Renal Pathology of Ciliopathies.

Renal ciliopathies are a group of genetic disorders that affect the function of the primary cilium in the kidney, as well as other organs. Since primary cilia are important for regulation of cell signaling pathways, ciliary dysfunction results in a range of clinical manifestations, including renal failure, cyst formation, and hypertension. We summarize the current understanding of the pathophysiological and pathological features of renal ciliopathies in childhood, including autosomal dominant and recessive polycystic kidney disease, nephronophthisis, and Bardet-Biedl syndrome, as well as skeletal dysplasia associated renal ciliopathies. The genetic basis of these disorders is now well-established in many cases, with mutations in a large number of cilia-related genes such as PKD1, PKD2, BBS, MKS, and NPHP being responsible for the majority of cases. Renal ciliopathies are broadly characterized by development of interstitial fibrosis and formation of multiple renal cysts which gradually enlarge and replace normal renal tissue, with each condition demonstrating subtle differences in the degree, location, and age-related development of cysts and fibrosis. Presentation varies from prenatal diagnosis of congenital multisystem syndromes to an asymptomatic childhood with development of complications in later adulthood and therefore clinicopathological correlation is important, including increasing use of targeted genetic testing or whole genome sequencing, allowing greater understanding of genetic pathophysiological mechanisms.

SARS-COV2 placentitis and pregnancy outcome: A multicentre experience during the Alpha and early Delta waves of coronavirus pandemic in England.

Background: Pregnant women with SARS-CoV-2 infection experience higher rates of stillbirth and preterm birth. A unique pattern of chronic histiocytic intervillositis (CHI) and/or massive perivillous fibrin deposition (MPFD) has emerged, coined as SARS-CoV-2 placentitis. Methods: The aim of this study was to describe a cohort of placentas diagnosed with SARS-CoV-2 placentitis during October 2020-March 2021. Cases with a histological diagnosis of SARS-CoV-2 placentitis and confirmatory immunohistochemistry were reported. Maternal demographic data, pregnancy outcomes and placental findings were collected. Findings: 59 mothers delivered 61 infants with SARS-CoV-2 placentitis. The gestational age ranged from 19 to 41 weeks with most cases (78.6%) being third trimester. 30 infants (49.1%) were stillborn or late miscarriages. Obese mothers had higher rates of pregnancy loss when compared with those with a BMI <30 [67% (10/15) versus 41% (14/34)]. 47/59 (79.7%) mothers had a positive SARS-CoV-2 PCR test either at the time of labour or in the months before, of which 12 (25.5%) were reported to be asymptomatic. Ten reported only CHI, two cases showed MPFD only and in 48 placentas both CHI and MPFD was described. Interpretation: SARS-CoV2 placentitis is a distinct entity associated with increased risk of pregnancy loss, particularly in the third trimester. Women can be completely asymptomatic and still experience severe placentitis. Unlike 'classical' MPFD, placentas with SARS-CoV-2 are generally normal in size with adequate fetoplacental weight ratios. Further work should establish the significance of the timing of maternal SARS-CoV-2 infection and placentitis, the significance of SARS-CoV2 variants, and rates of vertical transmission associated with this pattern of placental inflammation. Funding: There was not funding associated with this study.

A pragmatic evidence-based approach to post-mortem perinatal imaging.

Post-mortem imaging has a high acceptance rate amongst parents and healthcare professionals as a non-invasive method for investigating perinatal deaths. Previously viewed as a 'niche' subspecialty, it is becoming increasingly requested, with general radiologists now more frequently asked to oversee and advise on appropriate imaging protocols. Much of the current literature to date has focussed on diagnostic accuracy and clinical experiences of individual centres and their imaging techniques (e.g. post-mortem CT, MRI, ultrasound and micro-CT), and pragmatic, evidence-based guidance for how to approach such referrals in real-world practice is lacking. In this review, we summarise the latest research and provide an approach and flowchart to aid decision-making for perinatal post-mortem imaging. We highlight key aspects of the maternal and antenatal history that radiologists should consider when protocolling studies (e.g. antenatal imaging findings and history), and emphasise important factors that could impact the diagnostic quality of post-mortem imaging examinations (e.g. post-mortem weight and time interval). Considerations regarding when ancillary post-mortem image-guided biopsy tests are beneficial are also addressed, and we provide key references for imaging protocols for a variety of cross-sectional imaging modalities.

Outcomes of paediatric kidney transplant recipients using the updated 2013/2017 Banff histopathological classification for antibody-mediated rejection.

BACKGROUND: After the major changes with regard to acute and chronic ABMR in the Banff classification initiated in 2013, there has been an improvement in diagnosing antibody-mediated rejection (ABMR) in adult studies but no data have been published in the paediatric population. METHODS: We assessed 56 paediatric kidney transplant biopsies due to kidney dysfunction in patients with donor-specific antibodies (DSA) in a retrospective single-centre study between January 2006 and March 2012. The results were compared with 2003/2007 Banff classification noting the subsequent 2017 and 2019 modifications do not change the 2013 Banff classification with regard to acute antibody-mediated rejection (apart from the addition of gene transcripts/classifiers that do not affect our analysis). RESULTS: Following the 2013 Banff classification, there were seven cases (12.5%) diagnosed with ABMR that would have been misclassified when applying the 2003/2007 classification. Evaluating the histological features of all ABMR-related cases, we report the importance of v- (intimal arteritis) and t- (tubulitis) lesions: absence of v- and t- lesions in the biopsy is related to significantly higher kidney allograft survival (OR 7.3, 95%CI 1.1-48.8, p = 0.03 and OR 5.3, 95%CI 1.2-25.5, p = 0.04 respectively). Moreover, absence of t- lesions was associated with significantly fewer rejection episodes the year after the initial biopsy (OR 5.1, 95%CI 1.4-19.8, p = 0.01). CONCLUSIONS: Our study supports that the updated 2013 Banff classification shows superior clinicopathological correlation in identifying ABMR in paediatric kidney transplant recipients. Our results can be extrapolated to the recently updated 2019 Banff classification.

Biopsy-proven Henoch-Schönlein purpura nephritis: a single center experience.

BACKGROUND: Knowledge on normal progress and treatment of Henoch-Schönlein purpura nephritis (HSPN) is limited. This study reviews outcome, clinical, pathological, and therapeutic factors affecting the prognosis of HSPN patients. METHODS: Forty-nine children with biopsy-confirmed HSPN diagnosed between September 2008 and 2018 were included. Demographics, clinical and laboratory data, treatment, and outcome were recorded at the time of biopsy, 3, 6, 12, and 24 months and at last visit. Clinical outcome was graded according to Meadow's criteria. RESULTS: The median age at time of biopsy was 10.1 years (IQR:5.7) and female/male ratio 24/25. At presentation, 40.8% of patients had nonnephrotic proteinuria, 18.4% nephrotic syndrome (NS), 4.1% nephritic syndrome (NephrS), and 36.7% NephrS+NS. There were 11 patients with an estimated glomerular filtration rate below 90 ml/min/1.73 m2. Biopsy specimens were classified according to International Study of Kidney Diseases in Children (ISKDC) and Oxford Classification MEST-C scoring systems. Forty-one patients received angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, 37 patients steroids, and 35 patients other immunosuppressive medications. At last visit, 24 patients had stage 1 chronic kidney disease (CKD), three stage 2 CKD, and two had stage 5 CKD. Neither clinical parameters nor ISKDC biopsy grade or treatment modalities effected the final outcome. The Oxford classification showed significantly increased segmental glomerulosclerosis in patients with unfavorable outcome. Favorable outcome was associated with shorter time from kidney involvement to biopsy and start of treatment. CONCLUSION: A large proportion of patients continued to show signs of CKD at last follow-up while only a small proportion developed stage 5 CKD.

Plaque-like Myofibroblastic Tumor: 2 Cases of This Unusual Dermal Tumor Which Occurs in Infancy and Early Childhood.

Plaque-like myofibroblastic tumor (PLMT) is a rare dermal spindle cell tumor which occurs in infancy or childhood within the first 4 years of life. The tumor is often pruritic and mostly presents on the lower back. We describe 2 cases with characteristic clinical and histological features of this entity, thus adding to the 10 cases which have so far been reported. Histologically, the lesion resembles a dermatofibroma. However, diffuse and uniform immunohistochemical staining with smooth muscle actin favors a myofibroblastic lineage. PLMT should be considered in the differential diagnosis of a dermal spindle cell tumor in the pediatric age-group.