A comparative urinary proteomic and metabolomic analysis between renal aa amyloidosis and membranous nephropathy with clinicopathologic correlations.

Urinary omics has become a powerful tool for elucidating pathophysiology of glomerular diseases. However, no urinary omics analysis has been performed yet on renal AA amyloidosis. Here, we performed a comparative urine proteomic and metabolomic analysis between recently diagnosed renal AA amyloidosis (AA) and membranous nephropathy (MN) patients. Urine samples of 22 (8 AA, 8 MN and 6 healthy control) patients were analyzed with nLC-MS/MS and GC/MS for proteomic and metabolomic studies, respectively. Pathological specimens were scored for glomerulosclerosis and tubulointerstitial fibrosis grades. Functional enrichment analysis between AA and control groups showed enrichment in cell adhesion related sub-domains. Uromodulin (UMOD) was lower, whereas ribonuclease 1 (RNase1) and α-1-microglobulin/bikunin precursor (AMBP) were higher in AA compared to MN group. Correlations were demonstrated between UMOD-proteinuria (r = -0.48, p = 0.03) and AMBP-eGFR (r = -0.69, p = 0.003) variables. Metabolomic analysis showed myo-inositol and urate were higher in AA compared to MN group. A positive correlation was detected between RNase1 and urate independent of eGFR values (r = 0.63, p = 0.01). Enrichment in cell adhesion related domains suggested a possible increased urinary shear stress due to amyloid fibrils. UMOD, AMBP and myo-inositol were related with tubulointerstitial damage, whereas RNase1 and urate were believed to be related with systemic inflammation in AA amyloidosis. SIGNIFICANCE: Urinary omics studies have become a standard tool for biomarker studies. However, no urinary omics analysis has been performed yet on renal AA amyloidosis. Here, we performed a comparative urinary omics analysis between recently diagnosed renal AA amyloidosis (AA), membranous nephropathy (MN) patients and healthy controls. Pathological specimens were scored with glomerulosclerosis (G) and tubulointerstitial fibrosis (IF) grades to consolidate the results of the omics studies and correlation analyzes. Functional enrichment analysis showed enrichment in cell adhesion related sub-domains due to downregulation of cadherins; which could be related with increased urinary shear stress due to amyloid deposition and disruption of tissue micro-architecture. In comparative proteomic analyzes UMOD was lower, whereas RNase1 and AMBP were higher in AA compared to MN group. Whereas in metabolomic analyzes; myo-inositol, urate and maltose were higher in AA compared to MN group. Correlations were demonstrated between UMOD-proteinuria (r = -0.48, p = 0.03), AMBP-eGFR (r = -0.69, p = 0.003) and between RNase1-Urate independent of eGFR values (r = 0.63, p = 0.01). This study is the first comprehensive urinary omics analysis focusing on renal AA Amyloidosis to the best of our knowledge. Based on physiologic roles and clinicopathologic correlations of the molecules; UMOD, AMBP and myo-inositol were related with tubulointerstitial damage, whereas RNase1 and urate were believed to be increased with systemic inflammation and endothelial damage in AA amyloidosis.

Primary lymphomas of the intraabdominal solid organs and the gastrointestinal tract: spectrum of imaging findings with histopathological confirmation.

Unlike nodal lymphoma, primary lymphomas of the intraabdominal organs are uncommon neoplasms whose diagnosis may be challenging in certain clinical circumstances. Despite this difficulty for imaging diagnosis, there are several imaging features on ultrasonography, computed tomography, magnetic resonance imaging, and positron emission tomography that may suggest the correct diagnosis. The scope of this review is to describe and illustrate the imaging features of primary lymphoma of intraabdominal organs providing clues to the diagnosis, together with their pathological correlations.

Conjunctival extranodal natural killer/T-cell lymphoma, nasal type.

PURPOSE: To report a rare case of a patient with isolated primary conjunctival extranodal natural killer/T-cell lymphoma, nasal type (ENKTCL) without nasal involvement. METHODS: The clinical course, magnetic resonance imaging, positron emission tomographic and immunohistopathological features of the patient were evaluated. RESULTS: A 57-year-old man presented with rapidly progressing swelling and redness in his right eye for 2 months. A salmon-colored mass was present under all parts of the bulbar conjunctiva. Magnetic resonance imaging demonstrated a mass anterior to the globe without any sinus involvement. Positron emission tomographic study did not show other disease sites. Immunohistopathological studies on incisional biopsy specimen demonstrated ENKTCL with positive CD2, CD7, CD56, bcl-2, and T cell-restricted intracellular antigen, and negative CD20, CD8, CD123, and terminal deoxynucleotidyl transferase staining. Epstein-Barr virus (EBV)-encoded mRNA was also diffusely positive. Ki-67 index was more than 90%. The patient received cyclophosphamide, vincristine, hydroxydaunorubicin, cisplatin, and prednisone chemotherapy with 4500 cGY radiotherapy in 25 fractions to the right orbit, resulting in total resolution of the conjunctival tumor. He developed intracranial and gastrointestinal tumors and died of cardiopulmonary failure 11 months later. CONCLUSIONS: Extranodal natural killer/T-cell lymphoma, nasal type may primarily arise in the conjunctiva without nasal or paranasal sinus involvement. Despite initial successful local tumor control by systemic chemotherapy and local irradiation, the overall prognosis is poor due to systemic dissemination.