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Brown tumor mimicking maxillary sinus mucocele as the first manifestation of primary hyperparathyroidism
Auris Nasus Larynx 39 (2012) 418–421
Contents lists available at SciVerse ScienceDirect
Auris Nasus Larynx journal homepage: www.elsevier.com/locate/anl
Brown tumor mimicking maxillary sinus mucocele as the first manifestation of primary hyperparathyroidism Liviu-Adelin Guldfred a,*, Søren Daugaard b, Christian von Buchwald a a b
Copenhagen University Hospital, ENT Department, Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark
A R T I C L E I N F O
A B S T R A C T
Article history: Received 18 May 2011 Accepted 22 July 2011 Available online 30 August 2011
We describe the first case of brown tumor mimicking a maxillary sinus mucocele as the first manifestation of the patient’s primary hyperparathyroidism. A 34-year old woman presented with a 14 days history of elevation of the right orbit, retrobulbar pain and cheek anesthesia. The CT and MR evaluation showed a mass, initially described as mucocele of the right maxillary sinus. The laboratory studies revealed hyperparathyroidism. The patient underwent acute surgery, and the mass appeared clinically as mucocele. The histological examination of the resected lesion revealed changes representing either giant cell granuloma or brown tumor. The finding of hyperparathyroidism confirmed the diagnosis of brown tumor. To our knowledge, this is the first report of cystic brown tumor mimicking a mucocele of the maxillary sinus. ß 2011 Elsevier Ireland Ltd. All rights reserved.
Keywords: Brown tumor Mucocele Maxillary sinus Hyperparathyroidism Fluid–fluid levels
1. Introduction Osteitis fibrosa cystica, the last stage of hyperparathyroidisminduced bone changes, is characterized by cystic degeneration of the bone tissue. Histologically, there are areas of fibrosis, which contain reactive woven bone and haemosiderin-laden macrophages and many giant cells (osteoclasts). Due to their macroscopic appearance as friable red-brown masses these lesions have been termed ‘brown tumors’ [1]. Brown tumors often develop at multiple sites in the long bones while the maxillofacial region is only rarely affected [2]. When they occur in the facial bones the predilection site is the mandible, while the maxillar brown tumors are very rare. We herein report the first case of a brown tumor, which presented clinically as mucocele of the right maxillary sinus. The ophthalmological and neurological symptoms caused by the tumor were the first manifestations of the patient’s primary hyperparathyroidism. 2. Case report A 34-year old woman was transferred to our tertiary Otolaryngology Center after suffering for 14 days with protrusion and elevation of the right orbit, right-sided retrobulbar pain and
* Corresponding author at: Department of Otolaryngology, Head & Neck Surgery, Rigshospitalet, F 2071, Blegdamsvej 9, Copenhagen, Denmark. Tel.: +45 60 747 888. E-mail address: [email protected] (L.-A. Guldfred). 0385-8146/$ – see front matter ß 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.anl.2011.06.008
cheek anesthesia. The patient had also transitory headache and abdominal pain. CT in the local hospital identified a mass in the right maxillary sinus. Our examination confirmed the above description of asymmetric eyeballs, nasal obstruction and a mass under the inferior right concha. An ophthalmologic examination was unremarkable. The CT (Fig. 1) showed opacification of the right maxillary sinus consistent with either a tumor mass or mucocele. The MRI identified fluid–fluid level, destruction of bone tissue and marked enhancement of the periphery (Fig. 2), which initially was interpreted as mucocele. The acute laboratory evaluation revealed that ionized calcium was 1.95 mmol/L while alkaline phosphatase was 164 U/L (reference 1.15–1.35 mmol/L and 35–105 U/L respectively). The parathyroid hormone (PTH), only available after the acute treatment, was 37.6 pmol/L (reference 1.6–6.9 pmol/L). The patient underwent acute computer assisted endoscopic sinus surgery for the mass present in the right sinus maxillary. The medial wall of the maxillary sinus was found displaced medially, pushing against the nasal septum; the middle turbinate was atrophic. A solid mass was found in the medial and inferior wall of the maxillary sinus and a cystic component occupied the rest of the maxillary sinus. A large amount of yellowish fluid was found on opening the cystic component, which therefore was described as mucocele. No difference in the macroscopic appearance of the fluid from the different portions of the cystic mass was observed intraoperatively. The medial wall of the right maxillary sinus and the mass in the sinus was removed. The intraoperative findings
[(Fig._1)TD$IG]
L.-A. Guldfred et al. / Auris Nasus Larynx 39 (2012) 418–421
419
Fig. 1. Coronal and sagittal CT image of the lesion.
were interpreted as mucocele secondary to obstruction of the sinus ostium caused by the solid tumor. The operation and recovery were uneventful. The histology of the resected medial wall of the maxillary sinus revealed numerous osteoclast-like giant cells, haemosiderin-laden macrophages, loose bone tissue pieces, and spindle-shaped stromal cells without signs of malignancy, the said changes representing either giant cell granuloma or brown tumor of hyperparathyroidism (Fig. 3). The finding of hyperparathyroidism, i.e. hypercalcaemia, elevated PTH and alkaline phosphatase, confirmed the diagnosis of brown tumor. The radiological imaging was reevaluated in the light of the histological description, the findings being described as atypical for mucocele, but consistent with a cystic bone tumor. The laboratory findings at admission were interpreted as concomitant primary hyperparathyroidism, and treated with volume expansion and calcitonin infusion. The work-up for hyperparathyroidism included tests for multiple endocrine neoplasia type 1 and 2 (which were negative), and Technetium (99mTc) sestamibi (Cardiolite) parathyroid scintigraphy as well as 99mTc Pertechnetate thyroid scintigraphy. The latter was normal, but the parathyroid scintigraphy revealed a persistent focus of activity
localized at the caudal end of the right lobe of the thyroid gland (Fig. 4), interpreted as consistent with a parathyroid adenoma. The patient underwent parathyroid surgery 15 days after the initial operation. Intraoperatively, a well-defined tumor was found latero-posteriorly to the inferior part of the right thyroid lobe. The tumor was removed in toto, but the thyroid was left in situ. The recurrent laryngeal nerve was preserved and no vocal cord palsy was observed after surgery. Pathologic examination of the removed tumor revealed parathyroid adenoma. One day after the parathyroid surgery the patient was transferred to the endocrinological department. During the first postoperative week the PTH changed from unmeasurable (<0.6 pmol/L) to normal value (2.6 pmol/L, reference 1.6–6.9 pmol/L), while the ionized calcium decreased more rapidly from 1.89 to 1.26 and eventually stabilized at around 1.16 mmol/L (reference 1.15–1.35 mmol/L), without need of calcium supplementation. A normal alkaline phosphatase (68 U/L, reference 35–105 U/L) was measured one month postoperatively. The patient was discharged from the endocrinological department one week postoperatively. The tumor in the maxillary bone was not resected completely, but resolved following the surgical treatment of the patient’s
[(Fig._2)TD$IG]
Fig. 2. Coronal and axial magnetic resonance imaging of the lesion.
[(Fig._3)TD$IG]
420
L.-A. Guldfred et al. / Auris Nasus Larynx 39 (2012) 418–421
Fig. 3. Left: mucosa (upper region), a zone with reactive bone (in the middle), and the giant cell lesion (lower region) (original magnification 40). Right: note osteoclast-like giant cells, loose stroma and hemorrhage (original magnification 200).
[(Fig._4)TD$IG]
Fig. 4. Nuclear imaging. Results of
99m
Tc sestamibi (Cardiolite) parathyroid scintigraphy.
hyperparathyroidism. The patient’s symptoms disappeared already after the sinus surgery and the treatment of the hypercalcaemia. The follow-up in the ENT department was ended six months after the initial surgery, where no signs of residual tumor or recurrence could be found at endoscopy. The follow-up continued in the endocrinological department, and the patient remained asymptomatic, with normal calcium metabolism and recurrence-free at the two years follow-up. 3. Discussion Brown tumors are non-neoplastic lesions that occur in the late stage of hyperparathyroidism, osteitis fibrosa cystica. The pathogenesis of osteitis fibrosa cystica may be classified into three stages [1]. In the early stage, the increased PTH levels stimulate the osteoclasts to resorb bone, and at the same time collagen fibers are laid down in the marrow. In the second stage (osteitis fibrosa), the trabecular bone is resorbed and the marrow is replaced by loose fibrosis, hemosiderin-laden macrophages, areas of hemorrhage
from microfractures, and reactive woven bone. As the hyperparathyroidism and hemorrhage continues, cystic degeneration ultimately occurs, leading to the final stage of the disease (osteitis fibrosa cystica). The cysts are the results of intraosseous bleeding and tissue degeneration. The cystic spaces are filled up by clusters of giant cells (actually osteoclasts), hemosiderin-laden macrophages and plump fibroblasts. The presence of hemorrhage, hemosiderin and hypervascularity lead to the brownish color, which is responsible for the name. If routine biochemical screening is conducted, most patients with primary hyperparathyroidism will be diagnosed before manifesting symptoms of hyperparathyroidism and osteitis fibrosa cystica [2]. Even in populations with high osteitis fibrosa cystica prevalence, the occurrence of brown tumors in the bony surroundings of the maxillary sinus is extremely rare [3]. A review of the English-language literature revealed 14 cases of primary hyperparathyroidism and brown tumors localized in maxillary bone. All of these patients were diagnosed with a growing mass, either in the maxillary region of the face, or in the oral or nasal
L.-A. Guldfred et al. / Auris Nasus Larynx 39 (2012) 418–421
cavity. In none of the cases was the tumor cystic, as was the case with our patient, where the tumor was initially interpreted as mucocele of the maxillary sinus, both on imaging and peroperatively. The cystic component of the brown tumor in our case was also much larger, compared with cystic brown tumors described in other predilection sites, which partly may explain the initial interpretation as mucocele. The typical symptom for brown tumors in the maxillary region is a growing mass, which at examination presents firm, tender, and immobile. There may be chewing difficulties, nasal obstruction or bleeding, and the dentition can be affected [4–7]. The patient may also have general symptoms due to hyperparathyroidism, such as weakness, paresthesias, fatigue, vague abdominal complaints, and subtle mental disturbances (‘‘kidney stones, painful bones, abdominal groans, psychiatric moans, and fatigue overtones’’) [8]. Biochemical evaluation will reveal hyperparathyroidism. Histologically, brown tumors are indistinguishable from other giant cell tumors (giant cell granuloma, true giant cell tumors, fibrous dysplasia). Radiographically, brown tumors are well-defined lytic lesions that usually cause expansion of the affected bone, and there can be subperiosteal bone resorption and disappearance of the lamina dura surrounding the roots of teeth. Neither on CT nor on MRI, do the brown tumors exhibit specific changes. They may present as solid, mixed solid and cystic, or cystic lesions [9]. On CT the diagnosis of brown tumor is suggested by the presence of an expansile lytic lesion in a patient with other features of hyperparathyroidism [10]. Fluid–fluid levels on CT or MRI may occur whenever substances with different densities are confined to a cystic or compartmental area, and are nonspecific findings that may be observed in a variety of neoplastic, inflammatory, traumatic, and other miscellaneous pathologic conditions. Fluid– fluid levels on MRI have been reported before in brown tumors [11,12], but on the one hand, not all brown tumors display fluid– fluid levels, and on the other hand there are many other tumors of bone and soft tissue with fluid–fluid levels on MRI [13,14]. Past reports of brown tumors have demonstrated a large range of signal intensities from low to high signal intensity on T2-weighted MR images. Conversely, fluid–fluid levels have not been observed in mucoceles, although cystic lesions with fluid–fluid levels have been interpreted as mucoceles in the past [15]. The signal intensity, while very variable in mucoceles too, was unusual high in our case, a finding not typical for a mucocele. The initial radiological description as mucocele was therefore subsequently revised to cystic bone lesion. We have not performed biochemical analysis of the cyst content, but, as other authors have reported, one plausible explanation for the occurrence of fluid–fluid levels is repeated bleeding in the tumor [11]. This would lead to the formation of a xanthochromic supernatant with high signal intensity on T2weighted MR images, and a dependent low-intensity portion consisting of liquefied hematoma. The former would correspond to the yellowish fluid described on opening the cystic component, while the latter was presumably not reported/observed because of the brownish color, close to the color of the brown tumor. As brown tumors do not exhibit specific changes, neither on CT/ MR, nor histologically, the diagnosis of brown tumor must be based on the combination of a histological giant-cell lesion and biochemical evidence of hyperparathyroidism. The clinical value of diagnosing the hyperparathyroidism, once the histological diagnosis of giant-cell tumor is made, resides in the
421
fact that many brown tumors regress (though not always completely) after the treatment of the hyperparathyroidism, making surveillance a feasible option [2]. There are reports, however, of brown tumors persisting after 6 years of follow-up [3] or even growing after the treatment of the hyperparathyroidism [4], leaving surgery as the only adequate option. Surgery has also been used for cosmetic or functional reasons [6]. Furthermore, our patient had ophthalmological and neurological symptoms, and in a similar case, we will recommend surgical treatment of the brown tumor besides the treatment of the hyperparathyroidism. 4. Conclusions Brown tumors in the facial bones are extremely rare, but should be considered in the differential diagnosis of a mass in the facial skeleton. The diagnosis is based on a combination of a histological giant-cell lesion and biochemical evidence of hyperparathyroidism. The primary treatment of brown tumors consists in the management of the hyperparathyroidism, but for patients with large, symptomatic tumors, surgical treatment of the brown tumors is recommended. Conflict of interest None. References [1] Schiller AL, Teitelbaum SL. Bones and joints. In: Rubin E, Farber JL, editors. Pathology. 3rd ed., Philadephia, New York: Lippincott-Raven; 1999. p. 1336– 413. [2] Resendiz-Colosia JA, Rodriguez-Cuevas SA, Flores-Diaz R, Juan MH, GallegosHernandez JF, Barroso-Bravo S, et al. Evolution of maxillofacial brown tumors after parathyroidectomy in primary hyperparathyroidism. Head Neck 2008;30:1497–504. [3] Agarwal G, Mishra SK, Kar DK, Singh AK, Arya V, Gupta SK, et al. Recovery pattern of patients with osteitis fibrosa cystica in primary hyperparathyroidism after successful parathyroidectomy. Surgery 2002;132: 1075–83. [4] Yamazaki H, Ota Y, Aoki T, Karakida K. Brown tumor of the maxilla and mandible: progressive mandibular brown tumor after removal of parathyroid adenoma. J Oral Maxillofac Surg 2003;61:719–22. [5] Merz MN, Massich DD, Marsh W, Schuller DE. Hyperparathyroidism presenting as brown tumor of the maxilla. Am J Otolaryngol 2002;23:173–6. [6] Guney E, Yigitbasi OG, Bayram F, Ozer V, Canoz O. Brown tumor of the maxilla associated with primary hyperparathyroidism. Auris Nasus Larynx 2001;28:369–72. [7] Lessa MM, Sakae FA, Tsuji RK, Filho BC, Voegels RL, Butugan O. Brown tumor of the facial bones: case report and literature review. Ear Nose Throat J 2005;84:432–4. [8] Gould CF, Ly JQ, Lattin Jr GE, Beall DP, Sutcliffe III JB. Bone tumor mimics: avoiding misdiagnosis. Curr Probl Diagn Radiol 2007;36:124–41. [9] Hong WS, Sung MS, Chun KA, Kim JY, Park SW, Lee KH, et al. Emphasis on the MR imaging findings of brown tumor: a report of five cases. Skeletal Radiol 2010 . [10] Knowles NG, Smith DL, Outwater EK. MRI diagnosis of brown tumor based on magnetic susceptibility. J Magn Reson Imaging 2008;28: 759–61. [11] 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;24:631–4. [12] 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;22:265–8. [13] Tsai JC, Dalinka MK, Fallon MD, Zlatkin MB, Kressel HY. Fluid–fluid level: a nonspecific finding in tumors of bone and soft tissue. Radiology 1990;175: 779–82. [14] Kendi AT, Kara S, Altinok D, Keskil S. Sinonasal ossifying fibroma with fluid–fluid levels on MR images. AJNR Am J Neuroradiol 2003;24:1639–41. [15] Vaidya AM, Chow JM, Goldberg K, Stankiewicz JA. Juvenile aggressive ossifying fibroma presenting as an ethmoid sinus mucocele. Otolaryngol Head Neck Surg 1998;119:665–8.
Contents lists available at SciVerse ScienceDirect
Auris Nasus Larynx journal homepage: www.elsevier.com/locate/anl
Brown tumor mimicking maxillary sinus mucocele as the first manifestation of primary hyperparathyroidism Liviu-Adelin Guldfred a,*, Søren Daugaard b, Christian von Buchwald a a b
Copenhagen University Hospital, ENT Department, Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark
A R T I C L E I N F O
A B S T R A C T
Article history: Received 18 May 2011 Accepted 22 July 2011 Available online 30 August 2011
We describe the first case of brown tumor mimicking a maxillary sinus mucocele as the first manifestation of the patient’s primary hyperparathyroidism. A 34-year old woman presented with a 14 days history of elevation of the right orbit, retrobulbar pain and cheek anesthesia. The CT and MR evaluation showed a mass, initially described as mucocele of the right maxillary sinus. The laboratory studies revealed hyperparathyroidism. The patient underwent acute surgery, and the mass appeared clinically as mucocele. The histological examination of the resected lesion revealed changes representing either giant cell granuloma or brown tumor. The finding of hyperparathyroidism confirmed the diagnosis of brown tumor. To our knowledge, this is the first report of cystic brown tumor mimicking a mucocele of the maxillary sinus. ß 2011 Elsevier Ireland Ltd. All rights reserved.
Keywords: Brown tumor Mucocele Maxillary sinus Hyperparathyroidism Fluid–fluid levels
1. Introduction Osteitis fibrosa cystica, the last stage of hyperparathyroidisminduced bone changes, is characterized by cystic degeneration of the bone tissue. Histologically, there are areas of fibrosis, which contain reactive woven bone and haemosiderin-laden macrophages and many giant cells (osteoclasts). Due to their macroscopic appearance as friable red-brown masses these lesions have been termed ‘brown tumors’ [1]. Brown tumors often develop at multiple sites in the long bones while the maxillofacial region is only rarely affected [2]. When they occur in the facial bones the predilection site is the mandible, while the maxillar brown tumors are very rare. We herein report the first case of a brown tumor, which presented clinically as mucocele of the right maxillary sinus. The ophthalmological and neurological symptoms caused by the tumor were the first manifestations of the patient’s primary hyperparathyroidism. 2. Case report A 34-year old woman was transferred to our tertiary Otolaryngology Center after suffering for 14 days with protrusion and elevation of the right orbit, right-sided retrobulbar pain and
* Corresponding author at: Department of Otolaryngology, Head & Neck Surgery, Rigshospitalet, F 2071, Blegdamsvej 9, Copenhagen, Denmark. Tel.: +45 60 747 888. E-mail address: [email protected] (L.-A. Guldfred). 0385-8146/$ – see front matter ß 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.anl.2011.06.008
cheek anesthesia. The patient had also transitory headache and abdominal pain. CT in the local hospital identified a mass in the right maxillary sinus. Our examination confirmed the above description of asymmetric eyeballs, nasal obstruction and a mass under the inferior right concha. An ophthalmologic examination was unremarkable. The CT (Fig. 1) showed opacification of the right maxillary sinus consistent with either a tumor mass or mucocele. The MRI identified fluid–fluid level, destruction of bone tissue and marked enhancement of the periphery (Fig. 2), which initially was interpreted as mucocele. The acute laboratory evaluation revealed that ionized calcium was 1.95 mmol/L while alkaline phosphatase was 164 U/L (reference 1.15–1.35 mmol/L and 35–105 U/L respectively). The parathyroid hormone (PTH), only available after the acute treatment, was 37.6 pmol/L (reference 1.6–6.9 pmol/L). The patient underwent acute computer assisted endoscopic sinus surgery for the mass present in the right sinus maxillary. The medial wall of the maxillary sinus was found displaced medially, pushing against the nasal septum; the middle turbinate was atrophic. A solid mass was found in the medial and inferior wall of the maxillary sinus and a cystic component occupied the rest of the maxillary sinus. A large amount of yellowish fluid was found on opening the cystic component, which therefore was described as mucocele. No difference in the macroscopic appearance of the fluid from the different portions of the cystic mass was observed intraoperatively. The medial wall of the right maxillary sinus and the mass in the sinus was removed. The intraoperative findings
[(Fig._1)TD$IG]
L.-A. Guldfred et al. / Auris Nasus Larynx 39 (2012) 418–421
419
Fig. 1. Coronal and sagittal CT image of the lesion.
were interpreted as mucocele secondary to obstruction of the sinus ostium caused by the solid tumor. The operation and recovery were uneventful. The histology of the resected medial wall of the maxillary sinus revealed numerous osteoclast-like giant cells, haemosiderin-laden macrophages, loose bone tissue pieces, and spindle-shaped stromal cells without signs of malignancy, the said changes representing either giant cell granuloma or brown tumor of hyperparathyroidism (Fig. 3). The finding of hyperparathyroidism, i.e. hypercalcaemia, elevated PTH and alkaline phosphatase, confirmed the diagnosis of brown tumor. The radiological imaging was reevaluated in the light of the histological description, the findings being described as atypical for mucocele, but consistent with a cystic bone tumor. The laboratory findings at admission were interpreted as concomitant primary hyperparathyroidism, and treated with volume expansion and calcitonin infusion. The work-up for hyperparathyroidism included tests for multiple endocrine neoplasia type 1 and 2 (which were negative), and Technetium (99mTc) sestamibi (Cardiolite) parathyroid scintigraphy as well as 99mTc Pertechnetate thyroid scintigraphy. The latter was normal, but the parathyroid scintigraphy revealed a persistent focus of activity
localized at the caudal end of the right lobe of the thyroid gland (Fig. 4), interpreted as consistent with a parathyroid adenoma. The patient underwent parathyroid surgery 15 days after the initial operation. Intraoperatively, a well-defined tumor was found latero-posteriorly to the inferior part of the right thyroid lobe. The tumor was removed in toto, but the thyroid was left in situ. The recurrent laryngeal nerve was preserved and no vocal cord palsy was observed after surgery. Pathologic examination of the removed tumor revealed parathyroid adenoma. One day after the parathyroid surgery the patient was transferred to the endocrinological department. During the first postoperative week the PTH changed from unmeasurable (<0.6 pmol/L) to normal value (2.6 pmol/L, reference 1.6–6.9 pmol/L), while the ionized calcium decreased more rapidly from 1.89 to 1.26 and eventually stabilized at around 1.16 mmol/L (reference 1.15–1.35 mmol/L), without need of calcium supplementation. A normal alkaline phosphatase (68 U/L, reference 35–105 U/L) was measured one month postoperatively. The patient was discharged from the endocrinological department one week postoperatively. The tumor in the maxillary bone was not resected completely, but resolved following the surgical treatment of the patient’s
[(Fig._2)TD$IG]
Fig. 2. Coronal and axial magnetic resonance imaging of the lesion.
[(Fig._3)TD$IG]
420
L.-A. Guldfred et al. / Auris Nasus Larynx 39 (2012) 418–421
Fig. 3. Left: mucosa (upper region), a zone with reactive bone (in the middle), and the giant cell lesion (lower region) (original magnification 40). Right: note osteoclast-like giant cells, loose stroma and hemorrhage (original magnification 200).
[(Fig._4)TD$IG]
Fig. 4. Nuclear imaging. Results of
99m
Tc sestamibi (Cardiolite) parathyroid scintigraphy.
hyperparathyroidism. The patient’s symptoms disappeared already after the sinus surgery and the treatment of the hypercalcaemia. The follow-up in the ENT department was ended six months after the initial surgery, where no signs of residual tumor or recurrence could be found at endoscopy. The follow-up continued in the endocrinological department, and the patient remained asymptomatic, with normal calcium metabolism and recurrence-free at the two years follow-up. 3. Discussion Brown tumors are non-neoplastic lesions that occur in the late stage of hyperparathyroidism, osteitis fibrosa cystica. The pathogenesis of osteitis fibrosa cystica may be classified into three stages [1]. In the early stage, the increased PTH levels stimulate the osteoclasts to resorb bone, and at the same time collagen fibers are laid down in the marrow. In the second stage (osteitis fibrosa), the trabecular bone is resorbed and the marrow is replaced by loose fibrosis, hemosiderin-laden macrophages, areas of hemorrhage
from microfractures, and reactive woven bone. As the hyperparathyroidism and hemorrhage continues, cystic degeneration ultimately occurs, leading to the final stage of the disease (osteitis fibrosa cystica). The cysts are the results of intraosseous bleeding and tissue degeneration. The cystic spaces are filled up by clusters of giant cells (actually osteoclasts), hemosiderin-laden macrophages and plump fibroblasts. The presence of hemorrhage, hemosiderin and hypervascularity lead to the brownish color, which is responsible for the name. If routine biochemical screening is conducted, most patients with primary hyperparathyroidism will be diagnosed before manifesting symptoms of hyperparathyroidism and osteitis fibrosa cystica [2]. Even in populations with high osteitis fibrosa cystica prevalence, the occurrence of brown tumors in the bony surroundings of the maxillary sinus is extremely rare [3]. A review of the English-language literature revealed 14 cases of primary hyperparathyroidism and brown tumors localized in maxillary bone. All of these patients were diagnosed with a growing mass, either in the maxillary region of the face, or in the oral or nasal
L.-A. Guldfred et al. / Auris Nasus Larynx 39 (2012) 418–421
cavity. In none of the cases was the tumor cystic, as was the case with our patient, where the tumor was initially interpreted as mucocele of the maxillary sinus, both on imaging and peroperatively. The cystic component of the brown tumor in our case was also much larger, compared with cystic brown tumors described in other predilection sites, which partly may explain the initial interpretation as mucocele. The typical symptom for brown tumors in the maxillary region is a growing mass, which at examination presents firm, tender, and immobile. There may be chewing difficulties, nasal obstruction or bleeding, and the dentition can be affected [4–7]. The patient may also have general symptoms due to hyperparathyroidism, such as weakness, paresthesias, fatigue, vague abdominal complaints, and subtle mental disturbances (‘‘kidney stones, painful bones, abdominal groans, psychiatric moans, and fatigue overtones’’) [8]. Biochemical evaluation will reveal hyperparathyroidism. Histologically, brown tumors are indistinguishable from other giant cell tumors (giant cell granuloma, true giant cell tumors, fibrous dysplasia). Radiographically, brown tumors are well-defined lytic lesions that usually cause expansion of the affected bone, and there can be subperiosteal bone resorption and disappearance of the lamina dura surrounding the roots of teeth. Neither on CT nor on MRI, do the brown tumors exhibit specific changes. They may present as solid, mixed solid and cystic, or cystic lesions [9]. On CT the diagnosis of brown tumor is suggested by the presence of an expansile lytic lesion in a patient with other features of hyperparathyroidism [10]. Fluid–fluid levels on CT or MRI may occur whenever substances with different densities are confined to a cystic or compartmental area, and are nonspecific findings that may be observed in a variety of neoplastic, inflammatory, traumatic, and other miscellaneous pathologic conditions. Fluid– fluid levels on MRI have been reported before in brown tumors [11,12], but on the one hand, not all brown tumors display fluid– fluid levels, and on the other hand there are many other tumors of bone and soft tissue with fluid–fluid levels on MRI [13,14]. Past reports of brown tumors have demonstrated a large range of signal intensities from low to high signal intensity on T2-weighted MR images. Conversely, fluid–fluid levels have not been observed in mucoceles, although cystic lesions with fluid–fluid levels have been interpreted as mucoceles in the past [15]. The signal intensity, while very variable in mucoceles too, was unusual high in our case, a finding not typical for a mucocele. The initial radiological description as mucocele was therefore subsequently revised to cystic bone lesion. We have not performed biochemical analysis of the cyst content, but, as other authors have reported, one plausible explanation for the occurrence of fluid–fluid levels is repeated bleeding in the tumor [11]. This would lead to the formation of a xanthochromic supernatant with high signal intensity on T2weighted MR images, and a dependent low-intensity portion consisting of liquefied hematoma. The former would correspond to the yellowish fluid described on opening the cystic component, while the latter was presumably not reported/observed because of the brownish color, close to the color of the brown tumor. As brown tumors do not exhibit specific changes, neither on CT/ MR, nor histologically, the diagnosis of brown tumor must be based on the combination of a histological giant-cell lesion and biochemical evidence of hyperparathyroidism. The clinical value of diagnosing the hyperparathyroidism, once the histological diagnosis of giant-cell tumor is made, resides in the
421
fact that many brown tumors regress (though not always completely) after the treatment of the hyperparathyroidism, making surveillance a feasible option [2]. There are reports, however, of brown tumors persisting after 6 years of follow-up [3] or even growing after the treatment of the hyperparathyroidism [4], leaving surgery as the only adequate option. Surgery has also been used for cosmetic or functional reasons [6]. Furthermore, our patient had ophthalmological and neurological symptoms, and in a similar case, we will recommend surgical treatment of the brown tumor besides the treatment of the hyperparathyroidism. 4. Conclusions Brown tumors in the facial bones are extremely rare, but should be considered in the differential diagnosis of a mass in the facial skeleton. The diagnosis is based on a combination of a histological giant-cell lesion and biochemical evidence of hyperparathyroidism. The primary treatment of brown tumors consists in the management of the hyperparathyroidism, but for patients with large, symptomatic tumors, surgical treatment of the brown tumors is recommended. Conflict of interest None. References [1] Schiller AL, Teitelbaum SL. Bones and joints. In: Rubin E, Farber JL, editors. Pathology. 3rd ed., Philadephia, New York: Lippincott-Raven; 1999. p. 1336– 413. [2] Resendiz-Colosia JA, Rodriguez-Cuevas SA, Flores-Diaz R, Juan MH, GallegosHernandez JF, Barroso-Bravo S, et al. Evolution of maxillofacial brown tumors after parathyroidectomy in primary hyperparathyroidism. Head Neck 2008;30:1497–504. [3] Agarwal G, Mishra SK, Kar DK, Singh AK, Arya V, Gupta SK, et al. Recovery pattern of patients with osteitis fibrosa cystica in primary hyperparathyroidism after successful parathyroidectomy. Surgery 2002;132: 1075–83. [4] Yamazaki H, Ota Y, Aoki T, Karakida K. Brown tumor of the maxilla and mandible: progressive mandibular brown tumor after removal of parathyroid adenoma. J Oral Maxillofac Surg 2003;61:719–22. [5] Merz MN, Massich DD, Marsh W, Schuller DE. Hyperparathyroidism presenting as brown tumor of the maxilla. Am J Otolaryngol 2002;23:173–6. [6] Guney E, Yigitbasi OG, Bayram F, Ozer V, Canoz O. Brown tumor of the maxilla associated with primary hyperparathyroidism. Auris Nasus Larynx 2001;28:369–72. [7] Lessa MM, Sakae FA, Tsuji RK, Filho BC, Voegels RL, Butugan O. Brown tumor of the facial bones: case report and literature review. Ear Nose Throat J 2005;84:432–4. [8] Gould CF, Ly JQ, Lattin Jr GE, Beall DP, Sutcliffe III JB. Bone tumor mimics: avoiding misdiagnosis. Curr Probl Diagn Radiol 2007;36:124–41. [9] Hong WS, Sung MS, Chun KA, Kim JY, Park SW, Lee KH, et al. Emphasis on the MR imaging findings of brown tumor: a report of five cases. Skeletal Radiol 2010 . [10] Knowles NG, Smith DL, Outwater EK. MRI diagnosis of brown tumor based on magnetic susceptibility. J Magn Reson Imaging 2008;28: 759–61. [11] 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;24:631–4. [12] 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;22:265–8. [13] Tsai JC, Dalinka MK, Fallon MD, Zlatkin MB, Kressel HY. Fluid–fluid level: a nonspecific finding in tumors of bone and soft tissue. Radiology 1990;175: 779–82. [14] Kendi AT, Kara S, Altinok D, Keskil S. Sinonasal ossifying fibroma with fluid–fluid levels on MR images. AJNR Am J Neuroradiol 2003;24:1639–41. [15] Vaidya AM, Chow JM, Goldberg K, Stankiewicz JA. Juvenile aggressive ossifying fibroma presenting as an ethmoid sinus mucocele. Otolaryngol Head Neck Surg 1998;119:665–8.