Outcomes of atypical lobular hyperplasia managed by active surveillance or immediate surgery.

BACKGROUND: Atypical lobular hyperplasia (ALH) is typically diagnosed via needle core biopsy (NCB) and is commonly removed surgically in light of upgrade to malignancy rates of 1%-5%. As studies on radiographic outcomes of ALH managed by active surveillance (AS) are limited, we investigated the upgrade rates of surgically excised ALH as well as radiographic progression during AS. METHODS: In this retrospective study, 125 patients with 127 ALH lesions diagnosed via NCB at Weill Cornell Medicine from 2015 to 2021 were included. The upgrade rate to cancer was determined for patients who had surgical management ≤6 months after biopsy. Among patients with ALH managed by AS, we investigated radiographic progression on 6-month interval imaging. RESULTS: Of 127 ALH lesions, 75% (n = 95) were immediately excised and 25% (n = 32) were observed under AS. The upgrade rate of immediately excised ALH was 2.1% (n = 2; invasive ductal carcinoma [IDC], T1N0 and IDC, and T1Nx). In the AS cohort, no ALH lesions progressed radiographically during the follow-up period of 22.5 months (median), with all remaining stable (50%, n = 16), resolving (47%, n = 15), or decreasing in size (3%, n = 1). CONCLUSIONS: In this study, NCB-diagnosed ALH had a low upgrade to malignancy rate (2.1%), and no ALH lesions managed by AS progressed radiographically during the follow-up period of 22.5 months. These results support AS as the favorable option for patients with pure ALH on biopsy, with surgical excision for lesions that progress on surveillance.

Histologic grading of breast carcinoma: a multi-institution study of interobserver variation using virtual microscopy.

Breast carcinoma grading is an important prognostic feature recently incorporated into the AJCC Cancer Staging Manual. There is increased interest in applying virtual microscopy (VM) using digital whole slide imaging (WSI) more broadly. Little is known regarding concordance in grading using VM and how such variability might affect AJCC prognostic staging (PS). We evaluated interobserver variability amongst a multi-institutional group of breast pathologists using digital WSI and how discrepancies in grading would affect PS. A digitally scanned slide from 143 invasive carcinomas was independently reviewed by 6 pathologists and assigned grades based on established criteria for tubule formation (TF), nuclear pleomorphism (NP), and mitotic count (MC). Statistical analysis was performed. Interobserver agreement for grade was moderate (κ = 0.497). Agreement was fair (κ = 0.375), moderate (κ = 0.491), and good (κ = 0.705) for grades 2, 3, and 1, respectively. Observer pair concordance ranged from fair to good (κ = 0.354-0.684) Perfect agreement was observed in 43 cases (30%). Interobserver agreement for the individual components was best for TF (κ = 0.503) and worst for MC (κ = 0.281). Seventeen of 86 (19.8%) discrepant cases would have resulted in changes in PS and discrepancies most frequently resulted in a PS change from IA to IB (n = 9). For two of these nine cases, Oncotype DX results would have led to a PS of 1A regardless of grade. Using VM, a multi-institutional cohort of pathologists showed moderate concordance for breast cancer grading, similar to studies using light microscopy. Agreement was the best at the extremes of grade and for evaluation of TF. Whether the higher variability noted for MC is a consequence of VM grading warrants further investigation. Discordance in grading infrequently leads to clinically meaningful changes in the prognostic stage.

Radial Scars and Complex Sclerosing Lesions of the Breast: Prevalence of Malignancy and Natural History Under Active Surveillance.

BACKGROUND: When needle core biopsies (NCBs) of the breast reveal radial scar or complex sclerosing lesions (RSLs), excision is often recommended despite a low risk of malignancy in the modern era. The optimal management of NCBs revealing RSLs is controversial, and understanding of the natural history of unresected RSLs is limited. METHODS: We retrospectively analyzed pathology and imaging data from 148 patients with NCB revealing RSL without atypia from 2015 to 2019 to determine the prevalence of malignancy and the behavior of RSLs undergoing active surveillance (AS). RESULTS: The mean age of patients was 52 years, and most lesions were screen-detected (91%). The median lesion size was 6.0 mm (range 2-39). Most patients (66%, n = 98) underwent immediate surgery, while 34% (n = 50) of patients underwent AS, with a median follow-up of 16 months (range 6-51). Of the excised RSLs, 99% (n = 97) were benign and 1% (n = 1) revealed ductal carcinoma in situ (DCIS). In 17% (n = 17) of cases, additional high-risk lesions were discovered upon excision. Among the 50 patients undergoing AS, no lesions progressed on interval imaging. CONCLUSIONS: In this cohort, 99% of RSLs undergoing excision were benign, 1% revealed DCIS, and there were no invasive cancers. In the first study of patients with RSLs undergoing AS, we found that all lesions either remained stable or resolved. We propose that the vast majority of patients with RSL on NCB can be safely offered AS, and that routine excision is a low-value intervention.

High-Risk Lesions Detected by MRI-Guided Core Biopsy: Upgrade Rates at Surgical Excision and Implications for Management.

OBJECTIVE. The purpose of our study was to evaluate the upgrade rates of high-risk lesions (HRLs) diagnosed by MRI-guided core biopsy and to assess which clinical and imaging characteristics are predictive of upgrade to malignancy. MATERIALS AND METHODS. A retrospective review was performed of all women who presented to an academic breast radiology center for MRI-guided biopsy between January 1, 2015, and November 30, 2018. Histopathologic results from each biopsy were extracted. HRLs-that is, atypical ductal hyperplasia (ADH), lobular carcinoma in situ (LCIS), atypical lobular hyperplasia (ALH), radial scar, papilloma, flat epithelial atypia (FEA), benign vascular lesion (BVL), and mucocelelike lesion-were included for analysis. Clinical history, imaging characteristics, surgical outcome, and follow-up data were recorded. Radiologic-pathologic correlation was performed. RESULTS. Of 810 MRI-guided biopsies, 189 cases (23.3%) met the inclusion criteria for HRLs. Of the 189 HRLs, 30 cases were excluded for the following reasons: 15 cases were lost to follow-up, six cases were in patients who received neoadjuvant chemotherapy after biopsy, two lesions that were not excised had less than 2 years of imaging follow-up, and seven lesions had radiologic-pathologic discordance at retrospective review. Of the 159 HRLs in our study cohort, 13 (8.2%) were upgraded to carcinoma. Surgical upgrade rates were high for ADH (22.5%, 9/40) and FEA (33.3%, 1/3); moderate for LCIS (6.3%, 3/48); and low for ALH (0.0%, 0/11), radial scar (0.0%, 0/28), papilloma (0.0%, 0/26), and BVL (0.0%, 0/3). Of the upgraded lesions, 69.2% (9/13) were upgraded to ductal carcinoma in situ (DCIS) or well-differentiated carcinoma. ADH lesions were significantly more likely to be upgraded than non-ADH lesions (p = .005). CONCLUSION. ADH diagnosed by MRI-guided core biopsy warrants surgical excision. The other HRLs, however, may be candidates for imaging follow-up rather than excision, especially after meticulous radiologic-pathologic correlation.

Adenomyoepithelial tumors of the breast: molecular underpinnings of a rare entity.

Adenomyoepitheliomas (AMEs) of the breast are uncommon and span the morphologic spectrum of benign, atypical, in situ, and invasive forms. In exceptionally rare cases, these tumors metastasize to regional lymph nodes or distant sites. In the era of genomic characterization, data is limited regarding AMEs. The aim of this study was to provide insight into the molecular underpinnings of a spectrum of AMEs. Seven cases of AMEs of the breast (benign-1, atypical-2, in situ-1, invasive-3) were identified in our files. The seven samples were interrogated using the Oncomine Comprehensive Assay v3 (ThermoFisher). Two atypical AMEs and the malignant in situ AME harbored the same gain-of-function PIK3CA mutation. The malignant in situ AME also showed EGFR amplification, not described previously. Both a benign AME and a malignant invasive AME shared the same gain-of-function AKT1 variant. The benign AME also showed a GNAS mutation. Moreover, the same gain-of-function HRAS mutation was present in an atypical AME and a malignant invasive AME. We also identified co-occurring HRAS and PIK3CA mutations in an ER-positive atypical AME, which has not been previously described. No fusion drivers were detected. We describe the molecular characteristics of the spectrum of AME tumors of the breast, which harbor alterations in the PI3K/AKT pathway. Our findings are clinically relevant with respect to the current options of targeted therapy in the rare instances where malignant AME tumors of the breast progress.

A review of mucinous lesions of the breast.

Mucinous lesions of the breast include a variety of benign and malignant epithelial processes that display intracytoplasmic or extracellular mucin, including mucocele-like lesions, mucinous carcinoma, solid papillary carcinoma, and other rare subtypes of mucin-producing carcinoma. The finding of free-floating or stromal mucin accumulations is a diagnostic challenge of which the significance depends on the clinical, radiologic, and pathologic context. This article emphasizes the differential diagnosis between benign and malignant mucin-producing lesions, with a brief consideration of potential mimics, such as biphasic and mesenchymal lesions with associated with mucinous, myxoid, or matrix material.

Characterization of CD34-deficient myofibroblastomas of the breast.

Mammary myofibroblastoma is a benign spindle cell tumor that can show variable morphologic patterns and lines of differentiation. Diffuse and strong immunohistochemical expression of CD34 is a characteristic of myofibroblastoma and greatly aids in confirming a diagnosis. Myofibroblastoma has been shown to belong to a family of CD34-positive tumors with similar morphology that show a deletion of 13q14, which includes RB1 and FOXO1A genes. The purpose of this study was to better understand a subset of myofibroblastomas that is characteristically CD34-deficient by immunohistochemistry. Six myofibroblastomas were studied by immunohistochemistry and fluorescence in situ hybridization (FISH) for RB1. Patients included five women and one man, aged 41-85 years (median, 52.5). Tumor size ranged from 0.4 to 1.5 cm (mean, 0.95). Tumors showed spindle cell morphology in five cases and epithelioid features in one case. Two tumors showed complete lack of CD34 staining. The remaining showed weak focal or weak patchy CD34 staining. Dichotomous staining was seen in one case with CD34-positive spindle cell areas and CD34-negative myxoid areas. All six tumors showed ER expression, five of six showed desmin expression, and four of six showed bcl-2 positivity. Two of six (33.3%) tumors showed deletion of RB1 by FISH, including one that showed loss of Rb immunohistochemical staining. Myofibroblastomas uncommonly show absent/focal expression of CD34, a potential diagnostic pitfall, particularly in small samples. Characteristic staining with other immunohistochemical markers is seen which can aid in confirming the diagnosis. These tumors may harbor deletion of RB1, similar to CD34-positive myofibroblastomas, and this deletion may not correlate with loss of Rb by immunohistochemistry.

Exuberant Squamous Metaplasia with Calcification Following Intraoperative Radiotherapy for Breast Carcinoma: Report of an Unusual Case and Retrospective Review of Cases from a Single Institution.

Intraoperative radiotherapy (IORT) is a novel and increasingly utilized radiation technique in the treatment of breast carcinoma. There are few reports on the histologic changes seen in breast tissue from patients who have undergone IORT. We sought to evaluate the histologic changes observed in specimens received following IORT, as well as report an unusual case which prompted our study. A retrospective review of patients who received IORT and subsequently had breast tissue histologically evaluated at our institution was performed. Fifteen post-IORT specimens from 12 patients, including the patient from the reported case, were studied. We report a case of a 77-year-old woman found to have mammographic microcalcifications at the lumpectomy site 6 months following lumpectomy and IORT for ductal carcinoma in situ (DCIS). A stereotactic biopsy showed abundant desquamated anucleate squamous cells with calcification and keratin material associated with squamous metaplasia of ducts. Carcinoma was not present. The predominant findings in the post-IORT specimens were fat necrosis and scar (n = 5), recurrent invasive carcinoma (n = 5), surgical site changes (n = 3), abscess (n = 1), and exuberant squamous metaplasia with calcification (n = 1). Five of fifteen (33%) post-IORT specimens showed squamous metaplasia, all of which were collected within 6 months of IORT delivery. The morphologic changes observed after IORT are similar to those seen after external beam radiotherapy. Exuberant squamous metaplasia is an uncommon consequence of IORT; however, pathologists should be aware of this phenomenon and review a history of prior intraoperative radiation before raising concern for malignancy.

Squamous Cell Carcinoma In Situ of the Breast: Report of a Case.

We present the case of a 73-year-old woman with pure squamous cell carcinoma in situ of the left breast. This non-invasive malignancy exhibited pure squamous type of architectural and cytologic features without any evidence of glandular differentiation either in the initial needle core biopsy or in the subsequently performed excisional biopsy and simple mastectomy. The tumor spanned 1.6 cm, involved numerous ducts and terminal ducts and extended into lobules, and was characterized by keratinizing squamous cells with intermediate-grade nuclei. Intercellular bridges extended between the malignant squamous cells. Keratinous debris with "pearl" formation was evident in most involved glands. No invasive carcinoma was identified. There was no evidence of metastatic disease in the ipsilateral sentinel lymph nodes. Thus far, only three cases of squamous cell carcinoma in situ of the breast have been reported in one series-none of which showed any evidence of recurrent or metastatic disease at last follow-up. In our case, treated exclusively by surgery, there was no evidence of disease 11 years after diagnosis.

Elucidating encounters of atypical ductal hyperplasia arising in gynaecomastia.

AIMS: Atypical ductal hyperplasia (ADH) rarely arises in gynaecomastia. We set out to understand more clearly the clinical, histological and immunohistochemical features of ADH in this setting. METHODS AND RESULTS: Twenty-five cases of ADH arising in gynaecomastia, nine cases of ductal carcinoma in situ (DCIS) and 36 cases of gynaecomastia with usual ductal hyperplasia (UDH) were studied. Reviews of clinical, morphological and immunohistochemical findings were performed. The extent of cytokeratin 5/6 (CK5/6) luminal epithelial cell staining was assessed (0% = 0, < 10% = 1, 10-50% = 2 and > 50% = 3). Oestrogen receptor (ER) was evaluated using the H-scoring system. The average age of ADH patients was 35 years (range 14-78). ADH was bilateral in 20% and less frequent in active gynaecomastia (24%). ADH often showed a cribriform pattern (72%), with less nuclear variation/size and similar frequency of mitoses than UDH cells. CK5/6 luminal epithelial staining was decreased in ADH (68%) versus UDH (11%). ADH showed high ER expression compared to UDH (H score > 270 in 88% and 14%, respectively). CONCLUSIONS: ADH in gynaecomastia can be distinguished from UDH by morphological and immunohistochemical features. We also identified a subset of young patients (< 25 years) with extensive bilateral ADH. More studies are needed to characterize this patient subset more clearly.

More than just metastases: a practical approach to solid mesenteric masses.

The abdominal mesenteries are important peritoneal structures that give rise to a wide spectrum of abnormalities, including solid mesenteric masses. Despite similarities in appearance, solid masses in the mesentery may have diverse etiologies, ranging from benign to highly malignant. While metastases are the most common cause of solid masses in the mesentery, other less common conditions are also important diagnostic considerations. This article reviews four pathologic entities (sclerosing mesenteritis, carcinoid tumors, desmoids tumors, and gastrointestinal stromal tumors) that may be manifested on abdominal imaging examinations by one or more mesenteric masses. These four pathologic entities are used to present a systematic approach to the radiographic characterization of solid mesenteric masses based on the morphology of the lesions, locoregional effects, and distant findings on various abdominal imaging examinations.

Patient-derived tumor organoids with p53 mutations, and not wild-type p53, are sensitive to synergistic combination PARP inhibitor treatment.

Poly (ADP-ribose) polymerase inhibitors (PARPi) are used for patients with BRCA1/2 mutations, but patients with other mutations may benefit from PARPi treatment. Another mutation that is present in more cancers than BRCA1/2 is mutation to the TP53 gene. In 2D breast cancer cell lines, mutant p53 (mtp53) proteins tightly associate with replicating DNA and Poly (ADP-ribose) polymerase (PARP) protein. Combination drug treatment with the alkylating agent temozolomide and the PARPi talazoparib kills mtp53 expressing 2D grown breast cancer cell lines. We evaluated the sensitivity to the combination of temozolomide plus PARPi talazoparib treatment to breast and lung cancer patient-derived tumor organoids (PDTOs). The combination of the two drugs was synergistic for a cytotoxic response in PDTOs with mtp53 but not for PDTOs with wtp53. The combination of talazoparib and temozolomide induced more DNA double-strand breaks in mtp53 expressing organoids than in wild-type p53 expressing organoids as shown by increased γ-H2AX protein expression. Moreover, breast cancer tissue microarrays (TMAs) showed a positive correlation between stable p53 and high PARP1 expression in sub-groups of breast cancers, which may indicate sub-classes of breast cancers sensitive to PARPi therapy. These results suggest that mtp53 could be a biomarker to predict response to the combination of PARPi talazoparib-temozolomide treatment.

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.

Active Surveillance of Atypical Ductal Hyperplasia of the Breast.

BACKGROUND: When needle core biopsy (NCB) of the breast yields atypical ductal hyperplasia (ADH), excision is typically recommended. The natural history of ADH undergoing active surveillance (AS) is not well described. We investigate the rates of upgrade to malignancy of excised ADH and the rates of radiographic progression under AS. MATERIALS AND METHODS: We retrospectively reviewed records of 220 cases of ADH on NCB. Of patients who had surgery within 6 months of NCB, we examined the malignancy upgrade rate. In the AS cohort, we examined rates of radiographic progression on interval imaging. RESULTS: The malignancy upgrade rate among patients who underwent immediate excision (n = 185) was 15.7%: 14.1% (n = 26) ductal carcinoma in situ (DCIS) and 1.6% (n = 3) invasive ductal carcinoma (IDC). Upgrade to malignancy was less common in lesions <4 mm in size (0%) or with focal ADH (5%), and more common among lesions presenting with a radiographic mass (26%). Among the 35 patients who underwent AS, median follow-up was 20 months. Two lesions progressed on imaging (incidence 3.8% at 2 years). One patient without radiographic progression was found to have IDC at delayed surgery. The remaining lesions remained stable (46%), decreased in size (11%), or resolved (37%). CONCLUSIONS: Our findings suggest that AS is a safe approach to managing ADH on NCB for most patients. This could spare many patients with ADH from unnecessary surgery. Given that AS is being investigated for low-risk DCIS in multiple international prospective trials, these results suggest that AS should also be investigated for ADH.

Racial disparity in tumor microenvironment and distant recurrence in residual breast cancer after neoadjuvant chemotherapy.

Black, compared to white, women with residual estrogen receptor-positive (ER+) breast cancer after neoadjuvant chemotherapy (NAC) have worse distant recurrence-free survival (DRFS). Such racial disparity may be due to difference in density of portals for systemic cancer cell dissemination, called TMEM doorways, and pro-metastatic tumor microenvironment (TME). Here, we evaluate residual cancer specimens after NAC from 96 Black and 87 white women. TMEM doorways are visualized by triple immunohistochemistry, and cancer stem cells by immunofluorescence for SOX9. The correlation between TMEM doorway score and pro-metastatic TME parameters with DRFS is examined using log-rank and multivariate Cox regression. Black, compared to white, patients are more likely to develop distant recurrence (49% vs 34.5%, p = 0.07), receive mastectomy (69.8% vs 54%, p = 0.04), and have higher grade tumors (p = 0.002). Tumors from Black patients have higher TMEM doorway and macrophages density overall (p = 0.002; p = 0.002, respectively) and in the ER+/HER2- (p = 0.02; p = 0.02, respectively), but not in the triple negative disease. Furthermore, high TMEM doorway score is associated with worse DRFS. TMEM doorway score is an independent prognostic factor in the entire study population (HR, 2.02; 95%CI, 1.18-3.46; p = 0.01), with a strong trend in ER+/HER2- disease (HR, 2.38; 95%CI, 0.96-5.95; p = 0.06). SOX9 expression is not associated with racial disparity in TME or outcome. In conclusion, higher TMEM doorway density in residual breast cancer after NAC is associated with higher distant recurrence risk, and Black patients are associated with higher TMEM doorway density, suggesting that TMEM doorway density may contribute to racial disparities in breast cancer.

Patient-derived tumor organoids with p53 mutations, and not wild-type p53, are sensitive to synergistic combination PARP inhibitor treatment.

Poly (ADP-ribose) polymerase inhibitors (PARPi) are used for patients with BRCA1/2 mutations, but patients with other mutations may benefit from PARPi treatment. Another mutation that is present in more cancers than BRCA1/2 is mutation to the TP53 gene. In 2D breast cancer cell lines, mutant p53 (mtp53) proteins tightly associate with replicating DNA and Poly (ADP-ribose) polymerase (PARP) protein. Combination drug treatment with the alkylating agent temozolomide and the PARPi talazoparib kills mtp53 expressing 2D grown breast cancer cell lines. We evaluated the sensitivity to the combination of temozolomide plus PARPi talazoparib treatment to breast and lung cancer patient-derived tumor organoids (PDTOs). The combination of the two drugs was synergistic for a cytotoxic response in PDTOs with mtp53 but not for PDTOs with wtp53. The combination of talazoparib and temozolomide induced more DNA double-strand breaks in mtp53 expressing organoids than in wild-type p53 expressing organoids as shown by increased γ-H2AX protein expression. Moreover, breast cancer tissue microarrays (TMAs) showed a positive correlation between stable p53 and high PARP1 expression in sub-groups of breast cancers, which may indicate sub-classes of breast cancers sensitive to PARPi therapy. These results suggest that mtp53 could be a biomarker to predict response to the combination of PARPi talazoparib-temozolomide treatment.

Mucocele-like Lesion of the Breast Diagnosed on Core Biopsy.

CONTEXT.­: Mucocele-like lesion of the breast (MLL) is an uncommon entity, and recent studies show low rates of upgrade from core needle biopsy (CNB) to excision. OBJECTIVE.­: To evaluate features associated with upgrade of MLLs diagnosed on CNB. DESIGN.­: Seventy-eight MLLs diagnosed on CNB from 1998-2019 and subsequent excisions were reviewed. Histologic parameters evaluated included the presence of atypia, presence and morphology of calcifications, and morphologic variant (classic [C-MLL], duct ectasia-like [DEL-MLL], or cystic mastopathy-like [CML-MLL]). RESULTS.­: Overall, 45 MLLs lacked atypia and 33 were associated with atypia (atypical ductal hyperplasia, 32; atypical lobular hyperplasia, 1). Most were C-MLLs (61) with fewer DEL-MLLs (14) and CML-MLLs (3). Half showed both coarse and fine calcifications, with fewer showing only coarse or fine calcifications, and some showing none. Subsequent excision or clinical follow-up was available for 25 MLLs without atypia-of which 2 (8.0%) were upgraded to ductal carcinoma in situ (DCIS)-and 23 with atypia, of which 4 (17.4%) were upgraded to DCIS. No cases were upgraded to invasive carcinoma. All upgraded cases showed coarse calcifications on CNB, and all upgraded cases were associated with residual calcifications on post-CNB imaging. CONCLUSIONS.­: Most MLLs present as calcifications and nearly half are associated with atypia. Upgrade to DCIS is twice as frequent in MLLs with atypia versus those without. A predominance of coarse calcifications and the presence of residual targeted calcifications following core biopsy may be associated with higher upgrade rates.

Subareolar Tissue Biopsy Predicts Occult Nipple Involvement in Nipple-Sparing Mastectomies.

OBJECTIVES: Subareolar tissue is examined during nipple-sparing mastectomy (NSM) to minimize the risk of occult malignancy within the preserved nipple. A positive subareolar tissue biopsy typically warrants subsequent nipple excision. We study the factors associated with a positive subareolar tissue biopsy, the rate of residual malignancy in subsequent nipple excisions, and the value of subareolar tissue biopsy intraoperative frozen section (IOF). METHODS: We identified 1,026 consecutive NSMs with separately submitted subareolar tissue biopsies over a 5.5-year period. Clinicopathologic data were reviewed. We examined concordance rates between subareolar tissue biopsy and subsequent nipple excisions as well as IOF diagnosis and permanent control diagnosis. RESULTS: Among cases of therapeutic NSM, the rate of a positive subareolar tissue biopsy was 7.2%. Multifocal/multicentric disease (P = .0005), presence of lymphovascular invasion (P = .033), and nodal involvement (P = .006) were significantly associated with a positive subareolar tissue biopsy. Thirty-nine of 41 cases with positive subareolar biopsies underwent subsequent nipple excision, with 20 (51%) showing residual carcinoma. Among all IOF samples, 9 (3.3%) showed a discrepancy between the IOF and permanent diagnoses, mostly because of false-negatives. CONCLUSIONS: A positive subareolar tissue biopsy predicts residual carcinoma in the excised nipples in 51% of cases. IOF is accurate and reliable.