Tubulocystic carcinoma of bile ducts: a type of cholangiocarcinoma associated with adenofibroma-type lesions
A type of cholangiocarcinoma characterized by peculiar histologic patterns and underlying adenofibromatous lesions has been reported in the literature, primarily as individual case reports. The authors conducted a study to further clarify the defining characteristics of this spectrum of lesions. Clinicopathologic analysis of eight biliary tumors with tubulocystic architecture arising in the background of adenofibroma-type lesions was performed. Three of the tumors were also investigated using next-generation sequencing with a panel of 174 genes. Five of the patients were male and three were female (mean age, 64.6 years). All tumors were intrahepatic, except for one, which was perihilar and protruded into soft tissue. Mean tumor size was 4.4 cm. At histology, all cases showed a peculiar and cytologically bland tubulocystic pattern and a background of stromal changes that created a picture of adenofibroma. The glandular component of these lesions closely resembled tubulocystic-type kidney cancers, including back-to-back microcystic units that formed relatively demarcated nodules. One case showed perineural invasion by otherwise deceptively benign-appearing microcystic structures; one had areas transitioning to intraductal tubulopapillary neoplasm; and three harbored more conventional small-duct cholangiocarcinoma (CCA) foci. In the latter three cases, the tubulocystic and conventional CCA components were investigated separately using next-generation sequencing. They shared molecular alterations, including recurrent mutations in chromatin remodeling genes, such as ARID1A, BAP1, and PBRM1, and the actionable FGFR2-MCU fusion gene. In limited follow-up, all but one patient were alive and free of disease after surgical resection. In conclusion, the authors described a distinct entity of CCA with specific histo-molecular features, for which they propose the designation of tubulocystic carcinoma of bile ducts.
Masetto F, Mafficini A, Saka B, et al. Tubulocystic carcinoma of bile ducts: A distinct type of cholangiocarcinoma associated with adenofibroma-type lesions. Am J Surg Pathol. 2024;48(9):1082–1092.
Correspondence: Dr. Volkan Adsay at vadsay@kuh.ku.edu.tr or Dr. Claudio Luchini at claudio.luchini@univr.it
Superficial neurocristic EWSR1::FLI1 fusion tumor: a distinctive S100 protein- and SOX10-positive neoplasm of skin and subcutis
Different entities may share identical gene fusions. The authors reported on a distinctive neoplasm of the skin and subcutis harboring the Ewing sarcoma-associated EWSR1::FLI1 fusion but otherwise differing from Ewing sarcoma. Slides and blocks for five cutaneous neoplasms coded as other than Ewing sarcoma and harboring EWSR1::FLI1 were retrieved for the study. Immunohistochemical and molecular genetic results were abstracted from reports. Methylation profiling was performed and clinical information obtained. The tumors occurred in four men and one woman (median, 25 years of age; range, 19–69 years) and involved the skin and subcutis of the back (two), thigh (one), buttock (one), and chest wall (one) (median, 2.4 cm; range, 1–11 cm). Two tumors were present years before receiving clinical attention. The lesions were multinodular and circumscribed and consisted of nests of bland, round cells admixed with hyalinized collagenous bands containing spindle cells. Hemorrhage and cystic change were often present; necrosis was absent. All were diffusely S100 protein and SOX10 positive, and four of five were CD99 negative. One case was strongly positive for NKX2.2. A variety of other markers were focally positive, including glial fibrillary acidic protein and p63, or negative. Molecular genetic results were EWSR1 exon 7::FLI1 exon 8, EWSR1 exon 11::FLI1 exon 5, EWSR1 exon 11::FLI1 exon 6, EWSR1 exon 7::FLI1 exon 6, and EWSR1 exon 10::FLI1 exon 6. Methylation profiling performed on three of the tumors showed that they formed a unique cluster distinct from Ewing sarcoma. All patients underwent excision with negative margins and one received one cycle of chemotherapy. Clinical follow-up showed all patients to be alive without disease (median, 17 months; range, 11–62 months). The authors concluded that despite similar gene fusions, the morphologic, IHC, epigenetic, and clinical features of these unique EWSR1::FLI1-fused neoplasms of the skin and subcutis differ substantially from Ewing sarcoma. Interestingly, EWSR1 rearrangements involved exon 10 or 11 (rarely seen in Ewing sarcoma) in a majority of cases. Superficial neurocristic EWSR1::FLI1 fusion tumors should be rigorously distinguished from true cutaneous Ewing sarcomas.
Folpe AL, Tetzlaff MT, Billings SD. Superficial neurocristic EWSR1::FLI1 fusion tumor: A distinctive, clinically indolent, S100 protein/SOX10-positive neoplasm. Mod Pathol. 2024. doi.org/10.1016/j.modpat.2024.100537
Correspondence: Dr. Andrew L. Folpe at folpe.andrew@mayo.edu
Association between atypical squamous cells in urine cytology and risk of high-grade malignancy
Atypical squamous cells in urine cytology are rare, and their clinical significance is not well studied. Previous studies were limited by a small number of cases and a lack of objective grading of atypical squamous cells (ASC) or their correlation with accompanying urothelial cell abnormality (UCA), or both. The authors conducted a study to evaluate urine cytology cases with ASC, grade the squamous atypia, and correlate the findings with accompanying UCA or risks of high-grade malignancy. They searched their institutional database over 10 years for urine cytology reports containing the words squamous, atypical squamous cells, or squamous dysplasia, as well as for patients who had concurrent or previous urine cytologies and diagnoses of high-grade urothelial carcinoma with squamous differentiation or squamous cell carcinoma. ASC were defined as keratinized squamous cells and subcategorized as reactive, koilocytosis, low-grade atypia, and high-grade atypia. Correlations with age, sex, specimen type, accompanying UCA, number of ASC, and risk of high-grade malignancy (ROHM) were assessed. ASC was present in 0.15 percent of all urine specimens (123 of 81,018). Slides and clinical follow-up were available for 91 patients (median age, 71 years). Low- and high-grade squamous atypia had ROHM of 70 percent and 92 percent, respectively. ASC not accompanied by UCA and accompanied by UCA had ROHM of 37 percent and 94 percent, respectively. Fifty-one percent of malignancies (34 of 67) showed rare ASC in urine. Reactive changes and koilocytosis had zero ROHM. ASC in urine cytology is a significant finding and is associated with a high ROHM. In the absence of accompanying UCA, low-grade squamous atypia had a lower ROHM than high-grade atypia. In the presence of UCA, low- and high-grade squamous atypia had ROHM of more than 90 percent. These findings suggest that ASC and their grade of atypia should be noted in the cytology report, and clinicians should be made aware of their clinical significance.
Ho L, Elsheikh TM. Atypical squamous cells in urine cytology are associated with a significant risk of high-grade malignancy. Cancer Cytopathol. 2024;132:499–509.
Correspondence: Dr. Tarik M. Elsheikh at elsheit@ccf.org