Anatomic pathology selected abstracts

Create PDF

Correspondence: Dr. Daniel N. Johnson at daniel.johnson1@northwestern.edu

Use of targeted NGS to assess serrated epithelial change as a precursor to IBD-associated colorectal neoplasia

Serrated epithelial change manifests in patients with long-standing inflammatory bowel disease and is characterized by disorganized crypt architecture, irregular serrations, and goblet cell-rich epithelium. The serrated nature of serrated epithelial change (SEC) is reminiscent of serrated colorectal polyps, which frequently harbor KRAS/BRAF mutations. However, SEC is not only histologically distinct from sporadic serrated polyps but also associated with colorectal neoplasia. Whether SEC is a precursor to inflammatory bowel disease-associated neoplasia remains unclear. To further define the relationship of SEC with serrated colorectal polyps and inflammatory bowel disease-associated neoplasia, the authors performed targeted next-generation sequencing (NGS) on colorectal specimens that included SEC without dysplasia/neoplasia (n = 10), SEC with separate foci of associated dysplasia/adenocarcinoma from the same patients (n = 17), and uninvolved mucosa (n = 10) from 14 patients. In addition, they molecularly profiled specimens that were sessile serrated lesion (SSL)-like or serrated lesion, not otherwise specified (SL-NOS), from 11 patients who also had inflammatory bowel disease. This control cohort included SSL-like/SL-NOS without dysplasia/neoplasia (n = 11), SSL-like/SL-NOS with associated low-grade dysplasia (n = 2), and uninvolved mucosa (n = 8). Using NGS, the most frequently mutated gene in SEC without neoplasia and associated dysplasia/adenocarcinoma from separate foci in the same patients was determined to be TP53. Recurrent TP53 mutations were present in 50 percent of SEC specimens without dysplasia/neoplasia. Alterations in TP53 were detected at a prevalence of 71 percent in low-grade dysplasia, 83 percent in high-grade dysplasia, and 100 percent in adenocarcinoma. Paired sequencing of SEC and associated neoplasia revealed identical TP53 missense mutations in three patients. In contrast, 91 percent of SSL-like/SL-NOS specimens without dysplasia/neoplasia harbored KRAS/BRAF mutations, which were conserved in associated low-grade dysplasia. No genomic alterations were found in uninvolved mucosa from patients with SEC or patients with SSL-like/SL-NOS. Based on these findings, the authors concluded that SEC is distinct from SSL-like serrated colorectal lesions in patients with inflammatory bowel disease and an early precursor to inflammatory bowel disease-associated neoplasia that warrants colonoscopic surveillance.

Singhi AD, Waters KM, Makhoul EP, et al. Targeted next-generation sequencing supports serrated epithelial change as an early precursor to inflammatory bowel disease associated colorectal neoplasia. Hum Pathol. 2021;112:9–19.

Correspondence: Dr. Elizabeth A. Montgomery at eam305@med.miami.edu

Breast implant-associated ALCL: clinical follow-up and analysis of specimens of untreated patients

Breast implant-associated anaplastic large cell lymphoma (ALCL) is a distinctive type of T-cell lymphoma that arises around textured-surface breast implants. In a subset of patients, this disease can involve surrounding tissue, spread to regional lymph nodes, and rarely metastasize to distant sites. The authors conducted a study to assess sequential pathologic specimens from patients with breast implant-associated ALCL to better understand the natural history of early stage disease. To achieve this goal, they searched their files for patients who had breast implant-associated ALCL and who had undergone earlier surgical intervention with assessment of biopsies or cytologic specimens. They then focused on the patient subset in whom a definitive diagnosis was not established and, therefore, did not receive current standard-of-care therapy. The authors created a study group of 10 patients who had breast implant-associated ALCL and for whom pathologic specimens were collected 0.5 to four years before a definitive disease diagnosis was established. A comparison of these serial biopsy specimens showed persistent disease without change in pathologic stage in three patients, progression in five, and persistence versus progression in two. Six patients eventually had their implants removed via complete capsulectomy and four had partial capsulectomy. Seven patients also received chemotherapy because of invasive disease, of whom three received radiation therapy, two brentuximab vedotin after chemotherapy failure, and one allogeneic stem cell transplant. Eight patients achieved complete remission and two had partial remission after definitive therapy. At the time of last follow-up, six patients were alive without disease, one had evidence of disease, one had died of disease, and two had died of unrelated cancers. The authors concluded that this analysis of sequential specimens from patients with breast implant-associated ALCL suggests these neoplasms persist or progress over time if not treated with standard-of-care therapy.

Evans MG, Medeiros LJ, Marques-Piubelli ML, et al. Breast implant-associated anaplastic large cell lymphoma: clinical follow-up and analysis of sequential pathologic specimens of untreated patients shows persistent or progressive disease. Mod Pathol. 2021. https://doi.org/10.1038/s41379-021-00842-6

Correspondence: Dr. Roberto N. Miranda at roberto.miranda@mdanderson.org