Faculty Bibliography

KPC (Kras^G12D:Trp53^R172H:Pdx1-Cre) and CKS (Kras^G12D:Smad4^L/L:Ptf1a-Cre) mice are genetically engineered mouse (GEM) models that capture features of human pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasms (IPMN), respectively. We compared these autochthonous tumors using quantitative imaging metrics from diffusion-weighted MRI (DW-MRI) and dynamic contrast enhanced (DCE)-MRI in reference to quantitative histological metrics including cell density, fibrosis, and microvasculature density. Our results revealed distinct DW-MRI metrics between the KPC vs. CKS model (mimicking human PDAC vs. IPMN lesion): the apparent diffusion coefficient (ADC) of CKS tumors is significantly higher than that of KPC, with little overlap (mean ± SD 2.24±0.2 vs. 1.66±0.2, p<10-10) despite intratumor and intertumor variability. Kurtosis index (KI) is also distinctively separated in the two models. DW imaging metrics are consistent with growth pattern, cell density, and the cystic nature of the CKS tumors. Coregistration of ex vivo ADC maps with H&E-stained sections allowed for regional comparison and showed a correlation between local cell density and ADC value. In conclusion, studies in GEM models demonstrate the potential utility of diffusion-weighted MRI metrics for distinguishing pancreatic cancer from benign pancreatic cysts such as IPMN.

Mucin-producing neoplasms in the abdomen and pelvis are a distinct entity, separate from simple fluid-containing neoplasms and loculated fluid collections. Mucin is a thick gelatinous substance and-owing to its high water content-has imaging features that can be mistaken for those of simple fluid-containing neoplasms with multiple imaging modalities. However, mucin-producing neoplasms arise from specific organs in the abdomen and pelvis, with unique imaging appearances, knowledge of which is important to guide accurate diagnosis and management. With its large field of view and high soft-tissue resolution, MRI has advantages over other imaging modalities in characterizing these neoplasms. The authors focus on the spectrum of MRI features of such mucin-producing neoplasms and illustrate how-despite a varied organ origin-some of these neoplasms share similar MRI and histopathologic features, thereby helping narrow the differential diagnosis. One common finding in these tumors is that the presence of internal complexity and solid enhancing components increases as the degree of malignant transformation increases. Lack of internal complexity generally indicates benignity. These tumors have a varied range of prognosis; for example, a low-grade appendiceal mucinous neoplasm is indicative of a good prognosis, while a mucinous tumor of the rectum is known to manifest at an early age with aggressive behavior and poorer prognosis compared with its nonmucinous counterpart. Online supplemental material is available for this article. ^©RSNA, 2022.

The role of lymphadenectomy in endometrial carcinomas is controversial, especially in low-grade endometrioid carcinomas. In many institutions, lymphadenectomy in the latter neoplasms is undertaken only when there is deep myometrial invasion, defined as invasion involving 50% or more of the myometrium (FIGO stage IB). There has been considerable debate as to the best modality to detect deep myometrial invasion. In Europe, preoperative magnetic resonance imaging (MRI) is the most commonly used modality while in North America, intraoperative assessment (IOA) is undertaken in most, but not all, institutions. The aim of this study was to compare the diagnostic accuracy of these 2 modalities in identifying deep myometrial invasion in low-grade endometrioid carcinomas. Two patient cohorts were studied from Belfast, UK (n=253) and Boston, USA (n=276). With respect to detecting deep myometrial invasion, MRI had a sensitivity of 72.84%, positive predictive value of 75.64% and a positive likelihood ratio of 6.59 (95% confidence interval; 4.23-10.28). IOA had a sensitivity of 78.26%, positive predictive value of 80% and a positive likelihood ratio of 20.00 (95% confidence interval; 10.35-38.63). The superior positive likelihood ratio suggests that IOA is better than MRI in determining deep myometrial invasion and the nonoverlapping 95% confidence intervals suggest this is a significant finding. However, there are significant resource implications associated with IOA and preoperative MRI carries other advantages that are discussed herein.

A chemotherapy response score (CRS) system was recently described to assess the histopathologic response and prognosis of patients with tubo-ovarian high-grade serous carcinoma (HGSC) receiving neoadjuvant chemotherapy. The current study was performed as an independent assessment of this CRS system. We retrospectively identified advanced stage HGSC patients who received neoadjuvant chemotherapy and underwent interval debulking. If available, a hemotoxylin and eosin slide from the omentum and the adnexa was selected for the study. Slides were independently scored by 13 pathologists using the 3-tiered CRS system. Reviewers then received web-based training and rescored the slides. Overall survival and progression-free survival were estimated using the Kaplan-Meier method and compared using the log-rank test. A total of 68 patients with omental (n=65) and/or adnexal (n=59) slides were included in the study. Interobserver reproducibility was moderate for omentum (κ, 0.48) and poor for adnexa (κ, 0.40), which improved for omentum (κ, 0.62) but not for adnexa (κ, 0.38) after online training. For omental slides, a consensus CRS of 1/2 was associated with a shorter median progression-free survival (10.9 mo; 95% confidence interval, 9-14) than a CRS of 3 (18.9 mo; 95% CI, 18-24; P=0.020). In summary, a 3-tiered CRS system of hemotoxylin and eosin-stained omental deposits can yield prognostic information for HGSC patients receiving neoadjuvant chemotherapy, and web-based training improved reproducibility but did not alter determination of clinical outcomes. The CRS system may allow oncologists to identify potential nonresponders and triage HGSC patients for heightened observation and/or clinical trials.

BACKGROUND:Nonsteroidal anti-inflammatory drug (NSAID) use may affect ovarian cancer risk via prostaglandin synthesis and tumor-associated macrophage (TAM) infiltration. We evaluated if associations between aspirin or non-aspirin NSAID use and ovarian cancer risk differed by tumor expression of prostaglandin-related (COX1, COX2) and TAM-related (CD68, CD163) markers. METHODS:= 530) were included. We used polytomous logistic regression, adjusted for ovarian cancer risk factors, to estimate OR for NSAID use and ovarian cancer risk by marker level. RESULTS:< 0.001). Similar results were observed for aspirin duration and tablets and for recent non-aspirin NSAID use. Results were not clearly different by macrophage density defined by the less specific macrophage marker, CD68. CONCLUSIONS:NSAID use was inversely associated with risk of ovarian cancer with high density CD163, a marker for M2-type, immunosuppressive macrophages. However, the relationship did not differ by prostaglandin synthesis markers. IMPACT:Future research should explore prostaglandin-independent mechanisms for the association between NSAID use and ovarian cancer risk, including immune mechanisms.

The current World Health Organisation classification defines smooth muscle tumours of uncertain malignant potential (STUMPs) as neoplasms that cannot be diagnosed reliably as benign or malignant according to generally accepted criteria. This has led to the application of various sets of criteria; consequently, consistent and reliable outcome data are lacking. The aims of this study were: (i) to compare the frequency of adverse outcome in STUMP on the basis of enhanced criteria; and (ii) to perform failure analysis to identify feature(s) helpful in predicting outcome METHODS AND RESULTS: Cases of STUMP diagnosed between 1994 and 2009 were retrieved and follow-up data were collected. Morphological parameters were scored and correlated with outcome. Twenty-two subjects with a median follow-up of 74.5 months (range, 26-166 months) formed the study group. Their age ranged from 31.9 years to 51.8 years (median, 45.3 years). Sixteen subjects underwent hysterectomy and six underwent myomectomy. Adverse outcomes were noted in eight (36.4%) cases. In cases with adverse outcomes, notable features included moderate-severe nuclear atypia (seven), epithelioid features (one), infiltrative or irregular margins (five), atypical mitoses (two), and vascular intrusion (three) CONCLUSIONS: The frequency of adverse outcomes in our series (36.4%) was higher than that in previously published reports (7-26.7%), suggesting that the use of more stringent criteria can exclude some patients from further follow-up. Although 'significant' nuclear atypia was not discriminatory, its frequent association with adverse outcomes has pathobiological implications. The presence of necrosis was not particularly associated with adverse outcomes. Atypical mitoses, epithelioid differentiation, vascular involvement and infiltrative/irregular margins appear to herald adverse outcomes, and therefore merit inclusion in the diagnostic regimen.