Wolman disease presenting with hemophagocytic lymphohistiocytosis syndrome and a novel LIPA gene variant: a case report and review of the literature.

BACKGROUND: Wolman disease is a rare disease caused by the absence of functional liposomal acid lipase due to mutations in LIPA gene. It presents with organomegaly, malabsorption, and adrenal calcifications. The presentations can resemble hemophagocytic lymphohistiocytosis, the life threatening hyperinflammatory disorder. Since the disease is very rare, clinicians might not think of it when a patient presents with hemophagocytic lymphohistiocytosis, and the opportunity to treat it properly can be lost, thus leading to demise of the child. CASE PRESENTATION: We present a 4.5-month-old Caucasian boy with fever, icterus, and hepatosplenomegaly who was treated according to presumed hemophagocytic lymphohistiocytosis disease. Wolman disease was diagnosed after the death of the child. There are some case reports in the literature presenting patients with Wolman disease primarily diagnosed as hemophagocytic lymphohistiocytosis, which we discuss in this review. The genetic analysis revealed after his demise was compatible with Wolman disease, introducing a novel mutation in LIPA gene: exon 4: NM_001127605: c. G353A (p.G118D), which converts the glycine amino acid to aspartic acid. CONCLUSIONS: Considering the similarities in presentation of Wolman disease and hemophagocytic lymphohistiocytosis, the patient's life can be saved if special attention is paid to presenting features of a patient with suspected hemophagocytic lymphohistiocytosis, that is special attention to symptoms, findings on physical exams, laboratory values, and radiologic findings, and the proper treatment is urgently initiated. Reporting the novel mutations of Wolman disease can help geneticists interpret the results of their patients' genetic studies appropriately, leading to correct diagnosis and treatment.

Alteration of Plasma Amino Acid Concentrations in Iranian Children with COVID-19.

COVID-19 is an acute viral disease that has so far infected more than 200 million and killed more than four million worldwide. It affects the immune system and other organs. Here, we investigated the level of free plasma amino acids in COVID-19 patients and compared them with non-COVID-19 subjects. We also compared amino acids levels in critically ill patients admitted to the intensive care unit (ICU) with non-ICU patients and expired and recovered patients. Twenty-six COVID-19 patients and 32 non-COVID-19 subjects were included in the study. The mean of glutamic acid, serine, glycine, threonine, phenylalanine, leucine, lysine, alanine, arginine, aspartic acid, and ornithine was significantly higher in cases than controls. In addition, the mean of glutamine was significantly lower in patients than controls (443.89 ± 254.31 vs. 651.73 ± 107.38, PV < 0.001). Low level of glutamine and isoleucine was seen in the majority of ICU and expired patients, respectively. Logistic regression analysis showed low level of isoleucine as a predictor variable in mortality (P = 0.02, EXP (B) = 16.5, and CI 95% = (1.48, -183.07)). There was a positive and significant relationship between some amino acids levels, serum liver enzymes, and sodium concentrations. There was also a significant but negative correlation between histidine levels, ESR, and ferritin. Phenylalanine had a highly positive relationship with serum procalcitonin in patients (R 2 = 0.534, PV = 0.015). Our studies have shown the alteration of plasma amino acids concentration in COVID-19 patients. These changes are more evident in critically ill and at-risk patients.

Juvenile Polyps with Osseous Metaplasia: Report of Two Pediatric Cases and Review of the Literature.

BACKGROUND: Osseous metaplasia is considered as a response to insults such as chronic inflammation or mucin extravasation in colorectal polyps. CASE REPORT: we report two cases of osseous metaplasia in juvenile (retention) polyps as incidental histopathological findings in a case of rectal juvenile polyposis and a patient with solitary rectal juvenile polyp. CONCLUSION: Osseous metaplasia can occur in colorectal juvenile polyps and is considered a probable response to mucin extravasation and/or chronic inflammation. The clinical and prognostic significance of osseous metaplasia in these polyps is unknown.

Scrotal wall leiomyosarcoma: a case report and review of the literature.

BACKGROUND: Up to 30% of all scrotal masses are sarcomas. Leiomyosarcoma of the scrotal wall is rare, and its clinical significance and prognosis have not been well defined, since the most reported cases have little or no follow-up. CASE PRESENTATION: We report a 45-year-old Caucasian man who was admitted with a firm, nontender, mobile scrotal wall mass from 15 months ago. Laboratory data including testicular tumor markers were within normal range, and transscrotal ultrasonography revealed an oval-shaped, hypoechogenic, solid mass with blood flow and well-defined border. Histopathologic examination and immunohistochemistry staining, following surgical excision, were in favor of malignant leiomyosarcoma. CONCLUSION: Here we describe the morphological features and immunohistochemical presentations of the tumor and the patient's relatively long-term follow-up.

Pre-analytical Practices in the Molecular Diagnostic Tests, A Concise Review.

Molecular assays for detection of nucleic acids in biologic specimens are valuable diagnostic tools supporting clinical diagnoses and therapeutic decisions. Pre-analytical errors, which occur before or during processing of nucleic acid extraction, contribute a significant role in common errors that take place in molecular laboratories. Certain practices in specimen collection, transportation, and storage can affect the integrity of nucleic acids before analysis. Applying best practices in these steps, helps to minimize those errors and leads to better decisions in patient diagnosis and treatment. Widely acceptable recommendations, which are for optimal molecular assays associated with pre-analytic variables, are limited. In this article, we have reviewed most of the important issues in sample handling from bed to bench before starting molecular tests, which can be used in diagnostic as well as research laboratories. We have addressed the most important pre-analytical points in performing molecular analysis in fixed and unfixed solid tissues, whole blood, serum, plasma, as well as most of the body fluids including urine, fecal and bronchial samples, as well as prenatal diagnosis samples.

A Rare Cytogenetic Variant of Monosomy 18p Syndrome as a Consequence of Whole-Arm Translocation between Chromosomes 13 and 18.

Monosomy 18p syndrome is one of the prototypical examples of autosomal terminal deletions. This deletion can be the consequence of de novo deletions, malsegregation of a balanced parental translocation, cryptic subtelomeric deletions or ring chromosome 18. The present case is a rare cytogenetic variant of monosomy 18 as a consequence of whole-arm translocation between chromosomes 13 and 18 which has been reported only three times previously.

Apocrine mixed tumor of the eyelid: a case report.

BACKGROUND: Apocrine mixed tumor is usually found in parotid glands. Its cutaneous counterpart is rare and its occurrence in the eyelids is even rarer. CASE PRESENTATION: This study reports an apocrine mixed tumor of the upper left eyelid in a 68 year-old lady with a history of breast cancer. This mass appeared about 3 years ago, as a slowly growing small nodule, and was completely excised. On microscopic examination, an encapsulated mass with epithelial and mesenchymal features was seen. The epithelial component presented tubular, cystic and infundibular structures while the mesenchymal component was fibrous in some areas and myxoid in others. Plasmacytoid hyaline cells, lipomatous change and focal calcification were appreciated focally. Immunohistochemical studies showed stromal staining for CD10, S-100, α-SMA and p63. Luminal cell layer of the epithelial component was positive for EMA, CK-7 and GCDFP-15 markers. The capsule was unbreached and no satellite lesions were appreciated. No evidence of relapse was evident after 16 months of follow-up. CONCLUSIONS: The diagnosis of eyelid tumors of adnexal origin can be challenging because they are rare and display a wide range of morphological patterns, as the tumor cells might differentiate along any line of the folliculosebaceous-apocrine system. Immunohistochemistry helps improve the accuracy of assessment.

FLT3 Gene Mutation Profile and Prognosis in Adult Acute Myeloid Leukemia.

BACKGROUND: Internal tandem duplication (ITD) of FMS-related tyrosine kinase 3 (FLT3) gene, which occurs in exons 14 and 15, is one of the most prevalent somatic mutations in adult acute myeloid leukemia (AML) and has biological, prognostic, and therapeutic implications. The prognostic importance of codon 835 tyrosine kinase domain (TKD) mutation (exon 20), which occurs relatively frequently in adult AML, is often debated. We aimed to study the FLT3 gene mutation profile and prognosis in 139 adult Iranian patients with newly diagnosed AML. METHODS: We determined the status of ITD and TKD mutations using fragment analysis and the polymerase chain reaction-restriction fragment polymorphism method, respectively. In addition, we used direct sequencing to confirm the results of TKD mutation analysis. RESULTS: Twenty five percent of the patients had an ITD mutation. The mean size of the inserted fragment was 63.5 base pairs. Twenty percent of the ITD-positive patients showed more than one mutated population upon polymerase chain reaction. Statistical analyses showed that the ITD mutation was associated with a decreased overall survival among patients in the intermediate cytogenetic risk group (p-value = 0.013). The size of the ITD was not correlated with overall survival. Eight out of 139 patients (5.7%) had the codon 835 mutation. One new mutation of the insertion/deletion type was discovered. Analyses did not show any relationship between the TKD mutation and overall survival. Two patients (1.4%) showed concurrent TKD and ITD mutations. The TKD and ITD mutation rates of the FLT3 gene were consistent with previous studies on AML patients. CONCLUSIONS: This study supports the results of previous studies regarding the association of the FLT3-ITD mutation and poor prognosis.

NPM1 Mutation Detection in Acute Myeloid Leukemia: A Method Comparison Study.

BACKGROUND: Mutations in the nucleophosmin (NPM1) gene have been used as molecular biomarkers for prognostication of patients with adult acute myeloid leukemia (AML). METHODS: We designed a rapid and sensitive method using the allele-specific-refractory mutation system-polymerase chain reaction (ARMS-PCR) to detect the most common mutations of NPM1 gene, which are mostly four base pair insertions and compared its efficacy with direct sequencing and capillary electrophoresis which served as the gold standards. RESULTS: The incidence of mutation was 22% (33% of patients with normal karyotypes had mutation compared with 16% of patients with abnormal karyotypes) based on the results obtained with capillary electrophoresis analysis and direct sequencing. All of the specimens determined to be mutation-positive by the gold standard tests were also positive by the ARMS-PCR method. Significantly, the ARMS-PCR test also helped determine the mutation status of an extra set of patients who had low call rates on capillary electrophoresis and appeared normal on direct sequencing. DISCUSSION: The low mutation rate in some patients hindered its detection in the gold standard assays because of the interference of the mutation signal by high background noise. The low sensitivity of the gold standard assays for detecting low copy number mutations rates thus increase their risk of producing false negative results that adversely affects prognostication and therapy. Our results suggest that the mutation detection rate of the ARMS-PCR assay is better than existing tests. This is most probably because of the fact that in an ARMS-PCR-based method, the mutated variant is specifically amplified, based on a mutation-specific primer. CONCLUSIONS: We conclude that the high sensitivity of the ARMS-based method together with its rapidity and low expense should make it a suitable choice for clinical laboratories.