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.

SATB2 expression in tumors: a tissue microarray study

October 2023—Special AT-rich sequence-binding protein 2, or SATB2, induces local chromatin loops to facilitate transcription. SATB2 immunostaining is commonly used as a marker for colorectal adenocarcinoma and osteosarcoma. The authors conducted a study to better understand the prevalence and diagnostic value of SATB2 expression in cancer by analyzing a comprehensive set of human tumors. SATB2 expression was analyzed in 15,012 tissue samples from 120 tumor types and subtypes and 608 samples from 76 nonneoplastic tissue types using IHC in a tissue microarray format. SATB2 positivity was found in 89 of the 120 (74 percent) tumor types—59 of the 120 (49 percent) had at least one moderately positive tumor and 38 of the 120 (32 percent) had at least one strongly positive tumor. Expression was high in adenomas (n=42 of 44 and 44 of 47; 96 and 94 percent, respectively), adenocarcinomas of the colorectum (1,747 of 2,023; 86 percent), various subtypes of neuroendocrine tumors of the colorectum and appendix (n=3 of 7 and 12 of 12; 43 and 100 percent, respectively), Merkel cell carcinoma (n=25 of 34; 74 percent), osteosarcoma (n=15 of 25; 60 percent), and papillary renal cell carcinoma (n=121 of 235; 52 percent). Associations with clinicopathologic tumor features were assessed in colorectal and kidney cancers. In colorectal cancer, weak SATB2 expression was linked to high pT (P<.001), nodal metastasis (P<.001), right-sided tumor location (P<.001), microsatellite instability (P<.001), and BRAF mutations (P=.02). In papillary renal cell carcinoma, low SATB2 expression was associated with high pT (P=.02), distant metastasis (P=.04), and reduced tumor-specific survival (P=.04). In clear cell renal cell carcinoma, low SATB2 expression was linked to high pT (P<.001), high Union for International Cancer Control stage (P<.001), high Thoenes grade (P=.02), and reduced recurrence-free survival (P=.02). The authors concluded that strong SATB2 expression supports a colorectal origin for adenocarcinomas and neuroendocrine neoplasms. Weak SATB2 expression reflects progression and poor prognosis in colorectal and kidney cancers.

Dum D, Kromm D, Lennartz M, et al. SATB2 expression in human tumors: A tissue microarray study on more than 15,000 tumors. Arch Pathol Lab Med. 2023;147(4):451–464.

Correspondence: Dr. Ronald Simon at r.simon@uke.de

Impact of p53-abnormal ‘fields of dysplasia’ in HPV-independent vulvar squamous cell carcinoma

Abnormal p53 IHC staining patterns can be found in vulvar squamous cell carcinoma and differentiated vulvar intraepithelial neoplasia. They can also be found in the adjacent skin that shows morphology that falls short of the traditional diagnostic threshold for differentiated vulvar intraepithelial neoplasia (dVIN). The authors hypothesized that mutation-associated p53 IHC staining in the skin surrounding the vulvar squamous cell carcinoma (VSCC), referred to as the p53-abnormal field of dysplasia, is clinically significant and may explain the high rates of disease recurrence in human papillomavirus (HPV)-independent TP53-mutant VSCC. The authors conducted a study in which they selected from their institutional archive vulvectomy specimens containing HPV-independent abnormal p53 (p53abn) VSCC with margins originally reported as negative for invasive and in situ disease. Blocks showing the closest approach of the VSCC to a peripheral surgical margin were stained with p53 IHC stains. The authors assessed the detection of morphologically occult p53abn in situ neoplasia, rates of margin status change after p53 IHC staining, and effect of p53abn IHC staining at margins on two-year local recurrence rates. Seventy-three HPV-independent p53abn VSCCs were included in the study. Half (35 of 73; 48 percent) had an in situ lesion documented in the original report. The use of p53 IHC staining identified 21 (29 percent) additional cases with p53abn in situ lesions that were originally unrecognized. The histology of in situ lesions in the p53abn field varied and became more subtle (morphologically occult) farther away from the VSCC. Fifteen (21 percent) cases had a morphologically occult and previously unrecognized p53abn in situ lesion present at a resection margin, which conferred an increased risk of local recurrence (five of seven [71.4 percent] versus six of 22 [27.3 percent]; P = .036). The p53abn in situ lesions at a margin were confirmed to have TP53 mutations by sequencing. P53 IHC staining identified morphologically occult p53abn in situ lesions surrounding HPV-independent VSCC. P53abn IHC staining at a margin was associated with a threefold increased risk of local recurrence.

Thompson EF, Wong RWC, Trevisan G, et al. p53-abnormal “fields of dysplasia” in human papillomavirus-independent vulvar squamous cell carcinoma impacts margins and recurrence risk. Mod Pathol. 2023;36(2). https://doi.org/10.1016/j.modpat.2022.100010

Correspondence: Dr. L. N. Hoang at lien.hoang@vch.ca