David Parham

David Parham
University of Southern California | USC · Department of Pathology

MD

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326
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Publications

Publications (326)
Article
Full-text available
Pediatric sarcomas constitute one of the largest groups of childhood cancers, following hematopoietic, neural, and renal lesions. Partly because of their diversity, they continue to offer challenges in diagnosis and treatment. In spite of the diagnostic, nosologic, and therapeutic gains made with genetic technology, newer means for investigation ar...
Preprint
Rhabdomyosarcoma (RMS) is a well-described cancer in Li-Fraumeni Syndrome (LFS), resulting from germline TP53 pathogenic variants (PVs). RMS exhibiting anaplasia (anRMS) have been associated with a high rate of germline TP53 PVs. This study provides an updated estimate of the prevalence of TP53 germline PVs from a large cohort of patients (n=239) e...
Article
Context.— Rhabdomyosarcoma, the most common soft tissue sarcoma of children, is currently classified into the following 4 subtypes: embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma, spindle cell/sclerosing rhabdomyosarcoma, and pleomorphic rhabdomyosarcoma, based on recent molecular genetic knowledge and morphologic features. Objective.— To h...
Article
For the past 40 years, progress in rhabdomyosarcoma (RMS) has been focused on understanding its molecular basis and characterizing the mutations that drive its tumorigenesis and progression. Genetic predisposition to RMS has allowed discovery of key genetic pathways and driver mutations. Subclassification of RMS into embryonal (ERMS) and alveolar (...
Article
Background Established prognostic indicators in rhabdomyosarcoma (RMS), the most common childhood soft tissue sarcoma, include several clinicopathologic features. Among pathologic features, anaplasia has been suggested as a potential prognostic indicator, but the clinical significance of anaplasia remains unclear. Methods Patients enrolled on one...
Article
Background Treatment of children and adolescents with alveolar rhabdomyosarcoma (ARMS) and regional nodal involvement (N1) have been approached differently by North American and European cooperative groups. In order to define a better therapeutic strategy, we analyzed two studies conducted between 2005 and 2016 by the European paediatric Soft tissu...
Article
Background: An early and accurate diagnosis of liver antibody-mediated rejection (AMR) followed by timely intervention is important for clinical management but remains challenging. The aim of this study was to assess the clinicopathologic characteristics and outcomes of late acute AMR in pediatric liver transplantation recipients. Methods: We pe...
Article
Full-text available
To further understand the molecular pathogenesis of desmoplastic small round cell tumor (DSRCT), a fatal malignancy occurring primarily in adolescent/young adult males, we used next-generation RNA sequencing to investigate the gene expression profiles intrinsic to this disease. RNA from DSRCT specimens obtained from the Children’s Oncology Group wa...
Article
Background: Tumour grade, tumour size, resection potential, and extent of disease affect outcome in paediatric non-rhabdomyosarcoma soft-tissue sarcoma (NRSTS), but no risk stratification systems exist and the standard of care is poorly defined. We developed a risk stratification system from known prognostic factors and assessed it in the context...
Article
DICER1 syndrome is a hereditary cancer predisposition syndrome caused by deleterious germline DICER1 mutations. Characteristic “hotspot” somatic mutations of DICER1 have been identified in DICER1-associated tumors. With the exception of genitourinary embryonal rhabdomyosarcoma and anaplastic sarcoma of the kidney, sarcomas are rarely reported in DI...
Article
Full-text available
Objective To correlate imaging features of epithelioid sarcoma in children and young adults enrolled in Children’s Oncology Group study ARST0332 with clinical and pathological findings. Materials and methods Fifteen patients (6 males; median age 16.1 years, range 6.5–24.8 years) with epithelioid sarcoma enrolled in ARST0332 had preoperative imagin...
Article
Background The purpose of this study was to evaluate risk and response–based multi‐agent therapy for patients with rhabdomyosarcoma (RMS) at first relapse. Methods Patients with RMS and measurable disease at first relapse with unfavorable‐risk (UR) features were randomized to a 6‐week phase 2 window with 1 of 2 treatment schedules of irinotecan wi...
Article
Background: Data on the clinical features, optimal treatment and outcomes of paediatric patients with epithelioid sarcoma (ES) are limited and mostly retrospective. Methods: A subset analysis of ES patients < 30 years of age enrolled on two international prospective clinical trials conducted between 7/2005 and 11/2015 was performed. Risk-adapted...
Article
Pediatric mesenchymal tumors harboring variant NTRK fusions (ETV6-negative) are being increasingly described; however, the histologic and clinical features of these variant NTRK tumors and their relationship to classic infantile fibrosarcoma are not well characterized. A better understanding of the clinicopathologic features of these tumors is nece...
Article
Background: The outcome for patients with metastatic rhabdomyosarcoma (RMS) remains poor. A previous Children's Oncology Group (COG) study (ARST0431) for patients with metastatic RMS produced no improvement in outcome using multiple cytotoxic agents in a dose-intensive manner. The authors report results from the subsequent COG study (ARST08P1), wh...
Article
Purpose Intermediate-risk rhabdomyosarcoma (RMS) includes patients with either nonmetastatic, unresected embryonal RMS (ERMS) with an unfavorable primary site or nonmetastatic alveolar RMS (ARMS). The primary aim of this study was to improve the outcome of patients with intermediate-risk RMS by substituting vincristine and irinotecan (VI) for half...
Article
Background: Recent Children's Oncology Group (COG) trials tested the efficacy of reduced therapy in an effort to lessen late effects compared to the Intergroup Rhabdomyosarcoma Study (IRS) IV regimen with associated hematologic and hepatic toxicity, and infertility. Here, we analyze the efficacy of 45 Gray (Gy) local radiotherapy (RT) in patients...
Article
Background: Distinguishing alveolar rhabdomyosarcoma (ARMS) from embryonal rhabdomyosarcoma (ERMS) has historically been of prognostic and therapeutic importance. However, classification has been complicated by shifting histologic criteria required for an ARMS diagnosis. Children's Oncology Group (COG) studies after IRS-IV, which included the heig...
Article
Full-text available
Congenital Alveolar capillary dysplasia with misalignment of the pulmonary veins (ACD-MPV) is a rare and a lethal cause of neonatal respiratory failure and severe hypoxemia, secondary to persistent pulmonary hypertension (PPHN). It is refractory to all standard medical therapies including High Frequency Ventilation (HFV), inspired Nitric Oxide (iNO...
Article
Background: Failure-free survival (FFS) and overall survival (OS) rates were found to improve on Intergroup Rhabdomyosarcoma Study (IRS) IV (IRS-IV) compared with IRS-III for patients with subset 2 (IRS stage 1, group III nonorbit or stage 3, group I/II) low-risk embryonal rhabdomyosarcoma with the addition of cyclophosphamide (total cumulative cy...
Article
Full-text available
Background Schimke immuno-osseous dysplasia (SIOD) is a multisystemic disorder caused by biallelic mutations in the SWI/SNF-related matrix-associated actin-dependent regulator of chromatin, subfamily A-like 1 (SMARCAL1) gene. Changes in gene expression underlie the arteriosclerosis and T-cell immunodeficiency of SIOD; therefore, we hypothesized tha...
Article
Full-text available
Objectives Treatment of soft tissue tumors in young patients relies on the diagnostic information conveyed in the pathology report. We examined pathology reports from Children’s Oncology Group ARST0332 for inclusion of data elements required in published guidelines. Methods Pathology reports for 551 eligible patients were examined for required dat...
Article
Purpose: Patients with metastatic rhabdomyosarcoma (RMS), except those younger than 10 years with embryonal RMS, have an estimated long-term event-free survival (EFS) of less than 20%. The main goal of this study was to improve outcome of patients with metastatic RMS by dose intensification with interval compression, use of the most active agents...
Article
Full-text available
Schimke immuno-osseous dysplasia (SIOD) is an autosomal recessive disorder caused by mutations in SMARCAL1. A frequent complication is arteriosclerosis associated with reduced elastin expression, however the mechanism underlying the reduced elastin expression remains unknown. Expression of transcriptional regulators of elastin (ELN) and microRNA re...
Article
Full-text available
The purpose of this article is to determine the MRI and CT features of low-grade fibromyxoid sarcoma in children. We retrospectively analyzed images of 11 pediatric patients with low-grade fibromyxoid sarcoma from a phase 3 clinical trial of nonrhabdomyosarcoma soft-tissue sarcoma (Children's Oncology Group Protocol ARST0332). MRI and CT were perfo...
Article
Context: The World Health Organization Classification Since 1995, the International Classification of Rhabdomyosarcoma has provided prognostically relevant classification for rhabdomyosarcoma (RMS) and allowed risk stratification for children with RMS. The International Classification of Rhabdomyosarcoma includes botryoid and spindle cell RMS as s...
Article
Full-text available
Abstract Soft tissue tumors known as "Triton" tumors are rare lesions containing neural tissue and skeletal muscle at varying levels of maturity and malignant potential. Benign Triton tumors, also called neuromuscular choristomas or neuromuscular hamartomas, consist of neural tissue containing mature skeletal muscle in intimate relationship with pe...
Article
Pediatric rhabdomyosarcoma (RMS) is traditionally classified on the basis of the histologic appearance into alveolar (ARMS) and embryonal (ERMS) subtypes. The majority of ARMS contain a PAX3-FOXO1 or PAX7-FOXO1 gene fusion, but about 20% do not. Intergroup Rhabdomyosarcoma Study stage-matched and group-matched ARMS typically behaves more aggressive...
Article
Rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children, has traditionally been classified into embryonal rhabdomyosarcoma (ERMS) and alveolar rhabdomyosarcoma (ARMS) for pediatric oncology practice. This review outlines the historical development of classification of childhood RMS and the challenges that have been associated with i...
Article
Background: Rhabdomyosarcoma (RMS) is divided into two major histological subtypes: alveolar (ARMS) and embryonal (ERMS), with most ARMS expressing one of two oncogenic genes fusing PAX3 or PAX7 with FOXO1 (P3F and P7F, respectively). The Children's Oncology Group (COG) carried out a multi-institutional clinical trial to evaluate the prognostic va...
Article
Full-text available
PURPOSETo simplify the recommended staging evaluation by correlating tumor and clinical features with patterns of distant metastasis in newly diagnosed patients with embryonal rhabdomyosarcoma (ERMS) or alveolar rhabdomyosarcoma (ARMS). PATIENTS AND METHODS Patient data from the Intergroup Rhabdomyosarcoma Study Group and the Children's Oncology Gr...
Article
The clinical application of complex molecular classifiers as diagnostic or prognostic tools has been limited by the time and cost needed to apply them to patients. Using an existing fifty-gene expression signature known to separate two molecular subtypes of the pediatric cancer rhabdomyosarcoma, we show that an exhaustive iterative search algorithm...
Article
Full-text available
Objectives: To examine whether the frequency of fusion-negative alveolar rhabdomyosarcoma (ARMSn) increased coincident with changes in the definition of alveolar histology. Methods: We re-reviewed alveolar rhabdomyosarcoma (ARMS) in the Children's Oncology Group study D9803, comparing histopathology with fusion status. Results: Our review of 2...
Article
10012 Background: The prognostic significance of response to induction therapy for rhabdomyosarcoma (RMS) by anatomic imaging (computerized tomographic [CT] or magnetic resonance imaging [MRI] scan) is controversial. We previously reported no relationship between early response and failure-free survival (FFS) for patients on IRS-IV. We repeated the...
Article
10554 Background: Age at diagnosis is a prognostic factor in patients with RMS. We sought to determine whether AYA with metastatic alveolar (ARMS) or embryonal (ERMS) RMS had a different failure-free survival (FFS) compared to younger patients, and to identify treatment related factors that may be associated with outcome. Methods: COG ARST0431 pati...
Article
ABSTRACT We believe that this is the first translation into English of the first description, in French, of a disease previously unknown. JL Riopelle and JP Thériault, both pathologists, reviewed clinical and pathologic findings in six young patients with soft tissue tumors, and contributed autopsy information on four of the patients. Only one pati...
Article
Full-text available
Background Arteriosclerosis and emphysema develop in individuals with Schimke immuno-osseous dysplasia (SIOD), a multisystem disorder caused by biallelic mutations in SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1). However, the mechanism by which the vascular and pulmonary disease arises in...
Article
Full-text available
BACKGROUND: Arteriosclerosis and emphysema develop in individuals with Schimke immuno-osseous dysplasia (SIOD), a multisystem disorder caused by biallelic mutations in SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1). However, the mechanism by which the vascular and pulmonary disease arises i...
Article
9535 Background: Rhabdomyosarcoma (RMS) includes both alveolar (ARMS) and embryonal (ERMS) subtypes, with ARMS generally having a worse prognosis. Most ARMS express one of two fusion genes generated by balanced translocations fusing DNA binding domains of PAX3 or PAX7 with FOXO1 (P3F and P7F, respectively). The prognostic value of fusion gene versu...
Article
9509 Background: Intergroup Rhabdomyosarcoma Study (IRS) trials showed improved survival with VAC compared with VA for patients with Stage 1 Group III (non-orbit) or Stage 3 Group I/II ERMS (see table). In COG ARST0331, we hypothesized that VA in combination with lower doses of C (total cumulative dose=4.8 g/m ² ) would produce the benefit of IRS-I...
Article
Neoplasms of striated and smooth muscle in children are a diverse group of neoplasms that have some unique aspects in contrast to these tumors in adults. Rhabdomyosarcoma is the most common soft tissue sarcoma of infancy and childhood and is relatively common in adolescents. In contrast, smooth muscle tumors are relatively rare, and the various typ...
Article
Pediatric lipomas are rare and their etiology is unknown. As in adult lipomas, a segment of 12q13-q15 has been documented as a common chromosomal rearrangement region. Here, we report a pediatric lipoma case without rearrangement of 12q13-q15 but with an apparently balanced translocation involving chromosomes 8 and 13 [t(8;13)(q21;q22)] detected by...
Article
Collection of tumor tissue at autopsy can provide valuable tumor specimens to advance research for many types of cancer. Autopsy also has many other medical, scientific, and social benefits and should be encouraged in patients who are dying of cancer.
Article
Congenital infantile fibrosarcoma (CIFS) is a rare mesenchymal tumor that primarily presents in the soft tissue of the distal extremities and occasionally in unusual locations such as the lung and retroperitoneum. Herein, we report seven cases of unusual presentations of CIFS. These cases include three in the lungs, one in the retroperitoneum with...
Article
Full-text available
The European Journal of Human Genetics is the official Journal of the European Society of Human Genetics, publishing high-quality, original research papers, short reports, News and Commentary articles and reviews in the rapidly expanding field of human genetics and genomics.
Article
Langerhans cell histiocytosis (LCH) and juvenile xanthogranuloma (JXG) both belong to the histiocytosis group of disorders, which have varied prognostic and clinical significance. Their normal cellular counterparts share a common CD34-positive hematopoietic stem cell precursor that matures along CD14-negative or -positive pathways. Rare cases of LC...
Article
Embryonal rhabdomyosarcoma (eRMS) shows the most myodifferentiation among sarcomas, yet the precise cell of origin remains undefined. Using Ptch1, p53 and/or Rb1 conditional mouse models and controlling prenatal or postnatal myogenic cell of origin, we demonstrate that eRMS and undifferentiated pleomorphic sarcoma (UPS) lie in a continuum, with sat...
Article
Full-text available
Patients with localized, grossly resected, or gross residual (orbital only) embryonal rhabdomyosarcoma (ERMS) had 5-year failure-free survival (FFS) rates of 83% and overall survival rates of 95% on Intergroup Rhabdomyosarcoma Study Group (IRSG) protocols III/IV. IRSG D9602 protocol (1997 to 2004) objectives were to decrease toxicity in similar pat...
Article
Full-text available
Regional lymph node disease (RLND) is a component of the risk-based treatment stratification in rhabdomyosarcoma (RMS). The purpose of this study was to determine the contribution of RLND to prognosis for patients with RMS. Patient characteristics and survival outcomes for patients enrolled onto Intergroup Rhabdomyosarcoma Study IV (N = 898, 1991 t...
Article
Full-text available
Over the past three decades, the outcome of Ewing sarcoma family tumor (ESFT) patients who are nonmetastatic at presentation has improved considerably. The prognosis of patients with metastatic disease at the time of diagnosis and recurrence after therapy remains dismal. Drug-resistant disease at diagnosis or at relapse remains a major cause of mor...
Article
Cutaneous angiosarcomas are rare tumors, which predominantly arise in the sun-exposed skin of the head and neck of adult and elderly patients. Rarely, these tumors can be seen in children. We identified cutaneous angiosarcomas in 10 children and assessed clinical (patient age, tumor site, tumor size, and tumor focality) and histologic features incl...
Article
Full-text available
To compare response rates for two schedules of irinotecan with vincristine in patients with rhabdomyosarcoma at first relapse or disease progression. Patients with first relapse or progression of rhabdomyosarcoma and an unfavorable prognosis were randomly assigned to one of two treatment schedules of irinotecan with vincristine: regimen 1A included...
Article
To assess local control, event-free survival (EFS), and overall survival (OS) rates in 71 patients with localized, completely resected (Group I) alveolar rhabdomyosarcoma (ALV RMS) and their relation to radiation therapy (RT) on IRSG Protocols III and IV, 1984-1997. Chart review and standard statistical procedures. PATIENTS AND TUMORS: Patients wer...
Article
Rhabdomyosarcoma is a primitive neoplasm with a poorly understood etiology that exhibits features of fetal skeletal muscle. It represents the most frequent malignant soft tissue sarcoma affecting the pediatric population and is often treated very aggressively. Embryonal rhabdomyosarcoma (ERMS) and alveolar rhabdomyosarcoma constitute the two major...
Article
Anomalous coronaries arising in nontruncal regions of the pulmonary artery are exceedingly rare. We report an autopsy case of an anomalous left coronary artery that arose from the distal pulmonary artery at the hilum of the left lung in an infant with complex congenital heart disease. To the best of our knowledge, this is the first such report. Thi...
Article
Secondary bacterial infections that follow infection with influenza virus result in considerable morbidity and mortality in young children, the elderly, and immunocompromised individuals and may also significantly increase mortality in normal healthy adults during influenza pandemics. We herein describe a mouse model for investigating the interacti...
Article
Two systems for grading soft tissue sarcoma are widely used currently: the National Cancer Institute (NCI) and the Fédération Nationale des Centers de Lutte Contre le Cancer (FNCLCC) systems. Both were developed using cohorts of predominantly adult patients. The Pediatric Oncology Group (POG) system, based on the NCI system, was adapted for grading...