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Results for “flat epithelial atypia”

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PubMed2025

Genetic Analysis of Early Neoplasia in the Breast: Next-Generation Sequencing of Flat Epithelial Atypia and Associated Ductal and Lobular Lesions.

The molecular features of invasive breast cancers (IBC) have been well-characterized, but less is known about the earlier stages of neoplasia, including oncogenic drivers in early intraductal lesions. Flat epithelial atypia (FEA) is considered the earliest recognized precursor in the low-grade neoplasia pathway, but its mutational repertoire has not been studied, and drivers of the transition to morphologically more advanced lesions are unknown. Herein, we utilized next-generation sequencing to analyze 39 synchronous lesions from 13 patients, including FEA (n = 12) or predominantly FEA with early atypical ductal hyperplasia (FEA/early atypical ductal hyperplasia [ADH], n = 5) and associated ADH (n = 2), ductal carcinoma in situ (ductal carcinoma in situ [DCIS], n = 11), lobular carcinoma in situ (n = 3), and/or IBC with ductal and/or lobular differentiation (n = 6). Aside from 1 DCIS sample, all sequenced lesions in each patient were clonally related to one another. Recurrent alterations in FEA and FEA/early ADH included PIK3CA (69%), NCOR1 (31%), CBFB (31%), RUNX1 (15%), and GATA3 (23%). The mutational repertoire of FEA was similar to The Cancer Genome Atlas luminal IBC, except CBFB and NCOR1 mutations, which were more frequent in FEA and (along with PIK3CA, FOXA1, and CDKN1B) not always identified in paired morphologically advanced lesions. Compared with FEA, DCIS had more mutations and chromosomal copy number changes, including aberrations in PI-3 kinase pathway, transcription factors, chromatin remodeling genes, and TP53. CDH1 mutations identified in lobular carcinoma in situ were absent in paired FEA. Analysis of cases with ductal and lobular heterogeneity, including Rosen's triad, confirmed the shared clonality of the ductal and lobular components with features of genetic divergence. IBC of no special type were genetically similar to DCIS, and tubular carcinomas were similar to FEA. The results reveal the mutational repertoire of FEA and the genetics of early breast neoplasia, highlighting the clonal relationships of FEA to ductal and lobular carcinomas. Luminal breast cancer-associated genetic alterations are present at the earliest morphologically recognized stages of neoplasia.

Humans↗

PubMed2025

Image-guided biopsy of breast lesions-when to use what biopsy technique.

In recent years, minimally invasive diagnostic options for breast lesions have expanded, but consensus on optimal biopsy techniques and imaging combinations remains lacking. This study, driven by an adapted RAND-UCLA Appropriateness Method and insights from eight experts in breast biopsy from across the world, aims to create consensus for selecting biopsy techniques. Highlighted findings suggest Vacuum-Assisted Biopsy (VAB) for lesions visible exclusively at mammography/tomosynthesis (with or without contrast enhancement) or MRI. Core-needle biopsy (CNB) takes precedence for masses over 5 mm visible under US. The selection of other biopsy techniques during US-guided procedures depends on lesion type, size, and sampling indication. VAB is preferred for smaller masses (< 5 mm), complex cystic and solid lesions with small solid parts, small intraductal masses, architectural distortions, and calcifications visible on US. In re-biopsy scenarios for inconclusive findings or high-risk lesions, the panel suggests two VAB extensions: Extended Vacuum-Assisted Biopsy (EVAB) for unambiguous lesion classification and Vacuum-Assisted Excision (VAE) for complete lesion removal. Furthermore, the panel provides detailed input on how to handle specific cases, such as re-biopsy for lobular neoplasia, flat epithelial atypia and atypical ductal hyperplasia. Surgical excision is advised for DCIS and benign or borderline phyllodes tumors found through initial CNB or VAB. In conclusion, an international expert group formulated recommendations on diagnostic breast biopsies under image guidance, aiming to ensure accurate diagnosis worldwide by providing practical advice on needle selection and biopsy approach. KEY POINTS: Evidence-based literature on the preferred biopsy technique and imaging combination for the diagnosis of breast lesions is sparse, and a general consensus is not available. The selection of biopsy technique for different image-guided procedures depends on lesion type, size, and sampling indication. This international expert panel consensus statement addresses standard approaches for varying biopsy indications.

Breast cancer↗

PubMed1978

Pathogenesis of rat colon carcinomas induced by N-methyl-N-nitrosourea.

Colon specimens were obtained from 45 young male and female inbred CDF rats between 11 and 42 weeks after they began to receive intrarectal injections of the carcinogen N-methyl-N-nitrosourea (MNU) 43--108 mg, total dose); specimens were also obtained from 26 control rats. Well-developed tumors from rats receiving MNU generally presented grossly as polyps; histologically, as invasive adenocarcinomas that had not metastasized. These tumors resembled their human counterparts. Focal epithelial atypias were found in grossly normal mucosa both from rats that had not yet developed tumors and from tumor-bearing rats. Such foci typically consisted of low columnar cells with enlarged nuclei, increased number of mitoses, cytoplasmic basophilia, and reduced cytoplasmic mucus. Serial section studies of minute foci of atypia indicated that some of them arose from normal deep crypt cells. Transitions were frequently found between atypical foci and in situ or invasive carcinomas. Less commonly, adenomatous epithelium was identified in the early lesions or within the frank adenocarcinomas. It was concluded that most invasive carcinomas in this rat model originate in foci of epithelial atypia, which are found with increasing frequency in the flat mucosa during treatment with MNU, but that some carcinomas also arise from adenomatous epithelium.

Adenocarcinoma↗

PubMed1979

Morphologic survey of the condylomatous lesions in dysplastic and neoplastic epithelium of the uterine cervix.

One hundred eighty-four women with a histologically verified dysplastic or neoplastic lesion in the uterine cervical epithelium were histologically assessed with special reference to the presence of the various histological types of condyloma in these epithelial specimens. Histological changes fulfilling the previously outlined criteria of the flat, inverted, and papillomatous condylomas were encountered in 91 (49.4%) women. Condylomatous lesions were seen in association with all degrees of epithelial atypia from mild dysplasia to frankly invasive cervical carcinoma, which seemed to develop at significantly earlier age when concomitant condylomatous lesion was present than with its absence (p less than 0.001). The serious consideration of the relationship between the condylomatous lesions and the uterine cervical was emphasized.

Condylomata Acuminata↗