Clinical Presentation and Outcome of Sinonasal Extraosseous Plasmacytoma in Denmark: A Nationwide Cohort From 1980 to 2017.

OBJECTIVES: Extraosseous plasmacytoma (EOP) is a rare plasma cell neoplasm that tends to convert to plasma cell myeloma (PCM) in about 11% to 35% of cases. It has a predilection for the upper respiratory tract, prototypically affecting the nasal cavity and paranasal sinuses. Contemporary first-line treatment is radiotherapy, with more recent studies showing an added benefit of combining radiation with surgery. In this cohort study, we aimed to examine clinical presentation, treatment, and prognosis for all patients nationwide from 1980 through 2017. Furthermore, we determined the size and extension of tumors, investigating the rate at which minimally invasive surgery would have been possible. METHODS: Patients were found in the national pathology registry, and all biopsies were collected for pathology review by a hematopathologist. We performed survival statistics for overall survival (OS), progression-free survival (PFS), and the cumulative incidence of conversion to PCM. RESULTS: Twenty-three patients were included. The median age was 65, and patients were primarily men (78%). Tumors were located in either the nasal cavity (57%), maxillary sinus (39%), or sphenoid sinus (4%). In most cases, the tumor was <5 cm (65%) without extension to adjacent structures (60%). The national incidence was 0.02/100,000 person-years, the median symptom duration until diagnosis was 5 months, and none of the patients presented with contiguous spread to regional lymph nodes. Stand-alone radiotherapy was the predominant treatment (61%). In the entire cohort, one patient died from the initial disease, and six patients died from either relapse of EOP or PCM. The 5-year OS, PFS, and conversion rate to PCM were 78%, 56%, and 23%, respectively. CONCLUSION: SN-EOP responds well to radiotherapy, but relapse and conversion to PCM were not uncommon and entailed a poor prognosis. Most tumors were endoscopically resectable and non-invasive, making the majority of tumors suitable for surgery as an addition to radiation.

NK- and T-cell lymphoma of the nasal cavity and paranasal sinuses in Denmark 1980-2017: a nationwide cohort study.

Compared to Asian and Latin American populations, sinonasal NK- or T-cell lymphoma is rare in Europe. All patients with sinonasal NK- or T-cell lymphoma in Denmark from 1980 to 2017 were validated histologically, and the disease behavior and demographics were extracted from medical records and national registries. Prognostic factors associated with mortality were determined using survival statistics. We included 56 patients: 40 extranodal NK/T-cell lymphoma (nasal type) (ENKTCL) and 16 peripheral T-cell lymphoma (not otherwise specified) (PTCL). The median age was 66, and most patients were male (72%). The ENKTCL and PTCL 5-year overall survival was 48% and 50%, respectively; progression-free survival was 38% for both. With ENKTCL, stage and performance status increased mortality significantly (HR = 8.6; p < 0.001 and HR = 4.23; p = 0.04). In conclusion, disseminated disease had a dismal outcome and the onset of ENKTCL in this ethnically homogeneous European cohort was about a decade later than reported in Asian populations.

Sinonasal B-cell lymphomas: A nationwide cohort study, with an emphasis on the prognosis and the recurrence pattern of primary diffuse large B-cell lymphoma.

Lymphomas of the nasal cavity and paranasal sinuses (NPS) are rare. Knowledge on sinonasal B-cell lymphoma (SNBCL) primarily comes from case series or single-center studies on small cohorts. We sought to determine the subtype distribution, clinical characteristics, disease behavior, and prognosis on a nationwide scale, with an emphasis on prognostic factors for the most common sinonasal lymphoma, primary sinonasal diffuse large B-cell lymphoma (PSDLBCL). We collated all data from medical records and national databases on patients registered with SNBCL from 1980 through 2018 in the national pathology registry and collected all tissue samples for validation of diagnosis. We included 205 patients and found 10 different subtypes of lymphoma. Diffuse large B-cell lymphoma (DLBCL) was the predominant subtype (80%). The incidence of SNBCL was 0.14/100,000 person-years. The five-year progression-free survival (PFS) and overall survival rates for PSDLBCL were 50% and 56%, respectively. For PSDLBCL, Rituximab showed a statistically significant effect (Hazard Ratio 0.22, p < 0.001), whereas consolidative radiotherapy combined with immunochemotherapy was of limited value (PFS, p = 0.93). When treatment failure occurred, DLBCL showed a distinct pattern of recurrence/dissemination to the NPS, skin, breast, central nervous system (CNS), and/or testis. Collectively, DLBCL comprised a clear majority of SNBCLs, although nine other subtypes were represented. Data showed that immunochemotherapy increased survival for PSDLBCL and that the addition of radiotherapy did not benefit patients. Furthermore, treatment failure for sinonasal DLBCL showed a possible common pathogenesis with primary extranodal lymphomas of specific locations (e.g., CNS, skin, breast, and testis).

Partial nephrogenic diabetes insipidus caused by a novel AQP2 variation impairing trafficking of the aquaporin-2 water channel.

BACKGROUND: Autosomal dominant inheritance of congenital nephrogenic diabetes insipidus (CNDI) is rare and usually caused by variations in the AQP2 gene. We have investigated the genetic and molecular background underlying symptoms of diabetes insipidus (DI) in a Swedish family with autosomal dominant inheritance of the condition. METHODS: The proband and her father were subjected to water deprivation testing and direct DNA sequencing of the coding regions of the AQP2 and AVP genes. Madin-Darby canine kidney (MDCK) cells stably expressing AQP2 variant proteins were generated by lentiviral gene delivery. Localization of AQP2 variant proteins in the cells under stimulated and unstimulated conditions was analyzed by means of immunostaining and confocal laser scanning microscopy. Intracellular trafficking of AQP2 variant proteins was studied using transient expression of mutant dynamin2-K44A-GFP protein and AQP2 variant protein phosphorylation levels were assessed by Western blotting analysis. RESULTS: Clinical and genetic data suggest that the proband and her father suffer from partial nephrogenic DI due to a variation (g.4807C > T) in the AQP2 gene. The variation results in substitution of arginine-254 to tryptophan (p.R254W) in AQP2. Analysis of MDCK cells stably expressing AQP2 variant proteins revealed disabled phosphorylation, impaired trafficking and intracellular accumulation of AQP2-R254W protein. Notably, blocking of the endocytic pathway demonstrated impairment of AQP2-R254W to reach the cell surface. CONCLUSIONS: Partial CNDI in the Swedish family is caused by an AQP2 variation that seems to disable the encoded AQP2-R254W protein to reach the subapical vesicle population as well as impairing its phosphorylation at S256. The AQP2-R254W protein is thus unable to reach the plasma membrane to facilitate AVP mediated urine concentration.