Search

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of peripheral T-cell lymphoma affecting younger patients and associated with hemophagocytic lymphohistiocytosis. To clarify the molecular pathogenesis of SPTCL, we analyzed paired tumor and germline DNAs from 13 patients by whole-exome sequencing. All cases were Asians and were phenotypically sporadic with no family history of SPTCL. Consistent with a recent report, germline mutations in HAVCR2, encoding T-cell immunoglobulin mucin 3 (TIM3), were identified in 11 of 13 (85%) cases. All mutated cases were primary SPTCL, whereas the 2 cases without mutation were secondary SPTCL associated with underlying diseases, including viral infection and autoimmune disease. Ten patients harbored homozygous p.Y82C mutations, and 1 showed compound heterozygous mutations (p.Y82C and p.T101I). Both missense mutations altered highly conserved residues located in the extracellular immunoglobulin variable–like domain. According to the Genome Aggregation Database of >138 500 general individuals, both mutations were documented with minor allele frequencies < 0.007, indicating remarkable enrichment of these HAVCR2 alleles in SPTCL. SPTCL cells also harbored somatic mutations (6.2 per patient) that are frequently identified in genes associated with epigenetic regulation and signal transduction. In conclusion, individuals harboring biallelic HAVCR2 (TIM3) germline mutations were highly susceptible to sporadic SPTCL, which was also associated with clonal somatic mutations.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of peripheral T-cell lymphoma affecting younger patients and associated with hemophagocytic lymphohistiocytosis. To clarify the molecular pathogenesis of SPTCL, we analyzed paired tumor and germline DNAs from 13 patients by whole-exome sequencing. All cases were Asians and were phenotypically sporadic with no family history of SPTCL. Consistent with a recent report, germline mutations in HAVCR2, encoding T-cell immunoglobulin mucin 3 (TIM3), were identified in 11 of 13 (85%) cases. All mutated cases were primary SPTCL, whereas the 2 cases without mutation were secondary SPTCL associated with underlying diseases, including viral infection and autoimmune disease. Ten patients harbored homozygous p.Y82C mutations, and 1 showed compound heterozygous mutations (p.Y82C and p.T101I). Both missense mutations altered highly conserved residues located in the extracellular immunoglobulin variable–like domain. According to the Genome Aggregation Database of >138 500 general individuals, both mutations were documented with minor allele frequencies < 0.007, indicating remarkable enrichment of these HAVCR2alleles in SPTCL. SPTCL cells also harbored somatic mutations (6.2 per patient) that are frequently identified in genes associated with epigenetic regulation and signal transduction. In conclusion, individuals harboring biallelic HAVCR2(TIM3) germline mutations were highly susceptible to sporadic SPTCL, which was also associated with clonal somatic mutations.

Background Nasal cavity length (NCL) is important for determining analyzed nasal segment (ANS) of acoustic rhinometry (AR). AR is a technique for nasal airway assessment which nasal cross-sectional areas and nasal volume (NV) are obtained. NCL or ANS is the important parameter to determine NV measured by AR. The ANS used to calculate NV in previous literatures vary from 4 to 8 cm. However, there has not been any study regarding NCL of Asians which is probably different from that of Western countries.Objectives To measure NCL in Thai adults using nasal telescope and compared NCL between left and right sides as well as male and female as well as among age groups.Design Prospective studyMethods This study was performed on patients, aged 18–95 years, who underwent nasal telescopy under local anesthesia at the Department of Otorhinolaryngology, Siriraj Hospital. Baseline characteristics (sex and age) of patients were collected. NCL (from anterior nasal spine to posterior edge of nasal septum) of both nasal cavities was measured using rigid nasal telescope of 0 degree. Mean NCL length of both nasal cavities was calculated.Results There were 1277 patients, with 498 (39%) male and 779 (61%) female. The mean ± standard deviation (SD) of NCL of male was 6 ± 0.6 cm whereas that of female was 5.7 ± 0.5 cm. There were no significant differences in NCL between left and right sides as well as among age groups in each gender (p > 0.05 all). However, male had significantly longer NCL compared with that of female (p < 0.001). The mean ± SD of NCL of total population was 5.9 ± 0.6 cm.Conclusion The NCL of Thais was approximately 6 cm. These data are useful to determine ANS used to calculate NV when AR is performed.Plain Language Summaries

Extranodal NKT-cell lymphoma (ENKTL), nasal type, may be of NK or T-cell origin; however, the proportion of T-ENKTLs and whether they are of or type remains uncertain. To elucidate the cell of origin and detailed phenotype of ENKTL and assess any clinicopathologic associations, 67 cases of ENKTL from Thailand were investigated, together with 5 enteropathy-associated T-cell lymphomas (EATLs) for comparison. In all, 70 of the ENKTL were T-cell receptor (TCR) , and, in cases tested, negative (presumptive NK origin); 5 were TCR , 3 were TCR , 1 were TCR , and 21 were indeterminate. Out of 17 presumptive NK-ENKTLs tested, 3 had clonal TCR rearrangements. All cases were EBVand TIA-1; >85 were positive for CD3, CD2, granzyme B, pSTAT3, and LskMATK; and all were CD16−. Presumptive NK-ENKTLs had significantly more frequent CD56 (83 vs. 33) and CXCL13 (59 vs. 0) but less frequent PD-1 (0 vs. 40) compared with T-ENKTLs. Of the NK-ENKTLs, 38 were Oct-2compared with 0 of T-ENKTLs, and 54 were IRF4MUM1compared with 20 of T-ENKTLs. Only T-ENKTLs were CD5. Intestinal ENKTLs were EBVand had significantly more frequent CD30, pSTAT3, and IRF4MUM1 expression but less frequent CD16 compared with EATL. Significant adverse prognostic indicators included a primary non-upper aerodigestive tract site, high stage, bone marrow involvement, International Prognostic Index ≥2, lack of radiotherapy, Ki67 >40, and CD25 expression. The upper aerodigestive tract ENKTLs of T-cell origin compared with those of presumptive NK origin showed a trend for better survival. Thus, at least 11 of evaluable ENKTLs are of T-cell origin. Although T-ENKTLs have phenotypic and some possible clinical differences, they share many similarities with ENKTLs that lack TCR expression and are distinct from intestinal EATL.

T-cell acute lymphoblastic leukemia (T-ALL) comprises 15% of childhood leukemia. Although multiagent pulse chemotherapy has improved event-free survival in recent decades, the lack of reliable prognosticators and high rate of relapse remain a challenge. Described is a novel discovery of tumor-derived hyperprolactinemia in childhood T-ALL through a case associated with paraneoplastic galactorrhea. Prolactin production by tumor cells, although a rare phenomenon, is previously demonstrated in several adult cancers and 2 pediatric malignancies with unknown implications. This is the first report demonstrating tumor-derived prolactin in pediatric T-ALL and offers potential as a disease marker and therapeutic drug target.

Background: Siderophore is an iron chelator produced by microorganism. Pseudomonas aeruginosa produces two siderophores (pyoverdin and pyochelin). Desferrioxamine is a siderophore used in thalassemia patients to treat an iron overload of vital organs. Objective: Compare the ability of pyoverdin, pyochelin, and desferrioxamine for iron mobilization from ferritin. Materials and Methods: In vitro experiment, the ability of P. aeruginosa siderophores and desferrioxamine for iron mobilization from ferritin was compared by using a dialysis membrane assay at pH values of 7.4 and 6.0. Stimulation of P. aeruginosa PAO1 growth by all siderophores was studied in glucose minimum medium. Results: All three compounds were capable of iron mobilization at both pHs. At pH 6.0, the most effectiveness compound was desferrioxamine (31.6%), followed by pyoverdin (21.5%) and pyochelin (13.7%) compared on weight basis, each at 10 μg/mL. At equimolar concentration, their activities were desferrioxamine (38.5±1.2%), followed by pyoverdin (32.0±4.8%) and pyochelin (26.7±1.9%), respectively. Conclusion: The most effective compound in iron mobilization from ferritin was desferrioxamine, followed by pyoverdin and pyochelin respectively.

Malignant rhabdoid tumor has traditionally been defined by its histologic phenotype. However, genetic investigations of malignant rhabdoid tumor have revealed a characteristic loss of or mutation in the INI1gene on chromosome 22q. The occurrence and significance of soft tissue tumors meeting genetic criteria for malignant rhabdoid tumor but with an undifferentiated non-rhabdoid histology is poorly characterized. Seventeen undifferentiated sarcomas, lacking rhabdoid histology were identified either through the surgical pathology files of The Children's Hospital of Philadelphia (1980–2005) or in consultation. Immunohistochemistry for the INI1 protein showed a loss of nuclear expression within tumor cells in five of these cases. On histologic review, these five tumors had a featureless sheet-like architecture; four were small round blue cell tumors, and one showed focal spindling. Although they had variably prominent nucleoli, classic rhabdoid morphologic features were not identified in any of these cases at primary presentation. Additional immunohistochemistry showed a polyphenotypic profile. Four of the five tumors showed genetic abnormalities involving the INI1gene by a combination of fluorescent in situhybridization, reverse transcription-polymerase chain reaction, and/or mutational analysis. Patient ages ranged from 1 week to 5 years. Four patients were male, and one was female. Sites included two neck tumors, two extremity tumors, and one paraspinal tumor. Two patients are alive and well over 15 years from the time of diagnosis; the remaining four are alive and well but with less than 2 years follow-up. Thus, alterations of the INI1gene with consequent loss of expression identified a population of undifferentiated sarcomas lacking classic rhabdoid morphology in young patients, with evidence of favorable survival. Whether these undifferentiated sarcomas represent a clinicopathologic entity distinct from classic malignant rhabdoid tumor requires further investigation.

Cardiovascular dysfunction consistent with ischemia has been observed during episodes of painful crisis and following periods of heavy physical exertion in individuals with sickle cell disease. Similar findings have been observed in other individuals while taking the alpha-adrenergic agonist pseudoephedrine. However, acute myocardial infarction is extremely rare. The authors describe a case of sudden death in a child with sickle cell disease due to acute myocardial infarction and suggest that heavy exertional stress and use of pseudoephedrine may have precipitated the event.

We tested the hypothesis that decreasing nasal air volume (i.e., increasing nasal turbinate blood volume) improves nasal air conditioning. We performed a randomized, two-way crossover study on the conditioning capacity of the nose in six healthy subjects in the supine and upright position. Cold, dry air (CDA) was delivered to the nose via a nasal mask, and the temperature and humidity of air were measured before it entered and after it exited the nasal cavity. The total water gradient (TWG) across the nose was calculated and represents the nasal conditioning capacity. Nasal volume decreased significantly from baseline without changing the mucosal temperature when subjects were placed in the supine position (P< 0.01). TWG in supine position was significantly lower than that in upright position (P< 0.001). In the supine position, nasal mucosal temperature after CDA exposure was significantly lower than that in upright position (P< 0.01). Our data show that placing subjects in the supine position decreased the ability of the nose to condition CDA compared with the upright position, in contrast to our hypothesis.

Sinonasal polyposis represents a chronic inflammatory condition of unknown etiology. It is often associated with systemic diseases and is characterized by nasal obstruction, reduction in sense of smell, infection, and impaired quality of life. Endoscopy has enhanced the diagnosis and management of nasal polyps. The initial approach is medical management. Medical therapy consists of administration of intranasal steroids or a short course of systemic steroids. Other medical treatments considered are use of antibiotics, leukotriene modifiers, and acetylsalicylic acid avoidance. Surgical removal is performed for nonresponders to medical management. The purpose of surgery is to restore the nasal physiology by making the nose free from nasal polyps and allowing drainage of infected sinuses. With a computer-assisted navigation system and power instrumentation, surgical removal of polyps can be done more easily and accurately with fewer complications than previously. Medical therapy after surgery is essential for preventing recurrence.

Background:We have previously shown that subjects with seasonal allergic rhinitis out of season had a reduced ability to warm and humidify air compared with normal subjects. Objective:We sought to investigate whether allergic reactions induced by either seasonal exposure or nasal challenge with antigen would decrease the capacity of the nose to condition cold, dry air. Methods:We performed two prospective studies comparing the effects of allergic inflammation, induced by either seasonal exposure or nasal challenge with antigen, on nasal conditioning capacity (NCC). The total water gradient (WG) across the nose was used to represent the NCC. In the first study, the NCC was measured and compared before and during the allergy season in 10 subjects with seasonal allergic rhinitis. In the second study, 20 subjects with seasonal allergic rhinitis were recruited outside of the allergy season. NCC was measured and compared before and 24 hours after challenge with antigen. Results:In the first study, seasonal allergic subjects in season showed a significant increase in NCC when compared with their preseason baseline (total WG in season: 2050 ± 138 mg vs total WG preseason: 1524 ± 100 mg; P< .01). In the second study, antigen challenge led to early-phase and late-phase responses. There was a statistically significant increase in NCC 24 hours after antigen challenge compared with that before antigen challenge (total WG after antigen challenge: 1938 ± 101 mg vs total WG before antigen challenge: 1648 ± 84 mg; P= .01). Conclusion:Allergic reactions induced by either seasonal exposure or antigen challenge increase the ability of the nose to condition inspired air. We speculate that allergic inflammation increases this ability by changing the perimeter of the nasal cavity. (J Allergy Clin Immunol 2000;106:1045-52.)

Background: We have previously shown that hot, humid air partially reduces the early allergic response. Mechanisms for this effect have been suggested, but none has gained universal acceptance. The most likely explanations are a modification of mucosal temperature or a reduction in nasal secretion osmolality. Objective: We sought to investigate whether increasing the nasal mucosal surface temperature by immersing feet in warm water (WW) could decrease the immediate nasal response to challenge with allergen. Methods: We performed a randomized, 2-way crossover study on 14 subjects with seasonal allergic rhinitis outside of their allergy season. They immersed their feet in either WW (42^oC) or room-temperature water (RW; 30^oC) for 5 minutes before and during nasal challenge with diluent for the allergen extract, followed by 2 increasing doses of allergen. Results: There was a statistically significant increase in nasal mucosal temperature from baseline after warming of feet (WW, 1.9 +/- 0.1^oC, vs RW, 0.2 +/- 0.1^oC; P = .001), but there were no significant differences in body temperature (WW, 0.1 +/- 0.1^oC, vs RW, 0.4 +/- 0.1^oC; P = .1). Net changes from diluent challenge for all parameters were compared between immersion of feet in WW and RW. Immersion of feet in WW significantly inhibited allergen-induced sneezes (WW, 5.7 +/- 1.1, vs RW, 11.6 +/- 3.2; P < .01), human serum albumin levels (WW, 941.7 +/- 172.2 @mg/mL vs RW, 1524.8 +/- 220.6 @mg/mL; P < .01), and secretion weights (WW, 30.5 +/- 7.2 mg, vs RW, 41.8 +/- 6.8 mg; P < .01). Conclusion: Our data show that warming of feet decreases the early response to nasal challenge with antigen. This inhibitory effect is probably related to the increase in the nasal mucosal temperature. (J Allergy Clin Immunol 1999;104:285-93.)

Using intranasal corticosteroid (INCS) regularly is recommended for treating perennial allergic rhinitis. However, no studies have evaluated “as-needed” use.

Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is a rare subtype of peripheral T-cell lymphomas predominantly affecting younger individuals. Typically, SPTL presents with multifocal subcutaneous nodules, and nearly 20% of the patients have autoimmune disorders, including systemic lupus erythematosus, juvenile rheumatoid arthritis and Sjögren disease. Unlike other lymphomas, which usually require chemotherapy for long-term survival, immunosuppressive therapy alone yields favorable outcomes in SPTL. A previous study showed allelic NAV3gene aberrations (LOH or deletion by FISH) in 44% of the SPTL samples and comparative genomic hybridization (CGH) revealed numerous DNA copy number changes. In another study, recurrent mutations were identified in various epigenetic modifiers (72%) and components of the PI3K/AKT/mTOR signaling pathway (44%). However, molecular pathogenesis of this disease has not been clearly understood.

Radiofrequency inferior turbinate reduction (RFITR) of inferior turbinate hypertrophy (ITH) is an effective way to treat patients with intractable nasal mucosal obstruction. The objective of this study was to assess smell ability, nasal symptoms, inferior turbinate grading (ITG), peak nasal inspiratory flow (PNIF) of patients with chronic rhinitis (CR), and ITH before and after RFITR. Patients with CR and ITH, aged 18–60 years, who underwent RFITR, were prospectively recruited. Smell ability (measured by smell detection threshold [SDT]), visual analog scale (VAS) of nasal symptoms, ITG, and PNIF before and 6–10 weeks after RFITR were compared. Forty-eight subjects were included. All nasal symptoms were significantly decreased after RFITR. After surgery, SDT (tested by phenyl ethyl alcohol) was worsened in 7 patients (14.6%), improved in 8 patients (16.7%), and did not change in 33 patients (68.7%). SDT after RFITR of six patients in the worsened SDT group were still within normal range (> -6.5). There was only one patient whose SDT changed from normosmia to mild hyposmia (–7.25 to -5.38). In the improved SDT group, two of eight patients had obviously better SDT after RFITR, which changed from moderate hyposmia to normosmia (–3.65 to -10; -3.73 to -10), whereas six of eight patients had little better SDT after RFITR. RFITR also significantly reduced ITG and improved PNIF. In conclusion, the treatment of patients with CR and ITH with RFITR significantly improved PNIF, ITG, and nasal symptoms assessed by VAS, although SDT after RFITR could be the same or improved or worsened.

In 2007, a battery powered bone marrow aspiration and biopsy system (OnControl, Vidacare Corp, Shavano Park, TX) was developed and cleared by the US FDA for adult patients.  Multiple studies have evaluated the use of the Powered device in adults and found decreased procedure time, decreased patient pain, improved core biopsy specimens and a higher degree of operator satisfaction compared to traditional Manual Jamshidi-type devices; but there have been no studies demonstrating the system's utility for pediatric patients. In a study sponsored by Vidacare, we conducted a randomized controlled trial to compare the Powered bone marrow aspiration and biopsy system to Manual devices in children.

Abstract 4303

Falcon: Vidacare Corporation: Research Funding. Assanasen:Vidacare Corporation: Research Funding.

OBJECTIVE: To discuss pharmacotherapy challenges encountered during treatment of a pediatric oncology patient with Burkholderia cepaciasepticemia.CASE SUMMARY: An 11-year-old male with a history of aplastic anemia presented to the emergency department with a 1-day history of cough and purulent nasal discharge 6 months after undergoing bone marrow transplant. Blood cultures obtained from the patient's Broviac catheter revealed gram-negative rods. Piperacillin/tazobactam and tobramycin were administered, but the patient worsened clinically, with fever and chills. B. cepaciawas identified as the offending pathogen, and the therapy was changed to meropenem and ciprofloxacin, as piperacillin/ tazobactam and tobramycin are ineffective against Burkholderiaspp. Intravenous trimethoprim/sulfamethoxazole, the drug of choice for Burkholderiaspp. infections, was unavailable as it had been placed on national manufacturer backorder. The patient improved initially, but he later experienced recurrence of fever, and blood culture results were positive for Burkholderiaspp. Infection was eradicated after removal of the central line and administration of ceftazidime and oral minocycline.DISCUSSION: Literature reveals few cases of B. cepaciain pediatric oncology patients, and to our knowledge, no cases have been reported in bone marrow transplant patients in the US. Burkholderiaspp. is highly resistant to many antibiotics, and commonly used agents for the empiric treatment of febrile neutropenia are not active against this organism. This indicates that most oncology patients who present with this infection would not receive appropriate initial treatment. In addition, antibiotic therapy may need to be modified, based on drug availability.CONCLUSIONS: B. cepaciais an emerging multidrug-resistant pathogen that can produce severe infection in immunocompromised patients. It is pertinent to consider this organism in oncology patients who do not improve with standard therapy, as prompt use of correct pharmacotherapy is necessary to avoid serious morbidity as well as mortality in this population.

Background Bone marrow staging is important in determining the extent of disease and for making therapeutic decision in B-cell non-Hodgkin lymphoma (B-NHL). Flow cytometry has been widely used in this setting but its value has not been clearly demonstrated. Objectives To determine the usefulness of bone marrow flow cytometry in staging of B-NHL. Materials and Methods We compare the results of bone marrow studies using bone marrow aspirate (BMA), bone marrow biopsy (BMB) and three-color flow cytometry (FCM), in non-leukemic B-NHL patients performed during May 2003 to December 2006 at our institution and determine the concordant rate among these three methods in detecting bone marrow involvement by B-NHL. Results Two hundred and sixty-eight bone marrow samples were analyzed in this study. Diffuse large B-cell lymphoma (DLBCL) was the most common histologic subtype (60.8%). Bone marrow (BM) involvement as confirmed by immunohistochemistry of BMB was observed in 66 samples (24.6%). Prevalence of BM involvement was slightly higher in indolent B-NHL (32.2%) as compared to aggressive B-NHL (20.8%). Agreement among all three methods was observed in 163 samples (60.8%). BMA had the sensitivity of 77.3% and specificity of 73.8%. FCM alone had the sensitivity of 63.6% and specificity of 89.6%. FCM failed to demonstrate clonal B-cells mainly in patients with focal involvement pattern. When FCM was combined with BMA, the sensitivity was increased to 87.9% but the specificity was decreased to 67.8%. They did not perform significantly better than using morphological criteria in BMB alone, which showed sensitivity of 80.3% and specificity of 94.5%. Conclusion Based on these data, we conclude that flow cytometry may not be necessary in bone marrow staging of B-NHL in patients with non-leukemic presentation.