RESUMEN
PURPOSE: To detect the presence of MYD88 L265P mutation in the aqueous humor of patients with cytologically proven vitreoretinal lymphoma. METHODS: Eight consecutive patients with bilateral vitreoretinal lymphoma (16 eyes) were prospectively evaluated. Genomic DNA was extracted from aqueous samples after paracentesis and vitreous humor samples after diagnostic vitrectomy. MYD88 codon 265 mutation was investigated by both amplification-refractory mutation system polymerase chain reaction approach and pyrosequencing assay in the aqueous humor of all patients and in the vitreous of 6 patients. A control group of 8 age-matched patients with established diagnosis of noninfectious uveitis was also tested for the presence of MYD88 L265P mutation in the aqueous humor. RESULTS: Eight patients (three men, five women) with mean age of 69.5 years (range 50-85 years) were considered. All the patients tested for MYD88 L265P in the vitreous (six) were positive, and this result was consistent with cytological examination in all samples but one. The MYD88 L265P mutation was found in the aqueous of 6 patients (75%), and in 3 of them, the mutation was present in both eyes. Results of MYD88 L265P mutation in aqueous and vitreous sample were consistent in 7 of the 8 eyes with available samples. The aqueous humor of the noninfectious uveitis control group was negative for the detection of MYD88 L265P mutation. CONCLUSION: MYD88 mutation was detected in the aqueous humor of 75% of patients with cytologically proven vitreoretinal lymphoma. This technique may be considered as an additional diagnostic tool in the detection of the disease.
Asunto(s)
Humor Acuoso/metabolismo , Biomarcadores de Tumor/genética , ADN de Neoplasias/genética , Linfoma Intraocular/genética , Mutación , Factor 88 de Diferenciación Mieloide/genética , Macroglobulinemia de Waldenström/genética , Anciano , Anciano de 80 o más Años , Análisis Mutacional de ADN , Femenino , Humanos , Linfoma Intraocular/diagnóstico , Linfoma Intraocular/cirugía , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Estudios Prospectivos , Microscopía con Lámpara de Hendidura , Vitrectomía , Cuerpo Vítreo/metabolismo , Cuerpo Vítreo/patología , Macroglobulinemia de Waldenström/diagnóstico , Macroglobulinemia de Waldenström/cirugíaRESUMEN
Pulmonary adenocarcinoma with enteric differentiation (PAED) is a rare subtype of lung adenocarcinoma recently recognized in the WHO classification. It is defined as an adenocarcinoma in which the enteric component exceeds 50% and have to show the expression of at least 1 immunohistochemical marker of enteric differentiation. Although the definition of this tumor type is very important, above all in the differential diagnosis between a primary lung tumor and a metastasis of colorectal adenocarcinoma, this cancer still lacks a distinctive immunohistochemical and molecular signature. We recruited the largest series in the literature of PAEDs according to the morphology and the positivity for intestinal markers. Then, we evaluated the immunohistochemical and molecular profile of these adenocarcinomas. In our series, CDX-2 and CK7 were the immunohistochemical markers mostly expressed by PAEDs. There was an inverse relationship between the expression of pnuemocytes markers, such as TTF-1, and intestinal markers. Molecular analysis revealed KRAS as the most frequently mutated gene (>60% of cases), with very few cases harboring abnormalities affecting EGFR, BRAF, and ALK genes. PAEDs are morphologically very heterogenous. The immunohistochemical profile based on CDX-2 and CK7 positivity of PAEDs appears very robust to support this diagnosis, and it is applicable also on small biopsies. KRAS appears as the most important mutated gene in such tumors.