Transient myeloproliferative disorder in Down syndrome presenting with ascites: a case report

BACKGROUND: An increased frequency of acute myelogenous leukemia is a well known feature in children with Down syndrome. In addition, transient myeloproliferative disorders (TMD), which may mimic acute leukemia, also occur in neonates with Down syndrome. TMD is recognized shortly after birth or in the neonatal period and is characterized by leukocytosis and thrombocytopenia, which resolve spontaneously in four to six weeks. CASE: A 1.5-month-old, male infant born with Down syndrome and patent ductus arteriosus presented with abdominal distention due to ascites. Cytology of the fluid revealed immature myeloid cells and megakaryocytes. Flow cytometry of the ascitic fluid confirmed the presence of immature myelomonocytic cells. A complete hematologic evaluation along with the clinical findings supported the diagnosis of TMD in Down syndrome. CONCLUSION: TMD is an uncommon syndrome strongly associated with Down syndrome. Since the abnormal laboratory findings are seen primarily in the peripheral blood, it is usually diagnosed by a hematopathologist without much difficulty. Our case demonstrates the importance of cytopathologist familiarity with this entity so as not to erroneously diagnose a leukemic process. This is extremely important since most cases of TMD spontaneously resolve within a few weeks to months and do not require treatment other than supportive measures.     

Immunophenotype of a transient myeloproliferative disorder in a newborn with trisomy 21

Cytologic, immunologic, and cytogenetic studies were performed on the blast cells of a newborn with Down syndrome and transient myeloproliferative disease. This hematologic disorder is uncommon, and occurs primarily in infants with Down syndrome. This boy presented with a high white blood cell count and a high percentage of blast cells, without anemia or thrombocytopenia. Chromosome analysis showed a constitutional trisomy 21 without any other clonal abnormality. A three-color flow cytometric analysis was performed and revealed two different CD45 dim, CD34(+), CD117(+), CD56(+) immature subpopulations: the normal immature myeloid precursor and an immature blast cell population that expressed CD41, CD42, CD61, CD36, CD13, CD1a, and CD2. We postulate that this population could be the leukemic precursor involved in the acute megakaryoblastic leukemia frequently observed in children with Down syndrome.     

Mood disorder in a patient with Smith-Magenis syndrome: a case report

Smith-Magenis syndrome (SMS) is a microdeletion syndrome characterized by physical and neurobehavioural features. This report describes the case of a 27 year old female affected by SMS associated with a diagnosis, according to DSMIV criteria, of Mood Disorder N.O.S. and Intermittent Explosive Disorder. To our knowledge, the association of SMS with mood shifts has never been reported. Considering the genetic alterations that characterizes the SMS, further investigations on the region of the chromosome 17p11.2 could help produce more information on the role of melatonin in the genesis of mood disorder.     

Pulmonary tumor thrombotic microangiopathy successfully treated with corticosteroids: a case report

Background

Pulmonary tumor thrombotic microangiopathy is a special type of tumor thromboembolism. We report the case of a patient who developed pulmonary tumor thrombotic microangiopathy with alveolar hemorrhage. Almost all patients with pulmonary tumor thrombotic microangiopathy die within 1 week of the onset of dyspnea; however, the prognosis in this case was better, with 10 weeks of survival from presentation.

Case presentation

A 62-year-old Japanese man was referred to our hospital with a 4-week history of dyspnea on exertion and severe pulmonary hypertension. Five years previously, he had undergone distal gastrectomy for gastric cancer. He was afebrile, normotensive, and hypoxemic. A physical examination was unremarkable except for purpura on his upper extremities and trunk. Blood tests showed anemia and disseminated intravascular coagulation. Chest computed tomography revealed diffuse ground-glass opacities with emphysema in his upper lungs, moderate pleural effusions, mediastinal lymphadenopathy, and enlargement of the right ventricle and main pulmonary artery. A computed tomography pulmonary angiogram showed no evidence of pulmonary embolism. Lung perfusion scintigraphy showed multiple segmental defects. Although recurrence of gastric cancer was confirmed from the results of bone marrow biopsy, bronchoscopy was not performed due to bleeding diathesis. He was treated with corticosteroids, antibiotics, and platelet transfusion, following which resolution of the abnormal lung shadows and right ventricular pressure overload along with partial alleviation of respiratory failure was observed. Because of his poor performance status, he was eventually transited to palliative care and died 6 weeks after admission. Necropsy of the lung confirmed the diagnosis of pulmonary tumor thrombotic microangiopathy with alveolar hemorrhage.

Conclusions

Pulmonary tumor thrombotic microangiopathy should be considered in the differential diagnosis of patients with cancer who present with severe pulmonary hypertension. In pulmonary tumor thrombotic microangiopathy, local inflammation in pulmonary microvasculature may contribute to pulmonary hypertension, and regulation of inflammation using corticosteroids may help improve the prognosis.

     

Managing the risk of cancer in Cowden syndrome: a case report

ABSTRACT: INTRODUCTION: Cowden syndrome is a rare cancer predisposition syndrome inherited in an autosomaldominantfashion. The syndrome is characterized by hamartomatous polyps that affectmultiple organs: skin, mucous membranes, thyroid, breast, gastrointestinal tract,endometrium and brain. It is also associated with an increased risk of developing malignancyin many tissues but especially breast, thyroid and endometrium. CASE PRESENTATION: We present the case of a 30-year-old Tunisian woman with mental retardation who presentedto our facility with rectal hamartomatous polyps. Her medical history included fibrocysticdisease of the breast over the last three years. A physical examination revealed macrocephaly,hyperkeratotic papules on the mid-facial skin, palmoplantar keratosis and oral mucosalpapillomatosis. A breast examination revealed nodular breast tissue bilaterally and a diffusethyroid goiter. Our patient was clinically euthyroid. A total thyroidectomy was performed. Ahistopathologic examination revealed thyroid papillary carcinoma. A gastrointestinalevaluation revealed esophageal and gastric polyps. Biopsies showed hyperplastic andadenomatous lesions associated with Helicobacter pylori. A final diagnosis of Cowdensyndrome was made according to the syndrome testing criteria adapted by the US NationalComprehensive Cancer Network. A prophylactic bilateral mastectomy was proposed butrefused by our patient. Our patient was kept under surveillance for breast and colorectalmalignancies. CONCLUSIONS: Early and accurate diagnosis of Cowden syndrome is essential because it is a cancerpredisposition syndrome that carries an increased risk for developing malignancy in manytissues, especially breast and thyroid. For this reason, education regarding the signs andsymptoms of cancer is important. All patients must be screened for malignancies and optionsfor prophylactic mastectomy should be discussed. Guidelines for cancer screening includingsurveillance and management plans for these patients should be distinguished from those ofthe general population, and may lead to a more timely diagnosis and treatment of cancersassociated with this syndrome.     

Freeman-Sheldon (whistling face) syndrome with hyperpyrexia in the newborn: case report

Freeman Sheldon syndrome (FSS) is a rare, multiple congenital contracture syndrome that is relatively well-known, since affected children have a striking appearance. This entity was historically referred to as the "whistling-face syndrome". Malignant hyperthermia and hyperpyrexia have been documented in FSS after general anesthesia related to the neuropathy. We report a male neonate with FSS and hyperpyrexia without anesthesia. To our knowledge, our patient is the first in the literature with hyperpyrexia in the newborn period without anesthesia.     

46,XX ovotesticular disorder in a Mexican patient with Beckwith--Wiedemann syndrome: a case report

ABSTRACT: INTRODUCTION: Beckwith--Wiedemann syndrome is an overgrowth syndrome that is characterized by hypoglycemia at birth, coarse face, hemihypertrophy and an increased risk to develop embryonal tumors. In approximately 15% of patients, the inheritance is autosomal dominant with variable expressivity and incomplete penetrance, whereas the remainder of Beckwith--Wiedemann syndrome cases are sporadic. Beckwith--Wiedemann syndrome molecular etiologies are complex and involve the two imprinting centers 1 (IC1) and 2 (IC2) of 11p15 region. This case report describes, for the first time, the unusual association of ovotesticular disorder in a patient from Morelia, Mexico with Wiedemann-Beckwith syndrome. CASE PRESENTATION: We report the case of a Mexican six-year-old girl with Beckwith--Wiedemann Syndrome, ambiguous genitalia, and bilateral ovotestes. She has a 46,XX karyotype without evidence of Y-chromosome sequences detected by fluorescence in situ hybridization with both SRY and wcp-Y probes. CONCLUSION: Although a random association between these two conditions cannot be excluded, future analysis of this patient with Beckwith--Wiedemann syndrome and 46,XX ovotesticular disorder may lead to new insights into these complex pathologies. We speculate that a possible misregulation in the imprinted genes network has a fundamental role in the coexistence of these two disorders.     

Encephalopathy in a patient with loiasis treated with albendazole: A case report

BackgroundLoiasis is a vector-borne parasitic infection endemic across many areas of Central and West Africa. Its treatment is tricky due to the risk of serious neurologic adverse events occurring after the administration of microfilaricidal drugs, like diethylcarbamazine or ivermectin, in subjects with high pre-treatment microfilarial load. Albendazole is currently recommended to slowly reduce microfilaremia before curative regimen is prescribed.Case presentationWe report the case of a 25-year-old man from Guinea-Conakry who was incidentally diagnosed with highly microfilaremic Loa loa infection. A three weeks regimen of albendazole was prescribed. Minor neurologic side effects occurred after two weeks of administration, while serious encephalopathy developed one week later. Clinical and electroencephalographic features of the patient resembled those of an immune-mediated encephalitis. After exclusion of other causes of encephalopathy, treatment-related Loa loa encephalopathy induced by albendazole was suspected. Corticosteroid treatment was administered and the patient recovered.DiscussionOur case confirms that Loa loa treatment-related encephalopathy may occur even during albendazole treatment. The clinical and electroencephalographic similarities between Loa loa albendazole-related encephalopathy and immune-mediated encephalitis suggest the possibility of an underlying inflammation-based pathogenesis. Although corticosteroid administration is not recommended in Loa loa ivermectin-induced encephalopathy, in this case of Loa loa albendazole-induced encephalopathy it may have played a therapeutic role.     

Apert syndrome with omphalocele: A case report

Apert syndrome is a genetic disorder known as acrocephalopolysyndactyly type 1 caused by mutations in the fibroblast growth factor receptor 2 and characterized by coronal craniosynostosis, symmetric bone and skin syndactyly of hands and feet, and craniofacial dysmorphic features. The estimated prevalence of this syndrome is 10 to 15.5 cases per 1,000,000 live births. Apert syndrome has considerable clinical variability. We present a case of Apert syndrome and associated features reported to the National Registry of Congenital Anomalies of Argentina (RENAC). The reported case had omphalocele, esophageal atresia, and mega cisterna magna. The last two signs were reported several times as part of the clinical presentation of Apert syndrome. To our knowledge, this is the second reported case diagnosed with Apert syndrome associated with omphalocele. Birth Defects Research (Part A), 100:726–729, 2014. © 2014 Wiley Periodicals, Inc.     

Recognizing and managing the expanded risk of tumor lysis syndrome in hematologic and solid malignancies

Background

Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF) are Chronic Myeloproliferative Neoplasms (MPN) characterized by clonal myeloproliferation/myeloaccumulation without cell maturation impairment. The JAK2 V617F mutation and PRV1 gene overexpression may contribute to MPN physiopathology. We hypothesized that deregulation of the apoptotic machinery may also play a role in the pathogenesis of ET and PMF. In this study we evaluated the apoptosis-related gene and protein expression of BCL2 family members in bone marrow CD34⁺ hematopoietic stem cells (HSC) and peripheral blood leukocytes from ET and PMF patients. We also tested whether the gene expression results were correlated with JAK2 V617F allele burden percentage, PRV1 overexpression, and clinical and laboratory parameters.

Results

By real time PCR assay, we observed that A1, MCL1, BIK and BID, as well as A1, BCLW and BAK gene expression were increased in ET and PMF CD34⁺ cells respectively, while pro-apoptotic BAX and anti-apoptotic BCL2 mRNA levels were found to be lower in ET and PMF CD34⁺ cells respectively, in relation to controls. In patients' leukocytes, we detected an upregulation of anti-apoptotic genes A1, BCL2, BCL-X _L and BCLW. In contrast, pro-apoptotic BID and BIM _EL expression were downregulated in ET leukocytes. Increased BCL-X_L protein expression in PMF leukocytes and decreased BID protein expression in ET leukocytes were observed by Western Blot. In ET leukocytes, we found a correlation between JAK2 V617F allele burden and BAX, BIK and BAD gene expression and between A1, BAX and BIK and PRV1 gene expression. A negative correlation between PRV1 gene expression and platelet count was observed, as well as a positive correlation between PRV1 gene expression and splenomegaly.

Conclusions

Our results suggest the participation of intrinsic apoptosis pathway in the MPN physiopathology. In addition, PRV1 and JAK2 V617F allele burden were linked to deregulation of the apoptotic machinery.     

Development of tumor lysis syndrome (TLS): A potential risk factor in cancer patients receiving anticancer therapy

Tumor lysis syndrome (TLS) is characterized by hyperuricaemia, hyperphosphatemia, hyperkalaemia, as well as hypocalcaemia due to the breakdown of tumor cells undergoing cancer therapy (chemo/radio). Therefore it is of interest to evaluate oxidative stress using selective biological markers [Malondialdehyde (MDA), Superoxide Dismutase (SOD), Glutathione (GSH) and Catalase (CAT)] in TLS. We report the marked differences (statistically significant with control) observed among a selected set of biomarkers of oxidative stress (MDA = 8.66±1.37; SOD = 0.15±0.11; GSH = 2.25±.77; CAT = 0.76±.57) in TLS patients in addition to other conventional biomarkers. Moreover, correlation was investigated among the parameters of oxidative stress and other circulating biomarkers of TLS. Data suggest the use of SOD, MDA, and GSH as potential diagnostic biomarker for TLS with other biomarkers.     

A male newborn infant with fatco syndrome (fibular aplasia, tibial campomelia and oligodactyly): a case report

We report a male infant with fibular aplasia, tibial campomelia, and oligosyndactyly (FATCO syndrome). Radiographs showed a short angulated left tibia with fibular aplasia and ipsilateral oligodactyly. We consider our case the 7th patient with FATCO syndrome.     

Psychological stress contributed to the development of low-grade fever in a patient with chronic fatigue syndrome: a case report

Background

Low-grade fever is a common symptom in patients with chronic fatigue syndrome (CFS), but the mechanisms responsible for its development are poorly understood. We submit this case report that suggests that psychological stress contributes to low-grade fever in CFS.

Case presentation

A 26-year-old female nurse with CFS was admitted to our hospital. She had been recording her axillary temperature regularly and found that it was especially high when she felt stress at work. To assess how psychological stress affects temperature and to investigate the possible mechanisms for this hyperthermia, we conducted a 60-minute stress interview and observed the changes in the following parameters: axillary temperature, fingertip temperature, systolic blood pressure, diastolic blood pressure, heart rate, plasma catecholamine levels, and serum levels of interleukin (IL)-1β and IL-6 (pyretic cytokines), tumor necrosis factor-α and IL-10 (antipyretic cytokines). The stress interview consisted of recalling and talking about stressful events. Her axillary temperature at baseline was 37.2°C, increasing to 38.2°C by the end of the interview. In contrast, her fingertip temperature decreased during the interview. Her heart rate, systolic and diastolic blood pressures, and plasma levels of noradrenaline and adrenaline increased during the interview; there were no significant changes in either pyretic or antipyretic cytokines during or after the interview.

Conclusions

A stress interview induced a 1.0°C increase in axillary temperature in a CFS patient. Negative emotion-associated sympathetic activation, rather than pyretic cytokine production, contributed to the increase in temperature induced by the stress interview. This suggests that psychological stress may contribute to the development or the exacerbation of low-grade fever in some CFS patients.

     

Patau syndrome with a long survival. A case report

Trisomy 13 is a clinically severe entity; 85% of the patients do not survive beyond one year, and most children die before completing six months of age. We report a female child, 28 months old, white, the fourth child of a non-consanguineous couple, who presented trisomy 13. The child was born at term, from a vaginal delivery, weighing 2600 g. At birth, she was cyanotic, icteric, spastic, and cried weakly. The initial clinical examination detected polydactyly in the left hand, congenital clubfoot and convex soles, ocular hypertelorism, a low nasal bridge, numerous hemangiomas distributed throughout the body, cardiomegaly, and perimembranous inter-ventricular communication. There was no cleft lip or palate. On physical examination at 18 months old, the child weighed 6,900 g, had a cephalic perimeter of 41 cm, a thoracic perimeter of 43 cm and was 76 cm tall. At 28 months, she weighed 10,760 g and was 88.5 cm tall. Neuropsychomotor development retardation was evident from birth and, according to the psychologist and the social assistant of APAE (Handicapped Parents and Friends Association) in Cangu?u, Rio Grande do Sul, there was a noticeable improvement after physiotherapy and recreational sessions.     

Pulmonary arterial hypertension in a patient treated with dasatinib: a case report

Background

There have been several reports on dasatinib-induced reversible pulmonary hypertension. This is the first reported case in Latvia; the patient did not discontinue the drug after the first adverse effects in the form of pleural effusions, which we speculate led only to partial reversion of the disease.

Case presentation

A 67-year-old white man with chronic myelogenous leukemia was treated with the dual Src and BCR-ABL tyrosine kinase inhibitor dasatinib. After treatment with dasatinib he had multiple pleural effusions which were suspected to be caused by congestive heart failure. Later a transthoracic Doppler echocardiography and right-sided heart catheterization revealed severe pulmonary hypertension with pulmonary vascular resistance of 12 Wood units and mean pulmonary artery pressure of 53 mmHg. Computed tomography ruled out a possible pulmonary embolism; laboratory specific tests for human immunodeficiency virus, rheumatoid factor, and anti-nuclear antibodies were negative, and dasatinib-induced pulmonary arterial hypertension was diagnosed.A follow-up right-sided heart catheterization and 6-minute walk test done a month after the discontinuation of dasatinib showed significant improvement: mean pulmonary artery pressure of 34 mmHg and pulmonary vascular resistance of 4 Wood units.

Conclusions

Patients should always be closely monitored when using dasatinib for a prolonged time. Dasatinib-induced pulmonary hypertension may be fully reversible after the therapy is suspended, but the key factors involved are still unclear and need to be further studied.

     

On the existence of a myeloproliferative factor in patients with a myeloproliferative syndrome (author's transl)]

Serum of patients suffering from a chronic myeloproliferative disorder (polycythaemia, era, osteomyelofibrosis, chronic myeloid leukaemia) and serum of lethally irradiated rats injected before application of a single doses of erythropoietin did not enhance the effect of erythropoietin -- measured with the iron incorporation rate of polycythemic mice. The rationale for these experiments is to try to find a "myeloproliferative factor", which augments the number of stem cells as described in sera of patients with polycythaemia vera, osteomyelofibrosis, and lethally irradiated mice.     

Hypodipsic-hypernatremia syndrome in an adult with polycythemia: a case report

Background

Hypernatremia is a very common electrolyte disorder and is frequently encountered in out-patient as well as in-hospital settings. We describe an adult who was found to have unexplained relative polycythemia and episodic hypernatremia. A diagnosis of idiopathic hypodipsic-hypernatremia syndrome was made and the patient was managed with a water-drinking schedule.

Case presentation

A 24-year-old South African-Indian man was found to have polycythemia in association with episodes of hypernatremia. Investigations indicated that he had relative polycythemia. He experienced no thirst at a time when his serum sodium concentration was found to be 151?mmol/L. Further testing indicated that his renal response to arginine vasopressin was intact and magnetic resonance imaging of his brain revealed no hypothalamic lesions. A diagnosis of idiopathic hypodipsic-hypernatremia syndrome was made and he was managed with a water-drinking schedule that corrected his hypernatremia.

Conclusion

Hypodipsia should always be considered when a patient without physical or cognitive disability presents with unexplained episodic hypernatremia or with relative polycythemia.

     

Calcifying nested stromal epithelial tumor of the liver in a patient with Klinefelter syndrome: a case report and review of the literature

Background

Calcifying nested stromal epithelial tumor (CNSET) is a primary neoplasm of the liver, characterized by well-demarcated nests consisting of spindle and epithelioid cells with calcification and bone formation. An association of Cushing syndrome with CNSET has drawn attention, but the origin of CNSET has not been clarified.

Case presentation

We report here the case of a 20-year-old male with Klinefelter syndrome who underwent liver resection for an increasing liver tumor that was pathologically diagnosed with CNSET. He was postoperatively followed up and received several examinations, and recurrences and extrahepatic lymph node metastases were detected on the 64th day after surgery. Chemoembolization and chemotherapy were not effective, leading to tumor progression with development of progressive liver failure, and the patient finally died 164 days after hepatectomy.

Conclusions

This case suggests that an imbalance of hormones affects the genesis and progression of CNSET, and indicates the importance of closely following patients with CNSET by imaging with attention to hepatic recurrence and extrahepatic metastases.