Pancreatoblastoma: Cytologic and histologic analysis of 12 adult cases reveals helpful criteria in their diagnosis and distinction from common mimics

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152894/1/cncy22187_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152894/2/cncy22187.pd

Cytologic features and clinical implications of undifferentiated carcinoma with osteoclastic giant cells of the pancreas: An analysis of 15 cases

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137765/1/cncy21859.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137765/2/cncy21859_am.pd

Comprehensive Genomic Profiling of Pancreatic Acinar Cell Carcinomas

significantly enriched for genomic alterations (GAs) causing inactivation of DNA repair genes (45%); these GAs have been associated with sensitivity to platinum-based therapies and PARP inhibitors. Collectively, these results identify potentially actionable GAs in the majority of PACCs, and provide a rationale for using personalized therapies in this disease. Statement of Significance PACC is genomically distinct from other pancreatic cancers. Fusions in RAF genes and mutually exclusive inactivation of DNA repair genes represent novel potential therapeutic targets that are altered in over two-thirds of these tumors

Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer

Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors1,2, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8+ T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the specific neoantigen qualities promoting T-cell activation in long-term survivors, we discovered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as CA125). A neoantigen quality fitness model conferring greater immunogenicity to neoantigens with differential presentation and homology to infectious disease-derived peptides identified long-term survivors in two independent datasets, whereas a neoantigen quantity model ascribing greater immunogenicity to increasing neoantigen number alone did not. We detected intratumoural and lasting circulating T-cell reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer, including clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epitopes, consistent with neoantigen molecular mimicry. Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies

Squamoid cyst of pancreatic ducts: a distinct type of cystic lesion in the pancreas.

The clinicopathologic features of a hitherto unrecognized cystic tumor of the pancreas are documented, and its possible relationship to a more common incidental microscopic lesion is analyzed. Six patients (3 men and 3 women) had undergone resection specifically for this cyst type. The mean age of the patients was 63 years (range 52 to 79 y) and the mean size of the tumors was 2.6 cm (median 1.5, range 0.8 to 9 cm). The cysts had variable lining ranging from attenuated, flat squamoid cells to transitional, to stratified squamous without keratinization (no granular layer). The cells forming the basal/parabasal region expressed p63 (transitional/squamous cell marker, not detected in any normal pancreas or nonsquamous neoplasia) and the surface cells were positive for MUC 1 and MUC 6 (markers present in intercalated duct cells), and negative for GLUT-1 (consistent marker of serous adenomas). The lesions appeared to be unilocular cystic dilatation of the ducts that typically contained distinctive muco-proteinaceous acidophilic acinar secretions forming concretions, confirming their communication with the acinar system, and suggesting a localized obstruction in their pathogenesis (a form of "retention" cyst). A thin fibrous wall devoid of any lymphoid tissue separated the cysts from unremarkable parenchyma. There was no evidence of pancreatitis (fibrosis or inflammation). Separately, 110 pancreata resected for various reasons were analyzed, and what seems to be microscopic/incidental version of this process was identified in 10 examples (8%). These microcysts were found lying within compact acinar tissue, and appeared to be transforming from intercalated ducts, some focally connected to acinar elements, and they had abortive (nonbridging) septae with pseudo-loculated appearance, irregular contours and often showed tightly packed clusters of ducts with similar morphology described in the cases underwent resection specifically for this cyst type. In conclusion, the distinctive morphologic, immunophenotypic, and clinical characteristics of this cystic lesion warrant its classification as a separate entity. We propose to refer to it as squamoid cyst of pancreatic ducts. It seems to be a metaplastic cystic transformation beginning in the intercalated ducts. Although obstructive etiology is suspected, a specific factor or surrogate evidence of obstruction such as chronic pancreatitis is typically lacking

Whipple Grossing in the Era of New Staging: Should We Standardize?

Whipple procedure, also known as pancreatoduodenectomy, is the most common surgery for the removal of tumors of the head of the pancreas, ampulla, distal common bile duct, or periampullary duodenum. It is also one of the most challenging resection specimens grossed by surgical pathologists. A thorough and consistent evaluation of the gross surgical specimen is the most critical first step for accurate diagnosis, determination of tumor origin, staging, and evaluation of margin status. However, there has been no standard grossing protocol for Whipple specimens, which has led to inaccurate diagnoses, staging, and inconsistent reporting. This issue has become even more challenging in the era of the size-based tumor staging systems recommended by the new 8th Edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual. Moreover, new concerns have been raised regarding how to best evaluate margin status and lymph nodes. Studies have shown that different Whipple grossing methods can significantly impact margin assessment and lymph node yield and thus affect R0/R1 status and clinical stage. Other important issues under debate include nomenclature, definitions of margin (versus surface), and R1 status. Consistent Whipple grossing and standardization of reporting will provide better communication and more accurate diagnosis and staging, as well as prognostic prediction

Pancreatoblastoma with Metastatic Retroperitoneal Lymph Node and PET/CT

A previously healthy 4-year-old girl presented with petechial rash and low platelet count. There were no other symptoms. On abdominal ultrasound, a 4.7-cm heterogeneous mass was demonstrated anterior to the left kidney. An abdominal MRI subsequently performed demonstrated a heterogeneously enhancing mass at the same location extending to the pancreas and spleen. A surgical biopsy of the mass was obtained. Pathology reported a malignant epithelioid neoplasm consistent with pancreatoblastoma. The mass demonstrated intense FDG uptake on PET and an FDG avid retrocaval lymph node