Pancreatic ductal adenocarcinoma is a lethal disease with limited treatment options and poor survival. We studied 83 spatial samples from 31 patients (11 treatment-naïve and 20 treated) using single-cell/nucleus RNA sequencing, bulk-proteogenomics, spatial transcriptomics and cellular imaging. Subpopulations of tumor cells exhibited signatures of proliferation, KRAS signaling, cell stress and epithelial-to-mesenchymal transition. Mapping mutations and copy number events distinguished tumor populations from normal and transitional cells, including acinar-to-ductal metaplasia and pancreatic intraepithelial neoplasia. Pathology-assisted deconvolution of spatial transcriptomic data identified tumor and transitional subpopulations with distinct histological features. We showed coordinated expression of TIGIT in exhausted and regulatory T cells and Nectin in tumor cells. Chemo-resistant samples contain a threefold enrichment of inflammatory cancer-associated fibroblasts that upregulate metallothioneins. Our study reveals a deeper understanding of the intricate substructure of pancreatic ductal adenocarcinoma tumors that could help improve therapy for patients with this disease.

This study forms the largest documentation of DDLSs, including its wide histopathological spectrum, from our country. Rare cases overlap with pleomorphic liposarcoma. S100-P and MDM2 are useful in substantiating adipocytic differentiation, especially in selected cases. Analysis of adequate tumor sections is vital for correct identification of a DDLS. Surgical excision with adjuvant RT forms optimal treatment.

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Objective: The objective is to study the efficacy of fine-needle aspiration biopsy (FNAB) and core-needle biopsy (CNB) in the diagnosis of lymphoma in a single institution. Study Design: We retrospectively reviewed 635 FNAB/CNB cases performed in our institution to rule out lymphoma during a 4-year period and collected the relevant clinical and pathological information for statistical analysis. Results and Conclusions: This cohort comprised 275 males and 360 females, with a median age of 57 years. Among the 593 cases with adequate diagnostic materials for lymphoma work-up, 226 were positive for lymphoma, 286 were negative for lymphoma, and 81 were nondiagnostic. Each case had an FNAB, and 191 cases also underwent a CNB. The subclassification rate according to the WHO (2008) was 67% overall, 81% for the FNAB with CNB group, and 40% for the FNAB group. In the FNAB with CNB group, the subclassification rates for cases with and without a history of lymphoma were not significantly different. A definitive diagnosis of lymphoma relied on ancillary studies, but was not affected by location, or the needle gauge of CNB. Follow-up data revealed a high diagnostic accuracy of FNAB with CNB. In conclusion, the use of FNAB and CNB with ancillary studies is effective in providing a definitive diagnosis of lymphoma in our experience at the Northwell Health System.