CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
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.
Triple-positive breast carcinoma: histopathologic features and response to neoadjuvant chemotherapy
December 2021—It is unclear whether HER2+ tumors expressing estrogen receptor and progesterone receptor—that is, triple-positive breast carcinomas—show unique morphologic and clinical features and response to neoadjuvant chemotherapy. The authors conducted a study of the morphologic and immunohistochemical features of triple-positive breast carcinomas (TPBC) in patients who underwent neoadjuvant chemotherapy. They retrospectively reviewed the core biopsy and post-neoadjuvant chemotherapy slides of 85 TPBCs. H-scores were calculated for estrogen receptor (ER) and progesterone receptor (PR). HER2 slides and FISH reports were reviewed. The residual cancer burden was calculated for post-neoadjuvant chemotherapy specimens. Eighty-one of the 85 (95.3 percent) tumors showed ductal histology. Three (3.5 percent) were invasive lobular carcinomas and one (1.2 percent) showed mixed ductal and lobular features. A subset showed mucinous (n = 7, 8.2 percent), apocrine (n = 5, 5.9 percent), and/or micropapillary (n = 4, 4.7 percent) differentiation. Fifty-four (63.5 percent) TPBCs showed high ER expression (H-score greater than 200), including 27 (31.8 percent) with high ER and PR expression. Fifty-two (61.1 percent) tumors showed HER2 3+ staining. The mean HER2/CEP17 ratio by FISH was 3.6 (range, 2–12.2) and mean HER2 signals per cell was eight (range, 3.7–30.4). The pathologic complete response (pCR) rate was 35.3 percent (30 of 85). HER2 3+ staining was the only significant predictor of pCR on multivariate analysis (odds ratio, 9.215; 95 percent confidence interval [CI], 2.401–35.371; P < .001). The ER/PR expression did not correlate with response to therapy. The authors concluded that TPBCs are heterogeneous, with some showing mucinous, lobular, or micropapillary differentiation. The pCR rate of TPBCs is similar to that reported for ER+/PR–/HER2+ tumors. HER2 overexpression by IHC was associated with significantly better response to therapy and may help in selecting patients for treatment in the neoadjuvant setting.
Zeng J, Edelweiss M, Ross DS, et al. Triple-positive breast carcinoma: Histopathologic features and response to neoadjuvant chemotherapy. Arch Pathol Lab Med. 2021;145(6):728–735.
Correspondence: Dr. Timothy M. D’Alfonso at dalfonst@mskcc.org
Categorization of HER2 FISH results from invasive breast cancer patients treated with HER2-targeted agents
HER2 (ERBB2) gene status serves as a strong predictive marker of response to HER2-targeted agents in invasive breast cancers, albeit with heterogeneous response. The authors conducted a study to determine the distribution and prognosis of HER2 groups by FISH using the updated 2018 American Society of Clinical Oncology–College of American Pathologist (ASCO–CAP) guidelines, which contain five in situ hybridization categories. They identified 226 patients who had equivocal or positive HER2 FISH invasive breast cancer (interpreted by ASCO–CAP guidelines at the time of reporting) and who received HER2-targeted agents from 2006 to 2017. The authors subcategorized group one (a broad group and the dominant category in terms of number of patients in the authors’ cohort) into three subgroups: low amplified (HER2/CEP17 ratio ≥ 2.0–2.99, mean HER2 per cell 4.0–5.9), amplified (HER2/CEP17 ratio ≥ 2.0–2.99, mean HER2 per cell ≥ 6), and excessive amplification (HER2/CEP17 ratio ≥ 3, mean HER2 per cell ≥ 4). They recorded the outcomes of recurrence, metastasis, second breast primary, disease-free survival, and overall survival. Univariate analysis showed that the five categories of HER2 FISH were significantly associated with overall survival (p < .01) and that higher HER2 amplification was associated with fewer deaths. HER2 FISH status also was statistically significantly related to disease-free survival (p < .01) and metastasis (p = .01) but not to recurrence or second breast primary. Multivariate analysis showed that tumor type and HER2 ISH groups were independent predictors for overall survival and disease-free survival in the HER2-treated cohort. The group one subcategories were significantly associated with overall survival (p < .01) and disease-free survival (p < .01), and excessive HER2 amplification was associated with longer median survival. The Cox regression models showed better survival outcomes for the excessive amplification subgroup than the low-amplified subgroup with regard to overall survival (hazard ratio = 0.63; 95 percent confidence interval [CI], 0.42–0.93) and disease-free survival (hazard ratio = 0.55; 95 percent CI, 0.37–0.83). The authors demonstrated that in HER2 FISH group one patients, high HER2 amplification was significantly associated with longer overall and disease-free survival. Furthermore, these patients seemed to benefit more from HER2-targeted regimens. The authors recommend reporting these group one subcategories when assessing HER2 FISH.
Alhamar M, Alkamachi B, Mehrotra H, et al. Clinical significance of quantitative categorization of HER2 fluorescent in situ hybridization results in invasive breast cancer patients treated with HER2-targeted agents. Mod Pathol. 2021;34:720–734.
Correspondence: Dr. Dhananjay A. Chitale at dchital1@hfhs.org
Outcomes of the Milan system categories nondiagnostic and nonneoplastic for salivary gland FNA
The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) specifies six categories with estimated risks of malignancy and suggested management. The estimated risk of malignancy is 25 percent for the nondiagnostic and 10 percent for the nonneoplastic categories. The authors conducted a study to investigate the histopathologic and clinical outcomes of the MSRSGC categories nondiagnostic and nonneoplastic at the authors’ institution. Cytopathology fine-needle aspiration (FNA) reports from 2008 to 2020 were searched for the words salivary, parotid, and submandibular. Cases fitting the nondiagnostic and nonneoplastic categories were identified. Follow-up cytopathology/histopathology and clinical data were extracted. There were 43 nondiagnostic and 46 nonneoplastic cases. The average patient age was 58.3 years. Neoplastic lesions were found in 13 of 43 (30 percent) nondiagnostic and three of 46 (6.5 percent) nonneoplastic cases. The rate of malignancy was 14 percent (six of 43) in the nondiagnostic category and zero (of 46) in the nonneoplastic category. Four (9.3 percent) cases that were nondiagnostic and six (13 percent) that were nonneoplastic had no neoplasm and instead had an underlying reactive condition, such as chronic sialadenitis, or inflammatory lesion, such as lymphoepithelial cyst, on histologic follow-up. There was no follow-up pathology in 46.5 percent (20 of 43) of nondiagnostic and 82.6 percent (38 of 46) of nonneoplastic cases. However, no lesions were apparent clinically with a mean follow-up of three years and 1.5 years, respectively. The authors concluded that the MSRSGC categories nondiagnostic and nonneoplastic are helpful for reporting salivary gland FNA results. With proper clinical and radiologic correlation, risk of malignancy in the nonneoplastic group is low. Yet risk of malignancy in the nondiagnostic group remains significant. Repeat FNA after clinical and radiologic correlation for nondiagnostic cases seems prudent as neoplasms and malignancies may have gone undetected.
Johnson DN, Antic T, Reeves W, et al. Histopathologic and clinical outcomes of Milan system categories “non-diagnostic” and “non-neoplastic” of salivary gland fine needle aspirations. J Am Soc Cytopathol. 2021;10(4):349–356.