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Radiological patterns and significance of thyroid calcification
ClinicalRadiologY (1981) 32, 571-575 © 1981 Royal Collegeof Radiologists
0009-9260/81/01030571502.00
Radiological Patterns and Significance of Thyroid Calcification FUNSHO KOMOLAFE Department o f Radiology, University College Hospital, lbadan, Nigeria A study of 160 unselected patients with thyroid enlargement was undertaken. There was an overall calcification rate of 21.5%. Four patterns of calcification were observed: (i) nodular, (ii) flat, Off) curvilinear, (iv) cloudy, plus a mixed type consisting of varying combinations of the four basic patterns. Calcification is considered to follow previous haemorrhage, necrosis or epithelial degeneration, and since these can occur in both benign and malignant goitres, it explains why calcification cannot be reliably employed as an index of benignity or malignancy. Since the work presented by Holtz and Powers (1958) on calcifications in papillary carcinoma of the thyroid, several others have written on the subject, with particular reference to the significance of thyroid calcification observed on radiographs (Segal et al., 1960; Erazo and Wahner, 1966; Margolin and Steinbach, 1968; Park etal., 1976). The present report analyses the various patterns of calcification observed in a study of 160 unselected patients with thyroid enlargement correlated with clinical, surgical and histological findings. METHODS
Antero-posterior (AP) and lateral soft-tissue radiographs of the neck and thoracic inlet and a posteroanterior (PA) chest film are routine radiological studies performed for all patients attending the University College Hospital, Ibadan, because of thyroid enlargement. The average radiographic factors employed for the AP projection of the neck are 60 kV and 20 mA at a focus-f'tim distance of 90 cm (36 in). For the lateral projection, the patient is positioned with the predominant side of swelling next to the film, with average factors of 65 kV and 25 mA and a focal film distance of 180cm (72in), to compensate for the increased object-film distance in that projection. All the exposures are made with screen films and without a Bucky grid. The fdms obtained for 160 patients seen over a two year period (June 1977-June 1979) were studied for the presence and pattern of thyroid calcification. From the patients' hospital records, relevant clinical, biochemical, surgical and histological data were extracted. This information included each patient's name, sex, age, duration of symptoms, results of laboratory thyroid function tests, operative findings
Table 1 - Age incidence of goitres (both sexes) Age at presentation (years)
Number of patien ts
0-10 11-20 21-30 31-40 41-50 51-60 61-70 71-80
0 12 30 37 38 20 7 2
Total
146
Percentage
0 8.2 20.6 25.3 26.0 13.7 4.8 1.4 100
(in patients who had had thyroidectomy) and histological findings. There were 140 females (87.5%) and 20 males (12.5%), giving a female to male ratio of 7:1. The highest incidence of goitres in this series occurred between the third and fifth decades (Table 1). Of the 160 patients, 14 had their ages stated as 'adult' and these could therefore not be classified. RESULTS Thyroid Calcification
A total of 36 patients (21.5%) had either radiological or histological proof of calcification. Of these, 34 were correctly detected radiologically, with two false negatives which were subsequently shown to contain calcification at histology. This gives radiology an accuracy of 94.5% compared with histology. The radiological patterns of calcification encountered are illustrated in Fig. 1, and these are: (i) nodular, (ii) flat, (if) curvilinear, and (iv) cloudy. Whereas the former three patterns are dense and well marginated,
572
CLINICAL R A D I O L O G Y
PATTERNSOFTHYROIDCALCIFICATION
(i) NODULAR
(iv)a CLOUDY
(Gtheralised)
(ii) FLAT
(iii) CURVI-LINEAR
(iv)b CLOUDY
NON-CALCIFIED
(Focal)
Fig. 1 - Diagramatic representation of the observed patterns of thyroid calcification. Note that a mixture of patterns may occur within the same gland.
the fourth is indef'mite and is sometimes difficult to reproduce. Although a single pattern frequently occurs (Figs 2, 3) mixed patterns are sometimes observed within the same thyroid. (Figs. 4, 5). This explains why in Table 2 the number of patients showing calcification appears to exceed the stated 36, as some showed a mixture of patterns and each pattern was scored separately. Of these 36 patients, only 30 had adequate information regarding the duration of swelling. In Table 3
Fig. 3 - Lateral neck radiograph of 70-year-old female showing enlarged thyroid with multiple curvilinear calcifications (arrows). Histology: benign colloid goitre. Note severe spondylotic changes in the cervical spine.
Table 2 - Frequency of thyroid calcification patterns in 36 patients
Calcification pattern
Number o f patients
Nodular Flat Curvilinear Cloudy
32 7 4 1
Total
44
Percentage of to tal 72.6 15.9 9.1 2.3 100
Table 3 - Presence of calcification in goitres related to duration of swelling
Duration (years)
Fig. 2 - Antero-posterior view of giant benign multinodular goitre of eight years' duration showing multiple curvilinear calcifications (arrows).
Under 1 1-5 6-10 11-15 Over 15 Total
Number o f patients
Number with calcification
Percentage with calcification
25 43 21 10 7
1 11 6 5 7
4.0 26.6 28.6 50.0 100.0
106
30
PATTERNS
OF THYROID
Fig 4 - Huge goitre in a 47-year-old m a n , showing a super-
ficial flat calcification (arrow-head) and a single nodular calcification just above thoracic inlet (arrow). Histology: follicular carcinoma.
IN,
CALCIFICATION
573
Fig. 5 - Lateral neck showing a goitre with a single curvilinear (arrows) and multiple nodular calcifications. Histology:
benign colloid goitre.
the patients are classified according to the duration of thyroid swelling, and it is clearly shown that the rate of occurrence of calcification rises progressively with the duration of the goitre. This finding is further illustrated in the histogram (Fig. 6).
,c (J b
Thyroid Calcification and Malignancy Of the 160 patients, 13 (8.1%) had primary thyroid malignancy (Table 4). An analysis of Table 4 shows that no pattern of calcification typifies any histological type of thyroid carcinoma. Indeed, the large majority of patients in whom calcification was present were cases of benign multinodular colloid goitre. No patients had metastatic disease to the thyroid.
.o
(J (a
DISCUSSION
t.
Under I - 5 5-10 10-15 Over I 15 Duration (Years) Fig. 6 - Histogram showing the increasing rate o f thyroid
calcification with increasing duration of thyroid enlargement. This is a graphic representation of the data in Table 3.
Several reports exist in the literature in which particular patterns of thyroid calcification have been associated with certain histological types. Perhaps the best example is the report by Holtz and Powers (1958) of 53 patients with papillary carcinoma of the thyroid. Twenty-eight of them had radiographs of the neck for review and three of these had calcifications thought to be typical of carcinoma. Holtz and Powers established criteria for distinguishing between benign and malignant calcification. They described benign calcification as dense, sharply defined, well marginated and varying in size; whereas malignant calcification is said to be poorly marginated, hazy, not
CLINICAL RADIOLOGY
574
Table 4 - Analysis of 13 patients with thyroid carcinoma
Sex
Age (years)
Calcification and pattern
Histology
Other findings
F F M
60 60 47
Follicular Ca Not available FollicularCa
F
'Adult'
None None Nodular and flat Cloudy
Skull metastases Rib metastases Muscle invasion noted at thyroidectomy Recurrent. Invasion of trachea and rib metastases
M F
45 37
None Nodular
Follicular Ca Papillary Ca
M F M F F M
'Adult' 62 60 37 42 65
None Nodular Nodular None Flat None
Not available Papillary Ca Follicular Ca Medullary Ca Follicular Ca Not available
F
50
None
Follicular Ca
Follicular Ca
densely calcific, about equal in size and sometimes grouped in streaks or a nebular formation. Also in a study of 70 patients with medullary thyroid carcinoma, Wallace et al. (1970) wrote that 'detection of calcification by soft-tissue radiography of the neck, be it in the thyroid or cervical lymph nodes, should suggest medullary thyroid carcinoma'. Similarly Park et al. (1976) described egg-shell calcification (similar to the curvilinear pattern in the present report) in a case of mixed papillary and follicular carcinoma of the thyroid. T h a t dense calcifications also occur in thyroid carcinoma is supported by the report of Pearson et al. (1973). They studied a 21-member family with familial medullary carcinoma, adrenal phaeochromocytoma and parathyroid hyperplasia (Sipple's syndrome). Large, dense and discrete calcifications were observed in tumour deposits in the neck in nine of 19 patients. Similar dense calcifications were present in metastatic deposits in cervical lymph nodes of one patient and in the liver of two other patients. In the report of a case of a calcified thyroid nodule in a five-year-old gld, Olambiwonnu et al. (1975) noted the presence of psammoma bodies on histology of the nodule, which turned out to be a case of papillary adenocarcinoma. Psammoma bodies (calcopherites, microlithiasis) are roughly spherical, laminated structures measuring 1 0 - 1 0 0 # m in diameter (Margolin and Steinbach, 1968) and consist of an acid mucopoly saccharide which has a tendency to bind calcium (Segal et al. 1960). They therefore become radiologically visible if sufficiently conglomerate. They probably arise at the site of degenerating
Hoarseness
Recurrent. Pulmonary metastases Pulmonary metastases Hoarseness Rib metastases Recurrent goitre Skull and humeral metastases Hoarseness. Multiple bone metastases Hoarseness
or dead epithelium (Klinck and Winship, 1959). Although psammoma bodies have been most frequently associated with papillary carcinoma of the thyroid, they may occur in other types of epithelial neoplasms of the thyroid (Margolin and Steinbach, 1968), and occasionally in benign thyroid nodules (Segal et al., 1960). They have also been described in normal meninges, choroid plexus and in the pineal gland of the aged, as well as in neoplastic lesions such as in meningiomas, breast and ovarian tumours (Klink and Winship, 1959). Psammoma bodies are found more commonly in thyroid cancers in children (53%) than in adults (43%) (Klinck and Winship, 1959). In their own report of 16 patients with thyroid carcinoma, Margolin and Steinback (1968) had three patients who showed radiological evidence of psammoma bodies, but they were histologically present in 10 patients. It will be clear from the foregoing reports and the findings in the present series that dense, well marginated as well as hazy calcifications may occur in both benign and malignant thyroid masses. It would appear that dense calcifications (grouped as nodular, flat or curvilinear) are consequent upon previous haemorrhage and tissue necrosis, whereas hazy (grouped as cloudy) calcificiations follow psammoma bodies associated with epithelial death (Klinck and Winship, t 959). Further evidence for this suggestion is provided by Erazo and Wahner (1966) who found histologically that calcification in the thyroid was noted in areas of necrosis and haemorrhage. It is conceivable that any of these pathological processes can occur in either benign or malignant thyroid swellings, and would
PATTERNS OF THYROID CALCIFICATION explain why calcification pattern is so non-specific and mixed patterns frequently occur in the same thyroid. The finding in this series is that the rate of calcification rises steadily with duration of thyroid swelling, varying from 4% under one year to 100% in patients with goitre with a duration exceeding 15 years (Table 3 and Fig. 6). This further supports the explanation offered above, since it would be expected that the longer the duration the higher the chances for haemorrhage, tissue necrosis or epithelial degeneration to occur - i.e. factors that predispose to dystrophic calcification in general. Acknowledgements. I am grateful to Professor S. B. Lagundoye (Department of Radiology) and to Professor E. Olurin (Department of Surgery), both of the University of Ibadan; to the former for offering useful advice and criticism, and to the latter for granting access to his patients' records.
REFERENCES Erazo, S. T. & Wahner, H. W. (1966). Roentgenographic diagnosis of thyroid cancer in the presence of endemic goiter. American Journal of Roentgenology, 96, 596-603.
575
Holtz, S. & Powers, W. E. (1958). Calcification in papillary carcinoma of the thyroid. American Journal of Roentgenology, 8, 997-1000. Klinck, G. H. & Winship, T. (1959). Psammoma bodies in thyroid cancer. Cancer, 12, 656-662. Margolin, F. R. & Steinbach, H. L. (1968). Soft tissue roentgenography of thyroid nodules. American Journal of Roentgenology, 102, 844-852. Olambiwonnu, N. O., Penny, R. & Frasier, S. D. (1975). Roentgenographic calcifications in carcinoma of the thyroid. American Journal of Diseases of Children, 129, 371-372. Park, C. H., Rothermel, F. J. & Judge, D. M. (1976). Unusual calcifications in mixed papillary and follicular carcinoma of the thyroid gland. Radiology, 119, 554. Pearson, K. D., Wells, S. A. & Keiser, H. R. (1973). Familial medullary carcinoma of the thyroid, adrenal pheochromocytoma and parathyroid hyperplasia. Radiology, 107, 249-256. Segal, R. L., Zuckerman, H. & Friedman, E. W. (1960). Soft tissue roentgenography: its use in diagnosis of thyroid carcinoma. Journal of the American Medical Association, 173, 1890-1894. Wallace, S., Hill, C. S., Paulus, D. D., Ibanez, M. L. & Clark, R. L. (1970). The radiologic aspects of medullary (solid) thyroid carcinoma. Radiologic Clinics of North America, 8, 463-474.
0009-9260/81/01030571502.00
Radiological Patterns and Significance of Thyroid Calcification FUNSHO KOMOLAFE Department o f Radiology, University College Hospital, lbadan, Nigeria A study of 160 unselected patients with thyroid enlargement was undertaken. There was an overall calcification rate of 21.5%. Four patterns of calcification were observed: (i) nodular, (ii) flat, Off) curvilinear, (iv) cloudy, plus a mixed type consisting of varying combinations of the four basic patterns. Calcification is considered to follow previous haemorrhage, necrosis or epithelial degeneration, and since these can occur in both benign and malignant goitres, it explains why calcification cannot be reliably employed as an index of benignity or malignancy. Since the work presented by Holtz and Powers (1958) on calcifications in papillary carcinoma of the thyroid, several others have written on the subject, with particular reference to the significance of thyroid calcification observed on radiographs (Segal et al., 1960; Erazo and Wahner, 1966; Margolin and Steinbach, 1968; Park etal., 1976). The present report analyses the various patterns of calcification observed in a study of 160 unselected patients with thyroid enlargement correlated with clinical, surgical and histological findings. METHODS
Antero-posterior (AP) and lateral soft-tissue radiographs of the neck and thoracic inlet and a posteroanterior (PA) chest film are routine radiological studies performed for all patients attending the University College Hospital, Ibadan, because of thyroid enlargement. The average radiographic factors employed for the AP projection of the neck are 60 kV and 20 mA at a focus-f'tim distance of 90 cm (36 in). For the lateral projection, the patient is positioned with the predominant side of swelling next to the film, with average factors of 65 kV and 25 mA and a focal film distance of 180cm (72in), to compensate for the increased object-film distance in that projection. All the exposures are made with screen films and without a Bucky grid. The fdms obtained for 160 patients seen over a two year period (June 1977-June 1979) were studied for the presence and pattern of thyroid calcification. From the patients' hospital records, relevant clinical, biochemical, surgical and histological data were extracted. This information included each patient's name, sex, age, duration of symptoms, results of laboratory thyroid function tests, operative findings
Table 1 - Age incidence of goitres (both sexes) Age at presentation (years)
Number of patien ts
0-10 11-20 21-30 31-40 41-50 51-60 61-70 71-80
0 12 30 37 38 20 7 2
Total
146
Percentage
0 8.2 20.6 25.3 26.0 13.7 4.8 1.4 100
(in patients who had had thyroidectomy) and histological findings. There were 140 females (87.5%) and 20 males (12.5%), giving a female to male ratio of 7:1. The highest incidence of goitres in this series occurred between the third and fifth decades (Table 1). Of the 160 patients, 14 had their ages stated as 'adult' and these could therefore not be classified. RESULTS Thyroid Calcification
A total of 36 patients (21.5%) had either radiological or histological proof of calcification. Of these, 34 were correctly detected radiologically, with two false negatives which were subsequently shown to contain calcification at histology. This gives radiology an accuracy of 94.5% compared with histology. The radiological patterns of calcification encountered are illustrated in Fig. 1, and these are: (i) nodular, (ii) flat, (if) curvilinear, and (iv) cloudy. Whereas the former three patterns are dense and well marginated,
572
CLINICAL R A D I O L O G Y
PATTERNSOFTHYROIDCALCIFICATION
(i) NODULAR
(iv)a CLOUDY
(Gtheralised)
(ii) FLAT
(iii) CURVI-LINEAR
(iv)b CLOUDY
NON-CALCIFIED
(Focal)
Fig. 1 - Diagramatic representation of the observed patterns of thyroid calcification. Note that a mixture of patterns may occur within the same gland.
the fourth is indef'mite and is sometimes difficult to reproduce. Although a single pattern frequently occurs (Figs 2, 3) mixed patterns are sometimes observed within the same thyroid. (Figs. 4, 5). This explains why in Table 2 the number of patients showing calcification appears to exceed the stated 36, as some showed a mixture of patterns and each pattern was scored separately. Of these 36 patients, only 30 had adequate information regarding the duration of swelling. In Table 3
Fig. 3 - Lateral neck radiograph of 70-year-old female showing enlarged thyroid with multiple curvilinear calcifications (arrows). Histology: benign colloid goitre. Note severe spondylotic changes in the cervical spine.
Table 2 - Frequency of thyroid calcification patterns in 36 patients
Calcification pattern
Number o f patients
Nodular Flat Curvilinear Cloudy
32 7 4 1
Total
44
Percentage of to tal 72.6 15.9 9.1 2.3 100
Table 3 - Presence of calcification in goitres related to duration of swelling
Duration (years)
Fig. 2 - Antero-posterior view of giant benign multinodular goitre of eight years' duration showing multiple curvilinear calcifications (arrows).
Under 1 1-5 6-10 11-15 Over 15 Total
Number o f patients
Number with calcification
Percentage with calcification
25 43 21 10 7
1 11 6 5 7
4.0 26.6 28.6 50.0 100.0
106
30
PATTERNS
OF THYROID
Fig 4 - Huge goitre in a 47-year-old m a n , showing a super-
ficial flat calcification (arrow-head) and a single nodular calcification just above thoracic inlet (arrow). Histology: follicular carcinoma.
IN,
CALCIFICATION
573
Fig. 5 - Lateral neck showing a goitre with a single curvilinear (arrows) and multiple nodular calcifications. Histology:
benign colloid goitre.
the patients are classified according to the duration of thyroid swelling, and it is clearly shown that the rate of occurrence of calcification rises progressively with the duration of the goitre. This finding is further illustrated in the histogram (Fig. 6).
,c (J b
Thyroid Calcification and Malignancy Of the 160 patients, 13 (8.1%) had primary thyroid malignancy (Table 4). An analysis of Table 4 shows that no pattern of calcification typifies any histological type of thyroid carcinoma. Indeed, the large majority of patients in whom calcification was present were cases of benign multinodular colloid goitre. No patients had metastatic disease to the thyroid.
.o
(J (a
DISCUSSION
t.
Under I - 5 5-10 10-15 Over I 15 Duration (Years) Fig. 6 - Histogram showing the increasing rate o f thyroid
calcification with increasing duration of thyroid enlargement. This is a graphic representation of the data in Table 3.
Several reports exist in the literature in which particular patterns of thyroid calcification have been associated with certain histological types. Perhaps the best example is the report by Holtz and Powers (1958) of 53 patients with papillary carcinoma of the thyroid. Twenty-eight of them had radiographs of the neck for review and three of these had calcifications thought to be typical of carcinoma. Holtz and Powers established criteria for distinguishing between benign and malignant calcification. They described benign calcification as dense, sharply defined, well marginated and varying in size; whereas malignant calcification is said to be poorly marginated, hazy, not
CLINICAL RADIOLOGY
574
Table 4 - Analysis of 13 patients with thyroid carcinoma
Sex
Age (years)
Calcification and pattern
Histology
Other findings
F F M
60 60 47
Follicular Ca Not available FollicularCa
F
'Adult'
None None Nodular and flat Cloudy
Skull metastases Rib metastases Muscle invasion noted at thyroidectomy Recurrent. Invasion of trachea and rib metastases
M F
45 37
None Nodular
Follicular Ca Papillary Ca
M F M F F M
'Adult' 62 60 37 42 65
None Nodular Nodular None Flat None
Not available Papillary Ca Follicular Ca Medullary Ca Follicular Ca Not available
F
50
None
Follicular Ca
Follicular Ca
densely calcific, about equal in size and sometimes grouped in streaks or a nebular formation. Also in a study of 70 patients with medullary thyroid carcinoma, Wallace et al. (1970) wrote that 'detection of calcification by soft-tissue radiography of the neck, be it in the thyroid or cervical lymph nodes, should suggest medullary thyroid carcinoma'. Similarly Park et al. (1976) described egg-shell calcification (similar to the curvilinear pattern in the present report) in a case of mixed papillary and follicular carcinoma of the thyroid. T h a t dense calcifications also occur in thyroid carcinoma is supported by the report of Pearson et al. (1973). They studied a 21-member family with familial medullary carcinoma, adrenal phaeochromocytoma and parathyroid hyperplasia (Sipple's syndrome). Large, dense and discrete calcifications were observed in tumour deposits in the neck in nine of 19 patients. Similar dense calcifications were present in metastatic deposits in cervical lymph nodes of one patient and in the liver of two other patients. In the report of a case of a calcified thyroid nodule in a five-year-old gld, Olambiwonnu et al. (1975) noted the presence of psammoma bodies on histology of the nodule, which turned out to be a case of papillary adenocarcinoma. Psammoma bodies (calcopherites, microlithiasis) are roughly spherical, laminated structures measuring 1 0 - 1 0 0 # m in diameter (Margolin and Steinbach, 1968) and consist of an acid mucopoly saccharide which has a tendency to bind calcium (Segal et al. 1960). They therefore become radiologically visible if sufficiently conglomerate. They probably arise at the site of degenerating
Hoarseness
Recurrent. Pulmonary metastases Pulmonary metastases Hoarseness Rib metastases Recurrent goitre Skull and humeral metastases Hoarseness. Multiple bone metastases Hoarseness
or dead epithelium (Klinck and Winship, 1959). Although psammoma bodies have been most frequently associated with papillary carcinoma of the thyroid, they may occur in other types of epithelial neoplasms of the thyroid (Margolin and Steinbach, 1968), and occasionally in benign thyroid nodules (Segal et al., 1960). They have also been described in normal meninges, choroid plexus and in the pineal gland of the aged, as well as in neoplastic lesions such as in meningiomas, breast and ovarian tumours (Klink and Winship, 1959). Psammoma bodies are found more commonly in thyroid cancers in children (53%) than in adults (43%) (Klinck and Winship, 1959). In their own report of 16 patients with thyroid carcinoma, Margolin and Steinback (1968) had three patients who showed radiological evidence of psammoma bodies, but they were histologically present in 10 patients. It will be clear from the foregoing reports and the findings in the present series that dense, well marginated as well as hazy calcifications may occur in both benign and malignant thyroid masses. It would appear that dense calcifications (grouped as nodular, flat or curvilinear) are consequent upon previous haemorrhage and tissue necrosis, whereas hazy (grouped as cloudy) calcificiations follow psammoma bodies associated with epithelial death (Klinck and Winship, t 959). Further evidence for this suggestion is provided by Erazo and Wahner (1966) who found histologically that calcification in the thyroid was noted in areas of necrosis and haemorrhage. It is conceivable that any of these pathological processes can occur in either benign or malignant thyroid swellings, and would
PATTERNS OF THYROID CALCIFICATION explain why calcification pattern is so non-specific and mixed patterns frequently occur in the same thyroid. The finding in this series is that the rate of calcification rises steadily with duration of thyroid swelling, varying from 4% under one year to 100% in patients with goitre with a duration exceeding 15 years (Table 3 and Fig. 6). This further supports the explanation offered above, since it would be expected that the longer the duration the higher the chances for haemorrhage, tissue necrosis or epithelial degeneration to occur - i.e. factors that predispose to dystrophic calcification in general. Acknowledgements. I am grateful to Professor S. B. Lagundoye (Department of Radiology) and to Professor E. Olurin (Department of Surgery), both of the University of Ibadan; to the former for offering useful advice and criticism, and to the latter for granting access to his patients' records.
REFERENCES Erazo, S. T. & Wahner, H. W. (1966). Roentgenographic diagnosis of thyroid cancer in the presence of endemic goiter. American Journal of Roentgenology, 96, 596-603.
575
Holtz, S. & Powers, W. E. (1958). Calcification in papillary carcinoma of the thyroid. American Journal of Roentgenology, 8, 997-1000. Klinck, G. H. & Winship, T. (1959). Psammoma bodies in thyroid cancer. Cancer, 12, 656-662. Margolin, F. R. & Steinbach, H. L. (1968). Soft tissue roentgenography of thyroid nodules. American Journal of Roentgenology, 102, 844-852. Olambiwonnu, N. O., Penny, R. & Frasier, S. D. (1975). Roentgenographic calcifications in carcinoma of the thyroid. American Journal of Diseases of Children, 129, 371-372. Park, C. H., Rothermel, F. J. & Judge, D. M. (1976). Unusual calcifications in mixed papillary and follicular carcinoma of the thyroid gland. Radiology, 119, 554. Pearson, K. D., Wells, S. A. & Keiser, H. R. (1973). Familial medullary carcinoma of the thyroid, adrenal pheochromocytoma and parathyroid hyperplasia. Radiology, 107, 249-256. Segal, R. L., Zuckerman, H. & Friedman, E. W. (1960). Soft tissue roentgenography: its use in diagnosis of thyroid carcinoma. Journal of the American Medical Association, 173, 1890-1894. Wallace, S., Hill, C. S., Paulus, D. D., Ibanez, M. L. & Clark, R. L. (1970). The radiologic aspects of medullary (solid) thyroid carcinoma. Radiologic Clinics of North America, 8, 463-474.