Macroscopy of specimens from the genitourinary system.

Macroscopic specimen examination is often critical for accurate histopathology reporting but has generally received insufficient attention and may be delegated to inexperienced staff with limited guidance and supervision. This review discusses issues around macroscopic examination of some common urological specimens; highlighting findings that are critical for patient management and others that are clinically irrelevant. Macroscopic findings are of limited value in completely submitted radical prostatectomy specimens but may be critical in orchidectomy specimens where identification of focal non-seminomatous components can significantly impact patient management. The maximum tumour dimension is often an important prognostic indicator, but specimen dimensions are generally of little clinical utility. Specimens should be carefully examined and judiciously sampled to identify clinically important focal abnormalities such as sarcomatoid change in a renal cell carcinoma and a minor non-seminomatous component in a predominant testicular seminoma. Meticulous macroscopic examination is key as less than 0.2% of the specimen (or macroscopically abnormal area) would be histologically examined even if the entire specimen/abnormal area is submitted for microscopic examination. Retroperitoneal pelvic lymph node dissection specimens for testicular cancer must be handled very differently from other lymph nodal block dissections. Current sampling protocols for transurethral resection of prostate specimens that are based on pre-MRI era data need to be reconsidered because they were specifically designed to detect occult prostate cancer, which would amount to histological cancer screening. Prostatic sampling of cystoprostatectomy specimens should be directed at accurately staging the known bladder cancer rather than detection of incidental prostate cancer.

International Society of Urological Pathology (ISUP) Consensus Conference on Current Issues in Bladder Cancer. Working Group 2: Grading of Mixed Grade, Invasive Urothelial Carcinoma Including Histologic Subtypes and Divergent Differentiations, and Non-Urothelial Carcinomas.

The 2022 International Society of Urological Pathology (ISUP) Consensus Conference on Urinary Bladder Cancer Working Group 2 was tasked to provide evidence-based proposals on the applications of grading in noninvasive urothelial carcinoma with mixed grades, invasive urothelial carcinoma including subtypes (variants) and divergent differentiations, and in pure non-urothelial carcinomas. Studies suggested that predominantly low-grade noninvasive papillary urothelial carcinoma with focal high-grade component has intermediate outcome between low- and high-grade tumors. However, no consensus was reached on how to define a focal high-grade component. By 2004 WHO grading, the vast majority of lamina propria-invasive (T1) urothelial carcinomas are high-grade, and the rare invasive low-grade tumors show only limited superficial invasion. While by 1973 WHO grading, the vast majority of T1 urothelial carcinomas are G2 and G3 and show significant differences in outcome based on tumor grade. No consensus was reached if T1 tumors should be graded either by the 2004 WHO system or by the 1973 WHO system. Because of the concern for underdiagnosis and underreporting with potential undertreatment, participants unanimously recommended that the presence of urothelial carcinoma subtypes and divergent differentiations should be reported. There was consensus that the extent of these subtypes and divergent differentiations should also be documented in biopsy, transurethral resection, and cystectomy specimens. Any distinct subtype and divergent differentiation should be diagnosed without a threshold cutoff, and each type should be enumerated in tumors with combined morphologies. The participants agreed that all subtypes and divergent differentiations should be considered high-grade according to the 2004 WHO grading system. However, participants strongly acknowledged that subtypes and divergent differentiations should not be considered as a homogenous group in terms of behavior. Thus, future studies should focus on individual subtypes and divergent differentiations rather than lumping these different entities into a single clinicopathological group. Likewise, clinical recommendations should pay attention to the potential heterogeneity of subtypes and divergent differentiations in terms of behavior and response to therapy. There was consensus that invasive pure squamous cell carcinoma and pure adenocarcinoma of the bladder should be graded according to the degree of differentiation. In conclusion, this summary of the International Society of Urological Pathology Working Group 2 proceedings addresses some of the issues on grading beyond its traditional application, including for papillary urothelial carcinomas with mixed grades and with invasive components. Reporting of subtypes and divergent differentiation is also addressed in detail, acknowledging their role in risk stratification. This report could serve as a guide for best practices and may advise future research and proposals on the prognostication of these tumors.

Macroscopic examination of pathology specimens: a critical reappraisal.

Meticulous macroscopic examination of specimens and tissue sampling are crucial for accurate histopathology reporting. However, macroscopy has generally received less attention than microscopy and may be delegated to relatively inexperienced practitioners with limited guidance and supervision. This introductory paper in the minisymposium, Macroscopy Under the Microscope, focuses on issues regarding macroscopic examination and tissue sampling that have been insufficiently addressed in the published literature. It highlights the importance of specimen examination and sampling, discusses some general principles, outlines challenges and suggests potential solutions. It is critical to get macroscopy right the first time as it may not be possible to rectify errors even with expert histological assessment or to retrospectively collect missing data after the specimen retention period. Dissectors must, therefore, receive adequate guidance and supervision until they are proficient in macroscopic specimen examination. We emphasise the importance of the clinical context, optimal specimen fixation, succinct and clinically relevant macroscopic descriptions, macrophotography and judicious tissue sampling. We note that current recommendations based on the number of blocks to be submitted per maximum tumour dimension are ambiguous as the amount of tissue submitted in a cassette is not standardised and it is unclear whether 'block' refers to a tissue block or a paraffin block. Concerns around potential oversampling of 'therapeutic' specimens that could result in overdiagnosis due to detection of incidentalomas are also discussed. We hope that the issues discussed in this paper will engender debate on this clinically critical aspect of pathology practice.

Head-to-head: how many categories for grading urothelial carcinoma?

Tumour grade is a critical prognostic parameter for guiding the management of patients with non-muscle invasive bladder cancer. In 2004, the World Health Organisation (WHO) adopted a binary (low-grade/high-grade) grading system to replace the three-tier (grades 1-3) system used to grade urothelial carcinoma since 1973. However, there is significant global variation in the grading of urothelial carcinoma. Some pathology and clinical guidelines recommend reporting of the WHO 1973 and 2004 grades in parallel, while others require reporting only of the WHO 2004 grade. This variation in pathology practice is clinically significant, because the two grading systems are not readily translatable. Some experts have proposed novel systems for grading urothelial carcinoma that involve splitting of the WHO 1973 and 2004 grade categories. The arguments for and against splitting urothelial carcinomas into two-, three- and four-grade categories are independently discussed by the three authors.

Web-grading-a tool to test personal grading of renal and prostate cancer.

Only a few pathologists have the opportunity to verify their personal grading through objective assessment. This study introduces a web-based grading platform to facilitate and validate the grading of renal cell carcinoma and prostate cancer. Two representative images of two clinically annotated cohorts of 100 cases each of prostate and renal cell carcinoma were used. Each participant was asked to grade a tumor series utilizing a three tiered grading system. Finally, a Kaplan-Meier curve was drawn, and the log-rank test was used for statistical testing of the p-value. The grading of 22 participants (68%) achieved prognostic significance. Further analysis highlighted that only two pathologists were able to reliably separate low- and high-grade tumors from intermediate grades. The limitations of this study are the low number of participants in each of the cohorts and the potential selection bias of the tumor images. This web-based grading portal facilitates the assessment of the validity of grading by individual pathologists. The observation that most participants can only successfully identify high- or low-grade tumors but cannot discriminate between more subtle intermediate grades does indicate that there is a need for the development of more formal training programs for tumor grading.

International Opinions on Grading of Urothelial Carcinoma: A Survey Among European Association of Urology and International Society of Urological Pathology Members.

Background: Grade of non-muscle-invasive bladder cancer (NMIBC) is an important prognostic factor for progression. Currently, two World Health Organization (WHO) classification systems (WHO1973, categories: grade 1-3, and WHO2004 categories: papillary urothelial neoplasm of low malignant potential [PUNLMP], low-grade [LG], high-grade [HG] carcinoma) are used. Objective: To ask the European Association of Urology (EAU) and International Society of Urological Pathology (ISUP) members regarding their current practice and preferences of grading systems. Design setting and participants: A web-based, anonymous questionnaire with ten questions on grading of NMIBC was created. The members of EAU and ISUP were invited to complete an online survey by the end of 2021. Thirteen experts had previously answered the same questions. Outcome measurements and statistical analysis: The submitted answers from 214 ISUP members, 191 EAU members, and 13 experts were analyzed. Results and limitations: Currently, 53% use only the WHO2004 system and 40% use both systems. According to most respondents, PUNLMP is a rare diagnosis with management similar to Ta-LG carcinoma. The majority (72%) would consider reverting back to WHO1973 if grading criteria were more detailed. Separate reporting of WHO1973-G3 within WHO2004-HG would influence clinical decisions for Ta and/or T1 tumors according the majority (55%). Most respondents preferred a two-tier (41%) or a three-tier (41%) grading system. The current WHO2004 grading system is supported by a minority (20%), whereas nearly half (48%) supported a hybrid three- or four-tier grading system composed of both WHO1973 and WHO2004. The survey results of the experts were comparable with ISUP and EAU respondents. Conclusions: Both the WHO1973 and the WHO2004 grading system are still widely used. Even though opinions on the future of bladder cancer grading were strongly divided, there was limited support for WHO1973 and WHO2004 in their current formats, while the hybrid (three-tier) grading system with LG, HG-G2, and HG-G3 as categories could be considered the most promising alternative. Patient summary: Grading of non-muscle-invasive bladder cancer (NMIBC) is a matter of ongoing debate and lacks international consensus. We surveyed urologists and pathologists of European Association of Urology and International Society of Urological Pathology on their preferences regarding NMIBC grading to generate a multidisciplinary dialogue. Both the "old" World Health Organization (WHO) 1973 and the "new" WHO2004 grading schemes are still used widely. However, continuation of both the WHO1973 and the WHO2004 system showed limited support, while a hybrid grading system composed of both the WHO1973 and the WHO2004 classification system may be considered a promising alternative.

Low-risk prostate lesions: An evidence review to inform discussion on losing the "cancer" label.

BACKGROUND: Active surveillance (AS) mitigates harms from overtreatment of low-risk prostate lesions. Recalibration of diagnostic thresholds to redefine which prostate lesions are considered "cancer" and/or adopting alternative diagnostic labels could increase AS uptake and continuation. METHODS: We searched PubMed and EMBASE to October 2021 for evidence on: (1) clinical outcomes of AS, (2) subclinical prostate cancer at autopsy, (3) reproducibility of histopathological diagnosis, and (4) diagnostic drift. Evidence is presented via narrative synthesis. RESULTS: AS: one systematic review (13 studies) of men undergoing AS found that prostate cancer-specific mortality was 0%-6% at 15 years. There was eventual termination of AS and conversion to treatment in 45%-66% of men. Four additional cohort studies reported very low rates of metastasis (0%-2.1%) and prostate cancer-specific mortality (0%-0.1%) over follow-up to 15 years. Overall, AS was terminated without medical indication in 1%-9% of men. Subclinical reservoir: 1 systematic review (29 studies) estimated that the subclinical cancer prevalence was 5% at <30 years, and increased nonlinearly to 59% by >79 years. Four additional autopsy studies (mean age: 54-72 years) reported prevalences of 12%-43%. Reproducibility: 1 recent well-conducted study found high reproducibility for low-risk prostate cancer diagnosis, but this was more variable in 7 other studies. Diagnostic drift: 4 studies provided consistent evidence of diagnostic drift, with the most recent (published 2020) reporting that 66% of cases were upgraded and 3% were downgraded when using contemporary diagnostic criteria compared to original diagnoses (1985-1995). CONCLUSIONS: Evidence collated may inform discussion of diagnostic changes for low-risk prostate lesions.

Measuring cancer burden in prostatic needle core biopsies: simplified assessments outperform complex measurements in assessing outcome: evidence to assist pathologist efficiency and minimize datasets.

AIMS: The optimal method of measuring cancer extent in prostate cancer (PCa) biopsies is unknown. METHODS AND RESULTS: Nine hundred eighty-one men with clinically localised PCa managed conservatively were reviewed with follow up. The number of positive cores (NPC), the Maximum Cancer Length in a core (MCL), Total Cancer Length (TCL), and percentage of positive cores (%+cores) was calculated and univariate and multivariate analysis performed using prostate-specific antigen (PSA), T-stage, and Gleason score. The presence of stromal gaps (SG) was recorded. Univariate models were run where SG made a difference to the MCL. All variables showed significant association with PCa death in univariate models. In multivariate models, incorporating PSA, T-stage, and Gleason score, only %+cores was a significant predictor of outcome, with a 10% increase in %+cores resulting in a hazard ratio (HR) of 1.07 (likelihood-ratio test P > Χ2  = 0.01). There were 120 patients where SG made a difference to the MCL and a total of 20 events in this group. Including SG, on univariate analysis the median MCL was 10 mm and HR was 1.16 (P = 0.007), not including SG, the median MCL was 6 mm and HR was 1.23 (P = 6.3 × 10-4 ). Inclusion or exclusion of SG made no significant difference to TCL as a predictor of outcome. CONCLUSION: Cancer extent is a strong predictor of PCa death but only %+cores added to the multivariate model. Expressed as a fraction of NPC/total number of cores, this is the simplest method of assessment, which we favour over more complicated methods in nontargeted biopsies.

Reporting Trends, Practices, and Resource Utilization in Neuroendocrine Tumors of the Prostate Gland: A Survey among Thirty-Nine Genitourinary Pathologists.

Background. Neuroendocrine differentiation in the prostate gland ranges from clinically insignificant neuroendocrine differentiation detected with markers in an otherwise conventional prostatic adenocarcinoma to a lethal high-grade small/large cell neuroendocrine carcinoma. The concept of neuroendocrine differentiation in prostatic adenocarcinoma has gained considerable importance due to its prognostic and therapeutic ramifications and pathologists play a pivotal role in its recognition. However, its awareness, reporting, and resource utilization practice patterns among pathologists are largely unknown. Methods. Representative examples of different spectrums of neuroendocrine differentiation along with a detailed questionnaire were shared among 39 urologic pathologists using the survey monkey software. Participants were specifically questioned about the use and awareness of the 2016 WHO classification of neuroendocrine tumors of the prostate, understanding of the clinical significance of each entity, and use of different immunohistochemical (IHC) markers. De-identified respondent data were analyzed. Results. A vast majority (90%) of the participants utilize IHC markers to confirm the diagnosis of small cell neuroendocrine carcinoma. A majority (87%) of the respondents were in agreement regarding the utilization of type of IHC markers for small cell neuroendocrine carcinoma for which 85% of the pathologists agreed that determination of the site of origin of a high-grade neuroendocrine carcinoma is not critical, as these are treated similarly. In the setting of mixed carcinomas, 62% of respondents indicated that they provide quantification and grading of the acinar component. There were varied responses regarding the prognostic implication of focal neuroendocrine cells in an otherwise conventional acinar adenocarcinoma and for Paneth cell-like differentiation. The classification of large cell neuroendocrine carcinoma was highly varied, with only 38% agreement in the illustrated case. Finally, despite the recommendation not to perform neuroendocrine markers in the absence of morphologic evidence of neuroendocrine differentiation, 62% would routinely utilize IHC in the work-up of a Gleason score 5 + 5 = 10 acinar adenocarcinoma and its differentiation from high-grade neuroendocrine carcinoma. Conclusion. There is a disparity in the practice utilization patterns among the urologic pathologists with regard to diagnosing high-grade neuroendocrine carcinoma and in understanding the clinical significance of focal neuroendocrine cells in an otherwise conventional acinar adenocarcinoma and Paneth cell-like neuroendocrine differentiation. There seems to have a trend towards overutilization of IHC to determine neuroendocrine differentiation in the absence of neuroendocrine features on morphology. The survey results suggest a need for further refinement and development of standardized guidelines for the classification and reporting of neuroendocrine differentiation in the prostate gland.

Clinical utility of histopathology data: urological cancers.

Cancer datasets recommend standardised reporting of histopathological data items with elements categorised as either core (required) or non-core (recommended), irrespective of the clinical scenario. However, the clinical significance of a data item in an individual case would depend on the clinicopathological setting as well as local management guidelines. A data item that is critical for patient management in one clinical scenario may be largely irrelevant in another patient. Pathologists must understand how their data are used in clinical practice so that they can focus their limited resources appropriately. We briefly review the use of histopathological data in the management of urological cancers, highlighting scenarios where a data item may be of limited clinical utility.

Histopathology reporting for personalised medicine: focus on clinical utility.

Histopathology guidelines generally focus on standardised collection of data items to facilitate completeness and reproducibility of histopathology reporting. A data item is categorised as either core (mandatory) or non-core (recommended but not mandatory), irrespective of the clinical scenario. However, a data item that is critical for patient management in one clinical setting may have little clinical significance in another setting. A diagnosis of limited extent Gleason score 3+3=6 prostate cancer is critical in a patient being investigated for raised serum prostate-specific antigen but would be clinically irrelevant in a repeat biopsy from a patient on an active surveillance protocol. We outline an alternative approach that is focused on the clinical utility of the data items and the requirements of personalised medicine. While all core data items are required to be reported, understanding how these parameters are used to guide patient management will enable pathologists to focus time and resources on the critical aspects of an individual case. Detailed immunohistochemical workup and obtaining a second opinion would not be necessary if resolution of the differential diagnosis is of limited clinical significance. We also highlight some challenges encountered when adopting this approach and suggest some solutions that could positively impact histopathology reporting and patient care.

International Society of Urological Pathology Expert Opinion on Grading of Urothelial Carcinoma.

CONTEXT: Grading is the mainstay for treatment decisions for patients with non-muscle-invasive bladder cancer (NMIBC). OBJECTIVE: To determine the requirements for an optimal grading system for NMIBC via expert opinion. EVIDENCE ACQUISITION: A multidisciplinary working group established by the International Society of Urological Pathology reviewed available clinical, histopathological, and molecular evidence for an optimal grading system for bladder cancer. EVIDENCE SYNTHESIS: Bladder cancer grading is a continuum and five different grading systems based on historical grounds could be envisaged. Splitting of the World Health Organization (WHO) 2004 low-grade class for NMIBC lacks diagnostic reproducibility and molecular-genetic support, while showing little difference in progression rate. Subdividing the clinically heterogeneous WHO 2004 high-grade class for NMIBC into intermediate and high risk categories using the WHO 1973 grading is supported by both clinical and molecular-genetic findings. Grading criteria for the WHO 1973 scheme were detailed on the basis of literature findings and expert opinion. CONCLUSIONS: Splitting of the WHO 2004 high-grade category into WHO 1973 grade 2 and 3 subsets is recommended. Provision of more detailed histological criteria for the WHO 1973 grading might facilitate the general acceptance of a hybrid four-tiered grading system or-as a preferred option-a more reproducible three-tiered system distinguishing low-, intermediate (high)-, and high-grade NMIBC. PATIENT SUMMARY: Improvement of the current systems for grading bladder cancer may result in better informed treatment decisions for patients with bladder cancer.

Diagnosis of "cribriform" prostatic adenocarcinoma: an interobserver reproducibility study among urologic pathologists with recommendations.

Accurate diagnosis of cribriform Gleason pattern 4 (CrP4) prostate adenocarcinoma (PCa) is important due to its independent association with adverse clinical outcomes and as a growing body of evidence suggests that it impacts clinical decision making in PCa management. To identify reproducible features for diagnosis of CrP4, we assessed interobserver agreement among 27 experienced urologic pathologists of 60 digital images from 44 radical prostatectomies (RP) that represented a broad spectrum of potential CrP4. The following morphologic features were correlated with the consensus diagnosis (defined as 75% agreement) for each image: partial vs. transluminal glandular bridging, intraglandular stroma, <12 vs. ≥12 lumina, well vs. poorly formed lumina, mucin (mucinous fibroplasia, extravasation, or extracellular pool), size (compared to benign glands and number of lumina), number of attachments with gland border by tumor cells forming a "glomeruloid-like" pattern, a clear luminal space along the periphery of gland occupying <50% of glandular circumference, central nerve, dense (cell mass occupying >50% of luminal space) vs. loose, and regular vs. irregular contour. Interobserver reproducibility for the overall diagnostic agreement was fair (k=0.40). Large CrP4 had better agreement (k=0.49) compared to small CrP4 (k=0.40). Transluminal bridging, dense cellular proliferation, a clear luminal space along the periphery of gland occupying <50% of gland circumference, lack of intraglandular mucin, and lack of contact between the majority of intraglandular cells with stroma were significantly associated with consensus for CrP4. In contrast, partial bridging, majority of intraglandular cells in contact with stroma, mucinous fibroplasia, only one attachment to the gland border by tumor cells forming a "glomeruloid-like" pattern, and a clear luminal space along the periphery of gland accounting for >50% of the glandular circumference were associated with consensus against CrP4. In summary, we identified reproducible morphological features for and against CrP4 diagnosis, which could be used to refine and standardize the diagnostic criteria for CrP4.

ISUP Consensus Definition of Cribriform Pattern Prostate Cancer.

The presence of a cribriform pattern is now recognized as a clinically important, independent adverse prognostic indicator for prostate cancer. For this reason the International Society of Urological Pathology (ISUP) recently recommended its inclusion in standard reporting. In order to improve interobserver agreement as to the diagnosis of cribriform patterns, the ISUP assembled an international panel of 12 expert urogenital pathologists for the purpose of drafting a consensus definition of cribriform pattern in prostate cancer, and provide their opinions on a set of 32 images and on potential diagnostic criteria. These images were selected by the 2 nonvoting convenors of the study and included the main categories where disagreement was anticipated. The Delphi method was applied to promote consensus among the 12 panelists in their review of the images during 2 initial rounds of the study. Following a virtual meeting, convened to discuss selected images and diagnostic criteria, the following definition for cribriform pattern in prostate cancer was approved: "A confluent sheet of contiguous malignant epithelial cells with multiple glandular lumina that are easily visible at low power (objective magnification ×10). There should be no intervening stroma or mucin separating individual or fused glandular structures" together with a set of explanatory notes. We believe this consensus definition to be practical and that it will facilitate reproducible recognition and reporting of this clinically important pattern commonly seen in prostate cancer. The images and the results of the final Delphi round are available at the ISUP website as an educational slide set (https://isupweb.org/isup/blog/slideshow/cribriform-slide-deck/).

Intraductal Carcinoma of the Prostate: A Guide for the Practicing Pathologist.

Intraductal carcinoma of the prostate gland (IDCP) is characterized by an expansile, architecturally, and cytologically atypical proliferation of prostatic epithelial cells within preexisting prostatic ducts and acini. There has been a wider recognition of IDCP by practicing pathologists since its recognition as a separate category in the World Health Organization (WHO) 2016 classification of tumours of the prostate gland. However, there is also a lack of clarity regarding the diagnosis and reporting of IDCP, which has been compounded by divergent expert recommendations regarding the grading of invasive prostate cancers associated with an intraductal component. The International Society of Urological Pathologists (ISUP) recommends that the IDCP component should be incorporated into the Gleason score, while the Genitourinary Pathology Society (GUPS) recommends excluding it when grading prostate cancer. This review seeks to clarify some of these issues and outline a pragmatic approach to reporting IDCP, particularly in needle biopsies. Diagnostic issues and terminology for lesions falling short of IDCP but exceeding that of high-grade prostatic intraepithelial neoplasia are discussed. The management of patients whose prostate biopsies show only IDCP without an associated invasive component is controversial. Some experts recommend radical therapy, while others recommend prompt repeat biopsy. An alternative clinicopathologic approach that takes into consideration the extent, histomorphology, and location (with respect to a radiologic abnormality) of IDCP, as well as radiologic features, is outlined.

Cribriform prostate cancer: Morphologic criteria enabling a diagnosis, based on survey of experts.

Among four sub-patterns of Gleason grade 4 prostate cancer, voluminous evidence supports that the cribriform pattern holds an unfavorable prognostic impact, as compared with poorly-formed, fused, or glomeruloid. The International Society of Urological Pathology (ISUP) recommends specifying whether invasive grade 4 cancer is cribriform. Recently, ISUP experts published a consensus definition of cribriform pattern highlighting criteria that distinguish it from mimickers. The current study aimed to analyze morphologic features separately to identify those that define the essence of the cribriform pattern. Thirty-two selected photomicrographs were classified by 12 urologic pathologists as: definitely cribriform cancer, probably cribriform, unsure, probably not cribriform, or definitely not cribriform. Consensus was defined as 9/12 agree or disagree, with ≤1 strongly supporting the opposite choice. Final consensus was achieved in 21 of 32 cases. Generalized estimating equation (GEE) model with logit link was fitted to estimate effect of multiple morphologic predictors. Fisher exact test was used for categorical findings. Presence of intervening stroma precluded calling cribriform cancer (p = 0.006). Mucin presence detracted (p = 0.003) from willingness to call cribriform cancer (only 3 cases had mucin). Lumen number was associated with cribriform consensus (p = 0.0006), and all consensus cases had ≥9 lumens. Predominant papillary pattern or an irregular outer boundary detracted (p = NS). Invasive cribriform carcinoma should have absence of intervening stroma, and usually neither papillary pattern, irregular outer boundary, nor very few lumens. Setting the criteria for cribriform will help prevent over- or undercalling this important finding.