Comparison of three scoring methods using the FDA-approved 22C3 immunohistochemistry assay to evaluate PD-L1 expression in breast cancer and their association with clinicopathologic factors.

BACKGROUND: In the evaluation of PD-L1 expression to select patients for anti-PD-1/PD-L1 treatment, uniform guidelines that account for different immunohistochemistry assays, different cell types and different cutoff values across tumor types are lacking. Data on how different scoring methods compare in breast cancer are scant. METHODS: Using FDA-approved 22C3 diagnostic immunohistochemistry assay, we retrospectively evaluated PD-L1 expression in 496 primary invasive breast tumors that were not exposed to anti-PD-1/PD-L1 treatment and compared three scoring methods (TC: invasive tumor cells; IC: tumor-infiltrating immune cells; TCIC: a combination of tumor cells and immune cells) in expression frequency and association with clinicopathologic factors. RESULTS: In the entire cohort, positive PD-L1 expression was observed in 20% of patients by TCIC, 16% by IC, and 10% by TC, with a concordance of 87% between the three methods. In the triple-negative breast cancer patients, positive PD-L1 expression was observed in 35% by TCIC, 31% by IC, and 16% by TC, with a concordance of 76%. Associations between PD-L1 and clinicopathologic factors were investigated according to receptor groups and whether the patients had received neoadjuvant chemotherapy. The three scoring methods showed differences in their associations with clinicopathologic factors in all subgroups studied. Positive PD-L1 expression by IC was significantly associated with worse overall survival in patients with neoadjuvant chemotherapy and showed a trend for worse overall survival and distant metastasis-free survival in triple-negative patients with neoadjuvant chemotherapy. Positive PD-L1 expression by TCIC and TC also showed trends for worse survival in different subgroups. CONCLUSIONS: Our findings indicate that the three scoring methods with a 1% cutoff are different in their sensitivity for PD-L1 expression and their associations with clinicopathologic factors. Scoring by TCIC is the most sensitive way to identify PD-L1-positive breast cancer by immunohistochemistry. As a prognostic marker, our study suggests that PD-L1 is associated with worse clinical outcome, most often shown by the IC score; however, the other scores may also have clinical implications in some subgroups. Large clinical trials are needed to test the similarities and differences of these scoring methods for their predictive values in anti-PD-1/PD-L1 therapy.

Imaging features of triple-negative breast cancers according to androgen receptor status.

OBJECTIVE: Different molecular subtypes of triple-negative breast cancer (TNBC) have previously been identified through analysis of gene expression profiles. The luminal androgen receptor (LAR) subtype has been shown to have a lower rate of pathologic complete response to neoadjuvant chemotherapy than other TNBC subtypes. The purpose of this study was to determine if the imaging features of TNBCs differ by AR (androgen receptor) status, which is a surrogate immunohistochemical (IHC) marker for the chemoresistant LAR subtype of TNBC. MATERIALS AND METHODS: This sub-study was part of a clinical trial in patients with stage I-III TNBC who were prospectively monitored for response while receiving neoadjuvant systemic therapy (NAST) at a single comprehensive cancer center. This interim imaging analysis included 144 patients with known AR status measured by IHC. AR-positive (AR+) tumors were defined as those in which at least 10% of tumor cells had positive nuclear AR staining. Two experienced, fellowship-trained breast radiologists who were blinded to the IHC results retrospectively reviewed and reached consensus on all imaging studies for the index lesion (i.e., mammogram, ultrasound, and breast magnetic resonance imaging). The index lesion for each patient was reviewed and described according to the fifth edition of the Breast Imaging Reporting and Data System lexicon. Logistic regression modeling was used to identify imaging features predictive of AR status. p ≤ 0.05 was considered statistically significant. RESULTS: Univariate logistic regression models for AR status showed that AR+ TNBC was significantly associated with heterogeneously dense breast composition on mammography (p = 0.02), mass with calcifications (p = 0.05), irregular mass shape on mammography (p = 0.03), and irregular mass shape on sonography (p = 0.003). Multivariate logistic regression models for AR status showed that AR+ TNBC was significantly associated with heterogeneously dense breast composition on mammography (p = 0.01), high mass density on mammography (p = 0.003), and irregular mass shape on sonography (p = 0.0004). CONCLUSION: The imaging features of TNBCs differ by AR status. Multimodality breast imaging may help identify the LAR subtype of TNBC, which has been shown to be a subtype that is relatively resistant to neoadjuvant chemotherapy.

Role of RPL39 in Metaplastic Breast Cancer.

Background: Metaplastic breast cancer is one of the most therapeutically challenging forms of breast cancer because of its highly heterogeneous and chemoresistant nature. We have previously demonstrated that ribosomal protein L39 (RPL39) and its gain-of-function mutation A14V have oncogenic activity in triple-negative breast cancer and this activity may be mediated through inducible nitric oxide synthase (iNOS). The function of RPL39 and A14V in other breast cancer subtypes is currently unknown. The objective of this study was to determine the role and mechanism of action of RPL39 in metaplastic breast cancer. Methods: Both competitive allele-specific and droplet digital polymerase chain reaction were used to determine the RPL39 A14V mutation rate in metaplastic breast cancer patient samples. The impact of RPL39 and iNOS expression on patient overall survival was estimated using the Kaplan-Meier method. Co-immunoprecipitation and immunoblot analyses were used for mechanistic evaluation of RPL39. Results: The RPL39 A14V mutation rate was 97.5% (39/40 tumor samples). High RPL39 (hazard ratio = 0.71, 95% confidence interval = 0.55 to 0.91, P = 006) and iNOS expression (P = 003) were associated with reduced patient overall survival. iNOS inhibition with the pan-NOS inhibitor NG-methyl-L-arginine acetate decreased in vitro proliferation and migration, in vivo tumor growth in both BCM-4664 and BCM-3807 patient-derived xenograft models (P = 04 and P = 02, respectively), and in vitro and in vivo chemoresistance. Mechanistically, RPL39 mediated its cancer-promoting actions through iNOS signaling, which was driven by the RNA editing enzyme adenosine deaminase acting on RNA 1. Conclusion: NOS inhibitors and RNA editing modulators may offer novel treatment options for metaplastic breast cancer.

Low expression of galectin-3 is associated with poor survival in node-positive breast cancers and mesenchymal phenotype in breast cancer stem cells.

BACKGROUND: Galectin-3 (Gal3) plays diverse roles in cancer initiation, progression, and drug resistance depending on tumor type characteristics that are also associated with cancer stem cells (CSCs). Recurrence of breast carcinomas may be attributed to the presence of breast CSCs (BCSCs). BCSCs exist in mesenchymal-like or epithelial-like states and the transition between these states endows BCSCs with the capacity for tumor progression. The discovery of a feedback loop with galectins during epithelial-to-mesenchymal transition (EMT) prompted us to investigate its role in breast cancer stemness. METHOD: To elucidate the role of Gal3 in BCSCs, we performed various in vitro and in vivo studies such as sphere-formation assays, Western blotting, flow cytometric apoptosis assays, and limited dilution xenotransplant models. Histological staining for Gal3 in tissue microarrays of breast cancer patients was performed to analyze the relationship of clinical outcome and Gal3 expression. RESULTS: Here, we show in a cohort of 87 node-positive breast cancer patients treated with doxorubicin-based chemotherapy that low Gal3 was associated with increased lymphovascular invasion and reduced overall survival. Analysis of in vitro BCSC models demonstrated that Gal3 knockdown by small hairpin RNA (shRNA) interference in epithelial-like mammary spheres leads to EMT, increased sphere-formation ability, drug-resistance, and heightened aldefluor activity. Furthermore, Gal3negative BCSCs were associated with enhanced tumorigenicity in orthotopic mouse models. CONCLUSIONS: Thus, in at least some breast cancers, loss of Gal3 might be associated with EMT and cancer stemness-associated traits, predicts poor response to chemotherapy, and poor prognosis.

Transection of Radioactive Seeds in Breast Specimens.

Radioactive seed localization is a new procedure for localizing breast lesions that has several advantages over the standard wire-localization procedure. It is reported to be safe for both patients and medical personnel. Although it is theoretically possible to transect the titanium-encapsulated seed while processing the breast specimen in the pathology laboratory, the likelihood of such an event is thought to be exceedingly low. In fact, there are no previous reports of such an event in the literature to date. We recently encountered 2 cases in which a radioactive seed was inadvertently transected while slicing a breast specimen at the grossing bench. In this report, we describe each case and offer recommendations for minimizing radioactive exposure to personnel and for preventing radioactive contamination of laboratory equipment.

Improved Axillary Evaluation Following Neoadjuvant Therapy for Patients With Node-Positive Breast Cancer Using Selective Evaluation of Clipped Nodes: Implementation of Targeted Axillary Dissection.

PURPOSE: Placing clips in nodes with biopsy-confirmed metastasis before initiating neoadjuvant therapy allows for evaluation of response in breast cancer. Our goal was to determine if pathologic changes in clipped nodes reflect the status of the nodal basin and if targeted axillary dissection (TAD), which includes sentinel lymph node dissection (SLND) and selective localization and removal of clipped nodes, improves the false-negative rate (FNR) compared with SLND alone. METHODS: A prospective study of patients with biopsy-confirmed nodal metastases with a clip placed in the sampled node was performed. After neoadjuvant therapy, patients underwent axillary surgery and the pathology of the clipped node was compared with other nodes. Patients undergoing TAD had SLND and selective removal of the clipped node using iodine-125 seed localization. The FNR was determined in patients undergoing complete axillary lymphadenectomy (ALND). RESULTS: Of 208 patients enrolled in this study, 191 underwent ALND, with residual disease identified in 120 (63%). The clipped node revealed metastases in 115 patients, resulting in an FNR of 4.2% (95% CI, 1.4 to 9.5) for the clipped node. In patients undergoing SLND and ALND (n = 118), the FNR was 10.1% (95% CI, 4.2 to 19.8), which included seven false-negative events in 69 patients with residual disease. Adding evaluation of the clipped node reduced the FNR to 1.4% (95% CI, 0.03 to 7.3; P = .03). The clipped node was not retrieved as an SLN in 23% (31 of 134) of patients, including six with negative SLNs but metastasis in the clipped node. TAD followed by ALND was performed in 85 patients, with an FNR of 2.0% (1 of 50; 95% CI, 0.05 to 10.7). CONCLUSION: Marking nodes with biopsy-confirmed metastatic disease allows for selective removal and improves pathologic evaluation for residual nodal disease after chemotherapy.

GATA-binding protein 3 enhances the utility of gross cystic disease fluid protein-15 and mammaglobin A in triple-negative breast cancer by immunohistochemistry.

AIMS: We have demonstrated previously that gross cystic disease fluid protein-15 (GCDFP-15) and mammaglobin A (MAM) are of limited utility in triple-negative breast cancer (TNBC). GATA-binding protein 3 (GATA-3) is an emerging breast-associated immunohistochemical (IHC) marker with limited data in TNBC. Here, we examined GATA-3 expression in TNBC in comparison with GCDFP-15 and MAM. METHODS AND RESULTS: We studied GATA-3, GCDFP-15 and MAM IHC expression in 62 primary and 68 metastatic TNBCs. In primary TNBCs, GATA-3 staining was observed in 25 cases (40%), including 16 cases that were negative for GCDFP-15 and MAM. In metastatic TNBCs, GATA-3 staining was observed in 30 cases (44%), including 16 cases that were negative for GCDFP-15 and MAM. The expression frequency of any of the markers was 56% in primary and 62% in metastatic TNBCs. However, when focal staining was excluded, the expression frequency of any marker dropped to 31% and 44%, respectively. CONCLUSION: GATA-3 is expressed at a higher frequency by IHC in TNBC compared to GCDFP-15 and MAM, although the tissue specificity of the latter markers may be superior. When evaluating a triple-negative tumour, including GATA-3 in a panel of markers may increase the diagnostic accuracy for tissue origin in the appropriate clinical setting.

Benign papillomas without atypia diagnosed on core needle biopsy: experience from a single institution and proposed criteria for excision.

BACKGROUND: The management of benign papilloma (BP) without atypia identified on breast core needle biopsy (CNB) is controversial. In this study, we determined the upgrade rate to malignancy for BPs without atypia diagnosed on CNB and whether there are factors associated with upgrade. METHODS: Through our pathology database search, we studied 80 BPs without atypia identified on CNB from 80 patients from 1997 to 2010, including 30 lesions that had undergone excision and 50 lesions that had undergone ≥ 2 years of radiologic follow-up. Associations between surgery or upgrade to malignancy and clinical, radiologic, and pathologic features were analyzed. RESULTS: Mass lesions, lesions sampled by ultrasound-guided CNB, and palpable lesions were associated with surgical excision. All 3 upgraded cases were mass lesions sampled by ultrasound-guided CNB. None of the lesions with radiologic follow-up only were upgraded to malignancy. The overall upgrade rate was 3.8%. None of the clinical, radiologic, or histologic features were predictive of upgrade. CONCLUSION: Because the majority of patients can be safely managed with radiologic surveillance, a selective approach for surgical excision is recommended. Our proposed criteria for excision include pathologic/radiologic discordance or sampling by ultrasound-guided CNB without vacuum assistance when the patient is symptomatic or lesion size is ≥ 1.5 cm.

Primary squamous cell carcinoma of the breast: predictors of locoregional recurrence and overall survival.

Studies evaluating the biological behavior of primary squamous cell carcinoma (SCC) of the breast have yielded inconsistent results, perhaps in part because most studies have not taken into consideration specific histologic subtypes. We identified 21 cases of primary SCC of the breast diagnosed between the years 1985 and 2010 and analyzed the association between particular histologic features and disease outcome. Most tumors (17/21) were moderately or poorly differentiated, and most had a high nuclear grade (15/21). Five-year locoregional recurrence-free survival (LRRFS) for all patients was 54%±12%, and 5-year overall survival (OS) was 51%±13%. The only statistically significant feature associated with LRRFS was the presence of a spindle cell component in the tumor. Patients with >10% spindle cell component had decreased LRRFS (log rank; P=0.006). The only statistically significant features associated with OS were patient age and tumor keratinization. Patients more than 60 years of age had decreased OS (log rank; P=0.035), and patients with tumors having at least focal keratinization had improved OS (log rank; P=0.027). Lymph node status, mitotic rate, tumor necrosis, cystic degeneration, clear cell change, and the presence of a pleomorphic component or associated ductal carcinoma in situ were not associated with either LRRFS or OS. In summary, primary SCC of the breast tends to be aggressive, particularly in patients more than 60 years of age and those with tumors having >10% spindle cell component. The presence of at least focal keratinization, however, is associated with significantly improved OS.

Gross cystic disease fluid protein-15 and mammaglobin A expression determined by immunohistochemistry is of limited utility in triple-negative breast cancer.

AIMS: In addition to oestrogen and progesterone receptors, gross cystic disease fluid protein-15 (GCDFP-15) and mammaglobin A (MAM) are the most common markers used to identify breast origin by immunohistochemistry. GCDFP-15 expression has been reported in approximately 60% of breast carcinomas and MAM expression in approximately 80%. Data on their expression in triple-negative breast cancer (TNBC) are very limited. The aim of this study was to examine the expression of these markers in TNBC to determine their utility in pathological diagnosis. METHODS AND RESULTS: We studied the immunohistochemical (IHC) expression of GCDFP-15 and MAM in 63 primary and 118 metastatic TNBCs. GCDFP-15 staining was present in 14% of primary and 21% of metastatic TNBCs. MAM staining was present in 25% of primary and 41% of metastatic TNBCs. The frequency of expression of GCDFP-15 and/or MAM was 30% in primary and 43% in metastatic TNBCs, and many positive tumours had only focal staining. CONCLUSIONS: Staining for GCDFP-15 and/or MAM in triple-negative carcinomas helps to confirm breast origin, but most tumours in this subgroup of breast carcinomas lack expression of either marker.

Tissue-based predictors of germ-line BRCA1 mutations: implications for triaging of genetic testing.

BRCA testing of patients with breast cancer considered at high risk for having a germ-line BRCA mutation usually consists of comprehensive mutational analysis of both BRCA1 and BRCA2. A more cost-effective strategy of triaging patients for analysis of a single gene could be adopted if tissue-based predictors indicated a high risk specifically for either BRCA1 or BRCA2. To identify potentially useful tissue-based predictors of BRCA mutation status in breast cancer, we evaluated multiple histopathologic features of invasive breast carcinoma on archival tissue sections from 196 high-risk patients who had undergone BRCA testing, and we analyzed which individual or combination of features was most associated with BRCA mutations. Of the 196 patients with invasive breast carcinoma, there were 44 (22%) with a deleterious BRCA1 mutation and 27 (14%) with a deleterious BRCA2 mutation. For patients with available untreated surgical resection specimens for evaluation (n=172), estrogen receptor-positive phenotype was inversely associated with the presence of a BRCA1 mutation (odds ratio, 0.243; 95% confidence interval, 0.070-0.840; P=.025), and high mitotic activity (≥25 mitotic figures per 10 high-power fields) was directly associated with the presence of a BRCA1 mutation (odds ratio, 4.222; 95% confidence interval, 1.353-13.18; P=.013). The combination of estrogen receptor-negative phenotype and high mitotic rate had high specificity (99%; 95% confidence interval, 95%-100%) but low sensitivity (43%; 95% confidence interval, 26%-61%) for identifying a deleterious BRCA1 mutation. In patients with breast cancer at high risk for carrying a BRCA mutation, those with estrogen receptor-negative phenotype and high mitotic rate could be triaged specifically for BRCA1 testing instead of initially performing mutational analysis for both BRCA1 and BRCA2.

Imaging features of primary breast sarcoma.

OBJECTIVE: This purpose of this study is to describe the imaging findings in patients who presented with a diagnosis of primary breast sarcoma. MATERIALS AND METHODS: A search was performed of the pathology database at a single institution for patients with a histopathologic diagnosis of primary breast sarcoma or pure sarcomatoid carcinoma and who underwent preoperative mammography, sonography, or MRI. Patients with malignant phyllodes tumors were excluded. The imaging studies were retrospectively reviewed using the American College of Radiology BI-RADS lexicon. We documented clinical presentation, histopathologic characteristics, axillary nodal status, and the presence of distant metastases. RESULTS: Twenty-four women were included in the study; their mean age was 56 years (range, 21-86 years), and the mean tumor size was 6.1 cm (range, 0.9-15 cm). Only one tumor was identified in each patient. The predominant mammographic finding was a noncalcified oval mass with indistinct (9/14 [64%]) margins. Sonography most commonly revealed an oval (19/22 [86%]) solid mass with indistinct margins (17/22 [77%]). The masses were frequently hypoechoic (18/21 [86%]) and hypervascular (17/20 [85%]) and had posterior acoustic enhancement (13/21 [62%]). MRI showed a round or oval T2-hyperintense mass with irregular margins in four of five (80%) patients, and inhomogeneous enhancement was most common (3/4 [75%]). CONCLUSION: Primary breast sarcoma has imaging features that are not typically seen in infiltrating ductal carcinoma. A large oval hypervascular mass with indistinct margins should raise the suspicion for a primary breast sarcoma and prompt biopsy.

Metastatic neuroendocrine tumour in the breast: a potential mimic of in-situ and invasive mammary carcinoma.

AIMS: The aim of this study was to review the clinicopathological characteristics of neuroendocrine tumours (NETs) metastasizing to the breast, in order to identify features that could be useful in distinguishing these metastatic lesions from primary breast neoplasms. METHODS AND RESULTS: Eighteen metastatic NETs in the breast were identified from two large hospitals over a 15-year period. Eleven (62%) tumours originated in the gastrointestinal tract, 5 (28%) originated in the lung, and the other two were of indeterminate origin. Eight (44%) cases were initially misdiagnosed as primary mammary carcinomas. In retrospect, all metastatic tumours exhibited architectural and cytological features that would suggest neuroendocrine differentiation. Immunohistochemistry can further aid in the distinction between metastatic neuroendocrine and primary mammary carcinoma. All 11 tumours from the gastrointestinal tract expressed CDX-2, 3 (60%) of five tumours from the lung expressed thyroid transcription factor-1, and only 2 (11%) of 18 showed weak oestrogen receptor positivity. Additionally, unlike primary carcinomas, the majority (82%) of metastatic NETs were negative for cytokeratin 7, and all were negative for gross cystic disease fluid protein 15 and mammoglobin. CONCLUSIONS: There is a high propensity for metastatic NETs to mimic primary breast carcinomas. Careful attention to cytological and architectural features can help to identify cases that require further immunophenotypic workup with a panel of tissue-specific antibodies. However, clinical history is paramount for optimal diagnosis.

Invasive mammary carcinoma with neuroendocrine differentiation: histological features and diagnostic challenges.

AIMS: The aim of this study was to review the histomorphological features of primary neuroendocrine carcinomas (NEC) of the breast, in order to identify features useful in recognition of this entity for appropriate classification. METHODS AND RESULTS: 2003 World Health Organization (WHO) classification of tumors of the breast and female genital organs defined NEC of the breast as a subtype of invasive mammary carcinoma in which >50% of the tumor cells express neuroendocrine markers. Seventy-four cases that fulfilled the WHO diagnostic criteria for NEC of the breast, excluding small cell carcinoma and low-grade solid papillary carcinoma with a predominant in-situ component, were identified between 1984 and 2008 from MD Anderson Cancer Center, and were included in the study. NECs of the breast had variable histomorphological features. The most common histologic patterns were papillary (80%) and nested (64%). Mixed growth patterns were common (59%), including admixed ductal component. The tumor cells could be polygonal, round, plasmacytoid, spindled, or with signet ring cell features. The cytoplasm could be granular, eosinophilic, clear, or finely vacuolated. These tumors frequently mimicked invasive or in situ ductal carcinoma, or invasive lobular carcinoma. CONCLUSIONS: NEC of the breast is underrecognized. Careful attention to cytologic and architectural features can help to identify cases that require further immunophenotypic confirmation for correct tumor classification.

Do all mucocele-like lesions of the breast require surgery?

AIM: The objective of this study is to review the imaging features and percutaneous biopsy findings of mucocele-like lesions (MLLs) of the breast and correlate these with histopathology at surgical excision (SE), where available, to determine whether all MLLs of the breast require surgery for management. MATERIALS AND METHODS: A search of two pathology databases was performed to identify 44 patients who had been diagnosed with MLL of the breast and who had corresponding imaging findings available for review. These patients' medical records were reviewed to determine patient age at diagnosis, site of disease/affected breast, symptoms at diagnosis, mammographic and sonographic findings and methods used for histopathologic diagnosis (percutaneous biopsy and/or SE). RESULTS: The mean age of all patients was 56 years (range, 35-76 years). Sixteen patients had MLLs diagnosed by core needle biopsy (CNB) or fine needle aspiration biopsy followed by SE. Eighteen patients had CNB without SE and had clinical and imaging follow-up. Ten patients had MLL diagnosed at SE without prior percutaneous biopsy. In total, 29 patients (66%) had MLLs without atypia, while 10 patients had MLLs associated with atypical ductal hyperplasia (ADH) (23%) and five patients had MLLs associated with ductal carcinoma in situ (DCIS) (11%). Findings were upgraded at SE following the percutaneous biopsy from ADH to DCIS in 19% (3/16) of patients. CONCLUSION: Surgical excision following the identification of MLL is warranted to exclude coexisting in situ carcinoma in specific situations where CNB detects the presence of associated ADH or where a mass with indistinct or irregular margins is shown by mammography or sonography.

Prognostic significance of tumor grading and staging in mammary carcinomas with neuroendocrine differentiation.

Invasive mammary carcinoma with neuroendocrine differentiation has been controversial in terms of its definition and clinical outcome. In 2003, the World Health Organization histologic classification of tumors designated this entity as neuroendocrine carcinoma of the breast and defined mammary neuroendocrine carcinoma as expression of neuroendocrine markers in more than 50% of tumor cells. It is an uncommon neoplasm. Our recent study showed that it is a unique clinicopathologic entity and has a poor clinical outcome compared with invasive mammary carcinoma with similar pathologic stage. Other investigators have also demonstrated a different molecular profile in this type of tumor from that of invasive ductal carcinoma. It is unknown whether the current prognostic markers for invasive mammary carcinoma are also applicable for neuroendocrine carcinoma of the breast. In the current study, we reviewed the clinicopathologic features and outcome data in 74 cases of mammary neuroendocrine carcinoma from the surgical pathology files at The University of Texas, MD Anderson Cancer Center, to identify relevant prognostic markers for this tumor type. As shown previously by univariate analysis, large tumor size, high nuclear grade, and presence of regional lymph node metastasis are adverse prognostic factors for overall survival and distant recurrence-free survival. In the current study, multivariate analysis revealed that overall survival was predicted by tumor size, lymph node status, and proliferation rate as judged by Ki-67 immunohistochemistry. Only nodal status proved to be a significant independent prognostic factor for distant recurrence-free survival. Neither mitosis score nor histologic grade predicted survival in mammary neuroendocrine carcinoma. Our data suggest that routine evaluation of Ki-67 proliferation index in these unusual tumors may provide more valuable information than mitotic count alone.

Lipomatous variant of myofibroblastoma with epithelioid features: a rare and diagnostically challenging breast lesion.

Myofibroblastoma of the breast is an unusual benign spindle cell tumor composed of cells with histologic, immunohistochemical, and ultrastructural features of myofibroblasts. In addition to the classic form, a few variants of myofibroblastoma have been described. Recognition of these variants is important to prevent overdiagnosis of a malignant lesion, especially on core biopsy. Three variants that can cause particular confusion on core biopsy are the lipomatous, infiltrative, and epithelioid variants of myofibroblastoma. Thus far, there have been only a few reports of these variants in the English literature. We report a rare case of a lipomatous variant of myofibroblastoma with an epithelioid cell component and discuss the differential diagnosis and potential diagnostic pitfalls.

Histologic changes associated with false-negative sentinel lymph nodes after preoperative chemotherapy in patients with confirmed lymph node-positive breast cancer before treatment.

BACKGROUND: A wide range of false-negative rates has been reported for sentinel lymph node (SLN) biopsy after preoperative chemotherapy. The purpose of this study was to determine whether histologic findings in negative SLNs after preoperative chemotherapy are helpful in assessing the accuracy of SLN biopsy in patients with confirmed lymph node-positive disease before treatment. METHODS: Eighty-six patients with confirmed lymph node-positive disease at presentation underwent successful SLN biopsy and axillary dissection after preoperative chemotherapy at a single institution between 1994 and 2007. Available hematoxylin and eosin-stained sections from patients with negative SLNs were reviewed, and associations between histologic findings in the negative SLNs and SLN status (true negative vs false negative) were evaluated. RESULTS: Forty-seven (55%) patients had at least 1 positive SLN, and 39 (45%) patients had negative SLNs. The false-negative rate was 22%, and the negative predictive value was 67%. The negative SLNs from 17 of 34 patients with available slides had focal areas of fibrosis, some with associated foamy parenchymal histiocytes, fat necrosis, or calcification. These histologic findings occurred in 15 (65%) of 23 patients with true-negative SLNs and in only 2 (18%) of 11 patients with false-negative SLNs (P = .03, Fisher exact test, 2-tailed). The lack of these histologic changes had a sensitivity and specificity for identifying a false-negative SLN of 82% and 65%, respectively. CONCLUSIONS: Absence of treatment effect in SLNs after chemotherapy in patients with lymph node-positive disease at initial presentation has good sensitivity but low specificity for identifying a false-negative SLN.

Rosai-Dorfman disease confined to the breast.

Rosai-Dorfman disease (also known as sinus histiocytosis with massive lymphadenopathy) is an uncommon, idiopathic, benign histiocytic lesion. It usually involves the cervical lymph nodes and, less commonly, extranodal sites. Involvement of the breast is rare, with only 17 cases reported in the English literature to date. Here we describe 3 new patients with extranodal Rosai-Dorfman disease in the breast. All 3 patients-aged 45, 53, and 54 years-presented with solid breast lesions that were detected on screening mammography and had no clinical history of Rosai-Dorfman disease or radiographic evidence of extramammary involvement. Initial diagnoses were accomplished by needle core biopsy in the one case and excisional biopsy in the other two. We present the histopathologic findings and follow-up of each patient and conduct a literature review of mammary Rosai-Dorfman disease with emphasis on its differential diagnosis. Because Rosai-Dorfman disease frequently mimics invasive breast carcinoma in its clinical presentation and radiographic appearance-and can mimic other benign or malignant histiocytic lesions microscopically-awareness and appropriate diagnosis of this entity are essential for proper treatment.