Brown Tumor and Mark R.
Secondary Hyperparathyroidism
Levine, MD; Alfredo Chu, MD; Fadi W. Abdul-Karim, MD
tumor is a focal, bony lesion hyperparathyroidism that results from parathyroid hormone on bone increasing osteoclastic activity with bone resorp\s=b\ Brown
REPORT OF A CASE
of
tion and trabecular fibrosis. This leads to microfractures and hemorrhage and the appearance of brown tumors, which are most commonly in primary hyperparathyroidism and less frequently in secondary hyperparathyroidism. Rarely seen
do these tumors involve the orbit. We report the sixth case, to our knowledge, of orbital involvement, in a patient with chronic renal failure (secondary hyperparathyroidism) and review the literature.
(Arch Ophthalmol. 1991;109:847-849)
hemodialysis is employed more frequently for treating patients with chronic renal failure, a larger patient population with secondary hy¬ perparathyroidism has come into exis¬ tence. Ophthalmologists rarely en¬ counter these patients, except perhaps when they present with brown tumors involving the orbit. Brown tumor, as well as osteitis fibrosa cystica, are bone lesions associated with primary and secondary hyperparathyroidism, but are more common in primary hy¬ perparathyroidism. Orbital involve¬ ment is rare; to our knowledge, only five cases have been reported in the ophthalmic literature.12 We describe a patient with secondary hyperparathy¬ roidism who developed a brown tumor of the orbit, discuss the differential diagnosis, and review the literature. "^
s
Accepted for publication January 23, 1991. From the Division of Ophthalmology, The Mt Sinai Medical Center, Cleveland, Ohio (Drs Levine and Chu); the Departments of Ophthalmology (Dr Levine) and Pathology (Dr Abdul-Karim), Case Western Reserve University School of Medicine, Cleveland; and Oculoplastics Clinics, University Hospitals of Cleveland (Dr Levine). Reprint requests to 26900 Cedar Rd, Beachwood, OH 44122 (Dr Levine).
A 27-year-old woman with chronic renal failure secondary to Alport's syndrome (he¬ reditary nephritis) that had been diagnosed at age 17 years was admitted with proptosis and diplopia. She had been successfully receiving hemodialysis treatment for sever¬ al years when, 4 months prior to admission, she developed pain in her hands and knees. One month prior to admission the patient sustained a spontaneous rib fracture from coughing, and developed diplopia and pro¬ ptosis of the left eye. Twenty-four hours prior to admission she complained of diffuse headaches, generalized weakness, and fe¬ ver. She had no history of trauma and had been receiving antihypertensive medica¬ tions, vitamin D, calcium supplements, and phosphate binders for osteoporosis. Examination on admission revealed an alert, oriented, febrile woman. Blood pres¬ sure was 110/60 mm Hg; pulse, 60 beats per minute and regular; respiratory rate, 18 breaths per minute; and temperature, 38.6°C. The results of the physical examina¬ tion were normal. Ophthalmologic examination showed vi¬ sual acuity to be 20/20 OD and 20/25 OS. The left eye was 10 mm proptotic. A firm, nontender mass was present in the left superonasal orbit (Fig 1). Upgaze and right gaze were restricted. Pupillary, anterior segment, and fundus examination results were normal. Intraocular pressure was 18 mm Hg OU by applanation. Pertinent laboratory findings were as fol¬ lows: hematocrit, 0.29; hemoglobin, 96 g/L; and white blood cell count, 6.5xl07L. Electrolyte analysis showed sodium of 136 mmol/L (normal range, 135 to 145 mmol/L); potassium, 3.3 mmol/L (normal range, 3.5 to 5.0 mmol/L); calcium, 2.27 mmol/L (nor¬ mal range, 2.12 to 2.62 mmol/L); phospho¬ rus, 0.65 mmol/L (normal range, 0.81 to 1.45 mmol/L); creatinine, 680 µ /L (nor¬ mal range, 53 to 115 µ /L); magnesium, 1.16 mmol/L (normal range, 0.75 to 1.00 mmol/L); and alkaline phosphatase, 582 U/L (normal range, 33 to 110 U/L). The patient's serum protein level was 57 g/L (normal range, 60 to 80 g/L); albumin, 38 g/L (nor-
mal range, 34 to 53 g/L); bilirubin, 8.55 µ /L (normal range, 1.71 to 20.52 µ /L); uric acid, 238 µ /L (normal range, 125 to 380 µ /L); and parathyroid hormone N-terminal, 1457 kg/L (normal, 100 kg/L). Blood and spinal tap cultures
negative. Roentgenography of the orbit showed obscuration of the left innominate line by a radiolucent lesion; bony destruction was also apparent. Computed tomography dem¬ onstrated a well-circumscribed large mass were
in the area of the left frontoethmoid sinuses that extended into the superior nasal orbit displacing the globe inferotemporally (Figs 2 and 3). Erosion of the anterior and poste¬ rior table of the frontal sinus extended into the anterior cranial fossa. A computed tomographic scan of the mandible showed a lytic area in the anterior mandible. Magnet¬ ic resonance imaging offered no additional information. The patient underwent a diagnostic biop¬ sy via an internal ethmoidectomy that re¬ vealed a brown tumor, characterized by the presence of numerous osteoclastic-type gi¬ ant cells in a fibrovascular background with hemosiderin deposition (Fig 4). A definitive procedure through a semicircular incision from the medial brow to below the medial canthal tendon allowed excellent exposure to remove the tumor in toto (Fig 5). The tumor was peeled from the dura since it had eroded the frontal sinus tables, and was dissected off the periorbita. After surgery, the proptosis was totally reduced and the diplopia resolved (Fig 6). Approximately 6 weeks later, a subtotal parathyroidectomy was performed in which the residual para¬ thyroid gland was implanted into the pec¬ torales major muscle.
COMMENT
Brown tumor occurs most in the
commonly
ribs, clavicle, pelvic girdle, and
mandible.3 The disease is characterized
by bone pain and pathologic fracture. In the five previously reported cases, the age at diagnosis of orbital brown tumor
ranged from 7 to 70 years; most
patients
Downloaded From: http://archopht.jamanetwork.com/ by a Georgetown University Medical Center User on 05/21/2015
were seen
in the second de-
cade of life. Presenting symptoms in¬ clude a palpable mass, pain, proptosis, diplopia, nasal obstruction, and tear-
Fig
ing. Our patient complained of diplo¬ pia, proptosis, and pain. Although computed tomography suggested the
Patient with 10 mm of proptosis and fullness in the left superior nasal orbit.
1. —
Fig
2.—Axial computed tomographic scan shows a circumscribed in the left frontoethmoid sinus impinging on the left medial rectus muscle. mass
cation
50).
our patient did not manifest nasal obstruction or epiphora. The maxillary bone is most commonly involved in the orbital area, but the ethmoid and fron¬ tal bones may also be involved, as was noted in our patient. In our initial examination we overlooked a mass in the mandibular area. Subsequent roentgenographic studies of the mandi¬ ble demonstrated a lytic lesion. Laboratory determination of elevat¬ ed serum calcium, decreased phos¬ phate, elevated alkaline phosphatase, and increased parathyroid hormone levels is crucial for diagnosing hyper¬ parathyroidism/ Chronic renal failure results in decreased phosphate excre¬ tion, hyperphosphatemia, and hypocalcemia. These factors are believed to play a role in secondary hyperparathy¬ roidism by leading to chronic stimula-
area,
Fig 3. —Coronal computed tomographic scan shows the mass eroding into the anterior and posterior table of the frontal sinus, extending into the anterior cranial fossa.
4. —Photomicrograph shows prominent osteoblastic and osteoclastic activity (doublearrow), with intertrabecular fibrovascular proliferation and hemorrhage. Numerous osteoclastic-type giant cells are seen on the right (arrows) (hematoxylin-eosin, original magnifi¬
Fig
headed
involvement of the nasolacrimal duct
Fig 5.—A semicircular incision extending from beneath the left brow into the medial canthal area is shown, exposing a large mass that extends into the frontoethmoid sinuses.
Downloaded From: http://archopht.jamanetwork.com/ by a Georgetown University Medical Center User on 05/21/2015
Fig 6. Postoperative appearance, with reduction of proptosis and superior nasal fullness. —
tion of parathyroid hormone secretion and secondary hyperplasia of the para¬
thyroid gland. The constantly elevated parathyroid
hormone levels contribute to bone dis¬ ease and to the other clinical features of chronic renal failure. Parathyroid hormone effectively results in in-
creased osteoclastic activity with ré¬ sorption of bone and intertrabecular fibrosis. With progression of bone ré¬ sorption, microfractures and microhemorrhages occur, hemosiderin-laden
macrophages accumulate, and numer¬ ous osteoclastic-type multinucleated
giant cells are present in a background
of fibrovascular stroma. ' The hemosiderin pigment deposits can be promi¬ nent and impart a brown color to the tumor. The histopathologic differential diagnoses include giant-cell tumor, gi¬ ant-cell reparative granuloma, and an¬ eurysmal bone cysts; these are distin¬ guished clinically from brown tumor by the absence of metabolic alteration of hyperparathyroidism. Radiologie stud¬ ies show patchy demineralization of bone (moth-eaten appearance), erosion of outer and inner cortical surfaces, fractures, and locally destructive le¬ sions.'" Treatment is excision of the tumor followed by exploration and re¬ moval of the parathyroid. Prognosis is excellent. As more patients undergo long-term
hemodialysis treatment, we may en¬ counter patients with secondary hy¬ perparathyroidism more frequently. In patients with clinical manifestations of primary or secondary hyperparathy¬ roidism, brown tumor should be con¬ sidered in the differential diagnosis of orbital
masses.
References 1. Weiss
RR, Schoeneman MJ, Primack W, Bo-
zycki D, Bemet B, Greifer I. Maxillary brown tumor of secondary hyperparathyroidism in a hemodialysis patient. JAMA. 1980;243:1929-1930. 2. Naiman J, Green WR, D'Heurle D, et al. Brown tumor of the orbit associated with primary hyperparathyroidism. Am J Ophthalmol. 1980;
90:565. 3. Parrish CM, O'Day DM. Brown tumor of the orbit. Arch Ophthalmol. 1986;104:1199. 4. Cotran RS, Kumar V, Robbins SL. Robbins Pathologic Basis of Disease. Philadelphia, Pa: WB Saunders Co; 1989:1326-1328. 5. Aurbach G, Marx SJ, Spiegel AM. Parathy-
roid hormone, calcitonia, and calciferols. In: Wilson DD, Foster DW, eds. Williams Textbook of Endocrinology. Philadelphia, Pa: WB Saunders Co; 1985. 6. Som PM, Lawson W, Cohen BA. Giant cell lesions of the facial bones. Radiology. 1983;147:129.
Currently in Other AMA Journals JAMA
Resident Physician Substance Use in the United States P. H. Hughes; S. E. Conard; D. C. Baldwin, Jr; C. L. Storr; D. V. Sheehan (JAMA.
1991:265:2069) Substance Use Among Senior Medical Students D. C. Baldwin, Jr; P. H. Hughes; S. E. Conard; C. L. Storr; D. V. Sheehan (JAMA. 1991;265:2074) Do House Officers Learn From Their Mistakes? A. W. Wu; S. Folkman; S. J. McPhee; B. Lo (JAMA. 1991:265:2089)
Recent Approaches to the Treatment of Sickle Cell Anemia G. P. Rodgers (JAMA. 1991:265:2097)
Downloaded From: http://archopht.jamanetwork.com/ by a Georgetown University Medical Center User on 05/21/2015
Secondary Hyperparathyroidism
Levine, MD; Alfredo Chu, MD; Fadi W. Abdul-Karim, MD
tumor is a focal, bony lesion hyperparathyroidism that results from parathyroid hormone on bone increasing osteoclastic activity with bone resorp\s=b\ Brown
REPORT OF A CASE
of
tion and trabecular fibrosis. This leads to microfractures and hemorrhage and the appearance of brown tumors, which are most commonly in primary hyperparathyroidism and less frequently in secondary hyperparathyroidism. Rarely seen
do these tumors involve the orbit. We report the sixth case, to our knowledge, of orbital involvement, in a patient with chronic renal failure (secondary hyperparathyroidism) and review the literature.
(Arch Ophthalmol. 1991;109:847-849)
hemodialysis is employed more frequently for treating patients with chronic renal failure, a larger patient population with secondary hy¬ perparathyroidism has come into exis¬ tence. Ophthalmologists rarely en¬ counter these patients, except perhaps when they present with brown tumors involving the orbit. Brown tumor, as well as osteitis fibrosa cystica, are bone lesions associated with primary and secondary hyperparathyroidism, but are more common in primary hy¬ perparathyroidism. Orbital involve¬ ment is rare; to our knowledge, only five cases have been reported in the ophthalmic literature.12 We describe a patient with secondary hyperparathy¬ roidism who developed a brown tumor of the orbit, discuss the differential diagnosis, and review the literature. "^
s
Accepted for publication January 23, 1991. From the Division of Ophthalmology, The Mt Sinai Medical Center, Cleveland, Ohio (Drs Levine and Chu); the Departments of Ophthalmology (Dr Levine) and Pathology (Dr Abdul-Karim), Case Western Reserve University School of Medicine, Cleveland; and Oculoplastics Clinics, University Hospitals of Cleveland (Dr Levine). Reprint requests to 26900 Cedar Rd, Beachwood, OH 44122 (Dr Levine).
A 27-year-old woman with chronic renal failure secondary to Alport's syndrome (he¬ reditary nephritis) that had been diagnosed at age 17 years was admitted with proptosis and diplopia. She had been successfully receiving hemodialysis treatment for sever¬ al years when, 4 months prior to admission, she developed pain in her hands and knees. One month prior to admission the patient sustained a spontaneous rib fracture from coughing, and developed diplopia and pro¬ ptosis of the left eye. Twenty-four hours prior to admission she complained of diffuse headaches, generalized weakness, and fe¬ ver. She had no history of trauma and had been receiving antihypertensive medica¬ tions, vitamin D, calcium supplements, and phosphate binders for osteoporosis. Examination on admission revealed an alert, oriented, febrile woman. Blood pres¬ sure was 110/60 mm Hg; pulse, 60 beats per minute and regular; respiratory rate, 18 breaths per minute; and temperature, 38.6°C. The results of the physical examina¬ tion were normal. Ophthalmologic examination showed vi¬ sual acuity to be 20/20 OD and 20/25 OS. The left eye was 10 mm proptotic. A firm, nontender mass was present in the left superonasal orbit (Fig 1). Upgaze and right gaze were restricted. Pupillary, anterior segment, and fundus examination results were normal. Intraocular pressure was 18 mm Hg OU by applanation. Pertinent laboratory findings were as fol¬ lows: hematocrit, 0.29; hemoglobin, 96 g/L; and white blood cell count, 6.5xl07L. Electrolyte analysis showed sodium of 136 mmol/L (normal range, 135 to 145 mmol/L); potassium, 3.3 mmol/L (normal range, 3.5 to 5.0 mmol/L); calcium, 2.27 mmol/L (nor¬ mal range, 2.12 to 2.62 mmol/L); phospho¬ rus, 0.65 mmol/L (normal range, 0.81 to 1.45 mmol/L); creatinine, 680 µ /L (nor¬ mal range, 53 to 115 µ /L); magnesium, 1.16 mmol/L (normal range, 0.75 to 1.00 mmol/L); and alkaline phosphatase, 582 U/L (normal range, 33 to 110 U/L). The patient's serum protein level was 57 g/L (normal range, 60 to 80 g/L); albumin, 38 g/L (nor-
mal range, 34 to 53 g/L); bilirubin, 8.55 µ /L (normal range, 1.71 to 20.52 µ /L); uric acid, 238 µ /L (normal range, 125 to 380 µ /L); and parathyroid hormone N-terminal, 1457 kg/L (normal, 100 kg/L). Blood and spinal tap cultures
negative. Roentgenography of the orbit showed obscuration of the left innominate line by a radiolucent lesion; bony destruction was also apparent. Computed tomography dem¬ onstrated a well-circumscribed large mass were
in the area of the left frontoethmoid sinuses that extended into the superior nasal orbit displacing the globe inferotemporally (Figs 2 and 3). Erosion of the anterior and poste¬ rior table of the frontal sinus extended into the anterior cranial fossa. A computed tomographic scan of the mandible showed a lytic area in the anterior mandible. Magnet¬ ic resonance imaging offered no additional information. The patient underwent a diagnostic biop¬ sy via an internal ethmoidectomy that re¬ vealed a brown tumor, characterized by the presence of numerous osteoclastic-type gi¬ ant cells in a fibrovascular background with hemosiderin deposition (Fig 4). A definitive procedure through a semicircular incision from the medial brow to below the medial canthal tendon allowed excellent exposure to remove the tumor in toto (Fig 5). The tumor was peeled from the dura since it had eroded the frontal sinus tables, and was dissected off the periorbita. After surgery, the proptosis was totally reduced and the diplopia resolved (Fig 6). Approximately 6 weeks later, a subtotal parathyroidectomy was performed in which the residual para¬ thyroid gland was implanted into the pec¬ torales major muscle.
COMMENT
Brown tumor occurs most in the
commonly
ribs, clavicle, pelvic girdle, and
mandible.3 The disease is characterized
by bone pain and pathologic fracture. In the five previously reported cases, the age at diagnosis of orbital brown tumor
ranged from 7 to 70 years; most
patients
Downloaded From: http://archopht.jamanetwork.com/ by a Georgetown University Medical Center User on 05/21/2015
were seen
in the second de-
cade of life. Presenting symptoms in¬ clude a palpable mass, pain, proptosis, diplopia, nasal obstruction, and tear-
Fig
ing. Our patient complained of diplo¬ pia, proptosis, and pain. Although computed tomography suggested the
Patient with 10 mm of proptosis and fullness in the left superior nasal orbit.
1. —
Fig
2.—Axial computed tomographic scan shows a circumscribed in the left frontoethmoid sinus impinging on the left medial rectus muscle. mass
cation
50).
our patient did not manifest nasal obstruction or epiphora. The maxillary bone is most commonly involved in the orbital area, but the ethmoid and fron¬ tal bones may also be involved, as was noted in our patient. In our initial examination we overlooked a mass in the mandibular area. Subsequent roentgenographic studies of the mandi¬ ble demonstrated a lytic lesion. Laboratory determination of elevat¬ ed serum calcium, decreased phos¬ phate, elevated alkaline phosphatase, and increased parathyroid hormone levels is crucial for diagnosing hyper¬ parathyroidism/ Chronic renal failure results in decreased phosphate excre¬ tion, hyperphosphatemia, and hypocalcemia. These factors are believed to play a role in secondary hyperparathy¬ roidism by leading to chronic stimula-
area,
Fig 3. —Coronal computed tomographic scan shows the mass eroding into the anterior and posterior table of the frontal sinus, extending into the anterior cranial fossa.
4. —Photomicrograph shows prominent osteoblastic and osteoclastic activity (doublearrow), with intertrabecular fibrovascular proliferation and hemorrhage. Numerous osteoclastic-type giant cells are seen on the right (arrows) (hematoxylin-eosin, original magnifi¬
Fig
headed
involvement of the nasolacrimal duct
Fig 5.—A semicircular incision extending from beneath the left brow into the medial canthal area is shown, exposing a large mass that extends into the frontoethmoid sinuses.
Downloaded From: http://archopht.jamanetwork.com/ by a Georgetown University Medical Center User on 05/21/2015
Fig 6. Postoperative appearance, with reduction of proptosis and superior nasal fullness. —
tion of parathyroid hormone secretion and secondary hyperplasia of the para¬
thyroid gland. The constantly elevated parathyroid
hormone levels contribute to bone dis¬ ease and to the other clinical features of chronic renal failure. Parathyroid hormone effectively results in in-
creased osteoclastic activity with ré¬ sorption of bone and intertrabecular fibrosis. With progression of bone ré¬ sorption, microfractures and microhemorrhages occur, hemosiderin-laden
macrophages accumulate, and numer¬ ous osteoclastic-type multinucleated
giant cells are present in a background
of fibrovascular stroma. ' The hemosiderin pigment deposits can be promi¬ nent and impart a brown color to the tumor. The histopathologic differential diagnoses include giant-cell tumor, gi¬ ant-cell reparative granuloma, and an¬ eurysmal bone cysts; these are distin¬ guished clinically from brown tumor by the absence of metabolic alteration of hyperparathyroidism. Radiologie stud¬ ies show patchy demineralization of bone (moth-eaten appearance), erosion of outer and inner cortical surfaces, fractures, and locally destructive le¬ sions.'" Treatment is excision of the tumor followed by exploration and re¬ moval of the parathyroid. Prognosis is excellent. As more patients undergo long-term
hemodialysis treatment, we may en¬ counter patients with secondary hy¬ perparathyroidism more frequently. In patients with clinical manifestations of primary or secondary hyperparathy¬ roidism, brown tumor should be con¬ sidered in the differential diagnosis of orbital
masses.
References 1. Weiss
RR, Schoeneman MJ, Primack W, Bo-
zycki D, Bemet B, Greifer I. Maxillary brown tumor of secondary hyperparathyroidism in a hemodialysis patient. JAMA. 1980;243:1929-1930. 2. Naiman J, Green WR, D'Heurle D, et al. Brown tumor of the orbit associated with primary hyperparathyroidism. Am J Ophthalmol. 1980;
90:565. 3. Parrish CM, O'Day DM. Brown tumor of the orbit. Arch Ophthalmol. 1986;104:1199. 4. Cotran RS, Kumar V, Robbins SL. Robbins Pathologic Basis of Disease. Philadelphia, Pa: WB Saunders Co; 1989:1326-1328. 5. Aurbach G, Marx SJ, Spiegel AM. Parathy-
roid hormone, calcitonia, and calciferols. In: Wilson DD, Foster DW, eds. Williams Textbook of Endocrinology. Philadelphia, Pa: WB Saunders Co; 1985. 6. Som PM, Lawson W, Cohen BA. Giant cell lesions of the facial bones. Radiology. 1983;147:129.
Currently in Other AMA Journals JAMA
Resident Physician Substance Use in the United States P. H. Hughes; S. E. Conard; D. C. Baldwin, Jr; C. L. Storr; D. V. Sheehan (JAMA.
1991:265:2069) Substance Use Among Senior Medical Students D. C. Baldwin, Jr; P. H. Hughes; S. E. Conard; C. L. Storr; D. V. Sheehan (JAMA. 1991;265:2074) Do House Officers Learn From Their Mistakes? A. W. Wu; S. Folkman; S. J. McPhee; B. Lo (JAMA. 1991:265:2089)
Recent Approaches to the Treatment of Sickle Cell Anemia G. P. Rodgers (JAMA. 1991:265:2097)
Downloaded From: http://archopht.jamanetwork.com/ by a Georgetown University Medical Center User on 05/21/2015
