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, associate pathologist, Brigham and Women’s Hospital, Boston; and Amarpreet Bhalla, MD, assistant professor of pathology, Albert Einstein College of Medicine, Montefiore Medical Center.
Use of binary subclassification in risk stratifying thyroid fine-needle aspiration specimens as AUS
May 2024—The Bethesda System for Reporting Thyroid Cytopathology described four subclasses of atypia within the atypia of undetermined significance category: nuclear (AUS-Nuc), architectural (AUS-A), oncocytic (AUS-Onc), and atypia not otherwise specified (AUS-NOS). Accumulating evidence supports the use of a binary AUS subclassification scheme based primarily on the presence of nuclear atypia only. The authors conducted a study to compare the risk stratification of binary versus four-tier AUS subclassification systems among AUS nodules with molecular or histologic follow-up, or both. The study included thyroid aspirates classified as AUS and tested using Afirma (Veracyte Inc.) between June 2013 and July 2021. Histological classification was considered the final outcome for resected nodules. For unresected nodules, benign Afirma results were considered low-risk outcomes, similar to histologically benign nodules. Suspicious or nondiagnostic Afirma results were considered indeterminate outcomes. The prevalence of outcomes warranting surgery (noninvasive follicular thyroid neoplasm with papillary-like nuclear features [NIFTP] or cancer) was calculated for each AUS subclass. A total of 559 AUS nodules that had undergone Afirma testing were identified. After excluding nodules with indeterminate molecular outcomes, NIFTP or cancer prevalence for AUS-Nuc was 21 percent (57 of 266), which was higher than that for AUS-A (six percent, 11 of 188), AUS-Onc (eight percent, four of 53), and AUS-NOS (zero of nine). A binary AUS subclassification scheme based on nuclear atypia differed significantly with regard to NIFTP or cancer prevalence (21 percent versus six percent, P < .0001). The authors concluded that binary reporting of AUS subclasses based on nuclear atypia distinguishes cases with a higher risk of NIFTP or cancer. There is a low but non-negligible prevalence of NIFTP or cancer in cases without nuclear atypia.
Guzmán-Arocho YD, VanderLaan PA, Nishino M. Binary subclassification scheme (AUS-nuclear versus AUS-other) adequately risk-stratifies thyroid fine needle aspiration specimens classified as atypia of undetermined significance. J Am Soc Cytopathol. 2024;13:23–32.
Correspondence: Dr. Michiya Nishino at mnishin1@bidmc.harvard.edu
Efficacy of preoperative biopsy in predicting histologic grade of resected lung adenocarcinoma
A novel histologic grading system for invasive lung adenocarcinoma was included in the 2020 World Health Organization lung cancer classification. Studies have reported that this classification correlates more strongly with the prognosis of invasive lung adenocarcinoma (LUAD) than the previous classification. The authors conducted a study to evaluate the concordance of newly established LUAD grades, retrospectively, between preoperative biopsy and surgically resected samples. They also examined factors affecting grade concordance. The study included surgically resected specimens from 222 patients who had invasive LUAD and their preoperative biopsies collected between January 2013 and December 2020. The authors determined the histologic subtypes of preoperative biopsy and surgically resected specimens and classified them separately according to the novel World Health Organization (WHO) grading system. The overall concordance rate of the novel WHO grades between preoperative biopsy and surgically resected samples was 81.5 percent, which was higher than that of the predominant subtype. When stratified by grade, the concordance rates of grades 1 (well differentiated, 84.2 percent) and 3 (poorly differentiated, 89.1 percent) were found to be superior to that of grade 2 (moderately differentiated, 66.2 percent). Overall, the concordance rate was not significantly different based on biopsy characteristics, including the number of biopsy samples, biopsy sample size, and tumor area size. However, the concordance rates of grades 1 and 2 were significantly higher in tumors with smaller invasive diameters and that of grade 3 was significantly higher in tumors with larger invasive diameters. The authors concluded that preoperative biopsy specimens can predict the novel WHO grades, especially grades 1 and 3 of surgically resected specimens, more accurately than the former grading system, regardless of preoperative biopsy or clinicopathologic characteristics.
Ohtani-Kim SJ, Taki T, Tane K, et al. Efficacy of preoperative biopsy in predicting the newly proposed histologic grade of resected lung adenocarcinoma. Mod Pathol. 2023. doi:10.1016/j.modpat.2023.100209
Correspondence: Dr. Tetsuro Taki at tetaki@east.ncc.go.jp
Distinguishing lymphoglandular complex-like colorectal carcinoma from adenomas
It can be difficult to distinguish colorectal carcinoma that is surrounded by well-circumscribed lymphoid tissue from adenomas involving lymphoglandular complexes. The authors assessed a multi-institutional international cohort of 20 colorectal carcinomas with associated prominent lymphoid infiltrates, which they referred to as lymphoglandular complex-like carcinoma (LGCC). They obtained clinical information to evaluate for age, sex, and such endoscopic features as lesion size and shape, location, lymph node status, patient follow-up, American Joint Committee on Cancer stage, and mismatch repair status. They recorded the presence of histologic features, including haphazard gland distribution, gland angulation, gland fusion, solid nest formation, single-cell formation, stromal desmoplasia, lymphovascular invasion and perineural invasion, presence of lamina propria, low- or high-grade cytologic atypia, goblet cells in the invasive component, and presence of a surface lesion. Nine of 13 LGCC cases were described endoscopically as sessile polyps and were an average size of 1.56 cm. LGCCs were associated with a surface lesion in all but two cases (90 percent; 18 of 20). The majority of surface lesions (15 of 18) were tubular adenomas, though a subset was associated with sessile serrated lesions with dysplasia (three of 18). All cases of LGCC demonstrated haphazard gland distribution and gland angulation, fusion, or solid nest formation. A portion demonstrated single-cell infiltration (35 percent) and desmoplasia (50 percent). Lymphovascular invasion was rarely present (five percent). A subset of cases (10 percent) invaded beyond the submucosa. Deficient mismatch repair was present in 22 percent of cases (two of nine) for which it was performed. In cases of colectomy or completion colectomy, nodal metastasis was present in 38 percent (three of eight). No patients experienced disease recurrence or disease-specific mortality. The authors concluded that LGCC represents an enigmatic subset of carcinomas that should be distinguished from adenomas involving lymphoglandular complexes due to its varying prognostic outcomes.
Yilmaz O, Westerhoff M, Panarelli N, et al. Lymphoglandular complex-like colorectal carcinoma—a series of 20 colorectal cases, including newly reported features of malignant behavior. Am J Surg Pathol. 2024;48(1):70–79.
Correspondence: Dr. Osman Yilmaz at osmanhy@gmail.com
Age-related histopathological findings in temporal arteries
Giant cell arteritis is a systemic vasculitis affecting medium-sized and large arteries in patients 50 years and older. The involvement of temporal arteries can lead to such complications as blindness and stroke. While the diagnostic gold standard is temporal artery biopsy (TAB), comorbidities and age-related changes can make it difficult to interpret such specimens. The authors conducted a study to establish a baseline of temporal artery changes in subjects without giant cell arteritis to facilitate the interpretation of TAB. Bilateral temporal artery specimens were collected from 100 consecutive eligible postmortem examinations. Decedents were divided into four age groups and their specimens semiquantitatively evaluated for eccentric intimal fibroplasia; disruption and calcification of the internal elastic lamina (IEL); medial attenuation; and degree of lymphocytic inflammation of the peri-adventitia, adventitia, media, and intima. The individual scores of intimal fibroplasia, IEL disruption, and medial attenuation were added to yield a combined score. Seventy-eight decedents were included in the final analysis, after excluding 22 based on lack of clinical information or inability to collect temporal artery tissue. A total of 128 temporal artery specimens from 50 decedents with bilateral sampling and 28 with unilateral sampling were examined. The authors found that intimal proliferation, IEL loss, IEL calcification, and combined score increased with age in a statistically significant fashion. Comparison of the oldest age group with the others showed statistically significant differences, while no statistically significant differences were observed between the three youngest groups. The authors concluded that senescent arterial changes and those attributed to healed giant cell arteritis exhibit histological similarity, and such changes increase proportionally with age. The combined score demonstrates significant association with age overall and represents a potential summary parameter for continued development as a means to “normalize” the temporal artery biopsies of older people.
Kendziora RW, Maleszewski JJ, Lin T, et al. Age-related histopathological findings in temporal arteries. Histopathology. 2023;83(5):782–790.
Correspondence: Dr. J. J. Maleszewski at maleszewski.joseph@mayo.edu