Advertisement

A great masquerader disease…

      1. Case description

      A 64-year-old-man, with history of hypertension, dyslipidemia, serous chorioretinopathy and past-smoking history (15 pack-years) presented with asthenia and weight loss (6 kg in 6 months). His-physical examination was unremarkable and biological tests showed inflammation (CRP 20 mg/L). A retroperitoneal fibrosis was diagnosed on CT-scan with a left pulmonary nodule and mediastinal lymphadenopathy (Fig 1. A, B), these lesions being hypermetabolic on PET-scan. A lung nodule biopsy showed no malignant cells, but fibrosis associated with a lymphocytic infiltration. Despite a strong suspicion of cancer, the patient first refused further investigations. Nine months later, a control CT-scan revealed a mass of the left kidney while the pulmonary mass was stable. As the characteristics of the renal mass argued for a renal cancer on MRI (Fig 1.C), the diagnosis of cancer-associated retroperitoneal fibrosis was suspected, and a nephrectomy was performed.
      Fig. 1
      Fig. 1Radiologic explorations: A) CT-scan showing retroperitoneal fibrosis and B) lung pseudotumor; C) Magnetic Resonance Imaging showing a tumor of the lower part of the left kidney. T1 Fat Sat Gadolinium ponderation. Histopathology of the kidney: D) Hematoxylin-eosin-saffron staining of the renal tumor, showing an obliterative phlebitis (white arrow) surrounded by a storiform-pattern fibrosis (star) with an inflammatory lymphoplasmacytic infiltration (black arrow) and E) the presence of IgG4 plasma cells (Cell Marque, clone EP138, dilution 1/1000).

      2. What is the diagnosis?

      Pathological examination showed a storiform pattern fibrosis, associated with obliterative phlebitis and a lymphoplasmacytic infiltrate with an IgG4/IgG ratio greater than 50% (Fig 1. D, E). The diagnosis of IgG4-Related Disease with pseudotumors of the kidney and the lung, and retroperitoneal fibrosis was retained. The elevated plasma level of IgG4 (255 mg/dL, normal range <135 mg/dL) decreased to 188 mg/dL after nephrectomy. As a progression of retroperitoneal fibrosis would definitively alter renal function, a treatment was indicated. Because of the history of serous chorioretinopathy, steroids were contraindicated, and rituximab was given (1 g day 1 and 15) followed by a maintenance therapy (500 mg every 6 months), leading to persistent clinical and metabolic remission at 4-year follow-up. IgG4 concentration decreased to 54 mg/dL. Despite chronic B cell depletion, no infection nor hypogammaglobulinemia were observed.
      IgG4-RD is a pleomorphic disease with clinical manifestations including retroperitoneal fibrosis, pancreatitis, salivary gland swelling or ophthalmological involvement [
      • Vasaitis L
      IgG4-related disease: a relatively new concept for clinicians.
      ]. Pseudotumors are rare, usually periorbital [
      • Vasaitis L
      IgG4-related disease: a relatively new concept for clinicians.
      ], while pulmonary or renal localizations are exceptional [
      • Chougule A.
      • Bal A
      IgG4-related inflammatory pseudotumor: a systematic review of histopathological features of reported cases.
      ]. Steroids remain the first line therapy, but rituximab is interesting as second line therapy and for maintenance therapy [
      • Campochiaro C.
      • Della-Torre E.
      • Lanzillotta M
      Long-term efficacy of maintenance therapy with Rituximab for IgG4-related disease.
      ].
      In our case, while the first lung biopsy argued for IgG4-RD, the emergence of a kidney tumor prompt us to revise this diagnosis to suspect a kidney malignancy associated with paraneoplastic retroperitoneal fibrosis, thus motivating nephrectomy. However, clinicians should keep in mind that IgG4-RD can rarely be responsible for kidney tumor and that in such a situation, percutaneous biopsy must be favored to avoid the removal of a non-malignant functional organ.

      Declaration of Competing Interest

      The authors have no conflict of interest to report related to this manuscript.

      References

        • Vasaitis L
        IgG4-related disease: a relatively new concept for clinicians.
        Eur J Intern Med. 2016; 27: 1-9
        • Chougule A.
        • Bal A
        IgG4-related inflammatory pseudotumor: a systematic review of histopathological features of reported cases.
        Mod Rheumatol. 2016; 14: 1-6
        • Campochiaro C.
        • Della-Torre E.
        • Lanzillotta M
        Long-term efficacy of maintenance therapy with Rituximab for IgG4-related disease.
        Eur J Intern Med. 2020 Apr; 74: 92-98