Systemic Sclerosis Association with Malignancy

Abstract

The association of systemic sclerosis (SSc) and cancer is well known from several decades suggesting common genetic and environmental risk factors involved in the development of both diseases. Immunosuppressive drugs widely used in SSc may increase the risk of cancer occurrence and different SSc clinical and serological features identify patients at major risk to develop malignancy. In this context, among serological features, presence of anti-RNA polymerase III and anti-topoisomerase I autoantibodies seems to increase cancer frequency in SSc patients (particularly lung and breast cancers). Lung fibrosis and a long standing SSc pulmonary involvement have been largely proposed as lung cancer risk factors, and the exposure to cyclophosphamide and an upper gastrointestinal involvement have been traditionally linked to bladder and oesophagus cancers, respectively. Furthermore, immune checkpoint inhibitors used for cancer therapy can induce immune-related adverse events, which are more frequent and severe in patients with pre-existing autoimmune diseases such as SSc. The strong association between SSc and cancer occurrence steers clinicians to carefully survey SSc patients performing periodical malignancy screening. In the present review, the most relevant bilateral relationships between SSc and cancer will be addressed.

Pulmonary Nodules in Juvenile Systemic Sclerosis: A Case-Series from the National Registry for Childhood Onset Scleroderma (NRCOS)

“…Pulmonary nodules are well-known features in a number of autoimmune/rheumatologic conditions including vasculitides (e.g., giant cell arteritis, Behcet’s disease, ANCA-associated, Kawasaki disease), Crohn’s disease, IgG4-related disease, systemic lupus erythematosus, and Evan’s syndrome [ 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. Additionally, persons with aSSc are also at risk for pulmonary malignancy (adenocarcinoma) [ 28 ], although it is less clear whether jSSc is associated with similar risk. To our knowledge, there has been only one case report of jSSc associated with pulmonary adenocarcinoma, who also had a congenital pulmonary airway malformation which is known to be a risk for malignancy [ 29 ].…”

Comprehensive Exploration of Antinuclear Antibodies (ANAs): Unveiling Clinical Significance, Associations with Cancer, and the Nuances of Differential Diagnosis in Positive ANA Patients

“…Additionally, studies have highlighted a notable link between anti-RNA polymerase III antibodies and an elevated risk of cancer in patients with systemic sclerosis (SSc). These antibodies have been significantly associated with an increased likelihood of concomitant malignancy, leading researchers to recommend regular cancer screening for individuals testing positive for anti-RNA polymerase III antibodies in the context of SSc [29,30].…”

Anti-Th/To Antibodies in Scleroderma: Good Prognosis or Serious Concern?

“…Further research into this is required. Various studies have proved that anti-Th/To autoantibodies are valuable tools in risk stratifying among patients with SSc for malignancy [ 59 , 110 ]. Currently, there is a lack of comprehensive clinical studies that would assess the risk of carcinogenesis based on particular SSc-autoantigen.…”