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, associate pathologist, Brigham and Women’s Hospital, Boston; and Amarpreet Bhalla, MD, assistant professor of pathology, Albert Einstein College of Medicine, Montefiore Medical Center.

Relationship between cytomegalovirus hepatitis and acute cellular rejection

December 2023—Cytomegalovirus hepatitis in allograft livers is a significant infectious complication for which the histology historically has been described as overlapping that of acute cellular rejection, a diagnosis that compels a different treatment regimen. The authors conducted a study to update the clinicopathologic features of cytomegalovirus (CMV) hepatitis and explore its clinical and histologic relationship with acute cellular rejection (ACR). They performed a retrospective analysis of 26 patients, across four institutions, who were diagnosed with CMV hepatitis, assessing clinical, histologic, and IHC features. Patients were predominantly CMV donor positive/recipient negative (D+/R-; n=9 of 15) and received a diagnosis of CMV hepatitis at a mean age of 52 years (standard deviation [SD], 17 years) and at a mean interval of 184 days (SD, 165 days) from transplantation. Mean CMV viral load at diagnosis was 241,000 IU/mL (SD, 516 000 IU/mL), and liver biochemical enzymes were elevated (mean alanine aminotransferase, 212 U/L [SD, 180 U/L]; mean aspartate aminotransferase, 188 U/L [SD, 151 U/L]; and mean alkaline phosphatase, 222 U/L [SD, 153 U/L]). Ten cases did not show histologic features of acute cellular rejection, and 16 had such features as marked bile duct injury and endotheliitis. All patients had viral cytopathic change. They were treated with a combination of antiviral therapy and CMV intravenous immunoglobulin, and all patients with undetectable or nearly undetectable CMV viral titers showed near resolution of biochemical enzymes. The authors concluded that CMV hepatitis and acute cellular rejection are complex processes with interlinking mechanisms that should be distinguished from each other. A subset of transplant patients with CMV hepatitis showed histologic changes that mimic acute cellular rejection but were treated successfully with antiviral therapy alone.

Shih AR, Naini BV, Westerhoff M, et al. Cytomegalovirus hepatitis in allograft livers may show histologic features of acute cellular rejection. Arch Pathol Lab Med. 2023;147(6):655–664.

Correspondence: Dr. Angela R. Shih at ashih1@partners.org

Toker cell hyperplasia in the nipple-areolar complex of transmasculine people

In a previous study of breast histopathologic features, the authors observed a high frequency of intraepidermal glands formed by Toker cells in the nipple-areolar complex (NAC) of transmasculine chest-contouring surgical specimens. In the study reported herein, they analyzed Toker cell hyperplasia (TCH)—the presence of clusters of Toker cells consisting of at least three contiguous cells or glands, or both, with lumen formation—in the transmasculine population. Increased numbers of singly dispersed Toker cells were not considered TCH. Eighty-two (18.5 percent) of the 444 transmasculine subjects in the study cohort had a portion of their NAC excised and available for evaluation. The authors also reviewed the NACs from 55 cisgender women who were younger than 50 years old and had undergone full mastectomies. The proportion of TCH in transmasculine people (20 of 82; 24.4 percent) was 1.7-fold higher than in cisgender women (eight of 55; 14.5 percent) but did not achieve significance (P=.20). However, in those with TCH, the rate of gland formation was 2.4-fold higher in transmasculine people, achieving borderline significance (18 of 82 versus five of 55; P=.06). Among the transmasculine subjects, TCH was significantly more likely to be present in those with a higher body mass index (P=.03). An Akoya Biosciences assay was used to stain for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), androgen receptor (AR), cytokeratin 7, and Ki67 in a subset of five transmasculine and five cisgender cases. All 10 cases were cytokeratin 7+ and Ki67-, and nine out of 10 cases were AR+. Toker cells in transmasculine people demonstrated variable expression of ER, PR, and HER2. For cisgender cases, Toker cells were consistently ER+, PR-, and HER2-. The authors concluded that there is a higher rate of TCH in those who are transmasculine than in those who are cisgender, particularly among transmasculine people who have a high body mass index and are taking testosterone. To the authors’ knowledge, this is the first study to demonstrate that Toker cells are AR+. Toker cells display variable ER, PR, and HER2 immunoreactivity. The clinical significance of TCH in the transmasculine population remains to be elucidated.

Baker GM, Bret-Mounet VC, Xu J, et al. Toker cell hyperplasia in the nipple-areolar complex of transmasculine individuals. Mod Pathol. 2023;36(6). https://doi.org/10.1016/j.modpat.2023.100121

Correspondence: Dr. Y. J. Heng at yheng@bidmc.harvard.edu

Study of thyroid oncocytic nodules with longitudinal nuclear grooves

Thyroid nodules with longitudinal nuclear grooves have been widely considered synonymous with papillary thyroid carcinoma. The authors conducted a study in which they assessed 15 cases of thyroid nodules that exhibited oncocytic, or Hürthle cell, features and contained longitudinal nuclear grooves yet failed to display aggressive behavior or the full features of papillary thyroid carcinoma (PTC). Next-generation sequencing was performed to examine 161 genes for oncogenic driver alterations associated with thyroid neoplasia. The lesions occurred in 11 women and four men aged 27 to 80 years and measured 0.2 to 2.3 cm in diameter (mean, 1.1 cm). The tumors were well circumscribed and noninvasive and showed a proliferation of large cells with abundant granular cytoplasm and centrally placed nuclei displaying scattered longitudinal nuclear grooves. IHC stains were negative for HBME-1, galectin-3, and CK19 in all cases. NRAS pQ61R was detected in six cases, KRAS p.Q61E in one case, and AKT2 p.E17K in one case. None of the genetic changes classically associated with conventional PTC or high-grade thyroid malignant neoplasms were identified. Clinical follow-up in nine patients showed no evidence of recurrence or metastases between two and 13 years (mean, 5.7 years). The authors concluded that longitudinal nuclear grooves occasionally can be encountered in oncocytic tumors and should not lead to a diagnosis of PTC in the absence of other features supporting that diagnosis.

Suster D, Mackinnon AC, Suster S. Thyroid oncocytic (Hürthle cell) nodules with longitudinal nuclear grooves: clinicopathologic, immunohistochemical, and molecular genetic study of 15 cases. Arch Pathol Lab Med. 2023;147:684–691.

Correspondence: Dr. Saul Suster at ssuster@mcw.edu