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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; Rachel Stewart, DO, PhD, assistant professor, Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington; Nicole Panarelli, MD, associate professor of pathology, Albert Einstein College of Medicine, Montefiore Medical Center; and Shaomin Hu, MD, PhD, pathology resident, Albert Einstein College of Medicine, Montefiore Medical Center.

ALK expression in angiomatoid fibrous histiocytoma: a potential diagnostic pitfall

March 2019—The authors recently encountered a case of primary pulmonary angiomatoid fibrous histiocytoma (AFH), which was initially misdiagnosed as inflammatory myofibroblastic tumor based in part on anaplastic lymphoma kinase expression by IHC. Prompted by this experience, they evaluated anaplastic lymphoma kinase (ALK) expression in 11 AFH, 15 inflammatory myofibroblastic tumors (IMT), and 11 follicular dendritic cell sarcomas using three antibody clones: D5F3, 5A4, and ALK1. ALK IHC-positive cases were analyzed with FISH using a dual-color ALK break-apart probe kit. The majority of AFH cases studied were positive for ALK IHC with at least one antibody—nine of 11 D5F3, six of nine 5A4, one of nine ALK1—and most demonstrated moderate to strong cytoplasmic staining. AFH with positive ALK IHC showed no ALK gene rearrangement by FISH with ALK copy number ranging from 1.6 to 2.1. Sixty-seven percent of IMT were ALK positive by IHC—10 of 15 D5F3, eight of 15 5A4, seven of 15 ALK1—and nine of 10 cases were positive for ALK gene rearrangement by FISH. All follicular dendritic cell sarcomas were negative for ALK by IHC (D5F3 and 5A4). The results indicate that ALK expression in AFH is common, particularly with the highly sensitive D5F3 and 5A4 antibodies and enhanced detection systems, and potentially may present diagnostic confusion with IMT. The underlying mechanism of ALK expression in AFH is unclear, although it does not appear to be from ALK rearrangement or amplification.

Cheah AL, Zou Y, Lanigan C, et al. ALK expression in angiomatoid fibrous histiocytoma: a potential diagnostic pitfall. Am J Surg Pathol. 2019;43(1):93–101.

Correspondence: Dr. A. L. Cheah at alicheah@gmail.com or Dr. Y. Zou at zyr1988@hotmail.com

PD-1 and PD-L1 expression in primary HNSCC and related lymph node metastasis

The expression profiles and clinical impact of programmed cell death ligand 1 (PD-L1) and programmed cell death 1 (PD-1) expressing tumor-infiltrating lymphocytes in head and neck squamous cell carcinoma (HNSCC) are not elucidated fully. The authors conducted a study to evaluate expression patterns in primary HNSCC and related lymph node metastasis and the impact on patients’ clinical outcome. They analyzed IHC staining patterns of PD-L1 and PD-1 in 129 specimens of primary HNSCC and 77 lymph node metastases. The results were correlated with patients’ clinical data. PD-L1 expression was observed in 36 percent of primary carcinomas and 33 percent of lymph node metastases and correlated significantly with decreased overall survival (P = .01) and disease-free survival (P = .001) in oral cavity squamous cell carcinoma patients. PD-L1 expression was associated with lymph node metastasis (P = .0223). Infiltration of PD-1–expressing lymphocytes correlated significantly with favorable overall survival (P = .001) and disease-free survival (P = .001) in oropharyngeal cancer patients and hypopharyngeal cancer patients (overall survival, P = .007; disease-free survival, P = .001). The presence of PD-1 tumor-infiltrating lymphocytes also correlated significantly with better overall survival (P = .005) and disease-free survival (P = 0) in the human papilloma virus-negative cohort. Cox regression multivariate analysis revealed PD-1 tumor-infiltrating lymphocyte expression as an independent prognostic marker for overall survival (P = .004) and disease-free survival (P = .001), and T stage was validated as a negative prognostic marker for overall survival (P = .011). PD-1–expressing lymphocytes (P = .0412) and PD-L1 expression (P = .0022) patterns correlated significantly in matched primary cancers and lymph node metastases. These results characterize the expression profiles of PD-1 axis proteins in HNSCC, which may serve as possible clinical prognostic markers.

Schneider S, Kadletz L, Wiebringhaus R, et al. PD-1 and PD-L1 expression in HNSCC primary cancer and related lymph node metastasis—impact on clinical outcome. Histopathol. 2018;73(4):573–584.

Correspondence: Dr. Gregor Heiduschka at gregor.heiduschka@meduniwien.ac.at

Role of stroma in relationships between risk factor exposure and age-related epithelial involution in benign breast

Delayed age-related lobular involution has been associated with elevated breast cancer risk. However, intraindividual variability in epithelial involution status within a woman is undefined. The authors developed a novel measure of age-related epithelial involution—density of epithelial nuclei in epithelial areas using digital image analysis combined with stromal characteristics (percentage of section area comprising stroma). They evaluated approximately 1,800 hematoxylin-and-eosin–stained sections of benign breast tissue from 416 participants having breast surgery for cancer or benign conditions. They studied two to 16 slides per woman from different regions of the breast. Epithelial involution status varied within a woman and as a function of stromal area. Percentage stromal area varied between samples from the same woman. The median difference between highest and lowest stromal area within a woman was 7.5 percent, but it ranged from 0.01 to 86.7 percent. Restricting the assessment to women with at least 10 percent stromal area (n = 317), epithelial nuclear density decreased with age (−637.1 cells/mm2 per decade of life after age 40; P < .0001), increased with mammographic density (457.8 cells/mm2 per increasing Breast Imaging Reporting and Data System density category; P = .002), and increased nonsignificantly with recent parity, later age at first pregnancy, and longer and more recent oral contraceptive use. These associations were attenuated in women with samples categorized as mostly fat (fewer than 10 percent stroma [n = 99]). Thirty-one percent of women evaluated had both adequate stroma (10 percent or more) and regions of breast tissue that were mostly fat (less than 10 percent stroma). The probability of having both types increased with the number of breast tissue samplings. Several breast cancer risk factors are associated with elevated age-related epithelial content, but associations depend on stromal context. Stromal characteristics appear to modify relationships between risk factor exposures and breast epithelial involution.

Chollet-Hinton L, Puvanesarajah S, Sandhu R, et al. Stroma modifies relationships between risk factor exposure and age-related epithelial involution in benign breast. Mod Pathol. 2018;31:1085–1096.

Correspondence: Dr. Melissa A. Troester at troester@unc.edu

Link between treatment for perianal Paget disease and mimicry of recurrent disease

The histologic differential diagnosis of perianal Paget disease includes malignant melanoma, pagetoid spread of squamous cell carcinoma, and secondary involvement by colorectal carcinoma. While it is useful to consider these entities when establishing a diagnosis, such consideration does not apply when patients with Paget disease undergo surveillance for recurrent disease. Treatment of perianal Paget disease consists of a combination of surgical excision with skin grafts and topical chemotherapeutic agents that induce cytologic alterations in benign cells and simulate recurrent malignancy. To evaluate the therapy-related changes and possible diagnostic pitfalls for patients with Paget disease, the authors reviewed 412 post-treatment tissue samples from three women with primary perianal Paget disease who underwent wide excision, skin grafting, and topical 5-fluorouracil therapy. Biopsy samples from engrafted skin often displayed single and clustered cells with hyperchromatic nuclei dispersed in the deep epidermis. Similar cells were scattered throughout all levels of the epidermis in biopsy samples following topical chemotherapy. The abnormal cells were negative for cytokeratin 7 (CK7) and mucicarmine in both situations. Disease recurred in all patients. Some Paget cells showed classic features with eosinophilic or mucinous cytoplasm and eccentric nuclei, while others were smaller with less conspicuous atypia. All Paget cells showed strong, membranous CK7 staining. The authors concluded that treatment of perianal Paget disease can elicit cytologic abnormalities in benign epithelial cells that simulate the cytologic features of recurrent disease and can diminish the atypia of Paget cells. Immunohistochemical stains for CK7 can be helpful when evaluating surveillance samples from these patients.

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