A rare spindle cell tumor with a skeletal muscle phenotype, male predilection, exclusive involvement of the head and neck region, particularly the tongue, and a suggested indolent course has been previously reported as vestigial-like 3 (VGLL3)-rearranged spindle cell rhabdomyosarcoma (SRMS). We report 18 cases with extended clinical follow-up, detailed molecular results, and methylation profiling. Tumors occurred in 5 females, 12 males, and 1 patient of unknown sex with a median age of 58 years (range, 22-71). Tumors involved the tongue (n = 13), lower lip (2), retropharyngeal region (n = 1), thyroid/parathyroid (n = 1), and palatine tonsil (1), with a median size of 1.2 cm. Treatment details (15 patients) revealed that 13 patients underwent excision only, whereas 1 patient underwent adjuvant chemotherapy and 1 patient underwent adjuvant radiation therapy. Follow-up (11 patients) showed no local recurrence or metastases. At the last follow-up (median, 45 months; range, 1-326 months), all patients were alive without evidence of disease. Histologically, tumors showed spindled to histiocytoid cells arranged in a fascicular, storiform, or haphazard architecture with variably collagenous stroma, rounded to infiltrative borders, and often diffusely growing through skeletal muscle, adipose tissue, and entrapped nerves. Necrosis was consistently absent with a median mitotic rate of 1/10 high-power fields (range, 0-7/10). By immunohistochemistry, tumors diffusely expressed desmin (n = 18), multifocal MyoD1 (n = 15), and/or myogenin (n = 12), and sometimes smooth muscle actin (n = 7). Molecular testing revealed EP300::VGLL3 (n = 6), TCF12::VGLL3 (n = 5), and PPARGC1A::VGLL3 (n = 1) fusions with VGLL3 rearrangement by fluorescence in situ hybridization in 3 cases. One archival tumor failed molecular and methylation testing despite multiple attempts, likely due to decreased DNA/RNA integrity, yet was included given classic morphologic features. Methylation data (n = 12) revealed that all but 1 tumor formed a distinct group separate from other fusion-driven rhabdomyosarcomas, including 5 infantile/congenital SRMS. We describe a well-characterized series of these rare tumors with extended follow-up data confirming lack of progression or recurrence. Furthermore, our DNA methylation profiling data support the view that these tumors form a distinct cluster, regardless of VGLL3 fusion partner and are separate from morphologic mimics and other fusion-driven SRMS, including 5 cases of congenital SRMS. We propose that these neoplasms may be better classified as VGLL3-rearranged spindle cell rhabdomyoblastic tumors to reflect their indolent behavior and to prevent overtreatment.

Purpose: Lymph node (LN) excision is critical in oncologic surgery to provide important therapeutic and diagnostic information. LN evaluation helps in staging cancers, predicting prognosis and improving survival. The ultimate wish of a surgical oncologist would be to localize and dissect all pathologically positive LNs while avoiding the morbidity of removing true negative LNs. The goal of our study was to identify a reliable marker for clinical prediction of LNs with cancer cells from non-small cell lung cancer (NSCLC) versus LNs without. We identified epithelial cell adhesion molecule (EpCAM), a membrane protein normally expressed in epithelial tissues, including in lung. Patients and Methods: We used human specimens immunostained with anti-EpCAM monoclonal antibody. Results: EpCAM was expressed in NSCLC metastasis to LNs, as shown in 74 positive LNs from patients with resected primary NSCLC. Among pathologically negative LNs, regardless of PET avidity, EpCAM was absent; whereas among pathologically positive LNs, all PET uptake groups exhibited high EpCAM positivity. Together, these biomarkers had a 100% accuracy. There was no difference in expression between hilar and mediastinal LNs, nor between primary tumor histology. Conclusions: EpCAM may be useful for the surgical oncologist for preoperative or intraoperative detection of positive LNs from NSCLC.

Combining the Segment Anything Model with a deep learning classifier produced an efficient pipeline for classifying MRI ovarian lesions, improving segmentation speed and matching radiologists’ classification performance.

Adenoid cystic carcinoma (ACC) is a slow-growing but locally aggressive salivary gland tumor. ACC is composed of ductal/tubular epithelial cells and basal/myoepithelial cells, which form cribriform, tubular, and solid growth patterns in variable combinations and dominance. ACC from different anatomic sites have similar morphological, molecular, and genetic changes. The key molecular alteration in ACC is chromosomal fusion/rearrangement/translocation involving MYB or MYBL1, usually with NFIB as a fusion partner. In this review, we summarize the pathology and molecular alterations in ACC and their clinical significance.

Epithelioid hemangioma (EH) of the liver is an exceptionally rare vascular neoplasm, with only one pathology-confirmed case previously reported. We describe the second such instance, and the first to incorporate detailed radiologic characterization and RNA sequencing. A 68-year-old man presented with hepatic masses, portal lymphadenopathy, and a lytic pubic lesion initially concerning for metastatic carcinoma. Liver biopsy demonstrated a vascular proliferation of hobnail endothelial cells within myxoid stroma, with associated hemorrhage, hemosiderin, and eosinophil-rich inflammation. Immunohistochemistry showed diffuse ERG and focal FOSB expression, weak TFE3 staining, and a low proliferative index, while CAMTA1 and HMB-45 were negative. Imaging revealed multifocal, mildly FDG-avid hepatic lesions with nodal and osseous involvement. Whole-transcriptome sequencing was negative for pathogenic fusions. These findings confirmed a diagnosis of EH, illustrating its capacity to mimic malignancy. This case highlights the diagnostic value of integrating radio-genomic analysis and underscores the need for comprehensive workup to distinguish EH from epithelioid hemangioendothelioma, angiosarcoma, and Kaposi sarcoma, entities with distinct prognostic and therapeutic implications.

BACKGROUND:Deep learning (DL) models for accurate renal tumor characterization may benefit from multi-center datasets for improved generalizability; however, data-sharing constraints necessitate privacy-preserving solutions like federated learning (FL). PURPOSE:To assess the performance and reliability of FL for renal tumor segmentation and classification in multi-institutional MRI datasets. STUDY TYPE:Retrospective multi-center study. POPULATION:A total of 987 patients (403 female) from six hospitals were included for analysis. 73% (723/987) had malignant renal tumors, primarily clear cell carcinoma (n = 509). Patients were split into training (n = 785), validation (n = 104), and test (n = 99) sets, stratified across three simulated institutions. FIELD STRENGTH/SEQUENCE:MRI was performed at 1.5 T and 3 T using T2-weighted imaging (T2WI) and contrast-enhanced T1-weighted imaging (CE-T1WI) sequences. ASSESSMENT:FL and non-FL approaches used nnU-Net for tumor segmentation and ResNet for its classification. FL-trained models across three simulated institutional clients with central weight aggregation, while the non-FL approach used centralized training on the full dataset. STATISTICAL TESTS:Segmentation was evaluated using Dice coefficients, and classification between malignant and benign lesions was assessed using accuracy, sensitivity, specificity, and area under the curves (AUCs). FL and non-FL performance was compared using the Wilcoxon test for segmentation Dice and Delong's test for AUC (p < 0.05). RESULTS:No significant difference was observed between FL and non-FL models in segmentation (Dice: 0.43 vs. 0.45, p = 0.202) or classification (AUC: 0.69 vs. 0.64, p = 0.959) on the test set. For classification, no significant difference was observed between the models in accuracy (p = 0.912), sensitivity (p = 0.862), or specificity (p = 0.847) on the test set. DATA CONCLUSION:FL demonstrated comparable performance to non-FL approaches in renal tumor segmentation and classification, supporting its potential as a privacy-preserving alternative for multi-institutional DL models. EVIDENCE LEVEL:4. TECHNICAL EFFICACY:Stage 2.

Histiocytic sarcoma (HS) is a rare yet lethal malignancy with no established standard of care therapies. A lack of pre-clinical models limits our understanding of HS pathogenesis and identification of therapeutic targets. Canine HS shares multiple clinical and genetic similarities with human HS, supporting its use as a unique translational model. Prior studies have investigated the immunogenicity of HS. Although increased tumor infiltrating lymphocyte (TIL) density is associated with favorable outcomes in canine HS, virtually all canine patients eventually succumb to progressive disease consistent with ultimate failure of anti-tumor immunity. To investigate potential regulators of the immune tumor microenvironment (TME), we undertook a comparative transcriptional approach of three long-lived cases of canine pulmonary HS with heavy T cell infiltrate and three short-lived cases of splenic HS that lacked significant T cell inflammation and compared these data to corresponding grossly normal tissues from dogs undergoing necropsy. This comparison identified PDCD1, encoding the immune checkpoint PD-1, and SPP1, encoding the secreted pro-tumorigenic protein osteopontin, as positive differentially expressed genes (DEGs) in canine HS. TXNIP, encoding the tumor suppressor TXNIP, was the most significant negative DEG. Comparative transcriptomic studies revealed conservation of enriched (including SPP1) and depleted (including TXNIP) DEGs between canine and human HS patients. Immunohistochemistry demonstrated osteopontin in the TMEs of canine and human HS. Collectively, we uncover PD-1, osteopontin, and TXNIP as putative actionable targets in HS and further establish canine HS as a preclinical platform to screen novel immunotherapeutic approaches for this deadly disease.

Angiomyofibroblastoma is a benign, usually small neoplasm typically constituted by spindle-shaped and epithelioid cells in a vascularized, myxoid-fibrous stromal background. It is most often seen in the superficial genitalia of female patients of reproductive age. However, various clinical and histologic features have been reported, including tumors in male patients, malignant transformation, extragenital sites, huge sizes, and a prominent lipomatous pattern. We report the clinical and pathologic features of one such tumor: a 23.5 cm lipomatous angiomyofibroblastoma of the vulva in a 40-year-old female patient. We also discuss important diagnostic considerations when approaching such large tumors, particularly in the setting of a biopsy specimen.

Aim: To assess the utility of different radiomics feature selection methods in predicting transarterial chemoembolization (TACE) response in hepatocellular carcinoma (HCC) patients. Materials and methods: This study employed a dataset of 136 paired MR T1-weighted contrast-enhanced abdominal images with liver tumor masks before and after TACE. TACE response for each image pair was classified by European Association for the Study of the Liver (EASL) and modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines. 100D feature vectors were generated for the paired tumor areas. Eighteen existing feature selection methods were employed to select the top-k features to train and test a non-linear support vector machine (SVM) with a Gaussian kernel. Five-cross validation was performed to identify the highest performing feature selection methods. Results: For all benchmarks, a L0-based method selecting the top-5 or top-10 features achieved the highest performance. For images classified with EASL criteria that were analyzed with the L0-based method, the accuracy (ACC), area under curve (AUC), and balanced F score (F1-score) were 0.75 f 0.06, 0.75 f 0.09, and 0.80 f 0.05, respectively. For images classified with mRECIST criteria that were analyzed with the L0-based method, the ACC, AUC, and F1-score were 0.75 f 0.07, 0.71 f 0.16, and 0.82 f 0.04, respectively. Conclusion: A L0-based method that selected the top-5/10 most important features predicted TACE response in HCC patients with the highest accuracy under both EASL and mRECIST criteria. This proof-of-concept investigation represents a step forward in the development of a reliable clinical decision-making tool for management of intermediate HCC patients undergoing TACE.

ISLET-1 (ISL1) is a LIM-homeodomain transcription factor. Selective ISL1 expression is shown in neuroendocrine, non-neuroendocrine, and some soft tissue tumors including desmoplastic small round cell tumor (DSRCT). We assessed the specificity of ISL1 (clone EP283, 1:500, Cell Marque) in 288 soft tissue tumors, which included 17 DSRCTs and other histologic mimics. Positive staining threshold for ISL1 was set to >10 % of neoplastic cell nuclei at moderate intensity. ISL1 IHC was positive in 15/16 (94 %) DSRCTs with 75 % showing diffuse (>50 %) expression. ISL1 was positive in 1/10 (10 %) Ewing sarcomas (EWS), 7/13 (54 %) alveolar rhabdomyosarcoma (RMS), 14/22 (63 %) embryonal RMS, 7/14 (50 %) synovial sarcomas, 15/16 (93 %) neuroblastoma, 1/5 (20 %) Wilms tumor, 2/4 (50 %) olfactory neuroblastoma, and all 9 Merkel cell carcinomas. Other tumors, including all CIC::DUX4 sarcomas, were negative except 3/27 leiomyosarcomas, and 1 each of angiosarcoma, myxoid liposarcomas, inflammatory myofibroblastic tumor, malignant peripheral nerve sheath tumor, tenosynovial giant cell tumor, dedifferentiated LPS, and 1 ectomesenchymoma. In summary, among the soft tissue tumors tested, ISL1 is a highly sensitive but moderately specific marker for DSRCT and may be useful to distinguish from round cell mimics including EWS and CIC::DUX4 sarcomas. The oncogenic role of ISL1 in these tumors warrants further investigation.

BACKGROUND:Ewing's sarcoma is an uncommon, aggressive malignancy that typically presents as an osseous lesion, most commonly in children and adolescents. Very rarely Ewing's sarcoma can present as an intradural extramedullary mass mimicking more common tumors. OBSERVATIONS:A 32-year-old female had a left L3 nerve root-associated lesion identified in the setting of recent-onset radiculopathy. Contrast-enhanced magnetic resonance imaging of the lumbar spine was favored to demonstrate a schwannoma or neurofibroma. Hemilaminectomy, facetectomy, and resection of the mass led to improved radiculopathy and a tissue diagnosis of Ewing's sarcoma. Immediate referral to medical oncology facilitated expeditious initiation of adjuvant chemotherapy and radiation. LESSONS:The differential diagnosis for newly identified nerve root-associated tumors should remain broad, including common benign pathologies and rare malignant entities. Tissue remains the gold standard for diagnosis, as preoperative imaging suggested a nerve sheath tumor. Malignant pathologies such as Ewing's sarcoma must be considered, especially in the setting of rapidly progressive symptoms or interval growth on serial imaging. Early diagnosis allows for the timely initiation of comprehensive oncological care. Long-term multidisciplinary follow-up is necessary for the surveillance of disease progression.

To develop imaging biomarkers for tumors aggressiveness, our previous optical redox imaging (ORI) studies of the reduced nicotinamide adenine dinucleotide (NADH) and oxidized flavoproteins (Fp, containing flavin adenine dinucleotide, i.e., FAD) in tumor xenografts of human melanoma associated the high optical redox ratio (ORR = Fp/(Fp + NADH)) and its heterogeneity to the high invasive/metastatic potential, without having reported quantitative results for NADH and Fp. Here, we implemented a calibration procedure to facilitate imaging the nominal concentrations of tissue NADH and Fp in the mouse xenografts of two human melanoma lines, an indolent less metastatic A375P and a more metastatic C8161. Images of the redox indices (NADH, Fp, ORR) revealed the existence of more oxidized areas (OAs) and more reduced areas (RAs) within individual tumors. ORR was found to be higher and NADH lower in C8161 compared to that of A375P xenografts, both globally for the whole tumors and locally in OAs. The ORR in the OA can differentiate xenografts with a higher statistical significance than the global averaged ORR. H&E staining of the tumors indicated that the redox differences we identified were more likely due to intrinsically different cell metabolism, rather than variations in cell density.

Bizarre parosteal osteochondromatous proliferation (BPOP) is a benign but rare periosteal-originating chondrogenic tumor. It commonly arises from the hands and feet. It is slow-growing and often presents as a painless lump. On imaging, the mass is well-marginated and almost always remains contiguous with the cortical bone. Histologically, the lesion is composed of a disorganized admixture of fibrous tissue, bone, and cartilage with bizarre features. Treatment is surgical and local recurrence is common contiguous with bone. This case report demonstrates an uncommon acromial BPOP with the first reported recurrence not contiguous with the underlying cortex.

Supplemental Figure 3: The CD4pos Th1 immune response in the peripheral blood pre-vaccination and post-vaccination by tumor staging (DCIS vs. IBC), quantified by (A) response repertoire and (B) cumulative response

Supplemental Information and Legends

Supplemental Table 1. Biomarker Associations with Outcome