CA 15.3: a marker of disease activity in sarcoidosis

To the editors,

Carbohydrate antigen CA 15.3 is a mucin glycoprotein which is a well-known marker of breast cancer. Elevated levels of CA 15.3 are also found in patients with adenocarcinoma of the lung, pancreas, kidney, ovary and colon (1). Mucin glycoproteins are located on the surface of different epithelial cells and protect the cell against proteolytic enzymes. In malignant tissues, there is an upregulated expression of muc-1 gene resulting in higher concentrations of CA 15.3 in the circulation (1). However, few studies reported an association of CA 15.3 with benign diseases as well, in particular pulmonary fibrosis and advanced stage sarcoidosis (stage III-IV) (2-5). The exact mechanism of this correlation is not clear and this association is unknown by many clinicians. Therefore, we want to present a case in which a history of breast cancer, elevated CA 15.3 levels and lymphadenopathy leads toward a diagnosis of metastatic disease. However, after adequate analysis it turns out to be something else.

We present a 61-year-old woman with a history of breast cancer in 2004, which has been treated with curative intention. In 2012, she presented with symptoms consisting of non-intentional weight loss, easy fatigability, progressive dyspnoea and non-productive cough. Laboratory results showed only an increased CA 15.3 level of 68 kU/l (n<40 kU/l). CT scan of thorax/abdomen showed bihilar and mediastinal lymphadenopathy as well as multiple small noduli located in both lungs. There was no evidence of recurrence of mamma carcinoma both on CT and mammography. Histological needle biopsy of the mediastinal lymph nodes was performed and unexpectedly, the tissue showed well-formed, noncaseating granulomas without any evidence of malignant disease. Additional laboratory tests showed an increase of the Erythrocyte Sedimentation Rate (ESR) of 71 mm/hr (<20 mm/hr), an angiotensin-converting enzyme level of 31 U/L (5-21 U/L) and lysozyme of 810 kU/L (280-620 kU/L). The Quantiferon test was negative (<0.35 IU/ml). Furthermore, somatostatin scintigraphy demonstrated a typical lambda sign suggestive for sarcoidosis. Based on these findings, the diagnosis sarcoidosis stage II was made. Treatment with corticosteroids (prednisolone 10 mg/day) led to improvement of symptoms and decreased disease activity. The CT-scan showed a reduction in the size of hilar and mediastinal lymph nodes. Laboratory results showed normal levels of calcium (2.43 mmol/l). ACE and CA 15.3 levels decreased within 1 year of follow-up (figure 1). The dose of prednisolone was tapered to 5 mg daily and was stopped after seven months of treatment. After 1 year, the CT-scan showed a significant reduction in hilar and mediastinal lymphadenopathy as well as in the size of the pulmonary lesions.

Fig. 1.

Levels of CA-15.3 and ACE during treatment and follow-up

Our case demonstrates that CA 15.3 can be associated with early stage sarcoidosis. Furthermore CA 15.3 was a potential marker of disease activity in our patient, as CA 15.3 level significantly decreased with reduced disease activity. However, the exact mechanism of the correlation of CA 15.3 with sarcoidosis has to be further investigated. In clinical practice, we have to be aware that an elevated CA 15.3 level in patients with a history of breast cancer is not always associated with recurrence of breast cancer. In these patients, histological confirmation is required to obtain the right diagnosis.