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.

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.

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.

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.

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.

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.

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.

Interpretive Diagnostic Error Reduction in Surgical Pathology and Cytology: Guideline From the College of American Pathologists Pathology and Laboratory Quality Center and the Association of Directors of Anatomic and Surgical Pathology.

Context: Additional reviews of diagnostic surgical and cytology cases have been shown to detect diagnostic discrepancies.

Objective: To develop, through a systematic review of the literature, recommendations for the review of pathology cases to detect or prevent interpretive diagnostic errors.

Design: The College of American Pathologists Pathology and Laboratory Quality Center in association with the Association of Directors of Anatomic and Surgical Pathology convened an expert panel to develop an evidence-based guideline to help define the role of case reviews in surgical pathology and cytology.

Choroidal biopsy of a patient with AIDS and systemic tuberculosis: a clinicopathologic case report.

Purpose: To report a case of Mycobacterium tuberculosis choroidal granuloma confirmed by the presence of acid-fast bacilli seen on subretinal biopsy of the choroidal lesion.

Methods: Observational case report. A 54-year-old woman with AIDS and systemic tuberculosis reported decreased vision in the right eye for 2 months duration.

HER2 assessment by immunohistochemical analysis and fluorescence in situ hybridization: comparison of HercepTest and PathVysion commercial assays.

We determined HER2 protein overexpression by immunohistochemical analysis and HER2 gene amplification by fluorescence in situ hybridization (FISH) in 215 formalin-fixed, paraffin-embedded breast tumors. Pathologist concordance for immunohistochemical scoring, and HER2 status concordance, as determined by immunohistochemistry and FISH, were high for immunohistochemical 3+, 1+, and 0 tumors but poor for 2+ tumors. Consensus immunohistochemical scores correlated with absolute and chromosome 17 (CEPI 7)-corrected HER2 gene copy number Among HER2-nonamplified tumors, the immunohistochemical score and mean absolute chromosome 17 (CEP17) copy number were weakly correlated.

Metastatic Leydig cell tumor with sarcomatoid differentiation.

Leydig cell tumors of the testis are uncommon. Only about 10% of cases have a malignant course. It has been stated that the only definite criterion for malignancy is presence of metastasis.

Colorectal epithelial cell proliferative kinetics and risk factors for colon cancer in sporadic adenoma patients.

Colorectal epithelial cell proliferative kinetics are altered in patients at increased risk for colon cancer: proliferation rates [labeling index (LI)] are higher and there is a shift of the proliferative zone from one confined to the lower 60% of the colonic crypt to one that includes the entire crypt (higher phi(h)). To assess factors associated with LI and phi(h), we performed a cross-sectional analysis using baseline rectal mucosal biopsies from sporadic adenoma patients participating in a chemoprevention trial. Biopsies (taken without preparatory cleansing) were taken 10 cm above the level of the anus, and proliferation was assessed by detection of endogenous S-phase-associated proliferating cell nuclear antigen by immunohistochemical methods.

Methodological findings and considerations in measuring colorectal epithelial cell proliferation in humans.

The methodological issues for measuring colorectal epithelial cell proliferation, an intermediate end point for studies of colon neoplasia, in epidemiological studies are deceptively numerous and complex, with few methodological data available. Accordingly, during our experience with measuring colorectal epithelial cell proliferation from nearly 500 participants attending over 1300 study visits over a 6-year period, we recorded data on a variety of measurement variations. Methods investigated included rectal biopsy technique, general histological and labeling procedures [including the tritiated thymidine, 5-bromodeoxyuridine (BrdUrd), and the proliferating cell nuclear antigen (PCNA) immunohistochemical techniques used to label S-phase cells in colonic crypts in rectal biopsy specimens], biopsy scoring procedures, and summary scoring methods.

Calcium and colorectal epithelial cell proliferation in sporadic adenoma patients: a randomized, double-blinded, placebo-controlled clinical trial.

Background: The kinetics of colorectal epithelial cell proliferation is altered in patients at increased risk for colon cancer. Calcium administration ameliorates such proliferative changes in rodents. Findings in preliminary clinical trials have suggested similar effects in humans.

Malignant mixed müllerian tumor versus high-grade endometrial carcinoma and aggressive variants of endometrial carcinoma: a comparative analysis of survival.

To ascertain whether uterine malignant mixed müllerian tumors are biologically distinct from high-grade endometrial carcinomas (FIGO grade 3), we compared patient survival in 32 and 39 cases, respectively. The Cox proportional hazard model was employed to determine whether tumor type was an independent predictor of survival. The survival of patients with MMMT was also compared to that of patients with serous adenocarcinoma and clear cell carcinoma.

CD34 and factor XIIIa in the differential diagnosis of dermatofibroma and dermatofibrosarcoma protuberans.

To assess the use of anti-CD34 and anti-factor-XIIIa antibodies for the differential diagnosis of dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP), we stained 40 DFs and 13 DFSPs. A significant population of dendritic and spindle cells was reactive with anti-factor-XIIIa in 90% of DFs. In DFSP, most cases had very few or no reactive cells for this antiserum and reactivity was confined to the infiltrating edges of the neoplasm or to a very low percentage of cells within the bulk of the tumor.

Myogenous phenotype of epithelial-like areas in endometrial stromal sarcomas.

Approximately 25% of low-grade endometrial stromal sarcomas of the uterus contain areas of epithelial-like differentiation, which are often reminiscent of ovarian sex-cord tumors. It has been suggested that these areas may represent attempted differentiation toward either uterine glands or smooth muscle. To investigate these two possibilities, we examined the histologic and immunohistochemical features of 26 low-grade endometrial stromal sarcomas.

Gross cystic disease fluid protein-15 in salivary gland tumors.

Gross cystic disease fluid protein-15 (GCDFP-15) is a 15-kd glycoprotein that is expressed by normal apocrine epithelia and in a majority of breast carcinomas. However, recent studies have demonstrated that this substance is also present in tumors of the salivary glands, sweat glands, and prostate gland. To determine whether the expression of CGDFP-15 might aid in the differential diagnosis of salivary gland lesions, the anti-GCDFP-15 monoclonal antibody D6 was applied to paraffin sections of 133 such neoplasms.

Mesenchymal chondrosarcoma. An immunohistochemical study.

Mesenchymal chondrosarcoma is an uncommon small-cell neoplasm of bone and soft tissue, the chondrogenic nature of which has been generally accepted. However, the phenotypic attributes of the small-cell population in this neoplasm have not been well characterized, and its relationship to "precartilage mesenchyme" remains unclear. In an attempt to address this issue, we performed an immunohistochemical analysis of nine cases, using antibodies to vimentin, S100 protein, Leu-7 antigen, neuron-specific enolase, synaptophysin, desmin, muscle-specific actin, cytokeratin, and epithelial membrane antigen, and the avidin-biotin-peroxidase complex (ABC) method.

Gross cystic disease fluid protein-15 as a marker for breast cancer: immunohistochemical analysis of 690 human neoplasms and comparison with alpha-lactalbumin.

The identification of metastatic carcinoma of the breast may be difficult in the absence of a previous history of breast cancer. Various immunophenotypic markers have been introduced to aid in this process. A monoclonal antibody directed at a 15-kilodalton (kd) gross cystic disease fluid protein (GCDFP-15) was applied immunohistochemically to paraffin sections of 105 breast cancers and 585 nonmammary malignancies in order to assess its value in this context.