Summary
Ossifying fibromyxoid tumors with lipomatous and cartilaginous differentiation are rare mesenchymal neoplasms that can be challenging to diagnose. A study identified six cases with these features, expanding the tumor’s known histomorphological spectrum. Additionally, a study on pancreatic ductal adenocarcinoma found that KRAS G12R mutations are associated with longer overall survival compared to G12D mutations.
Editors: Rouzan Karabakhtsian, MD, PhD, professor of pathology and director of the Women’s Health Pathology Fellowship, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY; S. Emily Bachert, MD, associate pathologist, Brigham and Women’s Hospital, Boston; Amarpreet Bhalla, MD, assistant professor of pathology, Albert Einstein College of Medicine, Montefiore Medical Center; Divya Sharma, MD, associate professor, Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center; and Paula Toro, MD, gastrointestinal and hepatobiliary fellow, Cleveland Clinic.
Ossifying fibromyxoid tumors with lipomatous and cartilaginous differentiation: a diagnostic pitfall
January 2026—Ossifying fibromyxoid tumor is a rare mesenchymal neoplasm that predominantly affects adults and is characterized by a multinodular growth pattern and the presence of a fibrous pseudocapsule with areas of ossification. Prompted by the recognition of a non-ossifying ossifying fibromyxoid tumor with lipomatous differentiation and PHF1::TFE3, which causes diagnostic difficulty, the authors sought to further explore cases of ossifying fibromyxoid tumor with non-osseous heterologous elements. A search of their institutional and consultation archives identified four cases with lipomatous components and two with cartilaginous differentiation. RNA sequencing revealed fusions involving PHF1 (n=4) or EPC1 (n=1) in five of the cases tested. This included EPC1::PHC1 and JAZF1::PHF1 fusions, which have not been previously reported in ossifying fibromyxoid tumor. The authors concluded that these six cases expand the histomorphological spectrum of ossifying fibromyxoid tumor, introducing lipomatous differentiation as a hitherto undocumented feature. Awareness of these rare variants will ensure appropriate diagnosis and clinical management.
Klubíčková N, Billings S, Dermawan JKT, et al. Ossifying fibromyxoid tumours with lipomatous and cartilaginous differentiation: A diagnostic pitfall. Histopathology. 2025;86:891–899.
Correspondence: Dr. Natálie Klubíčková at klubickova@biopticka.cz
Association of mutant KRAS alleles with morphology and clinical outcomes in pancreatic ductal adenocarcinoma
Mutant KRAS is the main oncogenic driver in pancreatic ductal adenocarcinoma, but the clinical and phenotypic implications of harboring different mutant KRAS alleles remain poorly understood. The authors conducted a study to characterize the potential morphologic and clinical outcome differences in pancreatic ductal adenocarcinomas (PDACs) harboring distinct mutant KRAS alleles. Cohort one consisted of 127 primary conventional PDACs from the authors’ institution. Excluded from the study were patients who received neoadjuvant therapy or who presented with nonprimary pancreatic cancers, nonconventional PDACs, colloid/mucinous carcinomas, adenosquamous carcinomas, undifferentiated carcinomas, or intraductal papillary mucinous neoplasm–associated cancers. An in-house 42-gene mutational panel was performed for cohort one. A morphologic classification system was devised wherein each tumor was assigned as conventional, papillary/large duct (P+LD, defined as neoplastic glands with papillary structure or with length of 0.5 mm or greater, or both), or poorly differentiated (when the poorly differentiated component was 60 percent or more of the tumor). Cohort two consisted of 88 PDACs in The Cancer Genome Atlas cohort, who were similarly analyzed. In both cohorts, the authors found significant enrichment of P+LD morphology in PDACs with KRAS G12V and G12R compared with G12D. In the combined cohort, Kaplan-Meier analyses showed longer overall survival in patients with KRAS G12R than with G12D (median overall survival, 1,255 versus 682 days; P = .03) and in patients whose PDACs displayed P+LD morphology versus conventional morphology (median overall survival, 1,175 versus 684 days; P = .04). In the adjuvant-only subset, patients with KRAS G12R had the longest overall survival when compared with those who had G12D, G12V, and other alleles (median overall survival, unreached/undefined versus 1,009, 1,129, and 1,222 days, respectively). The authors concluded that the morphologic classification system for conventional PDAC described by the authors is applicable to the majority of cases. Using this classification scheme, they report that PDACs with KRAS G12V and G12R mutations are more likely to display P+LD morphology. They further showed that those patients with PDACs harboring the KRAS G12R allele have longer overall survival than those with G12D among patients who received adjuvant chemotherapy. In addition, those with P+LD morphology have significantly longer overall survival compared with those who have conventional tumors, especially in chemotherapy-naive patients. While this study highlights the morphologic and clinical significance of harboring distinct mutant KRAS alleles in PDAC, additional studies are needed to confirm these findings and uncover the biological mechanism leading to these novel associations.
Chao T, Wang Z, Bowne WB, et al. Association of mutant KRAS alleles with morphology and clinical outcomes in pancreatic ductal adenocarcinoma. Arch Pathol Lab Med. 2024;148(12):1299–1309.
Correspondence: Dr. Wei Jiang at wei.jiang@jefferson.edu