Scleroderma as paraneoplastic disease: A new case of a rare association with renal cell carcinoma

Dear Editor,

We read with interest the case of a 75-year-old male patient diagnosed with renal cell carcinoma (RCC) and systemic sclerosis (SSc) reported by Patel et al. ¹ SSc can be associated with increased risk of malignancy, most commonly lung, skin and breast cancers, while RCC in SSc is very rare and the relationship between the two diseases is not fully understood. ¹ We report an additional case of RCC associated with SSc further supporting the hypothesis that SSc can be a paraneoplastic disease also from RCC.

In September 2020 a 47-year-old Caucasian woman was hospitalized to our Rheumatology Unit with suspicion for SSc. In March 2020 she manifested the abrupt appearance of severe Raynaud’s phenomenon, sclerodactilitis, facial and forearms sclerosis and arthralgias of hands and wrists. In the following months “puffy hands,” weight loss and dyspnea for mild-moderate efforts appeared. Diffuse pulmonary crackles, more accentuated at the bases, were appreciable. Blood analysis documented mild thrombocytosis and increased erythrocyte sedimentation rate (ESR; 100 mm/h), C-reactive protein (2.2 mg/dL), gamma-globulins (23.4%), anti-nuclear antibody (ANA; 1/640) with high titer of Scl-70 (>240 U/mL); ANCA, C3, C4, LAC, anti-phospholipids, anti-cyclic citrullinate antibodies and rheumatoid factor were negative; kidney and liver function were normal. Capillaroscopy showed an “early scleroderma pattern.” Chest high-resolution computed tomography (HRCT) evidenced a non-specific interstitial pneumonia (NSIP)-type pulmonary interstitial disease with bilateral pulmonary micronodules. At abdominal ultrasound a 6 × 5 × 3.5 cm mass of the left kidney was revealed. Contrast-enhanced ultrasound (CEUS) and computed tomography (CT) confirmed the diagnosis of kidney neoplasia, brain CT and bone scintigraphy–excluded metastases.

After left nephrectomy, histology documented a high nuclear-grade unclassifiable renal carcinoma with a prevalent tubuloalveolar growth pattern and papillary features, in the absence of lymphnode involvement. Chemotherapy was ruled out owing to the absence of metastases. Due to lung micronodules, immunosuppressive therapy for SSc was temporarily avoided and CT follow-up was scheduled after 3 months.

In December 2020 the patient manifested remarkable clinical improvement with reduction of acrocyanosis, arthralgias and swelling of the hands, initial reduction of sclerodactilitis and skin sclerosis (mRSS from 16 to 12). However, chest CT revealed further micronodules, more evident in the subpleural area at left lung base. US-guided percutaneous biopsy was performed and histology was deemed compatible with pulmonary fibrosis. In agreement with oncologists, in February 2021, immunosuppressive therapy with mycophenolate mofetil was started at a dosage of 2 g/day. The patient was re-evaluated in July 2021 and a further clinical improvement of sclerodactilitis and cutaneous sclerosis was confirmed (mRSS = 10), with 5 kg of weight gain. The echocardiography excluded pulmonary arterial hypertension. Chest X-ray showed no appreciable nodules; according to oncologists, further CT follow-up after 3 months was decided.

In our case, the rapidly progressive course of the disease along with the short timeline between the onset of SSc and the diagnosis of RCC and the prompt clinical improvement after the treatment of the neoplasia support the hypothesis that SSc could be paraneoplastic.

Finally, it is interesting to notice that, although males with SSc have an overall increased risk of malignancy, ² the currently described cases of RCC associated with SSc seem to favor the female sex (a total of 6 females and 3 males, including our case).