RESUMEN
Comprehensive genetic profiling is increasingly important for the clinical workup of hematologic tumors, as specific alterations are now linked to diagnostic characterization, prognostic stratification and therapy selection. To characterize relevant genetic and genomic alterations in myeloid malignancies maximally, we utilized a comprehensive strategy spanning fluorescence in situ hybridization (FISH), classical karyotyping, Chromosomal Microarray (CMA) for detection of copy number variants (CNVs) and Next generation Sequencing (NGS) analysis. In our cohort of 569 patients spanning the myeloid spectrum, NGS and CMA testing frequently identified mutations and copy number changes in the majority of genes with important clinical associations, such as TP53, TET2, RUNX1, SRSF2, APC and ATM. Most importantly, NGS and CMA uncovered medically actionable aberrations in 75.6% of cases normal by FISH/cytogenetics testing. NGS identified mutations in 65.5% of samples normal by CMA, cytogenetics and FISH, whereas CNVs were detected in 10.1% cases that were normal by all other methodologies. Finally, FISH or cytogenetics, or both, were abnormal in 14.1% of cases where NGS or CMA failed to detect any changes. Multiple mutations and CNVs were found to coexist, with potential implications for patient stratification. Thus, high throughput genomic tumor profiling through targeted DNA sequencing and CNV analysis complements conventional methods and leads to more frequent detection of actionable alterations.
Asunto(s)
Cromosomas Humanos/genética , Citogenética/métodos , Genómica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Hibridación Fluorescente in Situ/métodos , Trastornos Mieloproliferativos/genética , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Estudios de Cohortes , Variaciones en el Número de Copia de ADN/genética , Humanos , Mutación/genética , Trastornos Mieloproliferativos/diagnóstico , Carga TumoralRESUMEN
Encapsulated papillary oncocytic neoplasms (EPONs) of the thyroid are rare tumors, whose relationship to other thyroid tumors has not been thoroughly elucidated. Earlier, they have been regarded as variants of papillary thyroid carcinoma (PTC), hyperplastic lesions, and follicular neoplasms. Eighteen EPONs were retrieved from our surgical pathology files and reviewed for defining morphologic features. Cases having the typical nuclear features of PTC were excluded. Immunohistochemistry (IHC) for CK19, HBME1, and CD56 was carried out. Microdissection, polymerase chain reaction, and sequencing of exon 15 of the BRAF gene were completed. Cases were evaluated for rearranged in transformation/papillary thyroid carcinoma RET/PTC rearrangement by fluorescent in situ hybridization (FISH). The majority of the tumors exhibited a distinctive histologic appearance. They were composed of true papillae lined by a single layer of predominantly cuboidal cells with oncocytic cytoplasm; hobnailing was typically prominent. Three tumors showed taller cells with uniformly apical nuclei and no hobnailing. Ten of 18 cases showed vascular and/or capsular invasion; hence, if the diagnostic criteria used to evaluate follicular neoplasms are applied, more than half of the tumors would be considered minimally invasive carcinomas. No cases were immunoreactive with antibodies to HBME1, whereas only 1 of 13 was immunoreactive for CK19. Six of 7 interpretable cases were immunoreactive for CD56. No BRAF point mutations or RET/PTC rearrangements were identified in the examined cases. All patients were alive at the time of last follow-up and no locally recurrent disease had been reported; however, 1 case was remarkable for a lymph node metastasis. Our results confirm that EPONs are histologically, immunohistochemically, and molecularly distinct from papillary thyroid carcinoma and seem to be most related to follicular neoplasms.
Asunto(s)
Adenoma Oxifílico/diagnóstico , Biomarcadores de Tumor , Carcinoma/diagnóstico , Neoplasias de la Tiroides/diagnóstico , Adenoma Oxifílico/química , Adenoma Oxifílico/clasificación , Adenoma Oxifílico/genética , Adenoma Oxifílico/mortalidad , Adenoma Oxifílico/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Antígeno CD56/análisis , Carcinoma/química , Carcinoma/clasificación , Carcinoma/genética , Carcinoma/mortalidad , Carcinoma/patología , Exones , Femenino , Reordenamiento Génico , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Queratina-19/análisis , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Reacción en Cadena de la Polimerasa , Pronóstico , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas c-ret/genética , Terminología como Asunto , Neoplasias de la Tiroides/química , Neoplasias de la Tiroides/clasificación , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/mortalidad , Neoplasias de la Tiroides/patología , Adulto JovenRESUMEN
Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare neoplasia of interdigitating dendritic cells. Two single case reports documenting IDCS harboring t(14;18) translocation involving immunoglobulin heavy chain (IGH) and BCL2 have been reported recently; however, one of the 2 IDCS has a synchronous follicular lymphoma, the absence or presence of a follicular lymphoma in the remaining case is not mentioned. In this study, by using polymerase chain reaction and fluorescence in situ hybridization techniques, we have showed that there is neither t(14;18)/IGH-BCL2 nor IGH gene rearrangement in 4 de novo IDCS without a concurrent or known history of a B-cell lymphoma, including follicular lymphoma, indicating that BCL2 chromosomal translocation is not a general feature of de novo IDCS.
Asunto(s)
Sarcoma de Células Dendríticas Interdigitantes/patología , Genes bcl-2 , Translocación Genética , Adulto , Anciano , Femenino , Reordenamiento Génico , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Hibridación Fluorescente in Situ , Masculino , Patología Molecular , Reacción en Cadena de la PolimerasaRESUMEN
Basaloid squamous cell carcinoma (BSCC) of the esophagus is rare, historically confused for adenoid cystic carcinoma, and recently shown to behave similar to conventional, keratinizing esophageal squamous cell carcinoma. At other sites (eg, oropharynx, anogenital tract) the basaloid phenotype is frequently associated with the presence of high-risk human papillomavirus (HPV). HPVs role in esophageal squamous cell carcinomas is less certain, and to our knowledge, a direct examination of esophageal BSCC for high-risk HPV has not been performed earlier. Nine cases of esophageal BSCC were retrieved from our surgical pathology files. Twenty-two cases of keratinizing esophageal squamous cell carcinoma served as controls. In situ hybridization (ISH) for high-risk HPV and immunohistochemistry for related molecular markers including p53, cyclin D1, and p16 (scored 0 to 4+ based on percentage of cells staining; p53 additionally scored for intensity) were performed. HPV ISH was nonreactive in all tested cases. Compared with controls, BSCC showed less immunoreactivity for p16 and p53 (P=0.003, 0.009). Esophageal BSCC is negative for high-risk HPV by ISH, distinguishing these lesions from other BSCCs. Differential p16 and p53 expression in BSCC suggests that these tumors are molecularly distinct from conventional esophageal squamous cell carcinomas.
Asunto(s)
Alphapapillomavirus/aislamiento & purificación , Carcinoma Basocelular/virología , Carcinoma Basoescamoso/virología , Carcinoma de Células Escamosas/virología , Neoplasias Esofágicas/virología , Infecciones por Papillomavirus/complicaciones , Anciano , Alphapapillomavirus/genética , Biomarcadores de Tumor/análisis , Carcinoma Basocelular/química , Carcinoma Basocelular/patología , Carcinoma Basoescamoso/química , Carcinoma Basoescamoso/patología , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/patología , Inhibidor p16 de la Quinasa Dependiente de Ciclina/análisis , ADN Viral/análisis , Neoplasias Esofágicas/química , Neoplasias Esofágicas/patología , Femenino , Humanos , Hibridación in Situ , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/metabolismo , Infecciones por Papillomavirus/patología , Proteína p53 Supresora de Tumor/análisisRESUMEN
BACKGROUND: A 39-year-old man presented with a 2-month history of abdominal pain, jaundice, non-bloody diarrhea, weakness, and weight loss. Initial evaluation revealed intrahepatic ductopenia consistent with vanishing bile duct syndrome and IBD, type unclassified. Although treatment with budesonide improved his symptoms, they worsened several months later. On repeat evaluation, he was found to have extensive lymphadenopathy and an elevated white blood cell count. INVESTIGATIONS: Physical examination, laboratory investigations, abdominal ultrasound, CT scans, magnetic resonance cholangiopancreatography, endoscopic retrograde cholangiopancreatography, colonoscopies with biopsies, hepatic biopsy, axillary lymph node biopsy. DIAGNOSIS: Hodgkin's lymphoma with secondary vanishing bile duct syndrome and IBD, type unclassified. MANAGEMENT: The initial symptoms were managed with budesonide, but following recurrence, the patient's underlying lymphoma was treated with nitrogen mustard and dexamethasone.
Asunto(s)
Enfermedades de los Conductos Biliares/etiología , Enfermedad de Hodgkin/complicaciones , Enfermedades Inflamatorias del Intestino/etiología , Adulto , Enfermedades de los Conductos Biliares/diagnóstico , Enfermedades de los Conductos Biliares/terapia , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/terapia , Humanos , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/terapia , Masculino , SíndromeRESUMEN
OBJECTIVE: To compare the outcomes of mitral repair and replacement in revascularized patients with ischemic mitral regurgitation. SUMMARY BACKGROUND DATA: Combined coronary bypass (CABG) and mitral procedures have been associated with the highest mortality (>10%) in cardiac surgery. Recent studies have suggested that mitral valve replacement (MVR) with sparing of the subvalvular apparatus had comparable results to mitral repair when associated with CABG. METHODS: Over the past 7 years, 54 patients had CABG/mitral repair versus 56 who had CABG/MVR with preservation of the subvalvular apparatus. The groups were similar in age at 69.2 years in the replacement group versus 67.0 in the repair group. We compared these 2 groups based on hospital mortality, incidence of complications including nosocomial infection, neurologic decompensation (stroke), pulmonary complication (pneumonia, atelectasis, and prolonged ventilation), and renal complications (acute renal failure or insufficiency). RESULTS: The mitral repair group had a hospital mortality of 1.9% versus 10.7% in the replacement group (P = 0.05). Infection occurred in 9% of repairs compared with 13% of replacements (P = 0.59). The incidence of stroke was no different between groups (2 of 54 repairs vs. 2 of 56 replacements, P = 1.00). Pulmonary complication rate was 39% in repairs versus 32% in replacements (P = 0.59). Worsening renal function occurred in 15% of repairs versus 18% of replacements (P = 0.67). CONCLUSIONS: Mitral repair is superior to mitral replacement when associated with coronary artery disease in terms of perioperative morbidity and hospital mortality. Although preservation of the subvalvular apparatus with MVR has a theoretical advantage in terms of ventricular function, mitral repair clearly adds a survival benefit in patients with concomitant ischemic cardiac disease.