Updates on Lobular Neoplasms and Papillary, Adenomyoepithelial, and Fibroepithelial Lesions of the Breast.

CONTEXT.­: This review article is a result of the breast pathology lectures given at the Sixth Chinese American Pathologists Association annual diagnostic pathology course in October 2020 (held virtually due to COVID-19). OBJECTIVE.­: To update recent developments, in this review article, the authors wrote minireviews in the following 4 areas: lobular neoplasm, adenomyoepithelial lesions, papillary lesions, and fibroepithelial lesions. DATA SOURCES.­: The sources include extensive literature review, personal research, and experience. CONCLUSIONS.­: With the wide practice of screening mammography, these lesions are not uncommon in image-guided core biopsies and excisional specimens. Many recent developments have emerged in understanding these lesions. We aim to provide readers with concise updates for each of these lesions with a focus on recent updates in definitions, diagnostic criteria, management, and molecular profiles that are most relevant to the daily practice of pathology and patient management.

Label-free Identification of Antibody-mediated Rejection in Cardiac Allograft Biopsies Using Infrared Spectroscopic Imaging.

BACKGROUND: Antibody-mediated rejection (AMR) in cardiac allograft recipients remains less well-understood than acute cellular rejection, is associated with worse outcomes, and portends a greater risk of developing chronic allograft vasculopathy. Diffuse immunohistochemical C4d staining of capillary endothelia in formalin-fixed, paraffin-embedded right ventricular endomyocardial biopsies is diagnostic of immunopathologic AMR but serves more as a late-stage marker. Infrared (IR) spectroscopy may be a useful tool in earlier detection of rejection. We performed mid-IR spectroscopy to identify a unique biochemical signature for AMR. METHODS: A total of 30 posttransplant formalin-fixed paraffin-embedded right ventricular tissue biopsies (14 positive for C4d and 16 negative for C4d) and 14 native heart biopsies were sectioned for IR analysis. Infrared images of entire sections were acquired and regions of interest from cardiomyocytes were identified. Extracted spectra were averaged across many pixels within each region of interest. Principal component analysis coupled with linear discriminant analysis and predictive classifiers were applied to the data. RESULTS: Comparison of averaged mid-IR spectra revealed unique features among C4d-positive, C4d-negative, and native heart biopsies. Principal component analysis coupled with linear discriminant analysis and classification models demonstrated that spectral features from the mid-IR fingerprint region of these 3 groups permitted accurate automated classification into each group. CONCLUSIONS: In cardiac allograft biopsies with immunopathologic AMR, IR spectroscopy reveals a biochemical signature unique to AMR compared with that of nonrejecting cardiac allografts and native hearts. Future study will focus on the predictive capabilities of this IR signature.

A Proposal for Separation of Nuclear Atypia and Architectural Atypia in Bethesda Category III (AUS/FLUS) Based on Differing Rates of Thyroid Malignancy.

Objectives: Bethesda category III (atypia of undetermined significance/follicular lesion of undetermined significance) includes sparsely cellular specimens with nuclear atypia (3N) and/or architectural atypia (3A). This study investigates whether the two types of atypia have different rates of malignancy (ROMs). Methods: Cytologic and histologic diagnoses of resected thyroid nodules were recorded. ROM was calculated for all Bethesda categories and for 3N and 3A subcategories. Possible noninvasive follicular thyroid neoplasms with papillary-like nuclear features were reviewed and removed from malignancies, and ROM was recalculated. Results: A total of 1,396 nodules were included. ROM of 3N (33.3%-26.0%) was higher than 3A (7.7%-5.0%) (P < .0001) and was similar to suspicious for follicular neoplasm (25.0%-20.3%) (P = .3). ROM of 3A approached benign (2.4%-1.5%) (P = .02). Conclusions: Strong consideration should be given to separating 3N (nuclear atypia with higher risk for papillary thyroid carcinoma) from 3A (architectural atypia with higher chance of being benign) to convey different ROMs.

Adenoid Cystic Carcinoma of the Oral Cavity: Radiology-Pathology Correlation.

Adenoid cystic carcinoma in the oral cavity is an uncommon salivary gland malignancy that has a propensity for perineural spread. A high-grade variant is evidenced by an abundance of pleomorphic cells, loss of the classic biphasic epithelial-myoepithelial growth pattern, and comedonecrosis, as well as elevated Ki-67. CT and MRI can both be useful for demonstrating the extent of invasion in oral cavity-associated adenoid cystic carcinoma, which can attain the inferior alveolar nerve for perineural spread by direct invasion through the mandible. Reflecting the aggressive nature of this high-grade malignancy, 18FDG-PET can demonstrate hypermetabolism and can be useful for staging. These features are exemplified in this sine qua non radiology-pathology correlation article.

Left ventricular structure and function in transthyretin-related versus light-chain cardiac amyloidosis.

BACKGROUND: Immunoglobulin amyloid light-chain (AL)-related cardiac amyloidosis (CA) has a worse prognosis than either wild-type (ATTRwt) or mutant (ATTRm) transthyretin (TTR) CA. Detailed echocardiographic studies have been performed in AL amyloidosis but not in TTR amyloidosis and might give insight into this difference. We assessed cardiac structure and function and outcome in a large population of patients with CA and compared findings in TTR and AL-related disease. METHODS AND RESULTS: We analyzed 172 patients with CA (AL amyloidosis, n=80; ATTRm, n=36; ATTRwt, n=56) by standard echocardiography and 2-dimensional speckle-tracking imaging-derived left ventricular (LV) longitudinal (LS), radial, and circumferential strains. Despite a preserved LV ejection fraction (55±12%), LS was severely impaired in CA. Standard measures of LV function and speckle-tracking imaging worsened as wall thickness increased, whereas apical LS was preserved regardless of the pathogenesis of CA and the degree of wall thickening. Compared with ATTRm and AL amyloidosis, ATTRwt was characterized by greater LV wall thickness and lower ejection fraction. LS was more depressed in both ATTRwt and AL amyloidosis (-11±3% and -12±4%, respectively, P=0.54) than in ATTRm (-15±4%, P<0.01 versus AL amyloidosis and ATTRwt). TTR-related causes were favorable predictors of survival, whereas LS and advanced New York Heart Association class were negative predictors. CONCLUSIONS: In patients with CA, worsening LV function correlated with increasing wall thickness regardless of pathogenesis. Patients with ATTRwt had a statistically greater wall thickness but lesser mortality than those with AL amyloidosis, despite very similar degrees of LS impairment. This paradox suggests an additional mechanism for LV dysfunction in AL amyloidosis, such as previously demonstrated light-chain toxicity.

Relation of N-terminal pro-B-type natriuretic peptide with diastolic function in hypertensive heart disease.

BACKGROUND: Elevated natriuretic peptide levels in asymptomatic individuals without heart failure are associated with increased risk of adverse cardiovascular outcomes and may reflect subclinical cardiac dysfunction. METHODS: In a sample of 313 asymptomatic individuals (51% women, mean age 61 years) with hypertension and diastolic dysfunction, we examined the association of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) with both conventional and advanced echocardiographic measures of systolic and diastolic function, including myocardial strain, using speckle-tracking-based analyses. RESULTS: In univariate analyses, higher NT-proBNP was associated with greater left ventricular mass index (P = 0.003), left atrial volume index (P = 0.007), lateral E' velocity (P < 0.0001), E/E' ratio (P < 0.0001), peak global longitudinal systolic strain (P = 0.015), systolic strain rate (P = 0.021), and early diastolic strain rate (P < 0.0001). In multivariable analyses, NT-proBNP remained associated with measures of diastolic dysfunction, including lateral E' velocity (P = 0.013) and the E/E' ratio (P = 0.008). However, early diastolic strain rate was the echocardiographic parameter most strongly associated with NT-proBNP (P = 0.003). CONCLUSIONS: In the setting of asymptomatic hypertensive heart disease and preserved ejection fraction, elevation in natriuretic peptide levels is predominantly associated with subclinical diastolic dysfunction.