Anatomic pathology selected abstracts

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, gastrointestinal and hepatobiliary fellow, Cleveland Clinic.

Serous-like breast carcinoma: characterization of a morphologically distinct group of tumors

December 2025—Unusual morphologic patterns of breast carcinoma can raise diagnostic consideration for metastasis or special breast cancer subtypes and, thereby, impact clinical management and treatment. The authors conducted a study in which they described rare invasive breast cancers that mimic serous carcinoma of the gynecologic tract (serous-like breast carcinomas, SLBC) and characterized their clinicopathologic, immunophenotypic, and genetic features. The patients evaluated in the study were female (n = 15; median age, 49 years) and did not have a history of gynecologic malignancy. SLBC were characterized histologically by angulated, branched, sometimes anastomosing glands with micropapillary or pseudopapillary luminal projections in desmoplastic stroma. Most SLBC were triple negative (n = 10) or HER2 positive (n = 2) and grade 2 or 3, while some were estrogen receptor low positive/HER2 negative and low grade (n = 3). CK5/6 was positive irrespective of grade or receptor status (10 of 10). All SLBC expressed GATA3, TRPS1, or mammaglobin. GATA3 was positive in 14 of 15 cases, TRPS1 in seven of seven, and mammaglobin in four of 13. SOX10 was positive in nine of 10 triple-negative and three of three estrogen receptor low-positive cases but negative in HER2-positive tumors. WT1 was universally negative, and PAX8 was focal in one mammaglobin-positive tumor. All estrogen receptor-negative SLBC were p53 aberrant and nine of 11 were p16 aberrant, whereas estrogen receptor-positive tumors were wild type for both markers (three of three). TP53 was the only frequently mutated gene and was altered in 10 of 10 estrogen receptor-negative but none of four estrogren receptor-positive tumors. Clinical behavior was variable. Only one of six patients achieved pathologic complete response to neoadjuvant chemotherapy. The authors concluded that SLBC is a rare morphologic pattern of invasive breast carcinoma that mimics metastatic serous gynecologic carcinoma. SLBC are heterogeneous with respect to grade, receptor profile, and oncogenic driver alterations. Additional studies are warranted to further evaluate the clinical behavior of these tumors.

Krings G, Shamir ER, Laé M, et al. Serous-like breast carcinomas: immunophenotypic, genetic, and clinicopathologic characterization of a morphologically distinct group of tumours. Histopathology. 2025;86(5):779–792.

Correspondence: Dr. Gregor Krings at [email protected]

Analysis of whole slide images of lymph node frozen sections in breast cancer

Various digital modalities are available for frozen section evaluation in surgical pathology practice. However, studies that demonstrate the potential of whole slide imaging (WSI) as a robust digital pathology option for frozen section diagnosis are limited. The authors compared the diagnostic accuracy of WSI to that of light microscopy for evaluating frozen sections of axillary sentinel lymph nodes (SLNs) and clipped lymph nodes from patients with breast cancer using two modalities. They initially conducted a retrospective analysis that evaluated hematoxylin-and-eosin (H&E)–stained frozen sections of 109 SLNs using WSI followed by light microscopy after a washout period of two to six weeks. The authors subsequently conducted a prospective analysis that assessed frozen sections of 132 SLNs, with one pathologist using light microscopy and another scanning and remotely interpreting H&E–stained frozen sections in real time. In the retrospective analysis, diagnostic accuracy using WSI ranged from 96 to 99 percent and was similar to that for light microscopy, which ranged from 94 to 99 percent. The prospective analysis also demonstrated comparable diagnostic accuracy between WSI (96.2 percent) and light microscopy (97 percent). Pathologists in the retrospective study required an additional 0.8 to 5.4 minutes to render diagnoses using WSI versus light microscopy (P < .0001). In the prospective study, conducted two years later, pathologists took only slightly longer to provide WSI frozen section diagnoses (3.95 minutes) compared with diagnoses via light microscopy (3.51 minutes; P > .05). The authors concluded that their study indicated that WSI-based evaluation showed comparable diagnostic accuracy to light microscopy for assessing lymph node frozen sections. Furthermore, the prospective study demonstrated the feasibility of real-time acquisition of high-quality WSIs for remote frozen section diagnosis of SLNs. These findings underscore the potential of using WSIs of SLNs and clipped lymph nodes in real-time frozen section evaluation of patients with breast cancer as a standard of care in surgical pathology practice.

Ye Q, Law T, Klippel D, et al. Prospective and retrospective analysis of whole-slide images of sentinel and targeted lymph node frozen sections in breast cancer. Mod Pathol. 2025. doi.org/10.1016/j.modpat.2025.100708

Correspondence: Dr. Skrishna Krishnamurthy at [email protected]

Identification of superficial malignant peripheral nerve sheath tumors

Superficial malignant peripheral nerve sheath tumors (SF-MPNST) are rare cancers and can be difficult to distinguish from spindle cell or desmoplastic melanomas. Their biology is poorly understood. The authors performed whole exome sequencing and RNA sequencing (RNA-seq) on SF-MPNST (n = 8) and compared them with cases of spindle cell melanoma (n = 7), desmoplastic melanoma (n = 8), and deep MPNST (D-MPNST, n = 8). They also performed IHC staining for H3K27me3 and PRAME. SF-MPNST demonstrated intermediate features between D-MPNST and melanoma. Patients were younger than those with melanoma and older than those with D-MPNST, and the outcome was worse and better, respectively. SF-MPNST tumor mutational burden (TMB) was higher than that of D-MPNST and lower than that of melanoma. Differences were significant only between SF-MPNST and spindle cell melanoma (P = .0454) and between D-MPNST and spindle cell melanoma (P = .001, Dunn’s Kruskal–Wallis post hoc test). Despite having an overlapping mutational profile in some common cancer-associated genes, the COSMIC mutational signatures clustered desmoplastic melanoma and spindle cell melanoma together with UV light exposure signatures (SBS7a and SBS7b), and SF- and D-MPNST together with defective DNA base excision repair (SBS30 and SBS36). RNA-seq revealed differentially expressed genes between SF-MPNST and spindle cell melanoma (1,670 genes), desmoplastic melanoma (831 genes), and D-MPNST (614 genes), some of which hold promise for development as IHC markers (SOX8 and PLCH1) or aids (MLPH, CALB2, SOX11, and TBX4). H3K27me3 immunoreactivity was diffusely lost in most D-MPNST (seven of eight, 88 percent) but showed variable and patchy loss in SF-MPNST (two of eight, 25 percent). PRAME was entirely negative in the majority of cases (0+ in 20 of 31, 65 percent), including 11 of 15 melanomas, and showed no significant difference between groups (P = .105, Kruskal–Wallis test). Expression of immune cell transcripts was upregulated in melanomas relative to MPNST. Next-generation sequencing revealed multiple differential features between SF-MPNST, D-MPNST, spindle cell melanoma, and desmoplastic melanoma, including tumor mutational burden, mutational signatures, and differentially expressed genes. The authors concluded that these findings help advance the medical community’s understanding of disease pathogenesis and improve diagnostic modalities.

McAfee JL, Alban TJ, Makarov V, et al. Genomic landscape of superficial malignant peripheral nerve sheath tumor. Lab Invest. 2025;105(2). doi.org/10.1016/j.labinv.2024.102183

Correspondence: Dr. Jennifer S. Ko at [email protected]

Concordance between IHC and MSI analysis for detecting MMR/MSI status in colorectal cancer patients

Screening of colorectal cancer patients for mismatch repair/microsatellite instability status has gained widespread use due to its potential predictive and prognostic roles, and it has become a crucial screening tool for detecting Lynch syndrome. The authors conducted a study to evaluate concordance between IHC and microsatellite instability (MSI) analysis methods for detecting mismatch repair (MMR)/MSI status, using colorectal cancer patients in Kuantan, Pahang, Malaysia. Fifty colorectal cancer (CRC) cases of deficient mismatch repair (dMMR) and proficient mismatch repair (pMMR), which were identified immunohistochemically in a previous study, were subjected to MSI analysis. The study used the MSI Analysis System 1.2 (Promega). The results were MSI high: 26 percent (13 of 50), MSI low: six percent (three of 50), and microsatellite stable: 68 percent (34 of 50). Concordance was perfect (kappa value, 0.896) between MSI analysis and IHC methods for assessing MMR/MSI status in CRC patients. Discordance was only four percent (two of 50). MSI analysis identified all but one dMMR case determined by IHC. The frequency of dMMR and pMMR cases was 11.4 percent (14 of 123) and 88.6 percent (109 of 123) by IHC method, respectively. The study findings support the universal practice of evaluating MMR/MSI status in all newly diagnosed CRC patients. Based on the perfect concordance of the two methods, the method of choice for identifying MMR/MSI status in CRC patients should be based on expertise in this area and availability of required equipment. Both factors determine the feasibility of the method. MSI analysis is appropriate for formalin-fixed, paraffin-embedded tissue samples because it does not require the involvement of an experienced pathologist; it can detect MSI cancers that have a nonfunctional MMR system but retained MMR protein expression on IHC due to nontruncated missense mutation; it can recognize MMR abnormality due to mutations of MMR proteins that are not listed in the IHC panel; and it is comparatively less exposed to alteration than IHC following radiation and neoadjuvant therapy. Tissue fixation, on the other hand, can affect polymerase chain reaction, requires a well-equipped molecular genetic lab and expert staff, and is comparatively more costly than the IHC method. Because IHC is an affordable, readily available, and reproducible method for most laboratories, the authors suggest that IHC may be used as a primary screening test for determining MMR/MSI status in CRC patients.

Faizee MI, Talib NA, Hamdan AHB, et al. Concordance between immunohistochemistry and MSI analysis for detection of MMR/MSI status in colorectal cancer patients. Diagn Pathol. 2024. doi.org/10.1186/s13000-024-01571-5

Correspondence: Dr. Ahmed Maseh Haidary at [email protected]