Anatomic Pathology Selected Abstracts

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Editors: Rouzan Karabakhtsian, MD, PhD, professor of pathology and director of the Women’s Health Pathology Fellowship, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY; Nicole Panarelli, MD, associate professor of pathology, Albert Einstein College of Medicine, Montefiore Medical Center; Shaomin Hu, MD, PhD, gastrointestinal/liver pathology fellow, University of Chicago; and S. Emily Bachert, MD, pathology resident, Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington.

Management of flat epithelial atypia in breast CNBs with radiologic-pathologic concordance

May 2020—Flat epithelial atypia is an alteration of terminal duct lobular units by a proliferation of ductal epithelium with low-grade atypia. No consensus exists regarding whether the diagnosis of flat epithelial atypia in core needle biopsy necessitates excision. The authors retrospectively identified all in-house core needle biopsies with flat epithelial atypia obtained at their institution between January 2012 and July 2018. They reviewed all core needle biopsy slides and assessed radiologic-pathologic concordance. An upgrade was defined as invasive carcinoma or ductal carcinoma in situ in the excision, or both. The excision slides of all upgraded cases were re-reviewed. Of approximately 15,700 consecutive core needle biopsies in the study period, 106, from as many patients, yielded flat epithelial atypia alone or with classic lobular neoplasia. Fifty-two core needle biopsies (40 patients with prior or concurrent carcinoma and 12 without excision) were excluded from the study. After re-review, the authors reclassified 14 cases—two as marked nuclear atypia, 10 as focal atypical ductal hyperplasia, and two as benign. The final flat epithelial atypia study cohort consisted of 40 core needle biopsies from 40 women. Core needle biopsy targeted mammographic calcifications in 36 (90 percent) cases, magnetic resonance imaging nonmass enhancement in three (eight percent), and a sonographic mass in one (two percent). All core needle biopsies were deemed radiologic-pathologic concordant. Flat epithelial atypia was present alone in 34 core needle biopsies and with lobular neoplasia in six. Excision yielded two low-grade invasive carcinomas, each spanning less than 2 mm, which were identified in tissue sections without biopsy site changes. The remaining 38 cases yielded no upgrade. Classic lobular neoplasia did not affect the upgrade. The authors demonstrated a low upgrade rate for flat epithelial atypia of five percent, which consisted of minute foci of low-grade “incidental” invasive carcinoma not associated with the biopsy site. They concluded that nonsurgical management may be considered for patients without prior or concurrent carcinoma and a radiologic-pathologic concordant core needle biopsy diagnosis of flat epithelial atypia.

Grabenstetter A, Brennan S, Salagean ED, et al. Flat epithelial atypia in breast core needle biopsies with radiologic-pathologic concordance: Is excision necessary? Am J Surg Pathol. 2020;44(2):182–190.

Correspondence: Dr. Anne Grabenstetter at grabensa@mskcc.org

Spectrum of gastrointestinal tract pathology in a multicenter cohort of 43 Cowden syndrome patients

Most patients with Cowden syndrome have lesions in the gastrointestinal tract that are characterized by multiple polyps of various histologic types in the large bowel, polyps in the upper gastrointestinal tract, and esophageal glycogenic acanthosis. However, pathologists are often unaware of the distinctive polyposis phenotype of Cowden syndrome. The authors conducted a multicenter study in which they reported on the spectrum of gastrointestinal manifestations in a series of 43 Cowden syndrome patients who had at least one endoscopy. The patients’ median age at the time of first endoscopy was 46 years, and 58 percent of them were women. In 24 of 29 (83 percent) patients tested, a pathogenic germline mutation in PTEN was identified. The histology from 199 endoscopy procedures—67 upper gastrointestinal tract endoscopies and 132 colonoscopies—was reviewed. Hamartomatous polyps of the large bowel were the most common lesions, present in 85 percent of patients. These polyps showed varied histology, including lymphoid aggregates in 55 percent of patients and a lipomatous component in 52 percent, ganglioneuromatous component in 52 percent, and fibrous-rich component in 14 percent. Polyps with at least two different stromal components were found in 55 percent of patients, and inflammatory polyps were present in 21 percent of patients. Conventional adenomas and serrated polyps were identified in 48 percent and 62 percent of patients, respectively. The most common lesions in the upper gastrointestinal tract were esophageal glycogenic acanthosis (37 percent), gastric hamartomatous polyps (47 percent), and duodenal hamartomatous polyps (20 percent). All patients with glycogenic acanthosis who had a colonoscopy had hamartomatous polyps of the large bowel. The diagnosis of Cowden syndrome in five patients was established after the pathology report raised suspicion for the diagnosis. The authors concluded that pathologists who are aware of the characteristic admixture of lesions in Cowden syndrome can play an essential role in recommending referral to genetic counseling and gene testing. Early diagnosis of Cowden syndrome is important, as these patients and their relatives are at increased risk for developing multiple cancers.

Borowsky J, Setia N, Rosty C, et al. Spectrum of gastrointestinal tract pathology in a multicenter cohort of 43 Cowden syndrome patients. Mod Pathol. 2019;32:1814–1822.

Correspondence: Dr. Ian S. Brown at ianbrown@envoi.com.au

Use of TFE3 in diagnosis of Xp11 translocation renal cell carcinoma and clear cell renal cell carcinoma

TFE3 has been deemed a good marker for the diagnosis of Xp11 translocation renal cell carcinoma. However, the significance of TFE3 in other types of renal cell carcinomas remains unclear. The authors conducted a study in which they performed TFE3 IHC staining using the automated Ventana BenchMark XT system in 1,818 consecutive renal cell carcinomas. They verified the strong positive cases with TFE3 break-apart FISH and RNA sequencing. Among the 27 renal cell carcinomas with TFE3 strong-positive immunostaining, 20 cases were diagnosed as Xp11 translocation renal cell carcinoma and seven as clear cell renal cell carcinoma. The authors further analyzed their morphology, clinicopathological features, and IHC markers—CK7, CD117, CD10, P504s, vimentin, CA-IX, AE1/AE3, EMA, HMB45, melan-A, and cathepsin K. Pale to eosinophilic flocculent cytoplasm and psammomatous calcification were seen only in Xp11 translocation renal cell carcinomas (P < .05). Within three years, the four patients with Xp11 translocation renal cell carcinomas with pT3a stage had local recurrence and distant metastasis, and two of them died. Expression of vimentin, CA-IX, AE1/AE3, and EMA differed significantly between them (P < .05). CA-IX was diffusely strong-positive in clear cell renal cell carcinomas but negative or focally mild-positive in Xp11 translocation renal cell carcinomas. The authors concluded that their study demonstrates that a very small minority (0.4 percent) of clear cell renal cell carcinomas have TFE3 strong-positive immunostaining, which highlights a potential pitfall of diagnosing Xp11 translocation renal cell carcinomas by TFE3 IHC. CA-IX is a good marker to distinguish clear cell renal cell carcinoma with TFE3 strong-positive immunostaining from Xp11 translocation renal cell carcinoma. Tumor necrosis could be a potential factor relevant to pT3a stage, which, in turn, may be a high-risk factor for patients with Xp11 translocation renal cell carcinomas.

Yang B, Duan H, Cao W, et al. Xp11 translocation renal cell carcinoma and clear cell renal cell carcinoma with TFE3 strong positive immunostaining: morphology, immunohistochemistry, and FISH analysis. Mod Pathol. 2019;32(10):1521–1535.