RESUMEN
Histological artefacts in cryosectioned tissue can hinder rapid diagnostic assessments during surgery. Formalin-fixed and paraffin-embedded (FFPE) tissue provides higher quality slides, but the process for obtaining them is laborious (typically lasting 12-48 h) and hence unsuitable for intra-operative use. Here we report the development and performance of a deep-learning model that improves the quality of cryosectioned whole-slide images by transforming them into the style of whole-slide FFPE tissue within minutes. The model consists of a generative adversarial network incorporating an attention mechanism that rectifies cryosection artefacts and a self-regularization constraint between the cryosectioned and FFPE images for the preservation of clinically relevant features. Transformed FFPE-style images of gliomas and of non-small-cell lung cancers from a dataset independent from that used to train the model improved the rates of accurate tumour subtyping by pathologists.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Aprendizaje Profundo , Neoplasias Pulmonares , Humanos , Formaldehído , Adhesión en Parafina/métodosRESUMEN
The cation-independent mannose 6-phosphate/insulin-like growth factor-2 receptor (M6P/IGF2R or IGF2R) traffics IGF2 and M6P ligands between pre-lysosomal and extra-cellular compartments. Specific IGF2 and M6P high-affinity binding occurs via domain-11 and domains-3-5-9, respectively. Mammalian maternal Igf2r allele expression exceeds the paternal allele due to imprinting (silencing). Igf2r null-allele maternal transmission results in placenta and heart over-growth and perinatal lethality (>90%) due to raised extra-cellular IGF2 secondary to impaired ligand clearance. It remains unknown if the phenotype is due to either ligand alone, or to both ligands. Here, we evaluate Igf2r specific loss-of-function of the domain-11 IGF2 binding site by replacing isoleucine with alanine in the CD loop (exon 34, I1565A), a mutation also detected in cancers. Igf2rI1565A/+p maternal transmission (heterozygote), resulted in placental and embryonic over-growth with reduced neonatal lethality (<60%), and long-term survival. The perinatal mortality (>80%) observed in homozygotes (Igf2rI1565A/I1565A) suggested that wild-type paternal allele expression attenuates the heterozygote phenotype. To evaluate Igf2r tumour suppressor function, we utilised intestinal adenoma models known to be Igf2 dependent. Bi-allelic Igf2r expression suppressed intestinal adenoma (ApcMin). Igf2rI1565A/+p in a conditional model (Lgr5-Cre, Apcloxp/loxp) resulted in worse survival and increased adenoma proliferation. Growth, survival and intestinal adenoma appear dependent on IGF2R-domain-11 IGF2 binding.
Asunto(s)
Adenoma/genética , Trastornos del Crecimiento/genética , Factor II del Crecimiento Similar a la Insulina/metabolismo , Neoplasias Intestinales/genética , Herencia Materna , Receptor IGF Tipo 2/genética , Adenoma/patología , Alelos , Animales , Proliferación Celular/genética , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Embrión de Mamíferos/patología , Femenino , Impresión Genómica , Trastornos del Crecimiento/patología , Células HEK293 , Heterocigoto , Homocigoto , Humanos , Hiperplasia/patología , Neoplasias Intestinales/patología , Mutación con Pérdida de Función , Masculino , Ratones , Ratones Transgénicos , Placenta/patología , Embarazo , Dominios Proteicos/genética , Receptor IGF Tipo 2/metabolismoRESUMEN
Hairy polyps are rare benign tumors that are derived from 2 germ layers: ectoderm and mesoderm. Although location in the head and neck area is rare, the soft palate as the site of origin is even more unusual. The clinical presentation depends on the polyp's location and size. These masses can commonly cause respiratory and feeding difficulties. We present a case of a soft palate hairy polyp causing respiratory and feeding difficulties in a 6-month-old female infant and review the literature.