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Carcinoma of the thyroid occurring in a diffuse toxic goiter
Carcinoma ELMER W.
of the Thyroid Occurring Diffuse Toxic Goiter
KONEMAN,
M.D. AND KENNETH C. SAWYER, M.D., Denver,
HE rarity of carcinoma of the thyroid in the presence of diffuse toxic goiter has been well established in recent reviews in the literature. In 1948 Pemberton and Black [I] showed that in a collected series of 1,210 patients with carcinoma of the thyroid gland this association occurred in onIy 1.74 per cent. Conversely, hy collecting previously recorded cases, Sokal 121 found that cancer occurred in only o. 15 per cent of 13,868 patients whose thyroid gland had been surgically removed because of diffuse toxic goiter. However, since this extensive review of the subject, only isolated cases have been reported in the literature [3-6]. Recently, Sawyer and Alfonso [7] reviewed sixty-five cases of carcinoma of the thyroid gland in patients who have been surgically treated at this institution since 1946. During this same period, 249 thyroid glands were removed because of diffuse toxic goiter and all cases were confirmed by histologic examination of the thyroid tissue removed. A recent case is reported herein in which carcinoma occurred in a diffuse toxic goiter. A second case was excIuded because the consulting pathoIogists did not concur that carcinoma was present in a thyroid showing diffuse hyperplasia. Thus one of the sixty-five carcinomas (1.54 per cent) was associated with diffuse hyperplasia of the thyroid and one of 249 cases of diffuse hyperpIasia (0.40 per cent) showed carcinoma. These statistics are comparable to those of Pemberton and Black, and Sokal.
in a Colorado
ever, her weight at this examination was rag pounds. Examination reveaIed an apprehensive and nervous patient. Blood pressure was 144/84 mm. Hg, and radia1 p&e was 88 per minute and regular. A fme tremor of the fingers was noted when the arms were outstretched. Palpation of the neck revealed a diffuse bilateral enlargement of the thyroid gland with no evidence of noduIation or cervical adenopathy. There was no evidence of exophthaImos. The remaining physical examination was noncontributory. Serum protein-bound iodine determination was 12.5 pg. per cent (4 to 8 pg. per cent is norma for this laboratory). Routine presurgical treatment with Lugol’s soIution, a high caIoric diet and rest were immediateIy instituted. The patient noted a dramatic relief of toxic symptoms and her weight was 120 pounds upon admission to the hospita1 six weeks Iater. Blood pressure was 120/80 mm. Hg, and radial puise was 70 per minute and regular. There was no evidence of nervousness or tremor but the thyroid was still palpable. On admission routine hemanalysis, urinalysis and roentgenograms of the chest reveaIed no abnormalities. On December I I, 1958, bilateral, subtotal thyroidectomy was performed without complication. Gross pathologic examination revealed the forLowing: the right and Ieft lobes of the thyroid totaled 39 gm. The right lobe measured 6 by 3.5 by 2.5 cm., and the Ieft Iobe measured 5 by 3.5 by 2.5 cm. Each lobe was firm with a smooth red-gray capsule. MuItipIe thin sections reveaIed a finely lobular, tan to red-brown, somewhat meaty cut surface in which the coIIoid content was grossIy diminished. The cut surface was homogeneous throughout with no gross evidence of nodules, although minute gray stippIed areas were diffusely dispersed. Microscopicahy, the irreguIar and variabIy sized follicles were empty or contained poorIy staining colloid which showed characteristic peripheraI vacuoIation. The epithelium was taI1 and cohrmnar with stratification and papiIIary infolding of the
T
CASE REPORT A seventeen year oId white married woman returned for a routine six-weeks postpartum examination on October 27, rg58, with the compIaints of progressive nervousness, sweating, shakiness, fatigue, fulbress in the neck and increased appetite. She had gained 24 pounds during pregnancy; how245
American
Journal
of Surgery,
Volume
IOI,
February
rq6r
Koneman
and Sawyer
IB
IA
FIG. I. A, section of thyroid gIand showing we11 differentiated papiIIary carcinoma to the left and diffuse hyperplasia with foIIicuIar Iymphocytic intiItration to the right. Note apparent invasion through the thin fibrous waII near the top of the figure. (HematoxyIin and eosin stain, origina magnification X 50.) B, high power, view of Figure IA showing calcified psammoma bodies at the fibrous junction of the papiIIary carcinoma and hyperpIastic thyroid tissue. (Hematoxylin and eosin stain, origina magnification X 200.)
epithelial cells in some follicles. A few mitotic figures were noted within this hyperpIastic epithelium. The characteristic invoIution usuaIIy seen folIowing iodine therapy was observed in onIy a few focal areas. There was some increase in the interstitia1 fibrous tissue which aIso showed both diffuse and foIIicuIar Iymphocytic infiltration. In one smaI1 foca1 area in a section from the right lobe and demarcated from the adjacent hyperpIastic thyroid parenchyma by a thin fibrous wall, there was a cancerous proIiferation of the gIanduIar epitheIium with a characteristic pattern of papiIIary carcinoma. (Figs. IA and B.) The fibrous waI1 was invaded on one side. Characteristic psammoma bodies were numerous throughout this cancerous growth. Since this smaI1 cancer was not suspected from gross examination, repeat sections of the wet specimen of each Iobe were made. Two simiIar areas of papiIIary carcinoma were found within the right lobe adjacent to the original one. Serial sections of the Ieft Iobe revealed no microscopic evidence of cancer. COMMENTS
There was strong clinica evidence of thyrotoxicosis in this case and it differed from the cIassica1 case of Graves’ disease only in the absence of ocuIar signs. The clinica diagnosis was supported by the eIevated protein-bound iodine and Iater by the rapid remission of toxic signs and symptoms when iodine therapy was administered. The diffuseIy enlarged gIand was easiIy removed and there was no evidence of cervica1 adenopathy. The fact that carcinoma was not suspected cIinicaIIy in this case is not surprising since 246
none of the twenty-two cases reported by Pemberton and BIack [I] had been suspected. In the majority of their cases, as in the present case, the carcinoma was not recognized as such even on gross examination of the surgica1 specimen. Their concIusion was that in many cases such Iesions can be recognized only if a11grossIy visibIe noduIes, however smaI1, are sectioned and examined microscopicaIIy. Since most patients are treated preoperatively with iodine, smaI1 noduIar areas of involution may obscure the presence of smaI1 true adenomas and may, therefore, escape the eye of the prosector. In a Iater report by Beahrs, Pemberton and BIack [8], fourteen carcinomas were found in 3,029 patients whose thyroid gIands showed diffuse a11 these cancers were hyperpIasia. AImost
smaI1, scIerosing papiIIary growths which showed little tendency to recur or metastasize. It is evident, therefore, that for the diagnosis to be made before surgica1 intervention there must be a rare, rapidly growing cancer or evidence of metastasis with clinica diffuse toxic goiter. BouIet et al. [3] report a case in which a diffuse toxic goiter grew rapidIy foIIowing treatment with antithyroid drugs. PathoIogic examination of the surgica1 specimen revealed carcinoma. They concIuded that antithyroid drugs may augment a pre-existent cancer and that the prognosis is guarded in any case in which a diffuse toxic goiter begins to grow rapidIy after treatment with antithyroid drugs.
Carcinoma
of the Thyroid
In the majority of cases, however, cancers associated with diffuse hyperplasia of the thyroid wiII be small and probabIy need not be seriousIy considered, especiaIIy in the case of papiIIary carcinoma. The patient’s age is of some interest in this case although carcinoma of the thyroid gland is not rare in young people. Duffy and Fitzgerald [g] found that twenty-eight of 403 (6.5 per cent) patients with carcinoma of the thyroid gIand were under eighteen years of age. In the folIowing year, Horn and Ravdin [IO] found that twenty-two of 159 (13.8 per cent) patients with carcinomas of the thyroid were under twenty-five years of age. FrazelI and Foote [I r] showed that papiIIary carcinoma is the characteristic thyroid cancer of young people and children. They reported twenty-five cases of carcinoma of the thyroid gland in patients under twenty years of age, and in twenty patients the cancer was papillary. Most of these were very smaI1 in size, 15 per cent measuring under I cm. in greatest dimension. The point was again stressed by these authors that papillary tumors of the thyroid are of Iow grade malignancy and have a proIonged cIinicaI course. SUMMARY
thyroid in which a smaI1 papiIIary carcinoma was found on microscopic examination of the surgica1 specimen. We believe the postoperative management of such patients shouId be conservative and Iimited to periodic examinations, reserving extensive surgica1 remova of the regional Iymphatics onIy when recurrence or regionat Iymph node metastasis becomes cIinicaIIy manifest. REFERENCES 1. PEMBERTON, .I. DEJ. and BLACK, B. M. The association of carcinoma of the thyroid gland and exophthalmic goiter. S. Clin. North America, 28: 935, 1948. 2. SOKAL, J. E. Incidence of maIignancy in toxic and nontoxic nodular goiter. J. A. M. A., 154: 1321, 1954. 3. BOULET, P., MIROUSE, J. and BARJON,P. Cancer thyroidien de’couvert chez deux grandes Basedowiennes apparemment guiries par antithyroidiens. Ann. endocrinok, 14: 927, 1953. 4. LONCO. 0. F. and FERRARIS, A. Cancer de tiroides en eI bocio Basedowificado. Bol. Sot. cir. Buenos Aires, 40: 393, 1956. 5. EASXOTT, H. H. G. and HEPTINSTALL, R. H. A case of carcinoma of the th.yroid arising in a diffuse toxic goiter. Brit. J. S&g., 45: 297; 1958. 6. HOLSINCER. D. R. and STEVENS. J. E. Hvoerthvroidism in a case of thyroid carcinoma presenting as diabetes melIitus. Ann. Int. Med., 46: 791, ‘957. 7. SAWYER, I<. C. and ALFONSO, R. S. UnpubIished data. 8. BEAHRS, 0. H., PEMBERTON, J. DEJ. and BLACK, B. M. NoduIar goiter and malignant lesions of the thyroid gland. J. CZin. Endocrinol., 11: I 157,
Carcinoma of the thyroid usually is not suspected clinicaIIy with diffuse toxic goiter. When the association occurs, the cancer is usuaIIy smaI1, often of the papillary type, especially in patients under twenty-five years of age. Often it is discovered onIy on microscopic examination of the surgicaI specimen. It has been estabIished that papiIIary carcinomas of the thyroid are of Iow grade maIignancy and have a prolonged cIinica1 course. This case presented herein occurred in a seventeen year old gir1 with diffuse toxic hyperpIasia of the
‘951. 9. DUFFY, B. J., JR. and FITZGERALD, P. .I. Thyroid cancer in childhood and adolescence. Cancer, 3: 1018, 1951. IO. HORN, R. C., JR. and RAVDIN, I. S. Carcinoma of the thyroid gland in youth. J. Clin. Endocrinol., II: 1166, 1951. I I. FRAZELL, E. L. and FOOTE, F. W., JR. The natural history of thyroid cancer: a review of 301 cases. J. Clin. Endocrinol., g: 1023, 1949.
247
of the Thyroid Occurring Diffuse Toxic Goiter
KONEMAN,
M.D. AND KENNETH C. SAWYER, M.D., Denver,
HE rarity of carcinoma of the thyroid in the presence of diffuse toxic goiter has been well established in recent reviews in the literature. In 1948 Pemberton and Black [I] showed that in a collected series of 1,210 patients with carcinoma of the thyroid gland this association occurred in onIy 1.74 per cent. Conversely, hy collecting previously recorded cases, Sokal 121 found that cancer occurred in only o. 15 per cent of 13,868 patients whose thyroid gland had been surgically removed because of diffuse toxic goiter. However, since this extensive review of the subject, only isolated cases have been reported in the literature [3-6]. Recently, Sawyer and Alfonso [7] reviewed sixty-five cases of carcinoma of the thyroid gland in patients who have been surgically treated at this institution since 1946. During this same period, 249 thyroid glands were removed because of diffuse toxic goiter and all cases were confirmed by histologic examination of the thyroid tissue removed. A recent case is reported herein in which carcinoma occurred in a diffuse toxic goiter. A second case was excIuded because the consulting pathoIogists did not concur that carcinoma was present in a thyroid showing diffuse hyperplasia. Thus one of the sixty-five carcinomas (1.54 per cent) was associated with diffuse hyperplasia of the thyroid and one of 249 cases of diffuse hyperpIasia (0.40 per cent) showed carcinoma. These statistics are comparable to those of Pemberton and Black, and Sokal.
in a Colorado
ever, her weight at this examination was rag pounds. Examination reveaIed an apprehensive and nervous patient. Blood pressure was 144/84 mm. Hg, and radia1 p&e was 88 per minute and regular. A fme tremor of the fingers was noted when the arms were outstretched. Palpation of the neck revealed a diffuse bilateral enlargement of the thyroid gland with no evidence of noduIation or cervical adenopathy. There was no evidence of exophthaImos. The remaining physical examination was noncontributory. Serum protein-bound iodine determination was 12.5 pg. per cent (4 to 8 pg. per cent is norma for this laboratory). Routine presurgical treatment with Lugol’s soIution, a high caIoric diet and rest were immediateIy instituted. The patient noted a dramatic relief of toxic symptoms and her weight was 120 pounds upon admission to the hospita1 six weeks Iater. Blood pressure was 120/80 mm. Hg, and radial puise was 70 per minute and regular. There was no evidence of nervousness or tremor but the thyroid was still palpable. On admission routine hemanalysis, urinalysis and roentgenograms of the chest reveaIed no abnormalities. On December I I, 1958, bilateral, subtotal thyroidectomy was performed without complication. Gross pathologic examination revealed the forLowing: the right and Ieft lobes of the thyroid totaled 39 gm. The right lobe measured 6 by 3.5 by 2.5 cm., and the Ieft Iobe measured 5 by 3.5 by 2.5 cm. Each lobe was firm with a smooth red-gray capsule. MuItipIe thin sections reveaIed a finely lobular, tan to red-brown, somewhat meaty cut surface in which the coIIoid content was grossIy diminished. The cut surface was homogeneous throughout with no gross evidence of nodules, although minute gray stippIed areas were diffusely dispersed. Microscopicahy, the irreguIar and variabIy sized follicles were empty or contained poorIy staining colloid which showed characteristic peripheraI vacuoIation. The epithelium was taI1 and cohrmnar with stratification and papiIIary infolding of the
T
CASE REPORT A seventeen year oId white married woman returned for a routine six-weeks postpartum examination on October 27, rg58, with the compIaints of progressive nervousness, sweating, shakiness, fatigue, fulbress in the neck and increased appetite. She had gained 24 pounds during pregnancy; how245
American
Journal
of Surgery,
Volume
IOI,
February
rq6r
Koneman
and Sawyer
IB
IA
FIG. I. A, section of thyroid gIand showing we11 differentiated papiIIary carcinoma to the left and diffuse hyperplasia with foIIicuIar Iymphocytic intiItration to the right. Note apparent invasion through the thin fibrous waII near the top of the figure. (HematoxyIin and eosin stain, origina magnification X 50.) B, high power, view of Figure IA showing calcified psammoma bodies at the fibrous junction of the papiIIary carcinoma and hyperpIastic thyroid tissue. (Hematoxylin and eosin stain, origina magnification X 200.)
epithelial cells in some follicles. A few mitotic figures were noted within this hyperpIastic epithelium. The characteristic invoIution usuaIIy seen folIowing iodine therapy was observed in onIy a few focal areas. There was some increase in the interstitia1 fibrous tissue which aIso showed both diffuse and foIIicuIar Iymphocytic infiltration. In one smaI1 foca1 area in a section from the right lobe and demarcated from the adjacent hyperpIastic thyroid parenchyma by a thin fibrous wall, there was a cancerous proIiferation of the gIanduIar epitheIium with a characteristic pattern of papiIIary carcinoma. (Figs. IA and B.) The fibrous waI1 was invaded on one side. Characteristic psammoma bodies were numerous throughout this cancerous growth. Since this smaI1 cancer was not suspected from gross examination, repeat sections of the wet specimen of each Iobe were made. Two simiIar areas of papiIIary carcinoma were found within the right lobe adjacent to the original one. Serial sections of the Ieft Iobe revealed no microscopic evidence of cancer. COMMENTS
There was strong clinica evidence of thyrotoxicosis in this case and it differed from the cIassica1 case of Graves’ disease only in the absence of ocuIar signs. The clinica diagnosis was supported by the eIevated protein-bound iodine and Iater by the rapid remission of toxic signs and symptoms when iodine therapy was administered. The diffuseIy enlarged gIand was easiIy removed and there was no evidence of cervica1 adenopathy. The fact that carcinoma was not suspected cIinicaIIy in this case is not surprising since 246
none of the twenty-two cases reported by Pemberton and BIack [I] had been suspected. In the majority of their cases, as in the present case, the carcinoma was not recognized as such even on gross examination of the surgica1 specimen. Their concIusion was that in many cases such Iesions can be recognized only if a11grossIy visibIe noduIes, however smaI1, are sectioned and examined microscopicaIIy. Since most patients are treated preoperatively with iodine, smaI1 noduIar areas of involution may obscure the presence of smaI1 true adenomas and may, therefore, escape the eye of the prosector. In a Iater report by Beahrs, Pemberton and BIack [8], fourteen carcinomas were found in 3,029 patients whose thyroid gIands showed diffuse a11 these cancers were hyperpIasia. AImost
smaI1, scIerosing papiIIary growths which showed little tendency to recur or metastasize. It is evident, therefore, that for the diagnosis to be made before surgica1 intervention there must be a rare, rapidly growing cancer or evidence of metastasis with clinica diffuse toxic goiter. BouIet et al. [3] report a case in which a diffuse toxic goiter grew rapidIy foIIowing treatment with antithyroid drugs. PathoIogic examination of the surgica1 specimen revealed carcinoma. They concIuded that antithyroid drugs may augment a pre-existent cancer and that the prognosis is guarded in any case in which a diffuse toxic goiter begins to grow rapidIy after treatment with antithyroid drugs.
Carcinoma
of the Thyroid
In the majority of cases, however, cancers associated with diffuse hyperplasia of the thyroid wiII be small and probabIy need not be seriousIy considered, especiaIIy in the case of papiIIary carcinoma. The patient’s age is of some interest in this case although carcinoma of the thyroid gland is not rare in young people. Duffy and Fitzgerald [g] found that twenty-eight of 403 (6.5 per cent) patients with carcinoma of the thyroid gIand were under eighteen years of age. In the folIowing year, Horn and Ravdin [IO] found that twenty-two of 159 (13.8 per cent) patients with carcinomas of the thyroid were under twenty-five years of age. FrazelI and Foote [I r] showed that papiIIary carcinoma is the characteristic thyroid cancer of young people and children. They reported twenty-five cases of carcinoma of the thyroid gland in patients under twenty years of age, and in twenty patients the cancer was papillary. Most of these were very smaI1 in size, 15 per cent measuring under I cm. in greatest dimension. The point was again stressed by these authors that papillary tumors of the thyroid are of Iow grade malignancy and have a proIonged cIinicaI course. SUMMARY
thyroid in which a smaI1 papiIIary carcinoma was found on microscopic examination of the surgica1 specimen. We believe the postoperative management of such patients shouId be conservative and Iimited to periodic examinations, reserving extensive surgica1 remova of the regional Iymphatics onIy when recurrence or regionat Iymph node metastasis becomes cIinicaIIy manifest. REFERENCES 1. PEMBERTON, .I. DEJ. and BLACK, B. M. The association of carcinoma of the thyroid gland and exophthalmic goiter. S. Clin. North America, 28: 935, 1948. 2. SOKAL, J. E. Incidence of maIignancy in toxic and nontoxic nodular goiter. J. A. M. A., 154: 1321, 1954. 3. BOULET, P., MIROUSE, J. and BARJON,P. Cancer thyroidien de’couvert chez deux grandes Basedowiennes apparemment guiries par antithyroidiens. Ann. endocrinok, 14: 927, 1953. 4. LONCO. 0. F. and FERRARIS, A. Cancer de tiroides en eI bocio Basedowificado. Bol. Sot. cir. Buenos Aires, 40: 393, 1956. 5. EASXOTT, H. H. G. and HEPTINSTALL, R. H. A case of carcinoma of the th.yroid arising in a diffuse toxic goiter. Brit. J. S&g., 45: 297; 1958. 6. HOLSINCER. D. R. and STEVENS. J. E. Hvoerthvroidism in a case of thyroid carcinoma presenting as diabetes melIitus. Ann. Int. Med., 46: 791, ‘957. 7. SAWYER, I<. C. and ALFONSO, R. S. UnpubIished data. 8. BEAHRS, 0. H., PEMBERTON, J. DEJ. and BLACK, B. M. NoduIar goiter and malignant lesions of the thyroid gland. J. CZin. Endocrinol., 11: I 157,
Carcinoma of the thyroid usually is not suspected clinicaIIy with diffuse toxic goiter. When the association occurs, the cancer is usuaIIy smaI1, often of the papillary type, especially in patients under twenty-five years of age. Often it is discovered onIy on microscopic examination of the surgicaI specimen. It has been estabIished that papiIIary carcinomas of the thyroid are of Iow grade maIignancy and have a prolonged cIinica1 course. This case presented herein occurred in a seventeen year old gir1 with diffuse toxic hyperpIasia of the
‘951. 9. DUFFY, B. J., JR. and FITZGERALD, P. .I. Thyroid cancer in childhood and adolescence. Cancer, 3: 1018, 1951. IO. HORN, R. C., JR. and RAVDIN, I. S. Carcinoma of the thyroid gland in youth. J. Clin. Endocrinol., II: 1166, 1951. I I. FRAZELL, E. L. and FOOTE, F. W., JR. The natural history of thyroid cancer: a review of 301 cases. J. Clin. Endocrinol., g: 1023, 1949.
247