Gino R Somers

SickKids · Department of Paediatric Laboratory Medicine (DPLM)

Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome associated with germline TP53 pathogenic variants. Here, we perform whole-genome sequence (WGS) analysis of tumors from 22 patients with TP53 germline pathogenic variants. We observe somatic mutations affecting Wnt, PI3K/AKT signaling, epigenetic modifiers and homologous reco...

We conducted integrative somatic–germline analyses by deeply sequencing 864 cancer-associated genes, complete genomes and transcriptomes for 300 mostly previously treated children and adolescents/young adults with cancer of poor prognosis or with rare tumors enrolled in the SickKids Cancer Sequencing (KiCS) program. Clinically actionable variants w...

Background: Food allergy affects up to 10% of the pediatric population. Despite ongoing efforts, treatment options remain limited. Novel models of food allergy are needed to study response patterns downstream of IgE-crosslinking and evaluate drugs modifying acute events. Here, we report a novel human ex vivo model that displays acute, allergen-spe...

Background: Food allergy affects up to 8% of the pediatric population. Despite ongoing efforts, treatment options remain limited. Novel models of food allergy are needed to study response patterns downstream of IgE-crosslinking and evaluate drugs modifying acute events. Here, we report a novel human ex vivo model that displays acute, allergen-speci...

Objectives: Sarcomas are mesodermal cancers of bone and soft tissue of which there are >60 malignant varieties, many of which can be difficult to diagnose or subtype using traditional histopathology. A universal molecular definition of sarcoma types would therefore be an invaluable tool to the diagnostic pathologist. RNA has the potential to offer...

Background Workload measurement is important to help determine optimal staffing and workload distribution for pathology laboratories. The Level 4 Equivalent (L4E) System is the most widely used Anatomical Pathology (AP) workload measurement tool in Canada. However, it was initially not developed with subspecialties in mind. Methods In 2016, a Pan-...

Glial heterotopia are rare, benign tumors most commonly found around the nasal cavity, but extra-nasal heterotopias have also been observed. We present an anatomically rare case of glial heterotopia overlying the left occipital condyle. Excisional biopsy was performed and histopathology was consistent with glial heterotopia. This case report discus...

Importance: Prompt recognition of a child with a cancer predisposition syndrome (CPS) has implications for cancer management, surveillance, genetic counseling, and cascade testing of relatives. Diagnosis of CPS requires practitioner expertise, access to genetic testing, and test result interpretation. This diagnostic process is not accessible in a...

Background Embryonal tumours with multi-layered rosettes (ETMRs) are a newly recognised, rare paediatric brain tumour with alterations of the C19MC microRNA locus. Due to varied diagnostic practices and scarce clinical data, disease features and determinants of outcomes for these tumours are poorly defined. We did an integrated clinicopathological...

Diseases of the thyroid occur frequently in children and range from developmental abnormalities through to inflammatory diseases, benign neoplasms and highly aggressive carcinomas. Papillary thyroid carcinoma is the most common malignancy arising within the thyroid in the pediatric population, and this entity is discussed at length. New concepts, i...

ETMR, an aggressive disease characterised by C19MC alterations, were previously categorised as various histologic diagnoses. The clinical spectrum and impact of conventional multi-modal therapy on this new WHO diagnostic category remains poorly understood as a majority of ~200 cases reported to date lack molecular confirmation. We undertook compreh...

Undifferentiated sarcomas of soft tissue and bone have been defined as tumors with no identifiable morphologic, immunohistochemical, or molecular features indicating tumor cell origin. In young patients, these tumors frequently have a round or spindle cell morphology. Recently described recurrent translocations within this category have led to the...

BACKGROUND - Survival of children with relapsed cancer remains unacceptably low. Cancer genomic testing may enhance diagnostic accuracy, identify new therapeutic options, and improve understanding of tumor origins and continued evolution. METHODS - We deeply sequenced 864 cancer-associated genes, together with genomes and transcriptomes, for 200 p...

Primary hyperparathyroidism is a condition that occurs infrequently in children. Parathyroid carcinoma as the underlying cause of hyperparathyroidism in this age group is extraordinarily rare with only a few cases reported in the literature. We present a 13‐year‐old boy with musculoskeletal pain who was found to have brown tumors from primary hyper...

Aim of the study Appendiceal carcinoid (neuroendocrine tumor or NET) is a rare neuroendocrine neoplasm often found incidentally following appendectomy for appendicitis. Surgery for appendicitis is currently under scrutiny and children are increasingly managed conservatively with antibiotics alone. Herein, we aimed to review our experience with the...

BACKGROUND Pineoblastoma (PB) is a rare but aggressive pediatric brain tumour arising from the pineal gland. Overall survival rates are estimated at 50–70%, with younger patients (< 5 years old) faring much worse (15–40%) despite intensive treatment regimens. Although germline RB1 and DICER1 alterations have been reported in a small proportion of P...

Chromosomal rearrangements resulting in fusion transcripts have been reported in precursor B-cell acute lymphoblastic leukemia (B-ALL). Identification of fusion events is critical in the diagnosis of B-ALL. In this study, we used nanoString technology to design, validate, and evaluate a multiplex panel for detection of B-ALL fusion transcripts. Fif...

Over 10% of children with Wilms tumour (WT) have an underlying cancer predisposition syndrome (CPS). Cognizant of increasing demand for genetic evaluation and limited resources across healthcare settings, there is an urgent need to rationalize genetic referrals for this population. The MIPOGG study, a Canadian multi‐institutional initiative, aims t...

Background, Rationale and Experimental Approach Oncogenic fusions are generated via chromosomal rearrangements resulting in an exchange of coding or regulatory DNA sequences. These mutations play an important role in disease onset and subsequent cancer progression, however the exact timing and mechanisms by which they arise are unknown. Through the...

Background, Rationale and Experimental Approach Oncogenic fusions are generated via chromosomal rearrangements resulting in an exchange of coding or regulatory DNA sequences. These mutations play an important role in disease onset and subsequent cancer progression, however the exact timing and mechanisms by which they arise are unknown. Through the...

Long before the classification of vascular anomalies from the International Society for the Study of Vascular Anomalies (ISSVA) provided a framework to differentiate vascular anomalies, otherwise known as vascular birthmarks, it was recognized that patients with such lesions can present with acute life-threatening hemostatic and/or thrombotic compl...

This case highlights the management of orbital rhabdomyosarcoma in a child with Li Fraumeni syndrome (LFS). Treatment with chemotherapy and eventual orbital exenteration enabled margin-free control of the tumor. Radiation therapy was avoided to reduce the risk of inducing additional malignancy. Reactive orbital hyperostosis was observed postoperati...

Looping together genes in cancer A subset of human cancers are characterized by aberrant fusion of two specific genes. In some cases, the activity of the resultant fusion protein drives tumor growth. Most fusion genes in cancer appear to arise from simple reciprocal chromosomal translocations. Anderson et al. found that the characteristic fusion ge...

Background: NanoString technology is an innovative barcode-based system that requires less tissue than traditional techniques and can test for multiple fusion transcripts in a single reaction. The objective of this study was to determine the utility of NanoString technology in the detection of sarcoma-specific fusion transcripts in pediatric sarco...

‘Cepacia syndrome’ caused by Burkholderia cepacia complex and often found to be associated in patients with cystic fibrosis, carries a high mortality rate. It is rare for Burkholderia multivorans, a species within the Burkhoderia cepacia complex to cause ‘cepacia syndrome’ even among the cystic fibrosis patients. This is the first reported fatal ca...

Pineoblastoma (PB) is a rare but aggressive pediatric brain tumour arising from the pineal gland. Outcomes remain dismal with long-term survival rates between 10–40% despite intensive treatment regimens. Although germline RB1 and DICER1 alterations have been reported in a small proportion of PB, the clinical significance of such alterations and the...

CIC-rearranged sarcomas rarely occur in visceral organs including the kidney. The most common fusion partner with CIC is the DUX4 gene, but variant fusion partners have also been reported. Herein, we describe the clinicopathologic features and comprehensive molecular profiling of 4 cases of primary renal CIC-rearranged sarcomas. All cases occurred...

Clinico-pathological studies that focus on sudden unexpected death (SUD) in the neonatal period are rare. The objective of this study was to elucidate the frequency and pathological spectrum of anatomical causes of death (CODs), found in the setting of sudden unexpected death in neonates (SUD-N), and to correlate the COD with premortem circumstanti...

Mucormycosis is a rare and potentially life‐threatening infection, typically affecting immunocompromised hosts. We report a case of an adolescent boy who developed primary isolated cutaneous mucormycosis in the early period following kidney transplantation. Surgical excision was performed using intraoperative fungal staining to obtain clear margins...

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous condition that predisposes to numerous proliferative lesions, including perivascular epithelioid cell tumors (PEComas), such as lymphangioleiomyomatosis (LAM) and angiomyolipomas, and rare neuroendocrine neoplasms. We describe herein a TSC2-harboring tuberous sclerosis patient...

Osteogenic sarcoma (OS) is the most common malignant bone tumor in children and adolescents. Despite advances in molecular genetic characterization of pediatric and adult tumors, the diagnosis of OS still depends almost entirely on light microscopy. The lack of consistent genetic changes in OS has greatly hindered the development of any diagnostic...

Coenzyme Q10 (CoQ10) or ubiquinone is one of the two electron carriers in the mitochondrial respiratory chain which has an essential role in the process of oxidative phosphorylation. Defects in CoQ10 synthesis are usually associated with the impaired function of CoQ10–dependent complexes I, II and III. The recessively transmitted CoQ10 deficiency h...

Purpose To retrospectively define the strength of association between testicular microlithiasis and testicular neoplasia in a large geographically diverse pediatric population. Materials and Methods Retrospective review of scrotal ultrasonographic (US) examination reports and pathology specimens obtained between January 2000 and May 2014 at six aca...

The autopsy is an integral part of the service of a large academic pathology department. Timely reporting is central to providing good service and is beneficial for many stakeholders, including the families, the clinical team, the hospital, and the wider community. The current study aimed to improve hospital-consented autopsy reporting times (turna...

Background: Pediatric intestinal failure (PIF) is a life-altering chronic condition with significant morbidity and mortality. Omegaven® therapy has been used to treat children with advanced intestinal failure associated liver disease. Our objective was to determine the evolution of hepatic fibrosis in PIF patients who received Omegaven® and descri...

We recently reported that atypical teratoid rhabdoid tumors (ATRTs) comprise at least two transcriptional subtypes with different clinical outcomes; however, the mechanisms underlying therapeutic heterogeneity remained unclear. In this study, we analyzed 191 primary ATRTs and 10 ATRT cell lines to define the genomic and epigenomic landscape of ATRT...

Translocation-associated renal cell carcinoma (RCC) is a distinct subtype of RCC with gene rearrangements of the . TFE3 or . TFEB loci. The . TFE3 gene is located at Xp11 and can fuse to a number of translocation partners, resulting in high nuclear expression of TFE3 protein. TFE3 immunostaining is often used as a surrogate marker for a . TFE3 tran...

Oral squamous cell carcinoma (OSCC) is extremely rare in patients younger than 20 years of age. We present here a case of OSCC of the maxillary alveolar ridge in an otherwise healthy 8-year-old patient. The clinicohistologic presentation was not typical for mucosal SCC, and the possibility of an intrabony origin from the odontogenic epithelium was...

The American Journal of Gastroenterology is published by Nature Publishing Group (NPG) on behalf of the American College of Gastroenterology (ACG). Ranked the #1 clinical journal covering gastroenterology and hepatology*, The American Journal of Gastroenterology (AJG) provides practical and professional support for clinicians dealing with the gastr...

Primary effusion lymphoma (PEL) is a rare lymphoma that occurs more frequently in immunocompromised adults and has a poor survival. We report a 9-year-old female with combined immunodeficiency with an Epstein-Barr virus positive/human herpes virus 8 negative PEL-like lymphoma. The treatment with systemic chemotherapy for non-Hodgkin lymphoma, zidov...

Tufted angioma is an uncommon benign vascular tumor that typically is noted during infancy or childhood, with variable clinical presentation. We report the case of an infant with a tufted angioma initially presenting as a port-wine stain–like patch of the left cheek.

The periosteum contributes to bone repair and maintenance of cortical bone mass. In contrast to the understanding of bone development within the epiphyseal growth plate, factors that regulate periosteal osteogenesis have not been studied as intensively. Osteofibrous dysplasia (OFD) is a congenital disorder of osteogenesis and is typically sporadic...

Background: Few clinico-pathological (C-P) studies focus on sudden unexpected death (SUD) in the neonatal period, despite generally accepted notions of an increased likelihood of finding an anatomic cause of death (COD), when compared to SUD in older infants (SUD-I). The objective of this study was to elucidate the nature of SUD in neonates (SUD-N)...

Children with Langerhans cell histiocytosis (LCH) and single-bone CNS-risk lesions have been reported to be at increased risk of diabetes insipidus (DI), central nervous system neurodegeneration (CNS-ND), and recurrence of disease. However, it is unknown whether the addition of chemotherapy or radiotherapy changes outcomes in these patients. Ten pe...

Coeliac disease (CD) is an autoimmune condition characterised by gluten-induced intestinal inflammation, and observed at a 5-10 fold greater prevalence in type 1 diabetes. While universal screening for CD in patients with diabetes is frequently advocated, objective data is limited as to benefits on diabetes control, bone health or quality of life r...

Rhabdoid brain tumours, also called atypical teratoid rhabdoid tumours, are lethal childhood cancers with characteristic genetic alterations of SMARCB1/hSNF5. Lack of biological understanding of the substantial clinical heterogeneity of these tumours restricts therapeutic advances. We integrated genomic and clinicopathological analyses of a cohort...

BACKGROUND Rhabdomyosarcoma (RMS) represents a diverse category of myogenic malignancies with marked differences in molecular alterations and histology. This study examines the question if RMS predisposition due to germline TP53 mutations correlates with certain RMS histologies. METHODS The histology of RMS tumors diagnosed in 8 consecutive childre...

Sarcomas are malignant tumours of the connective tissues and are proportionately much more common in children than in adults. The Ewing family of tumours (EFT) is a group of sarcomas sharing rearrangement of the EWSR1 gene on 22q12, and include Ewing sarcoma/primitive neuroectodermal tumour, desmoplastic small round cell tumour, angiomatoid fibrous...

Paediatric molecular diagnostics provides essential diagnostic and prognostic information that helps guide management for patients with a variety of tumours. Two specific tumour types will be discussed in this chapter: paediatric sarcomas and neuroblastoma. Paediatric sarcomas harbour specific and diagnostic molecular rearrangements, and the discus...

Classified by their histologic line of differentiation, bone and soft tissue tumours encompass a heterogenous population of neoplasms, with a spectrum of biologic potential. The molecular pathophysiology of most of these tumours can be basically divided into those with specific recurrent translocations or oncogenic mutations and nonspecific genetic...

Background: Doxycycline is a commonly prescribed antibiotic for the treatment of acne vulgaris. Often preferred to other tetracyclines due to a safer and milder side-effect profile, doxycycline is more frequently prescribed as a treatment of this common condition. Objective: To present a case report of a young patient who developed skin eruption...

Abstract Ectopic ACTH syndrome (EAS) is rare in children and is challenging to differentiate from Cushing's disease. A 9-year-old boy presented with a history of worsening fatigue, muscle weakness, weight gain and acne, and he appeared cushingoid with central obesity and hyperpigmentation of his palmar creases. Investigations demonstrated an elevat...

ABSTRACT The Accreditation Council for Graduate Medical Education (ACGME) has provided guidance for specialty and subspecialty fellowship training programs by defining 6 core competencies that must be met. Furthermore, the ACGME has defined several program requirements for pathology training, including those applicable to several pathology subspeci...

Sir, We appreciate the Letter to the Editor by Martin et al., 1 and welcome the opportunity to respond. Identification of the study population was based upon the cause of the fractures, as determined from autopsy findings and information gathered by the Coroner and police investigators. None of the study cases had a history of accidental trauma; no...

Heart disease accounts for a significant proportion of sudden unexpected deaths among children. We describe here demographic features, pathological conditions, and the frequency of premonitory symptoms in a retrospective series of cases of sudden unexpected cardiac death (SUCD) attributable to undiagnosed structural heart disease. A chart review of...

We report on the third case of cutis laxa and progeroid features caused by a homozygous mutation in ALDH18A1 that encodes Δ¹-pyrroline-5-carboxylate-synthase (P5CS). This severely affected child, born to consanguineous parents of Pakistani origin, presented with lax, wrinkled and thin skin with dilated and tortuous subcutaneous blood vessels, corne...

Pediatric undifferentiated soft tissue sarcomas are a group of diagnostically challenging tumors. Recent studies have identified a subgroup of undifferentiated soft tissue sarcomas with primitive round to plump spindle cell morphology and a t(4;19)(q35;q13.1) translocation resulting in the expression of a CIC-DUX4 fusion transcript, including 2 tum...

Autosomal-recessive polycystic kidney disease (ARPKD) is a developmental disorder known to affect both the kidneys and the liver. Renal involvement results in progressive renal insufficiency and hypertension, while hepatic involvement can result in portal hypertension and cholangitis. Pulmonary abnormalities relate mainly to pulmonary insufficiency...

Pediatric hand and wrist ganglia seem to have different epidemiological characteristics than those of adults - a majority are found on the volar aspect of the hands and wrists of patients younger than 10 years of age. To determine the epidemiology, etiological factors, clinical presentation, treatment and outcome of patients with ganglion cysts at...

Invasive aspergillosis is a rare complication of cystic fibrosis. In this article, we describe a case of an adolescent with cystic fibrosis, which was well-controlled previously, colonized with Aspergillus fumigatus. The patient developed fatal disseminated aspergillosis in the absence of any preexisting risk factors after a short course of intrave...

A recent increase in the number of infants presenting at autopsy with rib fractures associated with cardio-pulmonary resuscitation (CPR) precipitated a study to determine whether such a phenomenon was related to recent revision of paediatric resuscitation guidelines. We conducted a review of autopsy reports from 1997 to 2008 on 571 infants who had...

Pediatric undifferentiated soft tissue sarcomas (USTSs) are a group of malignancies composed predominantly of primitive round cell sarcomas, the histogenesis of which is uncertain. Thus, diagnosis and therapy remain a challenge. The aims of the current study were to determine whether differential expression of stem cell-associated proteins could be...

Primitive myxoid mesenchymal tumor of infancy is a recently recognized entity that has been added to the differential diagnosis of myxoid tumors of the soft tissue. Few cases have been reported of this entity in the literature, but none presenting in a preterm infant. We present the case and clinical course of a preterm boy with a primitive myxoid...

In neonates and children, sonographic examinations of the renal pyramids may depict a spectrum of unique changes in echogenicity due to the effects of physiologic processes or a wide variety of pathologic processes that may affect the collecting ducts or interstitium of the pyramids. Focused sonographic evaluation of the pyramids with high-frequenc...

Sentinel lymph node (SLN) biopsy has become integral in the staging of patients with melanoma, and entails detailed histologic examination with immunohistochemistry. Reverse transcriptase-polymerase chain reaction (RT-PCR) for tyrosinase transcripts has been used to increase sensitivity but requires a dedicated piece of tissue that does not undergo...

Background: We present a case of a 13-year-old girl with a congenital vascular lesion in her right ankle. Results and conclusions: Clinical and pathologic examinations led to the diagnosis of a verrucous hemangioma, a distinct, uncommon vascular lesion. The appearance of verrucous hemangiomas evolves with time and may represent a diagnostic chal...

Although benign and metastatic tumors occur in children, primary malignant skin tumors are uncommon in the pediatric population. In this study, the authors aimed to determine the incidence, risk factors, treatment, reconstruction details, and outcome of malignant skin tumors occurring in pediatric patients at the Hospital for Sick Children. The ele...

Friedreich ataxia (FRDA) is the most common cause of childhood onset ataxia. We report on a 4 year old boy who suffered sudden cardiac death and was found to have a dilated cardiomyopathy with left ventricular hypertrophy on post-mortem studies. Molecular genetic testing subsequently confirmed the diagnosis of Friedreich ataxia. To our knowledge, t...