Angiomatoid fibrous histiocytoma: A case of local recurrence and metastases to loco-regional lymph nodes that responded to chemotherapy.

Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumour with intermediate malignant potential. We report the case of a patient with local recurrence of AFH in two locations and lymph node metastases 18 months after primary surgical excision. The patient was treated with six cycles of ifosfamide and doxorubicin chemotherapy and a further three courses of ifosfamide monotherapy. Reassessment imaging showed a good response to chemotherapy with reduction in size of the two tumours of local recurrence and the lymph node metastases. This case demonstrates that AFH can respond to chemotherapy, even though it is rarely used.

Phenotypic variations of cartilage hair hypoplasia: granulomatous skin inflammation and severe T cell immunodeficiency as initial clinical presentation in otherwise well child with short stature.

We report a child with short stature since birth who was otherwise well, presenting at 2.8 years with progressive granulomatous skin lesions when diagnosed with severe T cell immunodeficiency. When previously investigated for short stature, and at the time of current investigations, she had no radiological skeletal features characteristics for cartilage hair hypoplasia, but we found a disease causing RMRP (RNase mitochondrial RNA processing endoribonuclease) gene mutation. Whilst search for HLA matched unrelated donor for haematopoietic stem cell transplantation (HSCT) was underway, she developed rapidly progressive EBV-related lymphoproliferative disorder requiring laparotomy and small bowel resection, and was treated with anti-B cell monoclonal antibody and eventually curative allogeneic HSCT. Screening for RMRP gene mutations should be part of immunological evaluation of patients with 'severe and/or combined' T cell immunodeficiency of unknown origin, especially when associated with short stature and regardless of presence or absence of radiological skeletal features.

Interval appendectomy in children clinical outcomes, financial costs and patient benefits.

BACKGROUND: Elective interval appendectomy (IA) is traditionally advocated for the management of appendiceal mass (AM) in children. Surgeons have debated the evidence and 'risks' vs. 'benefits' to support IA. There are currently no randomised controlled trials and guiding best practice and financial costings for IA are lacking. We herein report clinical outcomes, patient benefits and tariff charges linked with the provision of IA at a regional UK paediatric surgical centre. METHODS: Hospital case records of patients with AM were identified using pathology records and hospital admission codes during a 15-year period (1997-2011). Tariff costs (£ Sterling) were calculated for all admissions during the era 2007-2011. RESULTS: 69 children were admitted with AM (61% female, median age 10.5 years, range 2.1-16 years). Median initial hospital stay with resolution of symptoms was 8 days (range 3-14 days). 61 children (88%) had elective IA (median interval 76 days, range 29-230 days). Eight (12 %) patients required emergency readmission for early appendectomy (median interval 21 days, range 6-51 days). Hospital stay for emergency readmission appendectomy in these children was significantly longer than IA (median 6 vs. 3 days, p < 0.01). Laparoscopic appendectomy vs. 'open' appendectomy was associated with shorter length of stay in the IA cohort (median 3 vs. 2 days p < 0.01). No intra-operative morbidity was recorded in the study with only a single case developing a post-operative wound infection. Median cost for IA was £1,936. Costings were higher in the emergency appendectomy group-£2,171 vs. 1,936; p = 0.09, NS. CONCLUSION: Only 12% of children at this centre develop recurrent appendicitis after primary admission with AM. Interval and emergency appendectomy were associated with low morbidity. Parents should be informed that IA may be 'non essential' surgery. Paediatric surgeons not routinely advocating IA can potentially save the NHS £1,936 per patient. Future randomised studies are warranted to confirm or refute these findings.

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.

Childhood autoimmune liver disease: indications and outcome of liver transplantation.

BACKGROUND: Graft rejection and disease recurrence are well-recognized complications of liver transplantation (LT) for autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (AISC). We describe indications and outcome of LT for childhood AIH and AISC. PATIENTS AND METHODS: Twenty-year retrospective review of a cohort of children (n = 101) with AIH, AISC, or AIH/sclerosing cholangitis overlap syndrome from a single center. RESULTS: AIH type 1 (AIH1, n = 67) was more common than AIH type 2 (AIH2, n = 18), AISC (n = 8), or overlap syndrome (n = 8). Overall, 18 patients (18%) required LT, the indications being failure of medical therapy (n = 16) and fulminant liver failure (n = 2). Patients with AIH who required LT had a more prolonged prothrombin time at presentation compared with those who did not undergo transplantation (P = 0.01). Patients with AIH1 who received LT had a lower aspartate transaminase (P = 0.009) and alanine transaminase (P = 0.02) levels at initial diagnosis compared with those with AIH1 who did not undergo transplantation. Post-LT, 11 patients (61%) had 18 episodes of rejection, most were steroid sensitive. Disease recurrence was observed in 7 patients (39%, median duration post-LT 33 months), more common in AIH2 (80% recurrence rate), and those taking cyclosporine (71%, 5/7 patients) compared with those taking tacrolimus (18%, 2/11 patients; P < 0.05) and in 3 of 3 children who did not have maintenance steroids post-LT. The overall 5- and 7-year post-LT survival rate was 94% and 88%, respectively. CONCLUSIONS: LT is a good therapeutic option for progressive AIH and AISC, although recurrence of the primary autoimmune process limits the outcome.

Is tonsillectomy mandatory for asymmetric tonsils in children? A review of our diagnostic tonsillectomy practice and the literature.

INTRODUCTION: Diagnostic tonsillectomy is performed to exclude malignancy. It is associated with a post-operative hemorrhage rate of 3.5%, (1) which is more dangerous in small children. No previous case series for asymmetrical tonsils have detected tonsil lymphoma.(2-6) We aimed to review our local diagnostic tonsillectomy practice. METHOD: The authors reviewed the clinical notes and histological results for all diagnostic tonsillectomies carried out from June 2013 to June 2016. RESULTS: We recorded data for 168 patients. There were four post-operative bleeds and one return to theatre. Bilateral tonsillectomies accounted for 152 operations (90.5%). Lymphoid hyperplasia accounted for 95% of histological diagnosis with no malignancies found. Pre-operative tonsil grading demonstrated no statistically significant association with histological tonsil weight difference (ANOVA p = 0.10). Actinomyces colonisation had little affect on tonsil weight difference when we compared patients with bilateral colonisation and no colonisation (t-test p = 0.540) and between tonsils in patients with unilateral tonsil Actinomyces colonisation (paired t-test p = 0.448). Recurrent tonsillitis was more prevalent in patients with Actinomyces colonisation than OSA/sleep disordered breathing (39% vs 15%). CONCLUSION: A literature search yielded five smaller case series of palatine tonsil asymmetry in children with no malignancy found.(2-6) Case-control studies report tonsillar asymmetry as the most common presenting symptom (73%) in tonsillar lymphoma.(7) This enlargement usually occurs rapidly within 6 weeks with new obstructive or systemic B-type symptoms.(3) A Turkish epidemiological study found asymmetrical tonsils in 1.7% of the healthy paediatric population.(8) We therefore estimate there to be over 210,000 children with asymmetrical tonsils in the UK. With an unreliable grading system, we believe asymmetrical tonsils in isolation, unchanged for over 6 weeks may not warrant tonsillectomy.

Management and outcome of neuroendocrine tumours of the appendix-a two centre UK experience.

BACKGROUND: Neuroendocrine tumours (NET) of the appendix are rare histopathological neoplasms detected following operation for appendicitis in childhood. The role (if any) for radical surgery notably right hemicolectomy (RHC) has often reflected the 'expert opinion' of adult general surgeons with wider experience of managing NET lesions of the gastrointestinal tract. Critical decisions have focused on (a) tumour size, (b) histology, (c) tumour location/invasion and (d) positive lymph nodes. Against this background we report the clinical outcome of children with 'incidental' appendix carcinoid tumours managed at two regional UK paediatric surgery centres. A critical review of the literature is additionally provided in an effort to define contemporary patterns of care in paediatric surgical practice. METHODS: Hospital records and pathology database(s) identified 27 patients at two UK centres with a confirmed histological diagnosis of appendix NET lesions during January 1997-January 2013. A PUBMED and EMBASE search strategy-(English language publications only), 1975-present, was performed to gather information on all patients younger than 20years at primary diagnosis with NET appendix tumours to review their management and outcomes. RESULTS: All 27 patients treated at the two institutions had acute appendicitis including 3 cases presenting with an appendix mass. Twenty-five underwent appendicectomy with two having interval operations. Tumours had a maximum diameter of 2-18mm (median 9mm) with 73% of lesions located at the appendix tip. Fourteen (52%) had tumour invading the mesoappendix. All patients underwent appendicectomy only with no single case having RHC or additional surgery. Surveillance studies (5HIAA, chromogranin-A) and imaging including ultrasound or CT were deployed in a minority of patients revealing no abnormality. All 27 cases are alive and well-(mean follow up 5years; range: 9months-16years). The literature highlights varied management strategies and no recorded fatalities with radical surgery in children largely evolving from adult surgical practice. CONCLUSIONS: This study confirms that paediatric patients with 'incidental' NET tumours of the appendix have an excellent prognosis. Consensus guidelines should ideally be developed by paediatric oncology surgeons to avoid unnecessary radical surgery in many otherwise healthy children.

Gastrointestinal presentation and outcome of perinatal cytomegalovirus infection.

A term infant presented at birth with bilious vomiting and abdominal distension. Multiple investigations were undertaken, including two laparotomies and a rectal biopsy, as no obvious cause for his symptoms could be found. This included testing for human cytomegalovirus (CMV) infection as part of a TORCH screen, which was negative at 10 days of age. However, a repeat screen at 3 weeks of age demonstrated positive findings of CMV in both urine and blood PCR. This subsequently led to the diagnosis of gastrointestinal pseudoobstruction associated with perinatal CMV infection. This case is of interest though there is limited information regarding the recognition of gastrointestinal symptoms in relation to CMV infection. This report aims to highlight our experience with an infant with perinatal CMV infection and severe gastrointestinal symptoms.

The testicular regression syndrome--do remnants require routine excision?

AIM: Excision of testicular remnants is debatable in the scenario where hypoplastic vas and vessels can be seen entering a closed internal ring during laparoscopy for impalpable testes. We aimed to establish how frequently excised remnants have identifiable testicular tissue and, hence, malignant potential. METHODS: This study is a retrospective review of all excised testicular remnants in children with impalpable testis. Specimens that were excised for indications other than testicular regression syndrome were excluded. Pathology reports of excised specimens were reviewed, and the presence of multiple histologic features was noted. Histologic confirmation of testicular/paratesticular tissue required the presence of 1 or more of the following: seminiferous tubules, germ cells, Sertoli cells, Leydig cells, vas deferens, or epididymal structures. Malignancy potential was defined by the presence of germ cells or seminiferous tubules. All patients with seminiferous tubules were further examined by a single histopathologist. RESULTS: A total of 208 testicular remnants from 206 children were excised over the 11-year period (1999-2009). Histologic evidence confirmed excision of testicular/paratesticular tissue in 180 cases (87%). Seminiferous tubules were noted in 27 (15%), and germ cells were present in 19 (11%) cases. CONCLUSION: Viable germ cells were found in 11% of examined remnants, which, in our opinion, justifies their removal.

Apoptosis in chronic viral hepatitis parallels histological activity: an immunohistochemical investigation using anti-activated caspase-3 and M30 cytodeath antibody.

Apoptosis is implicated as a major pathogenic mechanism in chronic hepatitis B and C. Previous studies of the relationship between apoptotic rates and histological necroinflammatory activity have produced conflicting results. Hepatocyte apoptosis was assessed in liver tissue from 32 cases of chronic viral hepatitis, seven cases of hepatocellular carcinoma (HCC) and six cases of steatohepatitis as non-viral disease controls and eight cases of control liver. Apoptotic rates were measured using H&E morphological assessment and immunohistochemical staining with antibodies to activated caspase-3 and M30. Histological necroinflammatory activity of viral hepatitis cases was scored using the Knodell scoring system, and the cases were divided according to their score into group 1 (mean 2.43 +/- 0.48) and group 2 (mean 7.80 +/- 0.49). Apoptotic indices were significantly higher in group 2 than group 1 using H&E (11.53 +/- 2.70 vs. 0 +/- 0, P=0.015) and activated caspase-3 (22.01 +/- 5.27 vs. 1.79 +/- 1.79, P=0.03) methods but were not significantly higher with M30 (3.80 +/- 1.74 vs. 0 +/- 0, P=0.207). Apoptotic scores using an antibody to activated caspase-3 are significantly higher in cases of chronic viral hepatitis with greater histological necroinflammatory scores, supporting a central role for apoptosis in disease pathogenesis. This method offers an alternative to routine histological assessment for measuring disease activity.