Differentiating Brown Tumor From Bone Metastasis in Parathyroid Cancer Using 18 F-FDG PET and 99m Tc-MIBI SPECT.

ABSTRACT: A 69-year-old woman presented with a right clavicle pain. CT revealed a pathological fracture of the right clavicle, multiple osteolytic lesions, and a left cervical mass. 18 F-FDG PET/CT demonstrated a marked FDG uptake in the cervical mass and osteolytic lesions indicative of metastatic parathyroid cancer. 99m Tc-MIBI SPECT/CT revealed either faint or no uptake in the osteolytic lesions. However, a histopathological analysis after a parathyroidectomy and right clavicle biopsy confirmed the diagnosis of parathyroid cancer and the presence of benign brown tumors secondary to hyperparathyroidism. Postoperative imaging showed sclerotic change and a decreased FDG uptake in the bone lesions.

The refractory secondary hyperparathyroidism presenting with retro-orbital brown tumor: a case report.

BACKGROUND: Tertiary hyperparathyroidism describes the autonomous and excessive secretion of parathyroid hormone (PTH) by the parathyroid glands after longstanding secondary hyperparathyroidism in chronic kidney disease. Brown tumors are a sign of uncontrolled hyperparathyroidism. In this case, we have reported a refractory and destructive hyperparathyroidism storm. Also, it presented with atypical onset and unexpected adenoma location. CASE PRESENTATION: A 37-year-old man was diagnosed with end-stage kidney disease 22 years ago. He has been undergoing dialysis treatment since that time. Recently, he was admitted to the ophthalmology department due to the unilateral anterior bulging of the right eye and drooping of the eyelid. Magnetic resonance imaging exhibited an extraconal mass lesion located in the right orbital posterior superolateral position. Computerized tomography scans considered expansile bone lesion with peripheral calcification and originating from the sphenoid wing. The bone mass lesion was resected via craniotomy due to the compressive effect. The pathological findings were consistent with brown tumors. Plasma intact PTH level was 4557 pg/mL. The patient informed that he underwent parathyroidectomy and two leg fractures operation in a medical query. Parathyroid scintigraphy determined three distinct foci consistent with adenomas and one of them was in mediastenum. Second parathyroidectomy was recommended to the patient but the patient refused surgery. Despite his medication and dialysis regimen being revised, PTH levels were maintained at higher levels in follow-up. CONCLUSIONS: We presented a hyperparathyroidism case that was resistant to all treatments and exhibited all the severe complications in a long-term dialysis patient. Furthermore, this case has revealed the importance and difficulty of secondary hyperparathyroidism management.

Multiple brown tumors: a bone complication due to long-term untreated pseudohypoparathyroidism.

Bone lytic lesions are a possible complication of pseudohypoparathyroidism type 1B, in undertreated adult patients. Whole body [18F] F-fluorocholine PET/CT is a useful imaging tool to assess brown tumor progression in this context. We describe the case of a 33-year-old woman, referred for the diagnostic evaluation of lytic bone lesions of the lower limbs, in the context of asymptomatic pseudohypoparathyroidism. She had been treated with alfacalcidol and calcium during her childhood. Treatment was discontinued at the age of 18 years old because of the lack of symptoms. A femur biopsy revealed a lesion rich in giant cells, without malignancy, consistent with a brown tumor. Laboratory tests showed a parathyroid level at 1387 pg/ml (14-50). Whole-body Fluorocholine PET/CT revealed hypermetabolism of bone lesions. The final diagnosis was brown tumors related to hyperparathyroidism complicating an untreated pseudohypoparathyroidism. Genetic testing confirmed PHP type 1B. Pseudohypoparathyroidism with radiographic evidence of hyperparathyroid bone disease, is a very rare condition due to parathyroid hormone resistance in target organs, i.e., kidney resistance, but with conserved bone cell sensitivity. It has been reported in only a few cases of pseudohypoparathyroidism type Ib. Long-term vitamin D treatment was required to correct bone hyperparathyroidism. With this rationale, the patient was treated with calcium, alfacalcidol, and cholecalciferol. One-year follow-up showed complete resolution of pain, improvement in serum calcium, and regression of bone lesions on [18F]F-fluorocholine PET/CT. This case illustrates the usefulness of [18F]F-fluorocholine PET/CT for the imaging of brown tumors in pseudohypoparathyroidism type 1B, and emphasizes the importance of calcium and vitamin D treatment in adult patients, to avoid the deleterious effects of high parathyroid hormone on skeletal integrity.

Brown tumor due to primary hyperparathyroidism in a familial case: a case report.

BACKGROUND: Primary hyperparathyroidism (PHPT) is an uncommon disorder characterised by hypercalcemia with an increased parathyroid hormone level. We reported a PHPT familial case with two subjects, a father and a daughter, and both of them had suffered from the brown tumor. CASE PRESENTATION: The proband, a 43-year-old patient, developed parathyroid adenomas at the age of 15; a histologically confirmed right parathyroid adenoma was removed by parathyroidectomy; and after six months follow-up, the serum calcium level was normalised. At the age of thirty-three, a CT scan of his head and neck revealed a mass in the right maxilla, as well as PHPT (i.e., left inferior parathyroid adenoma). Then, he underwent a biopsy of an exophytic lesion in the right maxilla and was diagnosed by pathology as a brown tumor, with the serum calcium and PTH levels at 2.78 mmol/L and 221 pg/mL, respectively. Subsequently, the patient took a left inferior parathyroid microwave ablation with ultrasound guidance. After three months of follow-up, the serum calcium and PTH levels returned to normal, and the brown tumor was resolved. After three years, it mineralised as revealed in a CT scan. By the time he was 43 years old, during the 28-year follow-up period, the serum calcium and PTH levels were still within the normal range, and there was no discomfort reported. He has consistently taken calcium supplements throughout the 28 years. Since the initial diagnosis, his blood indicators of kidney function have been normal, and ultrasound showed renal calculus in the right kidney and a normal left kidney. The proband's daughter, a 15-year-old girl, experienced left upper extremity pain for ten months. CT scan revealed a mass in the distal left radius, and a giant cell tumor was suspected. A surgical internal fixation was performed, and the pathology showed a brown tumor. Laboratory tests revealed a serum parathyroid hormone (PTH) level of 1554pg/mL, calcium level of 3.14 mmol/L, phosphorus level of 0.72 mmol/L, and alkaline phosphatase level of 1892 U/L. Given the osteitic changes and elevated levels of calcium and PTH, ultrasonography was performed, after which a mass was detected measuring 19 × 9 × 7 mm mixed with solid components and cystic fluid in the right thyroid gland. The results of 99mTc-MIBI scintigraphy confirmed the abnormal accumulation of 99mTc-MIBI in the right thyroid gland but not seen in the bilateral parathyroid glands. The patient underwent thyroidectomy, and the postoperative pathology report indicated an intra-thyroid ectopic parathyroid adenoma. The serum calcium and PTH levels became normal at 4 h after surgery. One to three months after operation, the serum calcium level was low, while the serum PTH level was high. Then, the patient was advised to take calcium supplements. Until the sixth month after the operation, the serum calcium level and serum PTH level returned to normal, and the bone pain was relieved. The patient's blood tests for kidney function remained normal. There was no evidence of bilateral kidney disease (such as nephrolithiasis or nephrocalcinosis) detected by ultrasound scan. There were several similarities in the state of illness between these two subjects. Both the father and the daughter developed parathyroid adenomas at the age of 15, and there was no lesion in other endocrine glands. And genetic testing revealed mutations in the CDC73 genes in both father and daughter. On the other hand, there were also a few differences. The father's first signs of brown tumor were in the right maxilla, while the daughter's appeared in the distal left radius. The father presented pathological changes in the left and right parathyroid glands, whereas the daughter presented with an ectopic parathyroid adenoma in the right thyroid gland. CONCLUSION: We report a familial case in which father and daughter were diagnosed to have brown tumors due to parathyroid adenoma and ectopic parathyroid adenoma, and genetic testing revealed CDC73 gene mutations in both. Therefore, in the diagnostic and differential process of young patients having bone disease, clinicians should not only focus on the clinical manifestations of the skeleton, but also implement a comprehensive analysis of systemic symptoms, considering the possibility that the patient has familial PHPT.

Lytic Mastoid Lesion in a Patient with Otalgia.

The differential diagnosis for an isolated lytic mastoid lesion is broad, encompassing various conditions requiring careful consideration. These include granulomatous disorders such as Langerhans cell histiocytosis and sarcoidosis, neoplastic processes like multiple myeloma, leukemia, lymphoma, and metastases, primary bone diseases such as Paget's disease, fibrous dysplasia, and osteitis fibrosa cystica, as well as infectious causes like osteomyelitis. In this report, we present a patient with otalgia and an isolated lytic mastoid lesion.

Brown tumors of the jaw: an atypical manifestation of primary hyperparathyroidism.

Brown tumors represent the terminal stage of bone remodeling processes in primary hyperparathyroidism. Currently they are rare, and typically affect long bones, pelvis and ribs. Brown tumors may be not included in the initial differential diagnosis of bone disease, especially when they are present in atypical localizations. We reported two cases of oral brown tumors as the initial presentation of primary hyperparathyroidism. In the first case, a 44-year-old woman presented a painful and sessile lesion of 4 × 3 cm over the central body of the mandible which progressively increased in 4-month. The second case involved a 23-year-old woman who was referred with a 3-month history of a painful and ulcerated mass of 2 cm arising from left maxilla, episodes of gingival hemorrhage and difficulty of breathing. Both cases were solitary tumors with no evidence of palpable cervical lymphadenopathy. Incisional biopsy of oral tumors resulted in giant cell and primary hyperparathyroidism was confirmed by laboratory tests. After parathyroidectomy, histology confirmed adenoma in both cases. Although this type of clinical presentation has almost disappeared in the recent decades, brown tumors should be considered in the differential diagnosis of bone oral masses.

Los tumores pardos son raros y, por lo general, afectan huesos largos, pelvis y costillas. Pueden no estar incluidos en el diagnóstico diferencial inicial como manifestación de enfermedad esquelética, especialmente cuando se presentan en localizaciones atípicas. Comunicamos dos casos de tumores pardos orales como presentación inicial de hiperparatiroidismo primario. En el primer caso, una mujer de 44 años presentó una lesión dolorosa y sésil de 4 × 3 cm sobre el cuerpo central de la mandíbula que aumentó de tamaño progresivamente en 4 meses. El segundo caso corresponde a una mujer de 23 años que acudió por presentar una masa dolorosa y ulcerada de 2 cm en maxilar izquierdo de 3 meses de evolución, episodios de hemorragia gingival y dificultad para respirar. Todos fueron tumores solitarios sin evidencia de linfadenopatía cervical palpable. La biopsia incisional de los tumores orales resultó en células gigantes, y las pruebas de laboratorio confirmaron el hiperparatiroidismo primario. Tras la paratiroidectomía, la histología confirmó adenoma en ambos casos. Los tumores pardos representan la etapa terminal de los procesos de remodelación ósea en el hiperparatiroidismo primario. Aunque este tipo de presentación clínica casi ha desaparecido en las últimas décadas, los tumores pardos deben ser considerados en el diagnóstico diferencial de las masas óseas orales.

Localization of Brown Tumors With 18 F-Fluorocholine PET/CT Imaging in Severe Primary Hyperparathyroidism.

ABSTRACT: We present the case of a 68-year-old woman with a painful tibial tumor and fatigue. Histology and laboratory studies were consistent with a brown tumor secondary to initially unrecognized, severe primary hyperparathyroidism. 18 F-fluorocholine PET/CT revealed a large hypermetabolic parathyroid mass and multiple bone foci considered as brown tumors. Unilateral neck exploration confirmed a large parathyroid adenoma. Serum calcium and parathyroid hormone levels normalized quickly, and symptoms subsided gradually after parathyroidectomy. Brown tumors are a rare complication of severe hyperparathyroidism. 18 F-fluorocholine PET/CT allows the localization of parathyroid adenomas and brown tumors, and can be used as a single imaging modality.

Diffuse Calvarial Hyperstosis.

Calvarial hyperstosis can be an idiopathic benign finding or secondary to a metabolic pathology. We herein describe a case of diffuse calvarial hyperstosis. A 26-year-old man known to have end-stage renal disease on regular hemodialysis, tertiary hyperparathyroidism, extensive brown tumors, and severe developmental impairment with skeletal deformities was referred to us for macrocephaly. On examination, the patient was chairbound, with speech and motor developmental delay, and frontal bossing. Brain computed tomography revealed diffuse hyperstosis of the calvarium and facial bones expansion with multiple sclerotic and lytic areas, causing subsequent narrowing of the basilar skull foramina. Brain magnetic resonance imaging demonstrated an extensive expansile bone marrow abnormality in the calvarium and skull base. There was mild generalized prominence of cortical sulci and ventricular system. The findings were in keeping with his known hypermetabolic state and tertiary hyperparathyroidism. The patient was managed conservatively with regular follow-up in the clinic.

Large parathyroid adenomas: Potential mechanisms to reconcile adenoma size and disease phenotype.

Parathyroid adenomas weighing more than 3.5 g are reported variously as "atypical", "large" or "giant" parathyroid adenomas. All such adenomas are rare variants accounting for no more than 1.5% of all parathyroid adenomas. Large parathyroid adenomas are often associated with more severe form of the disease, including osteitis fibrosa cystica (OFC) and share many biochemical, histological, and molecular features of both benign and malignant parathyroid neoplasms, and are considered a distinct clinical entity. However, the pathogenesis of oversized parathyroid adenomas and the often-associated skeletal phenotype remains unclear. We present 5 cases of primary hyperparathyroidism (PHPT) with OFC, an uncommon manifestation of contemporary PHPT, associated with larger parathyroid adenomas, seen in the Bone and Mineral Disorders Clinic of the Henry Ford Health in the last 30 years to illustrate the critical role of vitamin D nutrition in the pathogenesis of both the OFC and adenoma size. The estimated prevalence of OFC was very low 0.2%, 5 of the >3000 surgically confirmed cases of PHPT seen during this time. The mean ± SD values were: age: 36.8 ± 22.1 years (4 of the 5 <36years), serum calcium 11.6 ± 1.1 mg/dl, alkaline phosphatase 799 ± 487 IU/L, PTH 1440 ± 477 pg/ml, 25-hydroxyvitamin D 13.0 ± 8.9 ng/ml, 1,25-dihyroxyvitamin D 26.5 ± 13.7 pg/ml, urine calcium 562 ± 274 mg/day, and parathyroid adenoma weight 4.53 ± 2.2 g. Parathyroidectomy led to the resolution of both the biochemical indices and OFC in each patient without recurrence over >10 years of follow-up. Because OFC is a very rare in the West, but very common areas of endemic vitamin D deficiency, we also examined the relationship between vitamin D nutrition, as assessed by serum 25-hydroxyvitamin D level, and parathyroid adenoma weight as well as prevalence of OFC in two large secularly diverse cohorts of patients with PHPT (Detroit, USA and Chandigarh, India). Based on this relationship and the relative prevalence of OFC in these two large cohorts, we propose that vitamin D nutrition (and perhaps calcium nutrition) best explains both the adenoma size and prevalence of OFC.

Brown tumor of the cervical spine with primary hyperparathyroidism: A case report and literature review.

RATIONALE: Brown tumor (BT), an uncommon focal lytic bone tumor, is a non-neoplastic and reactive process caused by increased osteoclastic activity and fibroblastic proliferation in primary or secondary hyperparathyroidism. Vertebral tumor causing neural compression is relatively rare, especially in the cervical spine. PATIENT CONCERNS: A 29-year-old man developed neck pain and arm radicular pain 4 months ago, with the level of serum calcium significantly higher than normal. Computed tomography scan of the cervical spine revealed an expansile lytic lesion occupying the C6 body, left pedicle, and left lamina of C5-6. DIAGNOSES: Osteoclastoma according to imaging and histopathological results. INTERVENTIONS: A laminectomy of C5-6 was performed. OUTCOMES: One month later, he was re-hospitalized due to nausea and vomiting and the serum calcium, was still, kept at a high level. Additionally, the parathormone (PTH) was greatly higher than normal. BT with primary hyperparathyroidism due to the parathyroid tumor was considered. After the surgery of the right parathyroid gland was performed, serum calcium and PTH both decreased, and computed tomography showed good recovery. LESSONS: BTs might be misdiagnosed as other giant cell tumors, thus when giant cell tumors are considered, serum calcium and PTH examination may be needed to exclude BTs.

Uncommon presentation of brown tumours revealing hyperparathyroidism: Three case reports.

Brown tumours (BTs) are focal bone lesions encountered in patients with uncontrolled hyperparathyroidism (HPT). They are due to a proliferation of multinucleated giant cells in osteolytic lesions. Because of early screening of bone metabolism disorders, BTs are rare bone manifestations. More importantly, they scarcely reveal the disease. We demonstrate through these two cases reports unusual locations of BT complicating the course of HPT due to parathyroid hyperplasia.

Pathological ankle fracture due to brown tumour: atypical presentation of low serum vitamin D with normal parathyroid hormone and bone profile.

Osteoclastomas or brown tumours are named as such due to increased vascularity, subsequent haemorrhage and haemosiderin deposition giving the lesion a reddish brown appearance under gross microscopic examination. It is due to an increase in parathyroid hormone activity from several causes, such as parathyroid adenomas, renal impairment and low vitamin D levels. The lesions increase the tendency of the bone to fracture. The challenging aspect of the diagnosis is that a histological diagnosis without immunohistochemistry is impossible to make. This is because, without special staining, brown tumours cannot be differentiated from giant cell tumours, which are also classed as benign but can be locally destructive and has potential for malignant transformation. Once tissue diagnosis is confirmed as a brown tumour, then aggressive forms of treatment are not needed, and they generally resolve once the underlying cause is treated. We describe a woman in her 80s who presented to the local Orthopaedic service with a pathological ankle fracture due to a brown tumour.

A patient with femoral osteitis fibrosa cystica mimicking bone neoplasm: a case report.

BACKGROUND: Osteitis fibrosa cystica is a rare, benign and osteolytic lesion attributed to hyperparathyroidism. The high level of parathyroid hormone cause rapid bone loss. CASE PRESENTATION: The patient is a 50-year-old male complaining of severe and persistent pain in the right knee joint. Imaging studies were suspicious for a benign tumor in the right distal femur. Biopsy under CT guidance showed numerous osteoclast aggregation and hemosiderin deposition around the bone trabeculae. Blood tests disclosed significantly elevated parathyroid hormone, serum calcium, serum alkaline phosphatase. Parathyroid ultrasonography and CT scan showed a solid mass in front of the trachea at the thoracic entrance plane. After resection of the mass, the clinical symptoms were relieved and the radiological results were significantly improved, which further confirmed the diagnosis. CONCLUSIONS: Metabolic diseases-associated bone lesions require a comprehensive diagnosis of multiple inspection items. An interprofessional team approach to the diagnosis and treatment of osteitis fibrosa cystica will provide the best outcome.

Misdiagnosis of brown tumour caused by primary hyperparathyroidism: a case report with literature review.

BACKGROUND: Brown tumour is a rare tumour-like lesion of the bone, which is considered as an end-stage lesion of abnormal bone metabolism caused by persistently high parathyroid hormone (PTH) levels. Brown tumour can be found in any part of the skeleton; in some cases, it can occur in multiple bones and can be easily misdiagnosed as a metastatic tumour. CASE PRESENTATION: We report the case of a 44-year-old man who presented to the Department of Oncology in our hospital with a 2-month history of local pain in his left shoulder joint. The initial diagnosis was an aneurysmal bone cyst by biopsy, for which the patient underwent tumour resection surgery. The diagnosis of a malignant tumour was made again following postoperative pathological examination. The pathological sections and all clinical data were sent to the Department of Pathology of the First Affiliated Hospital of Sun Yat-sen University; the diagnosis made there was brown tumour. His blood PTH level was 577 pg/ml (15-65 pg/ml). Colour Doppler ultrasonography of the parathyroid gland suggested a parathyroid adenoma. For further treatment, the left parathyroid adenoma was removed by axillary endoscopic resection. Postoperatively, a pathologic examination was performed, and the diagnosis of a parathyroid adenoma was confirmed. One year after the surgery, the left humerus was completely healed, and the left shoulder joint had a good range of movement. CONCLUSIONS: In summary, histopathological diagnosis is not sufficient for the diagnosis of brown tumours. A comprehensive analysis combining clinical symptoms with findings of imaging and laboratory tests is also required. Generally, the treatment of brown tumour includes only partial or complete resection of the parathyroid glands. However, when the tumour is large, especially when it involves the joint, surgery is indispensable.

Revisiting the Case of Sarah Newbury's Death from Mollities Ossium.

Multiple myeloma and its precursor and variant types represent some of the most common hematologic malignancies in adults. These plasma cell dyscrasias are well-known in modern medicine. There are well-established clinical, laboratory, and pathologic criteria for diagnosis and staging. There is debate about the diagnosis of some of the earliest cases of myeloma described in the literature. We present a critical review of one such case.

Manifestations of hyperparathyroidism in the jaws: Concepts, mechanisms, and clinical aspects.

Hyperparathyroidism is one of the most common endocrine disorders worldwide. In countries where routine biochemical screening is not common, symptomatic hyperparathyroidism predominates. Its manifestations include skeletal alterations, calcification of soft tissues, kidney stones, and functional alterations in other systems. Notably, jaw alterations can be the first clinical sign of hyperparathyroidism, including brown tumor, renal osteodystrophy, osteitis fibrosa, and leontiasis ossea, and knowing such conditions is of core importance for the multidisciplinary diagnosis and management of hyperparathyroidism. We aimed to perform a concise review, systematizing the concepts and mechanisms underlying hyperparathyroidism and associated gnathic alterations. In addition, a detailed description of the clinical aspects of the jaw manifestations is presented.