Thyroid heterotopic bone formation (HBF) in goiter is a rare finding. Five thyroid resection specimens were analyzed for HBF. The results were correlated with clinicomorphological features. All patients were women (33–82 years). The preoperative diagnosis was thyroid goiter or nodule. Treatment consisted in thyroidectomy and lobectomy (3 and 2, resp.). Microscopy showed sporadic nodular goiter. Malformative blood vessels and vascular calcifications were seen in intra- and extrathyroid location (5 and 3, resp.). The number and size of HBFs (total: 28) ranged between 1 and 23/thyroid gland (one bilateral) and 1 and 10 mm, respectively. Twelve HBFs were in contact with the thyroid capsule. Most were extranodular (21, versus 6 intranodular). The medical history was positive for dyslipidemia, hyperglycemia, renal dysfunction, and hyperuricemia (2, 3, and 3 cases and 1 case, resp.) without any parathyroid abnormality. In conclusion, thyroid HBF may be characterized by subcapsular or extranodular location, various size (usually ≥2 mm), and vascular calcifications and malformations. Features of metabolic syndrome and renal dysfunction may be present, but their exact role in the pathogenesis of HBFs remains to be elucidated.
Heterotopic bone formation (HBF) is defined as extraskeletal bone formation. Thyroid HBF, frequently designated as bone metaplasia, occurs rarely in the thyroid, being reported both in goiter and in tumors such as adenomas and carcinosarcomas [
Five thyroid resection specimens were analyzed for HBF as defined by the presence of lamellar bone trabeculae delimiting fat or fibrofat tissue with hematopoietic elements and capillaries. The number, size, and location of HBF foci (subcapsular or not, intranodular or not) were tabulated. Foci of ossification consisting only of bone trabeculae were considered separately. Thyroid parenchyma was also analyzed for nodules (hyperplastic, adenoma-type, or carcinoma), atrophy, necrosis, fibrosis, calcifications, inflammation, and vascular lesions (pseudoangioma lesions or vascular conglomerates, thrombosis, intima/media fibrosis and hyperplasia, and calcifications). Two thyroids were sampled quasi-entirely (Cases
The main features of the cases are demonstrated in Tables
Clinical features of the 5 patients with adult bone metaplasia.
Case |
Age (years) | Gender | Euthyroid | Punction | Presurgical diagnosis | Cardiovascular disease | Dyslipidemia | Diabetes | Osteoarticular disease | Impaired renal function | BMI | Type of thyroid surgery | Morphological diagnosis | Postsurgical hypocalcemia |
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1 | 51 | W | No | No | Toxic goiter | AHT, tachycardia cardiomegaly | NA | No | Odontoid chondrocalcinosis, C4–C7 arthrosis | No | 31.3 | Right and left thyroid lobectomies | Sporadic goiter | Yes |
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2 | 33 | W | Yes | No | Multinodular goiter (trachea deviation) | No | NA | No | No | Yes | 32 | Total thyroidectomy | Sporadic goiter | No |
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3 | 63 | W | Yes | No | Multinodular goiter | AHT, mitral stenosis | Yes | Yes | No | Yes | 22.5 | Total thyroidectomy | Sporadic goiter | Yes |
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4 | 83 | W | No | No | Left cystic nodule (trachea deviation) | AHT | NA | No | Osteoporosis | Yes | 26.4 | Left thyroid lobectomy | Goiter with adenoma-like nodule | No |
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5 | 71 | W | Yes | Yes |
Compressive cyst | AHT | Yes | No | Arthrosis, serum vitamin D OH 25D1 D3 insufficiency, and hyperuricemia | No | 41.9 | Right thyroidectomy | Follicular adenoma, cystic change | Yes |
BMI: body mass index, NA: nonavailable, W: woman, and AHT: arterial hypertension.
Hyperthyroidism was diagnosed in Cases
Decreased serum creatinine was diagnosed in Case
Case
There was no alcohol abuse in any of the cases; smoking habits (10 PA) were noted in Case
Main morphological characteristics of the 5 thyroidectomy specimens.
Number | Thyroid weight (grams) | Thyroid volume (mm3) | Number of HBF foci (size, mm) | Number of ossification foci | Thyroid calcifications | Thyroid fibrosis | Thyroid inflammation | Vascular calcifications | Thyroid adipose involution |
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1 | 48 | 93.75 | 1 (2.5 mm) | 0 | 1 | Severe | Moderate | No | Multifocal |
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2 | 32 | 72 | 27 (2–10 mm) | 11 | 1 | Severe | Moderate | No | Multifocal |
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3 | 38 | 51 | 1 (10) | 0 | 1 |
Mild | Mild | Intra-, perithyroid | No |
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4 | 115 | 195 | 2 (1 and 9.5 mm) | 14 | 1 |
Mild | Moderate | Intra-, perithyroid | No |
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5 | 43 | 180 | 1 (8 mm) | 0 | 1 |
Mild | Mild to moderate | Intra-, perithyroid | Multifocal |
Normal parathyroid tissue was seen in the perithyroid adipose tissue in Case
The patient (51-year-old woman) had undergone a total thyroidectomy for toxic goiter. The patient was treated with carbimazole and thyroxine for 1.5 years. The medical history was positive for arterial hypertension and tachycardia as well as for cardiomegaly. There was no evidence of anemia. Foci of micro- and macrocalcifications were observed on thyroid ultrasound examination (Figure
Microscopy showed sporadic multinodular goiter with malformative, large, and tortuous blood vessels (intra- and extrathyroidal) intermingled with rare nerves. There were no vascular thromboses. Parenchymal nodules, several encapsulated, were hyperplastic and adenoma-like. Inflammation was moderate. Fibrosis was severe and extensive with a band-like pattern without extrathyroid extension. One HBF was identified (2.5 mm) with no ossification foci. Multifocal adipose involution was seen.
At ultrasound examination the thyroid showed several nodules and micro- and macrocalcifications (a, b: white arrows, Case
The patient (33-year-old woman) had undergone a total thyroidectomy for goiter with trachea deviation. She was euthyroid. Smoking of 10 packs/year was noted. There was no evidence of anemia. Thyroid ultrasound examination showed foci of micro- and macrocalcifications (Figure
Microscopy showed sporadic multinodular goiter with malformative, large, and tortuous blood vessels (intra- and extrathyroidal) intermingled with rare nerves. Vascular cavities with tuft-like projections were associated. There were no vascular thromboses. Parenchymal nodules, several encapsulated, were hyperplastic and adenoma-like. Several atrophic nodules, some with intranodular fibrocollagen, were also seen. Inflammation was moderate. Fibrosis was severe and extensive with a band-like pattern, containing or being at proximity of large blood vessels (intra- or extrathyroid), without extrathyroid extension. Twenty-three HBFs (2–10 mm) were identified with 11 ossification foci. Three extranodular HBFs were in direct contact with the capsule of fibroatrophic nodules. For two HBFs, band-like fibrosis connected malformative vessels to the HBF. On serial sections, two ossification foci revealed intertrabecular spaces and were thus diagnosed as HBFs. Multifocal adipose involution was seen as well as intrathyroid muscle tissue (the closest at 6.5 mm from the HBF).
The patient (63-year-old woman) had undergone a thyroidectomy for goiter. The patient was euthyroid and was diagnosed with arterial hypertension and mitral stenosis. There was no evidence of anemia. Postsurgical hypocalcemia was treated with calcium. The patient was well at postsurgical consultation (after 1 month of follow-up).
Microscopy showed sporadic multinodular goiter with malformative, large, and tortuous blood vessels (intra- and extrathyroid) intermingled with rare nerves. There were no vascular thromboses. Parenchymal nodules, several encapsulated, were hyperplastic and adenoma-like. Calcifications of the internal elastic lamina and media (von Monckeberg sclerosis-type) were observed in the vessel wall, in peri- and intrathyroid locations [
The patient (83-year-old woman) had undergone left thyroidectomy for a cystic nodule with trachea deviation. The patient had been treated with carbimazole and thyroxine (15 days). The medical history was positive for arterial hypertension and osteoporosis. There was no evidence of anemia. The patient was well at postsurgical consultation (after 2 months of follow-up).
Microscopy showed sporadic multinodular goiter with malformative, large, and tortuous blood vessels (intra- and extrathyroidal) intermingled with rare nerves. Vascular cavities with tuft-like projections were associated. There were no thromboses. Parenchymal nodules, several encapsulated, were hyperplastic and adenoma-like. Calcifications of the internal elastic lamina and media (von Monckeberg sclerosis-type) were observed in the vessel wall. Perivascular calcifications of calcipheresis-type were also seen. Thyroid inflammation was moderate and fibrosis mild. Two HBFs were identified (1 and 9.5 mm) with 14 ossification foci. Abnormal blood vessels were seen around the largest HBF.
The patient (71-year-old woman) had undergone right thyroidectomy for compressive cyst. The patient was euthyroid. The medical history was positive for arterial hypertension. The patient also showed vitamin D deficiency (10.1 ng/mL) as well as hyperuricemia and arthrosis and did not show anemia. An evacuatory punction was followed by reincrease in size of the nodule (3 months afterwards). Postsurgical hypocalcemia occurred and was treated with calcium supplementation. The patient was well at postsurgical consultation (after 3 weeks of follow-up).
Microscopy showed sporadic multinodular goiter with malformative, large, and tortuous blood vessels (intra- and extrathyroidal) intermingled with rare nerves. There were no vascular thromboses. Parenchymal nodules, several encapsulated, were hyperplastic and adenoma-like. Calcifications of the internal elastic lamina and media (von Monckeberg sclerosis-type) were observed in the vessel wall. Perivascular calcifications of calcipheresis-type were seen in hyperplastic nodules. There were no vascular thromboses. Inflammation was mild to moderate and fibrosis was mild. One HBF (8 mm) was identified. Abnormal blood vessels were seen around the HBF. Adipose involution was multifocal.
The total number of HBF foci was 28. The number varied between 1 and 23 foci/thyroid specimen (bilateral: one) and size ranged from inframillimetric to 10 mm. Eighteen (64%) HBFs were ≥2 mm and six (21%) ≥5 mm. The shape varied: triangular (
Here we report five cases of thyroid HBF occurring in the context of sporadic goiter in euthyroid or hyperthyroid patients. The diagnosis of such lesions was microscopic. The imaging diagnosis was difficult; both micro- and macrocalcifications occurred. Although the HBFs were frequently extranodular and more than 2 mm in size when intranodular, the imaging features do not allow the precise diagnosis of HBF-type lesions. Whether the subcapsular location, seen in approximately one-third of the HBFs, might be useful remains to be further studied. The main relevance of intrathyroid HBFs is morphological, microscopical. Unlike on ultrasound examination, a misdiagnosis of carcinoma may be made on frozen-section examinations due to the presence of osteoclast-like elements [
The histogenesis of such lesions remains a matter of debate. The various thyroid topography, intraparenchymal or subcapsular, of the HBF foci we have seen, occurring in sheet-like fibrosis, more frequently extranodular, suggests a nonneoplastic origin. The presence of multiple, bilateral foci, round to oval more frequently, suggests a dysmetabolic rather than an ectopic nature. The most plausible hypothesis is that of degenerative changes, similar to those reported in the femoral arteries and, less frequently in the carotid, at ages above 60 [
HBF in the context of abnormal parathyroid functioning has been reported recently in one case [
Interestingly, the intranodular perivascular or intervesicular pattern of some calcifications observed in some of the nodules suggests a relationship with renal dysfunction, at least for early/initial lesions. Thyroid inflammatory disease may be also incriminated although there was no significant inflammation at the time of surgery. Riedel thyroiditis was ruled out based on microscopic features of the lesions: fibrosis, although focally extensive in two thyroids, remained intrathyroid [
In conclusion, HBF may occur in sporadic thyroid goiter. A subcapsular or extranodular location and size ≥2 mm may be useful for the imaging diagnosis. Histogenesis is multifactorial, dysmetabolic conditions, renal dysfunction or vascular abnormalities being possibly involved, without associated parathyroid pathologies. Whether a disturbed iodine metabolism can also be involved requires further investigation.
The authors declare that they have no conflict of interests.
The authors thank I. Alexandre, V. Ipotesi, N. Akdim, J. Raleche, L. Delagarde, A. Meloni, Professor A. Sapino, Dr. C. Westhoff, Dr. E. Dragoescu, Dr. I. Keller, Dr. SA Polyzos, Dr. T. Leger, MC Portenier, S. Chambris, P. Pausicles, the BIUM, CMDP/APHP, and NCA/Avicenne teams.