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The 2019 ASCCP Risk Based Management Consensus Guidelines for prevention of cervical cancer promote clinical management recommendations aligned with our increased understanding of HPV biology and cervical carcinogenesis. They employ HPV-based testing as the basis for risk estimation, allow for personalized risk-based management by incorporating knowledge of current results with prior results, and streamline incorporation of new test methods as they are validated. They continue to support the principles of "equal management for equal risk" and "balancing harms and benefits" adopted in the 2012 version of the guidelines. These updated guidelines will be able to adjust for decreasing CIN3+ risks as more patients who received HPV vaccination reach screening age. Pathology organizations were closely involved in the development of these guidelines. Herein the pathologists who served as representatives to the 2019 ASCCP guidelines steering committee and workgroups, summarize the changes that are relevant to laboratories, pathologists, and cytotechnologists. Prior relevant screening and reporting recommendations that have not been widely and/or inconsistently adopted by laboratories are also discussed and considerations for modification of laboratory practices offered.

PurposeSeveral pathologic staging systems characterize residual tumor in patients undergoing neoadjuvant chemotherapy for breast cancer. Pathologic complete response (pCR) is now accepted by the Food and Drug Administration as an endpoint for granting accelerated drug approval. Two other systems of post-neoadjuvant pathologic tumor staging-residual cancer burden (RCB) and the American Joint Committee on Cancer post-neoadjuvant therapy staging system (yAJCC)-have been developed to characterize residual tumors when patients do not achieve pCR. The optimal system and the ways in which these systems complement each other have not been fully determined.MethodsUsing data from the I-SPY 1 TRIAL, we compared pCR, RCB, and yAJCC as predictors of early recurrence-free survival (RFS) to identify ways to improve post-neoadjuvant pathologic evaluation.ResultsAmong 162 patients assessed, pCR identified patients at lowest risk of recurrence, while RCB and yAJCC identified patients at highest risk. Hormone-receptor (HR) and HER2 subtypes further improved risk prediction. Recursive partitioning indicated that triple-negative or HER2+ patients with yAJCC III or RCB 3 have the highest recurrence risk, with an RFS of 27%. Our analysis also highlighted discrepancies between RCB and yAJCC stratification: 31% of patients had discrepant RCB and yAJCC scores. We identified differential treatment of lymph node involvement and tumor cellularity as drivers of these discrepancies.ConclusionsThese data indicate that there is benefit to reporting both RCB and yAJCC for patients in order to identify those at highest risk of relapse.

* Context.--The coronavirus disease 19 (COVID-19) pandemic is placing unparalleled burdens on regional and institutional resources in medical facilities across the globe. This disruption is causing unprecedented downstream effects to traditionally established channels of patient care delivery, including those of essential anatomic pathology services. With Washington state being the initial North American COVID-19 epicenter, the University of Washington in Seattle has been at the forefront of conceptualizing and implementing innovative solutions in order to provide uninterrupted quality patient care amidst this growing crisis. Objective.--To conduct a rapid validation study assessing our ability to reliably provide diagnostic neuropathology services via a whole slide imaging (WSI) platform as part of our departmental COVID-19 planning response. Design.--This retrospective study assessed diagnostic concordance of neuropathologic diagnoses rendered via WSI as compared to those originally established via traditional histopathology in a cohort of 30 cases encompassing a broad range of neurosurgical and neuromuscular entities. This study included the digitalization of 93 slide preparations, which were independently examined by groups of board-certified neuropathologists and neuropathology fellows. Results.--There were no major or minor diagnostic discrepancies identified in either the attending neuropathologist or neuropathology trainee groups for either the neurosurgical or neuromuscular case cohorts. Conclusions.--Our study demonstrates that accuracy of neuropathologic diagnoses and interpretation of ancillary preparations via WSI are not inferior to those generated via traditional microscopy. This study provides a framework for rapid subspecialty validation and deployment of WSI for diagnostic purposes during a pandemic event. doi: 10.5858/arpa.2020-0372-SA, On December 29, 2019, official reports describing a cluster of patients suffering from a severe novel pneumonia of unknown etiology initially surfaced from Wuhan (Hubei province) in the People's Republic [...]

BackgroundFine-needle aspiration (FNA) is the most accurate and cost-effective method for evaluating thyroid nodules. However, FNA-induced secondary changes completely replacing thyroid tumors (vanishing tumors) may create a novel problem. In this study, we highlight the diagnostic and management issues associated with the unintended consequences of ultrasonography (US)-guided FNA.MethodsFourteen thyroid glands (11 women and 3 men, ages 33-64 years) with vanishing tumors were prospectively identified between 2009 and 2012 upon surgical resection. Cytology and histopathology slides were reviewed, and second opinions were obtained when necessary.ResultsThe cytology of the 14 vanishing tumors was suspicious/positive for papillary thyroid carcinoma (PTC) in 5, indeterminate (atypia of unknown significance) in 5, benign in 2, follicular neoplasm in 1, and nondiagnostic in 1 nodule. Upon thyroidectomy, the vanishing tumors ranged in size from 0.4 to 3.5 cm (median 0.7 cm). Microscopically, the nodules showed cystic degeneration, organizing hemorrhage, granulation tissue, fibrosis, and microcalcifications. In seven tumors, a few residual malignant cells (PTC in five) or residual benign follicles (hemorrhagic cyst in two) at the periphery of the vanishing tumors helped with the final diagnosis. The remaining seven tumors were completely replaced by FNA-induced secondary changes, and had the cytology diagnosis of benign in one, follicular neoplasm in one, and suspicious/positive for PTC in five. Of the latter five, two showed additional separate foci of PTC, while three vanishing tumors (0.5, 1.2, and 1.6 cm) had no residual malignant cells and no additional carcinoma leading to a final diagnosis of negative for malignancy.ConclusionsUS-guided FNA may lead to complete obliteration of thyroid nodules, rendering final diagnosis upon thyroidectomy difficult or impossible. In these unusual circumstances, the possibility that the surgical pathology may be nonrepresentative should be considered if the cytologic features on FNA are sufficient by themselves to support a definitive diagnosis of PTC.

PurposeNeoadjuvant chemotherapy for breast cancer provides critical information about tumor response; how best to leverage this for predicting recurrence-free survival (RFS) is not established. The I-SPY 1 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis) was a multicenter breast cancer study integrating clinical, imaging, and genomic data to evaluate pathologic response, RFS, and their relationship and predictability based on tumor biomarkers.Patients and methodsEligible patients had tumors ≥ 3 cm and received neoadjuvant chemotherapy. We determined associations between pathologic complete response (pCR; defined as the absence of invasive cancer in breast and nodes) and RFS, overall and within receptor subsets.ResultsIn 221 evaluable patients (median tumor size, 6.0 cm; median age, 49 years; 91% classified as poor risk on the basis of the 70-gene prognosis profile), 41% were hormone receptor (HR) negative, and 31% were human epidermal growth factor receptor 2 (HER2) positive. For 190 patients treated without neoadjuvant trastuzumab, pCR was highest for HR-negative/HER2-positive patients (45%) and lowest for HR-positive/HER2-negative patients (9%). Achieving pCR predicted favorable RFS. For 172 patients treated without trastuzumab, the hazard ratio for RFS of pCR versus no pCR was 0.29 (95% CI, 0.07 to 0.82). pCR was more predictive of RFS by multivariate analysis when subtype was taken into account, and point estimates of hazard ratios within the HR-positive/HER2-negative (hazard ratio, 0.00; 95% CI, 0.00 to 0.93), HR-negative/HER2-negative (hazard ratio, 0.25; 95% CI, 0.04 to 0.97), and HER2-positive (hazard ratio, 0.14; 95% CI, 0.01 to 1.0) subtypes are lower. Ki67 further improved the prediction of pCR within subsets.ConclusionIn this biologically high-risk group, pCR differs by receptor subset. pCR is more highly predictive of RFS within every established receptor subset than overall, demonstrating that the extent of outcome advantage conferred by pCR is specific to tumor biology.

Neoadjuvant chemotherapy for breast cancer allows individual tumor response to be assessed depending on molecular subtype, and to judge the impact of response to therapy on recurrence-free survival (RFS). The multicenter I-SPY 1 TRIAL evaluated patients with ≥ 3 cm tumors by using early imaging and molecular signatures, with outcomes of pathologic complete response (pCR) and RFS. The current analysis was performed using data from patients who had molecular profiles and did not receive trastuzumab. The various molecular classifiers tested were highly correlated. Categorization of breast cancer by molecular signatures enhanced the ability of pCR to predict improvement in RFS compared to the population as a whole. In multivariate analysis, the molecular signatures that added to the ability of HR and HER2 receptors, clinical stage, and pCR in predicting RFS included 70-gene signature, wound healing signature, p53 mutation signature, and PAM50 risk of recurrence. The low risk signatures were associated with significantly better prognosis, and also identified additional patients with a good prognosis within the no pCR group, primarily in the hormone receptor positive, HER-2 negative subgroup. The I-SPY 1 population is enriched for tumors with a poor prognosis but is still heterogeneous in terms of rates of pCR and RFS. The ability of pCR to predict RFS is better by subset than it is for the whole group. Molecular markers improve prediction of RFS by identifying additional patients with excellent prognosis within the no pCR group.