Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer.

Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3, and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options.

Breast lesions associated with mammographic architectural distortion: a study of 588 core needle biopsies.

Architectural distortion (AD) on mammography is a localized alteration in the uniform texture of the breast characterized by lines radiating from a central point. Radiologic/pathologic correlation is challenging because the types of lesions associated with AD are not well defined and, thus, what signifies a discordant finding requiring excision is less clear. This retrospective case series was performed to elucidate the pathologic lesions associated with AD. Over a 6-year period, 588 core needle biopsies (CNBs) were performed for AD. Thirty-eight percent of the lesions were AD alone (single feature AD) and 62% had additional imaging features (multi-feature AD). Overall, 31% showed invasive carcinoma or ductal carcinoma in situ (DCIS), 37% showed benign lesions likely to correlate with AD, and 32% showed nonspecific benign findings. The invasive carcinomas tended to be low-grade (60%), ER-positive (98%), HER2-negative (98%), and often had lobular features (52%). Ninety-two percent were AJCC pathologic stage group I. Ninety-four cases of benign findings that correlated with AD without atypia underwent excision, and only one was found to have DCIS adjacent to the sclerosing lesion (1%). The remaining cases had benign findings without a clear correlate for AD. Sixty-eight cases without atypia underwent excision, and six multi-feature AD were upgraded to invasive carcinoma (9%). In conclusion, about one-third of CNBs for lesions associated with AD reveal carcinomas that are predominantly invasive, low-grade, ER-positive, HER2-negative, and low stage. Single-feature AD differed from multi-feature AD due to a lower number of carcinomas on CNB (18% vs 39%). For CNBs showing benign lesions on biopsy with a correlate for AD, the finding of malignancy on excision is low (1%). Radiologic/pathologic correlation and decisions to recommend excision will continue to be a challenge after CNB reveals nonspecific findings as some patients with multi-feature AD were found to have undetected invasive carcinomas.

Invasive lobular carcinoma with extracellular mucin (ILCEM): clinicopathologic and molecular characterization of a rare entity.

Invasive lobular carcinoma with extracellular mucin (ILCEM) is a rare histologic subtype of breast cancer. Little is known about the pathologic or genomic signatures that distinguish ILCEM from classic invasive lobular carcinoma (ILC) or mucinous carcinoma. We studied 17 breast cancers with lobular morphology and extracellular mucin. Thirteen tumors with sufficient tissue for DNA extraction were analyzed by a next generation sequencing (NGS) assay that interrogates 447 genes for mutations and copy number variations (CNVs). Median patient age was 66 yrs (range: 31-77 yrs). Sixteen patients presented with masses, 7 of which were >2 cm. Seven patients had lymph node metastases. The cases of ILCEM were moderately (n = 13) or poorly differentiated (n = 4), frequently exhibiting variant morphology that has not been previously described or emphasized, including grade 3 nuclei (n = 11), diffuse signet ring cells (n = 10), solid growth (n = 4), tumor necrosis (n = 3) or apocrine features (n = 2). All tumors showed absent or reduced membranous E-cadherin expression. Concurrent lobular carcinoma in situ (LCIS) was seen in 11/17 cases, 1 of which was a striking example of signet ring cell LCIS with extracellular mucin. Receptor profiles were ER+/HER2- (n = 15) and ER+/HER2+ (n = 2). With a median follow-up of 83.5 months (range: 3-171 months) in 12 patients with available information, 8 patients had recurrences resulting in 4 cancer-related deaths. The most common CNVs were 16q loss (n = 11) and 1q gain (n = 9). CDH1 gene-level alterations were detected in all but one case, including frameshift (n = 7), nonsense (n = 2), and donor splice site (n = 1) mutations and indels (n = 2). Recurrent mutations were also seen in PIK3CA (n = 3), POLQ (n = 3), TP53 (n = 3), ERBB3 (n = 3), ERBB2 (n = 2), and RUNX1 (n = 2). Genes with recurrent amplifications included GATA3 (n = 4), FOXA1 (n = 3), CCND1 (n = 2). Our data highlights ILCEM as a distinct variant of ILC that often presents with higher-grade and variant morphologic features and is associated with an aggressive clinical course. NGS data support an overall lobular-type molecular profile and reveal potentially targetable alterations in a subset of cases with recurrence.

Histopathologic features of breast cancer in Li-Fraumeni syndrome.

Breast cancer is the most common malignancy in female patients with Li-Fraumeni syndrome (LFS), a rare autosomal dominant hereditary syndrome characterized by germline TP53 mutations. Recent studies have shown that the majority of these tumors are estrogen receptor (ER) positive with frequent HER2 co-expression. However, the morphologic features of these tumors have not been as well studied as other germline-associated breast cancers. We evaluated the pathologic features of 27 invasive and in situ carcinomas from patients with known germline TP53 mutations collected through the Li-Fraumeni Consortium. Overall, 60% of cases were HER2 positive and 44% showed ER co-expression. Most DCIS was high nuclear grade with central necrosis and associated periductal fibrosis and lymphocytic response. Invasive carcinomas were mostly of ductal type (NOS), modified Scarff-Bloom-Richardson (mSBR) high grade, with marked nuclear atypia and high mitotic rate. Prominent tumor infiltrating lymphocytes, syncytial growth pattern, or pushing borders were not seen in these tumors. High p53 IHC expression was seen in tumors from individuals with germline TP53 missense mutations whereas little or no protein expression (<1% nuclear expression, null pattern) was seen in tumors from carriers of non-missense mutations. In this study, we report in detail the morphologic features of invasive and in situ carcinomas in LFS. We found that these tumors share features with cancers harboring somatic TP53 mutations but are distinct from BRCA-associated breast cancers.

How image-guided core needle biopsies altered the treatment of breast disease: Challenges accepted and opportunities taken.

The technique of combining stereotactic targeting of breast lesions with an automated spring-loaded needle biopsy gun reported in 1990 by Steve Parker and colleagues not only ushered in the era of diagnosis almost exclusively by image guided core needle biopsy, but also profoundly changed the practice of pathologists, radiologists, surgeons, and medical oncologists and had major effects on the treatment of women with breast cancer. In this special issue of The Breast Journal celebrating 25 years of publication, it is of value to reflect back on these changes, some expected and some unanticipated, which have occurred over the past three decades and to consider the reasons why core needle biopsies should be considered a milestone in breast pathology.

Hyperechoic malignancies of the breast: Underlying pathologic features correlating with this unusual appearance on ultrasound.

Hyperechogenicity in the breast on ultrasound (US) is usually regarded as a benign feature with only rare hyperechoic malignancies reported to date. In this study, we evaluated the pathologic findings on core needle biopsy of hyperechoic lesions and investigated the histologic features in malignancies that give rise to an echogenic pattern. A total of 163 core needle biopsies (CNB) were performed for "hyperechoic" or "echogenic" lesions between 1/1/05 and 7/31/17. Lesions were classified based on the proportion of hyperechoic areas identified. We found that all lesions with a homogenous hyperechoic pattern (>90% hyperechoic) were benign (n = 17), regardless of the type of margins. Malignancies were found in 21% (7/34, six invasive carcinomas and one lymphoma) of heterogenous lesions with ≥50% hyperechoic areas (all with noncircumscribed margins) and in 31% of lesions with <50% hyperechoic areas (19/61, 14 invasive carcinomas, two lymphomas, and three metastases), including five with circumscribed margins (one invasive carcinoma, one lymphoma, and three metastases). Two major US patterns were identified in malignant lesions, those with a hypoechoic center and hyperechoic rim, corresponding to a central tumor area with dense stroma and tumor cells infiltrating adipose tissue at the periphery ("rim pattern"), and a second "dispersed pattern" with hyperechoic areas distributed throughout the lesion. Hyperechoic malignancies were found to be comprised of a complex intermixture of elements of differing echogenicity including tumor cells, adipose tissue, and fluid (in tubules, stromal clefts, or blood vessels). Our findings support the importance of radiologists specifying the echogenic pattern of hyperechoic lesions, as heterogenous lesions are associated with a higher risk of malignancy and pathologists should be alert to the associated pathologic findings.

Evaluating the Rate of Upgrade to Invasive Breast Cancer and/or Ductal Carcinoma In Situ Following a Core Biopsy Diagnosis of Non-classic Lobular Carcinoma In Situ.

BACKGROUND: A diagnosis of non-classic lobular carcinoma in situ (NC-LCIS) encompasses a variety of lesions with poorly characterized natural history. We evaluated upgrade rates and factors associated with upgrade to malignancy following a core biopsy diagnosis of NC-LCIS, and its natural history. METHODS: Upon Institutional Review Board approval, pathology databases were searched for NC-LCIS core biopsy diagnoses (carcinoma in situ [CIS], CIS with ductal and lobular features [CIS/DLF], pleomorphic LCIS [P-LCIS], variant LCIS [V-LCIS], LCIS with necrosis). Cases with available core and excision pathology were included, while cases with concurrent ipsilateral invasive carcinoma (IC), ductal carcinoma in situ (DCIS), and/or atypical ductal hyperplasia were excluded. RESULTS: Overall, 121 NC-LCIS cases were identified from 1998 to 2017. We excluded 46 cases with concurrent cancer; 75 patients with 76 NC-LCIS core biopsy diagnoses followed by excision formed our study cohort. Median age was 56 years (range 41-83), and all imaging findings were classified as Breast Imaging Reporting and Data System 4; calcifications were the most common biopsy indication (80%). Excision yielded malignancy in 27 (36%) patients (IC 17, 63%; DCIS alone 10, 37%). We were unable to identify radiologic or pathologic features predictive of upgrade. Of 49 pure NC-LCIS cases, 15 (31%) had mastectomy, 9 (18%) had excision and radiation, and 25 (51%) had excision alone. At a median follow-up of 58 months (range 1-224), 1/25 (4%) patients with excision alone developed ipsilateral DCIS 14 months later. CONCLUSIONS: In this series of NC-LCIS, 36% of cases were upgraded, supporting routine excision. We were unable to identify predictors of upgrade. Among 25 patients with pure NC-LCIS, only one patient developed a future ipsilateral cancer. Further study of the natural history of NC-LCIS is warranted.

The molecular basis of breast cancer pathological phenotypes.

The histopathological evaluation of morphological features in breast tumours provides prognostic information to guide therapy. Adjunct molecular analyses provide further diagnostic, prognostic and predictive information. However, there is limited knowledge of the molecular basis of morphological phenotypes in invasive breast cancer. This study integrated genomic, transcriptomic and protein data to provide a comprehensive molecular profiling of morphological features in breast cancer. Fifteen pathologists assessed 850 invasive breast cancer cases from The Cancer Genome Atlas (TCGA). Morphological features were significantly associated with genomic alteration, DNA methylation subtype, PAM50 and microRNA subtypes, proliferation scores, gene expression and/or reverse-phase protein assay subtype. Marked nuclear pleomorphism, necrosis, inflammation and a high mitotic count were associated with the basal-like subtype, and had a similar molecular basis. Omics-based signatures were constructed to predict morphological features. The association of morphology transcriptome signatures with overall survival in oestrogen receptor (ER)-positive and ER-negative breast cancer was first assessed by use of the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset; signatures that remained prognostic in the METABRIC multivariate analysis were further evaluated in five additional datasets. The transcriptomic signature of poorly differentiated epithelial tubules was prognostic in ER-positive breast cancer. No signature was prognostic in ER-negative breast cancer. This study provided new insights into the molecular basis of breast cancer morphological phenotypes. The integration of morphological with molecular data has the potential to refine breast cancer classification, predict response to therapy, enhance our understanding of breast cancer biology, and improve clinical management. This work is publicly accessible at www.dx.ai/tcga_breast. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Distinguishing papillary endothelial hyperplasia and angiosarcoma on core needle biopsy of the breast: The importance of clinical and radiologic correlation.

Papillary endothelial hyperplasia (PEH) is a rare non-neoplastic exuberant organizing hematoma that can closely mimic angiosarcoma due to a resemblance to malignant anastomosing blood vessels. It could be particularly difficult to distinguish PEH from angiosarcoma in breast core needle biopsies. We identified all cases of these lesions diagnosed on core needle biopsy in order to identify clinical, radiologic, and pathologic features that could prove helpful to arrive at the correct diagnosis. Four cases of PEH and 4 cases of angiosarcoma were identified. The mean age at diagnosis was 62 for PEH and 33 for primary angiosarcoma. All cases of PEH formed small masses with circumscribed or lobulated margins by imaging (mean size 0.9 cm). In 3 cases, the masses were difficult or impossible to identify after the biopsy. Angiosarcomas presented as larger masses with ill-defined margins (mean size 2.8 cm) that were unchanged in size after biopsy. PEH was surrounded by adipose tissue, whereas angiosarcoma invaded into fibrous stroma and involved lobules. The pseudopapillary structures of PEH were composed mainly of collagen, and thus, additional histologic stains for fibrin were not helpful for diagnosis. The 4 patients with PEH received no further treatment and are alive and disease-free at 2-11 years of follow-up. In contrast, the patients with angiosarcoma underwent mastectomy and chemotherapy or radiation therapy. Two of the patients with angiosarcoma died 3 years after diagnosis and the other 2 patients are alive without disease at 5 and 6 years. Therefore, distinguishing PEH and angiosarcoma is essential for appropriate management. This is the first series to compare these lesions on core needle biopsy and the first to note important clinical, imaging, and histologic differences that aid in making a diagnosis of PEH with confidence on breast core needle biopsy.

Eight-year update of a prospective study of wide excision alone for small low- or intermediate-grade ductal carcinoma in situ (DCIS).

Whether wide excision with margins ≥1 cm is sufficient treatment for small low- or intermediate-grade ductal carcinoma in situ (DCIS) is unclear. This is an updated analysis of a phase II, single-arm, prospective trial testing this hypothesis. A total of 158 patients with low- or intermediate-grade DCIS who underwent wide excision alone (without radiation or tamoxifen) were entered onto the trial from 1995 to 2002. Entry criteria included mammographic extent ≤2.5 cm, predominantly low or intermediate nuclear grade, and excision with final microscopic margins ≥1 cm. Eight-year minimum potential follow-up was required for inclusion in the analysis; the final population comprised 143 patients. Cumulative incidence curves were generated to assess rates of local recurrence (LR) or other events. Median follow-up time was 11 years. Nineteen patients (13 %) had LR as a first event within 8 years. Thirteen LR (68 %) were DCIS only and six (32 %) were invasive. Fourteen (74 %) occurred in the original quadrant. The 10-year estimated cumulative incidence of LR was 15.6 %. The estimated annual percentage rate of LR was 1.9 % per patient-year. With longer follow-up, there remains a substantial and ongoing risk of LR in patients with favorable DCIS treated with wide excision margins without radiation. This information should be useful as patients and clinicians weigh the options of wide excision with and without radiation.

Non-sclerosing (T-cell) and sclerosing (B-cell) lymphocytic lobulitis in diagnostic breast biopsies: Clinical, imaging, and pathologic features.

Lymphocytic lobulitis (LL) is characterized by prominent lymphocytic infiltrates centered on lobules. Sclerosing lymphocytic lobulitis (SCLL) associated with diabetes mellitus (DM) or autoimmune disease (AI) was the first type to be described. Subsequently, non-sclerosing LL (NSCLL) was reported as an incidental finding in prophylactic mastectomies due to high risk germline mutations or a family history of breast cancer. The two types of LL were distinguished by stromal features and a predominant population of B-cells in the former and T-cells in the latter. In this study, 8 cases of NSCLL detected clinically or by screening were compared to 44 cases of SCLL. One case of NSCLL presented as a palpable mass, 2 as masses on screening, and 5 as MRI enhancement. In contrast, 80% of SCLL cases presented as palpable masses. Half the cases of NSCLL were associated with a BRCA1 or 2 mutation compared to 1 case of SCLL (2%). Three additional cases of NSCLL were associated with a strong family and/or personal history of breast cancer. Almost half (52%) of SCLL cases were associated with DM or AI, but only 25% of NSCLL. Immunoperoxidase studies confirmed a predominance of T-cells in NSCLL and B-cells in SCLL associated with DM or AI. It is important for pathologists to be aware of this new observation that NSCLL can be detected as a palpable mass or an imaging finding in diagnostic biopsies, as its presence can be indicative of a significant risk for breast cancer.

HER2 heterogeneity and treatment response-associated profiles in HER2-positive breast cancer in the NCT02326974 clinical trial.

BACKGROUNDHER2-targeting therapies have great efficacy in HER2-positive breast cancer, but resistance, in part due to HER2 heterogeneity (HET), is a significant clinical challenge. We previously described that in a phase II neoadjuvant trastuzumab emtansine (T-DM1) and pertuzumab (P) clinical trial in early-stage HER2-positive breast cancer, none of the patients with HER2-HET tumors had pathologic complete response (pCR).METHODSTo investigate cellular and molecular differences among tumors according to HER2 heterogeneity and pCR, we performed RNA sequencing and ERBB2 FISH of 285 pretreatment and posttreatment tumors from 129 patients in this T-DM1+P neoadjuvant trial. A subset of cases was also subject to NanoString spatial digital profiling.RESULTSPretreatment tumors from patients with pCR had the highest level of ERBB2 mRNA and ERBB signaling. HER2 heterogeneity was associated with no pCR, basal-like features, and low ERBB2 expression yet high ERBB signaling sustained by activation of downstream pathway components. Residual tumors showed decreased HER2 protein levels and ERBB2 copy number heterogeneity and increased PI3K pathway enrichment and luminal features. HET tumors showed minimal treatment-induced transcriptomic changes compared with non-HET tumors. Immune infiltration correlated with pCR and HER2-HET status.CONCLUSIONResistance mechanisms in HET and non-HET tumors are distinct. HER2-targeting antibodies have limited efficacy in HET tumors. Our results support the stratification of patients based on HET status and the use of agents that target downstream components of the ERBB signaling pathway in patients with HET tumors.TRIAL REGISTRATIONClinicalTrials.gov NCT02326974.FUNDINGThis study was funded by Roche and the National Cancer Institute.

Identification of Glandular (Acinar)/Tubule Formation in Invasive Carcinoma of the Breast: A Study to Determine Concordance Using the World Health Organization Definition.

CONTEXT.­: The Nottingham Grading System (NGS) developed by Elston and Ellis is used to grade invasive breast cancer (IBC). Glandular (acinar)/tubule formation is a component of NGS. OBJECTIVE.­: To investigate the ability of pathologists to identify individual structures that should be classified as glandular (acinar)/tubule formation. DESIGN.­: A total of 58 hematoxylin-eosin photographic images of IBC with 1 structure circled were classified as tubules (41 cases) or nontubules (17 cases) by Professor Ellis. Images were sent as a PowerPoint (Microsoft) file to breast pathologists, who were provided with the World Health Organization definition of a tubule and asked to determine if a circled structure represented a tubule. RESULTS.­: Among 35 pathologists, the κ statistic for assessing agreement in evaluating the 58 images was 0.324 (95% CI, 0.314-0.335). The median concordance rate between a participating pathologist and Professor Ellis was 94.1% for evaluating 17 nontubule cases and 53.7% for 41 tubule cases. A total of 41% of the tubule cases were classified correctly by less than 50% of pathologists. Structures classified as tubules by Professor Ellis but often not recognized as tubules by pathologists included glands with complex architecture, mucinous carcinoma, and the "inverted tubule" pattern of micropapillary carcinoma. A total of 80% of participants reported that they did not have clarity on what represented a tubule. CONCLUSIONS.­: We identified structures that should be included as tubules but that were not readily identified by pathologists. Greater concordance for identification of tubules might be obtained by providing more detailed images and descriptions of the types of structures included as tubules.

Angiomyxoma of the Breast: A Clinicopathologic Analysis of 40 Cases.

Superficial angiomyxoma is an uncommon benign mesenchymal neoplasm that usually arises in dermis/subcutis of the extremities or trunk. Some tumors are associated with Carney complex. When arising in breast, these tumors are not well-recognized, mainly due to a lack of uniform nomenclature in the literature. This study therefore aims to improve recognition of angiomyxomas of the breast region. Forty cases were identified: demographics, presence of Carney complex, imaging and histologic features, PRKAR1A expression, and outcomes were evaluated. There were 22 female and 18 male patients (median age 40 years, range: 14 to 72). Most tumors presented as slowly-growing masses (77%). All but one were solitary, and median size was 1.5 cm. Tumors were superficial (dermal/subcutaneous) in 52.5% and deep/parenchymal in 47.5%. Nine involved the nipple-areola complex. All showed characteristic features of superficial angiomyxoma: poorly circumscribed, hypocellular, myxoid neoplasms with lobulated (55%) or infiltrative (45%) architecture, bland spindled fibroblasts, prominent thin-walled vessels, and admixed neutrophils. Tumors involving the nipple-areola complex infiltrated through areolar smooth muscle, and deep/parenchymal tumors showed entrapment of lobules mimicking myxoid fibroadenoma. Mitoses were typically absent, as was significant atypia. Cystic change was common. Two-thirds showed loss of PRKAR1A expression by immunohistochemistry. Two patients had Carney complex (7%). Recurrence after incomplete excision occurred in 1 patient. Angiomyxoma of breast may arise at superficial, nipple-areola or deep/parenchymal locations, where it can be difficult to recognize classic histologic features. Loss of expression of PRKAR1A is not invariable, but may be a helpful diagnostic clue. Recognizing angiomyxoma is important for 2 reasons: first, the recurrence rate is low and therefore wide excision is not essential, and second, it may allow detection of Carney complex in some patients.

Identifying Patterns and Barriers in OncotypeDX Recurrence Score Testing in Older Patients With Early-Stage, Estrogen Receptor-Positive Breast Cancer: Implications for Guidance and Reimbursement.

PURPOSE: To evaluate the clinical patterns of utilization of OncotypeDX Recurrence Score (RS) in early-stage, hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer (BC) at an academic center with previously established internal reflex testing guidelines. METHODS: RS testing in accordance with preexisting reflex criteria and predictors of utilization outside of reflex criteria were retrospectively analyzed for the years 2019-2021 in a quality improvement evaluation. Patients were grouped according to OncotypeDX testing within (cohort A) or outside (cohort B) of predefined criteria which included a cap at age older than 65 years. RESULTS: Of 1,687 patients whose tumors had RS testing, 1,087 were in cohort A and 600 in cohort B. In cohort B, nearly half of patients were older than 65 years (n = 279; IQR, 67-72 years). For patients older than 65 years, those with RS testing were younger (median age: 69 v 73 years), with higher grade cancers (G2-3: 84.9% v 54.7%) and were more likely to be treated with chemotherapy (15.4% v 4.1%). Issues for implementation of RS testing in older patients were identified, including potential structural barriers related to the current policy on the reimbursements of genomic tests. CONCLUSION: Internal guidelines may facilitate standardized utilization of the RS in early-BC. Our data suggest that clinicians preferred broader utilization of RS across the age spectrum, with therapeutically important consequences. Modifying the current policy for reimbursement of RS testing and in internal reflexive testing criteria for those older than 65 years is warranted.

The Critical Role of Breast Specimen Gross Evaluation for Optimal Personalized Cancer Care.

Gross examination is the foundation for the pathologic evaluation of all surgical specimens. The rapid identification of cancers is essential for intraoperative assessment and preservation of biomolecules for molecular assays. Key components of the gross examination include the accurate identification of the lesions of interest, correlation with clinical and radiologic findings, assessment of lesion number and size, relationship to surgical margins, documenting the extent of disease spread to the skin and chest wall, and the identification of axillary lymph nodes. Although the importance of gross evaluation is undeniable, current challenges include the difficulty of teaching grossing well and its possible perceived undervaluation compared with microscopic and molecular studies. In the future, new rapid imaging techniques without the need for tissue processing may provide an ideal melding of gross and microscopic pathologic evaluation.

Management of intraductal papillomas of the breast: an analysis of 129 cases and their outcome.

INTRODUCTION: The management of intraductal papillomas of the breast has been controversial; some advocate surgical excision of all lesions despite benign pathologic features, whereas others excise only those specimens with atypia. METHODS: We conducted a retrospective review of 129 core-biopsy-proven papillomas of the breast with atypia (n = 43) and without atypia (n = 86) and determined the rate of missed carcinoma in surgically excised specimen in each group. RESULTS: Carcinoma was found in 22.5% of the surgically excised specimens in the atypia group (9/40) and in 3% of the surgically excised specimens in the no atypia group (1/29). CONCLUSIONS: Our findings confirm the practice that papillomas with atypical features should be excised, and suggest that in patients with adequate follow-up, benign papillomas may be managed conservatively.

Hematologic Malignancies of the Breast: A Contemporary Series Investigating Incidence, Presentation, Accuracy of Diagnosis on Core Needle Biopsy, and Hormone Receptor Expression.

BACKGROUND: Distinguishing breast hematologic malignancies in core needle biopsies from other entities can be challenging. Misclassification as a breast carcinoma could result in inappropriate treatment. The aim of this study was to characterize the types, incidence, and helpful diagnostic features of hematologic malignancies of the breast. DESIGN: All hematologic malignancies of the breast diagnosed at our institution from 2004 to 2017 were identified. Clinical notes, imaging, and slides were reviewed. Immunohistochemical analysis of estrogen receptor α (ERα), estrogen receptor ß (ERß), and androgen receptor (AR) was performed when tissue was available. RESULTS: In all, 43 hematologic malignancies from biopsies of 37 women and 6 men were identified. Core needle biopsies (35 or 81%) were more common than excisions (8 or 19%). For 14 patients (40%), the core biopsy was the first diagnosis of a hematologic malignancy. Diagnoses included 37 lymphomas (7 primary), 4 leukemias, and 2 myelomas. There was 1 misdiagnosis of carcinoma. Low positivity for hormone receptors was observed in a minority of lymphomas. A definitive diagnosis of hematologic malignancy was made in 31 (89%) of the core needle biopsies. Only 3 patients undergoing core biopsy required excision for diagnosis. CONCLUSIONS: Most of the hematologic malignancies of the breast are currently diagnosed on core needle biopsy and 40% of patients do not have a prior history. To avoid errors, pathologists need to be aware of diagnostic features and morphologic mimics. A hematologic malignancy should be considered if tumor cells are discohesive, carcinoma in situ is absent, and hormone expression is low or absent.

Lobular breast cancer: patterns of intraabdominal metastatic spread on imaging and prognostic significance.

OBJECTIVE: To retrospectively review the frequency, patterns and intra-abdominal sites of metastatic invasive lobular breast cancer, and to correlate the findings with overall survival. MATERIALS AND METHODS: From a pathology database search revealing 327 patients with metastatic lobular breast cancer at our institution from January 2004 through August 2014, imaging was available in 116 patients (age range, 31-87 years, mean age, 55). Simple descriptive statistics were performed to record and tabulate the abdominal metastatic spread. Prognostic significance of abdominal metastases and individual abdominal metastatic sites was studied using the Log-rank test and construction of Kaplan-Meier curves. RESULTS: The most frequent sites of intra-abdominal metastatic invasive lobular breast cancer were peritoneum (55 patients, 47%), followed by liver (37 patients, 32%), bowel (34 patients, 29%), ovary (33 patients, 28%), retroperitoneum (16 patients, 14%), ureter (16 patients, 14%), and lymph nodes (15 patients, 13%). Bowel obstruction was noted in 15 patients (13%) and hydronephrosis in 25 patients (22%). The median abdominal metastasis-free survival was 76 months (interquartile range: 17-191). The overall survival (OS) was 86 months (interquartile range: 49-188). Patients with abdominal metastases had shorter OS. Patients with hepatic metastases had shorter overall survival than those patients without hepatic metastases (p = 0.02, Log-Rank test). CONCLUSION: Invasive lobular breast cancer has a predilection for metastasizing to both typical (liver) and atypical intra-abdominal sites (peritoneum, GI tract, and adnexa). Presence of intra-abdominal disease and hepatic metastases in patients with ILC negatively affects overall survival.

21-Gene Recurrence Score Adds Significant Value for Grade 3 Breast Cancers: Results From a National Cohort.

PURPOSE: The 21-gene recurrence score (RS) is used to identify patients with hormone receptor-positive early-stage breast cancer who may benefit from the addition of chemotherapy to endocrine therapy. We hypothesized that many women with poor prognostic histopathologic grade 3 disease may be offered chemotherapy irrespective of RS results, of whom a subset may not benefit from adjuvant chemotherapy. PATIENTS AND METHODS: A total of 30,864 women in the National Cancer Database were diagnosed with pT1c to pT2, pN0 to pN1, grade 3 estrogen receptor-positive, human epidermal growth factor receptor 2-negative invasive breast carcinoma from 2010 to 2015. RS was stratified as low (less than 18), intermediate (18 to 30), and high (31 or more). Overall survival by RS was evaluated by Kaplan-Meier, log-rank, and multivariable proportional hazards, with adjustment for relevant clinical and demographic variables. RESULTS: RS testing in grade 3 cancers increased between 2010 and 2015 (pN0, 53% to 72%; pN1, 16% to 36%). Among the 13,558 women with pN0 and the 2,840 with pN1 disease with RS testing, 27.1% and 30.0%, respectively, had low scores (less than 18). The 5-year overall survival rate for patients with a high RS, but not low RS, was significantly higher with chemotherapy (v no chemotherapy; absolute differences: high RS pN0 = 12.2% and pN1 = 25.5%, both P < .001; low RS pN0 = 2.5%, P = .07; and pN1 = 1.0%, P = .27), findings that were reinforced in multivariable analyses risk adjusted by clinicopathologic characteristics. CONCLUSION: Increased use of RS may help to better tailor treatment recommendations by stratifying patients with grade 3 disease into those who will and will not derive survival benefit and should be considered in all patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative T1c to T2, N0 to N1 disease.