Numerous rearrangements in the 8p23 chromosomal region have been reported; included in these rearrangements are isolated deletions in this area. Such deletions are associated with a wide range of phenotypic characteristics, including motor impairment, epilepsy, intellectual disability, cardiac defects and seizures. The present study describes the case of a 30-year-old asymptomatic man that carries a de novo deletion in 8p23.2-p23.3. Molecular karyotyping indicated that the detected deletion involves genes that are in the critical region which is hypothesized to be responsible for the phenotypic characteristics associated with such deletions. The normal phenotype of the patient supports the hypothesis that there is incomplete penetrance of 8p23.2-p23.3 deletions.

Spindle cell sarcoma with KIAA1549-BRAF fusion is a type of childhood sarcoma that closely resembles infantile fibrosarcoma by morphologic criteria and harbors molecular alteration other than the ETV6-NTRK3 fusion gene. This neoplasm was diagnostically challenging without molecular tests, including next-generation sequencing. The discovery of BRAF translocation in this tumor contributes to the promise of the clinical implication of selecting new therapeutic options for the treatment of progressive diseases that are refractory to conventional chemotherapy. Here we present the case of a three-year-old girl who was diagnosed with spindle cell sarcoma with KIAA1549-BRAF fusion gene and had a favorable outcome three years after surgery.

ETV6::ABL1 rearranged neoplasms are rare hematological diseases. To date, about 80 cases have been reported, including myeloid and lymphoid leukemias. The ETV6 gene codes for an ETS family transcription factor and several fusion partners have been described. When translocated, ETV6 causes the constitutive activation of the partner genes. Here, we report the case of a 54-year-old woman with a cryptic insertion of the 3\' region of ABL1 in the ETV6 gene. The patient was first diagnosed with idiopathic hypereosinophilic syndrome, according to the clinical history, conventional cytogenetics, standard molecular analyses and pathologist description. Next generation sequencing of diagnosis samples unexpectedly detected both ETV6::ABL1 type A and B fusion transcripts, which were then confirmed by FISH. The diagnosis was Myeloid/Lymphoid neoplasm with ETV6::ABL1 fusion, and the patient received imatinib mesylate treatment. In a follow-up after more than one year, the patient still maintained the molecular and complete hematological responses. This case highlights the importance of timely and proper diagnostics and prompt tyrosine kinase inhibitor treatment.

BACKGROUND: Acute lymphoblastic leukemia is the most common childhood cancer, with an 80% frequency in children between 1 and 10 years old. The outcome and prognosis of acute lymphoblastic leukemia in children depends on various factors, such as age, clinical and biological features, and cytogenetic factors.
METHODS: We report the case of a pediatric patient, a 4-year-old Moroccan female who was referred to the Hematology and Oncology Department of 20 August 1953 Hospital in Casablanca and diagnosed with B-cell acute lymphoblastic leukemia associated with a rare genetic chromosomal abnormality.
CONCLUSIONS: Translocation (1;4)(p21;p15) is a relatively rare chromosomal abnormality found in human leukemia and was never described isolated in pediatric B-cell acute lymphoblastic leukemia patients. It showed a good evolution by complete remission and recovery of this patient after receiving all chemotherapy and after 8 years of follow-up.

Activating mutations and fusions of the ALK oncogene have been identified as drivers in a number of malignancies. Crizotinib and subsequent ALK tyrosine kinase inhibitors have improved treatment outcomes for these patients. In this paper, we discuss the case of an adolescent patient with acute myeloid leukemia, who was identified to have an activating ALK fusion, which is a rare finding and has never been reported in cases of AML without monosomy 7. Crizotinib was added to this patient\'s frontline therapy and was well tolerated. In cases of more common gene alterations, existing data supports the use of targeted agents as post-HSCT maintenance therapy; however, crizotinib was not able to be used post-HSCT for this patient due to the inability to obtain insurance coverage.

The risk of toxicity attributable to radioiodine therapy (RIT) remains a subject of ongoing research, with a whole-body dose of 2 Gy proposed as a safe limit. This article evaluates the RIT-induced cytogenetic damage in two rare differentiated thyroid cancer (DTC) cases, including the first follow-up study of a pediatric DTC patient. Chromosome damage in the patient\'s peripheral blood lymphocytes (PBL) was examined using conventional metaphase assay, painting of chromosomes 2, 4, and 12 (FISH), and multiplex fluorescence in situ hybridization (mFISH). Patient 1 (female, 1.6 y.o.) received four RIT courses over 1.1 years. Patient 2 (female, 49 y.o.) received 12 courses over 6.4 years, the last two of which were examined. Blood samples were collected before and 3-4 days after the treatment. Chromosome aberrations (CA) analyzed by conventional and FISH methods were converted to a whole-body dose accounting for the dose rate effect. The mFISH method showed an increase in total aberrant cell frequency following each RIT course, while cells carrying unstable aberrations predominated in the yield. The proportion of cells containing stable CA associated with long-term cytogenetic risk remained mostly unchanged during follow-up for both patients. A one-time administration of RIT was safe, as the threshold of 2 Gy for the whole-body dose was not exceeded. The risk of side effects projected from RIT-attributable cytogenetic damage was low, suggesting a good long-term prognosis. In rare cases, such as the ones reviewed in this study, individual planning based on cytogenetic biodosimetry is strongly recommended.

Although Turner syndrome is most often sporadic, multigenerational recurrence has been reported more often in the offspring of women with mosaic or variant forms of Turner syndrome. We present a case in which natural conception in a woman with identified 45,X/46,XX mosaicism resulted in a fetus with a gain of a derivative X chromosome. The unexpected fetal finding prompted further cytogenetic evaluation of the patient and subsequent identification of an additional cell line with the same derivative X chromosome, not observed in the initial study. To our knowledge, this is the first case in which further investigation of an abnormal noninvasive prenatal screen resulted in the identification of both maternal and fetal sex chromosome abnormality. We discuss the discordant finding, similar cases, and potential phenotype with respect to skewed X inactivation. We also highlight the use of multiple testing methodologies to characterize the serendipitous identification of a derivative X chromosome.

Myelodysplastic syndromes (MDSs) are clonal hematopoietic stem cell disorders characterized by cytopenias, dysplasia in one or more of the major myeloid cell lines, ineffective hematopoiesis, with cellular marrow, and risk for leukemic transformation. We present a case of a 66-year-old male with a history of multiple packed red blood cell (PRBC) transfusions. Routine investigations, bone marrow aspiration, and biopsy were done. The clinical and morphological findings raised suspicion of MDS with isolated del (5q), so cytogenetics was done. When cytogenetics was done, there was a big mismatch in finding between clinical, morphological, and molecular findings which brought a major change in prognosis as well as treatment. It is, therefore, very essential to not rely only on the clinical and morphological findings to reach a diagnosis. Molecular findings play a pivotal role to come to a final conclusion.

Chromoanagenesis is a phenomenon of highly complex rearrangements involving the massive genomic shattering and reconstitution of chromosomes that has had a great impact on cancer biology and congenital anomalies. Complex chromosomal rearrangements (CCRs) are structural alterations involving three or more chromosomal breakpoints between at least two chromosomes. Here, we present a 3-year-old boy exhibiting multiple congenital malformations and developmental delay. The cytogenetic analysis found a highly complex CCR inherited from the mother involving four chromosomes and five breakpoints due to forming four derivative chromosomes (2, 3, 6 and 11). FISH analysis identified an ultrarare derivative chromosome 11 containing three parts that connected the 11q telomere to partial 6q and 3q fragments. We postulate that this derivative chromosome 11 is associated with chromoanagenesis-like phenomena by which DNA repair can result in a cooccurrence of inter-chromosomal translocations. Additionally, chromosome microarray studies revealed that the child has one subtle maternal-inherited deletion at 6p12.1 and two de novo deletions at 6q14.1 and 6q16.1~6q16.3. Here, we present a familial CCR case with rare rearranged chromosomal structures and the use of multiple molecular techniques to delineate these genomic alterations. We suggest that chromoanagenesis may be a possible mechanism involved in the repair and reconstitution of these rearrangements with evidence for increasing genomic imbalances such as additional deletions in this case.

Graft versus host disease is a rare but deadly complication of solid organ transplant. Clinical features of graft-versus-host-disease are non-specific, which may lead to delayed diagnosis as more common conditions including infections or drug reactions are considered. We describe a 54-year-old male patient who underwent liver transplantation for alcohol use disorder-related cirrhosis and developed acute graft-versus-host disease. Initial clinical presentation included dermatitis, bone marrow failure and enteritis. Results of skin biopsy and cytogenetic studies were consistent with liver transplant-associated acute graft-versus-host disease. The importance of this case is to highlight to transplant physicians and surgeons the challenges of diagnosing graft-versus-host-disease. In our case, pre-existing partnerships among the liver and hematopoietic stem cell transplant teams, transfusion medicine specialists, critical care specialists and facilitated timely communication relevant to confirming graft-versus-host disease. We propose an algorithm to assist in the workup of suspected graft-versus-host disease. Because this condition is characterized by high mortality, a high index of suspicion is imperative for prompt diagnosis and optimal management of the donor-recipient immune interaction when patients present with classic clinical features.