Inadequate Specimens Research Articles

Evaluation of Stability of Serum on Different Storage Temperatures for Routine Chemistry Analytes

The stability of 21 routine biochemistry analytes was evaluated from the specimens which had been stored under three different temperature conditions for 30 days. Most of the 17 analytes showed significant change, however, the specimens under lower temperature showed more stability than those under higher temperature. glucose, Albumin, -glutamyl transferase, HDL cholesterol analytes were stable over 30 days under 22oC, 4oC, and -66oC conditions. This study might be helpful in interpreting the results reflecting the rate of change when inadequate specimens are measured.

Strategic management of transthoracic needle aspirates for histological subtyping and EGFR testing in patients with peripheral lung cancer: An institutional experience.

Lung cancer therapy is personalized based on the histological subtype and molecular status. Totally, 70% of lung cancer patients present in advanced stages and are diagnosed on small biopsy or cytology specimens, hence an accurate but tissue-sparing approach is necessary. This study aimed to demonstrate efficient utilization of cell block (CB) on transthoracic needle aspiration (TTNA) for lung cancer subtyping, and to investigate the usefulness of needle washing after TTNA for assessing EGFR molecular status. Each TTNA specimen from the 79 peripheral lung masses was divided into three parts; liquid-based cytology (LBC), CB (with or without immunohistochemistry), and needle washing for analysis of EGFR mutation using peptide nucleic acid-mediated real-time PCR clamping. Totally 79 specimens were diagnosed as malignancy, 75 (94.9%), benign, 3 (3.8%), and inadequate specimen, 1 (1.3%). The combination of LBC and CB (92.0%) showed a higher diagnostic yield for definitive subtyping of lung cancer than LBC alone (72.0%). Of the 75 malignant cases, 17 (22.7%) showed an EGFR mutation in needle washing specimens. EGFR mutational status was compared in all paired needle washing and scraped CBs with a 100% concordance. We hereby proposed a strategy to maximize biological information retrieval from a limited TTNA specimen in patients with peripheral lung cancer. This algorithm indicated CB preparation for accurate histological subtyping and waste needle washing for molecular testing.

Pre‐bisection of a single skin biopsy does not produce technically inadequate specimens for direct immunofluorescence: a review of 3450 specimens

Evaluation of a potential immunobullous disorder typically requires two pieces of tissue obtained by skin biopsy: one placed in formalin for conventional microscopy and a second placed in a different transport medium suitable for direct immunofluorescence (DIF) testing. Clinical practice in this area is not standardized, with dermatologists either obtaining two biopsies or dividing (pre-bisecting) a single biopsy. Some DIF specimens are technically inadequate for interpretation of subepidermal imunobullous disorders because the basement membrane zone is not intact, but it is unknown whether pre-bisecting the tissue increases the risk of compromising the specimen. To investigate whether technically inadequate DIF specimens are associated with pre-bisection. DIF specimens were consecutively sampled from a single referral center and identified as whole (non-bisected) biopsy specimens or pre-bisected biopsy specimens. The proportion of inadequate specimens was calculated for both groups. A total of 3450 specimens were included. The percentage of inadequate specimens was 5.072% (153/3016) for whole (non-bisected) specimens and 5.299% for pre-bisected specimens. This difference was not significant (chi square, p = 0.84). The study was sufficiently powered to detect a relative risk of 1.685. Pre-bisection of a single skin biopsy does not significantly increase the risk of a technically inadequate specimen for direct immunofluorescence testing.

Surgeon-performed ultrasound-guided fine-needle aspiration cytology of head and neck mass lesions: sampling adequacy and diagnostic accuracy.

Studies of surgeon-performed ultrasound-guided fine-needle aspiration cytology (US-FNAC) have been limited largely to thyroid nodules. This study evaluated the sampling adequacy and diagnostic accuracy of surgeon-performed US-FNAC for a large range of head and neck mass lesions, including lesions of the thyroid, salivary glands, and lymph nodes. The study included 617 cases of US-FNAC performed by a single surgeon between 2009 and 2013. Their medical histories and ultrasound (US) findings were retrospectively reviewed. Sample adequacy was analyzed according to the surgeon's experience, anatomic tumor location, and US tumor characteristics. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of FNAC were calculated after correlation with the surgical histopathologic results. The overall adequacy rate for surgeon-performed US-FNAC was 91.9 % (567/617). Inadequate specimens were obtained from 9.7 % (29/282) of the thyroid glands, 6.1 % of the salivary glands (6/98), and 6.3 % (15/237) of the lymph nodes. The effect of the surgeon's experience plateaued (inadequate sampling rate, 6-8 %) after 100 US-FNAC procedures. Inadequate sampling was associated with tumor characteristics such as cystic change and rim calcification. Overall, US-FNAC showed a sensitivity of 88.2 %, a specificity of 98.2 %, a PPV of 98.5 %, an NPV of 85.7 %, and a diagnostic accuracy of 91.6 %. With proper training and experience managing at least 100 US-FNAC cases, surgeons can ensure a low inadequate sampling rate and good diagnostic accuracy for a range of head and neck mass lesions.

The significance of functional renal obstruction in predicting pathologic stage of upper tract urothelial carcinoma.

Assessing the severity of upper tract urothelial carcinoma (UTUC) has been difficult because of inadequate biopsy specimens. Additional predictive parameters of disease stage would be useful when deciding a treatment plan; it has been suggested that preoperative hydronephrosis can be a surrogate. We examined the relationship between preoperative ipsilateral renal obstruction identified by imaging with final pathologic stage after nephroureterectomy (NU) for UTUC. We then analyzed those patients with ipsilateral renal obstruction and examined if tumor location is associated with an advanced pathologic stage. Patients who underwent NU for UTUC between the years 2001 to 2013 were analyzed and relevant staging studies and pathology were reviewed. Criteria for ipsilateral renal obstruction were defined by the presence of a delayed nephrogram on CT scan, renal cortical atrophy with associated hydronephrosis on cross-sectional imaging, and/or >10% split function discrepancy on nuclear renal scintigraphy with associated hydronephrosis. Eighty-two patients met inclusion criteria; 26/82 (31.7%) had locally advanced disease (pT3/T4), while 56/82 (63.4%) had organ-confined (≤pT2) disease. Of the patients with pT3/T4 disease, 10/26 (38.5%) demonstrated radiographic evidence of functional obstruction of the ipsilateral renal unit; similarly, in patients with ≤pT2 disease, 21/56 (37.5%) demonstrated ipsilateral renal obstruction (P=0.93). Of the patients with ipsilateral renal obstruction, in those patients with pT3/T4 disease, 7/10 (70.0%) had ureteral tumor involvement while 9/21 (42.9%) patients with ≤pT2 disease had tumor in the ureter (P=0.25). This study suggests that renal obstruction by radiographic analysis does not always predict advanced stage. In addition, there is a trend toward advanced stage when a patient has radiographic evidence of ipsilateral renal dysfunction and a ureteral tumor.

Mo1477 FISH Analysis of Aspirates Increases the Sensitivity of EUS-Guided FNA for the Diagnosis of Pancreatic Adenocarcinoma

EUS to exclude, detect and stage ampullary lesions and perform biopsy or FNA. EUS excluded suspected malignant disease in 43% of cases. Mo1477 FISH Analysis of Aspirates Increases the Sensitivity of EUS-Guided FNA for the Diagnosis of Pancreatic Adenocarcinoma Jose-Guillermo De La Mora-Levy*, Juan O. Campuzano, Judith Cruz-Velazquez, Octavio Alonso, Julio Sanchez Del Monte, Sergio R. Sobrino-Cossio, Angelica Hernandez-Guerrero Gastroenterology, National Cancer Institute, Mexico City, Mexico; Cytogenetics, National Cancer Institute, Mexico City, Mexico Background: The sensitivity of EUS-guided cytology for the diagnosis of pancreatic adenocarcinoma is between 70 & O90%; among the identified factors that predict a positive result, the presence of a cytopathologist, number and passes and posible the type of needle have been identified as helpful. Aim: To study if the addition of FISH to cytology increases the sensitivity of EUS-guided FNA. Material & Methods: Consecutive patients with a pancreatic mass, sent for EUS-guided FNA to our Unit. An Olympus GF-UCT 160 echoendoscope and 22 gauge needles (EchoTip , Cook Medical), were used. Between 1-4 passes (median: 2) were performed for preparation of slides and cell block; 1 random slide was used for FISH analysis, which was performed using a commercially available kit (Urovision ). NO cytopathologist was present during the procedure. A total of 112 patients was calculated as the number needed to demonstrate at least a 10% increase in sensitivity, assuming an average of 80% sensitivity. A positive result was considered when either cytopathology or FISH alone or both were positive. Diagnostic values were calculated for Cytology, FISH and the combination; increase in sensitivity was the main variable. Inadequate specimens were purposely not included. The gold standard was considered to be: the surgical specimen, or a combination of CA 19-9 values, appropriate clinical and imaging picture plus compatible outcome on follow-up (FU). The study was approved by the IRB of our Institution. Results: A total of 105 patients were included; 16 were excluded for various reasons and analysis was performed on 89 patients. 49 were female, with a median age of 58 years (37-84); median FU was 4 months (1-12). Diagnostic values are shown in Table 1: A 13% increase in sensitivity was found, even when the calculated number was not reached. Conclusion: The addition of FISH analysis to EUS-guided FNA increases the sensitivity and positive results in patients with pancreatic adenocarcinoma. FISH could be used routinely, specially in settings without an onsite cytopathologist and with relatively few needle passes.

Incidence and Predictive Factors of Inadequate Fine-Needle Aspirates for BRAFV600E Mutation Analysis in Thyroid Nodules

BRAF(V600E) mutation (valine-to-glutamate substitution at residue 600 of the B-type Raf kinase gene) analysis from thyroid aspirates is increasingly used as a prognostic or diagnostic marker. However, it is limited under some conditions. The purpose of this study was to assess the incidence and predictive factors of thyroid nodules with specimens inadequate for BRAF(V600E) mutation analysis. We performed a retrospective cohort study of consecutive patients who underwent ultrasound-guided fine-needle aspiration (FNA) and molecular testing of aspiration specimens. Patients who had inadequate specimens in both allele-specific polymerase chain reaction and direct DNA-sequencing methods were selected. Univariate and multivariate logistic regression analyses were performed to identify predictive factors of specimens inadequate for molecular tests. Specimens inadequate for BRAF(V600E) mutation analysis were seen in 168 of 7001 (2.4%) patients. Factors, including patient age and sex, nodule size, ultrasound diagnosis, the presence of calcification, and cystic changes within thyroid nodules, were not significant predictors of inadequate mutation analysis. Oval-to-round or irregular shapes (e.g., not taller-than-wide) and final benign results were significant factors in univariate analysis (p = 0.0002 and p = 0.0013, respectively). However, nodules aspirated by operators with less than 1 year of experience (odds ratio [OR], 3.005; p = 0.0070), and those that had spiculated margins (OR, 6.139; p = 0.0142), isoechogenicity (OR, 10.374; p = 0.0442), or nondiagnostic cytologic findings (OR, 73.637; p = 0.0055) remained significant risk factors after adjustment in multivariable analysis. Thyroid nodule specimens inadequate for BRAF(V600E) mutation analysis were frequently associated with FNA aspiration performed by inexperienced operators, nondiagnostic cytologic findings, benign nodules on final diagnosis, and probably benign ultrasound findings, such as isoechogenicity and not-taller-than-wide shape.

Identifying a Subpopulation for a Tailored Therapy: Bridging Clinical Efficacy From a Laboratory-Developed Assay to a Validated In Vitro Diagnostic Test Kit

In the United States, regulatory approval of a therapy that is tailored to a subpopulation may require the coapproval of a companion in vitro diagnostic (IVD) tool for identifying that subpopulation. Unfortunately, for many reasons, development of the companion IVD may lag such that it is unavailable during a pivotal clinical trial of the therapy. Instead, a laboratory-developed test (LDT) may be used on clinical trial specimens to identify the subpopulation on whom to evaluate the therapy. However, remaining specimen material is saved so that when the companion IVD is ready for market, the specimens can be retested, in an effort to “bridge” from the LDT to the IVD. Unfortunately, retest results can be missing or invalid because some subjects lack remaining specimen material or because what remains is unevaluable (e.g., due to insufficient specimen material, inadequate specimen quality). We frame the bridging analysis problem as one of estimating drug efficacy in the IVD-defined subpopulation. We develop a closed-form approach, as well as approaches based on multiple imputation and bootstrapping to address the missing data problem. We discuss this in the context of a case study involving a recent submission and approval in the United States of a drug and IVD in oncology.

Comparison of two techniques for endoscopic ultrasonography fine-needle aspiration in solid pancreatic mass.

Background:Endoscopic ultrasonography (EUS) is a newly imagine procedure for assessment and therapeutic in option. The aims of this study are comparison two techniques about EUS-fine-needle aspiration (EUS-FNA), including successful tissue sampling, complication, procedure time, and safety.Materials and Methods:A total of 100 patients with pancreatic solid masses were in the study, 50 patients underwent EUS-FNA with negative pressure as Group 1 and 50 patients underwent EUS-FNA without negative pressure and stylet as Group 2 over a 36 months period.Results:The study period was from March 2011 to January 2014. In total case, the male-to-female ratio was 1.27 with a mean age of 61.7 ± 1.3 years. The involvement of different regions of the pancreas, pancreatic head had the most frequent (69%) after that uncinate (12%), body (11%) and tail (8%). In 100 pancreatic EUS-FNA samples, 48% were interpreted as malignant on pathology evaluation, 15% as suspicious for malignancy, 27% as benign processes and 10% inadequate specimen. There were no significant differences between the adequacy of sample cells in two techniques (P < 0.148).Conclusion:The EUS-FNA without negative pressure and stylet technique was related with less contamination by blood and raise the diagnostic yield. We recommend further studies for better evaluation of our study with higher the cases because clinically the low the inadequate samples (6% vs. 14%) and less contamination with blood (20% vs. 50%) in the second group (P < 0.002).

Basal Cell Adenocarcinoma of the Sublingual Gland: A Case of an Inadequate FNA Cytology Specimen Rendering Conclusive Diagnosis Difficult

A history of a gradual increase in swelling mass was presented in the sublingual gland of a 72-year-old female. The inadequate cytologic specimens retrospectively contained some clusters of three-dimensional monomorphic and round basaloid cells having hyperchromatic small nuclei and scant cytoplasm, along with a small amount of spherical globules of amorphous material and myxoid stroma, adjacent to few squamous metaplastic tumor nests. We first interpreted it as a pleomorphic adenoma, basal cell adenoma (BCA), or adenoid cystic carcinoma (ACC). A tumor extirpation was performed, and gross examination revealed a non-capsulated and ill-defined tumor lesion, looking grayish to yellowish-white, focally associated with fat invasion. On microscopic examination, the tumor was predominantly composed of a proliferation of small to medium-sized mildly atypical epithelial cells having very rare mitoses, often arranged in a cribriform or alveolar growth pattern with peripheral nuclear palisading and scattered squamous differentiation, embedded in a prominent eosinophilic hyaline material. Therefore, we finally made a diagnosis of invasive basal cell adenocarcinoma (BCAC), defined as the malignant counterpart of benign BCA. We should be aware that owing to its characteristic features, cytopathologists might be able to determine correct diagnosis, based on multiple and adequate samplings.

High-Grade Chondrosarcoma Associated with Spindle Cell Components of the Cricoid Cartilage

A history of recent frequency in cough and sputum was presented in a 73-year-old male. A neck CT scan revealed a heterogeneously enhanced and poorly-demarcated mass, measuring approximately 35 × 35 mm, arising from the right cricoid cartilage and projecting into the airway. The inadequate cytologic specimen contained few individual cells or small clusters of tumor cells having pleomorphic and sometimes spindle- or multi-nuclei, and abundant clear or vacuolated cytoplasm, along with an amount of metachromatic chondroid stroma. We first interpreted it merely as carcinoma. A total laryngectomy was performed, and gross examination showed a multilobulated and firm mass with a grayish to whitish, fleshy and glistening appearance, involving the cricoid cartilage and cricothyroid muscle. However, the overlying surface tracheal mucosa was smooth. Microscopically, the tumor was predominantly composed of a solid proliferation of atypical chondrocyte-like cells having hyperchromatic bi- or multi-nuclei in a lobular fashion, embedded in an abundant chondroid matrix, associated with cellular spindled cell foci. Therefore, we finally made a diagnosis of grade 2 chondrosarcoma with spindle cell components. We should be aware that owing to its characteristic features, cytopathologists might be able to determine correct diagnosis, based on multiple and adequate cytology samplings.

Adequacy of the endometrial samples obtained by the uterine explora device and conventional dilatation and curettage: a comparative study.

Aims. Our aim is to compare the adequacy and diagnostic yield of samples obtained by the endometrial Explora Sampler I-MX120 with endometrial specimens obtained by conventional dilatation and curettage (D&C). Methods. A total of 1270 endometrial samples were received in the histopathology laboratories at the King Khalid University Hospital, Riyadh, Saudi Arabia, between 2007 and 2010. In the outpatient clinic, the Uterine Explora Model I was used to obtain 996 samples. The remaining 274 samples were obtained by conventional D&C. Sample adequacy and the clustering of inadequate specimens according to age groups by the two different techniques were compared and statistically analyzed. Results. Out of 1270 endometrial samples, 253 (19.9%) were inadequate. The Uterine Explora was used in 88.5% of these inadequate samples (253 samples), and the remaining 11.5% were obtained by D&C. The insufficient tissue incidence was higher with the Explora (17.6%) than with the D&C (2.2%) and the difference was statistically significant (P < 0.0001). The ages of the patients, as well as the clinical indications for the procedures, were recorded. Conclusion. This retrospective study demonstrated better specimen adequacy when D&C was used compared to the higher rate of sample insufficiency obtained with the Explora.

Feline reference intervals for the Sysmex XT-2000iV and the ProCyte DX haematology analysers in EDTA and CTAD blood specimens.

Laser-based haematology analysers are routinely used in veterinary clinical pathology laboratories, and are available to practitioners. However, feline haematological reference intervals (RIs) determined according to international recommendations are, to our knowledge, not available. Furthermore, platelet count RI is difficult to establish in cats because of the frequent occurrence of platelet aggregation in blood specimens. The purpose of this study was to establish feline haematological RIs with the Sysmex XT-2000iV and ProCyte DX analysers, in ethylenediamine tetra-acetic acid (EDTA) and in citrate, theophylline, adenosine and dipyridamole (CTAD), which is a combination of anticoagulants limiting platelet aggregation. Blood specimens from 120 healthy cats were analysed in duplicate, and the degree of platelet aggregation was assessed on blood smears. After exclusion of inadequate specimens, 81 sets of results (from 44 males and 37 females, aged from 6 to 116 months) were available for the determination of RIs by the non-parametric method. The effects of the anticoagulant, analyser and aggregation score were assessed. When the aggregation effect was significant, the RIs were determined using the subgroup of blood specimens with no or little aggregation. The effects of sex, age and weight were also investigated, but were moderate. The different RIs obtained with the Sysmex XT-2000iV and ProCyte DX analysers, and the two anticoagulants, were very similar to previous RIs established in EDTA with the ADVIA 120, another laser-based analyser, except for the platelet count in CTAD specimens. Its lower reference limit was higher in CTAD vs EDTA specimens, which confirms the interest in this anticoagulant in cats.

Clinical Utility of Endoscopic Ultrasound-Guided Fine-Needle Aspiration in the Diagnosis of Mediastinal and Intra-Abdominal Lymphadenopathy

Introduction: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has proven to be helpful in obtaining tissue samples from enlarged mediastinal and intra-abdominal lymph nodes. This is especially beneficial in the diagnosis and staging of malignancy. We retrospectively reviewed the clinical utility of this method at a tertiary care cancer hospital in Pakistan. Patients and Methods: The medical records of 183 consecutive patients referred to the gastroenterology service from August 2008 to March 2012 were reviewed in this retrospective study. The mean age of the patients at presentation was 46.7 years (range 6-87; 62% males); 119 patients had mediastinal and 64 had intra-abdominal lymphadenopathy. Major indications for referral were diagnosis of lymphadenopathy of unknown origin detected on CT scan or PET-CT, to exclude lymph node metastasis in patients with a known primary tumor and to rule out relapse of lymphoma following treatment or during follow-up. Rapid on-site evaluation (ROSE) was performed in all patients to confirm the adequacy of sampling, followed by definitive cytopathological evaluation. Results: EUS-FNA with ROSE obtained adequate tissue for cytology in 97.3% of the patients in this cohort. These results were further confirmed on final cytopathological analysis in 96.2% of patients. Two patients (1.1%) had inadequate specimens for final interpretation (97.3 vs. 96.2; p = 0.001). Clinical utility was 95% for mediastinal lymphadenopathy and 98.4% for intra-abdominal lymphadenopathy. Only 1 patient had a serious complication requiring hospitalization and this was successfully managed conservatively. Conclusion: EUS-FNA is safe and has a high clinical utility in diagnosing unexplained mediastinal and intra-abdominal lymphadenopathy.

Fine‐Needle Aspiration Cytology versus Direct Laryngoscopic Biopsy in Suspicious Laryngo‐Hypopharyngeal Masses

Objectives: Evaluate the feasibility and performance of ultrasound-guided fine needle aspiration cytology (FNAC) of suspicious laryngo-hypopharyngeal masses. Methods: Cross-sectional study (2012-2013). After routine clinical and radiological evaluation, patients with advanced laryngo-hypopharyngeal masses were included in the study. Early lesions and vascular masses were excluded. In all patients, ultrasound guided FNACs were performed with a free-hand technique by a single radiologist and direct laryngoscopic biopsies were done on the subsequent day. Results: A total of 10 patients met the criteria for the study. Nine patients were primary cases and one was recurrent. There were 8 males and 2 females in the age group of 40-73 years. Ultrasound guided FNAC reported squamous cell carcinoma in 8 patients, atypical cells in one patient and the remaining one had inadequate specimen. There was no complication following the procedure. In direct laryngoscopic biopsies 8 patients were positive for squamous cell carcinoma and two were negative. Ultrasound guided FNACs in these two negative cases were positive for squamous cell carcinoma. One case was a recurrent tumor and in the other, direct laryngoscopic biopsies were done twice. Both the patients were inoperable due to advanced disease and palliative treatments were planned based on FNAC reports. Conclusions: Although biopsy under direct laryngoscopy remains the gold standard technique, ultrasound guided FNAC can be used to diagnose advanced laryngo hypopharyngeal lesions. It is simple, safe, cost effective, and done as an out-patient procedure. It seems to be more beneficial in deep seated submucosal tumors.

Diagnostic Yield of Transjugular Liver Biopsy Samples to Evaluate for Infectious Etiology of Liver Dysfunction in Bone Marrow Transplant Recipients

To determine the diagnostic yield of transjugular liver biopsy (TJLBx) samples to evaluate for infectious etiology (immunosuppressed protocol [ISP] of TJLBx) in bone marrow transplant (BMT) recipients. A retrospective review of 78 TJLBx in 61 patients who had undergone BMT was undertaken. Biopsy was performed with an automated 19-gauge needle set. The primary indication was suspected graft-versus-host disease in all; a subset also sought to detect infectious liver pathology. In these (n = 31 biopsy samples, 22 patients), an ISP was used with tissue sent for bacterial, viral, fungal, and mycobacterial analysis in addition to histology. In the remainder (n = 47 biopsy samples, 41 patients), tissue was sent for histology only (H). Sample adequacy, histological diagnosis, microorganism assay results (ISP), and complications were reviewed. To assess sample adequacy in BMT compared to non-BMT patients, random control sample of 77 biopsy samples in 75 inpatients during the same period was reviewed (C). All but 1 TJLBx (C group) were technically successful (99%). One major (ISP) and 5 minor complications occurred (H = 3, ISP = 1, C = 1). There were 3 inadequate specimens (6.4%) in the H group, 4 in the ISP group (12.9%), and 4 in the C group (5.2%) (p = NS). No organisms were isolated in any ISP biopsy samples (yield 0%). When ISP is requested in BMT recipients, biopsy yields were lower, for unclear reasons possibly relating to degree of liver injury. ISP adds no useful positive information over histology alone. The value of negative cultures in this population is unclear.

Evaluation of the necessity of bilateral bone marrow aspirates and biopsies for the diagnosis of metastatic disease in pediatric patients with solid tumors.

10054 Background: Standard practice for staging solid tumors has been to perform bilateral bone marrow aspirates (BMA) and biopsies (BMB). However, the diagnostic yield of performing all 4 tests has not been thoroughly evaluated. This study evaluated the concordance between test types (aspirate and biopsy) and sites (right and left) to evaluate whether one type or one side would be sufficient. Methods: All patients with solid tumors who underwent a diagnostic bilateral bone marrow biopsy and aspirate performed between 2006 and 2011 at Children’s Hospital Boston were identifed in a search of hematopathology records.. Kappa coeffcients were estimated. Results: A search of the hematopathology data records revealed a total of 112 patients who had had a diagnostic bilateral BMA and BMB including patients with neuroblastoma (n=70 ), Ewing’s Sarcoma (n=11), rhabdomyosarcoma (n=25), retinoblastoma (n=5), and undifferentiated sarcoma (n=1). 73% (n=82) of the patients were negative for all tests; 27% (n=30) had at least one positive test. The results between right and left and aspirate and biopsy were highly correlated.(Kappa statistics: BMA and BMB (0.85); BMA-left and BMB-left (0.82); BMA-right and BMB-right (0.84); BMA-left and BMA-right (0.77); BMB-left and BMB-right (0.95). All 4 tests were positive in 63%, 3 tests positive in 10%, 2 tests positive in 13% and one test positive in 13%. The distribution of positive results did not differ by disease. Among 11 patients with less than 4 positive tests, 10 would have been diagnosed correctly with bilateral aspirates; only one patient (neuroblastoma) had positive results on biopsy only. In this patient, neither aspirate had spicules and was therefore likely an inadequate specimen. Conclusions: Bone marrow biopsy may not be essential for accurate diagnosis of metastatic disease in pediatric solid tumor patients. Further confirmation of these findings in a larger sample is warranted.

Natural type-C olivine fabrics in garnet peridotites in North Qaidam UHP collision belt, NW China

Water is known to change the lattice-preferred orientation (LPO) of olivine, which significantly affects seismic anisotropy in the Earth's upper mantle. Research into the LPO of olivine in the deep interior of the Earth has been limited due to inadequate specimens. We report both the water-induced LPOs of olivine and the presence of large quantities of water inside olivine, enstatite, and garnet in garnet peridotites from the North Qaidam ultrahigh-pressure (UHP) collision belt in NW China. We show that the [001] axis of olivine is aligned subparallel to the lineation and that the [100] axis is strongly aligned subnormal to the foliation. This alignment is a known feature of type-C LPO of olivine formed experimentally under water-rich conditions (≥700ppmH/Si) at high pressure and temperature. Enstatite possessed an LPO with the [001] axis aligned parallel to the lineation and the [100] axis aligned normal to the foliation. FTIR analysis of this specimen revealed that olivine contained concentrations of water up to 1130±50ppmH/Si in clean areas, whereas olivine, enstatite, and garnet contained considerably more water, i.e., 2600±100ppmH/Si, 5000±100ppmH/Si, and 21,000±200ppmH/Si, respectively, when exsolved inclusions were visible. Confocal micro-Raman spectroscopy of these exsolved inclusions revealed that they were composed of hornblende and amphiboles. Straight dislocations were also commonly observed in olivine and are characteristic of olivine that had been experimentally deformed under hydrous conditions. These observations suggest that the type-C LPO of olivine in the North Qaidam UHP belt formed under water-rich conditions.

HPV genotypes detected in cervical cancers from Alaska Native women, 1980–2007

BackgroundHuman papillomavirus (HPV) vaccine prevents cervical pre-cancers and cancers caused by HPV types 16 and 18. This study provides information on the HPV types detected in cervical cancers of Alaska Native (AN) women.MethodsCases of invasive cervical cancer diagnosed in AN women aged 18 and above between 1980 and 2007 were identified from the Alaska Native Tumor Registry. A representative formalin-fixed, paraffin-embedded archived pathology block was retrieved and serially sectioned to allow histologic confirmation of lesion (first and last sections) and PCR testing of intervening sections. Extracted DNA was tested for HPV using Linear Array HPV Genotyping Test (Roche Diagnostics) with additional INNO-LiPA HPV Genotyping Assay (Innogenetics) testing on negative or inadequate specimens. All specimens were tested for a minimum 37 HPV types.ResultsOf 62 cervical cancer specimens evaluated, 57 (91.9%) contained one or more HPV types. Thirty-eight (61.2%) cancers contained HPV types 16 or 18, and 18 (29%) contained an oncogenic type other than type 16 or 18.ConclusionsOverall, almost two-thirds (61.2%) of the archived cervical cancers had detectible HPV types 16 or 18, a finding similar to studies of US women. As expected, a proportion of cancers would not be prevented by the current vaccines. HPV vaccination and cervical cancer screening are important prevention strategies for AN women.

Transient Elastography Is a Useful Noninvasive Tool for the Evaluation of Fibrosis in Paediatric Chronic Liver Disease

Outcome of liver disease in children is mainly determined by severity and progression of liver fibrosis. Liver biopsy is the accepted standard for evaluating fibrosis but is limited by the need for sedation in children, sampling error, and risks including bleeding. The aim of the present study was to compare tools for noninvasive assessment of liver fibrosis in a paediatric cohort. Children undergoing liver biopsy for chronic liver disease were recruited and underwent transient elastography (TE). Liver biopsies were scored by a hepatohistopathologist from F0 (no fibrosis) to F4 (cirrhosis). TE was compared with biopsy score. During the study period, 104 children (62 boys) were enrolled (median age 13.6 years). Diagnosis was autoimmune liver disease in 27; nonalcoholic fatty liver disease in 37; posttransplant in 16; hepatitis B/C in 8; Wilson disease in 5; and the remainder, miscellaneous. TE was successful in all but 7 patients and was a good discriminator of significant fibrosis (≥ F2) (P < 0.001), severe fibrosis (≥ F3) (P < 0.001), and cirrhosis (F4) (P = 0.003). The area under the receiver operating characteristic curve for the prediction of ≥ F2, ≥ F3, and F4 using TE was 0.78, 0.79, and 0.96, respectively. TE performed best in children with autoimmune liver disease and in those posttransplant. The present study demonstrates that TE is a reliable tool in distinguishing different stages of liver fibrosis in paediatric patients. Thus, TE may serve as a useful adjunct to liver biopsy for diagnostic purposes providing a reliable method of noninvasively monitoring liver disease progression in children.