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; S. Emily Bachert, MD, associate pathologist, Brigham and Women’s Hospital, Boston; Amarpreet Bhalla, MD, assistant professor of pathology, Albert Einstein College of Medicine, Montefiore Medical Center; Divya Sharma, MD, associate professor, Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center; and Paula Toro, MD, pathology resident, Cleveland Clinic.
Features of connective tissue disease-associated interstitial lung disease in transbronchial cryobiopsies
June 2025—Transbronchial cryobiopsies are increasingly used to diagnose interstitial lung disease, but published information on the features of specific manifestations of ILD in cryobiopsies is lacking. Therefore, the authors sought to provide pathologic guidelines for separating usual interstitial pneumonia (UIP) of idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis (FHP), and connective tissue disease-associated interstitial lung disease (CTD-ILD) in cryobiopsies. They examined 120 cryobiopsies from patients with CTD-ILD established via multidisciplinary discussion and compared them with a prior series of 121 biopsies from patients with IPF or FHP also established via multidisciplinary discussion. A nonspecific interstitial pneumonia (NSIP) pattern alone was seen in 36 of 120 (30 percent) CTD-ILD, three of 83 (3.6 percent) FHP, and two of 38 (5.2 percent) IPF cases, statistically favoring a diagnosis of CTD-ILD. A combination of NSIP plus organizing pneumonia was present in 29 of 120 (24 percent) CTD-ILD, two of 83 (2.4 percent) FHP, and none of 38 (zero) IPF cases, also favoring a diagnosis of CTD-ILD. A UIP pattern, defined as fibroblast foci plus patchy fibrosis that may include fibrotic architectural distortion or honeycombing, was identified in 28 of 120 (23 percent) CTD-ILD, 45 of 83 (54 percent) FHP, and 27 of 38 (71 percent) IPF cases and supported a diagnosis of FHP or IPF. The number of lymphoid aggregates/mm2 and fibroblast foci/mm2 did not differ in IPF, CTD-ILD, or FHP cases with a UIP pattern. Interstitial giant cells supported a diagnosis of FHP or CTD-ILD over IPF but were seldom present. In the correct clinical or radiological context, the pathological findings of NSIP, and NSIP plus organizing pneumonia in particular, favor a diagnosis of CTD-ILD in a cryobiopsy. However, CTD-ILD with a UIP pattern, FHP with a UIP pattern, and IPF generally cannot be distinguished.
Churg A, Poletti V, Ravaglia C, et al. Pathological features of connective tissue disease-associated interstitial lung disease in transbronchial cryobiopsies. Histopathology. 2025;86(2):260–267.
Correspondence: Dr. Andrew Churg at achurg@mail.ubc.ca
Use of AI to assess tumor cell nuclear size in esophageal squamous cell carcinoma
Tumor cell nuclear size indicates malignant potential in breast cancer. However, its clinical significance in esophageal squamous cell carcinoma (ESCC) is unknown. Artificial intelligence (AI) can be used to quantitatively evaluate histopathological findings. The authors conducted a study to measure nuclear size in ESCC using AI and elucidate its clinical significance. They investigated the relationship between nuclear size assessed by AI and prognosis in 138 patients with ESCC who underwent curative esophagectomy. H&E-stained slides from the deepest tumor sections were digitized. Using Indica Labs’ Halo AI DenseNet v2, the authors created a deep learning classifier that identified tumor cells with a nuclear size area greater than 20 μm2. Median nuclear size was 40.14 μm2, which was used to divide patients into nuclear size-high and nuclear size-low groups (n = 69 per group). Five-year overall survival and relapse-free survival rates were significantly lower in the nuclear size-high group (43.2 and 39.6 percent, respectively) than in the nuclear size-low group (67.7 and 49.6 percent, respectively). Multivariate analysis showed that greater tumor depth and nuclear size-high status (hazard ratio [HR], 1.79; P = .032) were independent risk factors for overall survival. In 77 cases with neoadjuvant chemotherapy, increased tumor depth and nuclear size-high status (HR, 1.99; P = .048) were independent prognostic factors for unfavorable overall survival. Compared with the nuclear size-low group, the nuclear size-high group had significantly higher anisokaryosis; higher Ki-67 expression, as calculated by AI analysis of immunostaining; and higher nuclear size heterogeneity, as examined by dividing the tumors equally into square tiles. The authors concluded that nuclear size assessed by AI may be a simple and useful prognostic factor for ESCC.
Kouzu K, Tsujimoto H, Nearchou IP, et al. Prognostic impact of tumor cell nuclear size assessed by artificial intelligence in esophageal squamous cell carcinoma. Lab Invest. 2025. doi.org/10.1016/j.labinv.2024.102221
Correspondence: Dr. Hironori Tsujimoto at tsujihi@ndmc.ac.jp
Inevitability of fragmentation of prostate core biopsies: a quality improvement initiative
Core biopsies are standard of care for the diagnosis and surveillance of prostate cancer. Fragmentation of prostate core biopsies makes numeric assessment of cancer challenging and increases the risk of inaccurate staging, with direct implications for management. The authors conducted a study to determine factors responsible for such fragmentation at their institution. Prostate core biopsies obtained at two hospitals during one week were prospectively identified. Biopsies submitted in formalin-filled specimen jars, either mounted on a nonadherent dressing pad (Telfa, Medtronic) or freely suspended, were grossed by pathologists’ assistants. Fragmentation was defined as the difference between the number of cores sent by the clinician and the number of cores counted by the pathologist on microscopy. Forty-six biopsies (15 benign and 31 malignant cases) were identified. The authors cumulatively received 535 specimen jars for patients, of which 309 (57.8 percent) contained more than one biopsy core per jar. A total of 230 of the 535 (43 percent) jars contained specimens mounted on Telfa, and 185 of the 535 (34.6 percent) specimens had histologic evidence of adenocarcinoma. The overall fragmentation rate was 157 of 535 (29.3 percent). The lowest fragmentation rate was seen when one core was submitted per jar, regardless of mounting method (31 of 226 [14 percent] for one per jar versus 126 of 309 [41 percent] for more than one per jar; P< .001). The rate of fragmentation was five of 18 (27.8 percent) for one Telfa-mounted core versus 26 of 203 (12.8 percent) for a single unmounted core (P = .24). A significant increase in fragmentation of Telfa-mounted cores was seen when there were three per jar (32 of 70 [46 percent] mounted fragmented specimens versus nine of 47 [19 percent] unmounted fragmented specimens; P = .01). The authors concluded that submission of more than one biopsy core per jar and use of Telfa for mounting are associated with increased fragmentation. They recommend limiting submission to one core per jar and avoiding the practice of mounting cores on Telfa pads.
Shenoy K, Cote RJ, Kini G, et al. Is fragmentation of prostate core biopsies inevitable? A quality improvement initiative. Arch Pathol Lab Med. 2025;149(1):50–54.
Correspondence: Dr. Richard J. Cote at rcote@wustl.edu
Clinicopathologic and molecular evaluation of botryoid-type embryonal rhabdomyosarcoma
Embryonal rhabdomyosarcoma is the most common subtype of rhabdomyosarcoma, occurring in the soft tissue and visceral sites of young children. It is associated with favorable outcomes. A subset that occurs in mucosal-lined luminal structures and displays a unique grape-like growth has been termed botryoid type. To further delineate the differences between conventional and botryoid-type rhabdomyosarcoma (cERMS and bERMS, respectively), the authors performed a comparative histologic review and comprehensive molecular profiling of 48 cases (25 bERMS and 23 cERMS). All tumors were subjected to a hybridization capture-based targeted, matched, tumor-normal DNA NGS assay. Mean patient age was 17 and seven years for bERMS and cERMS, respectively. Most bERMS occurred in females and had a predilection for the gynecologic tract (75 percent). CERMS had a slight male predominance and were preferentially located in abdominopelvic and paratesticular sites (30 percent each). All bERMS exhibited an exophytic, bulbous architecture accompanied by a subepithelial cambium layer. Distinctive germline alterations were detected with DICER1 (18 percent) and FH (six percent) mutations only in bERMS and rare TP53, VHL, and APC mutations in cERMS. Similarly, contrasting somatic genomic landscapes were observed, with frequent DICER1 (52 percent) and TP53 (36 percent) alterations exclusively in bERMS. Cartilaginous differentiation was only observed in DICER1-mutated bERMS. All patients had longitudinal follow-up. BERMS patients with somatic/germline DICER1 mutations showed significantly improved recurrence-free survival compared with DICER1 wild-type patients. Moreover, patients with bERMS showed a higher rate of disease-specific survival than those who had cERMS (eight percent and 30 percent died from the disease, respectively). The authors’ findings reveal divergent genomic topographies between the two groups, with bERMS showing unique germline and somatic abnormalities, including enrichment in DICER1 and TP53 alterations, and a trend toward improved patient survival.
Sharma AE, Dermawan JK, Chiang S, et al. Botryoid-type embryonal rhabdomyosarcoma: A comprehensive clinicopathologic and molecular appraisal with cross-comparison to its conventional-type counterpart. Am J Surg Pathol. 2024;48(12):1557–1567.
Correspondence: Dr. Cristina R. Antonescu at antonesc@mskcc.org