Scleroderma as a paraneoplastic syndrome and tumors associated with scleroderma

Abstract

Patients with systemic scleroderma, or systemic sclerosis (SS), have an increased risk of developing malignant neoplasms. Cancer can be diagnosed immediately prior to SS symptoms, at the stage of diagnosis and years after SS diagnosis. The first two cases may indicate scleroderma-like paraneoplastic syndrome. In this case, the main mechanism of paraneoplastic syndrome development is associated with immune system activation by antigens, expressed by tumor cells, which leads to the development of antibodies that cross-react with body tissues, causing damage and secondary regeneration. Thus, cancer induces autoimmunity – mutation-specific T-cell immune response, and pathogenetic mechanisms can be the same for fibrogenesis and oncogenesis.SS clinical and laboratory characteristics that indicate paraneoplastic etiology include minimum time difference between diagnosing scleroderma and cancer, as well as oncopathology in a patient’s or family cancer history, late disease onset (after 50 years), SS symptoms in a man, sudden onset and rapid progression of clinical symptoms, expressed or atypical SS symptoms (malaise, fever, significant weight loss), asymmetric or absent Raynaud syndrome, antibodies against RNA polymerase III, absence of anticentromeric antibodies and anti-Scl70, deviations in laboratory tests indicating possible oncopathology (anemia, hypercalcemia, hypergammaglobulinemia), no response to SS treatment, disappearance of SS symptoms after anticancer treatment and their appearance when cancer reactivation. On the other hand, patients with scleroderma have an increased risk of all types of cancer, with men at higher risk than women. Continuous autoimmune stimulation, B-cell activation, chronic inflammatory process and fibrosis in SS patients can lead to malignant transformation in certain organ systems, especially in lungs.The most important risk factor for lung cancer in SS patients is interstitial lung disease, requiring special attention from a physician. In addition to lung cancer, SS patients more likely than the general population suffer from malignant hematologic diseases, esophageal cancer, hepatocellular carcinoma and bladder cancer. Scleroderma-like skin changes are also possible when cytotoxic drugs are used to treat cancer (docetaxel, paclitaxel, bleomycin, etc.), as well as during radiation therapy.

Keywords

• systemic scleroderma
• systemic sclerosis
• malignancies
• scleroderma-like paraneoplastic syndrome
• borderline cancer
• tumorassociated scleroderma
• malignant transformation
• circumscribed scleroderma
• localized scleroderma
• morphea
• fibrogenesis
• sclerodactyly
• raynaud syndrome
• capillaroscopic changes of nailfold vessels
• autoimmunity
• antinuclear antibodies
• autoantibodies to toisomerase i
• anticentromeric antibodies
• autoantibodies to rna polymerase iii
• interstitial lung disease
• barrett’s esophagus
• lung cancer
• cytotoxicotherapy
• cyclophosphamide
• docetaxel
• bleomycin
• cancer prevention