Papillary renal cell carcinoma (PRCC) is defined by the WHO 2022 classification as a malignant tumor derived from the renal tubular epithelium. However, the WHO 2016 classification subdivided PRCC into two types, with type 1 PRCC showing papillae covered by a single layer of neoplastic cells, and type II PRCC, which can show multiple types of histologies and is more aggressive. The WHO 2022 classification eliminated the subcategorization of PRCC. Here, we present a histopathological case study with a 4-year follow-up diagnosed in 2018 as type I PRCC (WHO 2016) with intra-pyelocalyceal growth pattern in a 59-year-old male patient with a history of Type II diabetes mellitus, left-sided renal–ureteral lithiasis, and benign hypertrophy of the prostate. Microscopically the tumor was composed of small cuboidal cells with inconspicuous nucleoli, arranged on a single layer of tubulo-papillary cores, and scant, foamy macrophages. The tumor had a non-infiltrative, expansive pyelocalyceal growth pattern. Immunohistochemically (IHC), the tumor cells were CK7-intense and diffusely positive, and stained granular for AMACR. Next-generation sequencing (NGS) was performed for the tumor and the normal adjacent tissue for in-depth pathological characterization. To our knowledge, this is the first reported case where a PRCC displays this unique intra-pyelocalyceal growth pattern, mimicking a urothelial cell carcinoma of the renal pelvis system.

Background: Elevated plasma homocysteine, arising from impaired one-carbon metabolism, has been implicated in cerebral microvascular injury and in neurodegeneration. The methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is the commonest genetic determinant of homocysteine concentration, but whether it leaves a measurable structural footprint on the brain remains unresolved. We synthesised genotype-stratified structural MRI findings in Alzheimer’s disease, mild cognitive impairment, and vascular cognitive disorders. Methods: Four sources (PubMed, Europe PMC, OpenAlex, Semantic Scholar) were searched up to 20 September 2026. Eligible reports gave C677T-stratified structural MRI outcomes in adults with clinically defined cognitive disorders. Quality was appraised with an adapted Newcastle–Ottawa Scale, and exploratory random-effects meta-analyses supplemented a narrative synthesis. Results: Thirteen studies (3880 participants across partly overlapping cohorts) were included. Moderate-to-severe white matter lesions were modestly more frequent in TT homozygotes, consistently across contributing studies, with no consistent excess in heterozygotes. Regional volume findings were inconsistent and largely confined to one cohort, whereas whole-brain atrophy rate, hippocampal and medial temporal measures, lacunes, microbleeds, and diffusion metrics showed no genotype-only association. Homocysteine was higher in T-allele carriers wherever measured. Conclusions: The evidence is more compatible with a modest association with vascular white matter injury than with a reproducible neurodegenerative imaging phenotype and does not support genotype-guided clinical decision-making. Longitudinal, biomarker-characterised cohorts with harmonised imaging, adequately powered genotype groups, and measured nutritional status are the main priorities.