Metastatic Pleomorphic Lobular Carcinoma of the Breast to the Urinary Bladder: A Report of 10 Cases and Assessment of TRPS1 in the Differential Diagnosis With Plasmacytoid Urothelial Carcinoma.

CONTEXT.­: Metastatic pleomorphic lobular carcinoma (MPLC) to the bladder is rare and has considerable histologic and immunohistochemical overlap with plasmacytoid urothelial carcinoma (PUC). OBJECTIVE.­: To distinguish MPLC from PUC morphologically and immunohistochemically, including a newer marker, TRPS1. DESIGN.­: Ten MPLCs to the bladder were reassessed and stained with estrogen, progesterone, and androgen receptors; GATA3; keratin 5/6; HMWK; GCDFP-15; and TRPS1. Sixteen PUCs constituted controls. RESULTS.­: We studied 4 transurethral resections of bladder tumors and 6 biopsies from 10 women (median age, 69 years) who had breast cancer on average 15 years prior. Microscopic patterns included single cells and cords of cells (n = 4), nests/sheets of dyscohesive cells (n = 2), or both (n = 4). All tumors had cells with voluminous eosinophilic cytoplasm and eccentric nuclei mimicking PUC, and 7 of 10 tumors had signet ring cells. MPLCs were positive for estrogen (8 of 10), progesterone (3 of 7), and androgen receptors (4 of 10); GCDFP-15 (7 of 10); GATA3 (9 of 10); HMWK (7 of 8); and TRPS1 (7 of 10). No MPLCs stained for keratin 5/6 (n = 9). Of 16 PUCs, 2 showed faint and 2 demonstrated strong TRSP1 staining; 7 of 16 were negative for p63. CONCLUSIONS.­: MPLC to bladder often presents in patients with a remote history of breast cancer, exhibiting significant histologic and immunohistochemical overlap with PUC. Based on prior works and the current study, estrogen receptor (particularly SP-1), mammaglobin, and p63 help differentiate MPLC from PUC. Keratin 5/6 may aid in distinguishing a less frequent basal type PUC because it is typically negative in MPLC. Some PUCs express TRPS1. Caution should be exercised because immunophenotypes of these tumors greatly overlap, and ramifications of misclassification are major.

Immature natural killer cells promote progression of triple-negative breast cancer.

Natural killer (NK) cells are cytotoxic lymphocytes that accumulate within the tumor microenvironment and are generally considered to be antitumorigenic. Using single-cell RNA sequencing and functional analysis of multiple triple-negative breast cancer (TNBC) and basal tumor samples, we observed a unique subcluster of Socs3highCD11b-CD27- immature NK cells that were present only in TNBC samples. These tumor-infiltrating NK cells expressed a reduced cytotoxic granzyme signature and, in mice, were responsible for activating cancer stem cells through Wnt signaling. NK cell-mediated activation of these cancer stem cells subsequently enhanced tumor progression in mice, whereas depletion of NK cells or Wnt ligand secretion from NK cells by LGK-974 decreased tumor progression. In addition, NK cell depletion or inhibition of their function improved anti-programmed cell death ligand 1 (PD-L1) antibody or chemotherapy response in mice with TNBC. Furthermore, tumor samples from patients with TNBC and non-TNBC revealed that increased numbers of CD56bright NK cells were present in TNBC tumors and were correlated to poor overall survival in patients with TNBC. Together, our findings identify a population of protumorigenic NK cells that may be exploited for both diagnostic and therapeutic strategies to improve outcomes for patients with TNBC.

Low to Intermediate (Borderline) Grade Breast Spindle Cell Lesions on Needle Biopsy: Diagnostic Approach and Clinical Management.

Spindle cell proliferations of the breast are a heterogeneous group of lesions ranging from benign or reactive lesions to aggressive malignant neoplasms. Diagnosis on core biopsy can be particularly challenging as lesions displaying different lineages associated with variable outcomes share overlapping morphologies (scar vs. fibromatosis-like metaplastic carcinoma) whereas individual entities can exhibit a large variety of appearances (myofibroblastoma). In this review, lesions are grouped into lineage, when possible, including those showing fibroblastic/myofibroblastic differentiation, ranging from entities that require no additional management, such as scar and nodular fasciitis, to those with unpredictable clinical outcomes such as fibromatosis and solitary fibrous tumor or locally aggressive behavior such as dermatofibrosarcoma protuberans. The review of low-grade vascular lesions includes atypical vascular lesion and low-grade angiosarcoma. Also discussed are various adipocytic lesions ranging from lipoma to liposarcoma, and rare smooth muscle and neural entities more commonly encountered in locations outside the breast, such as leiomyoma, neurofibroma, schwannoma, or granular cell tumor. Optimal histological evaluation of these entities merges clinical and radiologic data with morphology and ancillary testing. We present our approach to immunohistochemical and other ancillary testing and highlight issues in pathology correlation with imaging. Recent updates in the management of breast spindle cell lesions are addressed. In a well-sampled lesion with radiographic concordance, the core biopsy diagnosis reliably guides management and we advocate the inclusion of management recommendations in the pathology report. Precise characterization using up to date guidelines is important to identify a subset of patients who may safely avoid unnecessary surgical procedures. A multidisciplinary approach with close collaboration with our clinical colleagues is emphasized.

HER2 Testing: Insights From Pathologists' Perspective on Technically Challenging HER2 FISH Cases.

OBJECTIVE: College of American Pathologists and the American Society of Clinical Oncology guidelines provide straightforward criteria for HER2 interpretation in breast carcinomas; however, a subset of cases present unusual diagnostic dilemmas. MATERIALS AND METHODS: Ten challenging HER2 fluorescence in situ hybridization (FISH) cases were selected for analysis. The study included a variety of problematic cases such as those with discordant immunohistochemistry (IHC) and FISH results, cases with high intratumoral variability in HER2 copy number, a case with a highly amplified clone in 5% to 10% of the tumor sample, and a case with tumor cells containing tightly clumped HER2 signals. Six high volume HER2 FISH laboratories performed and interpreted HER2 FISH (adding HER2 IHC if necessary). Interpretation strategies were discussed. RESULTS: There was 100% concordance between laboratories in 4/10 cases. Tumors with increased intratumoral variability (tumors with high variability in HER2 copy number per cell but which otherwise do not fulfill College of American Pathologists and the American Society of Clinical Oncology criteria for heterogeneity) exhibited 100% concordance in 3/4 cases, but 1 case had only 50% agreement. Low positive HER2 cases (group 1 cases with <6 average HER2 copies/cell) had 1 laboratory disagreeing with the majority in 4/4 cases, and this was the only category with discordance between IHC and FISH methodologies. All laboratories identified the case with heterogeneity and interpreted it as positive. Five of the 6 laboratories interpreted the case with tightly clustered HER2 signals as positive. CONCLUSIONS: This study offers specific observations and interpretation strategies that laboratories can use when confronted with difficult HER 2 cases. It then highlights communication strategies a laboratory may use to discuss these unusual HER2 results with the clinical team.

HER2 Testing Characteristics Can Predict Residual Cancer Burden following Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer.

OBJECTIVES: The response to HER2-targeted neoadjuvant chemotherapy (NAC) in HER2-positive (+) breast cancer can be quantified using residual cancer burden (RCB) pathologic evaluation to predict relapse free/overall survival. However, more information is needed to characterize the relationship between patterns of HER2 testing results and response to NAC. We evaluated clinicopathologic characteristics associated with RCB categories in HER2+ patients who underwent HER2-directed NAC. METHODS: A retrospective chart review was conducted with Stage I-III HER2+ breast cancer cases following NAC and surgical resection. HER2 immunohistochemistry (IHC) staining and fluorescence in situ hybridization (FISH), histologic/clinical characteristics, hormone receptor status, and RCB scores (RCB-0, RCB-I, RCB-II, and RCB-III) were evaluated. RESULTS: 64/151 (42.4%) patients with HER2+ disease had pathologic complete response (pCR). Tumors with suboptimal response (RCB-II and RCB-III) were more likely to demonstrate less than 100% HER2 IHC 3+ staining (p < 0.0001), lower HER2 FISH copies (p < 0.0001), and lower HER2/CEP17 ratios (p = 0.0015) compared to RCB-I and RCB-II responses. Estrogen receptor classification using ≥10% versus ≥1% staining showed greater association with higher RCB categories. CONCLUSIONS: HER2+ characteristics show differing response to therapy despite all being categorized as positive; tumors with less than 100% IHC 3+ staining, lower HER2 FISH copies, and lower HER2/CEP17 ratios resulted in higher RCB scores.

Effects of Germline Pathogenic Variants, Cancer Subtypes, Tumor-related Characteristics, and Pregnancy-associated Diagnosis on Outcomes.

BACKGROUND: Although breast cancer (BC) is uncommon in women age ≤ 35 years, women in this age group may have more aggressive cancer subtypes and high-risk pathogenic variants (HRPVs). Higher recurrence and mortality rates in young patients may be related to differences in tumor biology, pathologic mutation status, or treatment. The purpose of this study was to evaluate germline mutation status and other factors that affect recurrence-free survival (RFS) and overall survival (OS) in young women with BC. MATERIALS AND METHODS: This was a retrospective study of women diagnosed with BC at age ≤ 35 years at Allina Health System from 2000 through 2017 (n = 306). Information was collected on germline mutation status, tumor characteristics (grade, hormone receptor, and human epidermal growth factor receptor 2), molecular subtype, pregnancy-associated cancers, and treatment. Survival analyses using Kaplan-Meier curves were conducted for RFS and OS. RESULTS: With mean follow-up of 6.5 years, OS was 87.0% for invasive cancers, RFS was 84.7%; 69% obtained genetic testing, and 26.9% had HRPVs. There were no differences in RFS or OS between patients with HRPV versus unknown/low/moderate risk variants. Recurrence analysis showed increased recurrence rates in luminal B-like cancers followed by triple negative and human epidermal growth factor receptor 2-positive cancers (P = .041). Pregnancy-associated BC diagnoses, angiolymphatic invasion, and tumor stage were associated with reduced OS. In spite of young age at diagnosis, nearly one-third of patients did not receive germline genetic testing. CONCLUSIONS: Similar survival patterns were found between women with HRPV versus no known mutations. Luminal B-like subtype, pregnancy-associated BC, angiolymphatic invasion, and cancer stage were associated with reduced OS.

Predictive value of breast magnetic resonance imaging in detecting mammographically occult contralateral breast cancer: Can we target women more likely to have contralateral breast cancer?

BACKGROUND AND OBJECTIVES: Preoperative breast magnetic resonance imaging (B-MRI) staging in newly diagnosed breast cancer increases detection of synchronous contralateral findings, but may result in false-positive outcomes. This study objective was to identify women more likely of having mammographically occult, MRI detected contralateral breast cancer (CBC). METHODS: We performed a retrospective review of patients who had preoperative B-MRI prior to surgery from 2010 to 2015 and collected patient imaging and clinicopathologic data. Multivariate logistic regression was used to identify predictors of CBC. RESULTS: MRI resulted in contralateral findings in 201 of 1894 patients (10.6%). Overall 3.2% (60 of 1894) had synchronous CBC detected on B-MRI. The majority of CBCs (n = 60) were stage 0 or IA (85.0%), hormone receptor positive (94.9%), human epidermal growth factor receptor 2 (HER2/neu) negative (89.7%), and low/intermediate pathological grade (87.2%). Women more likely to have CBC were older (P < .001), had lobular index cancer (P = .03), and estrogen receptor (ER)+ (P = .027) or progesterone receptor (PR)+ (P = .002) tumors. On multivariate analysis (receiver operating characteristic curve area = 0.75), PR + status (P = .022), and older age (P = .004) were predictive of CBC. CONCLUSIONS: Preoperative MRI is most effective in detecting early stage, hormone receptor-positive CBC in older women.

Clinicopathologic analysis of a large series of microinvasive breast cancers.

Clinical management of microinvasive breast cancer (Tmic) remains controversial. Although metastases are infrequent in Tmic carcinoma patients, surgical treatment typically includes lymph node sampling. The objective of this study was to determine the rate and predictors of lymph node metastases, recurrence, and survival in a large series of Tmic breast carcinomas. Consecutive cases of Tmic were identified within our health care system from 2001 to 2015. We reviewed results of lymph node sampling and other pathologic factors including hormone receptor/HER2 status, associated in situ tumor size/grade, margin status, number of invasive foci, surgical/adjuvant therapies, and recurrence/survival outcomes. In this cohort, 294 Tmic cases were identified with mean follow-up of 4.6 years. Of 260 patients who underwent axillary staging, lymph node metastases were identified in 1.5% (all of which were ductal type). All Tmic cases with positive lymph node metastases had associated DCIS with size > 5 cm (5.3-8.5 cm) compared to a median DCIS tumor size of 2.5 cm (0.2-19.0 cm) for the entire cohort. No lymph node metastases were seen with microinvasive lobular carcinoma. During the follow-up period, there were no regional/distant recurrences or breast cancer-associated deaths in a mean follow-up period of 4.6 years. Two patients developed subsequent ipsilateral breast cancer (DCIS) in a different quadrant than the original Tmic. Clinical behavior of microinvasive breast cancer in this series is similar to DCIS. Lymph node metastases are uncommon and were only seen with ductal type microinvasive carcinoma. Our data suggest limited benefit for routine node sampling and support management of Tmic similar to DCIS, particularly for patients with DCIS < 5 cm in size.

Surgical Outcomes of Lobular Neoplasia Diagnosed in Core Biopsy: Prospective Study of 316 Cases.

BACKGROUND: Management recommendations for lobular neoplasia (LN) including lobular carcinoma-in-situ (LCIS) and atypical lobular hyperplasia (ALH) diagnosed in core biopsies (CB) are controversial. Our aim was to prospectively identify a subset of patients who do not require subsequent surgical excision (SE). PATIENTS AND METHODS: All patients diagnosed with LN on CB were enrolled and referred for SE. Cases with coexistent ductal carcinoma-in-situ or invasive carcinoma were excluded. Cases with coexistent ductal atypia (LN-DA) and LCIS variants (LN-V) were separated from pure classic LN (LN-C). Dedicated breast pathologists and radiologists reviewed cases with careful imaging/pathology correlation. RESULTS: Of 13,772 total percutaneous breast CB procedures, 302 of 370 patients diagnosed with LN underwent SE. Upgrade to carcinoma was present in 3.5% (8/228) LN-C, 26.7% LN-V (4/15), and 28.3% LN-DA (15/53). Calcifications were the imaging target for 180 (79%) of 228 LN-C cases; 7 were associated with upgrade (3.9%). Upgrades were rare for mass lesions (1/32) and magnetic resonance imaging-targeted lesions (0/14). Upgrades were similar for ALH and LCIS (3.4% vs. 4.5%). During postsurgical follow-up (mean, 34.5 months), 6.5% LN-C patients developed carcinoma in either breast. CONCLUSION: Although LN with nonclassic morphology or with associated ductal atypia requires SE, this can be avoided in LN-C diagnosed on CB targeting calcifications when careful imaging/pathology correlation is applied. Until larger numbers are studied, excising LN-C diagnosed as masses or magnetic resonance imaging-detected lesions may be prudent. Regardless of their selection for surgical management, LN patients need close surveillance in view of their long-term risk of breast cancer.

Utility of Oncotype DX Risk Assessment in Patients With Invasive Lobular Carcinoma.

INTRODUCTION/BACKGROUND: Oncotype DX (Genomic Health, Redwood City, CA) uses reverse transcriptase polymerase chain reaction analysis to measure tumor gene expression for determining recurrence risk (RR) and guiding chemotherapy decisions for breast cancer patients. Invasive lobular carcinoma (ILC) is a histologic subtype that has not been the focus of prior studies validating Oncotype DX. The study purpose was to develop a model using histologic tumor characteristics to predict uniformly low Oncotype DX Recurrence Scores (RS) in ILC. PATIENTS AND METHODS: ILC cases in our pathology database with Oncotype DX testing were identified. Histologic tumor characteristics, immunohistochemical (IHC) of estrogen receptor (ER)/progesterone receptor (PgR) percent, HER2, E-cadherin expression, and Ki-67 levels were obtained for cases. Discriminant analysis was used to test the hypothesis that tumors classified as lower/higher risk based on Oncotype DX RS would differ significantly on a linear combination of variables. RESULTS: From 2006 - 2014, 158 cases of ILC having Oncotype DX testing were identified; 90 low risk (RS < 18), 66 intermediate risk (RS 18 - 30) and 2 high risk (RS > 30). Discriminant analysis showed that PgR% followed by Ki-67 provided the greatest contribution to discern low versus elevated RS. A subset of 57 cases (∼36%) with predicted probabilities > 86% for either low or high RS yielded 96.5% correct classification, 92.3% sensitivity, and 97.7% specificity. CONCLUSION: Our analytical model may be useful in predicting lower RR in patients with ILC. If validated, this provides a faster and less expensive alternative to Oncotype DX testing in certain patients with ILC.

Multinucleation is an objective feature useful in the diagnosis of pleomorphic lobular carcinoma in situ.

OBJECTIVES: Bi- and multinucleated (B/M) cells are present in a variety of tumors. We evaluated lobular carcinoma in situ (classic and pleomorphic types) and ductal carcinoma in situ (DCIS) to determine if this objective morphologic feature aids the differential diagnosis. METHODS: The number of B/M cells was recorded in pleomorphic lobular carcinoma in situ (PLCIS) (n = 20), classic lobular carcinoma in situ (CLCIS) (n = 26), and DCIS (n = 37). RESULTS: Binucleated cells were significantly more frequent in PLCIS (100%) vs DCIS (43%; P < .0001) and CLCIS (54%; P = .0004). Multinucleated cells were present in 25% of PLCIS cases and 8% of DCIS cases, and they were absent in CLCIS. The quantity of B/M per high-power field (hpf) was less in DCIS (mean, 1.1) and CLCIS (mean, 2.5) compared with PLCIS (mean, 5.8). Thirty-five percent of PLCIS cases had more than five B/M per hpf. CONCLUSIONS: Binucleated cells are significantly more frequent in PLCIS vs CLCIS and DCIS. Multinucleated cells were never identified in CLCIS. PLCIS should be considered as a diagnosis when B/M is noted.

Office ductoscopy for surgical selection in women with pathologic nipple discharge.

BACKGROUND: Pathologic nipple discharge (PND) is diagnosed clinically and managed by diagnostic duct excision (DDE). Mammary ductoscopy in the office setting may change this standard. We performed a prospective study to assess the utility of office ductoscopy for surgical selection in women with nipple discharge. METHODS: Women with nipple discharge meeting at least 2 of 3 criteria of PND (spontaneous, single duct, bloody or serous) underwent office ductoscopy. Those showing papillomatous lesions underwent DDE in the operating room (surgical group, n = 38); if no lesion was present, women were followed clinically (observation group, n = 21). RESULTS: A papillomatous lesion was identified in 79% of women with 3-criteria PND and in 21% with 2 criteria (P = .001). DDE yielded a proliferative lesion in 35 of 38 women (92%). Of the 38, 27 (71%) had papillomata, 2 (5%) had florid hyperplasia, and 6 (16%) had ductal carcinoma in situ (DCIS) on final pathology. Also, 11 women with papilloma and 1 with DCIS presented with 2-criteria PND. Ductoscopy findings were a better predictor of the presence of intraductal neoplasia (area under curve [AUC] 0.9, 95% confidence interval [95% CI] 0.8-0.98) compared with 3-criteria PND (AUC 0.7, 95% CI 0.6-0.8). The 21 women in the observation group did not develop signs of malignancy or need biopsy during a 48-month follow-up period. CONCLUSIONS: Our findings suggest that office ductoscopy provides accurate surgical selection of women with nipple discharge and should be considered for women with 2 criteria of PND, and those with negative ductoscopy can be safely observed. These findings need confirmation in a larger study with longer follow-up.

Lobular carcinoma in situ variants in breast cores: potential for misdiagnosis, upgrade rates at surgical excision, and practical implications.

CONTEXT: Differentiating ductal carcinoma in situ (DCIS) from lobular carcinoma in situ (LCIS) on core biopsy has important clinical implications. Lobular carcinoma in situ variants, including LCIS with necrosis and pleomorphic LCIS, share morphologic features with solid DCIS that may lead to misclassification. OBJECTIVES: (1) To review all LCIS variants diagnosed in core biopsies at Northwestern University, Feinberg School of Medicine, and determine the frequency of misinterpretation of variant LCIS as solid DCIS in archival core biopsies, and (2) to determine the frequency of upgrade to invasive carcinoma or DCIS in the surgical excision. DESIGN: Consecutive core biopsies with original diagnoses of predominantly solid DCIS without invasion that were performed between January 2001 and December 2005 at Northwestern University, Feinberg School of Medicine, were selected for E-cadherin staining. The revised diagnosis of LCIS was based on E-cadherin negativity and morphology. The frequency of LCIS variants upgraded was then estimated from all core biopsies with original or revised diagnoses of pleomorphic LCIS or LCIS with necrosis. RESULTS: Among 75 cases of solid DCIS, 10 (13.3%) were reclassified as LCIS, including 9 variants (5 pleomorphic LCIS, 4 LCIS with necrosis) and 1 classic LCIS. Twenty-eight patients comprised the entire group of LCIS variant cases (both reclassified and originally diagnosed cases). Seven patients with LCIS variants (25%) were upgraded to invasive lobular carcinoma in surgical excision (4 of 11 cases of LCIS with necrosis [36%] versus 3 of 17 cases of pleomorphic LCIS [18%]). CONCLUSIONS: About one-tenth of solid DCIS diagnosed in core biopsies in the past may represent LCIS variants. These show a 25% upgrade to invasive lobular carcinoma in surgical excision. The distinction of an LCIS variant from DCIS is important because of its implications for radiation therapy, although it may not affect surgical management.

Clinical roundtable monograph: a multidisciplinary approach to the use of oncotype DX in clinical practice.

Recently, recommendations for the use of the Oncotype DX assay in estrogen receptor-positive node-negative breast cancer patients were incorporated into guidelines from both the American Society of Clinical Oncology and the National Comprehensive Cancer Network. The Oncotype DX assay is a diagnostic test which measures changes in a set of 21 genes in order to predict the likelihood of disease recurrence and also to predict which patients are most likely to respond to chemotherapy. Oncotype DX has been available commercially since January 2004 and has been used for more than 85,000 patients. Drs. William J. Gradishar, Nora M. Hansen, and Barbara Susnik answered questions regarding the incorporation of the Oncotype DX breast cancer assay into routine clinical practice. This expert dialog offers an update and clinical insights into when, how, and why clinicians might incorporate the Oncotype DX assay into the management of their breast cancer patients. Also, the latest research into the benefit of the Oncotype DX assay in node-positive patients is discussed. Finally, sample case studies offer clinically relevant examples of the practical application of the Oncotype DX assay.

Hypermethylated genes as biomarkers of cancer in women with pathologic nipple discharge.

PURPOSE: In a pilot study of women with pathologic nipple discharge (PND) undergoing ductoscopy, we tested quantitative assessment of gene promoter hypermethylation using quantitative multiplex methylation-specific PCR (QM-MSP) to enhance detection of duct carcinoma in situ (DCIS). EXPERIMENTAL DESIGN: Women with PND underwent ductoscopy; ducts with significant lesions were surgically resected (36 ducts in 33 women) and those with minimal findings were not (28 ducts in 16 women). QM-MSP was done on ductoscopy cell samples. Results were compared with cytology and tissue histology. RESULTS: Cells from ducts with significant lesions on ductoscopy had significantly higher levels of methylation than those with minimal findings. Furthermore, cells from ducts with DCIS displayed higher levels of methylation than those with benign lesions such as papilloma (P = 0.006); or ducts with minimal findings on ductoscopy (P = 0.0001). Cumulative RASSF1A, TWIST1, and HIN1 gene methylation accurately distinguished ducts with cancerous versus benign lesions (100% sensitivity, 72% specificity, and area under the curve of 0.91 according to receiving operating characteristic analyses). QM-MSP analysis was more informative than cytology (100% versus 29% sensitivity, respectively), for detecting DCIS. In a validation set of paraffin-embedded DCIS and papilloma samples from women presenting with PND, QM-MSP was significantly higher in DNA from DCIS than papilloma sections (P = 0.002). CONCLUSION: The positive predictive value of ductoscopy was more than doubled (19% versus 47%) with the addition of QM-MSP, demonstrating the benefit of targeting ducts having both high methylation and significant abnormalities on ductoscopy for surgical excision. Future large-scale studies to validate this approach are needed.

Paracortical axillary sentinel lymph node ectopic breast tissue.

Benign glandular inclusions in axillary lymph nodes are uncommon, and their presence in axillary sentinel lymph nodes is exceptionally rare. The possibility of over-staging due to misinterpretation of glandular inclusions as metastatic carcinoma is a concerning issue. We present a 54-year-old female with high grade ductal carcinoma in-situ undergoing simple mastectomy with sentinel lymph node biopsy. Permanent sections of the sentinel lymph node revealed scarce naked small glands without surrounding stroma scattered in the paracortex in the superficial level. Deeper levels showed glands spanning a much larger area (2mm), with bland ducts and tubules separated by abundant stroma. The myoepithelial layer was visible and was immunohistochemically confirmed. A final diagnosis of benign ectopic breast tissue within an axillary sentinel lymph node was rendered. Previous studies described axillary sentinel lymph nodes with glandular inclusions separated by stroma or subcapsular in location. It has been suggested that paracortical location and absence of stroma are characteristics of metastasis. As demonstrated in our report, benign inclusions may be paracortical and lack surrounding stroma. We recommend that glandular inclusions should be a diagnostic consideration for cases in which paracortically located naked glands do not histologically resemble the corresponding primary tumor.

Atypical lobular hyperplasia and classic lobular carcinoma in situ in core biopsy specimens: routine excision is not necessary.

Standardized recommendations for the management of lobular neoplasia in core biopsy specimens are not established. The aim of our study was to define morphologic features of lobular neoplasia in core biopsies that predict the finding of ductal carcinoma in situ or invasive carcinoma in the subsequent excisional specimen. We reviewed 333 cases of atypical lobular hyperplasia or lobular carcinoma in situ without ductal carcinoma in situ or invasive carcinoma diagnosed in core biopsies from 1996 to 2006. Subsequent excision was performed in 41% (136/333) of cases, including atypical lobular hyperplasia (n=48), lobular carcinoma in situ (n=39), and lobular neoplasia associated with atypical ductal hyperplasia (n=49). Upgrades were identified in 2% (1/48) of atypical lobular hyperplasia, 23% (9/39) of lobular carcinoma in situ, and 27% (13/49) of lobular neoplasia associated with atypical ductal hyperplasia cases. When further analyzed, the upgraded cases of lobular carcinoma in situ were associated with radiologic-pathologic discordance in 6/9 cases and with nonclassic pathology (two lobular carcinoma in situ with necrosis and one pleomorphic lobular carcinoma in situ) in the remaining three cases. The frequency of upgrade was 11% (3/26) in classic lobular carcinoma in situ, and 46% (6/13) in nonclassic types (pleomorphic or with necrosis). After excluding cases with discordant imaging/pathology, there was a 5% upgrade in our excisional specimens. After excluding cases where the upgrade was associated with nonclassic morphology, the upgrade in our study was 1%. Our results suggest that atypical lobular hyperplasia and classic lobular carcinoma in situ with concordant radiology and pathology can be appropriately managed with clinical follow-up without surgery.

Keratin immunohistochemistry does not contribute to correct lymph node staging in patients with invasive lobular carcinoma.

Studies suggest that immunohistochemistry improves rate of detecting sentinel lymph node metastases and is needed for adequate staging in invasive lobular carcinoma. Our study evaluates the use of cytokeratin immunohistochemistry in detecting sentinel lymph node metastases and its effect on staging patients with invasive lobular carcinoma. Material from 76 patients with invasive lobular carcinoma was reviewed. Cytokeratin immunostaining was performed on negative nodes, and deposits were classified as macrometastasis (>2.0 mm), micrometastasis (>0.2-2 mm), or isolated tumor cells (