Cystic neutrophilic granulomatous mastitis: sensitivity and specificity of 16s rRNA and Sanger sequencing for Corynebacterium spp.

AIMS: Cystic neutrophilic granulomatous mastitis (CNGM) is a subtype of granulomatous mastitis (GM) associated with Corynebacterium spp infection. We aimed to analyse the prevalence of Corynebacteria in CNGM and non-CNGM cases. METHODS: Breast specimens diagnosed as granulomatous inflammation between 2010 and 2020 were reviewed to identify a CNGM cohort and a non-CNGM cohort. Polymerase chain reaction-based identification of Corynebacteria by 16S ribosomal RNA (16S rRNA) primers, followed by confirmatory Sanger sequencing (SS), was performed on all cases. Clinical, radiological and microbiology data were retrieved from the electronic patient records. RESULTS: Twenty-eight CNGM cases and 19 non-CNGM cases were identified. Compared with the non-CNGM cohort, patients in the CNGM cohort were more likely to be multiparous (p=0.01), breast feeding (p=0.01) and presenting with a larger breast mass (p<0.01), spontaneous drainage (p=0.05) and skin irritation (p<0.01). No significant difference in the prevalence of Corynebacteria between the cohorts (7% vs 11%, p=0.68) by microbiological culture was identified. Compared with microbiology culture, the sensitivity and specificity of each Corynebacterial detection method were 50% and 81% for Gram stain, and 25% and 100% for 16S rRNA combined with SS. Regardless of the diagnosis, patients positive for Corynebacteria were more likely to have a persistent disease (p<0.01). CONCLUSION: CNGM presents as a large symptomatic breast mass in multiparous breastfeeding women. The importance of adequate sampling and repeated microbiology culture in conjunction with sequencing on all GM cases with persistent disease is paramount.

21-Gene Assay and Breast Cancer Mortality in Ductal Carcinoma In Situ.

BACKGROUND: The inability to identify individuals with ductal carcinoma in situ (DCIS) who are at risk of breast cancer (BC) mortality have hampered efforts to reduce the overtreatment of DCIS. The 21-gene recurrence score (RS) predicts distant metastases for individuals with invasive BC, but its prognostic utility in DCIS is unknown. METHODS: We performed a population-based analysis of 1362 individuals of DCIS aged 75 years or younger at diagnosis treated with breast-conserving therapy. We examined the association between a high RS (defined a priori as >25) and the risk of BC mortality by using a propensity score-adjusted model accounting for the competing risk of death from other causes, testing for interactions. All statistical tests were 2-sided. RESULTS: With 16 years median follow-up, 36 (2.6%) died of BC, and 200 (14.7%) died of other causes. The median value of the RS was 15 (range = 0-84); 29.6% of individuals had a high RS. A high RS was associated with an 11-fold increased risk of BC mortality (hazard ratio = 11.27, 95% confidence interval [CI] = 3.00 to 42.33; P < .001) in women aged 50 years or younger at diagnosis treated with breast-conserving surgery alone, culminating in a 9.4% (95% CI = 2.3% to 22.5%) 20-year risk of BC death. For women with a high RS, treatment with radiotherapy was associated with a 71% (hazard ratio = 0.29, 95% CI = 0.10 to 0.89; P = .03) relative and a 5% absolute reduction in the 20-year cumulative risk of death from BC. CONCLUSION: The 21-gene RS predicts BC mortality in DCIS and combined with age (50 years or younger) at diagnosis can identify individuals for whom radiotherapy reduces the risk of death from BC.

Lack of Standardization in the Processing and Reporting of Post-Neoadjuvant Breast Cancer Specimens.

CONTEXT.­: The use of neoadjuvant therapy in the management of early-stage invasive breast cancer is increasing. Residual Cancer Burden and other similar tools use pathologic characteristics of post-neoadjuvant therapy breast tumors to determine long-term outcome. However, there are no standardized guidelines for the pathologic evaluation of these specimens in the routine clinical setting. OBJECTIVE.­: To assess current practices among Canadian pathologists and pathology assistants with regard to the processing and reporting of post-neoadjuvant therapy breast specimens. DESIGN.­: An electronic survey was distributed to pathologists and pathology assistants across Canada. RESULTS.­: Sixty-three responses were obtained. A total of 48% (15 of 31) of surveyed pathologists reported familiarity with the Residual Cancer Burden tool. A total of 40% (25 of 63) of respondents reported a lack of routine use of specimen photography, and 35% (22 of 63) reported a lack of routine use of grossing diagrams. There was significant variation with respect to tumor bed sampling; the most common method was to submit 1 block per centimeter of tumor (20 of 63; 32%). There was also significant variation in the method of measuring residual tumor; the most common method was to measure the largest cross-section of residual tumor (16 of 32; 50%). CONCLUSIONS.­: There is a need for standardization of the evaluation of post-neoadjuvant therapy breast specimens in the routine clinical setting in Canada. We recommend the routine use of specimen mapping, submitting the largest cross section of tumor bed in toto, reporting tumor size as per American Joint Committee on Cancer and Residual Cancer Burden guidelines, and routinely including measurements of residual tumor cellularity and in situ disease in the final pathology report as per Residual Cancer Burden guidelines.

Pilot Study on the Utility of Circulating HER2/Neu Levels in the Serum of Breast Cancer Patients.

BACKGROUND/AIM: Accurate and timely assessment of the human epidermal growth factor receptor 2 (HER2/neu) overexpression is pivotal for the identification of breast cancer (BC) patients that could benefit from HER2-targeted therapy. Currently approved tissue-based HER2 assays (tHER2) are limited to testing HER2 status on tumor samples obtained at a few points in time during the course of the disease. Herein, we assessed serum HER2 (sHER2) status longitudinally in 81 serial samples prospectively collected from 43 consenting patients pre- and post-therapy to revisit the idea of serum testing in the follow-up of BC patients. PATIENTS AND METHODS: The cohort included 11 patients with early BC (EBC), 17 with locally advanced BC (LABC), and 15 with metastatic BC (MBC). sHER2 concentrations were measured using a quantitative ELISA-based technique, using 15 ng/ml as the cut-off for positivity. RESULTS: At baseline, sHER2 was negative in all EBC patients while positive in 1 LABC and 5 MBC patients. Sixteen BC patients (10 LABC, 1 EBC, and 5 MBC) were tHER2 positive. sHER2 and tHER2 results were discordant in 14 patients. Among the 16 tHER2 positive patients, 9 LABC, 1 EBC and 2 MBC patients were sHER2 negative. Conversely, 2 MBC patients were sHER2 positive, despite being tHER2 negative. A rise or drop of sHER2 by >20% correlated with disease progression or pathological response to therapy, respectively. CONCLUSION: The study demonstrated the technical validity and feasibility of the sHER2 assay. Findings suggest that post initial tissue diagnosis (tHER2), sHER2 assay may supplement subsequent tissue tests to monitor disease status and response to therapy. Further studies to assess the role of HER2 targeted therapies in sHER-positive/tHER2-negative cases upon disease progression are warranted.

Multiple foci of microinvasion is associated with an increased risk of invasive local recurrence in women with ductal carcinoma in situ treated with breast-conserving surgery.

PURPOSE: The impact of Ductal Carcinoma in Situ (DCIS) with multiple foci of microinvasion (MI) (≤ 1 mm) on the risks of local recurrence (LR) and invasive LR is unknown, leading to uncertainty if DCIS with multiple foci of MI requires more aggressive treatment. We report a population-based analysis of the impact of multiple foci of MI, confirmed by pathology review, on the 15-year risks of LR and invasive LR treated with breast-conserving surgery (BCS) ± radiotherapy (RT). METHODS: Cohort includes all women diagnosed with DCIS ± MI from 1994 to 2003 treated with BCS ± RT. Cox proportional hazards model was used to evaluate the impact of multiple foci of MI on the risks of LR and invasive LR, adjusting for covariates. The 15-year local and invasive local recurrence-free survival rates were calculated using the Kaplan-Meier method with differences compared by log-rank test. RESULTS: The cohort includes 2988 women treated by BCS; 2721 had pure DCIS (51% received RT), 267 had DCIS with one or more foci of MI (58% had RT). Median follow-up was 13 years. Median age at diagnosis was 58 years. On multivariable analyses, the presence of multiple foci of MI was associated with an increased risk of invasive LR (HR = 1.59, 95% CI 1.01-2.49, p = 0.04) but not DCIS LR (HR = 0.89, 95% CI 0.46, 1.76, p = 0.7). The 15-year invasive LRFS risks for cases with pure DCIS, with 1 focus or multiple foci of MI were 85.7%, 85.6%, 74.7% following treatment by BCS alone, 87.2%, 89.9%, and 77% for those treated with BCS + RT without boost and 89.2%, 91.3%, and 95% for women treated with BCS + RT and boost. CONCLUSIONS: The presence of multiple foci of MI in DCIS is associated with higher 15-year risks of invasive LR after breast-conserving therapy compared to women with pure DCIS but treatment with whole breast and boost RT can mitigate this risk.

Intraoperative Assessment of Sentinel Lymph Nodes in Breast Cancer Patients Post-Neoadjuvant Therapy.

BACKGROUND: Shift toward minimizing axillary lymph node dissection in patients with breast cancer post neoadjuvant therapy has led to the assessment of sentinel lymph nodes by frozen section intraoperatively to determine the need for axillary lymph node dissection. However, few studies have examined the accuracy of sentinel lymph node frozen section after neoadjuvant therapy. Our objective is to compare the accuracy of sentinel lymph node frozen section in patients with breast cancer with and without neoadjuvant therapy and to identify features that may influence accuracy. DESIGN: We identified 161 sentinel lymph node frozen section from 77 neoadjuvant therapy patients and 255 sentinel lymph node frozen section from 88 non-neoadjuvant therapy patients diagnosed between 2010 and 2016 in 2 institutions. The frozen section diagnoses were compared to the final diagnoses, and clinicopathologic data were analyzed. RESULTS: The sensitivity, specificity, and accuracy of frozen section analysis were comparable between neoadjuvant therapy patients and non-neoadjuvant therapy patients (71.9% vs 50%, 100% vs 100%, and 88.3% vs 81.8%). Nine (11.7%) of 77 neoadjuvant therapy patients had discordant results, most often due to undersampling (tumor absent on frozen section slide). Four of these patients subsequently underwent axillary lymph node dissection. Discordant results (all false negatives) were significantly more likely in neoadjuvant therapy patients with Estrogen Receptor-positive/HER2-negative status, and in sentinel lymph node with pN1mic and pN0i+ deposits; age, preneoadjuvant therapy lymph node status, histotype, nuclear grade, tumor size, and response to neoadjuvant therapy showed no significant differences. For non-neoadjuvant therapy cases, large tumor size, lobular histotype, and sentinel lymph node with pN1mic and pN0i+ were associated with false-negative frozen section assessment. CONCLUSION: Sentinel lymph node frozen section diagnosis post-neoadjuvant therapy has comparable sensitivity, specificity, and accuracy to the sentinel lymph node frozen section diagnosis in the non-neoadjuvant therapy setting.

Ductal carcinoma in situ of the breast: an update for the pathologist in the era of individualized risk assessment and tailored therapies.

Ductal carcinoma in situ (DCIS) is a neoplastic proliferation of mammary ductal epithelial cells confined to the ductal-lobular system, and a non-obligate precursor of invasive disease. While there has been a significant increase in the diagnosis of DCIS in recent years due to uptake of mammography screening, there has been little change in the rate of invasive recurrence, indicating that a large proportion of patients diagnosed with DCIS will never develop invasive disease. The main issue for clinicians is how to reliably predict the prognosis of DCIS in order to individualize patient treatment, especially as treatment ranges from surveillance only, breast-conserving surgery only, to breast-conserving surgery plus radiotherapy and/or hormonal therapy, and mastectomy with or without radiotherapy. We conducted a semi-structured literature review to address the above issues relating to "pure" DCIS. Here we discuss the pathology of DCIS, risk factors for recurrence, biomarkers and molecular signatures, and disease management. Potential mechanisms of progression from DCIS to invasive cancer and problems faced by clinicians and pathologists in diagnosing and treating this disease are also discussed. Despite the tremendous research efforts to identify accurate risk stratification predictors of invasive recurrence and response to radiotherapy and endocrine therapy, to date there is no simple, well-validated marker or group of variables for risk estimation, particularly in the setting of adjuvant treatment after breast-conserving surgery. Thus, the standard of care to date remains breast-conserving surgery plus radiotherapy, with or without hormonal therapy. Emerging tools, such as pathologic or biologic markers, may soon change such practice. Our review also includes recent advances towards innovative treatment strategies, including targeted therapies, immune modulators, and vaccines.

Molecular Evaluation of Breast Ductal Carcinoma in Situ with Oncotype DX DCIS.

A subset of patients with ductal carcinoma in situ (DCIS) of the breast develop ipsilateral invasive breast cancer after breast-conserving surgery with or without adjuvant radiotherapy. Risk assessment and prediction of adverse outcomes for individual patients based on traditional clinical and pathological parameters are limited. The Oncotype DCIS Score is a commercially available multigene assay that has been independently validated in a prospective clinical trial and a population-based cohort. The score helps to identify a subset of women >50 years old with unifocal disease that carries <10% risk of any local recurrence after breast-conserving surgery alone. In this population, individual patients and physicians may consider omitting adjuvant radiotherapy. In this article, we review the literature and summarize the evidence regarding the role of the Oncotype DCIS Score in estimating the risk of ipsilateral local recurrence and ipsilateral invasive breast cancer recurrence. The available data on clinical utility and cost-effective analysis for optimizing decisions on adjuvant treatments are discussed.

Atypical ductal hyperplasia on core needle biopsy: Development of a predictive model stratifying carcinoma upgrade risk on excision.

BACKGROUND: Although the rate of carcinoma upgrade for atypical ductal hyperplasia (ADH) diagnosed on core needle biopsy (CNB) is variable, current standard treatment consists of surgical excision (SE) for all ADH CNB diagnoses. Our objective was to identify features of ADH on CNB that may stratify carcinoma upgrade risk on SE. METHODS: We retrospectively analyzed cases diagnosed as ADH on CNB. An independent slide review and detailed analysis of radiological and clinical data was performed. Statistical analyses were used to identify predictors for upgrade. Using variables predictive of upgrade, a model to stratify the probability of upgrade of ADH diagnosed on CNB was constructed. RESULTS: We identified 124 ADH cases with subsequent SE. Of these, 62 cases (50%) were upgraded to carcinoma. Features predictive of upgrade were as follows: diagnosis of "At least ADH", percentage of cores involved by ADH, radiologic lesion size, presence of ipsilateral carcinoma, and patient age. A 4-tiered predictive model using percentage of cores involved by ADH, histologic extent of ADH, radiologic lesion size, and patient age was constructed. This predictive model has a fair accuracy, with an area under the ROC curve of 0.76. CONCLUSION: We have identified several predictors of carcinoma upgrade for ADH diagnosed on CNB. Our predictive model may be used to stratify the risk of carcinoma upgrade on SE.

Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update.

PURPOSE.­: To update key recommendations of the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) human epidermal growth factor receptor 2 (HER2) testing in breast cancer guideline. METHODS.­: Based on the signals approach, an Expert Panel reviewed published literature and research survey results on the observed frequency of less common in situ hybridization (ISH) patterns to update the recommendations. RECOMMENDATIONS.­: Two recommendations addressed via correspondence in 2015 are included. First, immunohistochemistry (IHC) 2+ is defined as invasive breast cancer with weak to moderate complete membrane staining observed in >10% of tumor cells. Second, if the initial HER2 test result in a core needle biopsy specimen of a primary breast cancer is negative, a new HER2 test may (not "must") be ordered on the excision specimen based on specific clinical criteria. The HER2 testing algorithm for breast cancer is updated to address the recommended workup for less common clinical scenarios (approximately 5% of cases) observed when using a dual-probe ISH assay. These scenarios are described as ISH group 2 ( HER2/chromosome enumeration probe 17 [CEP17] ratio ≥2.0; average HER2 copy number <4.0 signals per cell), ISH group 3 ( HER2/CEP17 ratio <2.0; average HER2 copy number ≥6.0 signals per cell), and ISH group 4 ( HER2/CEP17 ratio <2.0; average HER2 copy number ≥4.0 and <6.0 signals per cell). The diagnostic approach includes more rigorous interpretation criteria for ISH and requires concomitant IHC review for dual-probe ISH groups 2 to 4 to arrive at the most accurate HER2 status designation (positive or negative) based on combined interpretation of the ISH and IHC assays. The Expert Panel recommends that laboratories using single-probe ISH assays include concomitant IHC review as part of the interpretation of all single-probe ISH assay results.

Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update.

Purpose To update key recommendations of the American Society of Clinical Oncology/College of American Pathologists human epidermal growth factor receptor 2 (HER2) testing in breast cancer guideline. Methods Based on the signals approach, an Expert Panel reviewed published literature and research survey results on the observed frequency of less common in situ hybridization (ISH) patterns to update the recommendations. Recommendations Two recommendations addressed via correspondence in 2015 are included. First, immunohistochemistry (IHC) 2+ is defined as invasive breast cancer with weak to moderate complete membrane staining observed in > 10% of tumor cells. Second, if the initial HER2 test result in a core needle biopsy specimen of a primary breast cancer is negative, a new HER2 test may (not "must") be ordered on the excision specimen based on specific clinical criteria. The HER2 testing algorithm for breast cancer is updated to address the recommended work-up for less common clinical scenarios (approximately 5% of cases) observed when using a dual-probe ISH assay. These scenarios are described as ISH group 2 ( HER2/chromosome enumeration probe 17 [CEP17] ratio ≥ 2.0; average HER2 copy number < 4.0 signals per cell), ISH group 3 ( HER2/CEP17 ratio < 2.0; average HER2 copy number ≥ 6.0 signals per cell), and ISH group 4 ( HER2/CEP17 ratio < 2.0; average HER2 copy number ≥ 4.0 and < 6.0 signals per cell). The diagnostic approach includes more rigorous interpretation criteria for ISH and requires concomitant IHC review for dual-probe ISH groups 2 to 4 to arrive at the most accurate HER2 status designation (positive or negative) based on combined interpretation of the ISH and IHC assays. The Expert Panel recommends that laboratories using single-probe ISH assays include concomitant IHC review as part of the interpretation of all single-probe ISH assay results. Find additional information at www.asco.org/breast-cancer-guidelines .

Physical basis of the 'magnification rule' for standardized Immunohistochemical scoring of HER2 in breast and gastric cancer.

BACKGROUND: Detection of HER2/neu receptor overexpression and/or amplification is a prerequisite for efficient anti-HER2 treatment of breast and gastric carcinomas. Immunohistochemistry (IHC) of the HER2 protein is the most common screening test, thus precise and reproducible IHC-scoring is of utmost importance. Interobserver variance still is a problem; in particular in gastric carcinomas the reliable differentiation of IHC scores 2+ and 1+ is challenging. Herein we describe the physical basis of what we called the 'magnification rule': Different microscope objectives are employed to reproducibly subdivide the continuous spectrum of IHC staining intensities into distinct categories (1+, 2+, 3+). METHODS: HER2-IHC was performed on 120 breast cancer biopsy specimens (n = 40 per category). Width and color-intensity of membranous DAB chromogen precipitates were measured by whole-slide scanning and digital morphometry. Image-analysis data were related to semi-quantitative manual scoring according to the magnification rule and to the optical properties of the employed microscope objectives. RESULTS: The semi-quantitative manual HER2-IHC scores are correlated to color-intensity measured by image-analysis and to the width of DAB-precipitates. The mean widths ±standard deviations of precipitates were: IHC-score 1+, 0.64 ± 0.1 µm; score 2+, 1.0 ± 0.23 µm; score 3+, 2.14 ± 0.4 µm. The width of precipitates per category matched the optical resolution of the employed microscope objective lenses: Approximately 0.4 µm (40×), 1.0 µm (10×) and 2.0 µm (5×). CONCLUSIONS: Perceived intensity, width of the DAB chromogen precipitate, and absolute color-intensity determined by image-analysis are linked. These interrelations form the physical basis of the 'magnification rule': 2+ precipitates are too narrow to be observed with 5× microscope objectives, 1+ precipitates are too narrow for 10× objectives. Thus, the rule uses the optical resolution windows of standard diagnostic microscope objectives to derive the width of the DAB-precipitates. The width is in turn correlated with color-intensity. Hereby, the more or less subjective estimation of IHC scores based only on the staining-intensity is replaced by a quasi-morphometric measurement. The principle seems universally applicable to immunohistochemical stainings of membrane-bound biomarkers that require an intensity-dependent scoring.

Fibroepithelial lesions of the breast: a comprehensive morphological and outcome analysis of a large series.

Mammary fibroepithelial lesions encompass a wide spectrum of tumors ranging from an indolent fibroadenoma to potentially fatal malignant phyllodes tumor. The criteria used for their classification based on morphological assessment are often challenging to apply and there is no consensus as to what constitutes an adequate resection margin. We studied a retrospective cohort of 213 fibroepithelial lesions in 178 patients (80 fibroadenomas with unusual features and 133 phyllodes tumors: 63 benign, 41 borderline, and 29 malignant) in order to describe the spectrum of changes within each group, with special emphasis on margin evaluation. Outcome data were available for 153 fibroepithelial lesions in 139 patients (median 56 months, range 3-249 months). Positive final margin (tumor transected), age < 50 years and a predominantly myxoid stroma were statistically significant predictors of local recurrence, while age > 50, stromal overgrowth, diffuse marked atypia, necrosis and mitotic index of ≥ 10 per 10 HPF were predictive of distant metastases. Tumors with satellite/bulging nodules were at a significantly higher risk to have a final positive resection margin. Our findings highlight important aspects of the interpretation and reporting of fibroepithelial lesions: the amount of myxoid stroma and the presence of satellite nodules are clinically relevant and should be routinely assessed and reported; infiltrative border might not be a prerequisite for the diagnosis of malignant phyllodes tumor, while the presence of tumor necrosis, massive stromal overgrowth or mitotic index of ≥ 25 per 10 HPF is diagnostic of malignant phyllodes tumor. On the other hand, increased mitotic index outside of the range of the World Health Organization guidelines in the absence of other worrisome features should be treated with caution, as it can be found in benign tumors.

Omitting radiation therapy after lumpectomy for pure DCIS does not reduce the risk of salvage mastectomy.

PURPOSE: Radiation therapy (RT) after breast-conserving surgery (BCS) for Ductal Carcinoma in Situ (DCIS) halves the risk of local recurrence (LR). The omission of RT is often supported by the paradigm that patients who develop LR can be salvaged with further breast-conserving therapy leading to higher rates of breast preservation and improved quality of life. However, population-based, long-term rates of breast preservation in women treated by upfront BCS ± RT are unknown. METHODS AND MATERIALS: Women diagnosed with pure DCIS from 1994 to 2003 treated with BCS ± RT in Ontario were identified. Median follow-up is 12 years. The development and treatment of LR and contralateral breast cancers were determined by administrative databases with validation. The 10-year mastectomy-free survival was calculated using the Kaplan-Meier method. The impact of RT on breast preservation was determined by propensity-adjusted cox proportional hazards model. RESULTS: The cohort includes 3303 women with DCIS; 1649 (50%) underwent BCS alone, 1654 (50%) underwent BCS + RT. Women treated by BCS alone were more likely to develop a LR compared to those treated by upfront BCS + RT (20.8% versus 15.5%, p < 0.001). Mastectomy was used to treat LR in 57.4% (197/343) of women who recurred after BCS alone and 67.6% (174/257) of those who recurred after BCS + RT. Women treated with upfront BCS + RT had higher rates of bilateral breast preservation at 10 years compared to those treated by BCS alone (87.3% vs.82.7%, p = 0.0096). CONCLUSION: Local Recurrence after BCS alone does not favor breast preservation.

Comparative Analysis of Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer According to 2007 and 2013 American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations.

Purpose To study the effect of the 2013 updates to the 2007 American Society of Clinical Oncology/College of American Pathologists recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer on testing patterns and interpretation in a large regional reference laboratory. Patients and Methods Patient cases with HER2 testing scores for breast biomarker evaluation were selected from our laboratory information system during two 12-month periods (2012 and 2014). The number of tests performed, type of specimens, proportion of HER2-positive and equivocal patient cases, and number of repeat tests on subsequent excisional specimens were examined and compared. Results Although the number of samples tested increased between 2012 and 2014 (2,201 v 2,558 patient cases; 2,278 v 2,659 tumors), HER2 positivity remained constant (15.7% v 15.5%, respectively). The number of repeat tests performed within 6 months more than doubled (122 [5.5%) of 2,201 v 302 [11.8%] of 2,558; P < .001), and the proportion of immunohistochemistry (IHC) 2+ tumors was significantly lower in 2014 than in 2012 (20.3% v 25.3%; P < .001). However, the proportion of patient cases with unresolved HER2 statuses (equivocal by IHC and in situ hybridization) was significantly higher in 2014 (four of 2,278 v 90 of 2,660; P < .001). Conclusion Our findings indicate that the 2013 updates to the American Society of Clinical Oncology/College of American Pathologists recommendations for HER2 testing in breast cancer did not affect the overall HER2-positivity rate or the proportion of patients eligible for HER2-targeted therapy. The proportion of tests and repeat tests performed increased, as did the number of patient cases categorized as ISH equivocal. The benefit of targeted therapy in the equivocal group is not proven, so targeted therapy should not be considered for patients in this category which should be redefined in future iterations of the recommendations.

Multigene Expression Assay and Benefit of Radiotherapy After Breast Conservation in Ductal Carcinoma in Situ.

Background: Most women with ductal carcinoma in situ (DCIS) will receive breast-conserving surgery (BCS) and radiation (RT). RT can be omitted for women at low risk of local recurrence (LR). The Oncotype DX DCIS score (DS) predicts LR risk after BCS alone. This study assesses the impact of RT and DS on LR risk. Methods: Population-based cohort analysis of individuals with DCIS treated by BCS ± RT from 1994-2003. Treatment and outcomes were determined by linkage and chart review. We used a propensity score-adjusted multivariable model to examine associations between DS and LR and evaluate the impact of RT. All statistical tests were two-sided. Results: The cohort includes 571 individuals treated by BCS alone, 689 cases treated with BCS + RT. Median follow-up was 9.4 years. On multivariable analysis, factors associated with LR include RT, age at diagnosis, tumor size, and multifocality. Adjusting for these factors, the DS risk group was statistically significantly associated with LR risk (hazard ratio high/intermediate = 1.75, 95% confidence interval = 1.28 to 2.41, P < .001). Women with a low-risk DS treated by BCS alone had an LR risk of 10.6% at 10 years and a small benefit from RT, while those with a high DS had a higher risk of LR (25.4%) after BCS alone and greater benefit from RT. A subgroup of patients with favorable clinicopathological features had a high-risk DS; these patients had a higher than expected risk of LR after BCS alone and a greater benefit with RT. Conclusions: The DS molecular assay improves risk stratification and estimates of RT benefit in individuals with DCIS treated with breast-conserving therapy.

Cutaneous malakoplakia masquerading as pyoderma gangrenosum.

Cutaneous malakoplakia is a rare infection-related granulomatous disease frequently associated with immunocompromised states. Foamy macrophages containing basophilic granules, called the Michaelis-Gutman bodies, are pathognomonic. We report a case of cutaneous malakoplakia in a 77-year-old male with pyoderma gangrenosum and a 2-year history of a non-healing malleolar ulcer treated successfully with cotrimoxazole.

Close or positive resection margins are not associated with an increased risk of chest wall recurrence in women with DCIS treated by mastectomy: a population-based analysis.

Mastectomy is effective treatment for ductal carcinoma in situ (DCIS) but some women will develop chest wall recurrence. Most chest wall recurrences that develop after mastectomy are invasive cancer and are associated with poorer prognosis. Past studies have been unable to identify factors predictive of chest wall recurrence. Therefore, it remains unclear if a subset exists of women with DCIS treated by mastectomy experience a high rate of recurrence in whom more aggressive treatment may be of benefit. We report outcomes of all women in Ontario (N = 1,546) diagnosed with pure DCIS from 1994 to 2003 treated with mastectomy without radiotherapy and evaluate factors associated with the development of chest wall recurrence. Treatments and outcomes were validated by chart review. Proportional differences were compared using Chi square analyses. Survival analyses were used to study the development of chest wall recurrence in relation to patient and tumor characteristics. Median follow-up was 10.1 years. Median age was 57.1 years. 36 patients (2.3%) developed chest wall recurrence. The 10-year actuarial chest wall recurrence-free survival rates and invasive chest wall recurrence-free survival rates were 97.6 and 98.6%, respectively. There was no difference in cumulative 10 year rates of chest wall recurrence by age at diagnosis (<40 years = 5.2%, 40-44 years = 1.3%, 45-50 years = 2.9%, >50 years = 2.1%; p = 0.19), nuclear grade (high = 3.0%, intermediate = 1.4%, low = 1.0%, unreported = 2.5%; p = 0.41), or among women with close or positive resection margins (positive = 3.0%, 2 mm or less = 1.4%, >2 mm = 1.5%, unreported = 2.8%; p = 0.51). On univariate and multivariable analysis, none of the factors were significantly associated with the development of chest wall recurrence. In this population cohort, individuals treated by mastectomy experienced low rates of chest wall recurrence. We did not identify a subset of patients with a high rate of chest wall recurrence, including those with positive margins.