Lymphovascular invasion, higher nodal stage predict recurrence, breast cancer-related deaths

The presence of lymphovascular emboli and higher nodal stage (N2 or higher) in a breast carcinoma with medullary-like features are pathologic parameters that are predictive of its possible aggressive and fatal behaviour, a Singapore study suggests.

“Lymphovascular invasion and high nodal stage as well as triple negativity among typical and atypical medullary breast carcinomas (MBCs) that have basal-like phenotype represent a portion of invasive carcinomas with medullary features that may have poor outcomes in this otherwise relatively good prognostic group,” the researchers said.

In this study, clinicopathological features of MBs diagnosed at the Department of Pathology, Singapore General Hospital, were reviewed and correlated with immunohistochemical expression of hormonal markers and c-erbB-2, the basal markers p53, cytokeratin (CK) 14, epidermal growth factor receptor (EGFR) and 34BE12, and the follow-up outcome.

The researchers used Ridolfi’s criteria for histologic reviews and reclassified 62 patients previously diagnosed as having ‘typical MBC’ (n=26), ‘atypical MBC’ (n=32), and ‘invasive carcinoma with focal medullary-like features’ (n=4) as follows: ‘typical MBC’ (n=6; 9.7 percent), ‘atypical MBC’ (n=46; 74.2 percent), and ‘nonmedullary infiltrating carcinoma’ (n=10; 16.1 percent). [Singapore Med J 2021;doi:10.11622/smedj.2021031]

Clinicopathological parameters, such as age, ethnicity, tumour size, and concurrent ductal carcinoma in situ (DCIS), were not statistically significantly associated with review diagnoses and immunohistochemical findings. On the other hand, the presence of lymphovascular invasion and nodal stage significantly predicted recurrence and breast cancer-related deaths, respectively.

Furthermore, oesterogen receptor (ER) negativity showed a significant correlation with triple positivity for basal markers CK14, EGFR, and 34BE12, which comprised patients who showed a significantly reduced disease-free survival rate within a 10–15-year follow-up period.

“While all the cases presented with syncytial sheets of pleomorphic cells and mononuclear inflammation in variable amounts, adherence to the combination of the quantum >75 percent syncytial sheets, anastomosing pattern of the syncytial pleomorphic cells, diffuse rather than peritumoral distribution of at least moderate to marked mononuclear inflammation, complete rather than partial tumour circumscription, and absence of microglandular patterns and DCIS were the criteria to be fulfilled for a tumour to be classified as ‘typical medullary’,” the researchers said.

Of note, the diagnostic concordance was not strictly measured in this study, but the difference in diagnoses between the original reports and the reviewers’ consensus diagnoses indicated the high inter-observer variability in the morphologic interpretation of medullary carcinoma, as frequently reported. [https://www.cmcanceralliance.nhs.uk/application/files/3615/4815/5660/Guidelines_for_NHS BSP58_January_2005_Reviewed_CNG_June_2010.pdf; Breast Cancer Res Treat 1989;14:91-99; J Surg Oncol 1995;60:89-94; Eur J Cancer 1994;30A:1792-1797; Mod Pathol 2010;23:1357-1363]

“Ridolfi’s criteria have since been tested for not only their reproducibility but also prognostic significance, and have since been modified by several authors, with additional features such as sparse necrosis, absence of fibrosis, and nuclear pleomorphism proving to be prognostically significant,” the researchers said. [Hum Pathol 1998;19:1340-1346; Breast Cancer Res Treat 1989;14:91-99; J Surg Oncol 1995;60:89-94; Eur J Cancer 1994;30A:1792-1797; Mod Pathol 2010;23:1357-1363; Histopathology 1997;30:523-532; Eur J Cancer 2009;45:1780-1787; J Clin Oncol 2002;20:2310-2318]

“MBCs are distinguished by circumscribed, high-grade morphology with dense chronic inflammation; they are associated with the basal phenotype but have a relatively good prognosis,” they noted.