Clinical Radio"gy (1992) 45, 307-310
Undifferentiated Carcinoma of the Thyroid Gland: Sonographic Findings H. H A T A B U , K. KASAGI, K. Y A M A M O T O , S. KUBO, K. H I G U C H I * , A. H I D A K A , T. MISAKI, Y. IIDA, H. SAKAHARA, H. YAMABE*, K. E N D O and J. K O N I S H I
Department of Radiology and Nuclear Medicine, and *Laboratory of Anatomic Pathology, Kyoto University Hospital, Sakyo-ku, Kyoto, Japan We ~report high resolution sonographic (7.5 MHz) findings in four cases of undifferentiated carcinoma of the thyroid gland. Sonographic findings in these four cases included poorly marginated, hypoechoic masses associated with calcifications, and invasion of adjacent cervical structures. A knowledge of the sonographic features of undifferentiated carcinoma of the thyroid gland is of clinical importance, since the tumour has a grave prognosis, quite different from the relatively favourable prognosis of well differentiated thyroid carcinoma. Hatabu, H., Kasagi, K., Yamamoto, K., Kubo, S., Higuchi, K., Hidaka, A., Misaki, T., Iida, Y., Sakahara, H., Yamabe, H., Endo, K. & Konishi, J. (1992). Clinical Radiology 45, 307-310. Undifferentiated Carcinoma of the Thyroid Gland: Sonographic Findings
Undifferentiated carcinoma of the thyroid gland, which represents 10-15% of thyroid cancers, requires prompt diagnosis and treatment, since it is a highly aggressive lesion (Rafla, 1969; Aldinger et al., 1978; Gershengorn and Robbins, 1987; Walfish, 1988). We report the sonographic findings in four such cases. The sonographic features, which to our knowledge have not been described previously, may suggest the diagnosis. P A T I E N T S AND M E T H O D S Four cases, of undifferentiated carcinoma of the thyroid gland were found among 67 patients who were operated on for thyroid malignant neoplastic diseases from August 1987 to July 1989. These cases occurred among approximately 2000 sonographic examinations of the thyroid performed during the same period, using a real-time electronic scanner with 7.5 MHz transducer (Yokogawa RT-2800, Tokyo). Their US images were directly displayed on the monitor from an optical disc recorder, analysed, and photographed. The echogenicity of the tumour was evaluated in comparison with that of the normal thyroid tissue and anterior strap muscles. The scoring system was as follows: score 5, tumour more echogenic than the normal thyroid tissue; score 4, tumour echogenicity comparable to the normal thyroid tissue; score 3, tumour less echogenic than the normal thyroid tissue and more echogenic than anterior strap muscles; score 2, tumour echogenicity comparable to anterior strap muscles; score 1, tumour less echogenic than anterior strap muscles. The echogenicity of three undifferentiated carcinomas (Cases 1-3) and 20 well differentiated carcinomas was evaluated according to the criteria described above by two radiologists without knowledge of the diagnosis. The scores of the two radiologists were then averaged. The echogenicity of Case 4 was not evaluated because this tumour had both undifferentiated and well differentiated gross components. Correspondence to: Hiroto Hatabu, MD, Department of Radiology and Nuclear Medicine, Kyoto University Hospital, Sakyo-ku, Kyoto 606, Japan.
Invasion of the surrounding structures was diagnosed according to the following criteria: invasion of muscles was diagnosed if thyroid capsule between the tumour and the muscles was obliterated; invasion of carotid artery, internal jugular vein and/or oesophagus was diagnosed if the tumour was in contact with 90 ° or more of their circumference, and if the plane between them was lost; invasion of the trachea was diagnosed if hyperechoic tracheal cartilage was obliterated by the tumour. The diagnosis of lymph node metastasis was made if lymph nodes were larger than 1.5 cm in their greatest diameter in the submandibular and jugulodigastric regions or larger than 1.0 cm in the other regions (Som, 1987). The diagnosis of calcification was made if hyperechoic areas associated with acoustic shadows were observed (coarse calcification) or if multiple hyperechoic punctate foci were observed (fine calcification). Clinical records of the four patients were also reviewed and are summarized in Table 1. All patients were female, aged between 38 and 77 years, and had anterior neck masses. One subject with a 20 year history of such a neck mass presented with recent rapid growth of the lesion (Case 4). All patients were euthyroid when evaluated by clinical symptoms and laboratory tests. RESULTS Ultrasonograms in three cases (Cases 1-3) showed an ill defined hypoechoic area, which was less echogenic than anterior strap muscles (Figs 1-3). The sonogram in Case 4 showed a rather inhomogeneous appearance with a hyperechoic mass in the left thyroid gland and an ill defined hypoechoic area surrounding the left carotid sheath (Fig. 4). Calcification was observed in all cases, pre-operatively in three. All had invasion of surrounding cervical tissue, including the sternocleidomastoid muscle, oesophagus, trachea, carotid artery or internal jugular vein. Invasion of such tissues was correctly diagnosed except for invasion of sternocleidomastoid muscle in Case 2 and invasion of the trachea in Case 4 (Table 2). In Case 2, subtle findings of invasion of the left sternocleidomastoid muscle were detected only retrospectively (Fig. 2). In
308
CLINICAL RADIOLOGY
Table 1 - Clinical features, US findings, operation findings and treatment of patients
Case
Age~sex
Symptoms
US findings
Surgery (involvement)
Radiation ( Gy)
Pathology
1
77/F
Anterior neck mass, hoarseness
LN, SCM, CA, JV, TR, T4NtMt (lung)
-
Spindle and giant ceil type
2
38/F
Anterior neck ma~ss
SCM T4NOM1(lung)
40
Spindle cell type
3
76/F
Anterior neck mass
TR, ESO T4NOM0
60
Squamous cell type
4
73/F
Thyroid mass of 20 years with recent rapid growth
Hypoechoic large mass, calcification; LN; SCM invasion of CA and JV Hypoechoic mass; (calcification; invasion of SCM)*; posterior wN1 enhancement Hypoechoic mass, calcification; invasion of TR and ESO Hyperechoic mass with hypoechoic area; calcification; LN; invasion of CA
LN, CA, TR, ESO T4N3M 1 (bone)
53
Spindle cell type
LN, Lymph node; SCM, sternocleidomastoid muscle; JV, internal jugular vein; TR, trachea; ESO, oesophagus; CA, carotid artery. * Findings confirmed retrospectively. Case 4, m a r k e d a t t e n u a t i o n o f u l t r a s o u n d (US) by the echogenic c o m p o n e n t o f the t u m o u r p r e v e n t e d the accurate e v a l u a t i o n o f t r a c h e a l invasion (Fig. 4). All o f the t u m o u r s were staged as T4 ( T N M classification) at o p e r a t i o n . Three cases h a d d i s t a n t metastases. Case 3 was an undifferentiated c a r c i n o m a with s q u a m o u s metaplasia. All patients received r a d i a t i o n t h e r a p y except for Case 1, who died 2 weeks after an e m e r g e n c y o p e r a t i o n for d y s p h a g i a . The echogenicity scores o f undifferentiated c a r c i n o m a s a n d p a p i l l a r y c a r c i n o m a s were 1.33+0.58 and 2.88 _+0.48, respectively. T h e echogenicity score o f undifferentiated c a r c i n o m a s was lower t h a n that o f p a p i l l a r y c a r c i n o m a (Fig. 5).
DISCUSSION
(a)
(b) Fig. 1 - Case 1. (a) Transverse sonogram revealed an ill defined large anterior neck mass invading to the muscles (arrows), trachea (TR), and carotid sheath (curved arrows). (b) Longitudinal sonogram shows invasion of the tumour (T) to right internal jugular vein (V), an infrequent observation in thyroid cancer.
U n d i f f e r e n t i a t e d c a r c i n o m a o f the t h y r o i d gland is typically associated with a r a p i d onset o f growth, usually presents as a large b u l k y cervical mass, and m a y o b s t r u c t vital structures such as the larynx, trachea, o e s o p h a g u s a n d s u p e r i o r vena cava. A p p r o x i m a t e l y one fifth o f these patients have a history o f previous t r e a t m e n t for differentiated t h y r o i d c a r c i n o m a a n d a b r u p t l y d e v e l o p wides p r e a d metastasis, whereas a n o t h e r third have a history o f a l o n g - s t a n d i n g diffuse goitre or a discrete nodule t h a t s u d d e n l y begins to g r o w rapidly, as was seen in Case 4. This t u m o u r has a m u c h p o o r e r p r o g n o s i s t h a n differentiated t h y r o i d c a r c i n o m a ; m o s t patients are d e a d 6 m o n t h s to 1 y e a r after diagnosis. T h e m e a n survival m a y be as low as 2.5-4 m o n t h s (Rafla, 1969; A l d i n g e r et al., 1978; G e r s h e n g o r n a n d R o b b i n s , 1987; Walfish, 1988). O u r results indicate t h a t undifferentiated c a r c i n o m a o f the t h y r o i d is characterized by an ill-defined h y p o e c h o i c mass, which is less echogenic t h a n the a n t e r i o r s t r a p muscles, c o n t a i n s scattered calcification, a n d has a p r o pensity to invade a d j a c e n t structures. ~Rather h o m o geneous infiltration o f m a l i g n a n t cells m a y a c c o u n t for the h y p o e c h o g e n i c i t y o f the mass. In Case 4, s o n o g r a p h i c images s h o w e d two differing c o m p o n e n t s within the mass. This p a t i e n t h a d a 20 year history o f a t h y r o i d n o d u l e which grew rapidly, suggesting c o n v e r s i o n or t r a n s f o r m a t i o n o f a slow-growing p a p i l l a r y t u m o u r to an a n a p l a s t i c t y p e (Case R e c o r d s o f M a s s a c h u s e t t s G e n e r a l
309
CARCINOMA OF THE THYROID GLAND
(a)
(a)
(b)
(b)
Fig. 3 Case 3. (a) Transverse sonogram shows a hypoechoic nlass in the left lobe with invasion to trachea and esophagus (E). Calcification was also noted (curved arrows). (b) Pathological examination of operation specimens revealed undifferentiated carcinoma with squamous metaplasia. Definite keratinization in tumour cells is seen (H&E).
(c) Fig. 2 Case 2. (a) Transverse sonogram shows a hypoechoic mass in the left lobe. The hyperechoic punctate loci within the lesion (curved arrows), proved at pathology to be calcification. Note the ill defined anterior margin of the mass with disappearance of the thyroid capsule (arrows). Subtle finding of invasion to left sternocleidomastoid muscle can be interpreted only retrospectively (arrows). (b) Longitudinal sonogram shows an ill defined hypoechoic area with internal punctate echoes (curved arrows). (c) Pathological examination revealed undifferentiated carcinoma of spindle cell subtype. Diffuse proliferation of atypical spindle shaped turnout cells is seen (H&E).
Fig. 4 Case 4. Transverse sonogram Of left neck reveals a well-defined thyroid mass (arrows). Adjacent to this mass is an ill defined hypoechoic area surrounding the carotid sheath (curved arrows; C, left common carotid artery). Pathological examination at operation from the intrathyroid mass revealed papillary carcinoma, and that obtained from the perithyroid tissue showed undifferentiated carcinoma.
310
CLINICALRADIOLOGY
Table 2 - Detection of calcification, lymph node metastasis, and invasion of adjacent structures; U S vs surgical or pathological findings
Calcification Lymph nodes Sternocleidomastoid muscle Carotid artery Jugular vein Trachea Oesophagus 1.33 -+ 0.58
US
Surgery or pathology
3 2 1 2 1 2 2
4 2 2 2 1 3 2
2.88 __+0.48
I
I
I
I
I
]
2
3
4
5
Echogenicity score Fig. 5 - Scattergram of echogenicity of three undifferentiated carcinomas and 20 papillary carcinomas. The score was 1.33___0.58 and 2.88-1-0.48, respectively. The score of undifferentiated carcinoma was lower than that of papillary carcinoma, e, Undifferentiated carcinoma; o, welt differentiated carcinoma. Hospital, 1975). The specimen at operation obtained from the intrathyroid mass revealed papillary carcinoma, while that f r o m the perithyroid tissue revealed undifferentiated carcinoma. A rather ill defined, hypoechoic area extending to the adjacent structures m a y reflect the anaplastic c o m p o n e n t o f the cancer. In Case 3, pathological examination revealed a picture o f s q u a m o u s cell carcinoma (Fig. 3b). However, no other primary lesions were found, and there was a c o m p o n e n t o f papillary carcinoma observed in a small metastatic cervical lymph node. Therefore, the case was considered as undifferentiated carcinoma o f the thyroid gland with s q u a m o u s metaplasia. In our series, all cases except Case 4 had pre-operative needle biopsy. Two cases (Cases 2 and 3) were correctly diagnosed as undifferentiated carcinoma, while Case 1 was diagnosed as papillary carcinoma. High resolution real-time ultrasonography provides detailed morphological information o f the thyroid gland (Simeone et al., 1982). The diagnosis o f undifferentiated carcinoma by ultrasonography, in distinction f r o m well differentiated carcinoma, is not difficult, in typical cases having a large ill defined, hypoechoic, invading mass associated with calcification. The well differentiated carcinoma m a y be ill defined or lobulated and sometimes invades the surrounding cervical structures. However, the echogenicity o f well differentiated carcinoma is usually higher than that o f strap muscles (18/20). O n the other hand, the echogenicity o f undifferentiated carcinomas was equal to or less than that o f strap muscles. There was a tendency for echogenicity o f undifferentiated carcinoma to be lower than that o f papillary carcinomas, t h o u g h the numbers in this study were small (Fig. 5). Both malignant l y m p h o m a and subacute thyroiditis m a y be as hypoechoic as undifferentiated carcinoma (Takashima et aI., 1989; T o k u d a et al., 1990). However,
malignant l y m p h o m a rarely shows calcification or invasion o f the surrounding cervical structures. T a k a s h i m a et al. (1989) reported one case with calcification in the t u m o u r and one case with invasion o f the larynx a m o n g 16 cases o f malignant lymphoma. The high incidence o f associated chronic thyroiditis and hypothyroidism in addition to such sonographic findings m a y facilitate the differentiation of malignant l y m p h o m a from undifferentiated carcinoma. Takashima et al. (1990) recently reported the c o m p u t e d t o m o g r a p h i c (CT) features of undifferentiated carcinoma. They described the frequent incidence o f calcification (11/18) and t u m o u r necrosis (14/ 18) in undifferentiated carcinoma, findings which therefore help to differentiate it from malignant l y m p h o m a . Subacute thyroiditis also shows ill defined hypoechoic areas with swelling o f one or both lobes. The lesions, however, rarely have calcification or invasion o f the surrounding tissues, are often multiple and bilateral, and regress rapidly in response to treatment. The s y m p t o m s of subacute thyroiditis are usually quite typical, consisting of painful swelling o f the thyroid region, fever and mild thyrotoxicosis. N o r m a l or increased serum concentrations o f thyroid hormones, elevated levels o f C-reactive protein in serum, and low uptake o f 1231 or 99myc by the thyroid, will establish the diagnosis o f subacute thyroiditis ( T o k u d a et al., 1990). Therefore, the identification of invasion and calcification by US as well as the clinical and laboratory findings allow distinction o f undifferentiated carcinoma from malignant l y m p h o m a or subacute thyroiditis, which m a y have a similar appearance. O u r study has shown that a probable diagnosis o f undifferentiated carcinoma can be made by s o n o g r a p h y in c o m b i n a t i o n with clinical findings. The suspicion o f undifferentiated carcinoma by s o n o g r a p h y m a y lead to a p r o m p t biopsy to obtain a tissue diagnosis.
Acknowledgements. The authors gratefully acknowledge the various comments and helpful suggestions of Warren B. Gefter, MD and Peter H. Arger, MD. Gratitude is also extended to Ms Karen Weiss for her kind assistance in the manuscript preparation.
REFERENCES
Aldinger, KA, Samanna, NA, Ibanez, ML & Hill, CS Jr (1978). Anaplastic carcinoma of the thyroid: a review of 84 cases of spindle and giant cell carcinoma of the thyroid. Cancer, 41, 2267 2275. Case Records of Massachusetts General Hospital (Case 29 1975) (1975). New England Journal of Medicine, 293, 186-193. Gershengorn, MC & Robbins, J (1987). Thyroid neoplasia. In The Thyroid (Current Endocrinology), ed Green, WL, pp. 293-338. Elsevier Science Publishing Co, New York. Rafla, S (1969). Anaplastic tumors of the thyroid. Cancer, 23, 668-677. Simeone, JF, Daniels, GH, Mueller, PR, Maloof, F, van Sonnenberg, E, Hall, DA et al. (1982). High-resolution real-time sonography of the thyroid. Radiology, 145, 431-435. Som, PM (1987). Lymph nodes of the neck. Radiology, 165, 593-600. Takashima, S, Morimoto, S, Ikezoe, J, Arisawa, J, Hamada, S, Ikeda, H et al. (1989). Primary thyroid lymphoma: comparison of CT and US assessment. Radiology, 171,439 443. Takashima, S, Morimoto, S, Ikezoe, J, Takai, S, Kobayashi, T, Koyama, H et al. (1990). CT evaluation of anaplastic thyroid carcinoma. American Journal of Roentg enology, 154, 1079-1085. Tokuda, Y, Kasagi, K, lida, Y, Yamamoto, K, Hatabu, H, Hidaka, Aet al. (1990). Sonography of subacute thyroiditis: changes in the findings during the course of the disease. Journal of Clinical Ultrasound, 18, 21-26. Walfish, PG (1988). Miscellaneous tumors of the thyroid. In The Thyroid, eds lngbar, SH & Braverman, LE, pp. 1363-1376. J. B. Lippincon Co, Philadelphia.
Undifferentiated Carcinoma of the Thyroid Gland: Sonographic Findings H. H A T A B U , K. KASAGI, K. Y A M A M O T O , S. KUBO, K. H I G U C H I * , A. H I D A K A , T. MISAKI, Y. IIDA, H. SAKAHARA, H. YAMABE*, K. E N D O and J. K O N I S H I
Department of Radiology and Nuclear Medicine, and *Laboratory of Anatomic Pathology, Kyoto University Hospital, Sakyo-ku, Kyoto, Japan We ~report high resolution sonographic (7.5 MHz) findings in four cases of undifferentiated carcinoma of the thyroid gland. Sonographic findings in these four cases included poorly marginated, hypoechoic masses associated with calcifications, and invasion of adjacent cervical structures. A knowledge of the sonographic features of undifferentiated carcinoma of the thyroid gland is of clinical importance, since the tumour has a grave prognosis, quite different from the relatively favourable prognosis of well differentiated thyroid carcinoma. Hatabu, H., Kasagi, K., Yamamoto, K., Kubo, S., Higuchi, K., Hidaka, A., Misaki, T., Iida, Y., Sakahara, H., Yamabe, H., Endo, K. & Konishi, J. (1992). Clinical Radiology 45, 307-310. Undifferentiated Carcinoma of the Thyroid Gland: Sonographic Findings
Undifferentiated carcinoma of the thyroid gland, which represents 10-15% of thyroid cancers, requires prompt diagnosis and treatment, since it is a highly aggressive lesion (Rafla, 1969; Aldinger et al., 1978; Gershengorn and Robbins, 1987; Walfish, 1988). We report the sonographic findings in four such cases. The sonographic features, which to our knowledge have not been described previously, may suggest the diagnosis. P A T I E N T S AND M E T H O D S Four cases, of undifferentiated carcinoma of the thyroid gland were found among 67 patients who were operated on for thyroid malignant neoplastic diseases from August 1987 to July 1989. These cases occurred among approximately 2000 sonographic examinations of the thyroid performed during the same period, using a real-time electronic scanner with 7.5 MHz transducer (Yokogawa RT-2800, Tokyo). Their US images were directly displayed on the monitor from an optical disc recorder, analysed, and photographed. The echogenicity of the tumour was evaluated in comparison with that of the normal thyroid tissue and anterior strap muscles. The scoring system was as follows: score 5, tumour more echogenic than the normal thyroid tissue; score 4, tumour echogenicity comparable to the normal thyroid tissue; score 3, tumour less echogenic than the normal thyroid tissue and more echogenic than anterior strap muscles; score 2, tumour echogenicity comparable to anterior strap muscles; score 1, tumour less echogenic than anterior strap muscles. The echogenicity of three undifferentiated carcinomas (Cases 1-3) and 20 well differentiated carcinomas was evaluated according to the criteria described above by two radiologists without knowledge of the diagnosis. The scores of the two radiologists were then averaged. The echogenicity of Case 4 was not evaluated because this tumour had both undifferentiated and well differentiated gross components. Correspondence to: Hiroto Hatabu, MD, Department of Radiology and Nuclear Medicine, Kyoto University Hospital, Sakyo-ku, Kyoto 606, Japan.
Invasion of the surrounding structures was diagnosed according to the following criteria: invasion of muscles was diagnosed if thyroid capsule between the tumour and the muscles was obliterated; invasion of carotid artery, internal jugular vein and/or oesophagus was diagnosed if the tumour was in contact with 90 ° or more of their circumference, and if the plane between them was lost; invasion of the trachea was diagnosed if hyperechoic tracheal cartilage was obliterated by the tumour. The diagnosis of lymph node metastasis was made if lymph nodes were larger than 1.5 cm in their greatest diameter in the submandibular and jugulodigastric regions or larger than 1.0 cm in the other regions (Som, 1987). The diagnosis of calcification was made if hyperechoic areas associated with acoustic shadows were observed (coarse calcification) or if multiple hyperechoic punctate foci were observed (fine calcification). Clinical records of the four patients were also reviewed and are summarized in Table 1. All patients were female, aged between 38 and 77 years, and had anterior neck masses. One subject with a 20 year history of such a neck mass presented with recent rapid growth of the lesion (Case 4). All patients were euthyroid when evaluated by clinical symptoms and laboratory tests. RESULTS Ultrasonograms in three cases (Cases 1-3) showed an ill defined hypoechoic area, which was less echogenic than anterior strap muscles (Figs 1-3). The sonogram in Case 4 showed a rather inhomogeneous appearance with a hyperechoic mass in the left thyroid gland and an ill defined hypoechoic area surrounding the left carotid sheath (Fig. 4). Calcification was observed in all cases, pre-operatively in three. All had invasion of surrounding cervical tissue, including the sternocleidomastoid muscle, oesophagus, trachea, carotid artery or internal jugular vein. Invasion of such tissues was correctly diagnosed except for invasion of sternocleidomastoid muscle in Case 2 and invasion of the trachea in Case 4 (Table 2). In Case 2, subtle findings of invasion of the left sternocleidomastoid muscle were detected only retrospectively (Fig. 2). In
308
CLINICAL RADIOLOGY
Table 1 - Clinical features, US findings, operation findings and treatment of patients
Case
Age~sex
Symptoms
US findings
Surgery (involvement)
Radiation ( Gy)
Pathology
1
77/F
Anterior neck mass, hoarseness
LN, SCM, CA, JV, TR, T4NtMt (lung)
-
Spindle and giant ceil type
2
38/F
Anterior neck ma~ss
SCM T4NOM1(lung)
40
Spindle cell type
3
76/F
Anterior neck mass
TR, ESO T4NOM0
60
Squamous cell type
4
73/F
Thyroid mass of 20 years with recent rapid growth
Hypoechoic large mass, calcification; LN; SCM invasion of CA and JV Hypoechoic mass; (calcification; invasion of SCM)*; posterior wN1 enhancement Hypoechoic mass, calcification; invasion of TR and ESO Hyperechoic mass with hypoechoic area; calcification; LN; invasion of CA
LN, CA, TR, ESO T4N3M 1 (bone)
53
Spindle cell type
LN, Lymph node; SCM, sternocleidomastoid muscle; JV, internal jugular vein; TR, trachea; ESO, oesophagus; CA, carotid artery. * Findings confirmed retrospectively. Case 4, m a r k e d a t t e n u a t i o n o f u l t r a s o u n d (US) by the echogenic c o m p o n e n t o f the t u m o u r p r e v e n t e d the accurate e v a l u a t i o n o f t r a c h e a l invasion (Fig. 4). All o f the t u m o u r s were staged as T4 ( T N M classification) at o p e r a t i o n . Three cases h a d d i s t a n t metastases. Case 3 was an undifferentiated c a r c i n o m a with s q u a m o u s metaplasia. All patients received r a d i a t i o n t h e r a p y except for Case 1, who died 2 weeks after an e m e r g e n c y o p e r a t i o n for d y s p h a g i a . The echogenicity scores o f undifferentiated c a r c i n o m a s a n d p a p i l l a r y c a r c i n o m a s were 1.33+0.58 and 2.88 _+0.48, respectively. T h e echogenicity score o f undifferentiated c a r c i n o m a s was lower t h a n that o f p a p i l l a r y c a r c i n o m a (Fig. 5).
DISCUSSION
(a)
(b) Fig. 1 - Case 1. (a) Transverse sonogram revealed an ill defined large anterior neck mass invading to the muscles (arrows), trachea (TR), and carotid sheath (curved arrows). (b) Longitudinal sonogram shows invasion of the tumour (T) to right internal jugular vein (V), an infrequent observation in thyroid cancer.
U n d i f f e r e n t i a t e d c a r c i n o m a o f the t h y r o i d gland is typically associated with a r a p i d onset o f growth, usually presents as a large b u l k y cervical mass, and m a y o b s t r u c t vital structures such as the larynx, trachea, o e s o p h a g u s a n d s u p e r i o r vena cava. A p p r o x i m a t e l y one fifth o f these patients have a history o f previous t r e a t m e n t for differentiated t h y r o i d c a r c i n o m a a n d a b r u p t l y d e v e l o p wides p r e a d metastasis, whereas a n o t h e r third have a history o f a l o n g - s t a n d i n g diffuse goitre or a discrete nodule t h a t s u d d e n l y begins to g r o w rapidly, as was seen in Case 4. This t u m o u r has a m u c h p o o r e r p r o g n o s i s t h a n differentiated t h y r o i d c a r c i n o m a ; m o s t patients are d e a d 6 m o n t h s to 1 y e a r after diagnosis. T h e m e a n survival m a y be as low as 2.5-4 m o n t h s (Rafla, 1969; A l d i n g e r et al., 1978; G e r s h e n g o r n a n d R o b b i n s , 1987; Walfish, 1988). O u r results indicate t h a t undifferentiated c a r c i n o m a o f the t h y r o i d is characterized by an ill-defined h y p o e c h o i c mass, which is less echogenic t h a n the a n t e r i o r s t r a p muscles, c o n t a i n s scattered calcification, a n d has a p r o pensity to invade a d j a c e n t structures. ~Rather h o m o geneous infiltration o f m a l i g n a n t cells m a y a c c o u n t for the h y p o e c h o g e n i c i t y o f the mass. In Case 4, s o n o g r a p h i c images s h o w e d two differing c o m p o n e n t s within the mass. This p a t i e n t h a d a 20 year history o f a t h y r o i d n o d u l e which grew rapidly, suggesting c o n v e r s i o n or t r a n s f o r m a t i o n o f a slow-growing p a p i l l a r y t u m o u r to an a n a p l a s t i c t y p e (Case R e c o r d s o f M a s s a c h u s e t t s G e n e r a l
309
CARCINOMA OF THE THYROID GLAND
(a)
(a)
(b)
(b)
Fig. 3 Case 3. (a) Transverse sonogram shows a hypoechoic nlass in the left lobe with invasion to trachea and esophagus (E). Calcification was also noted (curved arrows). (b) Pathological examination of operation specimens revealed undifferentiated carcinoma with squamous metaplasia. Definite keratinization in tumour cells is seen (H&E).
(c) Fig. 2 Case 2. (a) Transverse sonogram shows a hypoechoic mass in the left lobe. The hyperechoic punctate loci within the lesion (curved arrows), proved at pathology to be calcification. Note the ill defined anterior margin of the mass with disappearance of the thyroid capsule (arrows). Subtle finding of invasion to left sternocleidomastoid muscle can be interpreted only retrospectively (arrows). (b) Longitudinal sonogram shows an ill defined hypoechoic area with internal punctate echoes (curved arrows). (c) Pathological examination revealed undifferentiated carcinoma of spindle cell subtype. Diffuse proliferation of atypical spindle shaped turnout cells is seen (H&E).
Fig. 4 Case 4. Transverse sonogram Of left neck reveals a well-defined thyroid mass (arrows). Adjacent to this mass is an ill defined hypoechoic area surrounding the carotid sheath (curved arrows; C, left common carotid artery). Pathological examination at operation from the intrathyroid mass revealed papillary carcinoma, and that obtained from the perithyroid tissue showed undifferentiated carcinoma.
310
CLINICALRADIOLOGY
Table 2 - Detection of calcification, lymph node metastasis, and invasion of adjacent structures; U S vs surgical or pathological findings
Calcification Lymph nodes Sternocleidomastoid muscle Carotid artery Jugular vein Trachea Oesophagus 1.33 -+ 0.58
US
Surgery or pathology
3 2 1 2 1 2 2
4 2 2 2 1 3 2
2.88 __+0.48
I
I
I
I
I
]
2
3
4
5
Echogenicity score Fig. 5 - Scattergram of echogenicity of three undifferentiated carcinomas and 20 papillary carcinomas. The score was 1.33___0.58 and 2.88-1-0.48, respectively. The score of undifferentiated carcinoma was lower than that of papillary carcinoma, e, Undifferentiated carcinoma; o, welt differentiated carcinoma. Hospital, 1975). The specimen at operation obtained from the intrathyroid mass revealed papillary carcinoma, while that f r o m the perithyroid tissue revealed undifferentiated carcinoma. A rather ill defined, hypoechoic area extending to the adjacent structures m a y reflect the anaplastic c o m p o n e n t o f the cancer. In Case 3, pathological examination revealed a picture o f s q u a m o u s cell carcinoma (Fig. 3b). However, no other primary lesions were found, and there was a c o m p o n e n t o f papillary carcinoma observed in a small metastatic cervical lymph node. Therefore, the case was considered as undifferentiated carcinoma o f the thyroid gland with s q u a m o u s metaplasia. In our series, all cases except Case 4 had pre-operative needle biopsy. Two cases (Cases 2 and 3) were correctly diagnosed as undifferentiated carcinoma, while Case 1 was diagnosed as papillary carcinoma. High resolution real-time ultrasonography provides detailed morphological information o f the thyroid gland (Simeone et al., 1982). The diagnosis o f undifferentiated carcinoma by ultrasonography, in distinction f r o m well differentiated carcinoma, is not difficult, in typical cases having a large ill defined, hypoechoic, invading mass associated with calcification. The well differentiated carcinoma m a y be ill defined or lobulated and sometimes invades the surrounding cervical structures. However, the echogenicity o f well differentiated carcinoma is usually higher than that o f strap muscles (18/20). O n the other hand, the echogenicity o f undifferentiated carcinomas was equal to or less than that o f strap muscles. There was a tendency for echogenicity o f undifferentiated carcinoma to be lower than that o f papillary carcinomas, t h o u g h the numbers in this study were small (Fig. 5). Both malignant l y m p h o m a and subacute thyroiditis m a y be as hypoechoic as undifferentiated carcinoma (Takashima et aI., 1989; T o k u d a et al., 1990). However,
malignant l y m p h o m a rarely shows calcification or invasion o f the surrounding cervical structures. T a k a s h i m a et al. (1989) reported one case with calcification in the t u m o u r and one case with invasion o f the larynx a m o n g 16 cases o f malignant lymphoma. The high incidence o f associated chronic thyroiditis and hypothyroidism in addition to such sonographic findings m a y facilitate the differentiation of malignant l y m p h o m a from undifferentiated carcinoma. Takashima et al. (1990) recently reported the c o m p u t e d t o m o g r a p h i c (CT) features of undifferentiated carcinoma. They described the frequent incidence o f calcification (11/18) and t u m o u r necrosis (14/ 18) in undifferentiated carcinoma, findings which therefore help to differentiate it from malignant l y m p h o m a . Subacute thyroiditis also shows ill defined hypoechoic areas with swelling o f one or both lobes. The lesions, however, rarely have calcification or invasion o f the surrounding tissues, are often multiple and bilateral, and regress rapidly in response to treatment. The s y m p t o m s of subacute thyroiditis are usually quite typical, consisting of painful swelling o f the thyroid region, fever and mild thyrotoxicosis. N o r m a l or increased serum concentrations o f thyroid hormones, elevated levels o f C-reactive protein in serum, and low uptake o f 1231 or 99myc by the thyroid, will establish the diagnosis o f subacute thyroiditis ( T o k u d a et al., 1990). Therefore, the identification of invasion and calcification by US as well as the clinical and laboratory findings allow distinction o f undifferentiated carcinoma from malignant l y m p h o m a or subacute thyroiditis, which m a y have a similar appearance. O u r study has shown that a probable diagnosis o f undifferentiated carcinoma can be made by s o n o g r a p h y in c o m b i n a t i o n with clinical findings. The suspicion o f undifferentiated carcinoma by s o n o g r a p h y m a y lead to a p r o m p t biopsy to obtain a tissue diagnosis.
Acknowledgements. The authors gratefully acknowledge the various comments and helpful suggestions of Warren B. Gefter, MD and Peter H. Arger, MD. Gratitude is also extended to Ms Karen Weiss for her kind assistance in the manuscript preparation.
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