Title

Renal Cell Carcinoma Masquerading as Iron-Deficiency Anemia: Unraveling the Inflammatory Twist in Two Cases

Authors

1. Ayushma Acharya, MD, Resident, Internal Medicine, Tower Health Reading Hospital 2. Swarup Sharma Rijal, MD, Internal Medicine, Tower Health Reading Hospital 3. Anthony A. Donato, MD MHPE, Professor of Medicine, Drexel University College of Medicine, Associate Program Director, Internal Medicine, Tower Health Reading Hospital 4. Daniel A Forman, DO, FACP, Hemato-oncology, Medical Director-Inpatient Oncology, Tower Health Reading Hospital

Introduction

Renal Cell Carcinoma (RCC) is often diagnosed incidentally and poses challenges due to nonspecific symptoms. RCC may present with non-specific paraneoplastic manifestations including anemia, which represent valuable diagnostic clues for renal malignancy.

Case Presentation

In the first case, a 60-year-old male with microcytic anemia presented with dyspnea on exertion, weakness, and dusky nail beds. Laboratory analysis revealed hemoglobin (Hb) of 8.8 g/dL, Mean Corpuscular Volume (MCV) 76.1 fL, iron saturation of 19%, ferritin 333 ng/ml, and platelet counts of 462 k/mcl. The patient received intravenous iron therapy and underwent a thorough evaluation, including endoscopy and colonoscopy to assess for acute blood loss. Urine analysis showed no evidence of hematuria. Subsequent laboratory results post iron therapy indicated a Hb of 7.1 g/dL, MCV of 76.2 fL, iron saturation of 15%, and ferritin of 3799 ng/ml. Test for vitamin B12, methylmalonic acid, folic acid, thyroid function testing, SPEP, UPEP, JAK2, BCR-ABL, and Coombs tests), provided no clear etiology. With persistent anemia of unclear etiology refractory to iron therapy, the patient underwent a bone marrow biopsy which showed a hypercellular marrow with adequate stainable iron. Elevated ESR, CRP, and ferritin indicated systemic inflammation. Rheumatological workup including ANA, ANCA, Anti-Jo1, anticentromere antibodies, Lyme disease titer, anti-SS-A, anti-SS-B, and MPO was normal. Finally, systemic imaging with CT chest, abdomen, and pelvis was performed to look for occult malignancy, which revealed an 8.6 cm right renal mass, para-aortic lymphadenopathy, left adrenal nodule, and T12 indeterminate sclerotic lesion. Biopsy confirmed type 2 papillary RCC. Due to advanced disease, systemic therapy was recommended, with surgery planned for later. Unfortunately, the patient succumbed before further investigation. In the second case, a 52-year-old male with chronic renal disease and gout presented to the hematology office for evaluation of anemia (Hb 8.3 g/dL, MCV 70 fL). Initial iron studies revealed a 10% iron saturation and ferritin of 796 ng/ml. The patient received 8 cycles of intravenous iron, resulting in a follow-up Hb of 9.4 g/dL, MCV 74 fL, iron saturation of 14%, reticulocyte count of 1.2, and ferritin 2094 ng/ml. The lack of improvement with iron therapy and a notable increase in ferritin levels prompted the investigation of an alternative cause. Urine analysis did not yield significant findings. Despite an exhaustive workup akin to the previously described case, which included endoscopy and colonoscopy, persistent anemia necessitated further evaluation. CT imaging revealed a 12 cm left kidney mass, highly suspicious for RCC. Biopsy confirmed chromophobe RCC and the patient underwent radical nephrectomy for Stage IV disease.

Discussion

Our cases highlight the tendency for RCC to present insidiously, with few symptoms until later-stage disease. Approximately 25–30% of patients present with metastatic disease, indicating a challenging prognosis. Anemia, especially of inflammation, is a common paraneoplastic syndrome associated with RCC, affecting 30-50% of cases. Anemia of inflammation is refractory to iron supplementation. Both cases underscore the role of anemia in prompting investigations leading to RCC diagnosis clinicians should consider RCC when faced with unexplained or refractory anemia, as it may serve as an indicator of an underlying malignancy.

References

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