Andrew E Horvai

University of California, San Francisco, San Francisco, California, United States

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Publications (63)235.44 Total impact

  • Yuna Kang · Andrew E. Horvai
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    ABSTRACT: Dedifferentiated liposarcoma (DDL) frequently involves the retroperitoneum. In the absence of a lipogenic component histologically, the differential diagnosis of a retroperitoneal DDL includes other sarcomas and, if the tumor has visceral involvement, sarcomatoid carcinoma. DDL demonstrates amplification of chromosome subregion 12q13-q15. Detection of the amplification itself, or the resulting overexpression of the MDM2 and CDK4 genes by genetic and immunohistochemical methods, is a useful ancillary test in the diagnosis of DDL. More recently, immunohistochemistry for p16, the product of the CDKN2A gene, was shown to be a useful adjunct in differentiating well-differentiated liposarcoma from benign adipocytic tumors. In the present study, we examined the utility of p16 immunohistochemistry to distinguish DDL (n=44) from other high-grade and low-grade retroperitoneal mimics (n=73). p16 positivity was observed in 43/44 (98%) DDLs, with the majority of these showing strong, diffuse, staining. The rate of p16 positivity in other retroperitoneal tumors was lower (37/73, 51%) and staining was not as consistently diffuse or intense. Furthermore, p16 positivity varied between the control sarcomas based on tumor type as follows: 11/11 leiomyosarcomas, 8/11 pleomorphic undifferentiated sarcomas, 9/39 sarcomatoid carcinomas, 7/7 desmoid tumors, 1/3 endometrial stromal sarcomas, and 1/2 malignant gastrointestinal stromal tumors. On the basis of these findings, we conclude that p16 is highly sensitive for retroperitoneal DDL. However, the lack of specificity limits the diagnostic utility compared with the more established markers MDM2 and CDK4.
    No preview · Article · Oct 2015 · Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry
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    ABSTRACT: Purpose. To investigate the efficacy and morbidity of limb-sparing surgery with intraoperative radiotherapy (IORT) for patients with locally recurrent extremity soft tissue sarcoma (ESTS). Methods and Materials. Twenty-six consecutively treated patients were identified in a single institution retrospective analysis of patients with locally recurrent ESTS treated with IORT following salvage limb-sparing resection from May 2000 to July 2011. Fifteen (58%) patients received external beam radiotherapy (EBRT) prior to recurrence (median dose 63 Gy), while 11 (42%) patients received EBRT following IORT (median dose 52 Gy). The Kaplan-Meier product limit method was used to estimate disease control and survival and subsets were compared using a log rank statistic, Cox's regression model was used to determine independent predictors of disease outcome, and toxicity was reported according to CTCAE v4.0 guidelines. Results. With a median duration of follow-up from surgery and IORT of 34.9 months (range: 4 to 139 mos.), 10 patients developed a local recurrence with 4 subsequently undergoing amputation. The 5-year estimate for local control (LC) was 58% (95% CI: 36-75%), for amputation-free was 81% (95% CI: 57-93%), for metastasis-free control (MFC) was 56% (95% CI: 31-75%), for disease-free survival (DFS) was 35% (95% CI: 17-54%), and for overall survival (OS) was 50% (95% CI: 24-71%). Prior EBRT did not appear to influence disease control (LC, p = 0.74; MFC, p = 0.66) or survival (DFS, p = 0.16; OS, p = 0.58). Grade 3 or higher acute and late toxicities were reported for 6 (23%) and 8 (31%) patients, respectively. The frequency of both acute and late grade 3 or higher toxicities occurred equally between patients who received EBRT prior to or after IORT. Conclusions. IORT in combination with oncologic resection of recurrent ESTS yields good rates of local control and limb-salvage with acceptable morbidity. Within the limitations of small subsets, these data suggest that prior EBRT does not significantly influence disease control or toxicity.
    Full-text · Article · Sep 2015 · Sarcoma
  • Soo-Jin Cho · Andrew Horvai
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    ABSTRACT: Soft tissue lesions can contain bone or cartilage matrix as an incidental, often metaplastic, phenomenon or as a diagnostic feature. The latter category includes a diverse group ranging from self-limited proliferations to benign neoplasms to aggressive malignancies. Correlating imaging findings with pathology is mandatory to confirm that a tumor producing bone or cartilage, in fact, originates from soft tissue rather than from the skeleton. The distinction can have dramatic diagnostic and therapeutic implications. This content focuses on the gross, histologic, radiographic, and clinical features of bone or cartilage-producing soft tissue lesions. Recent discoveries regarding tumor-specific genetics are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Sep 2015
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    ABSTRACT: Objective The objective of this study is to investigate the efficacy and toxicity of intraoperative radiotherapy (IORT) and limb-sparing surgery for patients with primary, non-metastatic extremity soft tissue sarcoma (ESTS). Methods Sixty-six consecutively treated patients at our institution were identified. Additional external beam radiation therapy (EBRT) was delivered to 67 % patients, while 61 % underwent perioperative chemotherapy. Median IORT and EBRT doses were 12.5 and 60 Gy, respectively. Close or positive margins were found in the majority patients (59 %), and most tumors were high grade (88 %), deep in location (79 %), and of advanced American Joint Committee on Cancer (AJCC) stage (88 %). The Kaplan-Meier method was used to estimate disease control with subsets compared using a log rank statistic, while multivariate methods were used to identify predictors of disease control and use of EBRT. Toxicity was reported according to Common Toxicity Criteria for Adverse Events, version 4.0 (CTCAE v4.0) guidelines. Results The median duration of follow-up from IORT was 51 months, and 5-year Kaplan-Meier estimates were as follows: 78 % for local control (LC), 94 % for amputation-free, 72 % for metastasis-free control, 64 % for disease-free survival, and 81 % for overall survival. Age older than 50 years and stage III disease resulted in increased local recurrence on univariate analysis (p = 0.02 and p = 0.06, respectively), while the addition of EBRT did not significantly influence LC (p = 0.27). Cox multivariate regression analysis indicated that age was the only independent predictor of local recurrence (p = 0.004). Among patients with close/positive margins, there was a benefit to including EBRT (p = 0.01). Acute and late ≥grade 3 toxicity was reported for 16 and 18 patients, respectively. Conclusion IORT in combination with oncologic resection of high-risk ESTS yields excellent rates of LC and limb salvage with acceptable morbidity.
    No preview · Article · Aug 2015
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    ABSTRACT: We present the case of a 46-year-old woman with no significant past medical history who developed left mid-thigh pain and fullness. Imaging demonstrated a mineralized soft-tissue mass, which increased in size during a year of monitoring, but retained a circumscribed appearance. The mass was located in the medial soft tissues of the thigh, separate from the bone on imaging studies, and this finding was confirmed during excision. The mass showed gross and microscopic features of an aneurysmal bone cyst. This diagnosis was supported by cytogenetic analysis revealing a t(17;17)(p13;q21) translocation corresponding to the USP6 and COL1A1 loci. Soft-tissue aneurysmal bone cyst is a rare entity, with fewer than 25 reports in the literature. Limited cytogenetic information about these tumors is available. To our knowledge, the USP6 and COL1A1 rearrangement has only previously been described in a pediatric soft-tissue aneurysmal bone cyst. We also discuss the differential diagnosis of ossifying soft-tissue lesions.
    No preview · Article · Jul 2015 · Skeletal Radiology
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    ABSTRACT: We present the case of a 33-year-old man with no significant medical history who developed right scapular pain, left-sided sacroiliac joint pain, and lower back pain, and was eventually diagnosed with chronic recurrent multifocal osteomyelitis (CRMO). Imaging demonstrated multiple scattered T2-hyperintense lesions on MRI at the spine and the left SI joint, some of which progressed and one regressed in size on follow-up. Histopathology demonstrated only non-specific chronic inflammation compatible with CRMO. No evidence of infectious organisms or neoplastic processes was found. The pain was relapsing and remitting in nature. Laboratory investigations were notable for no evidence of hematologic malignancy or infection, but only a mild increase in alkaline phosphatase. This case highlights that CRMO, despite being thought of as a childhood-onset disease, can present in adults as well, and also provides illustrative examples of imaging and histological findings.
    No preview · Article · Mar 2015 · Skeletal Radiology
  • David Solomon · Nancy Joseph · James Grenert · Andrew Horvai

    No preview · Conference Paper · Feb 2015
  • Jessica L. Davis · Andrew E. Horvai
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    ABSTRACT: Aims: Diagnosis of osteosarcoma, while important for eligibility in clinical trials and proper therapy, may be challenging when no bone or osteoid matrix is identified on biopsy. Therefore, other adjunct tests have been sought to help confirm the diagnosis. SATB2 has been shown as a reliable marker of osteoblastic differentiation. The aim of this study was to examine SATB2 expression in osteosarcomas and other primary bone sarcomas, to evaluate its diagnostic utility in discriminating osteogenic versus non-osteogenic sarcomas. Methods and results: Forty-eight pre-treated osteosarcoma biopsies, including 26 whole-section cases and 22 tumors on tissue microarrays (TMA), and 36 non-osteogenic bone sarcomas were evaluated. 45 of 48 cases (94%) of osteosarcomas demonstrated nuclear immunoreactivity for SATB2 (all whole slide sections showed expression). Positive SATB2 expression was observed in 11/22 (50%) undifferentiated pleomorphic sarcoma (UPS), 5/11 (45%) fibrosarcoma, 0/2 (0%) pleomorphic rhabdomyosarcomas, and 0/1 (0%) leiomyosarcoma. The sensitivity of SATB2 for osteosarcoma was 94% and the specificity was 55%. Stronger intensity staining was observed in osteosarcoma (p<0.0001). Conclusions: SATB2 is a sensitive marker for osteosarcoma; however, it is not specific, with expression observed in other high-grade primary bone sarcomas. Intriguingly, the lack of specificity may suggests that the undifferentiated sarcomas (UPS and fibrosarcomas) with SATB2 expression, in fact, represent osteosarcomas that produce too little matrix to detect with routine sampling or consist of osteoblast precursors that do not synthesize matrix. This article is protected by copyright. All rights reserved.
    No preview · Conference Paper · Feb 2015

  • No preview · Conference Paper · Feb 2015
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    ABSTRACT: We report a case of longstanding, large tumor involving spinal nerve roots of the cauda equina. The tumor showed small round cells arranged in nests and cords and immunophenotypic features of glomus tumor, along with infrequent mitoses and a low Ki-67 labeling index, but exhibited some rosette-like structures, CD99 and focal Neu-N expression. Subsequent molecular analysis showed the presence of an EWSR1-WT1 gene fusion by FISH, which was confirmed by RT-PCR. To our knowledge, this is the first case reported with EWSR1-WT1 fusion in a small round blue cell tumor with smooth muscle differentiation and an indolent course.
    No preview · Article · Oct 2014 · Human pathology
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    ABSTRACT: Purpose: To serially monitor bone remodeling in the swine femur after magnetic resonance (MR) imaging-guided high-intensity focused ultrasound (HIFU) ablation with MR imaging, computed tomography (CT), sodium fluorine 18 (Na(18)F)-positron emission tomography (PET), and histopathologic examination, as a function of sonication energy. Materials and methods: Experimental procedures received approval from the local institutional animal care and use committee. MR imaging-guided HIFU was used to create distal and proximal ablations in the right femurs of eight pigs. The energy used at the distal target was higher (mean, 419 J; range, 390-440 J) than that used at the proximal target (mean, 324 J; range, 300-360 J). Imaging was performed before and after ablation with 3.0-T MR imaging and 64-section CT. Animals were reevaluated at 3 and 6 weeks with MR imaging (n = 8), CT (n = 8), Na(18)F-PET (n = 4), and histopathologic examination (n = 4). Three-dimensional ablation lengths were measured on contrast material-enhanced MR images, and bone remodeling in the cortex was measured on CT images. Results: Ablation sizes at MR imaging 3 and 6 weeks after MR imaging-guided HIFU ablation were similar between proximal (low-energy) and distal (high-energy) lesions (average, 8.7 × 21.9 × 16.4 mm). However, distal ablation lesions (n = 8) demonstrated evidence of subperiosteal new bone formation at CT, with a subtle focus of new ossification at 3 weeks and a larger focus of ossification at 6 weeks. New bone formation was associated with increased uptake at Na(18)F-PET in three of four animals; this was confirmed at histopathologic examination in four of four animals. Conclusion: MR imaging-guided HIFU ablation of bone may result in progressive remodeling, with both subcortical necrosis and subperiosteal new bone formation. This may be related to the use of high energies. MR imaging, CT, and PET are suitable noninvasive techniques to monitor bone remodeling after MR imaging-guided HIFU ablation.
    No preview · Article · Oct 2014 · Radiology
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    ABSTRACT: Cellular schwannoma is an uncommon, but well-recognized, benign peripheral nerve sheath tumor, which can be misdiagnosed as malignant peripheral nerve sheath tumor. To develop consensus diagnostic criteria for cellular schwannoma, we reviewed 115 malignant peripheral nerve sheath tumor and 26 cellular schwannoma cases from two institutions. Clinical data were retrieved from the electronic medical records, and morphologic features, maximal mitotic counts, Ki67 labeling indices, and immunohistochemical profiles (SOX10, SOX2, p75NTR, p16, p53, EGFR, and neurofibromin) were assessed. Several features distinguish cellular schwannoma from malignant peripheral nerve sheath tumor. First, in contrast to patients with malignant peripheral nerve sheath tumor, no metastases or disease-specific deaths were found in patients with cellular schwannoma. More specifically, 5-year progression-free survival rates were 100 and 18%, and 5-year disease-specific survival rates were 100 and 32% for cellular schwannoma and malignant peripheral nerve sheath tumor, respectively. Second, the presence of Schwannian whorls, a peritumoral capsule, subcapsular lymphocytes, macrophage-rich infiltrates, and the absence of fascicles favored the diagnosis of cellular schwannoma, while the presence of perivascular hypercellularity, tumor herniation into vascular lumens, and necrosis favor malignant peripheral nerve sheath tumor. Third, complete loss of SOX10, neurofibromin or p16 expression, or the presence of EGFR immunoreactivity was specific for malignant peripheral nerve sheath tumor (P<0.001 for each). Expression of p75NTR was observed in 80% of malignant peripheral nerve sheath tumors compared with 31% of cellular schwannomas (P<0.001). Fourth, Ki-67 labeling indices ≥20% were highly predictive of malignant peripheral nerve sheath tumor (87% sensitivity and 96% specificity). Taken together, the combinations of these histopathological and immunohistochemical features provide useful criteria to distinguish between malignant peripheral nerve sheath tumor and cellular schwannoma with high sensitivity and specificity. Additional retrospective and prospective multicenter studies with larger data sets will be required to validate these findings.Modern Pathology advance online publication, 5 September 2014; doi:10.1038/modpathol.2014.109.
    No preview · Article · Sep 2014 · Modern Pathology
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    ABSTRACT: The Ewing sarcoma family of tumors (EFT) is a group of highly malignant small round blue cell tumors occurring in children and young adults. We report here the largest genomic survey to date of 101 EFT (65 tumors and 36 cell lines). Using a combination of whole genome sequencing and targeted sequencing approaches, we discover that EFT has a very low mutational burden (0.15 mutations/Mb) but frequent deleterious mutations in the cohesin complex subunit STAG2 (21.5% tumors, 44.4% cell lines), homozygous deletion of CDKN2A (13.8% and 50%) and mutations of TP53 (6.2% and 71.9%). We additionally note an increased prevalence of the BRCA2 K3326X polymorphism in EFT patient samples (7.3%) compared to population data (OR 7.1, p = 0.006). Using whole transcriptome sequencing, we find that 11% of tumors pathologically diagnosed as EFT lack a typical EWSR1 fusion oncogene and that these tumors do not have a characteristic Ewing sarcoma gene expression signature. We identify samples harboring novel fusion genes including FUS-NCATc2 and CIC-FOXO4 that may represent distinct small round blue cell tumor variants. In an independent EFT tissue microarray cohort, we show that STAG2 loss as detected by immunohistochemistry may be associated with more advanced disease (p = 0.15) and a modest decrease in overall survival (p = 0.10). These results significantly advance our understanding of the genomic and molecular underpinnings of Ewing sarcoma and provide a foundation towards further efforts to improve diagnosis, prognosis, and precision therapeutics testing.
    Full-text · Article · Jul 2014 · PLoS Genetics
  • Jessica L Davis · James P Grenert · Andrew E Horvai
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    ABSTRACT: Context.-Defects in mismatch repair proteins have been identified in Lynch syndrome-associated liposarcomas, as well as in rare sporadic sarcomas. However, it is unclear if mismatch repair defects have a role in sarcoma tumorigenesis. Microsatellite instability is a surrogate marker of mismatch repair defects. Objectives.-To determine whether sporadic dedifferentiated liposarcomas display microsatellite instability and, if so, to evaluate whether such instability differs between the lipogenic and nonlipogenic components of these tumors. Design.-The diagnoses of conventional dedifferentiated liposarcoma were confirmed by a combination of morphologic, immunophenotypic, and molecular studies. Standard fluorescence-based polymerase chain reaction, including 5 mononucleotide microsatellite markers (BAT25, BAT26, NR21, NR24, and MONO27), as well as 2 pentanucleotide repeat markers (Penta C and Penta D), was used to test for instability and loss of heterozygosity. Results.-We demonstrated only a single case (1 of 43) with microsatellite instability at one mononucleotide marker. No sarcomas showed high-level microsatellite instability. However, loss of heterozygosity at the pentanucleotide markers was observed in 8 of 43 cases. The presence of loss of heterozygosity was overrepresented in the nonlipogenic (dedifferentiated) components compared with the paired lipogenic (well differentiated) components. Conclusions.-Mismatch repair defects do not contribute to sporadic dedifferentiated liposarcoma tumorigenesis. Whether the observed loss of heterozygosity drives tumorigenesis in liposarcoma, for example by affecting tumor suppressor or cell cycle regulator genes, remains to be determined.
    No preview · Article · Jun 2014 · Archives of pathology & laboratory medicine
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    ABSTRACT: Precise regulation of bone resorption is critical for skeletal homeostasis. We report a 32-year-old man with a panostotic expansile bone disease and a massive hemorrhagic mandibular tumor. Originally from Mexico, he was deaf at birth and became "bow-legged" during childhood. There was no family history of skeletal disease. Puberty occurred normally, but during adolescence, he experienced difficulty straightening his limbs, sustained multiple fractures, and developed a bony tumor on his chin. By age 18 years, all limbs were misshapen. The mandibular mass grew and protruded from the oral cavity, extending to the level of the lower ribs. Other bony defects included a similar maxillary mass and serpentine limbs. Upon referral at age 27 years, biochemical studies showed serum alkaline phosphatase of 1760 U/L (Nl: 29-111) and other elevated bone turnover markers. Radiography of the limbs showed medullary expansion and cortical thinning with severe bowing. Although the jaw tumors were initially deemed inoperable, mandibular mass excision and staged partial maxillectomy were eventually performed. Tumor histopathology showed curvilinear trabeculae of woven bone on a background of hypocellular fibrous tissue. Fibrous dysplasia of bone was suspected, but there was no mutation in codon 201 of GNAS in samples from blood or tumor. His clinical findings, elevated serum markers, and disorganized bone histology suggested amplified receptor activator of nuclear factor-κβ (RANK) signaling, even though his presentation differed from conditions with known constitutive activation of RANK signaling (e.g., familial expansile osteolysis). We found a unique 12 base-pair duplication in the signal peptide of TNFRSF11A, the gene that encodes RANK. No exon or splice site mutations were found in the genes encoding RANK-ligand or osteoprotegerin. Alendronate followed by pamidronate therapies substantially decreased his serum alkaline phosphatase activity. This unique patient expands the known phenotypes of the disorders of RANK signaling activation.
    No preview · Article · Apr 2014 · Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research
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    Andrew E. Horvai · Richard C. Jordan
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    ABSTRACT: The canonical Wnt/β-catenin pathway is involved in the formation of craniofacial skeleton and oral tissues. Aberrant nuclear localization of β-catenin protein has been described in several human diseases including a subset of odontogenic tumors thereby suggesting an important role in tumor development. Fibro-osseous lesions of the craniofacial skeleton comprise several neoplastic, and reactive mesenchymal proliferations in which β-catenin status is unknown. To study this, we immunostained 171 fibro-osseous lesions for β-catenin protein and, for lesions with nuclear positivity, sequenced exon 3 of the CTNNB1 gene and exon 15 of the APC gene. Nuclear β-catenin immunostaining was detected in 34 (20 %) tumors with no correlation between nuclear positivity and either age, gender, or tissue decalcification status (p = 0.2, 0.17, 0.12, respectively). Absent nuclear β-catenin in fibrous dysplasia was the only diagnostically significant finding (p = 0.0034). A single point mutation at Asp56 of CTNNB1 was identified in one case of ossifying fibroma. A second ossifying fibroma and one desmoplastic fibroma demonstrated point mutations (Glu1229 and Tyr1475, respectively) in the APC gene. These findings show that apart from fibrous dysplasia where nuclear β-catenin is rare, nuclear β-catenin staining has limited utility in discriminating among the craniofacial fibro-osseous lesions. The molecular mechanisms underlying nuclear β-catenin accumulation in the positive tumors is unlikely to be mediated by CTNNB1 exon 3 or APC exon 15 mutations in most cases.
    Preview · Article · Mar 2014 · Head and Neck Pathology
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    ABSTRACT: Targeted therapies are increasingly being evaluated for patients with Ewing sarcoma (EWS). Optimal strategies for quantifying key signaling proteins in EWS remain unclear. We sought to quantify tumor expression of signaling pathway proteins in EWS using 3 methodologies. A total of 46 blocks of formalin-fixed paraffin-embedded tissue were obtained from 40 patients with EWS. Tumor was evaluated for the expression of proteins in the insulin-like growth factor type 1 receptor (IGF-1R), epithelial growth factor receptor (EGFR), and mTOR pathways using standard immunohistochemical analysis (IHC), automated quantitative analysis (AQUA) immunohistochemical analysis, and mass spectrometry quantification. The mean age at diagnosis was 14 years (range, 1 to 49 y). About 67.5% were male and 57.5% had localized disease. Samples displayed a wide range of expression by AQUA: mean (range) IGF-1R=10,702 (393 to 14,424); EGFR=2750 (672 to 9798); and phosphatase and tensin homolog (PTEN)=2250 (251 to 6557). Mean IGF-1R expression by AQUA did not differ between standard IHC expression categories (low IHC=11,255; medium IHC=11,070; high IHC=11,023; P=0.98). Mean PTEN expression by AQUA was higher in the medium and high IHC categories (low IHC=1229; medium IHC=2715; high IHC=2940; P=0.064). Only 2 samples expressed EGFR by standard IHC. Mass spectrometry trended toward correlation with standard IHC but did not yield interpretable results in the majority of samples. This study demonstrates that the relative quantification of signaling protein expression in EWS is dependent on the methodology used. Optimization and validation of these tools are necessary before clinical application for risk stratification of patients or measurement of biomarker expression.
    No preview · Article · Feb 2014 · Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry
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    ABSTRACT: Ewing sarcoma (ES) is a malignancy of bone and soft tissue in children and adults. Previous registry-based studies indicate that Latino patients with ES have inferior outcomes compared to non-Latino patients, though an etiology for this difference could not be identified. To explore possible differences that might underlie this disparity, we conducted a retrospective study to compare clinical characteristics, tumor features, healthcare access, and treatment outcomes between Latino and non-Latino patients with ES. Primary data for 218 ES patients treated at two academic medical centers between 1980 and 2010 were collected. Categorical data were compared using Fisher exact tests; Wilcoxon rank-sum tests were used for continuous variables. Survival was estimated using Kaplan-Meier analysis and compared using log-rank testing. Latino patients were diagnosed at a younger age (P = 0.014). All other clinical and histological data were similar between groups, including radiologic and histologic response to neoadjuvant chemotherapy. Latino patients had lower socioeconomic status (P = 0.001), were less likely to have insurance (P = 0.001), and were more likely to present to the emergency room at onset of symptoms (P = 0.031) rather than to primary care physicians. Five-year event free survival (EFS) and overall survival (OS) were similar between Latino and non-Latino patients (EFS: 60.5% vs. 50.9% P = 0.37; OS: 77.6% vs. 68.6% P = 0.54). Latino patients with ES present at a younger age, and have evidence of impaired access to healthcare. Response to initial therapy appears similar between Latino and non-Latino patients. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.
    No preview · Article · Feb 2014 · Pediatric Blood & Cancer
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    ABSTRACT: Pulmonary metastasectomy has become a standard approach for sarcoma, but uncertainty remains regarding risk factors that accurately assess postoperative prognosis and can be used to guide surgical decision making. We identified 145 patients who underwent 204 consecutive pulmonary metastasectomies for sarcoma between 1996 and 2009, and examined 174 complete resections in 118 patients. Predictors included surgical procedure, number/size of lesions, repeat resection, intervals to metastasis and to recurrence, chemotherapy, sarcoma subtype, distribution of pulmonary and extrapulmonary metastasis, and patient age/sex. Survival estimates were based on Kaplan-Meier analysis and compared using a log-rank test. Predictors were compared using univariate and multivariate Cox proportional hazards modeling. Among patients undergoing R0 resections, median survival was 35 months (95% confidence interval, 22-60 months), with 3-, 5- and 10-year survival of 48%, 42%, and 31%, respectively. The number or size of lesions did not influence survival. Metastasis synchronous to the primary tumor, but not disease-free interval, was a significant predictor of worse survival on single variable and adjusted modeling (hazard ratio, 3.0; 95% confidence interval, 1.4-6.6; P = .005); the presence of extrapulmonary metastasis and a need for anatomic resection were also likely predictors (P = .06 and P = .07). Recurrence of pulmonary metastasis was not associated with a reduction in survival if completely resected, and a more aggressive and less invasive surgical approach during the later half of the study period was not associated with a significant decline in survival. Evolving surgical practice may allow an increasingly aggressive approach to pulmonary sarcoma metastasis, which may be facilitated by increased use of a minimally invasive approach.
    No preview · Article · Jan 2014 · The Journal of thoracic and cardiovascular surgery

  • No preview · Article · Oct 2013 · The American journal of surgical pathology

Publication Stats

581 Citations
235.44 Total Impact Points


  • 2003-2015
    • University of California, San Francisco
      • • Department of Pathology
      • • Department of Laboratory Medicine
      • • Department of Orthopaedic Surgery
      San Francisco, California, United States
  • 2014
    • Stanford University
      • Department of Medicine
      Palo Alto, California, United States
  • 2013
    • Memorial Sloan-Kettering Cancer Center
      • Department of Pathology
      New York City, New York, United States
  • 2012
    • University of Cologne
      Köln, North Rhine-Westphalia, Germany
  • 2006
    • Mayo Clinic - Rochester
      Rochester, Minnesota, United States