Biomedical subjects

Josephine K Dermawan

Publications and source records attributed to Josephine K Dermawan.

3 recordsLinked to original sources

PubMed2026

Widespread Loss of Heterozygosity and Endoreduplication in Odontogenic Myxoma: Expanding the Clinicopathologic Spectrum of An Enigmatic Odontogenic Neoplasm.

Odontogenic myxoma (OM) is an uncommon, locally aggressive odontogenic neoplasm with characteristic histologic and clinico-radiographic features but with potential for histologic overlap with other odontogenic and non-odontogenic entities and a non-specific immunoprofile. Widespread loss of heterozygosity (LOH) has been recently described in rare cases of OM. The aim of this study was to determine whether widespread LOH represents a recurrent molecular signature that can be leveraged for clinical decision-making. Allele-specific copy number variation data from chromosomal microarray were generated from 7 OM, comprising a combined prospective and retrospective cohort. Four tumors arose in the mandible and 3 in the maxilla in patients ranging in age from 18 to 94 years (median: 44), with tumor size ranging from 2.2 to 13.0 cm. Variable amounts of fibrous stroma (odontogenic "fibromyxoma") were present in 4/7 OM, and hypercellularity not typically appreciated in conventional OM was present in 3/7 cases. All OM (7/7) demonstrated widespread LOH, with 5 cases showing a near-haploid/low hypodiploid genomes (multiple monosomies) and 2 cases showing evidence of pseudo-hyperdiploidy due to probable endoreduplication. Both pseudo-hyperdiploid cases were ≥10 cm in size; 1 represented local recurrence. Chromosomes 1 to 3, 6, 9, 11, 13, 15, and 22 demonstrated LOH in ≥75% of cases (chromosomes 1 to 3, 6, and 9 in 100% of cases), while chromosomes 5, 12, 19, and 20 universally retained heterozygosity. Altogether, widespread LOH is a recurrent event in OM and a novel finding in odontogenic pathology, and allele-specific copy number variation analysis can serve as a diagnostic adjunct in challenging cases.

copy number variation↗

PubMed2026

Management of Soft Tissue and Visceral Leiomyosarcomas.

IMPORTANCE: Leiomyosarcoma is a rare and heterogeneous malignant mesenchymal neoplasm associated with substantial morbidity and mortality. Given recent advances in biologic understanding and the complexity of leiomyosarcoma, a consensus-driven approach is needed to harmonize management and address remaining clinical and research gaps. OBJECTIVE: To provide an evidence-based synthesis of current diagnostic and therapeutic approaches for leiomyosarcoma by an international panel of physicians, researchers, and patient advocates, focusing on site-specific management, systemic therapy strategies, and key areas of clinical uncertainty, while identifying unmet needs and research priorities. EVIDENCE REVIEW: This review is based on a comprehensive evaluation of the literature, including clinical trials, observational studies, and international consensus guidelines. Sources were identified through MEDLINE (via PubMed) and Embase database searches and reference screening, then supplemented by multidisciplinary expert consensus. Emphasis was placed on studies informing diagnosis, surgical management, radiotherapy, and systemic therapy in leiomyosarcoma. FINDINGS: The rarity and heterogeneity of leiomyosarcoma poses substantial challenges in its management. In localized disease, complete surgical resection remains the cornerstone of treatment, with evidence supporting the use of site-specific perioperative treatment strategies. Prospective data supporting neoadjuvant or adjuvant chemotherapy are lacking, and the role of radiotherapy differs across anatomic disease sites and institutions. In advanced disease, multiple systemic therapies demonstrate activity, including anthracycline-based and gemcitabine-based combinations, trabectedin, and tyrosine kinase inhibitors, although optimal sequencing after first-line therapy remains undefined. Emerging data suggest potential benefit from treatment continuation strategies and selected use of local therapies in oligometastatic settings. Molecular heterogeneity is increasingly recognized but has not yet translated into routine clinical implementation, and integration of molecular profiling into diagnostic pathways for predictive and therapeutic insights remains an unmet need. CONCLUSIONS AND RELEVANCE: This international consensus addresses the diagnosis and management of leiomyosarcoma. Management requires a multidisciplinary, site-specific approach informed by limited but evolving evidence. Key uncertainties persist, particularly regarding perioperative therapy, optimal sequencing and combination of systemic treatments, and integration of molecular data. Continued international collaboration and leiomyosarcoma-specific clinical trials are needed to refine treatment strategies and improve patient outcomes.

Journal Article↗

PubMed2025

Ossifying Spindled and Epithelioid Tumor: A Novel Soft Tissue Tumor.

This investigation describes the clinicoradiologic, pathologic, and molecular features of a unique soft tissue tumor characterized by a peripheral shell of bone and composed of bland myoid spindle and epithelioid cells that are keratin-positive. Our study cohort consists of 6 men and 6 women, with a mean age of 32 years. The tumors arose in the extremities (n = 9) and proximal limb girdle (n = 3) and were equally distributed between deep and superficial soft tissues. Patients reported dull painless masses of several months to >10 years duration (mean: 2.9 years). Imaging demonstrated a complete or partial peripheral shell of bone that could extend centrally, and the tumor's mean size was 5.7 cm. Histologically, the tumors were composed of uniform, eosinophilic myoid spindled cells growing in sheets and intersecting fascicles, surrounded by mature lamellar and/or woven bone. Also present was an admixed component of intermediate-sized epithelioid cells with eosinophilic cytoplasm. Mitotic activity was consistently low. Immunohistochemistry showed strong multifocal staining for keratins, and 50% (5/10) showed focal staining for S100; however, all were negative for SMA, desmin, SOX10, ERG, and CD34. Genetic analysis by multiple targeted RNA sequencing panels was negative (n = 10); however, whole transcriptome sequencing (n = 8) revealed a recurrent and novel in-frame SRSF7::NFATC3 fusion in 4 tumors. Dual fluorescence in situ hybridization probes for SRSF7::NFATC3 successfully confirmed this fusion and identified a fifth case, which had not undergone whole transcriptome sequencing but was negative by a targeted RNA fusion panel. Methylation profiling (n = 8) demonstrated a shared epigenetic profile distinct from other entities. Clinical follow-up (n = 11) showed no evidence of recurrence after primary excision with a mean of 41.6 months. In summary, we describe a novel soft tissue tumor designated "ossifying spindled and epithelioid tumor" as a descriptive histologic term that also emphasizes its close radiologic mimic, ossifying fibromyxoid tumor. All cases have behaved in a benign fashion without recurrence following simple excision. Awareness of this entity is important, so that it can be distinguished from other neoplasms that have more aggressive biological potential.

Humans↗