An Unusual Case of Thrombocytopenia and Renal Failure Revealing Malignancy-Associated Thrombotic Microangiopathy

Thrombotic microangiopathy (TMA) is a process characterized by thrombocytopenia, microangiopathic hemolytic anemia, and end-organ injury. Malignancy-associated TMA is uncommon and may resemble primary TMA syndromes, particularly when renal dysfunction predominates and peripheral smear findings are limited. We present a case of biopsy-confirmed renal TMA in the setting of newly diagnosed metastatic squamous cell carcinoma (SCC) following significant diagnostic uncertainty. A 59-year-old man with insulin-dependent diabetes mellitus presented with worsening headache, neck pain, dysphagia, shortness of breath, poor oral intake, and significant weight loss. Initial evaluation demonstrated acute hypoxic respiratory failure, progressive renal failure, thrombocytopenia, and a newly identified right-sided neck mass. Laboratory studies showed anemia, elevated lactate dehydrogenase, low haptoglobin, and reticulocytosis, raising concern for TMA. Peripheral smear showed few schistocytes, while ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif member 13) activity was reduced but not severely deficient. Autoimmune and complement studies were unrevealing. Renal function progressively worsened, requiring initiation of hemodialysis. Renal biopsy demonstrated acute and chronic TMA with chronic vascular changes. Additional otolaryngologic evaluation confirmed invasive, moderately differentiated nonkeratinizing SCC of the uvula with metastatic cervical disease. Given the biopsy findings, lack of severe ADAMTS13 deficiency, unrevealing autoimmune workup, and overall clinical course, malignancy-associated TMA was favored over primary thrombotic thrombocytopenic purpura and other secondary causes. Renal TMA in patients with newly diagnosed malignancy may present with a broad and overlapping differential diagnosis. In this case, renal biopsy clarified this mechanism, as the limited peripheral smear findings and multiple overlapping causes of secondary TMA had posed significant diagnostic challenges.