Acute blood transfusion reactions in a tertiary care hospital in Pakistan - an initiative towards haemovigilance.

OBJECTIVE: In this study, we report acute blood transfusion reactions at our hospital, compare our analysis with the reported data and identify areas for improvement. BACKGROUND: Haemovigilance programmes have been implemented in many countries, and adverse events associated with blood transfusion are published in their annual reports. Pakistan has no current established programme. MATERIAL AND METHODS: A cross-sectional study was conducted, and all adverse reactions reported to the blood bank from January 2014 to March 2016 were included. An adverse response in the patient, related to administration of blood (within 24 h), was considered an immediate transfusion reaction. RESULTS: During the study period, 20 956 blood components were issued. A total of 32 (0·15%) adverse reactions were documented. Allergic reactions were the most common adverse event observed in 15 (46·8%) of the cases. Febrile non-haemolytic transfusion reaction (FNHTR) was the second most common reaction seen in nine (28%) followed by bacterial contamination in four (12·5%) and acute haemolytic reaction in two (6·2%) of the cases. CONCLUSION: The low incidence indicates underreporting and the need for a formal haemovigilance system. International benchmarking between different medical systems is helpful to identify areas in the transfusion process that have to be changed to improve transfusion safety.

Human placental PPAR-γ and SOX-2 expression in serologically proved toxoplasmosis.

To explore PPAR-γ and SOX-2 transcription factors expression in placenta according to maternal anti-Toxoplasma gondii serological profile during pregnancy and pregnancy outcome. The study included 240 placentas, grouped according to IgM and IgG serostatus and then subgrouped according to pregnancy outcome that varied between miscarriages, premature labour, stillbirth and giving birth to CNS anomaly or apparently healthy neonates. Samples were H&E stained and histopathologically scored blindly. PPAR-γ expression was measured by ELISA, while SOX-2-positive nuclei were stained immunohistochemically to be calculated by ImageJ. The mean pathological score was significantly higher in IgM+ve and IgG rising than IgG-ve and persistent low groups. Former groups showed significantly higher PPAR-γ (mean = 258.63, 227.11). However, PPAR-γ was higher in apparently healthy neonate subgroups. SOX-2 was significantly lower in IgM+ve and IgG rising groups (mean = 12.87, 43.13) and associated with obvious fibrosis. SOX-2 lowest count was in CNS anomaly subgroup. PPAR-γ and SOX-2 changes may give clues of how Toxoplasma induces pathogenesis during vertical transmission. Triggering PPAR-γ expression may be a tool to downregulate the inflammatory response and establish a metabolically permissive cellular environment for Toxoplasma persistence. Low SOX-2 is suspected to disturb placental mesenchymal stem cells pluripotency and neuroectoderm development.

Developmental Vitamin D Deficiency Affects Spatial Learning in Wistar Rats.

Background: Vitamin D deficiency is a global problem. Recent evidence suggests that vitamin D is involved in brain development and function. Vitamin D deficiency has been associated with poor cognitive function in adults, but the effect of developmental vitamin D deficiency (DVDD) on cognitive function and brain development in children has not been well established.Objective: We explored the effects of DVDD on cognitive functions and brain morphology of rat pups.Methods: Wistar rat pups born to control and vitamin D-deficient dams were divided into 4 groups: control (C), deficient during gestation (dG), deficient during lactation (dL), and deficient during gestation and lactation (dGL). Spatial learning and memory were assessed by the Morris water maze test at postnatal day (PND) 24 and PND 45. Cortical thickness at the level of the hippocampus was measured at PND 63, and synapses were counted in specified areas of the hippocampus at PND 32 and PND 63.Results: Repeated-measures ANOVA revealed that at PND 24, learning (escape latency) was impaired (by 42%) in the dGL group, whereas at PND 45, both the dL and the dGL groups showed learning impairment (by 47% and 45%, respectively) compared with their respective C groups (P < 0.05). Short-term or long-term memory was largely unaffected by DVDD either at PND 24 or PND 45. Compared with the C group, all the DVDD groups had fewer synapses in the molecular layer of the hippocampus (P < 0.001). The synapse number decreased by 54% in the dGL group at PND 33 and by 70% in the dL and dGL groups at PND 63. All the DVDD groups at PND 63 showed a reduced cortical thickness (by 22%) compared with the C group (P < 0.05).Conclusion: These results suggest that a combined prenatal and postnatal DVDD for ≥6 wk in rat pups affects learning but not memory.

Frequency and reasons of donor deferral prior to blood donation process: a single centre experience.

OBJECTIVE: The aim of the study was to determine the frequency and reasons for donor deferral prior to the blood donation process in our population. BACKGROUND: Transfusion is an irreversible event that carries potential risks as well as benefits to the recipient. Therefore, donor selection prior to blood donation is one of the most important steps in ensuring the safety of blood and blood products. METHODS: A cross-sectional study was carried out at the blood bank department in our hospital from January 2012 to December 2014. All the blood donors who visited our department in the study period were included in this study. RESULTS: A total of 25 901 potential donations were recorded during the study period, comprising 24 309 (93·8%) replacement and 1592 (6·2%) voluntary donations. Females accounted for only 222 (0·9%) of potential donations. Deferral occurred in 3156 (12·2%) of attempts; 280 (1·1%) were permanently deferred, while 2876 (11·1%) were temporarily deferred. The most common reason for permanent deferral was a history of hepatitis B infection (n = 147, 4·7% of all deferrals). Major reasons for temporary donor deferral were low levels of haemoglobin (n = 971, 30·76%), low levels of platelets (n = 611, 19·35%) and previous history of jaundice (n = 192, 6·1%). CONCLUSIONS: This study reported a fairly similar pattern of donor deferrals as in other regional studies. Low haemoglobin levels and a history of hepatitis B infection were the most common factors for temporary and permanent donor deferrals, respectively.

Factors Associated with Periodontal Disease in Pregnant Diabetic Women.

There have been an association between systemic diseases and hormonal changes particularly diabetes which has been cited as a risk factor in the progression of periodontitis in pregnant women. The incidence and severity of periodontal diseases are increasing at a higher rate and a common condition in pregnant diabetic women among Bangladeshi population. This cross sectional study included 200 pregnant women who were selected from gynecological department and examined at the dental unit. The clinical parameters used were the Silness and Loe plaque index (PI), gingival scores and periodontal status and any relationship to socio demographic variables (age, occupation, level of education and urban or rural residence) and clinical variables (gestation period, previous pregnancy, type of diabetes and periodontal maintenance) were evaluated. The results showed that these clinical parameters increased concomitantly with an increase in the stage of pregnancy and in women with multiple pregnancies. Increased age, lower level of education, unemployment and patients residing in rural areas were associated with significantly higher gingival scores and periodontal measures. Women with increased age and multiple pregnancies usually have less interest to frequent periodontal maintenance showing a significant statistical relation between an increased age and changes in gingival and periodontal status; however no significant association was found between increased age and plaque index. It is concluded that gingival inflammatory symptoms are aggravated during pregnancy in diabetic women and are related to different clinical and demographic variables.

Knowledge, Attitude, Practice, and Barriers Regarding Prediabetes Among Adults in Saudi Arabia.

Background Prediabetes refers to a clinical condition in which blood glucose levels are elevated but do not meet the threshold for diabetes. Prediabetes is now thought to be reversible; lifestyle changes and other interventions can be successfully implemented during the prediabetes phase to avoid the development of type 2 diabetes. This study aims to improve health outcomes among Saudi community members who are at risk of developing prediabetes by assessing their knowledge, attitudes, practices, and barriers using a validated prediabetes questionnaire. Methods This study employed a cross-sectional design across various regions of Saudi Arabia. It included patients who were all non-diabetic Saudi adults over 18 years old and visited outpatient clinics. Structured questionnaires, which included participants' demographic information, knowledge, attitudes, practices, and barriers related to prediabetes, were employed. The collected data were analyzed using Statistical Product and Service Solutions (SPSS; IBM SPSS Statistics for Windows, Armonk, NY) software program. Results Data from 641 patients were collected in this survey. The respondents were predominantly female (330, 51.5%), with the mean ± SD of age being 36.3 ± 12.3. The participant knowledge levels of prediabetes were found to be good (399, 62.2%), moderate (193, 30.1%), and poor (49, 7.6%). The knowledge scores were significantly associated with age (P = 0.027), educational level (P < 0.001), education in the medical field (P = 0.019), and monthly family income (P = 0.009). The overall attitude of the participants toward prediabetes was generally positive (468, 73%). The practices related to diet and lifestyle among the participants were generally poor (538, 84%). Some participants did not take blood sugar tests because they were not available (121, 18.9%), lacked time (179, 27.9%), and were afraid of learning the test results (130, 20.3%). Conclusion The study found that, despite possessing an adequate level of knowledge and positive attitudes, Saudi patients poorly practice prevention methods for prediabetes. It highlights the need for targeted interventions to improve prediabetes awareness, promote healthier lifestyles, and address screening barriers. Prioritizing evidence-based strategies that cater to diverse demographic needs can prevent the progression of type 2 diabetes and enhance public health. The findings emphasize the importance of health education in Saudi Arabia and suggest that future research should focus on overcoming barriers, such as management complexity, diagnosis apprehension, and time constraints for check-ups.

Effect of natural and synthetic androgen hormone on sex reversal of Nile Tilapia (Oreochromis niloticus).

The present study aimed to produce a monosex population of all male Nile tilapia (Oreochromis spp.) using 17α-methyl testosterone and common carp testes (as a source of natural androgen). Trial was conducted into two consecutive phases, the first was fry (4-5 days old)administration with negative control (without hormone) and positive control (with hormone) feed viz., MT1:60mg/kg, MT2:70mg/kg (17α-MT), carp testis CT1:70% and CT2:80% for 30 days to reverse the sex of male fish and the second phase was nursing the fingerlings for two months on control diet (32% Crude protein).Results revealed a significant growth rate (P<0.05) in the control group where final weight (4.8±0.34ab) and weight gained was recorded as 0.66±0.03ac. In proximate chemical composition of body meat, CT2 treatment showed maximum retention of crude protein, crude fat, and ash whereas dry matter showed maximum retention in MT2 and CT1 treatments. Morphological and histological examination revealed significant difference (p<0.05) in phenotypic males of Nile tilapia fed with the highest percent in MT-treated diet (MT2) of 95±0.58a while MT1, CT2 and CT1 had males of 85±6.0b, 70±5.0b and 65±6.5b, respectively. It was concluded that synthetic androgen (17αMT) was more effective for masculinization but natural androgen scan be an alternative method to produce male tilapia population in an environment-friendly manner as they are inexpensive, eco-friendly, and radially available. These results suggested that synthetic and natural androgen supplementation in the diet plays a significant role in improving growth performance and body composition.

Extensive tension pneumocephalus presented in the setting of a challenging etiology.

Background: Pneumocephalus (PNC) is a well-described consequence in postoperative settings and skull fractures that is usually self-limiting. It can get complicated into tension PNC on some rare occasions, leading to an intracranial mass effect. PNC was also reported after unintentional dural puncture throughout the epidural anesthesia process. However, tension PNC resulting from epidural anesthesia procedures is an extremely rare outcome that implies urgent intervention to relieve the tension within the brain. Here, we report a case of an extensive tension intraventricular PNC 2 days following an epidural anesthesia procedure for a femur fixation surgery. Case Description: A 23-year-old male presented to the emergency department with basal skull fractures and a femur fracture due to a motorcycle accident. His skull base fracture was managed conservatively then he underwent a femur fixation procedure under epidural anesthesia. Two days after, he developed a severe headache with a disturbed level of consciousness. Computed tomography of the brain revealed an extensive PNC that involved all the subarachnoid spaces down to the cervical region and compressing the cerebellum, which was not found in the initial imaging. The patient's status improved after the twist-drill burr-hole evacuation of air under the water seal. Conclusion: Extensive tension PNC can occur after traumatic brain injury, especially after epidural anesthesia. Such cases should gain high focus because they may differ from simple PNC regarding diagnosis, treatment, and follow-up.

Malignant fibrous histiocytoma two years after autologous stem cell transplant for Hodgkin lymphoma: evidence for genomic instability.

Secondary malignancies (SMs) in Hodgkin lymphoma (HL) are thought to be related to exposure to alkalating agents, topoisomerase II inhibitors and ionizing radiation, and tend to occur a decade after initial therapy. We report a 14 year old autistic male, who developed malignant fibrous histiocytoma (MFH) two years after autologous stem cell transplantation for advanced stage HL. The MFH and post-surgical reactive tissues exhibited multiple clonal abnormalities. In addition, PHA-stimulated peripheral blood lymphocytes showed increased frequency of non-clonal chromosomal aberrations. The potential role of genomic instability in early onset of SM in our patient is discussed.

Uses of a familial adenomatous polyposis registry.

OBJECTIVES: To improve the prognosis of patients with familial adenomatous polyposis (FAP) by early diagnosis and prophylactic treatment through a coordinated FAP register. DESIGN: The establishment and descriptive analysis of the prospective database of the FAP registry. SETTING: University surgical unit, Colombo North Teaching Hospital Ragama, Sri Lanka. PATIENTS: Probands were identified by tracing all diagnosed FAP patients from 1996 to 2010 and their family members at risk. INTERVENTIONS: The establishment of a polyposis register included the following stages: ascertainment of probands (first contact symptomatic FAP patients), construction of pedigrees, counselling relatives and prophylactic screening of family members at risk, treatment and follow up. RESULTS: Twenty seven enrolled probands (12 male and 15 female, age 11-52 years, median age 34 years) were investigated. Pedigree analyses showed 206 relatives at risk. Twenty four family members at risk were screened of a total of 51 registered individuals. The rate of spontaneous mutations was 41%. Thirty five were diagnosed with FAP. Eight were screen detected (median age - 32 years) and 27 symptomatic (median age - 34 years). Concomitant colorectal cancer was detected in 17 (63%) symptomatic individuals and in 1 (13%) screen detected individual. Colectomy was performed in 27 (77%) patients while 8 (23%) are on chemoprophylaxis. Congenital hypertrophic retinal pigment epithelium was detected in 15. Desmoids tumours (6%) and other extraintestinal manifestations including osteomas, sebacious cysts and dental abnormalities (34%) were also detected. A thyroid gland malignancy was screen detected while retinoblastoma, hepatoblastoma and cerebral tumours were seen in pedigrees. CONCLUSIONS: A polyposis register may improve prognosis of FAP by early detection. It will help coordinate, optimise and streamline clinical management of patients with FAP and their relatives at risk.

Prevalence of Dental Fear and Anxiety and Its Triggering Factors in the Dental Office among School-going Children in Al Ahsa.

AIMS AND OBJECTIVES: To estimate the prevalence of dental fear and anxiety (DFA) among school-going children in Al Ahsa.To identify the factors that trigger DFA in the dental office. MATERIALS AND METHODS: A cross-sectional questionnaire-based study was conducted. Eight hundred and sixteen, 7-12-year-old children studying in government and private schools spread across the city of Al-Ahsa, Saudi Arabia, participated in the study. A self-reported questionnaire with 15 close-ended questions pertaining to DFA in logical order was distributed to all the participants. Each question had three options as responses with images. The children were asked to choose the option that best fitted their response. RESULTS AND CONCLUSION: The prevalence of DFA among boys and girls was found to be 50.4 and 71.28%, respectively. The majority of the boys studying in government schools reported DFA when informed about the treatment in advance, while most of those studying in private schools reported DFA at the sight of the dental chair and dental injections, while walking into the clinic, in the waiting room, when informed about the treatment in advance and their tooth being drilled. On the contrary, the responses were very similar among girls irrespective of their school. Most of the boys and girls did not experience any DFA when their parents were allowed to accompany them. Hence, a tailor-made approach for the management of the child in the dental office is warranted. CLINICAL SIGNIFICANCE: A tailor-made approach for the management of DFA in the dental office plays a significant role in successful treatment. HOW TO CITE THIS ARTICLE: Alshuaibi AF, Aldarwish M, Almulhim AN, et a l. Prevalence of Dental Fear and Anxiety and Its Triggering Factors in the Dental Office among School-going Children in Al Ahsa. Int J Clin Pediatr Dent 2021;14(2):286-292.

Quality of Life and Awareness of Hypertension Among Hypertensive Patients in Saudi Arabia.

Background and aim Hypertension possesses significant public health challenges for both developing and developed economies. Therefore, it is crucial to evaluate the awareness of hypertension and health-related quality of life (HRQoL) among patients with hypertension. This study aims to evaluate the knowledge of hypertension and HRQoL among hypertensive patients. Materials and methods A cross-sectional study using an anonymous questionnaire was conducted over a period of 4 months (November 2020 to February 2021) in Riyadh, Kingdom of Saudi Arabia (KSA). This study included 437 questionnaires submitted by the hypertensive population. Results A total of 437 participants were included in this study, with 55.4% being males (n=242). The majority (85.1%) were aware of the normal values of blood pressure. Many participants had no problems with mobility, personal care, usual activities, pain or discomfort, and anxiety or depression. Age groups showed a significant association with mobility and usual activities. The knowledge of hypertension was significantly associated with HRQoL. Conclusion This study found that majority of the hypertensive patients were aware of the standard values of blood pressure. HRQoL concerning physical functioning and general health is found to be good based on the EuroQol visual analogue scale (EQ VAS) in the hypertensive population who are aware of their condition. This study reported a weak yet significant association between hypertension-related knowledge and HRQoL scores. Several factors can affect the HRQoL of the hypertensive population including gender, education, occupation, and income status.

I-kappa-kinase-2 (IKK-2) inhibition potentiates vincristine cytotoxicity in non-Hodgkin's lymphoma.

BACKGROUND: IKK-2 is an important regulator of the nuclear factor-κB (NF-κB) which has been implicated in survival, proliferation and apoptosis resistance of lymphoma cells. In this study, we investigated whether inhibition of IKK-2 impacts cell growth or cytotoxicity of selected conventional chemotherapeutic agents in non-Hodgkin's lymphoma.Two established model systems were used; Follicular (WSU-FSCCL) and Diffuse Large Cell (WSU-DLCL2) Lymphoma, both of which constitutively express p-IκB. A novel, selective small molecule inhibitor of IKK-2, ML120B (N-[6-chloro-7-methoxy-9H-ß-carbolin-8-yl]-2-methylnicotinamide) was used to perturb NF-κB in lymphoma cells. The growth inhibitory effect of ML120B (M) alone and in combination with cyclophosphamide monohydrate (C), doxorubicin (H) or vincristine (V) was evaluated in vitro using short-term culture assay. We also determined efficacy of the combination in vivo using the SCID mouse xenografts. RESULTS: ML120B down-regulated p-IκBα protein expression in a concentration dependent manner, caused growth inhibition, increased G0/G1 cells, but did not induce apoptosis. There was no significant enhancement of cell kill in the M/C or M/H combination. However, there was strong synergy in the M/V combination where the vincristine concentration can be lowered by a hundred fold in the combination for comparable G2/M arrest and apoptosis. ML120B prevented vincristine-induced nuclear translocation of p65 subunit of NF-κB. In vivo, ML120B was effective by itself and enhanced CHOP anti-tumor activity significantly (P = 0.001) in the WSU-DLCL2-SCID model but did not prevent CNS lymphoma in the WSU-FSCCL-SCID model. CONCLUSIONS: For the first time, this study demonstrates that perturbation of IKK-2 by ML120B leads to synergistic enhancement of vincristine cytotoxicity in lymphoma. These results suggest that disruption of the NF-κB pathway is a useful adjunct to cytotoxic chemotherapy in lymphoma.

Role of fine-needle aspiration cytology in evaluating thyroid nodules. A retrospective study from a tertiary care center of Western region, Saudi Arabia.

OBJECTIVES: To evaluate the accuracy and e cacy of ne-needle aspiration cytology (FNAC) in diagnosing thyroid nodules, correlating it with the histopathological findings. METHODS: A retrospective evaluation of 314 patients was undertaken at a tertiary referral center of King Abdullah Medical City (KAMC), Makkah, Kingdom of Saudi Arabia, between 2010-2019. Patients who presented with thyroid swellings underwent ultrasonography and FNAC. If indicated, surgery was performed. The FNAC findings were compared to the final histopathological reports. RESULTS: The findings for FNAC from our data set of 314 patients showed a sensitivity value of 79.8%, specificity of 82.1%, accuracy of 74.8%, positive predictive value of 74.8%, and negative predictive value of 85.9%. Conclusion: Our study showed that FNAC has high sensitivity and speci city in the initial evaluation of patients with thyroid nodules. When guided by ultrasonography, the accuracy can be markedly improved. Molecular markers once widely available can improve the diagnostic power of FNAC to be no less than the histopathologic evaluation of thyroid tissue.

Comparative assessment of conventional chromosomal analysis and fluorescence in situ hybridization in the evaluation of suspected myelodysplastic syndromes: a single institution experience.

BACKGROUND: Myelodysplastic syndromes (MDSs) are a heterogeneous group of clonal hematopoietic neoplasms, roughly half of which harbor cytogenetic abnormalities with diagnostic, prognostic, and therapeutic significance. Fluorescence in situ hybridization (FISH) for the most commonly seen abnormalities (5/5q, -7/7q, +8, and -20/20q-) is routinely performed alongside conventional cytogenetics (CC) in the evaluation of suspected MDS despite conflicting reports of its relative contribution compared to CC alone. OBJECTIVES: To assess the additional diagnostic and prognostic value of performing concurrent FISH versus CC alone in cases of suspected MDS. MATERIALS AND METHODS: A total of 127 bone marrow samples submitted to our cytogenetic laboratory with a presumptive diagnosis of MDS were evaluated by concurrent CC and an MDS FISH panel. RESULTS: CC was used as the gold standard method with 100% sensitivity in detecting suspected MDS-associated cytogenetic abnormalities. FISH alone had a sensitivity of 76%, whereas CC alone achieved a sensitivity of 97%. The addition of FISH did not change the diagnosis nor change the Revised International Prognostic Scoring System score in any patient. Moreover, in 12 cases identified as positive by both CC and FISH, CC identified multiple chromosomal aberrations of clinical significance not interrogated by the FISH probe panel. CONCLUSION: CC alone is sufficiently sensitive in detecting suspected MDS-associated cytogenetic abnormalities that influence clinical decision-making. Routine FISH testing does not provide a significant increase in test sensitivity when an adequate karyotype is obtained. Therefore, FISH testing is best reserved for suspected MDS cases lacking sufficient metaphases.

Open access colonoscopy in the training setting: which factors affect patient satisfaction and pain?

BACKGROUND AND STUDY AIM: Patient satisfaction with colonoscopy is important for quality assurance; it may be affected by various factors, including patient characteristics, physician training level, and procedural or organizational features. We aimed to analyze how these factors influenced patient satisfaction and pain in an outpatient training setting. METHODS: Consecutive patients for open access colonoscopy (OAC) were enrolled in a prospective, single-blinded, controlled study. Primary and secondary outcomes were satisfaction and pain scores with and without trainee participation. A multivariate analysis was designed to achieve an 80 % power with an alpha value of 0.05. RESULTS: 368 patients were enrolled. Satisfaction with the procedure was high (mean score 1.36; 1 = best to 5 = worst). In the multivariate analysis only waiting time in the endoscopy suite was significantly associated with lower satisfaction scores ( P = 0.024). Satisfaction was unaffected by patient factors (gender, American Society of Anesthesiologists' [ASA] score, anxiety, etc). Higher pain scores were associated with higher anxiety levels ( P = 0.02), female gender ( P = 0.02), longer procedure ( P< 0.001), and lower sedation levels ( P = 0.001); trainee involvement (49 % of procedures) did not adversely affect satisfaction or pain scores. CONCLUSIONS: Patient satisfaction with OAC using sedation appears to depend primarily on organizational factors (waiting time beforehand). In contrast, pain is associated with patient characteristics (female gender, anxiety) and procedural factors (lower sedation, longer procedure). Trainee participation did not affect satisfaction or pain scores, a finding which may help to reassure patients undergoing OAC with trainee participation.

"Acute myelogenous leukemia like" translocations in CML blast crisis: two new cases of inv(16)/t(16;16) and a review of the literature.

We describe two patients with CML blast crisis with clonal evolution affecting 16q22 (t(16;16)(p13;q22) and inv(16)(p13;q22), abnormalities of core binding factor, usually found in de novo acute myeloid leukemia (AML)). The bone marrow of both cases showed myelomonocytic (M4) differentiation and eosinophilia. Both patients had prominent extramedullary disease and had poor response to treatment. A literature search focused on patients with CML and additional chromosome changes more typical of AML, revealed that the morphology of the blasts correlated with the finding typical of the underlying "AML" cytogenetic abnormality and an overall very poor clinical outcome, even in the groups with "favorable" AML type translocations.

A case report of a patient with microcephaly, facial dysmorphism, mitomycin-c-sensitive lymphocytes, and susceptibility to lymphoma.

We report on a 17-year-old boy with a unique lymphocyte mitomycin-C (MMC)-sensitive chromosomal breakage syndrome. He had failure to thrive, and has microcephaly, slight facial dysmorphism, and constitutional short stature but no other phenotypic or hematological manifestations of Fanconi anemia (FA). He developed B-cell lymphoma of the neck, which was treated with standard doses of alkylating agents. Major side effects related to chemotherapy did not occur. Normal erythrocyte corpuscular volume, MMC-insensitive fibroblasts, and the occurrence of lymphoma rather than AML sets this patient apart from typical FA. The combination of constitutional dwarfism, microcephaly, MMC-sensitive lymphocytes, and susceptibility to lymphoma represents an unusual constellation of symptoms among genetic disorders.

Variant t(14;18) in malignant lymphoma: a report of seven cases.

The BCL2 gene was identified through molecular analysis of the breakpoints involved in the t(14;18)(q32;q21) found in the majority of follicular lymphomas (FL). Variant translocations leading to juxtaposing of the BCL2 with either the IGK or IGL gene have been recognized in B-cell malignant lymphoma, although they are rare. We identified seven lymphoma cases that had variant translocations. Three cases had simple translocations involving two chromosomal regions: t(18;22)(q21;q11.2) in two cases and t(2;18)(p11.2;q21) in the third case. Complex translocations affecting more than two chromosomes were seen in the remaining four cases. Fluorescence in situ hybridization using the LSI IGH/BCL2 DNA probes revealed rearrangements of the BCL2 gene locus in all cases. In addition, expression of BCL2 protein was seen in all cases; only five of the seven cases expressed BCL6 protein. Morphologically, the lymphomas were categorized as B-cell follicular lymphoma in six cases and in the seventh case as diffuse large cell lymphoma (Richter syndrome) transformed from preexisting chronic lymphocytic leukemia (CLL). In case 2, the variant t(18;22) was seen as a secondary aberration evolving from a trisomy 12 clone. The findings revealed that BCL2 rearrangements in some malignant lymphomas occur through variant simple or complex chromosomal translocations, but always involving the IGH, IGK, or IGL chromosomal site. In addition, fluorescence in situ hybridization proved to be an important tool in evaluating these cases by showing IGH/BCL2 gene fusion or repositioning of the BCL2 gene.

Pediatric EBV-positive T-cell/histiocyte-rich large B-cell lymphoma with clonal cells in the bone marrow without overt involvement.

T-cell/histiocyte-rich large B-cell lymphoma (TCHRLBCL) is a variant of large B-cell lymphoma only rarely encountered in children. Here we report the case of an 8-year-old African American boy with Epstein-Barr virus (EBV)-positive TCHRLBCL who initially presented with right submandibular, anterior cervical and supraclavicular lymphadenopathy. Cytogenetic analysis of the lymph node revealed a near-triploid karyotype with complex chromosomal aberrations. Although morphologically the bone marrow was normal, the same cytogenetically abnormal clone was detected. The patient responded to chemotherapy with CHOP (doxorubicin, cyclophosphamide, vincristine and prednisone) therapy, with disappearance of the abnormal clone from the bone marrow. The patient remains in remission 26 months after the initial diagnosis.