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* Purpose.--To update key recommendations of the American Society of Clinical Oncology/College of American Pathologists estrogen receptor (ER) and progesterone receptor (PgR) testing in breast cancer guideline. Methods.--A multidisciplinary international Expert Panel was convened to update the clinical practice guideline recommendations informed by a systematic review of the medical literature. Recommendations.--The Expert Panel continues to recommend ER testing of invasive breast cancers by validated immunohistochemistry as the standard for predicting which patients may benefit from endocrine therapy, and no other assays are recommended for this purpose. Breast cancer samples with 1% to 100% of tumor nuclei positive should be interpreted as ER positive. However, the Expert Panel acknowledges that there are limited data on endocrine therapy benefit for cancers with 1% to 10% of cells staining ER positive. Samples with these results should be reported using a new reporting category, ER Low Positive, with a recommended comment. A sample is considered ER negative if < 1% or 0% of tumor cell nuclei are immunoreactive. Additional strategies recommended to promote optimal performance, interpretation, and reporting of cases with an initial low to no ER staining result include establishing a laboratory-specific standard operating procedure describing additional steps used by the laboratory to confirm/adjudicate results. The status of controls should be reported for cases with 0% to 10% staining. Similar principles apply to PgR testing, which is used primarily for prognostic purposes in the setting of an ER-positive cancer. Testing of ductal carcinoma in situ (DCIS) for ER is recommended to determine potential benefit of endocrine therapies to reduce risk of future breast cancer, while testing DCIS for PgR is considered optional. Additional information can be found at www.asco.org/breast-cancer-guidelines. (Arch Pathol Lab Med. 2020;144:545-563; doi: 10.5858/arpa.2019-0904-SA), INTRODUCTION First released in 2010, the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) estrogen receptor (ER) and progesterone receptor (PgR) testing guideline is aimed at improving the [...]

The caudal-related homeobox transcription factor CDX2 regulates the differentiation of intestinal epithelial cells. Recent studies have suggested that CDX-2 immunoreactivity is strictly confined to benign and malignant intestinal epithelium. In the present study, we evaluated the prevalence of CDX2 immunoreactivity in a series of benign, borderline and malignant primary ovarian mucinous neoplasms. We tested 62 mucinous tumours of the ovary, including 28 benign cystadenomas, 18 borderline tumours, 16 adenocarcinomas, 35 serous and endometrioid ovarian lesions and 10 ovarian metastases of colonic adenocarcinoma. Overall, the CDX2 prevalence in primary mucinous tumours was 79%, including 20 of 28 (71.5%) cystadenomas, 14 of 18 (77.7%) borderline tumours and 15 of 16 (93.5%) adenocarcinomas. Immunoreactivity usually correlated with intestinal differentiation of tumour cells, although wide heterogeneity in the distribution of immunolabelled cells was noted. No immunoreactivity was observed in serous lesions; whereas, 1 of 13 (7.7%) endometrioid adenocarcinomas and all of the 10 metastatic colonic adenocarcinomas were immunostained. These results indicate that CDX2 is detectable in the majority of benign, borderline and malignant ovarian mucinous tumours and, therefore, makes this marker unsuitable when distinguishing primary from metastatic ovarian mucinous adenocarcinomas. However, CDX2 immunoreactivity could be useful in the distinction between endocervical and intestinal-type mucinous tumours of the ovary, which may have clinical relevance. [ABSTRACT FROM AUTHOR]

Most granular cell tumours (GCTs) are benign proliferations of purported Schwannian derivation, showing immunoreactivity for Schwann cell-related antigens. Due to incomplete agreement on the precise nature of GCTs (reactive vs neoplastic), we performed an immunohistochemical study with the alkaline phosphatase/anti-alkaline phosphatase (APAAP) technique on 30 GCTs. The aim was to evaluate their growth patterns and the possible relationships of granular cells with other nerve sheath-related cell types (i.e., Schwann and perineurial cells, and dendritic cells displaying CD34/vimentin immunoreactivity). An expansive growth pattern was detected in five cases, a pseudoinfiltrative growth pattern in nine cases and a mixture of the above in the remaining 16 cases. Besides immunoreactivity for S-100 protein, neuron-specific enolase, vimentin, CD57, CD68, MAC 387, alpha-1-antitrypsin and alpha-1-antichymotrypsin in granular cells, we documented intimate architectural relationships between granular cells, Schwann and perineurial cells, and a third type of CD34/vimentin-positive nerve sheath-related cell in most GCTs. These results suggest that GCTs are heterogeneous lesions. Some of them show a pseudoinfiltrative growth pattern and retain close relationships with the normal components of the nerve sheath. In other lesions, granular cells grow in an expansive fashion and constitute the predominant cell component of the tumour. These architectural and immunophenotypic differences may reflect a different nature of GCTs: they may initially represent reactive or hamartomatous lesions that subsequently acquire truly neoplastic potential. [ABSTRACT FROM AUTHOR]

Immunoreactivity for fascin, an actin-bundling protein related to cell motility, has been reported in breast, ovary, pancreas, skin, and non-small cell carcinomas, and associated with more advanced disease stage and poorer prognosis. Data on pulmonary neuroendocrine (NE) tumors, however, are lacking. We evaluated the expression of fascin by immunohistochemistry—using two different monoclonal antibodies—in surgical specimens of pulmonary NE tumors of all the diverse histological types from 128 consecutive patients recruited between 1987 and 2001, and investigated its relationship with the presence of lymph node metastases. Overall, fascin immunoreactivity was detected in 5% of 38 typical carcinoids (TC), 35% of 23 atypical carcinoids (AC), 83% of 40 large-cell neuroendocrine carcinomas (LCNEC), and 100% of 27 small-cell lung carcinomas (SCLC) (P<0.001), Normal NE cells or hyperplastic NE tumorlets were consistently unreactive. No statistically significant differences in fascin immunoreactivity were found between the two antibodies. In TC and AC but not high-grade NE tumors, fascin immunoreactivity closely correlated with the occurrence of lymph node metastases, the pN class and the number of involved lymph nodes (P<0.001). It was also significantly associated with an increased proliferative activity (Ki-67 labeling index >5%) (P=0.020), and with either down-regulation or altered subcellular compartmentalization of E-cadherin (P<0.001) and CD99 (P=0.030), two cell adhesion complexes in pulmonary NE tumors. At multivariate analysis, only fascin emerged as an independent predictor of lymph node metastases in this tumor group (HR 30.28; 95% confidence intervals: 1.59–574.49; P=0.023). This study indicates that fascin immunoreactivity may identify subsets of pulmonary carcinoid patients with different metastatic potential to regional lymph nodes. Targeting the fascin pathway could be a novel therapeutic strategy of pulmonary carcinoids. [Copyright &y& Elsevier]