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| CASE REPORT |
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| Year : 2023 | Volume
: 14
| Issue : 1 | Page : 97-102 |
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A rare case of “Brown tumor” of the axis with parathyroid adenoma and tertiary hyperparathyroidism
Umesh Srikantha1, Akshay Hari1, Yadhu K Lokanath1, DM Mahesh2
1 Department of Neurosurgery, Aster CMI Hospital, Bengaluru, Karnataka, India
2 Department of Endocrinology, Aster CMI Hospital, Bengaluru, Karnataka, India
| Date of Submission | 19-Nov-2022 |
| Date of Acceptance | 25-Dec-2022 |
| Date of Web Publication | 13-Mar-2023 |
Correspondence Address:
Akshay Hari
Department of Neurosurgery, Aster CMI Hospital, Bengaluru, Karnataka
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/jcvjs.jcvjs_144_22
 Abstract | | |
“Brown tumors (BTs)” of the spine are benign rare lesions, seen in about 5%–13% of all patients with chronic hyperparathyroidism (HPT). They are not true neoplasms and are also known as osteitis fibrosa cystica or occasionally osteoclastoma. Radiological presentations are often misleading and may mimic other common lesions such as metastasis. A strong clinical suspicion is therefore necessary, especially in the background of chronic kidney disease with HPT and parathyroid adenoma. Surgical spinal fixation in case of instability due to pathological fracture may be required along with excision of the parathyroid adenoma being the treatment of choice, that maybe usually curative and carries a good prognosis. We would like to report one such rare case of BT involving the axis, or C2 vertebra, presenting with neck pain and weakness that was treated surgically. Only a few cases of spinal BTs have been reported so far in the literature. Involvement of cervical vertebrae and in particular C2 is rarer still with the one in this report only being the fourth such case.
Keywords: Brown tumor, C2 cervical vertebra, chronic kidney disease, hyperparathyroidism, myelopathy, parathyroid adenoma
How to cite this article:
Srikantha U, Hari A, Lokanath YK, Mahesh D M. A rare case of “Brown tumor” of the axis with parathyroid adenoma and tertiary hyperparathyroidism. J Craniovert Jun Spine 2023;14:97-102 |
How to cite this URL:
Srikantha U, Hari A, Lokanath YK, Mahesh D M. A rare case of “Brown tumor” of the axis with parathyroid adenoma and tertiary hyperparathyroidism. J Craniovert Jun Spine [serial online] 2023 [cited 2023 Apr 1];14:97-102. Available from: https://www.jcvjs.com/text.asp?2023/14/1/97/371563 |
| Introduction | |  |
Brown tumor (BT) is a misnomer – it is not a true neoplasm.[1] It is an osteopathic reactive lesion due to persistent elevation of parathyroid hormone (PTH).[2] Hyperparathyroidism (HPT) may either be primary, secondary, or, less commonly, even tertiary. In primary HPT, there is increased secretion of PTH, which leads to increased calcium and decreased phosphate levels.[3] Secondary HPT is usually seen as a compensatory mechanism in chronic calcium-wasting conditions like chronic kidney diseases (CKDs), where there is hypocalcemia and hyperphosphatemia, which in turn leads to increased PTH levels.[4] Tertiary HPT is characterized by excessive secretion of PTH after long-standing secondary HPT. There is hyperplasia of the parathyroid gland, which becomes autonomous to the calcium feedback response. Hence, the PTH levels are excessively high, with high phosphate levels and calcium levels being either high or normal.[5]
Irrespective of the cause, the persistent elevation of PTH levels may be responsible for the abnormal progressive bone remodeling activities seen in BT.[2],[3] With increased osteoclastic activity, fibroblastic proliferation (a. k. a, osteitis fibrosa), collections of osteoclasts (so sometimes called “osteoclastoma,”) reactive giant cells, and hemorrhagic debris form a distinct hemosiderin-laden, “brown”-colored mass, leading to the term “BT.”[6]
BT can affect any part of the skeleton, being either monostotic or polyostotic.[7] While preferentially affecting sites such as the skull, jaw, phalanges, pelvis, clavicles, femur, and ribs, BTs may unusually affect the vertebrae as well. Involvement of the cervical spine, especially the axis (C2 vertebra) is exceedingly rare and there are only three other known reported cases in the literature.[8],[9],[10]
As a result, radiologically, BT may be mistaken for more common and more serious lesions such as metastasis, multiple myeloma, histiocytosis, or other malignant vertebral tumors.[1],[9] Clinical background of chronic HPT, CKD, or a parathyroid adenoma may necessitate a greater suspicion of this rare condition.
Due to the high risk of spontaneous pathological fractures, leading to instability, they may need to be addressed urgently.[6],[11] The possibility of rapid neurological deterioration as a result of spinal cord compression may require surgical decompression and stabilization in some cases.[2],[12] Timely diagnosis is key, thus helping to initiate treatment of the underlying disease process for achieving a complete cure.[13]
The authors report one such case of C2 BT associated with parathyroid adenoma in the background of CKD, presenting with neck pain and generalized weakness, where both lesions were treated surgically, followed by medical treatment of HPT.
| Case Report | | |
A 60-year-old female presented with persistent neck pain, restriction of neck movements, generalized weakness, and difficulty in walking for 1 year. She had a prior history of hypertension and polycystic kidney disease with end-stage renal disease – on dialysis for 11 years, awaiting a donor for a renal transplant. She also had chronic liver disease secondary to chronic hepatitis C infection. Two years prior, she had a traumatic fracture neck of the left femur requiring cemented bipolar hemiarthroplasty due to a trivial fall. She was also diagnosed to have a parathyroid adenoma during that time upon routine evaluation for osteoporosis. [Table 1] shows serum phosphate – 7.1 mg/dL, serum calcium – 10.2 mg/dL, serum vitamin D – 13.31 ng/mL, and plasma PTH – >2000 pg/mL, suggestive of HPT, which was managed medically. The data for the months from the onset of detection of HPT to date are presented in [Table 1] and [Figure 1]. Nevertheless, due to social reasons, her adherence to dialysis treatments and medications was irregular. | Figure 1: Graph showing laboratory biochemical data from the onset of detection to date
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She was then evaluated for her neck pain a year before presentation, with magnetic resonance imaging (MRI) of the cervical spine that revealed a C2 lytic lesion, with progression noted on computed tomography (CT) scan 4 months later and was advised surgery for both parathyroid and the C2 lesion elsewhere. However, she deferred surgery for personal reasons.
Her dialysis sessions continued, and her laboratory parameters were periodically monitored where PTH levels remained high (>4000 pg/mL). Further, her neck pain progressively worsened, and she also developed generalized weakness since then. On presentation, she had come in a wheelchair, referred from the otorhinolaryngology department for spine clearance in view of a planned parathyroidectomy surgery. On examination, she had weak hand grip bilaterally with grade 4 power in her lower limbs.
MRI and CT scans of the cervical spine were repeated, which revealed an expansile lytic lesion involving the vertebral body, odontoid process, and left pedicle of the C2 vertebra and as compared to the prior study, there was a moderate interval increase in the lesion, causing collapse with posterior and left lateral subluxation, impinging on the thecal sac and cord [Figure 2] and [Figure 3]. Furthermore, noted were diffuse radiologic lucencies (osteopenia vs. multiple lytic lesions) in the other visualized bones including multiple vertebrae, sternum, ribs, mandible, clavicle, and scapulae. | Figure 2: MRI of the cervical spine – T2WI (A: Sagittal, B: Axial, C: Coronal) showing an expansile lytic lesion involving the C2 vertebra, causing collapse with posterior impingement on the thecal sac and cord. MRI: Magnetic resonance imaging
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 | Figure 3: CT of the cervical spine – (A: Sagittal, B: Axial, C: Coronal) showing an expansile lytic lesion (red arrows) involving the vertebral body, odontoid process, and left pedicle of C2 vertebra, causing collapse with posterior and left lateral subluxation; diffuse radiologic lucencies (osteopenia vs. multiple lytic lesions) in the other visualized bones including multiple vertebrae (blue arrows). CT: Computed tomography
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Parathyroid adenoma, high levels of PTH, CKD on dialysis, and imaging findings raised the possibility of BT of the bone. In view of spinal instability and partial cord compression, it was planned to go ahead with an occipitocervical fixation along with a parathyroidectomy procedure.
Surgical procedure
After induction under general anesthesia, the patient was positioned prone over a radiolucent table, with the head fixed on pins. Extreme caution was taken to avoid neck extension or flexion including fiber-optic intubation and careful positioning techniques. Neurophysiological monitoring and 3D O-arm navigation were utilized during the entire surgery.
Using standard microsurgical techniques, an occipitocervical fusion procedure was performed from occiput to C4 using an occipital plate and bilateral cervical pedicle screws, connected by contoured rods. This was augmented with an autologous rib graft harvested from the patient, fashioned by splitting it and placed over the C1 to C4 laminae as a graft after decorticating the bone. A biopsy was also taken from the C2 vertebral body.
Subsequently, the patient was turned supine and a standard parathyroidectomy with left hemithyroidectomy procedure was performed.
Histopathology of the spinal lesion was suggestive of BT [Figure 4], with the parathyroid lesion representing a benign adenoma. | Figure 4: H and E stained histopathology sections showing scanty fragments of viable and necrotic cortical bone with very scanty fragments of fascicles of spindle-shaped fibrous stromal cells with bland nuclear features and admixed few osteoclastic giant cells and foci of hemosiderin-laden macrophages and focal new bone formation; no evidence of cytologic atypia, mitosis or malignant chondroid, or osteoid; no evidence of malignancy or metastasis
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The patient improved neurologically postsurgery with good progress on follow-up [Figure 5]. There were no signs of hypo- or hypercalcemia despite an initial dip in serum calcium levels (7.8 mg/dL) which normalized with conservative measures. With the involvement of the endocrinologist, she was started on cinacalcet and calcitriol therapy. However, the PTH levels continued to remain elevated (>2000 pg/mL), at the 6-month follow-up, with serum calcium levels also slightly high (10.1 mg/dL), and elevated phosphate levels (7.2 mg/dL). Cinacalcet was then stopped and denosumab was initiated along with a diet low in phosphates and phosphate binders. The cause for elevated PTH levels despite parathyroidectomy was perplexing and is still being followed up. | Figure 5: Postoperative AP and lateral X-ray showing occipitocervical fusion with implants in situ. AP: Antero-Posterior
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| Discussion | | |
In patients with long-standing uncorrected HPT, BT is a known complication.[3],[6],[7],[11] Primary HPT accounts for <5% of all BTs, while it is increasingly seen more in cases of secondary and tertiary HPT (8%–13%), probably due to the increased survival rates in patients of CKD due to dialysis and renal transplantation.[14] Determining the exact cause of the HPT plays a vital role in the management of BT. While BT commonly involves the mandible, ribs, and long bones, vertebral involvement is infrequent in this cohort of patients, with only 64 such reported cases in the literature.[10],[11]
Vertebral BT may present in the form of pain and/or neurological deficit, relating to the affected spinal level.[2],[12] Radiographically, there is no pathognomonic or diagnostic appearance, often mimicking those of metastases, giant cell tumors, multiple myeloma, or aneurysmal bone cysts.[1],[6] Routine X-rays may demonstrate solitary or multiple roundish lytic lesions, with the expansion of the cortex.[15] CT scans may reveal a relatively well-demarcated soft-tissue mass with uniform tissue density, local bone erosion, and expansion, replacing the cancellous bone of the vertebral body and neural arch, usually with an intact cortex.[3],[9],[14]
MRI is more definitive in evaluating the location, extent of spinal involvement, and neural compression. They may be hypointense on T1-weighted images and either hyper- or hypointense on T2-weighted sequences, causing expansion of the vertebra. Occasionally, blood-fluid levels maybe observed and the presence of hemosiderin within the lytic lesions may also be suggestive of BT[9],[10],[11],[15] Clinical history and background of HPT or parathyroid adenoma should be correlated with these findings to provide a strong differential diagnosis.
The histological examination provides a definitive diagnosis of BT. The macroscopic appearance of the typical brown-colored bony mass is due to its vascularity, hemosiderin deposition, and associated hemorrhage.[8],[9] Microscopically, sheets of fibroblasts are seen alongside numerous osteoclast-like multinucleated giant cells, characterized by the presence of hemosiderin pigment deposits. The presence of macrophages with scattered foci of bone production and resorption are also characteristic.[14] Malignant features are almost never seen.
Despite its benign nature and slow progression, there is a need for prompt diagnosis of BT in HPT patients to establish multidisciplinary management to prevent progression and neurologic complications.[10],[13]
Treatment is primarily focused on medical intervention to normalize blood levels of PTH, calcium, and phosphate to prevent the progression of a BT.[10],[14] Involvement of endocrinology and nephrology teams may help in the judicious administration of calcimimetics, calcium supplements, phosphate binders, Vitamin-D sterols as well as a diet low in phosphate. The foremost importance would lie in lowering PTH levels.[6],[8] If the medical regimen is unsuccessful or if a parathyroid adenoma is detected, total or subtotal parathyroidectomy maybe recommended.[9],[16] This would usually bring about an immediate reduction in PTH levels, leading to near-complete regression of the bony lesions by means of remineralization.[9],[14]
Spinal intervention maybe required depending on the neurological situation. Symptoms may slowly progress due to mass effect or acute spinal cord compression secondary to pathological fractures.[2],[12] In such scenarios, early spinal decompression and fixation in case of instability have to be considered.
In the present case, the patient presented to the hospital with clinical manifestations of HPT 2 years prior. She was initially managed pharmacologically but responded insufficiently. Studies show that among CKD patients, there is an increased risk of developing asymptomatic BTs within 5 years after starting dialysis, where PTH varied between 5 and 15 times the upper limit.[14],[17] Long-standing HPT may also lead to hyperplasia of the parathyroid gland, leading to adenoma formation.[18]
Similarly, this patient also was noted to have both parathyroid adenomas as well as spinal BT in the initial presentation itself, with persistently elevated PTH levels after few years of dialysis. When secondary HPT is refractory to medical therapy and/or PTH fails to suppress (as in this case), tertiary HPT should be suspected.[5],[19] Although parathyroidectomy and spinal surgery were recommended, the procedure was not followed through. The patient finally presented 1 year later with worsening clinical symptoms and additional neurological findings.
As already mentioned, BT in the cervical spine is rare, with only 15 reported cases.[10],[11] Among these, only three were involving the C2 vertebra, with the present case being the fourth. As such, there is a considerable challenge to devise any specific surgical strategy or technique to treat brown tumors involving the C2 spine, due to lack of sufficient data as well as due to generalized osteoporosis.[10] In all three prior cases, no spinal surgery was performed with only a guided biopsy of the lesion that confirmed BT. Medical management was initiated followed by immobilization with cervical spine orthosis.
However, surgery maybe indicated when there is symptomatic progression, neurological deficit, instability, and failure of conservative management. With such an unusual presentation of extensive osteolysis and involvement of the mobile vertebral segment, as seen in this case, it was decided to go ahead with both parathyroidectomy and occipitocervical fixation as was deemed vital and necessary.
Medical management must be continued, and biochemical parameters are to be strictly monitored and followed up after surgery. Rarely, as seen in this case, PTH levels may remain persistently elevated even after surgery, the exact etiology of which is unclear.[17],[20],[21],[22] Similarly, another study noted spinal BT to have occurred 7 years after subtotal parathyroidectomy – probably recurrence in case of the presence of residual parathyroid tissue.[23] This also raises the probability of the present case belonging to a tertiary HPT, the exact treatment for which is ambiguous due to sparse evidence in the literature.
BT is one condition where prevention is indeed better than cure. Especially since manifestations in locations such as the C2 cervical spine, the repercussions of delayed treatment could be disastrous. In patients with CKD, there should be high suspicion of a BT, even at the mildest of neurological indications. Secondary HPT should be monitored and prevented from becoming tertiary HPT in such patients requiring prolonged dialysis.
To the best of our knowledge, this case is probably the first reported case of BT involving the C2 vertebra, as a result of tertiary HPT with parathyroid adenoma secondary to long-standing CKD.
| Conclusion | | |
This report showcases the importance of considering BT as a differential diagnosis of lytic expansile vertebral lesions in the background of HPT and CKD. Treatment strategies would be to correct the underlying HPT, medically and/or surgically with parathyroidectomy, as well as spinal decompression and/or stabilization as required. Further, maintaining an optimal level of PTH will help prevent the recurrence of BTs.
Patient consent statement
- All participants provided written informed consent for the participation in the study
- Patient consent was obtained for purpose of the study with due care to maintain his/her privacy.”
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1]
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