BPH: benign prostatic hypertrophy, NSAIDs: nonsteroidal anti-inflammatory drugs; eGRF: estimated glomerular filtration rate

This case demonstrates the importance of the differential diagnosis because the events described above are associated to a case of hyperparathyroidism mimicking the signs and symptoms coherent with a suspicion of MM. Particularly, the diagnostic journey for this patient led to a evidence of a brown tumor (BT), a pathologic expression of “osteitis fibrosa cystica” associated to an uncontrolled hyperparathyroidism. This skeletal manifestation was first described by Recklinghausen in 1891 and is the result of the overproduction of PTH in primary or secondary hyperparathyroidism: osteoblasts will increase RANKL expression, which binds to its corresponding RANK receptor on osteoclasts and promotes osteoclast activity. PTH also reduces osteoprotegerin (PG) levels, preventing RANKL and RANK interactions and thus inhibiting bone resorption. Based on this process, this tumor-like lesion represents the terminal stage of the bone remodeling process with an overall incidence of 2–3%¹¹. BT can involve in any part of the skeleton, but most frequently they are found in the jaws, ribs, clavicles, extremities, and pelvic girdle and although the lack of malignant potential, it may be invasive. Clinical manifestations include swelling, pathological fracture diffuse skeletal pain and in case of multiple bones these lesions can mimic metastatic disease. The pathology features are characterized by non-neoplastic reactive tissue associated to an extensive osteoclastic bone resorption and osteoclast-like multinucleated giant cells, osseous microfractures, and hemorrhage as well as hemosiderin depositions The term brown tumor refers to an accumulation of hemosiderin pigment, giving the lesion its macroscopically brown appearance The radiological examination shows osteolytic lesions with well-defined borders and differential diagnosis includes primarily bone metastasis, Multiple Myeloma, amyloid cysts, chondroma, aneurysmal bone cyst, osteosarcoma, and giant cell tumor¹². Hyperparathyroidism (HPT) is the third most common endocrine disease after diabetes and thyroid disorders. HPT can be can be primary, secondary, or tertiary. Primary HPT occurs when ≥1 parathyroid glands produce too much PTH; the main causes of this clinical condition are a solitary adenoma in 80–85% of patients, multiple adenomas in 5%, parathyroid hyperplasia in 10–15%, and carcinoma in less than 1–5%. Secondary HPT occurs when the increased PTH secretion is due to an organic cause (such as kidney, liver, or bowel disease causing hypocalcemia and a subsequent increase in PTH secretion). Tertiary HPT is a consequence of persistent parathyroid stimulation (such as long-standing secondary hyperparathyroidism), which results in autonomous (unregulated) PTH function.

In this clinical case the overlap of symptoms makes the diagnosis very challenging because not only the signs and symptoms were very suspicious for MM but also the blood test and the radiological findings were typical for the plasma cells disease. Particularly the whole-body CT and PET-CT mimicked the myeloma bone disease. The refractoriness to the therapy with Zoledronic Acid, the absence of monoclonal protein and pathologic bone marrow plasma cells and the arising of PTH led us to consider an alternative cause of the clinic manifestations and only the histopathologic examination helped us to achieve a diagnosis. A prompt endocrinology evaluation and surgery therapy were essential to resolve the patient’s symptoms with an improvement of his outcome and quality-of-life.

Conclusions. Our case reminds clinicians they should always consider multiple differential diagnosis when face a cohort of signs or symptoms coherent with a suspicion of MM not confirmed by investigations because, particularly in elderly patients, the CRAB could be non-specific and associated with different non-neoplastic diseases.

Authorship and Disclosures . DD and MP reviewed the literature and wrote the paper. CC, TD, DP, SN and AML followed the patient and wrote the paper. GLS supervised the work.