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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 which 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.

Introduction: Wolman Disease (WD) is a rare disease caused by the absence of functional liposomal acid lipase (LAL) due to mutations in LIPA gene. It presents with organomegaly, malabsorption and adrenal calcifications. The presentations can resemble Hemophagocytic lymphohistiocytosis (HLH), the life threatening hyper-inflammatory disorder.Method: We present a 4.5-month-old boy with fever, icterus and hepatosplenomegaly who was treated according to presumed HLH disease. There are some case reports in the literature presenting patients with WD primarily diagnosed as HLH, which we discussed in this review.Results: The genetic analysis revealed after his demise was compatible with WD, 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 WD and HLH, the patient’s life can be saved if special attention is paid to presenting features of a patient with suspected HLH, i.e., symptoms, finding on physical exams, laboratory values and radiologic findings, and the proper treatment is urgently initiated. Reporting the novel mutations of WD can help geneticists interpret the results of their patients’ genetic studies appropriately, leading to correct diagnosis and treatment.

BACKGROUND: While both glial/glioneuronal neoplasia and ganglioneuroma have been reported as components of multiple primary neoplasms, no patient has been diagnosed with multiple primary neoplasms of cerebral glial/glioneuronal tumors with oligodendroglioma-like features and adrenal ganglioneuroma up to now. CASE: A previously healthy five-year-old girl was admitted with a two-week history of headaches and vomiting. Brain Magnetic resonance imaging (MRI) showed a massive heterogenous multi-cystic enhancing lesion in the right temporoparietal area with substantial vasogenic edema. The patient underwent craniotomy and tumor gross total resection. The intra-operative histomorphological assessment of the tumor was well-matched with a glial tumor. The patient developed systolic hypertension during postoperative care in the Intensive Care Unit. Subsequent abdominal CT scan unveiled a calcified mass of the left adrenal gland origin. Blood and urine catecholamine tests, vanillylmandelic acid (VMA), were within the normal range. The surgical excision specimen exhibited a clear cell neoplasm with diffuse infiltrative growth. A distinguishing combination of oligodendroglioma-like perinuclear haloes, clear cell appearance and vascular proliferation rendered the diffuse Glioneuronal tumor with Oligodendroglioma-like features. With the combination of oligodendroglial-like appearance, negative 1p/19q codeletion, Wild IDH, no BRAF mutation, weak GFAP, and positive synaptophysin altogether, the tumor was compatible with the novel diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC). The patient underwent laparotomy and tumor resection subsequently. Morphologic histopathological examinations of the adrenal mass were in line with ganglioneuroma. After discharge, no pathological uptake was identified with iodine-131 meta-iodobenzylguanidine scan (MIBG scan). No tumor residue was apparent on postoperative brain MRI. The patient received no adjuvant therapy for brain and adrenal tumors and underwent close surveillance for both tumors. No clinical or radiologic recurrence was recognized after six months of follow-up. CONCLUSIONS: Concurrent glioneuronal tumor and ganglioneuroma can be managed safely when diagnosed timely, leading to favorable outcomes.

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.

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.

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.

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.

Objective. Alteration of serum bilirubin level in acute episodes of psychosis in patients with schizophrenia has been reported but the pattern of this alteration is controversial. Methods. Patients diagnosed as schizophrenia (162, group S) or bipolar disorder (155, group B) entered the study. The control group consisted of 95 patients admitted to cardiac care unit who had no personal or family history of major psychiatric disorders. Pre- and post-admission levels of bilirubin were measured and compared within and between the groups. Patients were examined to exclude all other causes of hyperbilirubinemia. Group S and B participants were also evaluated using positive and negative syndrome subscale (PANSS) both at admission and discharge. Results. The mean admission bilirubin levels of all the groups were in the normal range (significantly higher in group S than groups B and C) and were affected by the score of general psychopathology subscale rather than the scores of positive symptoms subscale. Conclusions. Although bilirubin decreased in all three groups at discharge, the rate of decrease was significantly higher in group S. The reason for this is not clear and needs further study.