologic examination. Most PTLD cases are of B-lymphocyte origin. Histologically, the lesions are heterogeneous and may not meet the pathologic criteria for lymphoma as the term PTLD incorporates both
Otolaryngology– Head and Neck Surgery Volume 130 Number 3
HANASONO, PARRETT, AND BREITBART 373
Fig 1. Patient with cutaneous forehead mass diagnosed as posttransplant lymphoproliferative disorder by incisional biopsy before excision.
hyperplastic and neoplastic growths. Findings can vary from polyclonal, polymorphic B-cell hyperplasia to monoclonal B-cell lymphoid proliferation similar to a high-grade lymphoma. Clinical presentation is diverse and varies from a mild febrile syndrome with pharyngitis and lymphadenopathy to aggressive lymphomas involving nodal and extranodal sites. PTLD of the head and neck has been described in the literature, with Waldeyer’s ring the most common site of involvement.4,5 One study has observed a 10% incidence of PTLD involving the head and neck region of pediatric patients undergoing liver transplantation.5 However, cutaneous PTLD, as in this case, is rare with only 2 prior cases reported, one of which occurred on the midface. Treatment of PTLD consists of ganciclovir and decreasing the level of immunosuppressive medication. Other options are surgical resection
of localized PTLD tumors or chemotherapy, as in this case. The mortality rate of PTLD is approximately 50%. Although transplant patients are at increased risk for the development of cutaneous squamous and basal cell carcinomas, particularly in the head and neck, the possibility of cutaneous PTLD lesions occurring makes accurate and timely tissue diagnosis essential for appropriate treatment.4 Given the increasing number of solid organ transplants, otolaryngologists should be familiar with PTLD and its diversity of presentations in the head and neck. A high index of suspicion in the immunosuppressed transplant population and tissue diagnosis is critical for early therapeutic intervention. Skin lesions are among the potential sites for PTLD, and skin specimens from posttransplant immunosuppressed patients should be examined carefully for PTLD.
374 HANASONO, PARRETT, AND BREITBART
Otolaryngology– Head and Neck Surgery March 2004
Fig 2. Histologic section from the excised forehead mass demonstrating a dense lymphoid proliferation with immunoblastic and plasmacytoid features (original magnification ⫻60).
REFERENCES
1. Basgoz N, Preiksaitis JK. Post-transplant lymphoproliferative disorder. Infect Dis Clin North Am 1995;9:90123. 2. Ponder TB, Collins BT, Bee CS, et al. Fine needle aspiration biopsy of a posttransplant lymphoproliferative disorder with pronounced plasmacytic differentiation presenting in the face. A case report. Acta Cytol 2002;46: 384-94.
3. Schumann KW, Oriba HA, Bergfeld WF, et al. Cutaneous presentation of posttransplant lymphoproliferative disorder. J Am Acad Dermatol 2000;42:923-6. 4. Pollard JD, Hanasono MM, Mikulec AA, et al. Head and neck cancer in cardiothoracic transplant recipients. Laryngoscope 2000;110:1257-61. 5. Lattyak BV, Rosenthal P, Mudge C, et al. Posttransplant lymphoproliferative disorder presenting in the head and neck. Laryngoscope 1998;108:1195-8.
MD,
BRIAN M. PARRETT,
BA,
and ARNOLD S. BREITBART,
Posttransplant lymphoproliferative disorder (PTLD) is defined as the presence of an abnormal proliferation of lymphoid cells in the setting of posttransplant immunosuppression.1 PTLD has been described in patients receiving solid organ and bone marrow transplants. Although most often seen in the gastrointestinal tract, PTLD has been described as occurring in several other organ systems including the head and neck. PTLD presenting as nodules of the skin or superficial soft tissue is rare, with, to our knowledge, only 2 cases reported in the literature, one of which presented on the face.2,3 We report the case of a kidney-transplant recipient who presented with PTLD manifested as a rapidly growing forehead mass. CASE REPORT A 22-year-old man 8 years status post livingrelated donor kidney transplantation was referred to us for evaluation of a forehead mass that had rapidly grown over the past 2 months. On physical examination, the patient was observed to have a fleshy, lobulated mass measuring 6 ⫻ 5 cm protruding from his left forehead (Fig 1). His immunosuppressive medications included azathioprine and prednisone, and he had previously been treated with cyclosporine. A head computed tomography scan demonstrated a large, lobulated soft-tissue mass arising from the left frontal scalp without evidence for adjacent bone involvement or intracranial extension. A 10 ⫻ 5-mm biopsy sample of the mass was taken in wedge fashion. The biopsy demonstrated nodular and dense lymphoid proliferation present From the Division of Plastic and Reconstructive Surgery, Columbia Presbyterian Medical Center. Reprint requests: Arnold S. Breitbart, MD, Division of Plastic and Reconstructive Surgery, Columbia Presbyterian Medical Center, 161 Fort Washington Ave, New York, NY 10032-3784; e-mail, [email protected]. Otolaryngol Head Neck Surg 2004;130:372-4. 0194-5998/$30.00 Copyright © 2004 by the American Academy of Otolaryngology–Head and Neck Surgery Foundation, Inc. 10.1016/j.otohns.2003.08.019 372
MD,
New York, New York
in the subcutaneous tissue with extension into the dermis (Fig 2). Mitotic activity was brisk and apoptotic cells were numerous. Based on these features, a diagnosis of PTLD was made. The patient’s immunosuppressive medications were stopped, and he was treated with cyclophosphamide, rituximab, and solumedrol, but the forehead mass persisted with no decrease in size. The patient was taken to the operating room for excision of the mass and primary closure after relaxing incisions were made in the galea aponeurotica. Final pathologic examination demonstrated a dense lymphoid proliferation in the dermis and subcutaneous tissue. Immunohistochemical marker analysis of these cells was positive for the CD45 antigen and the CD138 antigen and negative for the CD20, CD79a, and Bcl-6 protein. CD20 negativity was attributed to the patient’s treatment with anti-CD20 antibody (rituximab). The diagnosis was PTLD of the skin and subcutaneous tissue, favoring a monomorphic type with immunoblastic and plasmacytoid features. DISCUSSION The use of immunosuppressive agents in solid organ transplantation is associated with a 20- to 50-fold increased risk of lymphoma.1 PTLD occurs in 2% to 5% of all transplant recipients and is associated with Epstein-Barr virus (EBV) infection in nearly all cases.1 Younger age and EBV seronegativity appear to increase the risk for developing PTLD. It is believed that PTLD is more common in children because many children are EBV naive at the time of transplantation. Although PTLD may occur at any time, the majority of cases arise within the first 2 posttransplantation years. It is believed that PTLD occurs due to the immunosuppression, limiting the cytotoxic T-lymphocyte response that normally controls EBV-infected B-cell proliferation. The diagnosis of PTLD is made by pathologic examination. Most PTLD cases are of B-lymphocyte origin. Histologically, the lesions are heterogeneous and may not meet the pathologic criteria for lymphoma as the term PTLD incorporates both
Otolaryngology– Head and Neck Surgery Volume 130 Number 3
HANASONO, PARRETT, AND BREITBART 373
Fig 1. Patient with cutaneous forehead mass diagnosed as posttransplant lymphoproliferative disorder by incisional biopsy before excision.
hyperplastic and neoplastic growths. Findings can vary from polyclonal, polymorphic B-cell hyperplasia to monoclonal B-cell lymphoid proliferation similar to a high-grade lymphoma. Clinical presentation is diverse and varies from a mild febrile syndrome with pharyngitis and lymphadenopathy to aggressive lymphomas involving nodal and extranodal sites. PTLD of the head and neck has been described in the literature, with Waldeyer’s ring the most common site of involvement.4,5 One study has observed a 10% incidence of PTLD involving the head and neck region of pediatric patients undergoing liver transplantation.5 However, cutaneous PTLD, as in this case, is rare with only 2 prior cases reported, one of which occurred on the midface. Treatment of PTLD consists of ganciclovir and decreasing the level of immunosuppressive medication. Other options are surgical resection
of localized PTLD tumors or chemotherapy, as in this case. The mortality rate of PTLD is approximately 50%. Although transplant patients are at increased risk for the development of cutaneous squamous and basal cell carcinomas, particularly in the head and neck, the possibility of cutaneous PTLD lesions occurring makes accurate and timely tissue diagnosis essential for appropriate treatment.4 Given the increasing number of solid organ transplants, otolaryngologists should be familiar with PTLD and its diversity of presentations in the head and neck. A high index of suspicion in the immunosuppressed transplant population and tissue diagnosis is critical for early therapeutic intervention. Skin lesions are among the potential sites for PTLD, and skin specimens from posttransplant immunosuppressed patients should be examined carefully for PTLD.
374 HANASONO, PARRETT, AND BREITBART
Otolaryngology– Head and Neck Surgery March 2004
Fig 2. Histologic section from the excised forehead mass demonstrating a dense lymphoid proliferation with immunoblastic and plasmacytoid features (original magnification ⫻60).
REFERENCES
1. Basgoz N, Preiksaitis JK. Post-transplant lymphoproliferative disorder. Infect Dis Clin North Am 1995;9:90123. 2. Ponder TB, Collins BT, Bee CS, et al. Fine needle aspiration biopsy of a posttransplant lymphoproliferative disorder with pronounced plasmacytic differentiation presenting in the face. A case report. Acta Cytol 2002;46: 384-94.
3. Schumann KW, Oriba HA, Bergfeld WF, et al. Cutaneous presentation of posttransplant lymphoproliferative disorder. J Am Acad Dermatol 2000;42:923-6. 4. Pollard JD, Hanasono MM, Mikulec AA, et al. Head and neck cancer in cardiothoracic transplant recipients. Laryngoscope 2000;110:1257-61. 5. Lattyak BV, Rosenthal P, Mudge C, et al. Posttransplant lymphoproliferative disorder presenting in the head and neck. Laryngoscope 1998;108:1195-8.