RESUMEN
Ectopic thymic tissue outside its core position in the antero-superior mediastinum is quite common owing to the complexity of embryonal thymus development, whereby reported prevalence values (1 to 90%) are heavily dependent on the method of investigation and the intensity of the workup. The debated prevalence and relevance of ectopic thymic tissue and its accessibility underlie the ongoing discussion whether modern, minimally invasive thymectomy strategies can match the proven benefit of the radical transsternal thymectomy procedure for the treatment of Myasthenia gravis. In this context, the following article covers the etiology, prevalence, and location of normal-looking, reactive, and neoplastic ectopic thymic tissue. Furthermore, ectopic tissues and tumors inside or adjacent to the thymus are mentioned.
Asunto(s)
Coristoma , Miastenia Gravis , Neoplasias del Timo , Humanos , Timectomía , TimoRESUMEN
BACKGROUND: The proliferation marker Ki67 has been suggested as a promising cancer biomarker. As Ki67 needs an exact quantification, this marker is a prototype of a new generation of tissue-based biomarkers. In this study, we have systematically evaluated different cut points for Ki67 using three different clinical end points in a large neoadjuvant study cohort. PATIENTS AND METHODS: We have evaluated pretherapeutic Ki67 levels by immunohistochemistry in 1166 breast cancer core biopsies from the neoadjuvant GeparTrio trial. We used the standardized cutoff-finder algorithm for three end points [response to neoadjuvant chemotherapy (pCR), disease-free (DFS) and overall-survival (OS)]. The analyses were stratified for hormone receptor (HR) and HER2 status by molecular subtype radar diagrams (MSRDs). RESULTS: A wide range of Ki67 cut points between 3%-94% (for pCR), 6%-46% (for DFS) and 4%-58% (for OS) were significant. The three groups of Ki67 ≤ 15% versus 15.1%-35% versus >35% had pCR-rates of 4.2%, 12.8%, and 29.0% (P < 0.0005), this effect was also present in six of eight molecular subtypes. In MSRD, Ki67 was significantly linked to prognosis in uni- and multivariate analysis in the complete cohort and in HR-positive, but not triple-negative tumors. CONCLUSIONS: Ki67 is a significant predictive and prognostic marker over a wide range of cut points suggesting that data-derived cut point optimization might not be possible. Ki67 could be used as a continuous marker; in addition, the scientific community could define standardized cut points for Ki67. Our analysis explains the variability observed for Ki67 cut points in previous studies; however, this should not be seen as weakness, but as strength of this marker. MSRDs are an easy new approach for visualization of biomarker effects on outcome across molecular subtypes in breast cancer. The experience with Ki67 could provide important information regarding the development and implementation of other quantitative biomarkers.
Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Antígeno Ki-67/genética , Receptor ErbB-2/genética , Adulto , Biopsia , Neoplasias de la Mama/patología , Ensayos Clínicos Fase III como Asunto , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Terapia Neoadyuvante , Ensayos Clínicos Controlados Aleatorios como Asunto , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismoAsunto(s)
Certificación/legislación & jurisprudencia , Educación Médica Continua/legislación & jurisprudencia , Programas Nacionales de Salud/legislación & jurisprudencia , Patología/educación , Curriculum , Europa (Continente) , Humanos , Patología/legislación & jurisprudencia , Publicaciones Periódicas como Asunto , Sociedades MédicasRESUMEN
BACKGROUND: The limited regeneration capacity of hyaline articular cartilage requires detailed studies concerning the tissue integration of cartilage transplants with meaningful but time and/or resource-consuming and in part ethically problematic animal models or, alternatively, with in vitro test systems for implant materials. MATERIAL AND METHODS: The present study describes a regeneration model with bovine cartilage rings (outer Ø 6 mm, central defect Ø 2 mm) for insertion, cultivation and biomechanical or histological testing of cartilage replacement materials (HE and safranin O staining). In this study, resorbable polymers composed of polyglycolic acid (PGA) were analyzed. RESULTS: Biomechanical testing showed a continuous decrease of the push-out force for the PGA inserts from the cartilage rings, probably due to the resorbability of the material. Histologically, clear immigration of cells into cell-free PGA was observed even after 4 weeks of culture, but in particular after 10 weeks. In addition, storage of proteoglycans was interpreted as an initial sign of the formation of new matrix. CONCLUSION: Thus, the new regeneration model is in principle suitable for the testing of biomaterials, but shows limitations in assessing the "lateral bonding" of resorbable materials.
Asunto(s)
Materiales Biocompatibles/química , Modelos Animales de Enfermedad , Fracturas del Cartílago/fisiopatología , Fracturas del Cartílago/cirugía , Regeneración Tisular Dirigida/instrumentación , Regeneración/fisiología , Andamios del Tejido , Animales , Bovinos , Diseño de Equipo , Análisis de Falla de Equipo , Fracturas del Cartílago/patología , Humanos , Ensayo de MaterialesRESUMEN
We describe a case of a testicular primitive neuroectodermal tumor (PNET) with intratubular germ cell neoplasia of the adjacent testicular parenchyma. The occurrence of testicular PNET is rare because malignant transformation of testicular germ cell tumors into somatic malignancy is uncommon. Based on morphological, immunohistochemical and molecular pathological findings these tumors resemble central PNETs as they otherwise typically occur in children without rearrangement of the Ewing sarcoma breakpoint region (EWSR) gene on chromosome 22. This case also showed no evidence for a translocation.
Asunto(s)
Biomarcadores de Tumor/genética , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Neoplasias de Células Germinales y Embrionarias/genética , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias Testiculares/genética , Neoplasias Testiculares/patología , Adulto , Proteínas de Unión a Calmodulina/genética , Carcinoma in Situ/genética , Carcinoma in Situ/patología , Carcinoma in Situ/cirugía , Cromosomas Humanos Par 21/genética , Cromosomas Humanos Par 22/genética , Reordenamiento Génico/genética , Humanos , Hibridación Fluorescente in Situ , Antígeno Ki-1/genética , Masculino , Neoplasias de Células Germinales y Embrionarias/cirugía , Tumores Neuroectodérmicos Periféricos Primitivos/cirugía , Factor 3 de Transcripción de Unión a Octámeros/genética , Orquiectomía , Proteína EWS de Unión a ARN , Proteínas de Unión al ARN/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias Testiculares/cirugía , Testículo/patología , Translocación Genética/genéticaRESUMEN
Infectious lymphadenitis is often biopsied in the differential diagnoses of malignant disease. Since the repertoire of lymph nodes which react to exogenous stimuli is limited, malignant lymphomas may enter the clinical and morphological differential diagnosis. In a morphological sense, infectious lymphadenitis is defined as an infection of lymph node tissue. Therefore, the effector phase of the inflammatory reaction will act against lymphatic tissue, in contrast to common physiological hyperplasia. Follicular reactions, in addition to follicular hyperplasia, are seen in HIV-associated lymphadenopathy. Other viruses, such as infectious mononucleosis, give rise to a cytotoxic T-cell reaction. Most infections, however, induce a histiocytic reaction; depending on the microorganism, this varies morphologically from a small clustered epithelioid cell reaction or histiocytic abscesses to epithelioid necrotizing granulomata.
Asunto(s)
Linfadenitis/patología , Infecciones Oportunistas/patología , Complejo Relacionado con el SIDA/patología , Absceso/patología , Linfocitos B/patología , Infecciones Bacterianas/patología , Biopsia , Diagnóstico Diferencial , Granuloma/patología , Humanos , Hiperplasia , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/patología , Linfadenitis/inmunología , Metástasis Linfática/patología , Activación de Linfocitos/fisiología , Linfoma/patología , Infecciones Oportunistas/inmunología , Linfocitos T/patologíaRESUMEN
We report on a rare case of bilateral oncocytic kidney tumors in a patient with Birt-Hogg-Dubé syndrome (BHD). BHD is an autosomal inherited cancer syndrome associated with multiple kidney tumors, benign cutaneous tumors, and pulmonary cysts with spontaneous pneumothorax. To date about 50 BHD families have been described. Patients are best treated with nephron-sparing surgery. Close follow-up is mandatory because recurrence in previously operated kidneys and metastatic tumor progression can occur. Family members at risk should also early be screened for BHD.
Asunto(s)
Síndrome de Birt-Hogg-Dubé/diagnóstico , Síndrome de Birt-Hogg-Dubé/cirugía , Neoplasias Primarias Múltiples/diagnóstico , Neoplasias Primarias Múltiples/cirugía , Adenoma Oxifílico/diagnóstico , Adenoma Oxifílico/cirugía , Humanos , Neoplasias Renales/diagnóstico , Neoplasias Renales/cirugía , Masculino , Persona de Mediana Edad , Síndrome , Resultado del TratamientoRESUMEN
Splenic vascular disturbances mainly affect the red pulp and can involve the venous or arterial blood flow. The venous blood flow may be impaired by congestion and morphologically shows dilated splenic sinuses. Disturbances of the arterial blood flow may occur in connection with anomalies of the erythrocyte membrane or in immune haemolysis and usually are characterized by narrow splenic sinuses. Infarction of the spleen is usually caused by arterial embolism.
Asunto(s)
Bazo/irrigación sanguínea , Enfermedades Vasculares/patología , Arteriopatías Oclusivas/patología , Arteriopatías Oclusivas/fisiopatología , Arterias/patología , Arterias/fisiopatología , Velocidad del Flujo Sanguíneo , Embolia/patología , Membrana Eritrocítica/patología , Hemólisis , Humanos , Infarto/patología , Venas/patología , Venas/fisiopatología , Insuficiencia Venosa/patología , Insuficiencia Venosa/fisiopatologíaRESUMEN
The spleen is commonly affected by malignant lymphomas and the macroscopic findings of the spleen correlate with different lymphoma entities. However, most lymphomas are not primarily diagnosed in splenectomy specimens. Exceptions include splenic marginal zone lymphomas and hepatosplenic T-cell lymphomas that are typically diagnosed from histological findings. In addition, hairy-cell leukemia, LGL leukemia and T-cell prolymphocytic leukemia typically show characteristic patterns of infiltration in the spleen which may be diagnostically useful. The different infiltration patterns of these tumors are discussed here.
Asunto(s)
Linfoma/patología , Neoplasias del Bazo/patología , Antígenos CD/análisis , Diagnóstico Diferencial , Humanos , Leucemia de Células Pilosas/patología , Leucemia Prolinfocítica de Células T/patología , Linfoma/cirugía , Linfoma de Células T/patología , Esplenectomía , Neoplasias del Bazo/cirugíaRESUMEN
Vascular proliferations of the spleen reflect the variability of vascular structures occurring in the normal spleen. Besides haemangiomas, there is a spleen-specific vascular neoplasm, littoral cell angioma, that often occurs as a paraneoplastic lesion and thus may require the differential diagnostic delineation of metastases to the spleen in patients with known neoplasms. The most common malignant vascular tumours of the spleen are angiosarcomas. A recently described vascular lesion of unknown pathogenesis, sclerosing angiomatoid nodular transformation (SANT) of the spleen, usually is an incidental finding detected in the course of imaging studies.
Asunto(s)
Hemangioma/patología , Hemangiosarcoma/patología , Bazo/irrigación sanguínea , Neoplasias del Bazo/patología , Transformación Celular Neoplásica/patología , Diagnóstico Diferencial , Hamartoma/patología , Histiocitoma Fibroso Benigno/patología , Humanos , Linfangioma/patología , Síndromes Paraneoplásicos/patología , Bazo/patología , Enfermedades Vasculares/patologíaRESUMEN
From a pathologic-anatomic perspective, the splenic parenchyma is divided into red and white pulp, which react to a certain extent independently from one another in the context of systemic and local processes. While the red pulp serves to filter blood, the white pulp, together with the perifollicular marginal zone, organizes immune reactions. In the marginal zone, innate and acquired immune responses are integrated. The vast majority of splenectomies serve therapeutic purposes in the context of already known disease. Therefore, only about 10% of splenectomy specimens are diagnostic challenges, including the diagnosis of haematological diseases, splenomegaly or splenic tumors. Differential diagnosis considerations are discussed based on the clinical presentation.
Asunto(s)
Enfermedades Hematológicas/patología , Bazo/patología , Esplenectomía , Neoplasias del Bazo/patología , Esplenomegalia/patología , Arteriolas/patología , Capilares/patología , Diagnóstico Diferencial , Enfermedades Hematológicas/cirugía , Humanos , Macrófagos/patología , Bazo/anatomía & histología , Bazo/irrigación sanguínea , Neoplasias del Bazo/cirugía , Esplenomegalia/cirugíaRESUMEN
Inflammatory reactions of the spleen occur in the context of two pathophysiological settings. First, lymphoid hyperplasia of the spleen can be the result of a principally physiological production of immune effector cells e.g. due to systemic viral infections, autoimmune diseases and acquired or inherited immunodeficiencies. Second, the spleen itself may be the target of a pathological inflammatory reaction; this setting is exemplified by abscess formation due to septicopyemic spread of bacteria and by granulomatous inflammations, e.g. due to tuberculosis or sarcoidosis. Differential diagnostic considerations have to include splenic inflammatory pseudotumors, mycobacterial spindle cell tumors and lymphomas with granulomatous or histiocyte-rich reactive changes.
Asunto(s)
Enfermedades Autoinmunes/patología , Inflamación/patología , Bazo/patología , Enfermedades del Bazo/patología , Absceso/patología , Enfermedades Autoinmunes/fisiopatología , Diagnóstico Diferencial , Granuloma/patología , Granuloma de Células Plasmáticas/patología , Humanos , Infarto/patología , Inflamación/fisiopatología , Leucemia Mieloide/patología , Policitemia Vera/patología , Esferocitosis Hereditaria/patología , Enfermedades del Bazo/fisiopatologíaRESUMEN
A 28-year-old female with worsening dyspnea showed miliary nodules of 2 mm in diameter on chest X-ray and high-resolution CT (HRCT). Histological evaluation and clinical outcome revealed an uncommon presentation of cryptogenic organizing pneumonia.
Asunto(s)
Neumonía en Organización Criptogénica/complicaciones , Neumonía en Organización Criptogénica/diagnóstico por imagen , Disnea/etiología , Adulto , Disnea/diagnóstico , Femenino , Humanos , Radiografía TorácicaRESUMEN
The pathogenesis of mature T-cell non-Hodgkin lymphomas (T-NHLs) is poorly understood. Analogous to B-cell lymphomas, in which the immunoglobulin (IgH) receptor loci are frequently targeted by chromosomal translocations, the T-cell receptor (TCR) gene loci are affected by translocations in a subset of precursor T-cell malignancies. In a large-scale analysis of 245 paraffin-embedded mature T-NHLs, arranged in a tissue microarray format and using improved FISH assays for the detection of breakpoints in the TCRalpha/delta, TCRbeta, and TCRgamma loci, we provide evidence that mature T-NHLs other than T-cell prolymphocytic leukaemia (T-PLL) also occasionally show a chromosomal rearrangement that involves the TCRalpha/delta locus. In particular, one peripheral T-cell lymphoma (not otherwise specified, NOS) with the morphological variant of Lennert lymphoma displayed a chromosomal translocation t(14;19) involving the TCRalpha/delta and the BCL3 loci. A second case, an angio-immunoblastic T-cell lymphoma (AILT), carried an inv(14)(q11q32) affecting the TCRalpha/delta and IgH loci. FISH signal constellations as well as concomitant comparative genomic hybridization (CGH) data were also suggestive of the occurrence of an isochromosome 7, previously described to be pathognomonic for hepatosplenic T-cell lymphomas, in rare cases of enteropathy-type T-cell lymphoma.
Asunto(s)
Rotura Cromosómica , Reordenamiento Génico de Linfocito T , Genes Codificadores de los Receptores de Linfocitos T , Linfoma de Células T/genética , Proteínas del Linfoma 3 de Células B , Estudios de Casos y Controles , Cromosomas Humanos Par 14 , Cromosomas Humanos Par 19 , Cromosomas Humanos Par 7 , Perfilación de la Expresión Génica , Reordenamiento Génico de la Cadena alfa de los Receptores de Antígenos de los Linfocitos T , Reordenamiento Génico de la Cadena delta de los Receptores de Antígenos de los Linfocitos T , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Hibridación Fluorescente in Situ , Análisis de Secuencia por Matrices de Oligonucleótidos , Adhesión en Parafina , Proteínas Proto-Oncogénicas/genética , Factores de Transcripción/genética , Translocación GenéticaRESUMEN
Enteropathy type T-cell lymphomas (ETL) are the most frequent T-cell lymphomas arising in the gastrointestinal tract. Commonly, the neoplasm is clinically associated with symptoms of malabsorption, and it frequently manifests as a spontaneous bowel perforation. Among ETL, two types can be distinguished by morphology, immunophenotype and, possibly, by pathogenesis. A total of 80% of ETL are characterized by a close association with celiac disease, pleomorphic cytomorphology and the rare expression of CD8 and CD56. In contrast, 20% of ETL show a monomorphic small to medium size cytomorphology and frequent expression of CD8 and CD56, an association with celiac disease is rare in the latter cases. Genetically, ETL is characterized by frequent and recurrent chromosomal gains of 9q33-q34.
Asunto(s)
Aberraciones Cromosómicas , Linfoma de Células T/patología , Mapeo Cromosómico , Humanos , Inmunofenotipificación , Linfoma de Células T/clasificación , Linfoma de Células T/genética , Linfoma de Células T/inmunologíaRESUMEN
Primary cutaneous B-cell lymphomas include cutaneous follicle centre lymphoma (PCFCL), cutaneous marginal zone B-cell lymphoma (PCMZL) and cutaneous diffuse large B-cell lymphoma (PCLBCL) "leg type" which are the three main types in the new WHO-EORTC classification for cutaneous lymphomas. PCFCL and PCMZL are indolent lymphomas with an excellent prognosis while PCLBCL shows an aggressive clinical course. All three types must be distinguished from a secondary skin involvement by systemic lymphomas. Since histological and immunohistochemical findings are not decisive, making this distinction requires appropriate staging procedures. In contrast, the pathologist can make an important contribution to the differential diagnosis between neoplastic and reactive cutaneous lymphoproliferations.
Asunto(s)
Linfoma de Células B/clasificación , Linfoma de Células B/patología , Neoplasias Cutáneas/clasificación , Neoplasias Cutáneas/patología , Humanos , Incidencia , Linfoma de Células B/epidemiología , Linfoma de Células B/genética , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/genéticaRESUMEN
Peripheral T-cell lymphomas comprise 8% of the malignant lymphomas in Germany. About 25% of these cases present primarily in extranodal localizations. Such localizations are typical for the respective disease and form the basis for the classification of extranodal peripheral T-cell lymphoma. The morphology, immunophenotype and lineage specificity of the tumor cells (originating from T- or NK-cells) is only secondary for the classification. Extranodal NK/T-cell lymphomas of the nasal type are characterized by an angiocentric growth pattern and large confluent areas of necrosis. In addition, there is a clonal infection by Epstein-Barr virus in the T-lymphocytes. In the differential diagnosis, B-cell lymphomas are more frequent at all localizations than T- or NK-cell lymphomas.
Asunto(s)
Células Asesinas Naturales/patología , Linfoma de Células T/patología , Linfocitos T/inmunología , Diagnóstico Diferencial , Humanos , Inmunofenotipificación , Células Asesinas Naturales/inmunología , Linfoma de Células B/clasificación , Linfoma de Células B/inmunología , Linfoma de Células B/patología , Linfoma de Células T/clasificación , Linfoma de Células T/inmunología , Linfocitos T/patologíaRESUMEN
Peripheral T-cell lymphomas (PTCL) have not been successfully correlated with specific developmental stages of reactive T-cells. Mature T-cells pass through distinct stages upon antigen encounter. Naïve T-cells are CD45RA(+)/CD45R0(-)/CD27(+)/CCR7(+). After antigen contact they replace CD45RA expression with CD45R0. The mature T-cells differentiate to central memory cells, which retain CD27 and CCR7, or to effector memory cells, which lose expression of both molecules depending on the strength of the antigen interaction. In this study, we evaluated lymph node biopsies from eight PTCL-not otherwise specified (PTCL-NOS), seven angioimmunoblastic T-cell lymphomas (AILT), and 15 anaplastic large cell lymphomas (ALCL). Detection of tumour cells with antibodies that recognize specific rearranged T-cell receptor Vbeta segments allowed us to investigate the expression of various differentiation-associated molecules. Results were analysed by hierarchical cluster analysis. All AILT and ALCL showed a homogeneous effector cell phenotype (CD45RA(-)/CD45R0(+)/CD27(-)), but differed in the cytotoxic and activation markers expressed. Several (5/8) PTCL-NOS clustered together; these cases all exhibited a CD4(+) central memory cell phenotype (CD45RA(-)/CD45R0(+)/CD27(+)) and four expressed the lymph node homing receptor CCR7. In conclusion, AILT and ALCL tumour cells correspond to different subsets of effector cells, while a subset of PTCL-NOS correlates with a non-effector T-cell population.
Asunto(s)
Linfoma de Células T Periférico/inmunología , Subgrupos de Linfocitos T/inmunología , Linfocitos T CD4-Positivos/inmunología , Diferenciación Celular/inmunología , Análisis por Conglomerados , Humanos , Linfadenopatía Inmunoblástica/inmunología , Memoria Inmunológica , Inmunofenotipificación , Antígenos Comunes de Leucocito/metabolismo , Linfoma Anaplásico de Células Grandes/inmunología , Receptores CCR7 , Receptores de Quimiocina/metabolismo , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/metabolismoRESUMEN
AIMS: To investigate whether an antibody against an intracellular epitope can detect CD19 in routine biopsy specimens and thus to document in detail its expression in human lymphomas. METHOD AND RESULTS: A polyclonal antibody to the C terminus of CD19 was used to immunostain paraffin-embedded samples of normal and neoplastic lymphoid tissues. CD19 was widely expressed in normal B cells and in extramedullary plasma cells. It was found in most B-cell neoplasms, but expression in follicular lymphoma was weak (33/69) or negative (four cases). Similarly, CD19 expression in diffuse large B-cell lymphomas was weak (28/56) or negative (eight cases). In T-cell-rich B-cell lymphomas, CD19 was also weak (4/10) or negative (three cases). CD19 was often absent in post-transplant B lymphoproliferative disease, classical Hodgkin's disease and plasma cell neoplasms. An unexpected finding was the frequent absence of CD19 in the neoplastic cells in lymphocyte predominant Hodgkin's disease. CONCLUSIONS: CD19 can now be detected in routine biopsy specimens. In contrast to the classical pan-B marker CD20, CD19 is not always strongly expressed in B-cell neoplasms. Furthermore, the lymphocytic and histiocytic (L&H) cells of lymphocyte predominant Hodgkin's disease (which express most B-cell-associated markers) commonly lack CD19.