RESUMEN
Post-transplant lymphoproliferative disorders (PTLDs) are serious, life-threatening complications of solid-organ transplantation (SOT) and bone marrow transplantation, and are associated with high mortality. PTLDs represent a heterogeneous group of lymphoproliferative diseases, which show a spectrum of clinical, morphologic, and molecular genetic features ranging from reactive polyclonal lesions to frank lymphomas. We describe clinicopathologic features of 17 cases of PTLD after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which were analyzed by in situ hybridization for EBV and a panel of antibodies directed against numerous antigens, including CD20, PAX5, CD3, bcl-6, CD10, MUM-1/IRF4, CD138, Kappa, Lambda, CD30, CD15, and Ki67. The cases included 13 males and 4 females with a median age of 31 years (range 9-49 years) and the PTLDs developed 1.5-19 months post-transplant (mean 4.7 months). The histological types indicated five cases of early lesions, two of plasmacytic hyperplasia and three of infectious mononucleosis-like PTLD. Eight cases were polymorphic PTLD, and four were monomorphic PTLD, including three of diffuse large B cell lymphoma, and one of plasmablastic lymphoma. Foci and sheets of necrosis were observed in five cases. The infected ratio of EBV was 88.2 %. Some cases were treated by reduction of immunosuppression, antiviral therapy, donor lymphocyte infusion, or anti-CD20 monoclonal rituximab. Eight cases died. The first half year after allo-HSCT is very important for the development of PTLD. The diagnosis of PTLD relies on morphology and immunohistochemistry, and EBV plays an important role in the pathogenesis of PTLD. The prognosis of PTLD is poor, and, notably, PTLD after allo-HSCT exhibits some features different from those of PTLD after SOT.
Asunto(s)
Infecciones por Virus de Epstein-Barr/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/patología , Adolescente , Adulto , Niño , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Hibridación in Situ , Ganglios Linfáticos/patología , Trastornos Linfoproliferativos/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Membrana Mucosa/patología , Trasplante Homólogo , Adulto JovenRESUMEN
OBJECTIVE: To study the clinical and histopathologic features, diagnosis, pathogenesis and therapy of post-transplant lymphoproliferative disorders (PTLD). METHODS: The clinical and pathologic features of 15 cases of PTLD were retrospectively analyzed by light microscopy, immunohistochemistry and in-situ hybridization, according to the updated 2008 WHO classification of tumors of hematopoietic and lymphoid tissues. RESULTS: Amongst the 15 cases studied, 14 cases had received allogenic hematopoietic stem cell transplantation (AHSCT) and 1 case had received renal transplantation. There were altogether 12 males and 3 females. The male-to-female ratio was 4:1. The mean age was 30.4 years and the median age was 31 years (range from 9 to 60 years). PTLD developed 1.5 to 132 months after transplantation (median 13.0 months). The mean age of the 14 patients with AHSCT was 28.3 years (range from 9 to 45 years) and PTLD developed 1.5 to 19 months after transplantation (mean 4.5 months). Major clinical presentation included fever and lymphadenopathy. Twelve cases involved mainly lymph nodes and the remaining 3 cases involved tonsils, stomach and small intestine, respectively. The histologic types in 4 cases represented early lesions, including plasmacytic hyperplasia (n = 1) and infectious mononucleosis-like PTLD (n = 3). Seven cases were polymorphic PTLD, with 4 cases containing a predominance of large cells. Graft-versus-host disease was also seen in the case of small intestinal involvement. Four cases were monomorphic PTLD, 3 of which were diffuse large B-cell lymphoma, 1 was plasmablastic lymphoma and 1 was a mixture of monomorphic and polymorphic PTLD. Foci of necrosis were seen in 5 cases. The proliferating index of Ki-67 was high. The positive rate of EBV-encoded RNA in AHSCT was 92.9%. The duration of PTLD onset was shorter in EBV-positive cases (range from 1.5 to 7 months) than EBV-negative cases (range from 19 and 132 months). Some cases were treated by reduction of immunosuppression, antiviral agents or anti-CD20 monoclonal antibody Rituximab. The duration of follow-up in 14 patients ranged from 0 to 8 months. Five of the patients died of the disease. CONCLUSIONS: The diagnosis of PTLD relies on morphologic examination and immunohistochemistry. Most of them are of B-cell origin. EBV plays an important role in the pathogenesis of PTLD. The duration of disease onset is shorter in EBV-positive cases. PTLD in AHSCT cases occurs in younger age group, with shorter duration of onset, as compared to solid organ transplantation. The prognosis of PTLD is poor. The modalities of treatment include reduction of immunosuppression, antiviral agents or anti-CD20 monoclonal antibody Rituximab.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/patología , ADP-Ribosil Ciclasa 1/metabolismo , Adolescente , Adulto , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Antígenos CD20/metabolismo , Antineoplásicos/uso terapéutico , Niño , Infecciones por Virus de Epstein-Barr , Femenino , Estudios de Seguimiento , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Inmunosupresores/uso terapéutico , Antígeno Ki-1/metabolismo , Trasplante de Riñón/efectos adversos , Leucemia/terapia , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/etiología , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/virología , Trastornos Linfoproliferativos/tratamiento farmacológico , Trastornos Linfoproliferativos/virología , Masculino , Persona de Mediana Edad , ARN Viral/metabolismo , Estudios Retrospectivos , Rituximab , Adulto JovenRESUMEN
OBJECTIVE: To study clinical and histopathological features, and diagnosis of mediastinal tumours of haematopoietic and lymphoid tissues (MTHL). METHODS: Forty cases of MTHL were analyzed for clinicopathology by microscopy and immunohistochemical staining and in situ hybridization, according to the updated 2008 WHO classification of tumours of haematopoietic and lymphoid tissues. RESULTS: In 40 cases of MTHL, there were 20 males and 20 females. The ratio of male/female was 1:1. The mean age was 31.8 years and median age was 29 years (range, 12 - 70 years).Superior vena cava syndrome was observed in 28 cases. The specimens of 4 cases were obtained by lumpectomy, whereas 36 cases by biopsy (25 cases by thoracoscopy, 1 by core needle aspiration). Twenty cases lay in anterior mediastinum, and 2 in posterior, 1 in superior, 8 in anterior and superior, 2 in posterior and superior, 2 in anterior and middle, 1 in middle and anterior mediastinum.Frozen section were performed in 28 cases, and 17 cases were diagnosed as tumours of haematopoietic and lymphoid tissues (consistency ratio was 60.7%). Twelve cases were classical Hodgkin lymphomas (cHL) (8 were nodular sclerosis subtype, and 3 were mixed cellarity, 1 was lymphocyte-rich subtype), and 10 were primary mediastinal (thymic) large B cell lymphoma (PMBCL), 10 were precursor lymphocyte neoplasm [8 were T lymphoblastic leukemia/lymphomas (T-LBL), 2 were B-LBL], 1 was MALT lymphoma, 1 was composite lymphoma (PMBCL and cHL), 2 were myeloid sarcomas, 4 were gray zone lymphomas (GZL) (3 had morphology reminiscent of cHL, and 1 of DLBCL, all cases were positive for CD20, PAX5, CD30 and CD15).EBER were detected in 11 cases by in situ hybridization, 2 of which were positive (18.2%), and the 2 positive cases were cHL. CONCLUSIONS: MTHLs occur predominantly in adolescents and young adults, mainly present as superior vena cava syndrome and anterior mediasinal masses. cHL, PMBCL, T-LBL were the most common MTHLs.GZLs mainly occur in young adults, those whose morphology reminiscent of cHL, immunohistochemistry reminiscent of PMBCL, and vice versa. Thoracoscopy, frozen section and a suitable panel of antibodies were practical approaches to MTHL.
Asunto(s)
Enfermedad de Hodgkin/patología , Linfoma de Células B/patología , Neoplasias del Mediastino/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patología , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Adolescente , Adulto , Anciano , Antígenos CD20/metabolismo , Niño , Femenino , Estudios de Seguimiento , Enfermedad de Hodgkin/metabolismo , Humanos , Antígeno Ki-1/metabolismo , Antígeno Lewis X/metabolismo , Linfoma de Células B/metabolismo , Linfoma de Células B de la Zona Marginal/metabolismo , Linfoma de Células B de la Zona Marginal/patología , Masculino , Neoplasias del Mediastino/metabolismo , Persona de Mediana Edad , Factor de Transcripción PAX5/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Estudios Retrospectivos , Síndrome de la Vena Cava Superior/metabolismo , Síndrome de la Vena Cava Superior/patología , Tasa de Supervivencia , Adulto JovenRESUMEN
OBJECTIVES: To study the morphologic changes of fallopian tubal epithelium in patients with ovarian serous epithelial tumors and to explore the relationship between the tubal epithelial changes and tumorigenesis of serous ovarian carcinoma. METHODS: The fallopian tubes in 79 cases of high-grade serous ovarian carcinoma, 12 cases of low-grade serous ovarian carcinoma, 16 cases of serous borderline ovarian tumor and 11 cases of non-ovarian benign tumors were serially examined under light microscope. Immunohistochemical study with EnVision method was used to detect the expression of p53 and bcl-2 protein in the fallopian tubal epithelium in all cases. The occurrences of secretory cell outgrowth (SCOUT), p53 signature, serous tubal intraepithelial carcinoma (STIC) and serous invasive carcinoma were analyzed. RESULTS: SCOUT in tubal epithelium was observed in 60.8% (48/79) of the high-grade serous carcinoma group, 4/12 of the low-grade serous carcinoma group, 3/16 of the serous borderline tumor group and 2/11 of the non-ovarian benign tumor group (P = 0.001). P53 signature, STIC and serous invasive carcinoma occurred only in the fallopian tubal epithelium of patients with high-grade serous ovarian carcinoma, with the positive rates being 29.1% (23/79), 15.2% (12/79) and 44.3% (35/79), respectively. Of the 23 cases with p53 signature, 17 cases had solitary lesion and 6 cases involved more than two sites. A total of 33 p53 signature positive foci were found, with 22 foci located at fimbria and 11 at ampulla. Bcl-2 expression was demonstrated in 90.9% of those foci (30/33). Of the 12 patients with STIC, 7 cases were solitary and 5 cases involved more than two sites. A total of 18 STIC foci were found, with 16 foci located at fimbria and 2 at ampulla. All of them were positive for bcl-2. CONCLUSIONS: SCOUT is found in fallopian tubal epithelium in patients with serous ovarian epithelial tumors, especially high-grade serious carcinoma. On the other hand, p53 signature, STIC and invasive serous carcinoma of tubal epithelium are observed only in patients with high-grade serous ovarian carcinoma, with a predilection of fimbrial involvement. Correlation exists between SCOUT, p53 signature, STIC and high-grade serous ovarian carcinomas. Bcl-2 and p53 immunostaining is helpful for demonstrating such lesions.
Asunto(s)
Transformación Celular Neoplásica , Cistadenocarcinoma Seroso/patología , Neoplasias de las Trompas Uterinas/patología , Trompas Uterinas/patología , Neoplasias Ováricas/patología , Adulto , Anciano , Cistadenocarcinoma Seroso/metabolismo , Células Epiteliales/patología , Epitelio/patología , Neoplasias de las Trompas Uterinas/metabolismo , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/metabolismo , Lesiones Precancerosas/metabolismo , Lesiones Precancerosas/patología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
OBJECTIVE: To investigate the role of p57 and p53 immunohistochemistry in the differential diagnosis of hydropic abortion, partial hydatidiform mole and complete hydatidiform mole. METHODS: Immunohistochemical stains (EnVision method) for p57 and p53 were performed in tissue samples of normal placenta chorionic villi (n=10), abortion chorionic villi (n=12), partial hydatidiform (n=23) and complete hydatidiform moles (n=20). RESULTS: The expression of p57 was predominantly localized in the nuclei of villous cytotrophoblasts and stromal cells. The positive rates of p57 in normal placenta, hydropic abortion and partial hydatidiform mole were 10/10, 12/12, and 100% (23/23), respectively, with no significant difference among the groups (P>0.05). However, none of the complete hydatidiform moles analyzed exhibited p57 positivity in cytotrophoblasts and stromal cells. There was a significant difference between partial and complete hydatidiform moles (P<0.05). The expression of p53 was observed in the nuclei of cytotrophoblastic cells and intermediate trophoblasts. No p53 expression was seen in normal placenta and only 1 of 12 hydropic abortion showed p53 positivity. The positive rates of p53 expression in partial and complete hydatidiform mole were 60.9% (14/23) and 85.0% (17/20) respectively. It was significantly higher in partial hydatidiform mole than that in hydropic abortion. A significant difference was also found between partial and complete hydatidiform moles (P<0.05). CONCLUSIONS: Our findings confirm that p57 immunohistochemistry assists the differential diagnosis of complete hydatidiform mole from partial hydatidiform mole. Expression of p53 may be helpful in distinguishing partial hydatidiform mole from hydropic abortion.
Asunto(s)
Aborto Espontáneo/diagnóstico , Inhibidor p57 de las Quinasas Dependientes de la Ciclina/metabolismo , Mola Hidatiforme/diagnóstico , Proteína p53 Supresora de Tumor/metabolismo , Neoplasias Uterinas/diagnóstico , Aborto Espontáneo/metabolismo , Aborto Espontáneo/patología , Diagnóstico Diferencial , Femenino , Humanos , Mola Hidatiforme/metabolismo , Mola Hidatiforme/patología , Inmunohistoquímica , Embarazo , Células del Estroma/metabolismo , Trofoblastos/metabolismo , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/patologíaAsunto(s)
Leiomiosarcoma/patología , Neoplasias Uterinas/patología , Proteínas de Unión a Calmodulina/metabolismo , Femenino , Humanos , Histerectomía , Leiomiosarcoma/metabolismo , Leiomiosarcoma/secundario , Leiomiosarcoma/cirugía , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Metástasis Linfática , Persona de Mediana Edad , Neprilisina/metabolismo , Neoplasias Ováricas/secundario , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/cirugíaAsunto(s)
Leucemia Linfocítica Crónica de Células B/patología , Linfoma de Células B Grandes Difuso/patología , Anciano , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Antígenos CD20/metabolismo , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígenos CD5/metabolismo , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/metabolismo , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/metabolismo , Masculino , Prednisona/uso terapéutico , Receptores de IgE/metabolismo , Rituximab , Vincristina/uso terapéuticoRESUMEN
OBJECTIVE: To study the expression and significance of PLAC1/CP1 genes in patients with primary colorectal carcinoma. METHODS: The expression of PLAC1/CP1 genes in 97 cases of colorectal carcinoma was studied using tissue chip technology and immunohistochemistry. RESULTS: The rate of PLAC1/CP1 proteins expression in the cases studied was 56.7% (55/97), with 27.8% (27/97) being nuclear staining and 43.3% (42/97) being cytoplasmic staining. The percentage of expression was higher in women than in men (χ(2) = 6.567, P = 0.010). The expression in poorly differentiated colorectal carcinoma was significantly higher than that in the well or moderately differentiated carcinoma (χ(2) = 8.321, P = 0.016). The expression was also significantly higher in stage TNM III or IV tumors than in stage TNM I or II tumors (χ(2) = 18.726, P = 0.000). The rate was higher in cases with lymph node metastasis than in those with negative lymph nodes (χ(2) = 17.407, P = 0.000), and was higher as the number of metastasis increasing (χ(2) = 22.632, P = 0.000). CONCLUSION: The expression of PLAC1/CP1 genes correlates with various clinical and pathologic parameters. It carries prognostic significance and may represent a potential target for immunotherapy.