Amyloidosis is a rare and complex disease characterized by pathological extracellular tissue deposition of insoluble fibrillar protein in tissues which can cause severe organ dysfunction and result in various clinical manifestations depending on the affected area and the amount of material deposited. The symptoms of the disorder are nonspecific and, therefore, it may be difficult to suspect a diagnosis.

To show the diagnostic spectrum in a disease with broad clinical and nonspecific manifestations, such as extreme weight loss, macroglossia and nephrotic syndrome.

A 70-year-old man seeked medical attention due to important edema of ankles with Godet Sign 3+. During clinical evaluation, urinalysis exhibited proteinuria of 6000mg/24h, indicating nephrotic proteinuria. The patient reported mild fatigue and dyspnea. An echocardiogram suggested cardiac amyloidosis, which was confirmed after a fat pad biopsy stained with Congo Red under polarized light. The patient performed autologous bone marrow transplantation and is doing well after a two year follow up.

An 83-year-old woman presented with macroglossia, leading her to have difficulty in eating. At physical examination, the skin manifestation known as raccoon's eyes due to vascular infiltration of amyloid fibrils in a symmetrical periorbital distribution was present. A fat pad biopsy was performed and revealed amyloid deposits. Furthermore, due to the presence of anemia, a bone marrow smear detected Multiple Myeloma (20% plasmocytes), suggesting secondary amyloidosis. The patient began treatment with daratumumab two months ago.

A 62-year-old man seeked medical attention due to intense weight loss of over 39 pounds in a 6-month period. At physical examination, the patient was pale (3+/4), had intense muscle atrophy, depicting a consumptive syndrome. Due to anemia, a bone marrow trephine was performed, surprisingly revealing amyloid deposits.

This report shows three very different clinical presentations of amyloidosis, reinforcing the extreme heterogeneity of the disorder. Besides the most common sites for amyloid deposits, it's important to notice the possibility of bone marrow infiltration and extreme weight loss. Therefore, it's crucial to beware of amyloidosis's multiple manifestations for better clinical investigation. In case 1, the patient was diagnosed with nephrotic syndrome, hence the kidneys being one of the most affected organs by amyloid deposits. The patient also showed cardiac involvement, where manifestations may include arrhythmias and heart failure. Those symptoms, when associated with signs of nephrotic syndrome, should raise suspicion for amyloidosis as the underlying cause. In case 2, a woman presenting with macroglossia developed, later on, periorbital purpura from amyloid deposits. The manifestation, known as raccoon's eyes, is characteristic of amyloidosis, but it is rare and only present in less than 10% of cases. In case 3, a 62-year-old patient presented with extreme weight loss and a consumptive syndrome. Due to his state of anemia, a bone marrow biopsy was performed and revealed amyloid deposits. A bone marrow biopsy is highly useful when determining the precursor protein while also screening for possible tissue infiltration and deposition.