In contrast to NKCE and LG, extranodal NK/T cell lymphoma, nasal type: is malignant and often aggressive; causes serious, persistent, and often progressive GI tract and other symptoms; commonly involves the head and neck areas and/or multiple organs outside of the GI tract; is deeply invasive, extending beyond the lamina propia of the GI tract; and consists of lesions which contain malignant Epstein-Barr virus-infected NK cells that have numerous gene mutations and chromosome abnormalities and that center around and destroy blood vessels. Monomorphic epitheliotropic intestinal T cell lymphoma (MEITL): MEITL is a malignant and extremely aggressive GI tract disease. It is manifested by serious, sometimes life-threatening GI tract symptoms such as GI tract obstructions and perforations; is usually localized to the small intestine but may involve other areas of the GI tact; is invasive, e.g. spreads to the submucosa; commonly metastasizes to GI tract lymph nodes; and is composed of lesions which contain Epstein-Barr virus-negative homogenously appearing, medium-sized, malignant T cells that may have mutations or other genetic abnormalities in their STAT5B, JAK3, TP53, SETD2, BRAF, KRAS, GNA12, CREBBP, and/or Myc genes. Indolent T cell lymphoproliferative disorder of the gastrointestinal tract: This recently described disease, while generally considered benign, has in rare cases been lethal with disease spreading to the bone marrow and blood. This disease is a potentially precancerous condition.
The hypothesis of autosomal recessive inheritance of Vici syndrome was strengthened in 2002 with the clinical description of two new cases, one brother and one sister, by Chiyonobu et al. Gene
Vici syndrome is caused by mutations in the gene EPG5 (OMIM # 615068), which encodes an important regulator of the autophagy pathway, the ectopic P-granules autophagy protein 5, involved in the formation of lysosomes. EPG5 is the human homolog of the C.elegans epg5 gene. The gene EPG5 has been cloned for the first time by Nagase et al. by sequencing clones obtained from a size-fractionated fetal brain cDNA library, and was initially named KIAA1632.The EPG5 human gene is located on chromosome 18q12.3, has a length of 119,67Kb (NC_000018.10), consists of 44 exons and is transcriptionally driven from the centromere toward the telomere. The messenger RNA (mRNA) is 12633bp long (NM_020964.2) and contains a CDS of 7740 bp translated into a protein sequence of 2579 amino acids (NP_066015.2) with a molecular weight of 280kDa, presumed. The protein EPG5 is expressed primarily in the central nervous system (CNS), skeletal muscle, heart, thymus, cells of the immune system, lungs and kidneys.Mutations in the EPG5 gene interfere with the autophagy. This appears to be due to a block in the autophagosome-lysosome fusion mechanism. Diagnosis
The diagnostic workup usually includes an MRI of the brain, an EEG, ophthalmic examination and a cardiac ECHO. Muscle biopsy – which is not commonly done – may show storage of abnormal material and secondary mitochondrial abnormalities in skeletal muscle.