Co-circulation of diverse paramyxoviruses in an urban African fruit bat population.

Bats constitute a reservoir of zoonotic infections and some bat paramyxoviruses are capable of cross-species transmission, often with fatal consequences. Determining the level of viral diversity in reservoir populations is fundamental to understanding and predicting viral emergence. This is particularly relevant for RNA viruses where the adaptive mutations required for cross-species transmission can be present in the reservoir host. We report the use of non-invasively collected, pooled, neat urine samples as a robust sample type for investigating paramyxoviruses in bat populations. Using consensus PCR assays we have detected a high incidence and genetic diversity of novel paramyxoviruses in an urban fruit bat population over a short period of time. This may suggest a similarly unique relationship between bats and the members of the family Paramyxoviridae as proposed for some other viral families. Additionally, the high rate of bat-human contact at the study site calls for the zoonotic potential of the detected viruses to be investigated further.

Endemic Lagos bat virus infection in Eidolon helvum.

Phylogenetic analyses suggest lyssaviruses, including Rabies virus, originated from bats. However, the role of bats in the maintenance, transmission and evolution of lyssaviruses is poorly understood. A number of genetically diverse lyssaviruses are present in Africa, including Lagos bat virus (LBV). A high seroprevalence of antibodies against LBV was detected in Eidolon helvum bats. Longitudinal seroprevalence and age-specific seroprevalence data were analysed and capture-mark-recapture (CMR) analysis used to follow 98 bats over 18 months. These data demonstrate endemic infection, with evidence of horizontal transmission, and force of infection was estimated for differing age categories. The CMR analysis found survival probabilities of seronegative and seropositive bats were not significantly different. The lack of increased mortality in seropositive animals suggests infection is not causing disease after extended incubation. These key findings point towards acute transmission of bat lyssaviruses in adapted bat hosts that occurs at a far higher rate than the occurrence of disease.

Changes in biomarkers of bone resorption over the first six months after pediatric hematopoietic cell transplantation.

Bone loss has been observed within the first six months after HCT in both children and adults. While there is some evidence that bone formation may be reduced in children after HCT, it is currently unknown whether bone resorption is increased. The objective of this prospective study was to evaluate changes in markers of bone resorption over the first six months after pediatric HCT. Twenty-six participants (eight females) aged 10.9 ± 3.4 yr entered the study prior to HCT. Bone resorption was measured by urine DPD and PYD, and by plasma NTX and CTX. Seventeen participants who completed day +30 visit and either day +100 or +180 visits were included in the analysis. DPD increased between days +30 and +100 (mean change, 11.3 nmol/nmol creatinine; p = 0.012) and between days +30 and +180 (13.7 nmol/nmol creatinine; p = 0.036). PYD increased between days +30 and +100 (32 nmBCE/L; p = 0.019). CTX increased between baseline and day +100 (5.9 µg/L; p = 0.012). Changes in NTX levels were not statistically significant. This study shows that markers of bone resorption increase in children after HCT, suggesting that increased resorption may be a contributing factor to the pathophysiology of bone loss after pediatric HCT.

Evidence for re-infection and persistent carriage of Shigella species in adult males reporting domestically acquired infection in England.

OBJECTIVES: We analysed national surveillance typing data of Shigella isolated from adult males with domestically acquired infection (a cohort largely consisting of men who have sex with men (MSM)) to establish whether multiple isolates from the same individual over time represented persistent carriage or re-infection. METHODS: We carried out a retrospective cohort study of adult males diagnosed with Shigella from 2004 to 2018. Median time intervals between multiple isolations of Shigella flexneri and S. sonnei were compared. Analysis of whole genome sequencing data provided strain discrimination at the single nucleotide level and was used to quantify the genetic distance among isolates. Maximum likelihood phylogenies were constructed to determine whether persistent carriage (characterized by multiple isolations of the same strain) or re-infection (characterized by multiple isolations of different strains) was best supported by the phylogenetic analysis. A comparison analysis was carried out using data linked to adult females with domestically acquired shigellosis. RESULTS: The number of men reporting multiple isolations of Shigella species was 165/4733 (3.5%) compared with 31/2423 (1.3%) females (p < 0.001). For isolate pairs from men associated with persistent carriage, the isolation time interval range was 6-176 days (median 23.5; IQR 8-70) and single nucleotide polymorphism (SNP) distance range was 0-7 SNPs (median 0.5; IQR 0-2). For those associated with re-infection, the isolation time interval was 34-2636 days (median 732; IQR 191-1258) and the SNP distance was 10-1462 SNPs (median 120; IQR 29-377). DISCUSSION: Multiple Shigella isolations in individuals with domestically acquired infections was more frequently observed in adult males than in adult females. Following the acute phase of infection, carriage can persist for months, and infection can recur within months, even with strains belonging to the same species and the same serotype. A combination of multiple sexual partners, persistent carriage following the acute phase of infection and evidence of recurrent re-infection is likely to contribute to sustained transmission in this population.

Stratospheric ozone, middle ultraviolet radiation, and carbon-14 measurements of marine productivity.

The effects of increased ultraviolet radiation, due to decreased stratospheric ozone, on marine phytoplankton have been investigated with the use of static bottle in situ carbon-14 productivity measurements. The relative biological efficiency for photoinhibition may be used to calculate biologically effective doses and resultant amplification factors. The carbon-14 technique (short-term incubations) is inadequate for assessment of possible large amplification factor photoprocesses that may be ecologically significant.

Phytoplankton blooming off the u.s. East coast: a satellite description.

A "bloom" of near-surface phytoplankton occurs in the Atlantic Slope region of the western Atlantic Ocean off the U.S. East Coast in the spring. Satellite time series of sea-surface temperature and phytoplankton pigment concentration, derived from measurements of the National Oceanic and Atmospheric Administration NOAA-7 Advanced Very-High-Resolution Radiometer and the National Aeronautics and Space Administration Nimbus-7 Coastal Zone Color Scanner, respectively, give information on the spatial extent and temporal development of such a bloom for a 28-day period in April through May 1982. The phytoplankton concentration of the slope area is comparable to that of the Atlantic Shelf. Total primary productivity of the slope during this period is equivalent to that of the shelf. The primary productivity within a warm-core ring and in the Gulf Stream system is less by a factor of 2.

Ozone depletion: ultraviolet radiation and phytoplankton biology in antarctic waters.

The springtime stratospheric ozone (O3) layer over the Antarctic is thinning by as much as 50 percent, resulting in increased midultraviolet (UVB) radiation reaching the surface of the Southern Ocean. There is concern that phytoplankton communities confined to near-surface waters of the marginal ice zone will be harmed by increased UVB irradiance penetrating the ocean surface, thereby altering the dynamics of Antarctic marine ecosystems. Results from a 6-week cruise (Icecolors) in the marginal ice zone of the Bellingshausen Sea in austral spring of 1990 indicated that as the O3 layer thinned: (i) sea surface- and depth-dependent ratios of UVB irradiance (280 to 320 nanometers) to total irradiance (280 to 700 nanometers) increased and (ii) UVB inhibition of photosynthesis increased. These and other Icecolors findings suggest that O3-dependent shifts of in-water spectral irradiances alter the balance of spectrally dependent phytoplankton processes, including photoinhibition, photoreactivation, photoprotection, and photosynthesis. A minimum 6 to 12 percent reduction in primary production associated with O3 depletion was estimated for the duration of the cruise.

Chronic liver injury drives non-traditional intrahepatic fibrin(ogen) crosslinking via tissue transglutaminase.

Essentials Fibrin clots are often implicated in the progression of liver fibrosis. Liver fibrosis was induced in transgenic mice with defects in clot formation or stabilization. Liver fibrosis and fibrin(ogen) deposition do not require fibrin polymerization or factor XIIIa. Fibrin(ogen) is an in vivo substrate of tissue transglutaminase in experimental liver fibrosis. SUMMARY: Background Intravascular fibrin clots and extravascular fibrin deposits are often implicated in the progression of liver fibrosis. However, evidence supporting a pathological role of fibrin in hepatic fibrosis is indirect and based largely on studies using anticoagulant drugs that inhibit activation of the coagulation protease thrombin, which has other downstream targets that promote fibrosis. Therefore, the goal of this study was to determine the precise role of fibrin deposits in experimental hepatic fibrosis. Methods Liver fibrosis was induced in mice expressing mutant fibrinogen insensitive to thrombin-mediated proteolysis (i.e. locked in the monomeric form), termed FibAEK mice, and factor XIII A2 subunit-deficient (FXIII-/- ) mice. Female wild-type mice, FXIII-/- mice and homozygous FibAEK mice were challenged with carbon tetrachloride (CCl4 ) twice weekly for 4 weeks or 6 weeks (1 mL kg-1 , intraperitoneal). Results Hepatic injury and fibrosis induced by CCl4 challenge were unaffected by FXIII deficiency or inhibition of thrombin-catalyzed fibrin polymer formation (in FibAEK mice). Surprisingly, hepatic deposition of crosslinked fibrin(ogen) was not reduced in CCl4 -challenged FXIII-/- mice or FibAEK mice as compared with wild-type mice. Rather, deposition of crosslinked hepatic fibrin(ogen) following CCl4 challenge was dramatically reduced in tissue transglutaminase-2 (TGM2)-deficient (TGM2-/- ) mice. However, the reduction in crosslinked fibrin(ogen) in TGM2-/- mice did not affect CCl4 -induced liver fibrosis. Conclusions These results indicate that neither traditional fibrin clots, formed by the thrombin-activated FXIII pathway nor atypical TGM2-crosslinked fibrin(ogen) contribute to experimental CCl4 -induced liver fibrosis. Collectively, the results indicate that liver fibrosis occurs independently of intrahepatic fibrin(ogen) deposition.

Unrelated donor hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis.

We report outcomes after unrelated donor hematopoietic cell transplantation (HCT) for 91 patients with hemophagocytic lymphohistiocytosis (HLH) transplanted in the US in 1989-2005. Fifty-one percent were <1 year at HCT and 29% had Lansky performance scores<90%. Most (80%) were conditioned with BU, CY, and etoposide (VP16) with or without anti-thymocyte globulin. Bone marrow was the predominant graft source. Neutrophil recovery was 91% at day-42. The probabilities of grades 2-4 acute GVHD at day-100 and chronic GVHD at 5 years were 41 and 23%, respectively. The overall mortality rate was higher in patients who did not receive BU/CY/VP16-conditioning regimen (RR 1.95, P=0.035). The 5-year probability of overall survival was 53% in patients who received BU/CY/VP16 compared to 24% in those who received other regimens. In the subset of patients with known disease-specific characteristics, only one of five patients with active disease at HCT is alive. For those in clinical remission at HCT (n=46), the 5-year probability of overall survival was 49%. Early mortality rates after HCT were high, 35% at day-100. These data demonstrate that a BU/CY/VP16-conditioning regimen provides cure in approximately 50% of patients and future studies should explore strategies to lower early mortality.

Relationship between self-reported cognitive difficulties, objective neuropsychological test performance and psychological distress in chronic pain.

BACKGROUND: Persons with chronic pain often report problems with cognitive abilities, such as memory or attention. There is limited understanding of whether objective performance is consistent with subjective reports, and how psychological factors contribute. We aimed to investigate these relationships in a group of patients expressing cognitive concerns, and evaluate the utility of self-report tools for pain management settings. METHOD: Participants with chronic pain (n = 41) completed standardized neuropsychological tests, and self-report measures of cognitive functioning, pain, mood and sleep, as part of a broader study investigating cognitive performance in pain. RESULTS: Average neuropsychological test performance was subtly below normative means (within one standard deviation). Twenty-five percent of the sample scored substantially below age-adjusted norms on one or more objective tests. There were moderate-to-large associations between objective performance (e.g. Trail-Making B) and subjective cognitive complaints (e.g. Everyday Memory Questionnaire - Revised), controlling for age and education level. This was moderated by anxiety, such that subjective-objective relationships were particularly strong in those with higher anxiety. Poorer test performance was associated with higher pain intensity and catastrophizing. Subjective-objective cognition relationships remained after controlling for catastrophizing. CONCLUSION: Patients' self-reported cognitive concerns concurred with objectively measured performance, independent of age, education and catastrophizing. Moreover, those with severe anxiety were more accurate in predicting their cognitive performance. The findings highlight some interesting cognition-mood relationships, and suggest that easy-to-administer questionnaires, such as the Everyday Memory Questionnaire - Revised and the Behavior Rating Inventory of Executive Function - Adult Version, may be useful to capture cognitive concerns in clinical settings. SIGNIFICANCE: Cognitive concerns in chronic pain reflected objective neurocognitive performance. This was moderated by anxiety, such that self-reported cognition was more consistent with objective performance in those with high anxiety. Our findings suggest that reported cognitive concerns should be heeded, and self-report measures may be used clinically to facilitate dialogue about cognitive functioning.

Hematopoietic cell transplantation for Chediak-Higashi syndrome.

We reviewed outcomes after allogeneic hematopoietic cell transplantation (HCT) in 35 children with Chediak-Higashi syndrome (CHS). Twenty-two patients had a history of the life-threatening accelerated phase of CHS before HCT and 11 were in accelerated phase at transplantation. Thirteen patients received their allograft from an human leukocyte antigen (HLA)-matched sibling, 10 from an alternative related donor and 12 from an unrelated donor. Eleven recipients of HLA-matched sibling donor, three recipients of alternative related donor and eight recipients of unrelated donor HCT are alive. With a median follow-up of 6.5 years, the 5-year probability of overall survival is 62%. Mortality was highest in those with accelerated phase disease at transplantation and after alternative related donor HCT. Only four of 11 patients with active disease at transplantation are alive. Seven recipients of alternative related donor HCT had active disease at transplantation and this may have influenced the poor outcome in this group. Although numbers are limited, HCT appears to be effective therapy for correcting and preventing hematologic and immunologic complications of CHS, and an unrelated donor may be a suitable alternative for patients without an HLA-matched sibling. Early referral and transplantation in remission after accelerated phase disease may improve disease-free survival.

Metabolic syndrome and cardiovascular disease following hematopoietic cell transplantation: screening and preventive practice recommendations from CIBMTR and EBMT.

Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors that increases the risk of cardiovascular disease, diabetes mellitus and all cause mortality. Long-term survivors of hematopoietic cell transplantation (HCT) have a substantial risk of developing MetS and cardiovascular disease, with the estimated prevalence of MetS being 31-49% among HCT recipients. Although MetS has not yet been proven to impact cardiovascular risk after HCT, an understanding of the incidence and risk factors for MetS in HCT recipients can provide the foundation to evaluate screening guidelines and develop interventions that may mitigate cardiovascular-related mortality. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal of reviewing literature and recommend practices appropriate to HCT recipients. Here we deliver consensus recommendations to help clinicians provide screening and preventive care for MetS and cardiovascular disease among HCT recipients. All HCT survivors should be advised of the risks of MetS and encouraged to undergo recommended screening based on their predisposition and ongoing risk factors.

Whole genome sequencing of Shigella sonnei through PulseNet Latin America and Caribbean: advancing global surveillance of foodborne illnesses.

OBJECTIVES: Shigella sonnei is a globally important diarrhoeal pathogen tracked through the surveillance network PulseNet Latin America and Caribbean (PNLA&C), which participates in PulseNet International. PNLA&C laboratories use common molecular techniques to track pathogens causing foodborne illness. We aimed to demonstrate the possibility and advantages of transitioning to whole genome sequencing (WGS) for surveillance within existing networks across a continent where S. sonnei is endemic. METHODS: We applied WGS to representative archive isolates of S. sonnei (n = 323) from laboratories in nine PNLA&C countries to generate a regional phylogenomic reference for S. sonnei and put this in the global context. We used this reference to contextualise 16 S. sonnei from three Argentinian outbreaks, using locally generated sequence data. Assembled genome sequences were used to predict antimicrobial resistance (AMR) phenotypes and identify AMR determinants. RESULTS: S. sonnei isolates clustered in five Latin American sublineages in the global phylogeny, with many (46%, 149 of 323) belonging to previously undescribed sublineages. Predicted multidrug resistance was common (77%, 249 of 323), and clinically relevant differences in AMR were found among sublineages. The regional overview showed that Argentinian outbreak isolates belonged to distinct sublineages and had different epidemiologic origins. CONCLUSIONS: Latin America contains novel genetic diversity of S. sonnei that is relevant on a global scale and commonly exhibits multidrug resistance. Retrospective passive surveillance with WGS has utility for informing treatment, identifying regionally epidemic sublineages and providing a framework for interpretation of prospective, locally sequenced outbreaks.

Autologous stem cell transplantation for high-risk Ewing's sarcoma and other pediatric solid tumors.

The prognosis for many pediatric and young adult patients with solid tumors that have metastasized at the time of diagnosis or have relapsed after therapy remains very poor. The steep dose-response curve of many of these tumors to alkylating agents makes myeloablative chemotherapy followed by autologous stem cell transplantation (ASCT) an attractive potential therapy. The role of ASCT for these high-risk patients is yet to be conclusively determined. We have transplanted 36 patients on two consecutive protocols with a variety of histological diagnoses. Overall survival (OS) was 63% (95% CI: 47-79%) at 1 year and 33% (95% CI: 16-50%) at 3 years. Patients with a diagnosis of Ewing's sarcoma (ES) or desmoplastic small round cell tumor (DSRCT) had significantly better survival than those with other diagnoses with estimated 3-year OS of 54% (95% CI: 29-79%) for this group of patients (P = 0.03). There were two transplant-related deaths both attributable to hepatic veno-occlusive disease. Median follow-up among survivors is 3.5 years (range: 0.6-7.9 years). These data justify continued investigation of ASCT as a consolidation therapy in patients with metastatic or relapsed ES and DSRCT.

Prevalence of conception and pregnancy outcomes after hematopoietic cell transplantation: report from the Bone Marrow Transplant Survivor Study.

We conducted a retrospective study to describe the magnitude of compromise in reproductive function and investigate pregnancy outcomes in 619 women and partners of men treated with autologous (n=241) or allogeneic (n=378) hematopoietic cell transplantation (HCT) between 21 and 45 years of age, and surviving 2 or more years. Median age at HCT was 33.3 years and median time since HCT 7.7 years. Mailed questionnaires captured pregnancies and their outcomes (live birth, stillbirth, miscarriage). Thirty-four patients reported 54 pregnancies after HCT (26 males, 40 pregnancies; eight females, 14 pregnancies), of which 46 resulted in live births. Factors associated with reporting no conception included older age at HCT (> or =30 years: odds ratio (OR)=4.8), female sex (OR=3.0), and total body irradiation (OR=3.3). Prevalence of conception and pregnancy outcomes in HCT survivors were compared to those of 301 nearest-age siblings. Although the risk for not reporting a conception was significantly increased among HCT survivors (OR=36), survivors were not significantly more likely than siblings to report miscarriage or stillbirth (OR=0.7). Although prevalence of conception is diminished after HCT, if pregnancy does occur, outcome is likely to be favorable. Patients should be counseled prior to transplant regarding strategies to preserve fertility.

Benefit of intensified therapy for patients with local or regional embryonal rhabdomyosarcoma: results from the Intergroup Rhabdomyosarcoma Study IV.

PURPOSE: To compare failure-free survival (FFS) and survival for patients with local or regional embryonal rhabdomyosarcoma treated on the Intergroup Rhabdomyosarcoma Study (IRS)-IV with that of comparable patients treated on IRS-III. PATIENTS AND METHODS: Patients were retrospectively classified as low- or intermediate-risk. Low-risk patients were defined as those with primary tumors at favorable sites, completely resected or microscopic residual, or orbit/eyelid primaries with gross residual disease and tumors less than 5 cm at unfavorable sites but completely resected. Intermediate-risk patients were all other patients with local or regional tumors. RESULTS: Three-year FFS improved from 72% on IRS-III to 78% on IRS-IV for patients with intermediate-risk embryonal rhabdomyosarcoma (P =.02). Subset analysis revealed two groups that benefited most from IRS-IV therapy. FFS at 3 years for patients with resectable node-positive or unresectable (group III) embryonal rhabdomyosarcoma arising at certain favorable sites (head and neck [not orbit/eyelid or parameningeal] and genitourinary [not bladder or prostate]) improved from 72% on IRS-III to 92% on IRS-IV (P =.01). Similarly, 3-year FFS for patients with completely resected tumor or with only microscopic disease remaining (group I or II) at unfavorable sites improved from 71% on IRS-III to 86% on IRS-IV (P =.04). Only patients with unresectable embryonal rhabdomyosarcoma (group III) at unfavorable sites had no improvement in outcome on IRS-IV (3-year FFS for IRS-III and IRS-IV, 72% and 75%, respectively; P =.31). CONCLUSION: IRS-IV therapy benefited certain subgroups of patients with intermediate-risk embryonal rhabdomyosarcoma. A doubling of the intensity of cyclophosphamide (or ifosfamide equivalent) dosing per cycle between IRS-III and IRS-IV is thought to be a key contributing factor for this improvement.

Autologous hematopoietic stem-cell transplantation for relapsed or refractory Hodgkin's disease in children and adolescents.

PURPOSE: To determine the treatment outcome and clinical factors that are of prognostic significance for children and adolescents with relapsed or refractory Hodgkin's disease (HD) who received treatment with high-dose chemotherapy and autologous hematopoietic stem-cell transplantation (HSCT). PATIENTS AND METHODS: Fifty-three consecutive children and adolescents 21 years of age or younger with relapsed or refractory HD underwent HSCT. RESULTS: At day 100 after transplantation, 29 patients (55%) were in a complete remission or maintained a continuous complete response, six (11%) had a partial response, and 11 (21%) failed to respond or had progressive disease. The failure-free survival (FFS) at 5 years was 31%, and overall survival was 43%. Twenty-one patients died of progressive HD, and nine died secondary to transplantation-related complications, including two secondary leukemias. Prognostic factors important for FFS were normal pretransplantation lactate dehydrogenase levels (5-year FFS = 42%), compared with patients with elevated LDH levels (5-year FFS = 0%) (P < .001), and disease sensitivity at the time of HSCT with FFS in untreated relapse, sensitive disease, and resistant disease 44%, 35%, and 9%, respectively (P = .06). There was no statistically significant difference in FFS or overall survival between age subgroups that were analyzed (< 13, 13 to 18, 19 to 21) or in comparison with an adult cohort. CONCLUSION: HSCT is an effective treatment modality that can result in long-term cures and should be considered for children and adolescents with relapsed HD.

Secondary solid cancer screening following hematopoietic cell transplantation.

Hematopoietic stem cell transplant (HCT) recipients have a substantial risk of developing secondary solid cancers, particularly beyond 5 years after HCT and without reaching a plateau overtime. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to facilitate implementation of cancer screening appropriate to HCT recipients. The working group reviewed guidelines and methods for cancer screening applicable to the general population and reviewed the incidence and risk factors for secondary cancers after HCT. A consensus approach was used to establish recommendations for individual secondary cancers. The most common sites include oral cavity, skin, breast and thyroid. Risks of cancers are increased after HCT compared with the general population in skin, thyroid, oral cavity, esophagus, liver, nervous system, bone and connective tissues. Myeloablative TBI, young age at HCT, chronic GVHD and prolonged immunosuppressive treatment beyond 24 months were well-documented risk factors for many types of secondary cancers. All HCT recipients should be advised of the risks of secondary cancers annually and encouraged to undergo recommended screening based on their predisposition. Here we propose guidelines to help clinicians in providing screening and preventive care for secondary cancers among HCT recipients.

Adamantinoma-like Ewing's sarcoma: genomic confirmation, phenotypic drift.

Ewing's sarcoma, a highly malignant neoplasm, is characterized by an 11;22 translocation [t(11;22) (q24;q12)], resulting in the fusion of genes FLII and EWS. Adamantinoma of extragnathic bones, a low-grade malignant neoplasm with epithelial features, is not typically considered in the differential diagnosis of Ewing's sarcoma. In this study, three osseous Ewing's sarcomas with histological, immunohistochemical, or ultrastructural epithelial features were subjected to reverse transcription-polymerase chain reaction and sequencing studies for the Ewing's sarcoma molecular rearrangement. (Two of the three cases were originally described as adamantinomas or nontypical Ewing's sarcoma before the availability of genetic characterization.) In addition, traditional cytogenetic analysis and a unique combined interphase molecular cytogenetic/ immunocytochemical approach with bicolor 11;22 translocation breakpoint flanking probes (cosmids) and pancytokeratin antibodies were performed on one neoplasm. At(11;22) (q24;q12) was found in one neoplasm and a type II EWS/FLI-1 fusion transcript was detected in all three neoplasms. The combined genetic/immunocytochemical approach revealed the presence of the 11 ;22 translocation in the nuclei of cytokeratin immunoreactive cells. These genotypic and phenotypic findings delineate a novel Ewing's sarcoma histologic variant, "adamantinoma-like Ewing's sarcoma."