Monogenic diseases are frequent causes of neonatal morbidity and mortality, and disease presentations are often undifferentiated at birth. More than 3500 monogenic diseases have been characterized, but clinical testing is available for only some of them and many feature clinical and genetic heterogeneity. Hence, an immense unmet need exists for improved molecular diagnosis in infants. Because disease progression is extremely rapid, albeit heterogeneous, in newborns, molecular diagnoses must occur quickly to be relevant for clinical decision-making. We describe 50-hour differential diagnosis of genetic disorders by whole-genome sequencing (WGS) that features automated bioinformatic analysis and is intended to be a prototype for use in neonatal intensive care units. Retrospective 50-hour WGS identified known molecular diagnoses in two children. Prospective WGS disclosed potential molecular diagnosis of a severe GJB2-related skin disease in one neonate; BRAT1-related lethal neonatal rigidity and multifocal seizure syndrome in another infant; identified BCL9L as a novel, recessive visceral heterotaxy gene (HTX6) in a pedigree; and ruled out known candidate genes in one infant. Sequencing of parents or affected siblings expedited the identification of disease genes in prospective cases. Thus, rapid WGS can potentially broaden and foreshorten differential diagnosis, resulting in fewer empirical treatments and faster progression to genetic and prognostic counseling.

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Objective: Cytospin preparations and immunocytochemistry are common methods in hospitals to evaluate malignancies in body fluids. Characteristics of malignant cells in pediatric body fluids have not been adequately evaluated. Study Design: 183 pleural, peritoneal and pericardial pediatric fluid specimens were examined by cytospin preparations and immunocytochemistry from two hospitals using similar procedural techniques. Cytologic diagnoses were correlated with the results of clinical history, histology and ancillary studies. Results: Forty cases with malignancy were identified (21.9%); the most common diagnoses were rhabdomyosarcoma and acute lymphoblastic lymphoma (9 and 8 cases, respectively). Small round cell tumors revealed similar morphology as clusters of small round cells with central nuclei and scant cytoplasm with frequent small vacuoles. Twenty-one cases were evaluated by immunocytochemistry, 12 by flow cytometry and 5 by cytogenetic analysis. CD3, CD20, TdT, CD10, desmin and myogenin were the most common markers. Staining artifacts causing interpretation difficulties were noted in 5 cases that were resolved by molecular studies and deferral for surgical specimens. Conclusions: Small round cell tumors are the most common malignancies encountered in pediatric body fluids and share a nonspecific morphology. Although immunocytochemistry is helpful to arrive at the correct diagnosis, other ancillary studies may be necessary, particularly in hematologic malignancies and other difficult cases.

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INTRODUCTION: Gastric cancer has been known to have a poor prognosis worldwide. It frequently leads to a metastatic disease, but rarely to the colon. CASE DESCRIPTION/METHODS: A 73-year-old male presented for a routine surveillance colonoscopy. He reported new onset constipation over the last 6-8 months that was not relieved by over-the-counter laxatives. He was found to have a stricture approximately 30 cm from the anal verge (Figure 1). This stricture was not seen on previous colonoscopy in 2014. He had a history of gastric adenocarcinoma 4 years ago, underwent a subtotal gastrectomy followed by chemotherapy and radiation and was closely followed in the oncology clinic. In addition, he also had a gastrointestinal stromal tumor (GIST) in the stomach. Histopathology was consistent with gastric adenocarcinoma (Figure 2). Widespread metastatic disease was found on PET scan (Figure 3). DISCUSSION: Although gastric cancer metastasizes to the liver, peritoneum and distant lymph nodes commonly, colon metastasis is rare and even rarer is sigmoid metastasis. We report a case of a patient with a change on bowel habits and was found to have gastric adenocarcinoma that has metastasized to the sigmoid colon causing a structuring lesion. In addition, both gastric adenocarcinoma and a concurrent GIST have been reported in literature. It has been suggested that C-KIT or PDGFR-a mutations can lead to both cancer types but more information on this subject is lacking in current literature. It appears though that having both types of cancers do not significantly influences symptoms or disease outcome.

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