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Case of the Month
Case of the Month
A Diagnostic Deception: In Primary hyperparathyroidism, a Brown Tumor Mistaken for a Giant Cell Tumor
A Diagnostic Deception: In Primary hyperparathyroidism, a Brown Tumor Mistaken for a Giant Cell Tumor
Contributed by Dr. Shubham Shashikant Avhad
Contributed by Dr. Shubham Shashikant Avhad
Introduction :
Introduction :
Hyperparathyroidism is a condition characterised by increased bone resorption and impaired bone formation. Based on a biochemical approach, it is divided into three types: primary, secondary and tertiary. In the primary type, the cause is at the parathyroid level, most commonly a parathyroid adenoma. Secondary hyperparathyroidism occurs in patients with chronic kidney disease. Tertiary hyperparathyroidism is characterised by autonomous production of the parathyroid hormone. We can differentiate primary from secondary hyperparathyroidism based on radiological findings.
Hyperparathyroidism is a condition characterised by increased bone resorption and impaired bone formation. Based on a biochemical approach, it is divided into three types: primary, secondary and tertiary. In the primary type, the cause is at the parathyroid level, most commonly a parathyroid adenoma. Secondary hyperparathyroidism occurs in patients with chronic kidney disease. Tertiary hyperparathyroidism is characterised by autonomous production of the parathyroid hormone. We can differentiate primary from secondary hyperparathyroidism based on radiological findings.
An elevated level of parathyroid hormone leads to increased bone resorption. It shows diffuse osteopenia and coarsening of trabeculae on radiographical images. Brown tumor, also known as osteitis fibrosa cystica, is a benign lytic lesion caused by rapid turnover of osteoclasts, hemorrhage and fibrosis and is seen in primary as well as secondary hyperparathyroidism.
An elevated level of parathyroid hormone leads to increased bone resorption. It shows diffuse osteopenia and coarsening of trabeculae on radiographical images. Brown tumor, also known as osteitis fibrosa cystica, is a benign lytic lesion caused by rapid turnover of osteoclasts, hemorrhage and fibrosis and is seen in primary as well as secondary hyperparathyroidism.
We present a case of primary hyperparathyroidism and its radiological manifestations in different modalities. This case emphasises the importance of a thorough clinical, radiological and biochemical work-up in such cases where a brown tumor can mimic other lytic lesions.
We present a case of primary hyperparathyroidism and its radiological manifestations in different modalities. This case emphasises the importance of a thorough clinical, radiological and biochemical work-up in such cases where a brown tumor can mimic other lytic lesions.
Clinical Profile:
Clinical Profile:
A 19-year-old woman came with pain and swelling in the right knee for nine months. There was no history of trauma or fever. She has had arthralgia and myalgia for three years. She also had pain in her left hip. She underwent a biopsy for the right knee swelling, performed in a private hospital. The histopathology report stated ‘giant cell tumor’ as the diagnosis. No other radiological or biochemical investigations had been done prior to this.
A 19-year-old woman came with pain and swelling in the right knee for nine months. There was no history of trauma or fever. She has had arthralgia and myalgia for three years. She also had pain in her left hip. She underwent a biopsy for the right knee swelling, performed in a private hospital. The histopathology report stated ‘giant cell tumor’ as the diagnosis. No other radiological or biochemical investigations had been done prior to this.
At out hospital, on examination, the swelling was localised to the distal end of the right thigh. The overlying skin was stretched and appeared shiny without erythema. There was no local rise of temperature or tenderness (Figure A) .
At out hospital, on examination, the swelling was localised to the distal end of the right thigh. The overlying skin was stretched and appeared shiny without erythema. There was no local rise of temperature or tenderness (Figure A) .
Fig A- Swelling over the right knee predominantly at the distal end of the right thigh.
Radiological Findings-
Radiological Findings-
The lateral radiograph of the right knee (Figure 1) shows a 5 cm. diameter, expansile osteolytic lesion in the distal femur.associated with a a well-defined soft tissue opacity.
The lateral radiograph of the right knee (Figure 1) shows a 5 cm. diameter, expansile osteolytic lesion in the distal femur.associated with a a well-defined soft tissue opacity.
Figure 1-Radiograph of the right knee shows destruction of the distal femur,with a a well-defined soft tissue opacity.
Frontal and lateral radiographs of the skull (Figure 1b) show a ‘salt and pepper’ appearance with granular trabecular de-ossification.
Frontal and lateral radiographs of the skull (Figure 1b) show a ‘salt and pepper’ appearance with granular trabecular de-ossification.
Figure 1b. Frontal and lateral radiographs of the skull show a ‘salt and pepper’ appearance with granular trabecular de-ossification.
Lateral radiographs of the dorsal and lumbar spine (Figure 1c) show diffuse osteopenia with coarse trabeculae. There is a reduction of the vertebral height with maintenance of the disc height and biconcave shape of the vertebral bodies, giving a ‘codfish’ appearance.
Lateral radiographs of the dorsal and lumbar spine (Figure 1c) show diffuse osteopenia with coarse trabeculae. There is a reduction of the vertebral height with maintenance of the disc height and biconcave shape of the vertebral bodies, giving a ‘codfish’ appearance.
Figure 1c. Lateral radiographs of the dorsal and lumbar spine show reduction of the vertebral body height, maintenance of disc height and a biconcave shape giving a ‘codfish’ appearance (black arrow).
Frontal radiograph of the pelvis with both the hips (Figure 1d) shows a sub-capital fracture of the neck of the left femur.. There is a well-defined lytic lesion in the left iliac bone with a narrow zone of transition.
Frontal radiograph of the pelvis with both the hips (Figure 1d) shows a sub-capital fracture of the neck of the left femur.. There is a well-defined lytic lesion in the left iliac bone with a narrow zone of transition.
Figure 1d. Frontal radiograph of the pelvis with both the hips shows a sub-capital fracture of the neck of the left femur and a well-defined lytic lesion in the left iliac bone with a narrow zone of transition.
Frontal radiograph of the left forearm (Figure 1d) shows well-defined, expansile lytic lesions with a narrow zone of transition in the meta-diaphyseal region of the left radius. There is no matrix mineralisation or sclerotic rim. There is cortical thinning and remodelling. There is no periosteal reaction or soft tissue swelling.
Frontal radiograph of the left forearm (Figure 1d) shows well-defined, expansile lytic lesions with a narrow zone of transition in the meta-diaphyseal region of the left radius. There is no matrix mineralisation or sclerotic rim. There is cortical thinning and remodelling. There is no periosteal reaction or soft tissue swelling.
Figure 1d. Frontal radiograph of the left shows well-defined, expansile lytic lesions with a narrow zone of transition in the meta-diaphyseal region of the left radius. There is no matrix mineralisation, sclerotic rim, periosteal reaction or soft tissue swelling.
Ultrasonography of the neck (Figure 2a) shows an ovoid, heterogeneously hypoechoic lesion at the inferior pole of the left thyroid gland-caudal to the isthmus. The lesion shows no fatty hilum. Three more lesions with a similar morphology are noted adjacent to it. They show polar vascularity with strong arterial flow (Figure 2b)
Ultrasonography of the neck (Figure 2a) shows an ovoid, heterogeneously hypoechoic lesion at the inferior pole of the left thyroid gland-caudal to the isthmus. The lesion shows no fatty hilum. Three more lesions with a similar morphology are noted adjacent to it. They show polar vascularity with strong arterial flow (Figure 2b)
Figure 2a. Ultrasonography of the neck shows ovoid heterogeneously hypoechoic lesions seen at the inferior pole of the left thyroid gland and caudal to the isthmus.
Figure 2b. They show polar vascularity with strong arterial flow.
A contrast-enhanced CT scan of the neck (Figure 3) shows hypodense, arterially enhancing lesions inferior to the lower pole of the left thyroid lobe.
A contrast-enhanced CT scan of the neck (Figure 3) shows hypodense, arterially enhancing lesions inferior to the lower pole of the left thyroid lobe.
Figure 3. Contrast enhanced CT scan of the neck (parathyroid protocol) shows hypodense (compared to the thyroid), arterially enhancing lesions noted at the inferior thyroid lobe.
MRI of the right knee shows T2/T1 heterointense expansile lesion with solid areas involving the distal metaphysis more than the epiphysis of the right femur with cortical erosion and destruction. There are multiple fluid-fluid levels in the lesion, some of them showing hyperintense content consistent with haemorrhage. There is extension of soft tissue superiorly into the medullary cavity.
MRI of the right knee shows T2/T1 heterointense expansile lesion with solid areas involving the distal metaphysis more than the epiphysis of the right femur with cortical erosion and destruction. There are multiple fluid-fluid levels in the lesion, some of them showing hyperintense content consistent with haemorrhage. There is extension of soft tissue superiorly into the medullary cavity.
Figure 4. MRI of the right knee shows a T2/T1 hetero intense expansile multicentric lesion with solid areas involving the distal metaphysis and epiphysis of the right femur, causing cortical erosion and destruction. There are multiple fluid-fluid levels seen within the lesion.
Biochemical investigations:
Biochemical investigations:
Given the osteopenia, multifocal lytic lesions and parathyroid adenomas noted on radiological imaging, hyperparathyroidism was suspected and parathyroid hormone levels were checked, which were found to be raised (465 pg/ml).
Given the osteopenia, multifocal lytic lesions and parathyroid adenomas noted on radiological imaging, hyperparathyroidism was suspected and parathyroid hormone levels were checked, which were found to be raised (465 pg/ml).
Radiological diagnosis:
Radiological diagnosis:
Primary hyperparathyroidism with multiple brown tumors.
Primary hyperparathyroidism with multiple brown tumors.
Pathological diagnosis:
Pathological diagnosis:
After discussing the radiological, clinical and biochemical findings with the pathologists, the slides were reviewed .
After discussing the radiological, clinical and biochemical findings with the pathologists, the slides were reviewed .
The biopsy (Figure 5) showed a giant cell-rich tumor composed of mononuclear cells with vesicular nuclei, mild pleomorphism, prominent nucleoli and scant to moderate amounts of cytoplasm. Areas of hemorrhage were seen with few cystic blood blood-filled, aneurysmal bone cyst-like spaces. The histopathological diagnosis of ‘giant cell tumor’ was revised to ‘brown tumor’.
The biopsy (Figure 5) showed a giant cell-rich tumor composed of mononuclear cells with vesicular nuclei, mild pleomorphism, prominent nucleoli and scant to moderate amounts of cytoplasm. Areas of hemorrhage were seen with few cystic blood blood-filled, aneurysmal bone cyst-like spaces. The histopathological diagnosis of ‘giant cell tumor’ was revised to ‘brown tumor’.
Figure 5. Histopathological examination shows a giant cell-rich tumor composed of mononuclear cells with vesicular nuclei, mild pleomorphism, prominent nucleoli and scant to moderate amounts of cytoplasm. Areas of hemorrhage are seen with few cystic blood blood-filled, aneurysmal bone cyst-like spaces.
Management:
Management:
Parathyroid adenectomy was performed
Parathyroid adenectomy was performed
Timeline
Timeline
Discussion:
Discussion:
The parathyroid glands play a crucial role in maintaining calcium homeostasis through the secretion of parathyroid hormone (PTH). PTH increases serum calcium levels by promoting renal tubular reabsorption of calcium, decreasing phosphate reabsorption, and stimulating osteoclastic bone resorption. Additionally, PTH enhances the production of vitamin D, which further raises serum calcium by increasing gastrointestinal absorption [1]. Primary hyperparathyroidism is diagnosed when serum calcium levels are elevated alongside elevated or inappropriately normal PTH levels. This condition is more prevalent in women. Hypercalcemia presents with a variety of often nonspecific symptoms. Common clinical manifestations include fatigue, hypertension, bone pain, muscle weakness, and psychiatric disturbances [2].
The parathyroid glands play a crucial role in maintaining calcium homeostasis through the secretion of parathyroid hormone (PTH). PTH increases serum calcium levels by promoting renal tubular reabsorption of calcium, decreasing phosphate reabsorption, and stimulating osteoclastic bone resorption. Additionally, PTH enhances the production of vitamin D, which further raises serum calcium by increasing gastrointestinal absorption [1]. Primary hyperparathyroidism is diagnosed when serum calcium levels are elevated alongside elevated or inappropriately normal PTH levels. This condition is more prevalent in women. Hypercalcemia presents with a variety of often nonspecific symptoms. Common clinical manifestations include fatigue, hypertension, bone pain, muscle weakness, and psychiatric disturbances [2].
Primary hyperparathyroidism is most frequently caused by parathyroid adenomas, which result in excessive secretion of PTH. This hormonal imbalance leads to bone erosions and osteopenia. Classic sites of bone resorption include subperiosteal, subchondral, subligamentous, subtendinous, trabecular, and endosteal regions. Subperiosteal resorption, especially in the hands, is considered pathognomonic. Subligamentous resorption commonly affects the distal clavicle, while subchondral resorption is often seen in the sacroiliac joints, pubic symphysis, and acromioclavicular joints [3].
Primary hyperparathyroidism is most frequently caused by parathyroid adenomas, which result in excessive secretion of PTH. This hormonal imbalance leads to bone erosions and osteopenia. Classic sites of bone resorption include subperiosteal, subchondral, subligamentous, subtendinous, trabecular, and endosteal regions. Subperiosteal resorption, especially in the hands, is considered pathognomonic. Subligamentous resorption commonly affects the distal clavicle, while subchondral resorption is often seen in the sacroiliac joints, pubic symphysis, and acromioclavicular joints [3].
Osseous changes are typically observed in the proximal and middle phalanges on the radial aspects of the second and third fingers [4]. Subperiosteal resorption refers to the destruction of bone beneath the cortical periosteum of long bones due to increased bone turnover. In the skull, granular de-ossification leads to the loss of distinction between the inner and outer tables.
Osseous changes are typically observed in the proximal and middle phalanges on the radial aspects of the second and third fingers [4]. Subperiosteal resorption refers to the destruction of bone beneath the cortical periosteum of long bones due to increased bone turnover. In the skull, granular de-ossification leads to the loss of distinction between the inner and outer tables.
Hyperparathyroidism may also cause well-defined lytic bone lesions with narrow zones of transition. These lesions, known as brown tumors, result from prolonged PTH hypersecretion. In brown tumors, bone marrow is replaced by rapidly proliferating, highly vascularized connective tissue due to heightened resorptive activity. [5, 6]Haemorrhage within the lesion leads to hemosiderin deposition in the surrounding tissue. Brown tumors commonly affect the maxilla, pelvis, and ribs, although long bones may also be involved. Histologically, brown tumors are characterized by soft tissue swelling containing areas of haemorrhage and cyst-like spaces, lined by fibrous connective tissue and populated by multinucleated giant cells. Due to the presence of these giant cells, brown tumors are histologically indistinguishable from other lesions such as aneurysmal bone cysts, giant cell tumors, and central giant cell granulomas [7, 8].
Hyperparathyroidism may also cause well-defined lytic bone lesions with narrow zones of transition. These lesions, known as brown tumors, result from prolonged PTH hypersecretion. In brown tumors, bone marrow is replaced by rapidly proliferating, highly vascularized connective tissue due to heightened resorptive activity. [5, 6]Haemorrhage within the lesion leads to hemosiderin deposition in the surrounding tissue. Brown tumors commonly affect the maxilla, pelvis, and ribs, although long bones may also be involved. Histologically, brown tumors are characterized by soft tissue swelling containing areas of haemorrhage and cyst-like spaces, lined by fibrous connective tissue and populated by multinucleated giant cells. Due to the presence of these giant cells, brown tumors are histologically indistinguishable from other lesions such as aneurysmal bone cysts, giant cell tumors, and central giant cell granulomas [7, 8].
In our case, the lesion in the right knee was initially misdiagnosed as a giant cell tumor. However, further diagnostic workup revealed it to be a brown tumor secondary to primary hyperparathyroidism.
In our case, the lesion in the right knee was initially misdiagnosed as a giant cell tumor. However, further diagnostic workup revealed it to be a brown tumor secondary to primary hyperparathyroidism.
Conclusion
Conclusion
This was a rare case of a brown tumor resulting from primary hyperparathyroidism that was initially diagnosed as a giant cell tumor.
This was a rare case of a brown tumor resulting from primary hyperparathyroidism that was initially diagnosed as a giant cell tumor.
In some situations, relying solely on histopathological findings is insufficient for diagnosing brown tumors. A comprehensive evaluation that includes clinical presentation, imaging studies, and laboratory tests is essential. In particular, when widespread osteolytic bone lesions are observed alongside marked osteoporosis and hypercalcemia, we should consider metabolic bone disorders, especially brown tumors associated with hyperparathyroidism, as a possible diagnosis.Tumor board meetings help achieve this.
In some situations, relying solely on histopathological findings is insufficient for diagnosing brown tumors. A comprehensive evaluation that includes clinical presentation, imaging studies, and laboratory tests is essential. In particular, when widespread osteolytic bone lesions are observed alongside marked osteoporosis and hypercalcemia, we should consider metabolic bone disorders, especially brown tumors associated with hyperparathyroidism, as a possible diagnosis.Tumor board meetings help achieve this.
References:
References:
1. Naik, M., Khan, S. R., Owusu, D., Alsafi, A., Palazzo, F., Jackson, J. E., Harvey, C. J., & Barwick, T. D. (2022). Contemporary multimodality imaging of primary hyperparathyroidism. RadioGraphics, 42(3), 841–860. doi:10.1148/rg.210170
1. Naik, M., Khan, S. R., Owusu, D., Alsafi, A., Palazzo, F., Jackson, J. E., Harvey, C. J., & Barwick, T. D. (2022). Contemporary multimodality imaging of primary hyperparathyroidism. RadioGraphics, 42(3), 841–860. doi:10.1148/rg.210170
2. Lee, J. H., Kim, M. J., Choi, H. J., & Kim, S. W. (2015). Primary hyperparathyroidism with extensive brown tumors and multiple fractures. Endocrinology and Metabolism, 30(4), 614–620. doi:10.3803/EnM.2015.30.4.614
2. Lee, J. H., Kim, M. J., Choi, H. J., & Kim, S. W. (2015). Primary hyperparathyroidism with extensive brown tumors and multiple fractures. Endocrinology and Metabolism, 30(4), 614–620. doi:10.3803/EnM.2015.30.4.614
3. Bennett, J., Suliburk, J. W., & Morón, F. E. (2020). Osseous manifestations of primary hyperparathyroidism: Imaging findings. International Journal of Endocrinology, 2020, Article ID 3146535. doi:10.1155/2020/3146535
3. Bennett, J., Suliburk, J. W., & Morón, F. E. (2020). Osseous manifestations of primary hyperparathyroidism: Imaging findings. International Journal of Endocrinology, 2020, Article ID 3146535. doi:10.1155/2020/3146535
4. Zhong, Y., Huang, Y., Luo, J. et al. Misdiagnosis of brown tumor caused by primary hyperparathyroidism: a case report with literature review. BMC Endocr Disord, 22, 66 (2022). doi:10.1186/s12902-022-00971-2
4. Zhong, Y., Huang, Y., Luo, J. et al. Misdiagnosis of brown tumor caused by primary hyperparathyroidism: a case report with literature review. BMC Endocr Disord, 22, 66 (2022). doi:10.1186/s12902-022-00971-2
5. Aghaghazvini, L., Sharifian, H., & Rasuli, B. (2016). Primary hyperparathyroidism misdiagnosed as giant cell bone tumor of maxillary sinus: A case report. Iranian Journal of Radiology, 13(1), e13260. doi:10.5812/iranjradiol.13260
5. Aghaghazvini, L., Sharifian, H., & Rasuli, B. (2016). Primary hyperparathyroidism misdiagnosed as giant cell bone tumor of maxillary sinus: A case report. Iranian Journal of Radiology, 13(1), e13260. doi:10.5812/iranjradiol.13260
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8. Johnson, N. A., Tublin, M. E., & Ogilvie, J. B. (2007). Parathyroid imaging: Technique and role in the preoperative evaluation of primary hyperparathyroidism. American Journal of Roentgenology, 188(6), 1706–1715. doi:10.2214/AJR.06.0938
8. Johnson, N. A., Tublin, M. E., & Ogilvie, J. B. (2007). Parathyroid imaging: Technique and role in the preoperative evaluation of primary hyperparathyroidism. American Journal of Roentgenology, 188(6), 1706–1715. doi:10.2214/AJR.06.0938
Acknowledgement
Acknowledgement
We would like to thank the Department of Pathology, at the Tata Memorial Hospital, for providing the histopathology image and its description.
We would like to thank the Department of Pathology, at the Tata Memorial Hospital, for providing the histopathology image and its description.
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