Cellular Spindled Histiocytic Pseudotumor: A Benign Mimic of Spindle Cell Neoplasia of the Breast.

CONTEXT.­: Cellular spindled histiocytic pseudotumor (CSHPT) is an exuberant, dense histiocytic proliferation seen in the setting of mammary fat necrosis. CSHPT has a broad histologic differential diagnosis, including benign, malignant, and inflammatory etiologies. OBJECTIVES.­: To highlight the most important histologic and immunohistochemical findings of CSHPT and provide comparisons to entities within the broad differential diagnosis. DATA SOURCES.­: Recently published literature regarding CSHPT and other diagnostic considerations. CONCLUSIONS.­: CSHPT is a benign histiocytic proliferation with a broad differential diagnosis, for which comprehensive ancillary studies may be required to exclude malignant and infectious entities.

Repeat Biomarker Status in Breast Resection Specimens With Controlled Cold Ischemic Time.

OBJECTIVES: Current College of American Pathologists/American Society of Clinical Oncology guidelines recommend cold ischemic time (CIT) of 1 hour or less for breast specimens to preserve biomarker expression, although some publications support an acceptable CIT of 4 hours or less. We retrospectively evaluated changes in estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) from biopsy to resection specimens that were triaged to optimize CIT. METHODS: We identified breast resection specimens collected after institutional implementation of a triage protocol. Clinicopathologic features were assessed. RESULTS: In total, 295 excisions had a prior malignant diagnosis, with CIT of 4 hours or less and repeat ER, PR, and/or HER2; 230 (78%) had CIT of 1 hour or less, and 65 (22%) had CIT of more than 1 hour but 4 hours or less. Categorical change was seen in 10 (17.9%) of 56 with repeated ER/PR and 38 (13.3%) of 285 with repeated HER2 (of which five [1.8%] had meaningful change). CONCLUSIONS: When CIT is optimized, a meaningful change in biomarker expression is infrequent. This study supports that when specimens are appropriately triaged, CIT of 4 hours or less may be acceptable.

Biphenotypic Sinonasal Sarcoma: A Review and Update.

CONTEXT.­: Biphenotypic sinonasal sarcoma (BSNS) is a rare, slow-growing soft tissue sarcoma of the sinonasal tract, typically presenting with nonspecific obstructive nasal symptoms. Although recurrences are common, no metastases have been reported, and only 1 patient has died of disease thus far. It characteristically demonstrates rearrangements of PAX3 with multiple fusion partners, the most common of which is MAML3. OBJECTIVES.­: To highlight the most important diagnostic features, including morphologic, immunohistochemical, and molecular findings, and to provide comparisons to other entities in the differential diagnosis. We also aim to provide a summary of the clinical features and outcomes in cases reported to date. DATA SOURCES.­: Recently published literature encompassing BSNS and its synonym, low-grade sinonasal sarcoma with neural and myogenic differentiation. CONCLUSIONS.­: BSNS is a sinonasal tumor that is important to recognize because its biologic behavior differs from most of the entities in the differential diagnosis. The diagnosis can typically be rendered through a combination of morphology, immunohistochemical stains, and ancillary testing for characteristic PAX3 rearrangements.

Atypical Ductal Lesions of the Breast: Criteria, Significance, and Laboratory Updates.

CONTEXT.­: Atypical ductal hyperplasia (ADH) is a challenging diagnosis defined by cytologic and architectural features that carries an increased risk of subsequent carcinoma when diagnosed in isolation. In addition, ADH may secondarily involve benign breast lesions, wherein it carries variable clinical significance. OBJECTIVES.­: To review the diagnostic criteria and clinical significance of ADH in isolation and as it involves benign breast lesions, and to review the evolving literature on its molecular signature. DATA SOURCES.­: Recently published studies that collectively examine ADH were reviewed. CONCLUSIONS.­: Atypical ductal hyperplasia carries an increased risk of subsequent carcinoma in isolation and when it involves most benign breast lesions. Identifying which cases of ADH will be upgraded to carcinoma has been challenging, and new laboratory developments, such as EZH2 overexpression, may have a future role.

A rapid triage protocol to optimize cold ischemic time for breast resection specimens.

Prolonged time from specimen excision to adequate formalin exposure, or cold ischemic time (CIT), negatively impacts estrogen receptor (ER), progesterone receptor (PR) and HER-2 biomarker studies routinely performed on breast specimens. Current guidelines recommend CIT of ≤1 h. Since formalin penetrates resections slowly, optimal fixation requires incision. We evaluated the efficacy of a rapid triage protocol developed to optimize CIT. We identified 2821 specimens: 650 (23.0%) excisional biopsies (EB), 1051 (37.3%) lumpectomies, and 1120 (39.7%) mastectomies. CIT was available for 2362 (83.7%), with 1845 (78.1%) ≤1 h and 2323 (98.3%) ≤4 h. IHC was performed in 533/2821 (18.9%) and was associated with lumpectomy and mastectomy procedures when compared to EB. However, IHC was also performed on 11.1% (72/650) of EB specimens despite EB being significantly less likely to have CIT recorded (468/650; 72% for EB vs. 1894/2171; 87.2% for lumpectomies/mastectomies). Our study highlights the need for rapid triage of breast resections with known or suspected malignant diagnoses and outlines our procedure for optimizing CIT. Additionally, we advocate treating ALL breast resections as having the potential of being malignant and requiring biomarker studies for which optimal CIT is of great importance.

Clinicopathological findings in female-to-male gender-affirming breast surgery.

AIMS: Gender dysphoria is a diagnosis whereby an individual identifies as the opposite gender. The management of patients seeking female-to-male (FTM) transition includes hormonal therapy and surgical intervention, including mastectomy. The aim of this study was to characterize the immunohistological findings in resection specimens from FTM patients. METHODS AND RESULTS: We reviewed 68 cases (67 patients, one with re-excision) of FTM breast tissue resection by collecting clinical data, reviewing breast imaging and pathology reports (gross fibrous density, specimen weight, and number of cassettes submitted), and reviewing pathology slides [number of tissue pieces submitted, number of terminal duct lobule units (TDLUs), and the presence of histological findings]. Significant histological findings were present in 51 of 68 (75.0%) cases, including one case (1.5%) of flat epithelial atypia. Fibrocystic changes were the most common finding (27/68, 39.7%), followed by gynaecomastoid change, fibrotic stage, (22/68, 32.4%), and fibroadenomatoid change (11/68, 16.2%). Fibrocystic change was associated with increased numbers of TDLUs, and gynaecomastoid change was associated with lower body mass index and decreased numbers of TDLUs. Gynaecomastoid change showed a moderate proportion of luminal epithelial cells with strong-intensity immunohistochemical staining for oestrogen receptor, progesterone receptor, and androgen receptor, and a three-layered epithelium demonstrated by the use of cytokeratin 5/6 immunohistochemistry. CONCLUSIONS: We identified gynaecomastoid change at a significantly higher rate than previously reported in female patients. We support the continued gross and histological evaluation of FTM specimens in light of the identification of atypia in one case.

Characteristics of a Breast Pathology Consultation Practice.

CONTEXT: - Intradepartmental consultation is a routine practice commonly used for new diagnoses. Expert interinstitutional case review provides insight into particularly challenging cases. OBJECTIVE: - To investigate the practice of breast pathology consultation at a large tertiary care center. DESIGN: - We reviewed breast pathology cases sent for private consultation and internal cases reviewed by multiple pathologists at a tertiary center. Requisitions and reports were evaluated for diagnostic reason for consultation, rate of multiple pathologist review at the tertiary center, use of immunohistochemistry, and, for private consultation cases, type of sender and concordance with the outside diagnosis. RESULTS: - In the 985 private consultation cases, the most frequent reasons for review were borderline atypia (292 of 878; 33.3%), papillary lesion classification (151 of 878; 17.2%), evaluating invasion (123 of 878; 14%), subtyping carcinoma (75 of 878; 8.5%), and spindle cell (67 of 878; 7.6%) and fibroepithelial (65 of 878; 7.4%) lesion classification. Of 4981 consecutive internal cases, 358 (7.2%) were reviewed, most frequently for borderline atypia (90 of 358; 25.1%), subtyping carcinoma (63 of 358; 17.6%), staging/prognostic features (59 of 358; 16.5%), fibroepithelial lesion classification (45 of 358; 12.6%), evaluating invasion (37 of 358; 10.3%), and papillary (20 of 358; 5.6%) and spindle cell (18 of 358; 5.0%) lesion classification. Of all internal cases, those with a final diagnosis of atypia had a significantly higher rate of review (58 of 241; 24.1%) than those with benign (119 of 2933; 4.1%) or carcinoma (182 of 1807; 10.1%) diagnoses. Immunohistochemistry aided in diagnosis of 39.7% (391 of 985) and 21.2% (76 of 359) of consultation and internally reviewed cases, respectively. CONCLUSIONS: - This study confirms areas of breast pathology that represent diagnostic challenge and supports that pathologists are appropriately using expert consultation.

Utility of estrogen receptor, progesterone receptor, and HER-2/neu analysis of multiple foci in multifocal ipsilateral invasive breast carcinoma.

OBJECTIVES: To determine the frequency of estrogen receptor (ER), progesterone receptor (PR), and HER-2/neu (HER2) testing multiple foci of ipsilateral invasive breast carcinoma at our institution and to evaluate resulting change in treatment recommendation. METHODS: We identified 165 consecutive cases of multifocal invasive breast cancer over a 10-year period (2005-2014). Clinicopathologic features and treatment recommendation were assessed by slide and chart review. RESULTS: Seventy (42.4%) of 165 patients had two or more foci tested. In the first 6 years (2005-2010), frequency of testing two or more foci was 31.6% and increased to 70.6% in 2014. Seven (10%) of 70 had a clinically significant difference in ER/PR and/or HER2 status, five (7.1%) with a difference in HER2, one (1.4%) in ER/PR, and one (1.4%) in both ER/PR and HER2. All cases with difference in status had different histology and/or the largest focus was the most positive one. CONCLUSIONS: Our findings support current recommendations to evaluate additional smaller tumor foci in multifocal invasive breast cancer if the focus is of different grade or histology. Additional features, including specific histology, grade, and ER, PR, and HER2 status of the largest focus, should also be considered when selecting cases for which testing of additional foci may be of benefit.