Multifocal osteolytic lesions of jaw as a road map to diagnosis of brown tumor of hyperparathyroidism: A rare case report with review of literature

Abstract

Brown tumor is unifocal or multifocal bone disease which represents terminal stage of hyperparathyroidism (HPT)-dependent bone pathology. It is recognized as a component of metabolic bone disease called osteitis fibrosa cystica generalisata or Von Recklinghausen disease of bone. HPT was first described by Von Recklinghausen in 1891. Brown tumor diagnosis nowadays is less frequently encountered because of early stage detection of HPT. This early detection is possible due to routine blood screening in asymptomatic adults or during evaluation of osteoporosis. Histologically, it may resemble any other giant cell lesion of the jaw that imposes diagnostic challenge and delay in treatment. We are introducing a case report of a 30-year-old female patient presented with multifocal osteolytic lesions in mandible with histopathology depictive of giant cell granuloma. Further biochemical investigations and X-ray skeletal changes raised the suspicion of primary HPT which was confirmed by parathyroid scintigraphy revealing parathyroid adenoma. The main purpose of this case report is to reinforce the role of oral examination in diagnosis of systemic diseases and to propose a diagnostic layout/algorithm when giant cells are present in biopsy specimen. Review of literature showing brown tumor of oral cavity associated with PHPT is discussed.

Keywords: Brown tumor; giant cell lesion; parathyroid adenoma; parathyroid scintigraphy; primary hyperparathyroidism.

Figure 1

Traditional calcium, parathyroid hormone, and Vitamin D axis for the regulation of calcium homeostasis.[6] Under conditions of dietary calcium restriction, a decrement in serum calcium concentration induces release of parathyroid hormone from the parathyroid gland. Increased parathyroid hormone acts on the kidneys to stimulate renal 25(OH) D3-1α hydroxylase activity (1α-hydroxylase), which increases synthesis of the active form of Vitamin D (1α, 25-(OH) 2D3; calcitriol). Increased parathyroid hormone and 1α, 25-(OH) 2D3 target bone to induce a net resorption of calcium and phosphorus from mineralized tissue into circulation. Increased 1α, 25-(OH) 2D3 also targets the small intestine to stimulate active absorption of calcium and phosphorus through upregulation of proteins involved in calcium transport including calmodulin (calcium M), calbindin (calcium BP), transient receptor potential channel vanilloid 6 (TRPV6, also referred to as calcium transport protein 1) and calcium ATPase. The kidneys are ultimately required to restore serum calcium concentrations and maintain a calcium-to-phosphorus ratio. The increased 1α, 25-(OH) 2D3 stimulates renal calcium reabsorption through upregulation of calcium transport proteins and downregulation of phosphorus transport proteins (NaPi2a and NaPi2c). The net renal response results in a decreased excretion of calcium and an increased urinary excretion of P. Increased 1α, 25-(OH) 2D3 also serves as a feedback regulator to decrease 1α-hydroxylase activity. The net response to a decrement of serum calcium is a restoration of serum calcium with no effect on serum phosphorus

Figure 2

Extraoral and intraoral presentation of patient. Normal facial symmetry (a) and multifocal osteolytic lesions in anterior mandible, left posterior body, and right ramus of mandible (b)

Figure 3

Cone-beam computed tomography showing radiolucencies in the mandibular anterior region and left posterior region. In anterior region, radiolucency is measuring about 13.5 mm × 11.3 mm extending till periapical region from 32 to 42, with round to oval in shape. Periphery of pathology is well defined with scalloped and corticated borders. No cortical expansion is seen. Perforation of lingual cortex and thinning of buccal cortex seen with irregular bone destruction in some areas is seen. No root resorption. (a-d). In the posterior region, radiolucency is measuring approximately 23.4 mm × 16.6 mm in length involving edentulous region of 37 and 38. Superior-inferiorly, it is extending from crest of alveolus to involve the inferior border of mandible. Periphery is ill-defined noncorticated with irregular shape. The presence of irregular bone destruction with loss of trabecular pattern. Thinning of cortex of the nerve canal in missing tooth space of 37 (e-g). (h) The 3D image of the affected site showing destruction of the bone

Figure 4

Three-dimensional re-construction of cone-beam computed tomography images and skeletal survey. Osteolytic lesions on right ramus, left postbody, and anterior region of mandible (yellow arrows a-c). Multiple discrete osteolytic lesions on spine, tibia, chest, and pelvis (d-g)

Figure 5

Histopathology of lesion. Incisional biopsy showed multinucleated giant cells in the background of abundant hemorrhage (a and b). Excisional biopsy revealed similar picture (c and d)

Figure 6

Parathyroid scintigraphy. The Tc-99M-tetrofosmin scan reveals abnormal large focus of intense tracer uptake in midline anterior neck, inferior to both lobes of the thyroid gland. Significant washout of tracer from thyroid gland is seen on delayed images with persistently seen focal tracer activity

Figure 7

Algorithm for diagnosis and treatment of primary hyperparathyroidism and exclusion of other giant cell lesions