Cascade Fumarate Hydratase mutation screening allows early detection of kidney tumour: a case report.

BACKGROUND: Fumarate hydratase (FH) deficiency is a rare autosomal recessive disorder which results in a major defect in cellular metabolism. It presents in infancy with progressive encephalopathy, hypotonia, seizures and failure to thrive and is often fatal in childhood. It is caused by mutations in the FH gene (1q42.1) that result in deficiency of the citric acid cycle enzyme fumarate hydratase, resulting in accumulation of fumaric acid. Heterozygous germline mutations in the FH gene predispose to an aggressive autosomal dominant inherited early-onset kidney cancer syndrome: hereditary leiomyomatosis and renal cell cancer (HLRCC). CASE PRESENTATION: Cascade FH mutation screening enabled the early diagnosis of a renal tumour in an asymptomatic parent of a child with fumarate hydratase deficiency, resulting in timely and possibly life-saving treatment. CONCLUSION: While the theoretical risk of kidney cancer in parents of children with recessive fumarate hydratase deficiency is well recognized, to our knowledge this is the first report of a kidney tumour being detected in a parent by screening performed for this indication. This underscores the importance of offering lifelong kidney surveillance to such parents and other heterozygous relatives of children born with fumarate hydratase deficiency.

Paneth cell metaplasia in newly diagnosed inflammatory bowel disease in children.

BACKGROUND: Paneth cell metaplasia (PCM) is well described in adults but little is known about the distribution of colonic Paneth cells and the occurrence of PCM in a paediatric population. The aim of this study is to determine whether Paneth cell hyperplasia or metaplasia characteristically occurs in the colons of children with newly diagnosed idiopathic inflammatory bowel disease (IBD). METHODS: We retrospectively reviewed colonic series from 28 new diagnoses of paediatric IBD at a tertiary referral centre, and from a further 14 children with IBD-like symptoms whose colonic biopsies and ancillary investigations were normal. Paneth cells were counted at 6 anatomical sites in the colon, and at each site acute and chronic inflammation were assessed semi-quantitatively and the presence or absence of crypt architectural distortion and eosinophilia was documented. RESULTS: In control, ulcerative colitis (UC) and Crohn's disease (CD) groups there was a gradient of decreasing Paneth cell numbers from caecum to rectum. Paneth cells were not seen in the distal colon in the control group, but they were present there in 11 of 13 patients with ulcerative colitis and 14 of 15 with Crohn's disease. Only patients with IBD showed Paneth cell hyperplasia, assessed as more than 10 Paneth cells per 10 well-oriented crypts at any site. There was a statistically significant increase in Paneth cells in the caecum, ascending, transverse and descending colon in UC and in the ascending, transverse, descending and sigmoid colon in CD compared with controls. There was no significant difference between UC and CD. There was no correlation between the site of PCM and acute or chronic inflammation, crypt distortion or eosinophilia. CONCLUSION: Paneth cells are found in the proximal but not the distal colon in otherwise normal paediatric colonic series. A high proportion of UC and CD patients show PCM in the distal colon. This is present early in the disease and does not correlate with histological features of chronicity.

Characteristics of Coronial Autopsy Cases in the London Area of the United Kingdom, Pre and Post COVID-19 Lockdown.

Introduction: In order to reduce transmission of COVID-19, in March 2020 the UK national and devolved governments imposed restrictions including spatial distancing, stay-at-home orders, and travel restrictions. The aim of this study is to compare the characteristics of cases referred to the Coronial system for autopsy in the months before and during the lockdown period. Methods: In all, 580 autopsy cases, performed in the London area between January and June 2020 were included in the study. Results: In the postlockdown period, there was an increase in the proportion of black individuals referred for autopsy, which just attained statistical significance (p = 0.047). The proportion of decomposed bodies submitted for examination was significantly increased (p = 0.011). The study did not show a significant increase in the proportion of out-of-hospital (community) deaths, traumatic deaths, or deaths due to alcohol or drug abuse or overdose. Conclusion: The study shows no evidence that COVID-19 preventative measures led to a change in the causes of death referred to the Coroner, except, of course, for COVID-related deaths. The proportion of black people among subjects for autopsy increased, probably because of a relatively higher incidence of COVID deaths among this group. Decomposed subjects were more common, probably due to social isolation.

Retrogressive development: transcendental anatomy and teratology in nineteenth-century Britain.

In 1855 the leading British transcendental anatomist Robert Knox proposed a theory of retrogressive development according to which the human embryo could give rise to ancestral types or races and the animal embryo to other species within the same family. Unlike monsters attributed to the older theory of arrested development, new forms produced by retrogression were neither imperfect nor equivalent to a stage in the embryo's development. Instead, Knox postulated that embryos contained all possible specific forms in potentia. Retrogressive development could account for examples of atavism or racial throwbacks, and formed part of Knox's theory of rapid (saltatory) species change. Knox's evolutionary theorizing was soon eclipsed by the better presented and more socially acceptable Darwinian gradualism, but the concept of retrogressive development remained influential in anthropology and the social sciences, and Knox's work can be seen as the scientific basis for theories of physical, mental and cultural degeneracy.

Inflammatory myofibroblastic tumour arising in the adrenal gland: a case report.

INTRODUCTION: Inflammatory myofibroblastic tumour arising in the adrenal gland is exceptional. As far as we are aware, there have been only three previous reports in the literature. We report a fourth case. CASE PRESENTATION: A 29-year-old Caucasian man presented with upper quadrant pain due to a 15cm heterogenous adrenal mass that displaced his liver. He underwent an open right adrenalectomy. Histopathological examination showed the mass to be an inflammatory myofibroblastic tumour, a histologically distinctive lesion composed of myofibroblasts, plasma cells, lymphocytes and histiocytes. Ten months later he is well with no sign of recurrence. CONCLUSIONS: The lesion was indistinguishable on imaging from an adrenal cortical tumour. Surgical treatment is the same but inflammatory myofibroblastic tumour carries a favourable prognosis.

Diagnosing eosinophilic colitis: histopathological pattern or nosological entity?

Reports of "eosinophilic colitis"-raised colonic mucosal eosinophil density in patients with lower gastrointestinal symptoms-have increased markedly over the last fifteen years, though it remains a rarity. There is no consensus over its diagnosis and management, and uncertainty is compounded by the use of the same term to describe an idiopathic increase in colonic eosinophils and an eosinophilic inflammatory reaction to known aetiological agents such as parasites or drugs. In patients with histologically proven colonic eosinophilia, it is important to seek out underlying causes and careful clinicopathological correlation is advised. Because of the variability of eosinophil density in the normal colon, it is recommended that histological reports of colonic eosinophilia include a quantitative morphometric assessment of eosinophil density, preferably across several sites. Few reported cases of "eosinophilic colitis" meet these criteria. As no correlation has been shown between colonic eosinophil density and symptoms in older children or adults, it is suggested that treatment should be directed towards alleviation of symptoms and response to treatment assessed clinically rather than by histological estimates of intramucosal eosinophils.

Fibro-osteochondroma of the uterus.

A case of a uterine fibro-osteochondroma in a 61-year-old woman with postmenopausal bleeding was presented. Ultrasound revealed a calcified lesion in the posterior wall of the uterus and a hysterectomy was performed. Histopathologic examination showed a well-circumscribed triphasic tumor composed of peripheral lobules of mature hyaline cartilage and foci of trabecular bone with a core of loosely arranged fibroblast-like, spindle cells. This is the second reported case of fibro-osteochondroma, which has been described only in the uterus. Diagnosis requires thorough histopathologic examination to exclude metaplasia within a leiomyoma or uterine sarcoma. It is histologically benign and complete excision should be curative.