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.