Discussion

Mixed connective tissue disease and psoriatic arthropathy

Mixed connective tissue disease was first described as a new autoimmune rheumatic disease in 1972 based on the claim of a distinct clinical picture associated with antiribonucleoprotein antibody positivity. This systemic syndrome consists of overlapping features between scleroderma, systemic lupus erythematosus, polymyositis/dermatomyositis, with a favorable prognosis. Although breast involvement in autoimmune diseases is uncommon, possible presentation at mammography includes either localized disease or indirect signs of systemic involvement. Imaging findings can include breast masses, axillary lymphadenopathies, calcifications, and skin changes.

The interest of this case lies in the fact that diffuse lymphadenopathies detected at screening mammography can lead to multiple differential diagnoses and are not always synonymous with lymph node malignancy, including metastases from overt or occult breast cancer. According to the American College of Radiology Breast Imaging Reporting and Data System (ACR BI-RADS), enlarged axillary lymph nodes require clinical correlation and additional imaging, particularly when new or modified in comparison to previous examinations. Thus, the patient’s medical history may explain the axillary lymphadenopathy, avoiding further evaluation.

Axillary ultrasound is the main imaging tool for the assessment of lymph nodes, which are divided into three levels in relation with the pectoralis minor muscle: level I axillary lymph nodes are lateral to the lateral border of the pectoralis minor muscle; level II axillary lymph nodes are between the medial and lateral borders of the pectoralis minor muscle; level III axillary lymph nodes are medial to the medial margin of the pectoralis minor muscle and inferior to the clavicle.

Infectious diseases, lymphoma, leukemia, breast cancer, and melanoma of the areas drained by axillary lymph nodes (i.e., upper arms, trunk, and breast) must always be considered as possible differential diagnoses. In particular, axillary lymph nodes have been reported to be involved in the 11.9% of cases of non-Hodgkin and Hodgkin lymphomas. Rarely, axillary lymphadenopathy (mostly unilateral) can also originate from a primary breast lymphoma, with regional nodal involvement at diagnosis ranging from 28.3% to 37.9%.It is also common for patients suffering from connective tissue diseases such as rheumatoid arthritis, systemic lupus erythematosus, et al, to present with bilateral axillary lymphadenopathies, which reflect the inflammatory activity and severity of the disease, and can be visualized on mediolateral oblique mammographic projections.

In all these cases, the appearance and morphology of lymph nodes observed on mammograms, and subsequently evaluated with bilateral axillary ultrasound, can be suggestive of their malignancy or rather of their benign nature: according to the ACR BI-RADS, although there is no consensus and there is wide individual variability, a normal axillary lymph node may be up to 2 cm at its longest dimension and contain hyperechoic fatty hilum. Indeed, while fatty hilum, oval shape, and regular margins are characteristic features of normal or benign lymph nodes, round shape, absence of the fatty hilum, and increased eccentric or focal cortical thickness are characteristics concerning for malignancy. Of note, the cortical thickness measure used as a cut-off point for metastatic disease is highly variable in the literature, ranging from 2.3 to 3 mm. Therefore, the cortex to hilum ratio can also be adopted, suggesting malignancy when the former parameter is greater than or equal to the latter. Furthermore, bilateralism and the enlargement of many lymph nodes in a specific chain are also very important, suggesting a systemic etiology and potentially excluding the involvement of singular nodes, as in the case of metastatic diseases.

Nonetheless, comparison with previous imaging examinations and correlation with the clinical status of the patient are important, especially when lymphadenopathies are newly identified, as in our case. Thus, investigation and collection of a detailed anamnesis have a key role in the clinical decision-making.

It is also important to recall the possibility of occult breast cancer, described as an axillary metastatic carcinoma with no evidence of a primary breast lesion accounting for up to 1% of all breast cancers. In such cases, breast MRI or contrast-enhanced mammography should be performed, when digital breast tomosynthesis and ultrasound are also negative.

Finally, lymph node biopsy is recommended in the event of any doubt, when additional breast imaging examinations yield to inconclusive results, when the lymph nodes do not show clearly benign features, and when the clinical history of the patient is unknown or not reassuring.

Learning points

When dealing with axillary lymphadenopathies, several differential diagnoses must be taken into consideration, including benign and malignant diseases.
Implementation of clinical information and imaging examinations is pivotal for the decision-making process in the management of axillary lymphadenopathy.
Exclusion of primary breast cancer and morphologic characterization of lymph nodes using mammographic views and additional imaging (i.e., digital breast tomosynthesis, ultrasound, additional views, breast MRI) might guide the diagnosis.
In case of bilateral axillary lymphadenopathy, autoimmune systemic conditions such as mixed connective tissue disease must be considered as the potential underlying condition.

References

View the original case report for a complete list of references.

Our appreciation is extended to Dr. Emilia Giambersio, Postgraduate School in Radiodiagnostics, Università degli Studi di Milano, Milano, Italy, Dr. Veronica Magni, Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milano, Italy, and Prof. Francesco Sardanelli, Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milano, Italy, for contributing this case. Case was originally published in BJR|case reports.