Brown tumor of the rib as a first presentation of primary hyperparathyroidism: Report of three cases and literature review
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1 Thoracic Cancer ISSN CASE REPORT Brown tumor of the rib as a first presentation of primary hyperparathyroidism: Report of three cases and literature review Jie Zhang 1, Hao Wang 2, Weijun Tian 3, Qing He 2 & Mei Zhu 2 1 Department of Ultrasonography, Tianjin Medical University General Hospital, Tianjin, China 2 Department of Endocrinology, Tianjin Medical University General Hospital, Tianjin, China 3 Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China Keywords Brown tumor; hyperparathyroidism; ribs; ultrasonography. Correspondence Mei Zhu, Department of Endocrinology, Tianjin Medical University General Hospital, Tianjin , China. Tel: Fax: meichuqin@yahoo.com.cn Abstract A brown tumor is a non-neoplasm mainly caused by hyperparathyroidism. It often occurs in the pelvis, ribs, long bone shaft, clavicle, and jaw. We introduce three cases of primary hyperparathyroidism, with the first symptom of brown tumor of the ribs, and discuss the image characteristics within the literature. We then propose the value of ultrasound in the diagnosis of brown tumor. Received: 12 March 2013; accepted 4 April doi: / Hyperparathyroidism is caused by the development of a parathyroid adenoma, hyperplasia or a carcinoma. Over secretion of parathyroid hormone will promote osteoclasts to absorb the bone. The lesions of brown tumor are often located in areas of serious bone resorption and become filled with fibroblastic tissue. These tumors always have a brown or yellow hue, thus, the name brown tumor. We report three cases of primary hyperparathyroidism, with the first presentation of brown tumor of the ribs, and, subsequently, review the literature. Case reports Case 1 A 55-year-old woman was admitted to our clinic for a mass on the left chest wall. She had been diagnosed by pathology with a giant cell granuloma, in the local hospital. She had a history of humeral fracture on the right side and bilateral urinary calculus. Physical examination showed a 3 cm 3 cm 2.5 cm mild mass on the lower lope of the left thyroid, which was moveable and did not display any tenderness. There was another 5 cm 3cm 3 cm mass on the 10th. The tumor was solid. The laboratory examination and assistant examination are summarized in Table 1 and Figure 1. The tumor of the rib was resected and diagnosed by pathology as brown tumor. Two years later, she presented to our hospital with a mass on the left malar. Computed tomography (CT) of the maxilla and an ultrasound of the maxilla are shown in Figure 1. Combined with her medical history and a laboratory examination, the diagnosis was brown tumor. She was advised to receive parathyroid tumor resection. Case 2 A 67-year-old woman was admitted to our clinic for pain in her chest and back for a period lasting two months. Five days later, she underwent a CT examination. The result showed space-occupying lesions on the superior lobe of the left lung with bone destruction of the left ribs. She attended our clinic for further treatment. Physical examination showed a mass on the inferior lope of the left thyroid. Another mass was located in third rib on the left chest wall. The laboratory examination and assistant examination are shown in Table 1 and Figure 2. Part of the third rib was resected and the pathological report showed brown tumor. She was transferred to 474 Thoracic Cancer 4 (2013) Tianjin Lung Cancer Institute and Wiley Publishing Asia Pty Ltd
2 J. Zhang et al. Hyperparathyroidism with brown tumor Table 1 Laboratory findings of the three cases Case Ca (mmol/l) P (mmol/l) ALP (IU/L) PTH (pmol/l) 24hUCa (mg) 1# > # # > Normal 2.15~ ~ ~ ~7.3 <200 ALP, alkaline phosphatase; PTH, parathyroid hormone. the department of general surgery for further treatment. The mass on the parathyroid was resected and pathology showed parathyroid adenoma invading the local capsule.after surgery, the pain began to ease. Parathyroid hormone (PTH), serum calcium, and serum phosphate levels were reduced. Case 3 A 56-year-old man was admitted to our clinic 15 days after surgical resection of a mass on the 11th rib on the left chest wall. The pathological result showed brown tumor. Magnetic a b c d e f Figure 1 (a) The ultrasound shows that there is a cm hypoechoic mass on the left malar. The tumor is of a standard shape, with clear margins, and a cystic area within. (b) Computed tomography (CT) of the skull shows expansive destruction of the left zygomatic process of the maxilla and malar bone, a separation of sclerotin, and local bone destruction. (c) The image of soft tissue is of a fusiform shape can be seen on 9th and 10th intercostal space. There is no enhancement or zone of necrosis. The 10th rib has distensibility and has suffered bone destruction. Multiple bone densities are low.(d) A multinucleated giant cell can be seen in much of the fibrous tissue, which is hyperplastic (Hematoxylin and eosin [HE] 100). (e) Bone trabecula can be seen in the fibrous tissue. In top left corner, we can see the multinucleated giant cell (HE 100). (f) There is a great deal of macrophage, which surrounds the hemosiderin. (HE 100). Thoracic Cancer 4 (2013) Tianjin Lung Cancer Institute and Wiley Publishing Asia Pty Ltd 475
3 Hyperparathyroidism with brown tumor J. Zhang et al. Figure 2 (a) Chest computed tomography (CT) reveals many local lesions in the left 3rd rib and a local soft tissue mass has formed. The limit of it is clear. (b) A multinucleated giant cell can be seen with much hyperplastic fibrous tissue. (Hematoxylin and eosin ([HE] 100). resonance imaging (MRI) of the neck showed multiple nodules and masses in the thyroid region. The patient attended our clinic for further treatment. He had a history of recurrent renal calculus. The laboratory examination and assistant examination are summarized in Table 1 and Figure 3. The patient went to the department of general surgery for further treatment. The pathologic result shows parathyroid adenoma. Discussion The incidence of brown tumor is reported to be 3% in primary hyperparathyroidism, and parathyroid adenoma is the etiologic factor in 80 90% of brown tumor cases diagnosed in patients with primary hyperparathyroidism, while parathyroid carcinoma and parathyroid hyperplasia are among the other causes. Brown tumor is often located in the pelvis, ribs, long bone shaft, clavicle, and jaw. In our three cases, the patients suffered from primary hyperparathyroidism, with the first symptom of brown tumor being in the ribs. All received surgical treatment and the pathological results showed brown tumors. In differential diagnosis of brown tumor with a solitary bone lesion, it may be difficult to differentiate from aneurysmal bone cyst, giant cell tumor, solitary bone cyst or giant cell reparative granuloma. The differential diagnosis of brown tumor with multiple bone lesions includes metabolic osteopathy, multiple myeloma, Langerhans cell histiocytosis, leukemia, multiple bone cysts, multiple non-ossifying fibroma, and fibrous dysplasia. 1 3 In our three cases, the patients were found during physical examination to have a mass on the thyroid area, different levels of hypercalcemia, a level of serum phosphorus lower than normal, and an increase in alkaline phosphatase prior to surgery. In case 1, the patient had a history of bone fracture and urinary calculus. These factors will point to a diagnosis of brown tumor. However, doctors generally focus the point of diagnosis on local lesion of the ribs. After pathological results revealed brown tumor, doctors found the parathyroid hormone had increased. Therefore, in the process of diagnosis and differential diagnosis, a clinician should focus not only on the clinical manifestation of the bone, but also analyse the condition combined with systemic symptoms to avoid erroneous or missed diagnoses. Brown tumors are non-neoplastic, osteolytic lesions of the bone, 2 therefore, the preferred imaging evaluation method is still traditional radiation, such as X-ray and CT. X-rays reveal that brown tumors are well-defined lytic lesions that usually cause expansion of the affected bone. 4 7 CT can reveal the liquidity of cystic lesions with fibrosis and calcinosis. There is a great deal of literature showing the characteristics of brown tumor in MRI. It explains the low intensity of the solid area of brown tumor on T1 and T2-weighted images. But the cyst wall explains the high intensity on T2-weighted images. 8,9 Some literature also reports positron emission tomography (PET)-CT results, which show unusual radioactivity intake. Because the manifestation of brown tumor is shown in osteolytic lesions, thinning and destruction of the bone cortex, and cystic lesions, we used ultrasound to explore the lesions of Case 2 and Case 3 patients. Sonography revealed the features of the brown tumor to be internally homogenous oval or round hypoechoic masses with clear smooth margins. The solid part of the lesion shows the color Doppler signal (Figs 2,3). We infer that ultrasound has some benefit in the retrospective evaluation of brown tumors. First, ultrasound will reveal when a neoplasm with expansive growth makes the 476 Thoracic Cancer 4 (2013) Tianjin Lung Cancer Institute and Wiley Publishing Asia Pty Ltd
4 J. Zhang et al. Hyperparathyroidism with brown tumor a b c d e Figure 3 (a) Chest computed tomography (CT) reveals many local lesions in the left 11th rib and a local soft tissue mass has formed. (b) Parathyroid gland scintigraphy shows an image of a high function lesion on the right inferior parathyroid. (c) The ultrasound shows an oval or round hypoechoic mass with clear, smooth margins and an internal homogeneous hyperechogenicity band. The solid part of the lesion shows the color Doppler signal. (d) On the technetium-99m methylene diphosphonate ( 99 TC m -MDP) bone image, increased radioactivity can be seen in the skull, mandible, spine, ribs, pelvis, and other axial bones and limbs. The image of the skull is a sign of capping. These signs prompt obvious activity in the bones of the entire body. (e) Multinucleated giant cells and new bone (HE 100). bone cortex thinner, or even destroys the cortex and extends into soft tissue to form a homogeneous mass Second, it can scan the parathyroid gland at the same time, which can provide more evidence for the diagnosis. Third, sonography is an ideal tool to monitor the alteration of lesions during treatment. Therefore, the value of ultrasound for the diagnosis of brown tumor needs further evaluation. Treatment of brown tumors must address the region of anatomy and the underlying etiologic factor for hyperparathyroidism. Generally speaking, the primary disease should be treated before removal of the brown tumor. However, if the lesion is located in a critical anatomical region or any sign of neurological deficit is detected, surgery is necessary. After resection of the pathological parathyroid, the bone lesion tends to resolve spontaneously. Two of the patients in our cases underwent surgical excision of the parathyroid adenoma. Two months after the surgery, the symptoms of bone pain eased. The laboratory results were normal. Acknowledgments This work was supported by Grants from the National Natural Science Foundation of China. (No ) and the Technology Foundation of Tianjin Public Health Bureau of China (No. 2012KZ104). Disclosure No authors report any conflict of interest. References 1 Takeshita T, Tanaka H, Harasawa A, Kaminaga T, Imamura T, Furui S. Brown tumor of the sphenoid sinus in a patient with secondary hyperparathyroidism: CT and MR imaging findings. Radiat Med 2004; 22: Thoracic Cancer 4 (2013) Tianjin Lung Cancer Institute and Wiley Publishing Asia Pty Ltd 477
5 Hyperparathyroidism with brown tumor J. Zhang et al. 2 Takeshita T, Takeshita K, Abe S, Takami H, Imamura T, Furui S. Brown tumor with fluid-fluid levels in a patient with primary hyperparathyroidism: radiological findings. Radiat Med 2006; 24: Cebesoy O, Karakok M, Arpacioglu O, Baltaci ET. Brown tumor with atypical localization in a normocalcemic patient. Arch Orthop Trauma Surg 2007; 127: Perman JS, Pletcher SD, Schmidt BL, Eisele DW. Pathology quiz case 2. Giant cell lesion (brown tumor) of the mandible, associated with primary hyperparathyroidism (HPT). Arch Otolaryngol Head Neck Surg 2004; 130: Davies AM, Evans N, Mangham DC, Grimer RJ. MR imaging of brown tumour with fluid-fluid levels: a report of three cases. Eur Radiol 2001; 11: Mafee MF, Yang G, Tseng A, Keiler L, Andrus K. Fibro-osseous and giant cell lesions, including brown tumor of the mandible, maxilla, and other craniofacial bones. Neuroimaging Clin N Am 2003; 13: Scholl RJ, Kellett HM, Neumann DP, Lurie AG. Cysts and cystic lesions of the mandible: clinical and radiologichistopathologic review. Radiographics 1999; 19: Miyakoshi M, Kamoi K, Takano T et al. Multiple brown tumors in primary hyperparathyroidism caused by an adenoma mimicking metastatic bone disease with false positive results on computed tomography and Tc-99 m sestamibi imaging: MR findings. Endocr J 2007; 54: Hong WS, Sung MS, Chun KA et al. Emphasis on the MR imaging findings of brown tumor: a report of five cases. Skeletal Radiol 2011; 40: Steiner GM, Sprigg A. The value of ultrasound in the assessment of bone. Br J Radiol 1992; 65: Mukuno DH, Lee TG, Watanabe AS, McIff EB. Aneurysmal bone cyst presenting as a pelvic mass on sonographic examination. J Ultrasound Med 1986; 5: Adler RS. Bone and articular cartilage. In: Fornage BD (ed.). Musculoskeletal Ultrasound. Churchill Livingstone, New York 1995; Thoracic Cancer 4 (2013) Tianjin Lung Cancer Institute and Wiley Publishing Asia Pty Ltd
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