Discordance of Oncotype DX scores in synchronous bilateral and unilateral multifocal breast cancers.

PURPOSE: Oncotype DX, a 21-gene expression profiling test, has become standard of care in the management of estrogen receptor (ER)-positive breast cancer. In multifocal tumors, it is unclear whether testing of the different foci is necessary. We evaluated the concordance of Oncotype DX recurrence scores (RS) between 2 tumor foci in synchronous bilateral or unilateral multifocal tumors and characterized pathological predictors of discordance. METHODS: We reviewed 713 ER+, HER2- primary invasive breast cancer patients with Oncotype RS and identified 17 bilateral synchronous patients (34 tumors) and 13 unilateral multifocal patients (26 tumors) with available Oncotype RS on all foci. Discordance in Oncotype RS between synchronous tumors was recorded and associations with clinicopathologic features including tumor size, histology, Nottingham histologic grade, progesterone receptor staining, and Ki67 index were analyzed. RESULTS: Bilateral synchronous tumors were present in older patients (median age 59 years) and had larger tumor (median size 17 mm) and more discordant histology (10/17, 59%) as compared to unilateral multifocal tumors (median age 49 years, p < 0.01; median tumor size 12 mm, p = 0.01; discordant histology 2/13, 15%, p = 0.03). Oncotype RS were discordant in 47% (8/17) of bilateral and 54% (7/13) of unilateral multifocal tumors. Concordant Oncotype RS was associated with similar histologic grade and Ki67 index in 78% (7/9) of bilateral and 100% (6/6) of multifocal tumors. In contrast, only 25% (2/8) of bilateral (p = 0.06) and 14% (1/7) of unilateral multifocal (p < 0.01) cases with discordant Oncotype RS had concordant histology grades and Ki67 levels. In synchronous tumors with discordant Oncotype RS and Ki67 index, all (4/4) foci with higher RS had higher Ki67 index. CONCLUSION: Discordance of Oncotype RS is common in both bilateral and unilateral multifocal breast cancer and is likely associated with discordant histologic grade or Ki67.

Triple-Negative Breast Cancer: Histopathologic Features, Genomics, and Treatment.

Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive group of tumors that are defined by the absence of estrogen and progesterone receptors and lack of ERBB2 (formerly HER2 or HER2/neu) overexpression. TNBC accounts for 8%-13% of breast cancers. In addition, it accounts for a higher proportion of breast cancers in younger women compared with those in older women, and it disproportionately affects non-Hispanic Black women. TNBC has high metastatic potential, and the risk of recurrence is highest during the 5 years after it is diagnosed. TNBC exhibits benign morphologic imaging features more frequently than do other breast cancer subtypes. Mammography can be suboptimal for early detection of TNBC owing to factors that include the fast growth of this cancer, increased mammographic density in young women, and lack of the typical features of malignancy at imaging. US is superior to mammography for TNBC detection, but benign-appearing features can lead to misdiagnosis. Breast MRI is the most sensitive modality for TNBC detection. Most cases of TNBC are treated with neoadjuvant chemotherapy, followed by surgery and radiation. MRI is the modality of choice for evaluating the response to neoadjuvant chemotherapy. Survival rates for individuals with TNBC are lower than those for persons with hormone receptor-positive and human epidermal growth factor receptor 2-positive cancers. The 5-year survival rates for patients with localized, regional, and distant disease at diagnosis are 91.3%, 65.8%, and 12.0%, respectively. The early success of immunotherapy has raised hope regarding the development of personalized strategies to treat TNBC. Imaging and tumor biomarkers are likely to play a crucial role in the prediction of TNBC treatment response and TNBC patient survival in the future. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Characteristics of Microinvasive Ductal Carcinoma In Situ Versus Noninvasive and Invasive Breast Cancer.

BACKGROUND: The present literature is conflicting regarding the management of microinvasive ductal carcinoma in situ (miDCIS) as to following recommendations for DCIS (margin status, surgical axillary staging, and possible observation) versus invasive breast cancer. We hypothesize that miDCIS represents more aggressive disease than pure DCIS. METHODS: We performed a retrospective review of female miDCIS patients compared with age-matched cohorts of DCIS and T1b/c patients with invasive breast cancer. We collected demographic, clinicopathologic, treatment, and outcome information. Analysis of variance or Kruskal-Wallis tests were used to analyze continuous variables and chi-square or Fisher's exact tests for categorical variables. Survival outcomes were analyzed using Kaplan-Meier curves. RESULTS: We included 375 patients (125 in each group) with median age 59 y (range 33-91 y). miDCIS tumors were more likely to be hormone receptor negative and human epidermal growth factor receptor 2 positive compared with DCIS or invasive ductal carcinoma (IDC; all P < 0.001). Subgroup analysis by miDCIS focality demonstrated no significant differences. The number of involved lymph nodes was not significantly different from DCIS patients but was significantly fewer than invasive cancer patients. Of 115 miDCIS patients (88%) staged with sentinel lymph node biopsy, eight (7%) had nodal metastases. Six miDCIS patients (5%) were treated with adjuvant chemotherapy. Over a median follow-up of 23.3 mo, there were no significant differences in local or distant recurrence. CONCLUSIONS: Based on our results, miDCIS has more aggressive pathologic features compared with DCIS and warrants surgical treatment and nodal staging similar to the management of IDC. In addition, similar to IDC, nodal and receptor status may influence medical management.

Male Mammary Paget Disease: A Tale of 2 Contrasting Cases.

Mammary Paget disease (MPD) comprises 1.45% all male breast cancers, compared with only 0.68% of all female breast cancers. Patients usually present in the fifth and sixth decades of life with ulceration, eczematous changes, discharge, bleeding, itching, and induration of the nipple and areola. Typically, there is a delay in definitive diagnosis and treatment from the onset of symptoms because most patients are initially treated for a rash. At the time of diagnosis, about half of the patients may have palpable breast mass, positive lymph nodes, or both. In this article, we present 2 cases of male MPD representing the extremes of clinical, radiologic, and histopathologic spectrum of the disease. One patient presented with a rash of the nipple of several months duration without an underlying lesion, whereas the other presented with sensitivity and pain of the nipple for 1 year and an underlying mass. Biopsies were diagnostic of MPD in both cases, and definitive surgery revealed an underlying ductal carcinoma in situ in the first case and an invasive ductal carcinoma in the second, highlighting the importance of early biopsy to initiate appropriate management.

Suboptimal Agreement Among Cytopathologists in Diagnosis of Malignancy Based on Endoscopic Ultrasound Needle Aspirates of Solid Pancreatic Lesions: A Validation Study.

BACKGROUND & AIMS: Despite the widespread use of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) to sample pancreatic lesions and the standardization of pancreaticobiliary cytopathologic nomenclature, there are few data on inter-observer agreement among cytopathologists evaluating pancreatic cytologic specimens obtained by EUS-FNA. We developed a scoring system to assess agreement among cytopathologists in overall diagnosis and quantitative and qualitative parameters, and evaluated factors associated with agreement. METHODS: We performed a prospective study to validate results from our pilot study that demonstrated moderate to substantial inter-observer agreement among cytopathologists for the final cytologic diagnosis. In the first phase, 3 cytopathologists refined criteria for assessment of quantity and quality measures. During phase 2, EUS-FNA specimens of solid pancreatic lesions from 46 patients were evaluated by 11 cytopathologists at 5 tertiary care centers using a standardized scoring tool. Individual quantitative and qualitative measures were scored and an overall cytologic diagnosis was determined. Clinical and EUS parameters were assessed as predictors of unanimous agreement. Inter-observer agreement (IOA) was calculated using multi-rater kappa (κ) statistics and a logistic regression model was created to identify factors associated with unanimous agreement. RESULTS: The IOA for final diagnoses, based on cytologic analysis, was moderate (κ = 0.56; 95% CI, 0.43-0.70). Kappa values did not increase when categories of suspicious for malignancy, malignant, and neoplasm were combined. IOA was slight to moderate for individual quantitative (κ = 0.007; 95% CI, -0.03 to -0.04) and qualitative parameters (κ = 0.5; 95% CI, 0.47-0.53). Jaundice was the only factor associated with agreement among all cytopathologists on multivariate analysis (odds ratio for unanimous agreement, 5.3; 95% CI, 1.1-26.89). CONCLUSIONS: There is a suboptimal level of agreement among cytopathologists in the diagnosis of malignancy based on analysis of EUS-FNA specimens obtained from solid pancreatic masses. Strategies are needed to refine the cytologic criteria for diagnosis of malignancy and enhance tissue acquisition techniques to improve diagnostic reproducibility among cytopathologists.

Comparison of HER2 testing among laboratories: Our experience with review cases retested at Moffitt Cancer Center in a two-year period.

Determination of human epidermal receptor protein-2 (HER2) is a crucial step in the treatment of patients diagnosed with invasive breast carcinoma. HER2 status is an independent clinical prognostic factor and a predictive factor of tumor response to chemotherapeutic agents such as trastuzumab. Accurate testing is necessary to offer adequate therapy to patients. To evaluate the variation in HER2 testing results, we analyzed our data from review cases in which HER2 testing was repeated at our institution from January 2013 to December 2014. For the study, the reason for repeating the test, the testing methodology used, and the tests results were collected. Concordance between outside and in-house HER2 results was compared. Discrepancies were classified as major and minor. A total of 173 cases were retested during this period. One-hundred and twenty-eight cases met the inclusion criteria. Sixteen cases were originally tested at large reference laboratories and two in international laboratories. In the 110 remaining cases, the test was performed at small community laboratories or the testing facility was not available. Forty-one (32%) discrepancies were identified. Of these, 15 (12% of 128 total) were major and 26 (20% of 128 total) were considered minor discrepancies. Our study confirms that significant discrepancies in HER2 results persist even after stricter and well-developed testing guidelines have been embraced.

Use of Immunohistochemical Stains in Epithelial Lesions of the Breast.

BACKGROUND: During the last few decades, immunohistochemistry (IHC) has become an integral part of pathology. Although hematoxylin and eosin (H & E) stain remains the fundamental basis for diagnostic pathology of the breast, IHC stains provide useful and sometimes vital information. Moreover, considering the role of hormonal therapy in hormone receptor-positive breast tumors, as well as the availability of targeted chemotherapeutic agents for HER2-positive cases, IHC studies represent a major part of workups. METHODS: A literature search was performed to explore the uses of IHC stains related to the diagnoses of breast lesions and prognostic/predictive information. RESULTS: Selective use of IHC stains in conjunction with H & E examination helps resolve most diagnostic issues encountered by surgical pathologists during their day-to-day practice. Pathologists should be familiar with the use of each immunostain and its limitations to avoid interpretative errors. CONCLUSIONS: IHC stains help guide the differential diagnosis of challenging epithelial lesions of the breast. They should be selectively and judiciously used and their findings must be interpreted with the differential diagnoses in mind and with an understanding of possible pitfalls.

Breast pathology second review identifies clinically significant discrepancies in over 10% of patients.

BACKGROUND: Patients seeking a second opinion or continuation of care at our hospital will routinely have their pathology reviewed prior to initiating treatment. To assess the relevance of this review in patients with breast cancer, we compared original pathology reports submitted during the referral with second-review reports issued at our institution. We also assessed compliance with College of American Pathologists (CAP) requirements regarding inclusion of scientifically validated data elements (SVDE) in these pathology reports. METHODS: We retrospectively studied all 1,970 breast pathology referral cases reviewed during one calendar year. The variables studied were histologic classification; tumor grade, necrosis, size, margin status, lymphatic/vascular invasion, dermal involvement, and biomarker profile (ER, PR, and Her-2). Each variable was rated as "agree," "disagree," "missing information," or "not applicable." RESULTS: A significant discrepancy, defined as a disagreement that affected patient care, was found in 226 cases (11.47%). Additionally, in 418 resection cases (31.6%), some CAP-checklist specific required information was missing. The most common areas of significant discrepancy were histologic category (66 cases; 33%) and biomarker reporting (50 cases; 25%). The most problematic diagnostic categories were intraductal lesions, lobular carcinoma, metaplastic carcinomas, and phyllodes tumors. Most disagreements in the biomarker-profile category were interpretive, but in 20% of discrepant cases, findings were supported by repeat immunohistochemical analysis. CONCLUSIONS: Our results confirm the value and utility of obtaining a second opinion to optimize patient care. Changes in diagnoses obtained after second review should be interpreted and reported in a collaborative fashion, noting the benefit of a review from second pair of experienced eyes. Our results support the use of second review to ensure inclusion of CAP-required data elements in pathology reports.

PTEN in triple-negative breast carcinoma: protein expression and genomic alteration in pretreatment and posttreatment specimens.

Background: Recent advances have been made in targeting the phosphoinositide 3-kinase pathway in breast cancer. Phosphatase and tensin homolog (PTEN) is a key component of that pathway. Objective: To understand the changes in PTEN expression over the course of the disease in patients with triple-negative breast cancer (TNBC) and whether PTEN copy number variation (CNV) by next-generation sequencing (NGS) can serve as an alternative to immunohistochemistry (IHC) to identify PTEN loss. Methods: We compared PTEN expression by IHC between pretreatment tumors and residual tumors in the breast and lymph nodes after neoadjuvant chemotherapy in 96 patients enrolled in a TNBC clinical trial. A correlative analysis between PTEN protein expression and PTEN CNV by NGS was also performed. Results: With a stringent cutoff for PTEN IHC scoring, PTEN expression was discordant between pretreatment and posttreatment primary tumors in 5% of patients (n = 96) and between posttreatment primary tumors and lymph node metastases in 9% (n = 33). A less stringent cutoff yielded similar discordance rates. Intratumoral heterogeneity for PTEN loss was observed in 7% of the patients. Among pretreatment tumors, PTEN copy numbers by whole exome sequencing (n = 72) were significantly higher in the PTEN-positive tumors by IHC compared with the IHC PTEN-loss tumors (p < 0.0001). However, PTEN-positive and PTEN-loss tumors by IHC overlapped in copy numbers: 14 of 60 PTEN-positive samples showed decreased copy numbers in the range of those of the PTEN-loss tumors. Conclusion: Testing various specimens by IHC may generate different PTEN results in a small proportion of patients with TNBC; therefore, the decision of testing one versus multiple specimens in a clinical trial should be defined in the patient inclusion criteria. Although a distinct cutoff by which CNV differentiated PTEN-positive tumors from those with PTEN loss was not identified, higher copy number of PTEN may confer positive PTEN, whereas lower copy number of PTEN would necessitate additional testing by IHC to assess PTEN loss. Trial registration: NCT02276443.

Standardizing Pathologic Evaluation of Breast Carcinoma After Neoadjuvant Chemotherapy.

CONTEXT.­: Neoadjuvant systemic therapy refers to the use of systemic agent(s) for malignancy prior to surgical treatment and has recently emerged as an option for most breast cancer patients eligible for adjuvant systemic therapy. Consequently, treated breast carcinomas have become routine specimens in pathology practices. A standard protocol has not yet been universally adopted for the evaluation and reporting of these specimens. The American Joint Committee on Cancer staging system recognizes the challenges in staging breast carcinomas after neoadjuvant treatment and provides important data points but does not currently provide detailed guidance in estimating the residual tumor burden in the breast and lymph nodes. The Residual Cancer Burden system is the only Web-based system that quantifies treatment response as a continuous variable using residual tumor burden in the breast and the lymph nodes. OBJECTIVE.­: To provide clarifications and guidance for evaluation and reporting of postneoadjuvant breast specimens, discuss issues with the current staging and reporting systems, and provide specific suggestions for future modifications to the American Joint Committee on Cancer system and the Residual Cancer Burden calculator. DATA SOURCES.­: English-language literature on the subject and the data from the I-SPY 2, a multicenter, adaptive randomization phase 2 neoadjuvant platform trial for early-stage, high-risk breast cancer patients. CONCLUSIONS.­: This article highlights challenges in the pathologic evaluation and reporting of treated breast carcinomas and provides recommendations and clarifications for pathologists and clinicians. It also provides specific recommendations for staging and discusses future directions.

Association of Residual Ductal Carcinoma In Situ With Breast Cancer Recurrence in the Neoadjuvant I-SPY2 Trial.

Importance: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer strongly correlates with overall survival and has become the standard end point in neoadjuvant trials. However, there is controversy regarding whether the definition of pCR should exclude or permit the presence of residual ductal carcinoma in situ (DCIS). Objective: To examine the association of residual DCIS in surgical specimens after neoadjuvant chemotherapy for breast cancer with survival end points to inform standards for the assessment of pathologic complete response. Design, Setting, and Participants: The study team analyzed the association of residual DCIS after NAC with 3-year event-free survival (EFS), distant recurrence-free survival (DRFS), and local-regional recurrence (LRR) in the I-SPY2 trial, an adaptive neoadjuvant platform trial for patients with breast cancer at high risk of recurrence. This is a retrospective analysis of clinical specimens and data from the ongoing I-SPY2 adaptive platform trial of novel therapeutics on a background of standard of care for early breast cancer. I-SPY2 participants are adult women diagnosed with stage II/III breast cancer at high risk of recurrence. Interventions: Participants were randomized to receive taxane and anthracycline-based neoadjuvant therapy with or without 1 of 10 investigational agents, followed by definitive surgery. Main Outcomes and Measures: The presence of DCIS and EFS, DRFS, and LRR. Results: The study team identified 933 I-SPY2 participants (aged 24 to 77 years) with complete pathology and follow-up data. Median follow-up time was 3.9 years; 337 participants (36%) had no residual invasive disease (residual cancer burden 0, or pCR). Of the 337 participants with pCR, 70 (21%) had residual DCIS, which varied significantly by tumor-receptor subtype; residual DCIS was present in 8.5% of triple negative tumors, 15.6% of hormone-receptor positive tumors, and 36.6% of ERBB2-positive tumors. Among those participants with pCR, there was no significant difference in EFS, DRFS, or LRR based on presence or absence of residual DCIS. Conclusions and Relevance: The analysis supports the definition of pCR as the absence of invasive disease after NAC regardless of the presence or absence of DCIS. Trial Registration: ClinicalTrials.gov Identifier NCT01042379.

Endobronchial ultrasound-guided transbronchial needle aspiration biopsy is useful evaluating mediastinal lymphadenopathy in a cancer center.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) biopsy is used to stage mediastinal lymph nodes in cancer patients to optimize treatment strategies. In this retrospective study, the authors determined the utility of EBUS-TBNA biopsy in the evaluation of mediastinal lymphadenopathy at a high-volume cancer center. MATERIALS AND METHODS: The pathology database was searched for all patients who had undergone EBUS-TBNA biopsy of mediastinal lymph nodes over a one-year period. Cytologic diagnoses were correlated with clinical histories, subsequent resection, and clinical follow-up data. RESULTS: Of 928 lymph node samples, 226 (24%) were diagnosed as malignant, 4 (0.4%) were suspicious for malignancy, 9 (1%) were atypical, 640 (69%) were benign, and 47 (5%) were insufficient for evaluation. In 89 (9.6%) cases, the patients had surgical resection. There was one false positive, in which the primary tumor contained infiltrating lymphocytes, had been sampled. There were five false-negative cases, which resulted from sampling errors, including two with micrometastases. The sensitivity, specificity, and positive and negative predictive value rates for EBUS-TBNA biopsy in the evaluation of mediastinal lymph nodes were 68.7% and 98.6% and 91.6% and 93.5%, respectively on a per lymph node basis. The overall clinical sensitivity, specificity, and positive and negative predictive value rates after one year clinical/radiological and histologic follow-up were 97%, 99.3%, 96.7% and 99.4%, respectively. CONCLUSIONS: EBUS-TBNA biopsy is a sensitive and specific method for evaluating mediastinal lymphadenopathy in patients with lung and other primary tumors.

Assessment of Residual Cancer Burden and Event-Free Survival in Neoadjuvant Treatment for High-risk Breast Cancer: An Analysis of Data From the I-SPY2 Randomized Clinical Trial.

IMPORTANCE: Residual cancer burden (RCB) distributions may improve the interpretation of efficacy in neoadjuvant breast cancer trials. OBJECTIVE: To compare RCB distributions between randomized control and investigational treatments within subtypes of breast cancer and explore the relationship with survival. DESIGN, SETTING, AND PARTICIPANTS: The I-SPY2 is a multicenter, platform adaptive, randomized clinical trial in the US that compares, by subtype, investigational agents in combination with chemotherapy vs chemotherapy alone in adult women with stage 2/3 breast cancer at high risk of early recurrence. Investigational treatments graduated in a prespecified subtype if there was 85% or greater predicted probability of higher rate of pathologic complete response (pCR) in a confirmatory, 300-patient, 1:1 randomized, neoadjuvant trial in that subtype. Evaluation of a secondary end point was reported from the 10 investigational agents tested in the I-SPY2 trial from March 200 through 2016, and analyzed as of September 9, 2020. The analysis plan included modeling of RCB within subtypes defined by hormone receptor (HR) and ERBB2 status and compared control treatments with investigational treatments that graduated and those that did not graduate. INTERVENTIONS: Neoadjuvant paclitaxel plus/minus 1 of several investigational agents for 12 weeks, then 12 weeks of cyclophosphamide/doxorubicin chemotherapy followed by surgery. MAIN OUTCOMES AND MEASURES: Residual cancer burden (pathological measure of residual disease) and event-free survival (EFS). RESULTS: A total of 938 women (mean [SD] age, 49 [11] years; 66 [7%] Asian, 103 [11%] Black, and 750 [80%] White individuals) from the first 10 investigational agents were included, with a median follow-up of 52 months (IQR, 29 months). Event-free survival worsened significantly per unit of RCB in every subtype of breast cancer (HR-positive/ERBB2-negative: hazard ratio [HZR], 1.75; 95% CI, 1.45-2.16; HR-positive/ERBB2-positive: HZR, 1.55; 95% CI, 1.18-2.05; HR-negative/ERBB2-positive: HZR, 2.39; 95% CI, 1.64-3.49; HR-negative/ERBB2-negative: HZR, 1.99; 95% CI, 1.71-2.31). Prognostic information from RCB was similar from treatments that graduated (HZR, 2.00; 95% CI, 1.57-2.55; 254 [27%]), did not graduate (HZR, 1.87; 95% CI, 1.61-2.17; 486 [52%]), or were control (HZR, 1.79; 95% CI, 1.42-2.26; 198 [21%]). Investigational treatments significantly lowered RCB in HR-negative/ERBB2-negative (graduated and nongraduated treatments) and ERBB2-positive subtypes (graduated treatments), with improved EFS (HZR, 0.61; 95% CI, 0.41-0.93) in the exploratory analysis. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, the prognostic significance of RCB was consistent regardless of subtype and treatment. Effective neoadjuvant treatments shifted the distribution of RCB in addition to increasing pCR rate and appeared to improve EFS. Using a standardized quantitative method to measure response advances the interpretation of efficacy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01042379.

Clinical and radiologic data and core needle biopsy findings should dictate management of cellular fibroepithelial tumors of the breast.

Fibroepithelial lesions with cellular stroma identified on core needle biopsy (CNB) may prove to be either fibroadenoma or phyllodes tumor at excision; therefore, management of these rare lesions is highly controversial. We aim to assess the management and the outcome of 101 cellular fibroepithelial lesions diagnosed on CNB over a 6-year period in one institution. Consensus on clinical management in each individual patient was reached during multi-disciplinary conferences, based on careful correlation of clinical data with results of imaging studies and pathology of CNB samples. Radiologic findings (mammogram and sonogram) and multiple histologic parameters on CNB specimen were blindly re-evaluated by one experienced breast radiologist and two breast pathologists, respectively, and results were correlated with final diagnosis at excision. Cellular fibroepithelial lesions with indeterminate or suspect imaging findings, with larger size, and with an equivocal comment such as "cannot rule out phyllodes tumor" in the pathology report were excised more frequently (p = 0.05, p = 0.034, and p = 0.01, respectively). Of 43 excised lesions, 13 were classified as benign phyllodes tumors, 23 as fibroadenoma and seven as benign cellular fibroepithelial lesion. The final diagnosis at excision did not significantly correlate with any clinical data, or with retrospective evaluation of imaging findings or comprehensive evaluation of multiple histologic parameters. In 58 patients who had clinical and radiologic follow-up (mean ± SD: 30 ± 21 months) there was no evidence of disease progression. No clinical and radiologic findings and/or comprehensive evaluation of multiple histologic parameters on CNB specimen are distinctive enough to predict final classification of equivocal cellular fibroepithelial lesions. However, careful clinico-pathologic and radiologic correlation may help to select the most clinically significant lesions for proper immediate surgical management. Follow-up alone may be an appropriate alternative for a subset of patients, given a good clinical, pathologic, and radiologic correlation.

Diagnostic value of intraoperative rapid cytokeratin immunostain in the cytological evaluation of sentinel lymph nodes in patients with invasive lobular carcinoma.

BACKGROUND: Sentinel lymph node (SLN) biopsy is the standard of practice in clinically node-negative patients with breast carcinoma. Intraoperative imprint cytology (IC) is often used in this setting. In cases of invasive lobular carcinoma (ILC), interpretation of IC slides may be challenging. Rapid cytokeratin immunohistochemistry (R-CK) has been used in this scenario. This study evaluated if the combination of IC and R-CK improves the sensitivity of intraoperative SLN evaluation of ILC in our setting. METHODS: SLN of all cases of ILC in which IC and R-CK were performed in a 4 year period were included. Final tissue diagnosis was used as the gold standard. RESULTS: Four hundred and twenty-seven of the 802 IC performed during the study period corresponded to paired IC and R-CK for ILC. Independently, IC and R-CK correctly classified the SLN as negative or positive in 355 cases (83%) and 324 (76%) cases, respectively. In combination, IC and R-CK correctly classified 304 (71%) of cases. R-CK failed in 56 cases. R-CK aided in rendering an accurate diagnosis in 59% of atypical cases (19/32). Patients with atypical IC and positive R-CK did not undergo axillary dissection. The addition of R-CK increased the turnaround time (TAT) by 24 minutes. CONCLUSIONS: In this study, the addition of R-CK did not improve the diagnostic accuracy in cases classified as negative or positive by IC, but resulted in a considerable increase in TAT. Although R-CK proved to be of diagnostic value in atypical IC cases, it did not appear to influence clinical management.

Ultrasound characterization for thyroid nodules with indeterminate cytology: inter-observer agreement and impact of combining pattern-based and scoring-based classifications in risk stratification.

BACKGROUND: The American Thyroid Association (ATA) sonographic patterns stratify the risk of malignancy of cytologically indeterminate thyroid nodules (ITNs). This study aimed to (1) assess inter-observer agreement for sonographic features and patterns; (2) identify potential sources of disagreement; and (3) evaluate whether the number of suspicious features risk-stratifies non-ATA and high-suspicion patterns. METHODS: Three observers independently reviewed the ultrasound images of 463 ITNs with histological follow-up consecutively evaluated between October 2008 and June 2015 at an academic cancer center. Each observer evaluated individual sonographic features. ATA sonographic patterns were derived from the interpretation of sonographic features. Nodules not fitting into any of the proposed patterns were clustered into a non-ATA pattern. RESULTS: The inter-observer agreement for ATA sonographic patterns and echogenicity was fair, moderate for margins, good for composition and echogenic foci, and very good for extrathyroidal extension and lymph node metastasis. The interpretation of each sonographic feature was significantly different between observers, and there was complete disagreement in at least one of the features in 104 (22%) nodules. A total of 169 nodules (37%) were classified into the non-ATA pattern. The number of suspicious features allowed risk stratifying nodules with non-ATA and high-suspicion sonographic patterns. Most Non-invasive Follicular Thyroid Neoplasms with Papillary-like Nuclear Features had 0-1 suspicious features and none had >2. CONCLUSIONS: Echogenicity interpretation was the greatest source of disagreement. The number of suspicious features risk-stratifies ITNs with non-ATA or high-suspicion patterns. Future studies attempting to objectivize the interpretation of echogenicity and heterogeneity are needed.

P40 Immunostain Does Not Outperform p63 as a Myoepithelial Cell Marker in the Daily Practice of Breast Pathology.

P40 antibody has been shown to be a more specific squamous and basal cell marker compared with p63. As detection of myoepithelial cells (MECs) plays a critical role in breast pathology, and the fact that p40 targets an isoform of p63, this study was designed to compare these antibodies in a variety of lesions, especially those with an sclerotic stroma and carcinoma in situ. All studied lesions were selected from the daily cases of the 3 authors and stained with p63, p40, and calponin immunohistochemical stains. Thirty-four cases (and 19 internal controls) were included. Seventy percent constituted sclerotic lesions (12 cases) and ductal carcinoma in situ (12 cases). P40 and p63 stained all lesions and showed a similar patchy staining pattern in 50% of ductal carcinoma in situ and sclerotic lesions. Compared with internal controls, p40 and p63 demonstrated decreased staining intensity in up to 70% and 8% of all cases, respectively, with no cross-reactivity with mesenchymal cells and minor cross-reactivity with epithelial cells. In our study, p40 did not outperform p63 as a MEC marker. p40 showed a decreased intensity in a higher number of cases (P<0.0001). In our opinion, p63 continues to be the best nuclear marker for the detection of MECs in the daily practice of breast pathology.

Invasive Breast Carcinoma Tumor Size on Core Needle Biopsy: Analysis of Practice Patterns and Effect on Final Pathologic Tumor Stage.

INTRODUCTION: In the absence of nodal metastasis, pathologic tumor (pT) size remains one of the most important factors in adjuvant treatment decisions and patient prognosis in breast cancer. The aim of this study was to evaluate the effect of core needle biopsy (CNB) tumor size on final pT stage. MATERIALS AND METHODS: Our information system was searched to identify all patients who underwent excisional procedures for invasive breast carcinoma from January 1, 2014 to December 31, 2015. The tumor size on CNB and final excision, the number of cases in which the CNB size was larger, and the percentage of cases in which using the CNB tumor size changed the final pT stage were recorded. RESULTS: From 1380 primary breast excisions/mastectomies, a total of 870 cases were included. In 82 (9.4%) the CNB tumor size was larger (63 of 82 cases) or no residual tumor was identified on excision (19 of 82 cases). From these 82 cases, 40 (48.7%) were properly staged on the basis of CNB tumor size, 16 (19.5%) were not staged, and 26 (31.7%) were staged using the final excision tumor size. Change in stage occurred in 7 of these 26 patients. CONCLUSION: Our study revealed that in most cases, the largest tumor size is found in the excision/mastectomy specimen. However, in 9.4% (82 of 870), the CNB contains the most accurate tumor size for pT staging. On the basis of our results, including the largest linear tumor extent on the CNB report is recommended.