RESUMEN
The pathogenesis of plasmablastic lymphoma (PBL) involves the Epstein-Barr virus (EBV), human immunodeficiency virus (HIV), and MYC gene aberrations. We aimed to determine the EBV latent infection pattern and frequency of MYC gene aberrations in PBLs. Immunohistochemistry was performed using antibodies for EBNA1, EBNA2, and LMP1 while fluorescence in situ hybridization was performed using a MYC probe. The patient cohort comprised 49 adult cases (44 were HIV-positive and three were HIV-negative). Forty-one cases were EBV-positive with 11 EBNA1-positive cases, all cases EBNA2-negative, and four LMP1-positive cases. Latency 0 was determined in 29 cases, latency I in eight cases, and latency II in four cases. The MYC gene was rearranged in eight cases, showed copy number alterations in 11 cases and, no rearrangement in 11 cases. This is the largest cohort of PBLs from South Africa to show a predominantly restricted EBV latency pattern with MYC gene aberrations as a common finding.
Asunto(s)
Infecciones por Virus de Epstein-Barr , Linfoma Plasmablástico , Proteínas Proto-Oncogénicas c-myc , Adulto , Antígenos Nucleares del Virus de Epstein-Barr/genética , Genes myc , Herpesvirus Humano 4/genética , Humanos , Hibridación Fluorescente in Situ , Linfoma Plasmablástico/diagnóstico , Linfoma Plasmablástico/genética , Linfoma Plasmablástico/virología , Proteínas Proto-Oncogénicas c-myc/genética , Latencia del VirusRESUMEN
Lymphomas remain a leading cause of morbidity and mortality for HIV-positive patients. The most common lymphomas include diffuse large B-cell lymphoma, Burkitt lymphoma, primary effusion lymphoma, plasmablastic lymphoma and Hodgkin lymphoma. Appropriate approach is determined by lymphoma stage, performans status, comorbidities, histological subtype, status of the HIV disease and immunosuppression. Treatment outcomes have improved due to chemotherapy modalities and effective antiretroviral therapy. This review summarizes epidemiology, pathogenesis, pathology, and current treatment landscape in HIV associated lymphoma.
Asunto(s)
Infecciones por VIH/complicaciones , Linfoma Relacionado con SIDA/virología , Fármacos Anti-VIH/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Burkitt/tratamiento farmacológico , Linfoma de Burkitt/patología , Linfoma de Burkitt/virología , Enfermedad de Castleman/tratamiento farmacológico , Enfermedad de Castleman/patología , Enfermedad de Castleman/virología , Infecciones por VIH/tratamiento farmacológico , Seropositividad para VIH/complicaciones , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/virología , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Huésped Inmunocomprometido , Incidencia , Linfoma Relacionado con SIDA/tratamiento farmacológico , Linfoma Relacionado con SIDA/epidemiología , Linfoma Relacionado con SIDA/patología , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/virología , Linfoma de Efusión Primaria/tratamiento farmacológico , Linfoma de Efusión Primaria/patología , Linfoma de Efusión Primaria/virología , Linfoma Plasmablástico/tratamiento farmacológico , Linfoma Plasmablástico/patología , Linfoma Plasmablástico/virología , Pronóstico , RecurrenciaRESUMEN
AIMS: We utilised chromogenic and fluorescence in-situ hybridisation (CISH and FISH) to evaluate MYC gene copy numbers and rearrangements within HIV-associated plasmablastic lymphomas (PBLs). Thereafter, clinicopathological features were explored retrospectively. METHODS AND RESULTS: Sixty-seven (n = 67) patients were included and the HIV seropositive status was confirmed in 98% (63 of 64) with a median viral load of 55 587 (IQR 273 582) copies/ml and median CD4 count of 170 (IQR 249) cells/µl. The mean age was 41 ± 10.1 years and females comprised 54%. PBL was documented predominantly at extra-oronasal topographic regions. Starry-sky (SS) appearance was evident in 33% in association with monomorphic morphology (P-value 0.02). c-MYC protein was expressed in 81% and latent EBV infection was detected in 90%. EBER ISH-positive status and MYC rearrangement occurred in 67% of HIV PBL. MYC aberrations included MYC rearrangement (70%), low-level increase in MYC gene copy numbers (43%), concurrent MYC rearrangement and increased MYC gene copy numbers (49%) as well as low-level chromosome 8 polysomy (6%). MYC aberrations in HIV PBLs were significantly associated with SS appearance (P -0.01), monomorphic morphology (P - 0.03), c-MYC protein expression ≥40% (P - 0.03) and mortality (P - 0.03). There was advanced stage (Ann Arbor III/IV) at presentation (77%) and the median overall survival for HIV PBL was 75 days (95% CI 14-136). CONCLUSION: Majority of the HIV-associated PBL tumours harbour MYC aberrations. Due to the persistently inferior survival outcome of HIV-associated PBL in the era of antiviral treatment, targeted and/or intensified therapy of oncogenic MYC may need to be explored in future.
Asunto(s)
Infecciones por VIH/complicaciones , Linfoma Plasmablástico/genética , Linfoma Plasmablástico/virología , Proteínas Proto-Oncogénicas c-myc/genética , Adulto , Femenino , Dosificación de Gen , Reordenamiento Génico , Genes myc , Humanos , Inmunohistoquímica , Hibridación in Situ , Masculino , Persona de Mediana EdadAsunto(s)
Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Encía/patología , Infecciones por VIH/tratamiento farmacológico , Mandíbula/patología , Linfoma Plasmablástico/tratamiento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Antirretroviral Altamente Activa/métodos , Biopsia , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Infecciones por Virus de Epstein-Barr/diagnóstico por imagen , Infecciones por Virus de Epstein-Barr/patología , Infecciones por Virus de Epstein-Barr/virología , Rayos gamma , Encía/diagnóstico por imagen , Encía/efectos de los fármacos , Encía/virología , VIH/efectos de los fármacos , VIH/crecimiento & desarrollo , Infecciones por VIH/diagnóstico por imagen , Infecciones por VIH/patología , Infecciones por VIH/virología , Herpesvirus Humano 4/efectos de los fármacos , Herpesvirus Humano 4/crecimiento & desarrollo , Humanos , Masculino , Mandíbula/diagnóstico por imagen , Mandíbula/efectos de los fármacos , Mandíbula/virología , Linfoma Plasmablástico/diagnóstico por imagen , Linfoma Plasmablástico/patología , Linfoma Plasmablástico/virología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Prednisona/uso terapéutico , Costillas/diagnóstico por imagen , Costillas/efectos de los fármacos , Costillas/patología , Costillas/virología , Escápula/diagnóstico por imagen , Escápula/efectos de los fármacos , Escápula/patología , Escápula/virología , Vincristina/uso terapéuticoRESUMEN
HIV infection is associated with an increased risk for developing B-cell lymphoproliferative disorders. The spectrum of disease differs in HIV-infected versus HIV-uninfected persons, with aggressive B-cell non-Hodgkin lymphomas constituting a higher proportion of all lymphoproliferative disorders in the HIV-positive population. Although antiretroviral therapy (ART) has significantly changed the landscape of lymphomas arising in HIV-infected persons, population growth and aging are reflected in the steady increase in non-AIDS-defining cancers. In the ART era, outcomes for HIV-infected lymphoma patients are similar to those of HIV-negative patients. This article reviews the diagnostic features and summarizes current biologic understanding of HIV-associated lymphomas.
Asunto(s)
Infecciones por VIH/patología , Linfoma de Células B/virología , Fármacos Anti-VIH/uso terapéutico , Linfoma de Burkitt/patología , Linfoma de Burkitt/virología , Diagnóstico Diferencial , Infecciones por VIH/tratamiento farmacológico , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/virología , Humanos , Linfoma Relacionado con SIDA/patología , Linfoma de Células B/patología , Linfoma de Efusión Primaria/patología , Linfoma de Efusión Primaria/virología , Linfoma Plasmablástico/patología , Linfoma Plasmablástico/virologíaRESUMEN
Plasmablastic lymphoma (PBL) is a rare subtype of diffuse large B-cell lymphoma, highly associated with HIV and Epstein-Barr virus (EBV) infections. It commonly presents in extranodal sites, often an oral mass, but reports of primary central nervous system PBL (PCNSPBL) are exceedingly rare. Here, we report on a 33-year-old man with newly diagnosed HIV infection who presented with acute-onset unilateral visual disturbance and was found to have biopsy-proven PCNSPBL. The neoplastic cells displayed a plasmacytoid appearance, with the expression of CD38 and CD138, and were positive for EBV by in situ hybridisation for EBV-encoded RNA. Systemic workup revealed the presence of Kaposi sarcoma, but no evidence of lymphoma. He is currently being treated with high-dose methotrexate, as well as antiretroviral therapy for his HIV infection, and has achieved a complete response.
Asunto(s)
Neoplasias del Sistema Nervioso Central/patología , Infecciones por VIH/complicaciones , Linfoma Plasmablástico/patología , Adulto , Antimetabolitos Antineoplásicos/uso terapéutico , Terapia Antirretroviral Altamente Activa/métodos , Neoplasias del Sistema Nervioso Central/metabolismo , Neoplasias del Sistema Nervioso Central/virología , Infecciones por Virus de Epstein-Barr/complicaciones , VIH/aislamiento & purificación , Infecciones por VIH/tratamiento farmacológico , Herpesvirus Humano 4/genética , Humanos , Masculino , Metotrexato/administración & dosificación , Metotrexato/uso terapéutico , Linfoma Plasmablástico/tratamiento farmacológico , Linfoma Plasmablástico/metabolismo , Linfoma Plasmablástico/virología , Enfermedades Raras , Sarcoma de Kaposi/complicaciones , Sarcoma de Kaposi/patología , Resultado del TratamientoRESUMEN
A 48-year-old female patient presented to the ENT department of the University Medical Center of the Johannes Gutenberg University Mainz with subfebrile temperatures, one-sided nasal obstruction, and left-sided cephalgia. Clinical examination and CT scans showed a mass occupying the left nasal cavity and left paranasal sinuses. Further diagnosis and histopathological examination showed an HIV-associated plasmablastic lymphoma of the left paranasal sinuses. This case report with literature review discusses the diagnosis and treatment of this rare nasal tumor.
Asunto(s)
Infecciones por VIH , Neoplasias de los Senos Paranasales , Linfoma Plasmablástico , Femenino , Infecciones por VIH/complicaciones , Humanos , Hallazgos Incidentales , Persona de Mediana Edad , Neoplasias de los Senos Paranasales/virología , Linfoma Plasmablástico/virologíaRESUMEN
Plasmablastic lymphoma is a non-Hodgkin lymphoma characterized by its plasmacytic differentiation and predilection for the oral cavity. It is among the lymphomas most commonly associated with AIDS. This report details a case of a HIV-positive patient with a 1-month history of an exophytic mass in the gingival area of the upper left quadrant. The diagnosis of plasmablastic lymphoma was made based on its histopathological and immunophenotypical features. She was treated with chemotherapy followed by autologous hematopoietic stem cell transplantation. Despite complete resolution of the lesion, the patient died of cardiorespiratory arrest. This case illustrates plasmablastic lymphoma as the first clinical manifestation of AIDS, highlighting the importance of differentiating between a potentially malignant lesion and other pathologic processes.
Asunto(s)
Linfoma Relacionado con SIDA/patología , Neoplasias de la Boca/patología , Neoplasias de la Boca/virología , Linfoma Plasmablástico/patología , Linfoma Plasmablástico/virología , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/patología , Biopsia , Femenino , Humanos , Inmunohistoquímica , Linfoma Relacionado con SIDA/terapia , Persona de Mediana Edad , Neoplasias de la Boca/terapia , Linfoma Plasmablástico/terapiaRESUMEN
Plasmablastic lymphoma (PBL) is an aggressive form of non-Hodgkin's lymphoma (NHL) classically seen in patients infected with the human immunodeficiency virus, but can also be seen in other immunocompromised states such as transplant recipients, autoimmune diseases and the elderly. PBL is generally associated with a poor prognosis despite chemotherapy. There is evidence supporting the use of bortezomib in combination with standard chemotherapy to achieve durable responses in patients with PBL. We describe a patient with acquired immunodeficiency syndrome who presented with rectal pain and bright red blood per rectum. He was diagnosed with stage IVA PBL with anorectal, nodal, calvarial and hepatic involvement. Along with highly active antiretroviral therapy, he was treated with six cycles of dose adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA-EPOCH) plus bortezomib resulting in durable complete remission 30 months after diagnosis.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Antirretrovirales/administración & dosificación , Antineoplásicos/administración & dosificación , Bortezomib/administración & dosificación , Quimioterapia de Inducción/métodos , Linfoma Plasmablástico/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Humanos , Masculino , Linfoma Plasmablástico/virología , Prednisona/administración & dosificación , Vincristina/administración & dosificaciónAsunto(s)
Terapia de Inmunosupresión/métodos , Linfoma Plasmablástico/terapia , Linfoma Plasmablástico/virología , Anciano , Brentuximab Vedotina , Terapia Combinada/métodos , Ciclosporina/administración & dosificación , Ciclosporina/efectos adversos , Relación Dosis-Respuesta a Droga , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/terapia , Herpesvirus Humano 4/fisiología , Humanos , Inmunoconjugados/administración & dosificación , Terapia de Inmunosupresión/efectos adversos , Trasplante de Riñón/efectos adversos , Linfoma Inmunoblástico de Células Grandes/inmunología , Linfoma Inmunoblástico de Células Grandes/patología , Linfoma Inmunoblástico de Células Grandes/terapia , Linfoma Inmunoblástico de Células Grandes/virología , Masculino , Estadificación de Neoplasias , Linfoma Plasmablástico/inmunología , Linfoma Plasmablástico/patología , Radioterapia , Inducción de RemisiónRESUMEN
AIMS: To determine the utility of clinical, morphological and phenotypical features in the differential diagnosis of plasmablastic lymphoma and myeloma with plasmablastic features. METHODS: All plasmablastic neoplasms identified from a 15-year retrospective search were reviewed and classified into 'lymphoma', 'myeloma' or 'indeterminate'. The classification was then compared with the previously established clinical diagnosis. Lessons learned from this review were used to design a diagnostic algorithm for pathologists to use in the absence of known clinical history. RESULTS: The classification was possible in 10 of 11 cases, 8 lymphomas and 2 myelomas (n=2). No distinctive morphological or phenotypical features were identified. The most useful histopathological parameter was a positive Epstein-Barr virus in situ hybridisation. Presence of associated lymphadenopathy and/or oral mass in the absence of complete myeloma-defining signs was used to favour a diagnosis of lymphoma in 4 of 8 cases. CONCLUSIONS: The distinction between plasmablastic lymphoma from plasmablastic myeloma warrants detailed knowledge of clinical, radiological and laboratorial findings. New studies identifying distinctive phenotypical or genetic features are needed to improve the histopathological differentiation of plasmablastic neoplasms.
Asunto(s)
Mieloma Múltiple/diagnóstico , Linfoma Plasmablástico/diagnóstico , Adulto , Anciano , Algoritmos , Biomarcadores de Tumor/análisis , Biopsia , Técnicas de Apoyo para la Decisión , Diagnóstico Diferencial , Errores Diagnósticos/prevención & control , Femenino , Citometría de Flujo , Herpesvirus Humano 4/genética , Humanos , Inmunohistoquímica , Hibridación in Situ , Masculino , Persona de Mediana Edad , Mieloma Múltiple/química , Mieloma Múltiple/patología , Mieloma Múltiple/virología , Fenotipo , Linfoma Plasmablástico/química , Linfoma Plasmablástico/patología , Linfoma Plasmablástico/virología , Valor Predictivo de las Pruebas , ARN Viral/genética , Estudios RetrospectivosAsunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Linfoma Plasmablástico/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resistencia a Medicamentos , Resistencia a Antineoplásicos , Infecciones por Virus de Epstein-Barr , Femenino , Seronegatividad para VIH , Humanos , Huésped Inmunocomprometido , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Linfoma Plasmablástico/diagnóstico por imagen , Linfoma Plasmablástico/tratamiento farmacológico , Linfoma Plasmablástico/virología , Inducción de Remisión , Acondicionamiento Pretrasplante/métodosRESUMEN
Effusion-based lymphoma is a rare and unique type of large B-cell lymphoma presenting in effusion without a mass lesion. It shares many clinicopathological features with primary effusion lymphoma (PEL), but is distinct from PEL by the absence of HHV8 association. Double hit lymphoma (DHL) is an aggressive B-cell lymphoma, defined by concurrent rearrangement of MYC and BCL2 or BCL6. DHL often presents as lymphadenopathy or an extranodal mass, but rarely occurs in effusion. Here we report a 61-year-old male with alcoholic cirrhosis presenting as massive ascites and left pleural effusion. He has no HIV, HBV or HCV infection and no mass lesion by CT scans. Cytology of both pleural effusion and ascites show large lymphoma cells with plasmablastic morphology characterized by pleomorphic and eccentric nuclei, prominent nucleoli and frequent mitoses. Immunohistochemical study with cell block shows that the lymphoma cells express plasma cell-related markers (CD138, MUM-1 and EMA), but not CD3, CD30, CD45, B-cell markers (CD19, CD20, CD79a, and PAX5), HHV8, ALK or cytokeratin. EBER is positive in most lymphoma cells. Fluorescence in situ hybridization reveals rearrangement at the IGH, BCL2, and MYC loci, but not at BCL6. It is diagnosed as an EBV-associated but HHV8-unrelated double hit effusion-based lymphoma with plasmablastic features. The patient passed away soon after diagnosis without chemotherapy. This is the first reported case of double-hit effusion-based lymphoma with MYC and BCL2 rearrangement. This case illustrates the importance of integrating clinical, cytological, immunophenotypical, and molecular findings to reach a correct diagnosis. Diagn. Cytopathol. 2017;45:257-261. © 2016 Wiley Periodicals, Inc.
Asunto(s)
Infecciones por Virus de Epstein-Barr/diagnóstico , Linfoma Plasmablástico/diagnóstico , Derrame Pleural Maligno/diagnóstico , Resultado Fatal , Herpesvirus Humano 8 , Humanos , Masculino , Persona de Mediana Edad , Linfoma Plasmablástico/virología , Derrame Pleural Maligno/virologíaRESUMEN
Abstract Plasmablastic lymphoma is a non-Hodgkin lymphoma characterized by its plasmacytic differentiation and predilection for the oral cavity. It is among the lymphomas most commonly associated with AIDS. This report details a case of a HIV-positive patient with a 1-month history of an exophytic mass in the gingival area of the upper left quadrant. The diagnosis of plasmablastic lymphoma was made based on its histopathological and immunophenotypical features. She was treated with chemotherapy followed by autologous hematopoietic stem cell transplantation. Despite complete resolution of the lesion, the patient died of cardiorespiratory arrest. This case illustrates plasmablastic lymphoma as the first clinical manifestation of AIDS, highlighting the importance of differentiating between a potentially malignant lesion and other pathologic processes.
Asunto(s)
Humanos , Femenino , Persona de Mediana Edad , Neoplasias de la Boca/patología , Neoplasias de la Boca/virología , Linfoma Relacionado con SIDA/patología , Linfoma Plasmablástico/patología , Linfoma Plasmablástico/virología , Biopsia , Neoplasias de la Boca/terapia , Inmunohistoquímica , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/patología , Linfoma Relacionado con SIDA/terapia , Linfoma Plasmablástico/terapiaRESUMEN
Plasmablastic lymphoma is a rare subtype of diffuse large B-cell lymphoma more frequently diagnosed in immunosuppressed patients, mainly HIV-infected. Primary cutaneous plasmablastic lymphoma is extremely rare, and in this patient it was the first clinical manifestation of unsuspected HIV-infection.
Asunto(s)
Infecciones por VIH/patología , Linfoma Relacionado con SIDA/patología , Linfoma Plasmablástico/patología , Linfoma Plasmablástico/virología , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/virología , Biopsia , Femenino , Infecciones por VIH/complicaciones , Humanos , Persona de Mediana Edad , Piel/patologíaRESUMEN
Plasmablastic lymphoma (PBL) is a rare AIDS-related malignancy with a poor prognosis. Little is known about this entity, and no standard treatment regimen has been defined. To establish an adequate treatment strategy, we investigated 24 cases of PBL arising in human immunodeficiency virus-positive individuals. Most of the patients were in the AIDS stage, with a median CD4 count of 67.5/µL. Lymph nodes (58 %), gastrointestinal tract (42 %), bone marrow (39 %), oral cavity (38 %), and CNS (18 %) were the most commonly involved sites. Histology findings for the following were positive at varying rates, as follows: CD10 (56 %); CD30 (39 %); CD38 (87 %); MUM-1 (91 %); CD138 (79 %); EBER (91 %); and LMP-1 (18 %). There was a marked increase in patients in 2011-12, and the cases found in that period appeared to be more aggressive, showing a higher rate of advanced-stage PBL. Fourteen cases were treated with CHOP, while the others were treated with more intensive regimens, including bortezomib and hematopoietic stem cell transplantation. The overall median survival time was 15 months. A CD4 count of >100/µL at diagnosis and attaining complete remission in the first-line chemotherapy were associated with better outcomes (P = 0.027 and 0.0016, respectively). Host immune status and chemosensitivity are associated with improved prognosis in PBL.
Asunto(s)
VIH/aislamiento & purificación , Linfoma Relacionado con SIDA/terapia , Linfoma Relacionado con SIDA/virología , Linfoma Plasmablástico/terapia , Linfoma Plasmablástico/virología , Adulto , Antirretrovirales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recuento de Linfocito CD4 , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Infecciones por Virus de Epstein-Barr/complicaciones , Femenino , Trasplante de Células Madre Hematopoyéticas , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Linfoma Relacionado con SIDA/diagnóstico , Linfoma Relacionado con SIDA/patología , Masculino , Persona de Mediana Edad , Linfoma Plasmablástico/diagnóstico , Linfoma Plasmablástico/patología , Prednisona/uso terapéutico , Pronóstico , Análisis de Supervivencia , Resultado del Tratamiento , Vincristina/uso terapéutico , Adulto JovenRESUMEN
Abstract: Plasmablastic lymphoma is a rare subtype of diffuse large B-cell lymphoma more frequently diagnosed in immunosuppressed patients, mainly HIV-infected. Primary cutaneous plasmablastic lymphoma is extremely rare, and in this patient it was the first clinical manifestation of unsuspected HIV-infection.
Asunto(s)
Humanos , Femenino , Persona de Mediana Edad , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/virología , Infecciones por VIH/patología , Linfoma Relacionado con SIDA/patología , Linfoma Plasmablástico/patología , Linfoma Plasmablástico/virología , Piel/patología , Biopsia , Infecciones por VIH/complicacionesRESUMEN
Monomorphic post-transplant lymphoproliferative disorder commonly resembles diffuse large B-cell lymphoma or Burkitt lymphoma, and most are Epstein-Barr virus (EBV) positive. We retrospectively identified 32 cases of monomorphic post-transplant lymphoproliferative disorder from two institutions and evaluated EBV in situ hybridization; TP53 mutation status; p53, CD30, myc, and BCL2 expression by immunohistochemistry; proliferation index by Ki67; and germinal center vs non-germinal center immunophenotype by Hans criteria. Post-transplant lymphoproliferative disorder arose after hematopoietic stem cell transplant in five and solid organ transplant in 27 patients, a median of 4 and 96 months after transplant, respectively (overall median latency 71 months, range 2-295). The most common morphology was diffuse large B-cell lymphoma (28 cases), with three cases of Burkitt lymphoma, and one case of plasmablastic lymphoma. Ten cases (31%) were EBV negative. Of those with the morphology of diffuse large B-cell lymphoma, the EBV-negative cases were more frequently TP53-mutated (P<0.001), p53 positive by immunohistochemistry (P<0.001), CD30 negative (P<0.01), and of germinal center immunophenotype (P=0.01) compared with EBV-positive cases. No statistically significant difference in overall survival was identified based on EBV, TP53 mutation status, germinal center vs non-germinal center immunophenotype, or other immunohistochemical parameters evaluated. Patients who died of post-transplant lymphoproliferative disorder were older with a longer latency from time of transplant to diagnosis (P<0.05). Our study demonstrates that diffuse large B-cell lymphoma-related immunohistochemical prognostic markers have limited relevance in the post-transplant setting and underscores differences between EBV-positive and EBV-negative post-transplant lymphoproliferative disorder in terms of immunophenotype and TP53 mutation frequency, supporting an alternative pathogenesis for EBV-negative post-transplant lymphoproliferative disorder.