A challenging diagnosis of Langerhans' cell histiocytosis with hypothalamic-pituitary and mandibular involvement: case report and literature review.

Background: Langerhans cell histiocytosis (LCH) is a rare bone marrow derived neoplasm that mainly affects children. It is a multiorgan disorder and hypothalamic-pituitary involvement is uncommon. LCH reveals a wide spectrum of indications; thus, the diagnosis and treatment are usually challenging. Case Report: A 22-year-old male presented with polydipsia, polyuria with nonspecific radiological findings, later on, developed a mandibular lesion and a biopsy was conducted which led to LCH diagnosis. After many improper treatments due to unclear diagnosis, the patient was finally placed on chemotherapy and is now under surveillance. Discussion: LCH is a rare disease with diverse clinical manifestations affecting various organs. Associated mutations, such as BRAF V600E, contribute to its complexity. In adults, initial symptoms include pain, weight loss, and fever, with potential pituitary involvement leading to Arginine vasopressin (AVP) deficiency. Commonly affected organs include bone, skin, and the pituitary gland. The disease can be categorized into single-system and multisystem. Pathological diagnosis involves electron microscopy or immunohistochemical staining. Treatment options vary; the presented case utilized Desmopressin acetate and prednisolone before transitioning to cyclophosphamide for multisystemic LCH. Conclusion: AVP deficiency can suggest hypothalamic-pituitary LCH, and a biopsy, if possible, is recommended to confirm the diagnosis.

The frequency of NUDT15 rs116855232 and its impact on mercaptopurine-induced toxicity in Syrian children with acute lymphoblastic leukemia.

Introduction: Polymorphisms in NUDT15 may result in differences in mercaptopurine-induced toxicity. This study aimed to identify the frequency of the NUDT15 (c.415C>T; rs116855232) polymorphism and investigate the effect of this polymorphism on mercaptopurine-induced toxicity in a population of Syrian patients with childhood acute lymphoblastic leukemia (ALL). Methods: This is a retrospective study that included children with ALL reaching at least 6 months of maintenance therapy. The NUDT15 genotyping was determined using standard targeted sequencing of polymerase chain reaction products. The odds ratio (OR) for the association between toxicity and genotype was evaluated. Results: A total of 92 patients were enrolled. The majority of the patients in the study population were low-risk (63.04%), followed by intermediate-risk (25%), and high-risk (11.96%). There were 5 patients (5.4%) with NUDT15 (c.415C>T; rs116855232) CT genotype, and 1 patient (1.08%) with NUDT15 TT genotype, with allele frequencies of C=0.962 and T=0.038. The mercaptopurine median dose intensity was 100%, 54.69%, and 5% for the genotypes CC, CT, and TT, respectively (P=0.009). Early onset leukopenia was significantly associated with the NUDT15 polymorphism (OR: 6.16, 95% CI: 1.11-34.18, P=0.037). There was no association between the NUDT15 genotype and hepatotoxicity. Conclusion: Approximately 6.5% of the study population exhibited reduced NUDT15 activity. The mercaptopurine dose intensity was considerably low in NUDT15 rs116855232 TT genotype compared with CT and CC. The dosage of mercaptopurine should be adjusted according to the NUDT15 genotype in pediatric patients with ALL.

Optimizing the Treatment for Advanced Non-Small-Cell Lung Cancer with Mutated Epidermal Growth Factor Receptor in Low-Income Countries: A Review.

Introduction: Osimertinib is the treatment of choice for epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC). Because of its high price, many low-income countries, such as Syria, cannot provide osimertinib, which makes it difficult to choose the appropriate treatment for these patients. This study aimed to review articles that assessed tyrosine kinase inhibitors (TKIs) for advanced NSCLC and developed an appropriate treatment plan for Syrian patients. Methods: An electronic literature search was conducted of published phase II and III studies that assessed the efficacy of EGFR-TKIs for advanced NSCLC between January 2003 and May 2022. Results: Seventeen articles were reviewed. The results were similar when erlotinib or icotinib was compared with gefitinib. Progression-free survival and overall survival for afatinib and dacomitinib were longer than for gefitinib, with small significant differences. Osimertinib was the only TKI that showed efficacy against the T790M mutation, which showed an improvement over the first- and second-generation TKIs. Osimertinib as a first-line therapy is not cost-effective compared with first- and second-generation TKIs. Conclusion: Osimertinib is the preferred first-line treatment in patients with advanced EGFR-mutated NSCLC. First- and second-generation TKIs are still considered good options, especially in low-income countries that cannot cover the costs of osimertinib.

Frequencies of CYP2D6 genetic polymorphisms in Arab populations.

CYP2D6 is a key drug-metabolizing enzyme implicated in the biotransformation of approximately 25% of currently prescribed drugs. Interindividual and interethnic differences in CYP2D6 enzymatic activity, and hence variability in substrate drug efficacy and safety, are attributed to a highly polymorphic corresponding gene. This study aims at reviewing the frequencies of the most clinically relevant CYP2D6 alleles in the Arabs countries. Articles published before May 2021 that reported CYP2D6 genotype and allelic frequencies in the Arab populations of the Middle East and North Africa (MENA) region were retrieved from PubMed and Google Scholar databases. This review included 15 original articles encompassing 2737 individuals from 11 countries of the 22 members of the League of Arab States. Active CYP2D6 gene duplications reached the highest frequencies of 28.3% and 10.4% in Algeria and Saudi Arabia, respectively, and lowest in Egypt (2.41%) and Palestine (4.9%). Frequencies of the loss-of-function allele CYP2D6*4 ranged from 3.5% in Saudi Arabia to 18.8% in Egypt. The disparity in frequencies of the reduced-function CYP2D6*10 allele was perceptible, with the highest frequency reported in Jordan (14.8%) and the lowest in neighboring Palestine (2%), and in Algeria (0%). The reduced-function allele CYP2D6*41 was more prevalent in the Arabian Peninsula countries; Saudi Arabia (18.4%) and the United Arab Emirates (15.2%), in comparison with the Northern Arab-Levantine Syria (9.7%) and Algeria (8.3%). Our study demonstrates heterogeneity of CYP2D6 alleles among Arab populations. The incongruities of the frequencies of alleles in neighboring countries with similar demographic composition emphasize the necessity for harmonizing criteria of genotype assignment and conducting comprehensive studies on larger MENA Arab populations to determine their CYP2D6 allelic makeup and improve therapeutic outcomes of CYP2D6- metabolized drugs.

Gestational breast cancer in a patient with Crohn's disease: two case reports.

BACKGROUND: Diagnosis of breast cancer during gestation is a rare occurrence. In addition, the diagnosis of breast cancer in a patient with Crohn's disease is not common. We present a rare case of gestational breast cancer in a patient with Crohn's disease, with a concurrent breast cancer diagnosis in her sister. CASE PRESENTATION: A 31-year-old Syrian woman with Crohn's disease was diagnosed with breast cancer at 30 weeks gestation; she received neoadjuvant chemotherapy during gestation. Incidentally, her 37-year-old sister was also diagnosed concomitantly with breast cancer. Both sisters underwent and successfully completed surgery and adjuvant therapy. At a 5-year review, both patients showed no signs of recurrence. The Crohn's disease symptoms have also improved after chemotherapy, and the baby born after gestational chemotherapy is currently 5 years old with normal psychomotor development and without any congenital malformations. CONCLUSIONS: This case report highlights the impact of gestation on breast cancer outcomes, the possibility of giving chemotherapy during gestation, and the effect of chemotherapy on the symptoms of Crohn's disease.