Panencephalopathic Creutzfeldt‐Jakob Disease with Distinct Pattern of Prion Protein Deposition in a Patient with D178N Mutation and Homozygosity for Valine at Codon 129 of the Prion Protein Gene

Prion diseases include sporadic, acquired and genetic forms linked to mutations of the prion protein (PrP) gene (PRNP). In subjects carrying the D178N PRNP mutation, distinct phenotypes can be observed, depending on the methionine/valine codon 129 polymorphism. We present here a 53‐year‐old woman with D178N mutation in the PRNP gene and homozygosity for valine at codon 129. The disease started at age 47 with memory deficits, progressive cognitive impairment and ataxia. The clinical picture slowly worsened to a state of akinetic mutism in about 2 years and the disease course was 6 years. The neuropathologic examination demonstrated severe diffuse cerebral atrophy with neuronal loss, spongiosis and marked myelin loss and tissue rarefaction in the hemispheric white matter, configuring panencephalopathic Creutzfeldt‐Jakob disease. PrP deposition was present in the cerebral cortex, basal ganglia and cerebellum with diffuse synaptic‐type pattern of immunoreactivity and clusters of countless, small PrP deposits, particularly evident in the lower cortical layers, in the striatum and in the molecular layer of the cerebellum. Western blot analysis showed the presence of type 1 PrP^Sc (Parchi classification). These findings underline the clear‐cut distinction between the neuropathological features of Creutzfeldt‐Jakob disease associated with D178N PRNP mutation and those of fatal familial insomnia.     

Field effect in oral precancer as assessed by DNA flow cytometry and array-CGH

J Oral Pathol Med (2012) 41 : 119–123 Objective: ‘Field cancerization’ is an accepted model for oral carcinogenesis. So far, genetically altered fields have been just reported in the presence of carcinomas. This study assessed the distant mirror fields (MFs) of oral precancer by DNA high‐resolution flow cytometry (hr DNA‐FCM) and array‐Comparative Genomic Hybridization (a‐CGH). Methods: Five leukoplakias without dysplasia (OLs), seven dysplastic leukoplakias (DOLs), and 12 corresponding visually normal and non‐dysplastic MFs were analyzed. DNA aneuploidy (DNA Index, DI ≠ 1) was detected by hr DNA‐FCM on DAPI stained nuclei suspensions. The epithelial DNA aneuploid subclones were FCM‐sorted to obtain genomic DNA for a‐CGH. Results: Mirror fields, OLs, and DOLs showed increasing prevalence of DNA aneuploidy of, respectively, 8%, 20%, and 57%. The average number of chromosome aberrations (Ch‐Abs) was 2.8 in MFs, 3 in OLs, and 10.6 in DOLs. MFs relative to OLs and DOLs had average numbers of Ch‐Abs, respectively, of 1.8 and 3.6. Ch‐Abs were also observed in DNA diploid sublines, and often the same aberrations were observed in both MFs and corresponding OLs/DOLs. Conclusion: DNA aneuploidy and Ch‐Abs in MFs, the last ones being mainly gains, indicate an early onset of field effect in oral carcinogenesis.     

Head and neck polypoid melanoma

Polypoid melanoma represents a rare clinical variant of nodular melanoma skin cancer in which the tumor is connected to the skin by a pedicle, characterized by exophytic growth, ulceration, and young age at onset (20-39 years) with a special predilection for the back and with a survival rate at 5 years ranging from 32% to 42% as compared with 57% 5-year survival for nodular subtype and 77% for the superficial subtype. We present a case of a deeply pigmented polypoid melanoma arising on the face of a 77-year-old man. We performed a literature review to clarify its surgical management and prognosis.