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; Shaomin Hu, MD, PhD, staff pathologist, Cleveland Clinic; S. Emily Bachert, MD, breast pathology fellow, Brigham and Women’s Hospital, Boston; and Amarpreet Bhalla, MD, assistant professor of pathology, Albert Einstein College of Medicine, Montefiore Medical Center.

Pseudocarcinomatous squamous hyperplasia involving bone

August 2021—Pseudocarcinomatous squamous hyperplasia within the bone is uncommon and closely mimics well-differentiated squamous cell carcinoma. It arises from cutaneous or mucosal surfaces and grows directly into the bone. The authors conducted a study in which they analyzed a series of 31 pseudocarcinomatous squamous hyperplasia (PSH) cases and discussed the clinicopathologic features that distinguished PSH from squamous cell carcinoma (SCC). The 31 cases were composed of 21 males, nine females, and one person of unknown gender, all of whom were between the ages of 20 and 87 years (average, 59 years). Involved anatomical sites included the mandible (17), maxilla (five), toes (four), and finger, femur, tibia, ischium, and unknown (one case each). Fourteen patients had a history of SCC of the oral cavity with extension into the mandible. Thirteen of these were treated with resection and chemoradiation, while one was treated with only resection. Four patients had medication-related osteonecrosis of the jaw, while three had peripheral vascular disease and diabetes mellitus, three had previous trauma, three had osteomyelitis, three had unknown medical histories, and one had hematologic malignancy. All cases exhibited severe osteomyelitis and nests of reactive keratinizing squamous epithelium that matured toward the bone surface and lacked significant atypia or mitotic activity but permeated the medullary cavity. Patients with previous SCC developed PSH after two months to eight years (average, four years). Nineteen of 30 patients had follow-up of two to 48 months (average, 17 months). Six patients experienced repeated debridements over two months to one year, and no patient developed SCC. The authors concluded that PSH involving bone is infrequent, complicates severe osteomyelitis, and is often therapy related. The clinical findings usually are not concerning for malignancy. However, the histologic findings are an important diagnostic pitfall because they mimic SCC.

Spasić S, Kryvenko ON, Kerr DA, et al. Pseudocarcinomatous squamous hyperplasia involving bone: A diagnostic pitfall mimicking squamous cell carcinoma. Am J Surg Pathol. 2021;45(2):263–269.

Correspondence: Dr. A. E. Rosenberg at arosenberg@med.miami.edu

Intraoperative frozen consultation for GI signet ring cell carcinoma

Signet ring cell carcinoma is difficult to recognize on intraoperative frozen sectioning and has high false-negative rates. The authors conducted a study to investigate common factors that contribute to discrepancies between intraoperative frozen diagnoses and those made on review of permanent sections. They summarized their experiences and lessons learned regarding minimizing errors on intraoperative frozen diagnoses of gastrointestinal signet ring cell carcinoma (SRCC). The authors retrospectively examined their pathology database from May 25, 2000 to Jan. 1, 2018 and re-reviewed intraoperative frozen sections and permanent hematoxylin-and-eosin (H&E) slides for specimens with confirmed SRCC on permanent sections. The study included 83 specimens from 50 patients and found an accuracy rate of 85.5 percent when comparing initial intraoperative frozen interpretations with the subsequent permanent section diagnoses for all SRCC cases. Among the most common factors causing discrepancies in diagnosing SRCC between intraoperative frozen procedures and permanent sections were the resemblance of clusters of SRCC cells to a myxoid background; SRCC cells frequently presenting as normal or reactive cells (histiocytes, macrophages, large reactive lymphocytes, plasma cells, or adipocytes) due to their relatively clear or depleted cytoplasmic mucin; and histological sampling errors leading to misses of small foci of SRCC on frozen section slides. An accurate diagnosis of SRCC during intraoperative frozen consultations remains challenging. Based on the authors’ experiences and lessons, the most important strategies to reduce diagnostic errors are understanding the unusual histomorphological features of SRCC cells on frozen sections, including, but not limited to, intracellular mucin depletion, absence of desmoplasia, and lack of adjacent precancerous changes. Another strategy to reduce diagnostic errors involves paying close attention to the abrupt pattern transition from normal architecture (for example, glandular or submucosal loose connective tissue) to a myxoid or inflammatory-like appearance, or both, as SRCC cells with rich intracellular mucin may present a myxoid appearance after frozen processing.

Chen F, Jiang K, Han B. Diagnostic challenges of intra-operative frozen consultation for gastrointestinal signet ring cell carcinoma. Histopathology. 2021;78:300–309.

Correspondence: Dr. Bing Han at bhan@pennstatehealth.psu.edu

IHC analysis of gastrointestinal and Müllerian phenotypes of ovarian mucinous cystadenomas

Mucinous cystadenoma is one of the most common benign ovarian neoplasms. However, the immunophenotypes and histogenetic relationships of mucinous cystadenomas with a Müllerian-type epithelium have not been explored fully. The authors conducted a study in which they elucidated the direction of differentiation of the mucinous epithelium that constitutes mucinous cystadenomas. They paid special attention to the gastrointestinal (GI)-type mucinous epithelium and its association with background Müllerian-type epithelium. IHC was performed in 139 cases of mucinous cystadenoma to evaluate the expression of Claudin-18 (CLDN18), a novel marker of gastric differentiation; CDX2, a marker of intestinal differentiation; and estrogen receptor (ER), a marker of Müllerian differentiation. GI differentiation characterized by CLDN18 or CDX2 positivity, or both, was observed in the mucinous epithelium of most mucinous cystadenomas (129 of 139 cases; 93 percent). In a subset of these cases, the tumor was composed of mucinous epithelium exhibiting an intermediate GI and Müllerian phenotype (CLDN18+/CDX2±/ER+). Of note, a transition from background Müllerian-type epithelium to mucinous epithelium with GI differentiation was identified in 12 cases. A minor subset (six percent) of mucinous cystadenomas was considered a pure Müllerian type because the epithelium exhibited a CLDN18–/CDX2–/ER+ immunophenotype. The authors concluded that mucinous cystadenomas consist of three major subtypes: GI, Müllerian, and intermediate. Most mucinous cystadenomas are GI type and should be considered a precursor of GI-type mucinous borderline tumors. The presence of intermediate-type mucinous cystadenomas and areas of transition from Müllerian-type to GI-type epithelium suggest that GI-type mucinous epithelium can arise from Müllerian duct derivatives or surface epithelium exhibiting Müllerian metaplasia in the ovary.

Halimi SA, Maeda D, Ushiku-Shinozaki A, et al. Comprehensive immunohistochemical analysis of the gastrointestinal and Müllerian phenotypes of 139 ovarian mucinous cystadenomas. Hum Pathol. 2021;109:21–30.

Correspondence: Dr. D. Maeda at maeda-tky@umin.ac.jp

Spectrum of serrated colorectal lesions: new entities and unanswered questions

Hyperplastic polyps of the colon and rectum historically were not associated with an increased risk of developing colorectal cancer. Recognition of variants of serrated colorectal lesions that possess relatively subtle but significant morphological differences to those of hyperplastic polyps and that could be associated with epithelial dysplasia and colorectal cancer led to the characterization of sessile serrated lesions (SSLs) and traditional serrated adenomas (TSAs). These links were supported by the identification of genetic alterations—for example, BRAF and KRAS mutations—that are commonly found in hyperplastic polyps, SSLs, TSAs, and colorectal cancer. The “serrated pathway” to colorectal cancer may progress faster than the traditional adenoma-carcinoma sequence, emphasizing the importance of identifying these lesions. The diagnostic histological criteria for SSLs have been more clearly defined in parallel with efforts to increase recognition of these lesions at endoscopy. Lesions showing morphological and molecular features overlapping those of hyperplastic polyps, SSLs, and TSAs have been described. These include the mucin-rich TSA, serrated tubulovillous adenoma, and those showing mixed histological features—for example, comprising differing combinations of hyperplastic polyps, SSLs, and TSAs. Morphological and molecular study of this range of lesions is providing insights into the relationship of serrated colorectal lesions to each other and with colorectal cancer.

Bateman AC. The spectrum of serrated colorectal lesions—new entities and unanswered questions. Histopathology. 2021;78:780–790.