No consensus exists on the need to excise breast lesions that yield classic lobular carcinoma in situ (LCIS) or atypical lobular hyperplasia (ALH) (known together as classic lobular neoplasia [LN]) as the highest risk lesion at percutaneous core-needle biopsy (CNB). Here, the authors report findings from 72 consecutive lesions with LN at CNB and prospective surgical excision (EXB).Lesions that yielded LN at CNB at the authors' center have been referred for EXB since June 2004, regardless of imaging-histologic concordance. A lesion was "concordant" if histologic findings provided sufficient explanation for imaging. An upgrade consisted of ductal carcinoma in situ and/or invasive carcinoma at EXB. Statistical analysis, including 95% confidence intervals (CIs), was performed.Between June 2004 and May 2009, CNB of 85 consecutive lesions yielded LN without other high-risk histologies. Eighty of 85 lesions (94%) underwent prospective EXB. Seventy-two of 85 lesions (90%; 42 LCIS, 30 ALH) had concordant imaging-histologic findings. EXB yielded low-grade carcinoma in 2 of 72 cases (3%; 95% CI, 0%-9%). In both patients, stereotactic, 11-gauge, vacuum-assisted biopsy of calcifications yielded calcifications in benign parenchyma and ALH. CNB results were discordant in 8 of 80 lesions (10%; 4 LCIS, 4 ALH), and EXB yielded cancer in 3 of those 8 lesions (38%; 95% CI, 9%-76%). The upgrade rate was significantly higher for discordant lesions versus concordant lesions (38% vs 3%; P < .01).Prospective excision of LN identified carcinoma in 3% (95% CI, 0%-9%) of concordant cases versus 38% (95% CI, 9%-76%) of discordant cases. The current data provide an unbiased assessment of the upgrade rate of LN diagnosed at CNB.
<p>Supplementary Table S4: Somatic single nucleotide variants (SNVs) and insertion/deletions (indels). Supplementary Table S5: Frequencies of mutations found in ER-positive/HER2-negative male breast cancer vs subsets of female breast cancer from the TCGA study. Supplementary Table S6: MutSigCV analysis of significantly mutated genes in MaBCs.</p>
<p>Supplementary Table S7: Comparative analysis of the frequencies of mutations in luminal A-like and luminal B-like male breast cancer. Supplementary Table S8: Comparative analysis of genes affecting selected functional pathways. Supplementary Table S9: Mutational frequency of male breast cancer vs subsets of female breast cancer from the TCGA study. Supplementary Table S10: Potentially targetable genes mutated exclusively in ER-positive/HER2-negative male breast cancer.</p>
Confocal microscopy is in clinical use to diagnose skin cancers in the United States and in Europe. Potentially, this technology may provide bed-side pathology in breast cancer surgery during tumor removal. Initial studies have described major findings of invasive breast cancers as seen on fluorescence confocal microscopy. In many of these studies the region of interest (ROI) used in the analysis was user-selected and small (typically 15 square-mm). Although these important findings open exploration into rapid pathology, further development and implementation in a surgical setting will require examination of large specimens in a blinded fashion that will address the needs of typical surgical settings. In post surgery pathology viewing, pathologists inspect the entire pathology section with a low (2X) magnification objective lens initially and then zoomed in to ROIs with higher magnification lenses (10X to 40X) magnifications to further investigate suspected regions. In this study we explore the possibility of implementation in a typical surgical setting with a new microscope, termed confocal strip-mosaicking microscope (CSM microscope), which images an area of 400 square-mm (2 cm x 2 cm) of tissue with cellular level resolution in 10 minutes. CSM images of 34 human breast tissue specimens from 18 patients were blindly analyzed by a board-certified pathologist and correlated with the corresponding standard fixed histopathology. Invasive tumors and benign tissue were clearly identified in CSM images. Thirty specimens were concordant for images-to-histopathology correlation while four were discordant. Preliminary results from on-going work to molecularly target tumor margin will also be presented.
Abstract Context.—Placental transmogrification of the lung is a term introduced to describe a peculiar histologic pattern characterized by formation of placental villuslike structures in the lung parenchyma. It has been reported to occur in association with bullous emphysema and lipomatosis. Objectives.—To study the relationship between placental transmogrification and pulmonary hamartomas. Design and Methods.—Reports of 38 cases of pulmonary hamartomas during 18 years (1982–1999) were reviewed. All histologic slides of these cases were examined for the presence of villuslike papillary projections and placenta-like structures. Hamartomas with prominent papillary projections or placenta-like structures were further investigated to assess the histogenesis and proliferation of epithelial and stromal cells. Immunohistochemical analysis was performed on paraffin-embedded tissue using monoclonal antibodies against Ki-67 and thyroid transcription factor 1 (TTF-1) and polyclonal antibodies against c-Kit antigen (a stem cell factor receptor/mast cell growth factor receptor) in conjunction with Leder stain for naphthol-ASD-chloroacetate esterase. Results.—Placental transmogrification was identified in 6 of 38 cases of pulmonary fibrochondromatous hamartomas. The histologic change consisted of an abundant myxoid or edematous fibroadipose stroma with a respiratory epithelial lining, resulting in papillary projections that resembled immature placental villi. Epithelium lining the papillary projections was positive for TTF-1 (70%–90%) and Ki-67 (3%–5%). In contrast, stromal cells were negative for TTF-1 with only rare cells immunoreactive for Ki-67. A number of stromal spindle cells and occasional cells in epithelium were c-Kit immunoreactive; however, concurrent Leder stain demonstrated that these c-Kit–positive cells were mast cells and not stem cells. Conclusions.—Placental transmogrification is frequently associated with pulmonary fibrochondromatous hamartomas and may be induced by or associated with a proliferation of lining epithelial components in the hamartomas. The significance of numerous mast cells within stroma of placental transmogrification is unclear and their possible role in inducing stromal proliferation needs to be further evaluated.
Context.— The Ventana programmed death ligand-1 (PD-L1) SP142 immunohistochemical assay (IHC) is approved by the US Food and Drug Administration as the companion diagnostic assay to identify patients with locally advanced or metastatic triple-negative breast cancer for immunotherapy with atezolizumab, a monoclonal antibody targeting PD-L1. Objective.— To determine interobserver variability in PD-L1 SP142 IHC interpretation in invasive breast carcinoma. Design.— The pathology database was interrogated for all patients diagnosed with primary invasive, locally recurrent, or metastatic breast carcinoma on which PD-L1 SP142 IHC was performed from November 2018 to June 2019 at our institution. A subset of cases was selected using a computerized random-number generator. PD-L1 IHC was evaluated in stromal tumor-infiltrating immune cells using the IMpassion130 trial criteria, with positive cases defined as immunoreactivity in immune cells in 1% or more of the tumor area. IHC was interpreted on whole slide images by staff pathologists with breast pathology expertise. Interobserver variability was calculated using unweighted κ. Results.— A total of 79 cases were assessed by 8 pathologists. Interobserver agreement was substantial (κ = 0.727). There was complete agreement among all 8 pathologists in 62% (49 of 79) of cases, 7 pathologists or more in 84% (66 of 79) of cases, and 6 pathologists or more in 92% (73 of 79) of cases. In 4% (3 of 79) of cases, all of which were small biopsies, pathologists' interpretations were evenly split between scores of positive and negative. Conclusions.— The findings show substantial agreement in PD-L1 SP142 IHC assessment of breast carcinoma cases among 8 pathologists at a single institution. Further study is warranted to define the basis for discrepant results.
The purpose of our study was to determine the frequency of complete removal of the imaging target at MRI-guided vacuum-assisted biopsy of breast cancer and to assess the residual cancer rate at surgery in these lesions.With the approval of our institutional review board, retrospective review was performed of 416 consecutive lesions that underwent MRI-guided 9-gauge vacuum-assisted biopsy, of which 76 (18%) yielded cancer. Medical and pathology records were reviewed.Vacuum-assisted biopsy histology in 76 cancers was ductal carcinoma in situ in 39 (51%) and invasive cancer in 37 (49%). Median MRI lesion size in these 76 cancers was 1.2 cm (range, 0.4-8.0 cm). The median number of samples obtained was 12 (range, 6-24 samples). Among 76 cancers, the MRI target was completely excised in 23 (30% [95% CI, 20-42%]), sampled in 52 (69% [57-79%]), and possibly missed in one (1% [0-7%]). Complete MRI target excision rather than sampling was significantly more likely in lesions < or = 1 cm than in lesions >1 cm (18/34 = 53% vs 5/41 = 12%; p < 0.001). Surgery, performed in 67 of 76 cancers, showed residual cancer in 55 (82% [71-90%]). The residual cancer rate was significantly lower if the MRI target was completely excised rather than sampled (14/22 = 64% vs 40/44 = 91%; p < 0.02).Complete excision of the MRI target occurred in 30% of breast cancers diagnosed at MRI-guided vacuum-assisted biopsy. Among cancers in which the MRI target was percutaneously excised, surgery yielded residual cancer in 64%. Complete removal of the MRI target does not ensure complete histologic excision of the cancer.
Hepatic steatosis, a common histological finding in hepatitis C virus (HCV)-infected patients, is associated with severity of fibrosis. The prevalence and significance of steatosis in patients coinfected with human immunodeficiency virus (HIV) and HCV are not well characterized.To determine the prevalence and severity of steatosis, a single pathologist evaluated liver-biopsy samples from 106 patients coinfected with HIV and HCV but without hepatitis B infection (negative results for hepatitis B surface antigen) for findings associated with steatosis or steatohepatitis and viral hepatitis. Medical records were reviewed retrospectively to elucidate risk factors for steatosis.Steatosis was present in 56% of biopsy samples, with moderate to severe grades in 9%. Severity of steatosis was associated with fibrosis (odds ratio [OR], 1.84 [95% confidence interval (CI), 1.06-3.20]; P=.03) but not with necroinflammation. In multivariate analysis, the severity of steatosis was associated with lower levels of high-density lipoprotein cholesterol (OR, 0.71 per 10-mg/dL increase [95% CI, 0.52-0.95]; P=.02), higher body-mass index (OR, 1.30 per kg/m2 increase [95% CI, 1.13-1.49]; P<.001), and the presence of lipodystrophy (OR, 3.82 [95% CI, 1.13-12.88]; P=.03). There was a trend toward an association between the severity of steatosis and fibrosis in multivariate analysis (OR, 1.69 [95% CI, 0.91-3.16]; P=.10).In patients coinfected with HIV and HCV, hepatic steatosis is common and associated with more-advanced fibrosis. Lower levels of high-density lipoprotein cholesterol, higher body-mass index, and lipodystrophy are potentially modifiable risk factors associated with the severity of steatosis.
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