Spiculation of breast masses seen on mammography represents adipose invasion

1. In patients with invasive breast cancer who underwent surgery, tumor spiculation was detected on mammographic evaluation in all patients with histologic evidence of marginal adipose tissue while only three-quarters of non-spiculated masses showed adipose invasion.

2.Mammographic evidence of spiculation was independently associated with adipose tissue invasion, higher histologic grade, increased breast density, and higher body mass index (BMI).

Evidence Rating Level: 2 (Good)

Study Rundown: Breast cancer is one of the most common malignancies diagnosed in women worldwide, and the second greatest cause of female morbidity and mortality in the United States. Invasive breast cancers are frequently difficult to manage, and any insight into the complex interaction between tumor cells and their interaction with the surrounding microenvironment could help catch these high risk tumors early. The mammographic finding of masses with “spiculation,” or dense regions with radiating lines with clustered, star-like, pleomorphic microcalcifications, is suspicious for malignancy.  To this end, a deeper understanding of the histopathologic mechanism by which tumors come to display spiculation or other mammographic findings suggestive of malignancy may help predict tumor subtype and provide prognostic clues. The current study sought to characterize the histologic basis for breast tumors displaying spiculation on mammography. Spiculated masses are the most commonly observed mammographic finding suggestive of invasive carcinoma and were therefore the subject of the present study. However, some post-operative scars may appear quite spiculated and resemble cancer; a careful clinical examination, additional mammographic views, and needle or surgical biopsy are often required to confirm disease. This study retrospectively compared histological findings in patients with biopsy-proven invasive breast cancer and mammographically spiculated masses to those without spiculation, finding that marginal adipose tissue invasion was present in all patients with spiculated masses but only in 77% of those without mammographic evidence of spiculation. This suggested that the development of spiculation may be due to the interaction between tumor cells and their fatty local environment and may be of a different character than non-spiculated tumors, which adds to a body of evidence that showed that spiculated tumors were more likely to be of the non-basal phenotype and of the luminal A subtype. Additionally, other factors independently associated with spiculation were found to be higher histologic grade, dense breast tissue, and greater body mass index. Limitations of this study include its observational and retrospective nature, in addition to a limited interval of follow-up, which may have contributed to lack of significance found for disease-free survival between comparison groups. Additionally, the researchers note that several of the lesions were miscategorized on imaging analysis, which may have further skewed the data.

Click to read the study in Radiology

Relevant Reading: Prognostic impact of marginal adipose tissue invasion in ductal carcinoma of the breast

In-Depth [retrospective cohort]: Patient medical records of 478 individuals with primary invasive carcinoma of the breast diagnosed between 1999 and 2009 were reviewed for this study. All subjects (median age: 56 yrs; age range: 26 to 96 yrs) underwent surgery and were followed for a median length of 74 months (range: 4–165 months). 136 spiculated tumors and 342 nonspiculated tumors were characterized on mammography. Using regression models and the Kaplan-Meier method, comparisons of clinical-pathologic findings between subjects with and without appearance of spiculation on mammography were studied. 100% (136 of 136 tumors) of the spiculated tumors were positive for adipose tissue invasion on histological examination, while 77% (264 of 342) of nonspiculated masses were observed for adipose invasion (P < 0.001). Other factors independently associated with spiculation were concluded on multivariate analysis included histologic grade (P < 0.001), dense breast (P = 0.002), and BMI (P = 0.02). Events used to determine the disease-free survival analysis included death due to primary, recurrent and metastatic breast cancers. No significant difference in overall survival rate between patients with spiculation on mammography and those without was found (disease-free survival: p = 0.09; overall survival: p = 0.23). Despite the similar prognoses between groups, patients who had tumors with spiculation were more likely to have hormone sensitive disease (estrogen receptor positive: p = 0.004; progesterone receptor positive: p = 0.001) and low grade tumors (p < 0.001) than patients without mammographically spiculated tumors.

Image: PD

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