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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.

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.

Mammary Paget disease (MPD) is considered an intraepidermal manifestation of an underlying mammary carcinoma. In contrast to extramammary Paget disease, invasion of mammary Paget cells into the dermis (invMPD) has not been reported, except for 2 cases described in Rosen's textbook. Our study was designed to identify the presence of dermal invasion of mammary Paget cells and characterize the associated clinicopathologic features. Slides from 146 MPD patients were retrieved. Six cases of invMPD were identified. One case of invMPD was not associated with an underlying breast cancer, 1 was associated with invasive ductal carcinoma (IDC), 1 with ductal carcinoma in situ (DCIS) with microinvasion, and 3 with DCIS only. The underlying breast carcinomas was separate from the area of invMPD. The depth of invasion, measured from the dermal-epidermal junction to the focus of deepest invasion, ranged from 0.02 to 0.9 mm. The horizontal extent ranged from 0.01 to 4.0 mm. Lymph node with isolated tumor clusters was present in case 1, which had no underlying carcinoma but had the greatest extent of invasion, and in case 3, which had DCIS with microinvasion. One patient (case 1) died of unrelated causes 2 years later, and the remaining patients were alive without disease at last follow-up. In summary, we describe 6 cases of MPD with invasion of Paget cells into the dermis and provide histopathologic criteria for the diagnosis of this rare and underrecognized entity. Further studies are required to determine whether invasion in MPD has clinical significance.

The World Health Organization classification of tumors of the breast includes a rare variant of invasive ductal carcinoma termed pleomorphic carcinoma. This variant has marked nuclear pleomorphism (>6-fold variation in nuclear size by definition, but often>10-fold) and characteristically contains multinucleated tumor giant cells. Approximately one-third of the cases in the initial series contained a focal spindle cell metaplastic component. The tumors are reported to have an aggressive behavior, but because some contain a spindle cell metaplastic component, it is unclear whether the metaplastic component or other clinicopathologic features account for the poor clinical outcome. We identified 37 cases of pleomorphic carcinoma of the breast and evaluated the association between clinical outcome and multiple clinicopathologic features. Patients with invasive pleomorphic lobular carcinoma and those without at least a tissue biopsy before chemotherapy were excluded. Patients ranged in age from 23 to 78 years (median, 49 y). Tumor size was >5 cm in 12 cases and <5 cm in 22. A focal spindle cell component (<25% of the tumor) was present in 14 tumors (38%). Clinical follow-up was available for 36 patients (median, 17 mo). In multivariate analysis, when the 2 stage-IV patients were excluded, the presence of a spindle cell component and tumor size >5 cm were each independently associated with decreased overall survival. The actuarial 5-year overall survival for patients with and without a metaplastic spindle cell component was 38%+/-15% and 89%+/-7%, respectively. Poor clinical outcome, therefore, is associated with the subset of pleomorphic carcinomas with a spindle cell metaplastic component. As the morphologic features of pleomorphic carcinoma can be seen in primary tumors from other sites, it is important to recognize this tumor as a rare variant of invasive breast carcinoma.

HER2 is an important predictive marker for response to trastuzumab and lapatinib in breast cancer. It is also a powerful prognostic marker in node-positive patients. Although standardized assays are used to help select patients for anti-HER2 therapy, there are no standardized criteria for assessing HER2 as a prognostic marker. Recent data using quantitative image analysis suggest that both high and low HER2 expression are associated with poor clinical outcome. Using the immunohistochemical scoring criteria currently recommended by the College of American Pathologists and American Society of Clinical Oncology to help select patients for trastuzumab, we evaluated HER2 protein expression in tumor tissue microarrays of 91 node-positive patients with invasive breast carcinoma treated with mastectomy and doxorubicin-based chemotherapy without trastuzumab and without irradiation with a median follow-up of 12.5 years. A wide range of HER2 expression (HER2 >or=1+) in the primary tumor was significantly associated with decreased locoregional recurrence-free survival (P=0.014), decreased disease-specific survival (P=0.001), and decreased overall survival (P=0.001). Even in the subset considered HER2 negative by current College of American Pathologists and American Society of Clinical Oncology guidelines, HER2=1+ was associated with worse outcome than HER2=0 in this patient cohort. The association between HER2 >or=1+ and worse outcome had the greatest statistical significance in the hormone receptor-positive subset of patients. These findings support the hypothesis that low-level HER2 expression may have significant clinical implications. Although the assessment of HER2 expression is most important for predicting response to anti-HER2 therapy, detection of low-level HER2 expression might also be useful in helping to select a more aggressive treatment regimen for patients ineligible for anti-HER2 therapy.

Matrix-producing carcinoma (MPC) of the breast is a subtype of metaplastic carcinoma defined as an invasive breast carcinoma with a direct transition of carcinoma to cartilaginous or osseous matrix without an intervening spindle cell component. Our aims were (1) to evaluate specific histologic characteristics of MPC and correlate these with disease recurrence; and (2) to determine whether rates of locoregional and distant recurrence for MPC are significantly different from those of invasive ductal carcinoma. Thirty-two cases of MPC were identified. Fourteen patients (44%) were < or =50 years of age; 10 (31%) had tumors of size < or =2 cm, and 6 (19%) had tumors > or =5 cm. In this series, all tumors contained chondromyxoid or chondroid matrix, and 1 (3.1%) also contained focal (<5%) osseous matrix. High-grade matrix was present in 9 cases (28%), and low-grade matrix was present in 23 (72%). Matrix comprised < or =10% of the tumor in 14 cases (44%), >10% but <40% in 9 (28%), and > or =40% in 9 (28%). The carcinomatous component was high grade in 30 cases (94%), and 19 tumors (59%) had central necrosis. Seven patients (22%) had positive axillary lymph nodes, and 8 (25%) had lymphovascular space invasion (LVSI). LVSI was the only factor independently associated with locoregional recurrence-free survival in multivariate analysis (P=0.043). Although > or =40% matrix was associated with improved distant recurrence-free (DFS) survival in univariate analysis (P=0.044), only LVSI and tumor stage were independently associated with DFS survival in multivariate analysis (P=0.027 and P=0.001, respectively). Compared with matched controls with invasive ductal carcinoma, patients with MPC had decreased locoregional recurrence-free survival (P=0.001) and decreased DRF survival (P=0.001). In summary, MPC is an aggressive subtype of metaplastic carcinoma with a worse clinical outcome than invasive ductal carcinoma.

Metaplastic carcinomas of the breast are a heterogeneous group of neoplasms ranging from tumors with a predominant component of overt carcinoma and focal mesenchymal differentiation to keratin-positive tumors with pure sarcomatoid morphology. We examined the clinicopathologic features of 22 patients previously diagnosed at M.D. Anderson Cancer Center with metaplastic carcinoma of the breast with pure or almost pure sarcomatoid morphology. Patients were included in the study if their tumors had sarcomatoid morphology and: 1) an invasive carcinomatous component identifiable on hematoxylin and eosin stains comprising less than 5% of the invasive tumor; or 2) associated ductal carcinoma in situ; or 3) immunohistochemical expression of keratin in the sarcomatoid areas. Patients with low-grade fibromatosis-like metaplastic tumors and those who received neoadjuvant chemotherapy were excluded. Axillary lymph node dissection or limited axillary node excision was performed in 17 patients, including 1 patient who had a sentinel lymph node biopsy. Lymph node involvement occurred in only 1 patient and consisted of a single 3.5-mm metastasis. Clinical follow-up was available for 21 patients and ranged from 4 months to 155 months (median follow-up, 35 months). Ten patients experienced local relapse, including 7 of 11 patients treated with breast-conserving surgery, and 9 developed distant metastases, most frequently to the lungs. These findings suggest that metaplastic sarcomatoid carcinomas that lack or have only a minimal overt invasive carcinomatous component have a biologic behavior similar to that of sarcomas. In addition to systemic treatment, early aggressive local therapy is recommended, as these patients have a high rate of local relapse.

Data from a recent study support the hypothesis that axillary lymph node metastases frequently localize near the inflow junction of the afferent lymphatic vessel. Our goal was to evaluate the microscopic location of axillary sentinel lymph node metastases in a prospective study of breast cancer patients. A total of 305 axillary sentinel lymph nodes from 213 breast cancer patients undergoing surgery at our institution were evaluated. Preoperative lymphoscintigraphy using technetium-labeled sulfur colloid and intraoperative isosulfan blue dye injection were used for identifying the sentinel lymph node. Intraoperatively, the surgeon placed a suture either at the point of entry of isosulfan blue dye or at the area with the highest radioactive counts, and this area was inked at the grossing bench before processing. Metastases were identified in 55 of the 305 lymph nodes examined. Thirty-four nodes contained metastases in both the inked half and the opposite half. Metastatic tumor was identified in the inked half alone in 18 lymph nodes. Only three nodes contained metastatic tumor in the opposite half with no tumor in the inked half (p <0.001). Similar results were found when nodes tagged at the point of blue dye entry and nodes tagged at the area with the highest radioactive counts were analyzed separately. Our findings suggest that metastatic tumor has a higher probability of being present in the region of the inflow junction of the afferent lymphatic vessel. This information may be useful in determining the optimal method for evaluating axillary sentinel lymph node specimens from breast cancer patients.