Bilateral secondary mucinous adenocarcinoma of thyroid: Case report DAN NACHTIGAL, MD, MURAlEE DHARAN, MD, RAFAEl lUBOSHITZKY, MD, JOSEPH HONIGMAN, MD, and GABRiEl ROSEN, MD, FACS, Afula, Israel
Metastatic adenocarcinoma to the thyroid gland, though not uncommon in autopsies, is rarely encountered in clinical practice. Tumors of breast, kidney, or lung and melanomas are occasionally sources of solitary "cold" nodules in the thyroid. Rarely, the gastrointestinal tract, such as colon, may be the primary site. Extensive involvement of the thyroid by a metastatic colon carcinoma can cause diagnostic difficulties for both the clinician and the pathologist. Differentiation from a primary mucinous carcinoma of the thyroid, in such an instance, would require immunohistochemical stains and electron microscopic study to facilitate correct diagnosis. Such a case of secondary adenocarcinoma of colon bilaterally involving the thyroid, 8 years after removal of the primary, is reported here. CASE REPORT
P.P., a 69-year-old woman, had undergone left hemicolectomy for tumor of the sigmoid colon 8 years before admission to our ENT clinic. Adenocarcinoma with infiltration up to the deep muscular layer of the colon was found on pathologic examination. Regional lymph nodes were free of carcinoma. Cholecystectomy was required at the same operation because of asymptomatic cholelithiasis, leading to the finding of a carcinoma in situ on histologic examination. After uneventful recovery from the operation, the patient was referred to the oncology unit for followup. Six years after the first operation, chest x-ray film and CT scan revealed an additional tumor in the lower lobe of the left lung, necessitating lobectomy. Histologically, the tumor was diagnosed as a metastasis of adenocarcinoma, identical to the primary colon carcinoma. Six months later, the patient noticed a swelling on her right lower neck. It was slow-growing and did not affect her swallowing or breathing. Three months before admission to the
FromtheDepartments of Otolaryngology (Drs. Nachtigal andRosen), Pathology (Dr. Dharan), Endocrinology (Dr. Luboshitzky), and Oncology (Dr. Honigman), Central EmekHospital, Afula. Received for publication Del. 11, 1991; revision received Jan. 14, 1992; accepted Jan. 22, 1992. Reprint requests: Dan Nachtigal, MD, Ear, Nose, and Throat Department, Central EmekHospital, Afula 18101, Israel. 23/4/37907
466
ENT department, the patient reported constant hoarseness and a weight loss of 15 kg. On admission to our department, right vocal cord paralysis in the paramedian position was evident on indirect laryngoscopy. Examination of the neck revealed a hard, fixed, nontender nodule, about 3 cm in diameter, located in the inferior portion of the right thyroid lobe. It moved with swallowing. The rest of the physical examination was unremarkable, except for attenuated respiration voices at the right chest. Thyroid function tests were normal. Repeated fine-needle aspirates were not diagnostic because of lack of material. Scintiscanning of the thyroid with 131 1 demonstrated a "cold" nodule in the lower part of the right lobe, with 10% and 33% uptake of the radionuclide after 2 and 24 hours, respectively. Scanning by 99mTc of the liver and spleen was normal. A neoplasm of the thyroid was diagnosed clinically, and a right hemithyroidectomy was planned. During the operation the right thyroid lobe was found to be stone-hard, fixed to the surrounding connective tissue, the right recurrent laryngeal nerve, the larynx, the esophagus, and the vertebrae. Several hard nodules were palpated in the left lobe as well. Therefore a total thyroidectomy was performed. The adjacent infiltrated connective tissue was only partially resected. The patient recovered normally. Pathologic examination revealed the right thyroid lobe to be enlarged, measuring 2.5 x 3.0 x 4.5 cm. A firm brownyellow tissue was seen at the cross-section, filling about 90% of the lobe. Several white hard nodules were observed in the left lobe, which measured 2.0 x 2.5 x 4.5 cm. The largest of the nodules, 0.7 x 1.2 x 2.0 cm in size, had macroscopically penetrated beyond the capsule. Microscopic examination demonstrated infiltration of both thyroid lobes with extensive areas of moderately differentiated adenocarcinoma. The tumor was comprised of glandular and tubular structures of varying sizes made of atypical columnar cells. Periodic acid-Schiff (PAS) and mucicarmine stains demonstrated abundant secretory granules within the cytoplasm and the luminae. The tumor infiltration was accompanied by marked stromal fibrosis and foci of necrosis. Normal thyroid follicles, some atrophic, could be seen entrapped within infiltrating tumor (Fig. 1). Immunoperoxidase stains showed strong positivity of the tumor cells to cytokeratin and carcinoma embryonic antigen (CEA). Staining was negative for both thyroglobulin and calcitonin. Comparison of sections of the present tumor to slides of the adenocarcinoma of the colon, resected 8 years ago, revealed histological similarity.
Volume 107 Number 3 September 1992
Case Reports 467
Fig. 1. Histologic section shows adenocarcinoma infiltrating the thyroid. Colloid-containing follicles are seen on the left (Hematoxylin-eosin stain; original magnification x 200.)
The patient was treated with t.-thyroxinc (0.1 mg/day) and attained normal serum Ff4 (1.3 f.Lg/dl) and TSH (1.4 u.Ll/rnl). Blood calcium levels decreased during the postoperative period to 7.2 mg/ dl, but spontaneouslyand gradually increased to 8.9 mg/dl. Three months later she reported severe backache. CT scan showed multiple metastasis in the lungs, vertebrae, and ribs. The patient died as a result of widespread metastasis 8 months after the thyroidectomy. DISCUSSION
Metastatic tumors in the thyroid are rarely seen in clinical practice."? The majority of metastatic neoplasms in the thyroid are found only at autopsy, in about 9% of patients who die of cancer. 2 Most of these metastases originate from renal (32%), lung (28%), and breast (20%) cancers. 2-5 In Japan carcinoma of the esophagus seems to be a more common source (19%).6 Other malignant neoplasms known to metastasize to the thyroid include malignant melanoma, lymphoma," and leiomyosarcoma." Gastric carcinoma is yet another source of metastasis to the thyroid." Secondary carcinomas of colorectal origin are rare. 2 •9- 11 Recent reports revealed that the prevalence of metastatic involvement of the thyroid is more frequent than has been previously appreciated. 12.13 These studies used the fine-needle aspiration technique
(FNA) and showed that metastases to the thyroid could be diagnosed with great accuracy. However, several studies emphasize that FNA may not yield diagnostic material in cases such as the present one, where tumor is diffuse, accompanied by productive fibrosis.5.9.12.13 In our case, the conventional FNA did not disclose the nature of the tumor and since suspicious cold nodules of the thyroid are routinely excised," the patient underwent thyroidectomy. The workup of our case included light microscopy, immunohistochemical staining, and ultramicroscopy. Our case was negative for both thyroglobulin and calcitonin, whereas cytokeratin and CEA positivity suggested the possibility of colon adenocarcinoma." It is worth remembering that primary mucinous carcinoma of the thyroid is a recognized entity," and has to be distinguished from a secondary mucinous carcinoma. Ultrastructurally, primary mucinous thyroid carcinoma shows evidence of both colloid and mucin secretion by the same neoplastic cell," in contrast to the case presented here, in which only mucin granules were found. Metastasis to the thyroid gland may appear many years after the removal of the primary tumor,":" as happened in our case 8 years after resection of the primary. In these cases, the thyroid nodules may be the only remains of the primary malignant disease. Prompt di-
468 Case Reports
agnosis of a secondary thyroid tumor and its surgical removal may render some degree of palliation to the patient. 4,8 The prolonged history in our patient with metastasis to various organs demonstrate how common cancer can behave in an unpredictable way. In summary, metastatic disease must be considered in the differential diagnosis of solitary cold nodules of the thyroid. In cases in which primary tumor can not be differentiated from a primary one by FNA alone, excisional biopsy and meticulous histologic study, including light microscopy, immunohistochemical staining and electron microscopy, will be required to establish the correct diagnosis. REFERENCES
I, Rosen Y, Rosenblatt P, Saltzman E. Intraoperative pathologic diagnosis of thyroid neoplasms. Report on experience with 504 specimens. Cancer 1990;66:2001-6. 2. Katsutaro S, Sokal JE, Pickren JW. Metastatic neoplasms in the thyroid gland: pathological and clinical findings. Cancer 1962;15:557-65. 3. Meissner W, Warren S. Tumors of the thyroid gland. In: Firminger H, ed. Atlas of tumor pathology. 2nd series. Washington D.C.: Armed Forces Institute of Pathology, 1969:127-9. 4. Schroder S, Burk CG, de-Heer K. Metastases to the thyroid gland-morphology and clinical aspects of 25 secondary thyroid neoplasms. Langenbecks Arch Chir 1987;370:25-35. 5. Schroder S, Boeker W. Clear-cell carcinomas of thyroid gland: a clinicopathological study of 13 cases. Histopathology 1986;10:75-89. 6. Takashima S, Saeki H, Moriwaki S, Yamamoto Y. An autopsy case of metastatic thyroid tumor. Gan No Rinsho 1984;30: 880-4.
OlolaryngologyHead and Neck Surgery
7. Cruickshank Je. Leiomyosarcoma metastatic to the thyroid gland. Ear Nose Throat J 1988;67:899-900,902,904. 8. Yoshida A, Imamura A, Tanaka H, et al. A case of metastatis from gastric cancer to the thyroid gland. J Jpn Surg 1989;19: 480-4. 9. Cristal1ini EG, Balis GB, Francucci M. Diagnosis of thyroid metastasis of colonic adenocarcinoma by fine needle aspiration biopsy. Acta Cytol 1990;34:363-5. 10. Lertprasertsuke N, Kakudo K, Satoh S, Tada N, Osamura Y. Rectal carcinoid tumor metastasizing to the thyroid and pancreas. An autopsy case exploiting immunohistochemistry for differentiation from tumors involving multiple endocrine organs. Acta Pathol Jpn 1990;40:352-60. II. Lester JW Jr, Carter MP, Berens SV, Long RF, Caplan GE. Colon carcinoma metastatic to the thyroid gland. Clin Nucl Med 1986;11:634-5. 12. Watts NB. Carcinoma metastatic to the thyroid: prevalence and diagnosis by fine-needle aspiration cytology. Am J Med Sci 1987;293:13-7. 13. Smith SA, Gharib H, Goellner JR. Fine-needle aspiration. Usefulness for diagnosis and management of metastatic carcinoma to the thyroid. Arch Int Med 1987;147:311-2. 14. Mazzaferri EL. Management of thyroid neoplasms. In: Cummings CW, Fredrickson JM, Harker LA, Krause CJ, Schuller DE, eds. Otolaryngology-head and neck surgery. Update 2. SI. Louis: The C.Y. Mosby Co., 1990:224-60. 15. Primus FJ, Clark CA, Goldenberg OM. Immunohistochemical detection of carcinoembryonic antigen. In: Delellis RA, ed. Diagnostic immunohistochemistry. Masson monographs in diagnostic pathology. New York: Masson Publishing USA Inc., 1981:263-76. 16. Deligdisch L, Subhani Z, Gordon RE. Primary mucinous carcinoma of the thyroid gland. Report of a case and ultrastructural study. Cancer 1980;45:2564-7.
Metastatic adenocarcinoma to the thyroid gland, though not uncommon in autopsies, is rarely encountered in clinical practice. Tumors of breast, kidney, or lung and melanomas are occasionally sources of solitary "cold" nodules in the thyroid. Rarely, the gastrointestinal tract, such as colon, may be the primary site. Extensive involvement of the thyroid by a metastatic colon carcinoma can cause diagnostic difficulties for both the clinician and the pathologist. Differentiation from a primary mucinous carcinoma of the thyroid, in such an instance, would require immunohistochemical stains and electron microscopic study to facilitate correct diagnosis. Such a case of secondary adenocarcinoma of colon bilaterally involving the thyroid, 8 years after removal of the primary, is reported here. CASE REPORT
P.P., a 69-year-old woman, had undergone left hemicolectomy for tumor of the sigmoid colon 8 years before admission to our ENT clinic. Adenocarcinoma with infiltration up to the deep muscular layer of the colon was found on pathologic examination. Regional lymph nodes were free of carcinoma. Cholecystectomy was required at the same operation because of asymptomatic cholelithiasis, leading to the finding of a carcinoma in situ on histologic examination. After uneventful recovery from the operation, the patient was referred to the oncology unit for followup. Six years after the first operation, chest x-ray film and CT scan revealed an additional tumor in the lower lobe of the left lung, necessitating lobectomy. Histologically, the tumor was diagnosed as a metastasis of adenocarcinoma, identical to the primary colon carcinoma. Six months later, the patient noticed a swelling on her right lower neck. It was slow-growing and did not affect her swallowing or breathing. Three months before admission to the
FromtheDepartments of Otolaryngology (Drs. Nachtigal andRosen), Pathology (Dr. Dharan), Endocrinology (Dr. Luboshitzky), and Oncology (Dr. Honigman), Central EmekHospital, Afula. Received for publication Del. 11, 1991; revision received Jan. 14, 1992; accepted Jan. 22, 1992. Reprint requests: Dan Nachtigal, MD, Ear, Nose, and Throat Department, Central EmekHospital, Afula 18101, Israel. 23/4/37907
466
ENT department, the patient reported constant hoarseness and a weight loss of 15 kg. On admission to our department, right vocal cord paralysis in the paramedian position was evident on indirect laryngoscopy. Examination of the neck revealed a hard, fixed, nontender nodule, about 3 cm in diameter, located in the inferior portion of the right thyroid lobe. It moved with swallowing. The rest of the physical examination was unremarkable, except for attenuated respiration voices at the right chest. Thyroid function tests were normal. Repeated fine-needle aspirates were not diagnostic because of lack of material. Scintiscanning of the thyroid with 131 1 demonstrated a "cold" nodule in the lower part of the right lobe, with 10% and 33% uptake of the radionuclide after 2 and 24 hours, respectively. Scanning by 99mTc of the liver and spleen was normal. A neoplasm of the thyroid was diagnosed clinically, and a right hemithyroidectomy was planned. During the operation the right thyroid lobe was found to be stone-hard, fixed to the surrounding connective tissue, the right recurrent laryngeal nerve, the larynx, the esophagus, and the vertebrae. Several hard nodules were palpated in the left lobe as well. Therefore a total thyroidectomy was performed. The adjacent infiltrated connective tissue was only partially resected. The patient recovered normally. Pathologic examination revealed the right thyroid lobe to be enlarged, measuring 2.5 x 3.0 x 4.5 cm. A firm brownyellow tissue was seen at the cross-section, filling about 90% of the lobe. Several white hard nodules were observed in the left lobe, which measured 2.0 x 2.5 x 4.5 cm. The largest of the nodules, 0.7 x 1.2 x 2.0 cm in size, had macroscopically penetrated beyond the capsule. Microscopic examination demonstrated infiltration of both thyroid lobes with extensive areas of moderately differentiated adenocarcinoma. The tumor was comprised of glandular and tubular structures of varying sizes made of atypical columnar cells. Periodic acid-Schiff (PAS) and mucicarmine stains demonstrated abundant secretory granules within the cytoplasm and the luminae. The tumor infiltration was accompanied by marked stromal fibrosis and foci of necrosis. Normal thyroid follicles, some atrophic, could be seen entrapped within infiltrating tumor (Fig. 1). Immunoperoxidase stains showed strong positivity of the tumor cells to cytokeratin and carcinoma embryonic antigen (CEA). Staining was negative for both thyroglobulin and calcitonin. Comparison of sections of the present tumor to slides of the adenocarcinoma of the colon, resected 8 years ago, revealed histological similarity.
Volume 107 Number 3 September 1992
Case Reports 467
Fig. 1. Histologic section shows adenocarcinoma infiltrating the thyroid. Colloid-containing follicles are seen on the left (Hematoxylin-eosin stain; original magnification x 200.)
The patient was treated with t.-thyroxinc (0.1 mg/day) and attained normal serum Ff4 (1.3 f.Lg/dl) and TSH (1.4 u.Ll/rnl). Blood calcium levels decreased during the postoperative period to 7.2 mg/ dl, but spontaneouslyand gradually increased to 8.9 mg/dl. Three months later she reported severe backache. CT scan showed multiple metastasis in the lungs, vertebrae, and ribs. The patient died as a result of widespread metastasis 8 months after the thyroidectomy. DISCUSSION
Metastatic tumors in the thyroid are rarely seen in clinical practice."? The majority of metastatic neoplasms in the thyroid are found only at autopsy, in about 9% of patients who die of cancer. 2 Most of these metastases originate from renal (32%), lung (28%), and breast (20%) cancers. 2-5 In Japan carcinoma of the esophagus seems to be a more common source (19%).6 Other malignant neoplasms known to metastasize to the thyroid include malignant melanoma, lymphoma," and leiomyosarcoma." Gastric carcinoma is yet another source of metastasis to the thyroid." Secondary carcinomas of colorectal origin are rare. 2 •9- 11 Recent reports revealed that the prevalence of metastatic involvement of the thyroid is more frequent than has been previously appreciated. 12.13 These studies used the fine-needle aspiration technique
(FNA) and showed that metastases to the thyroid could be diagnosed with great accuracy. However, several studies emphasize that FNA may not yield diagnostic material in cases such as the present one, where tumor is diffuse, accompanied by productive fibrosis.5.9.12.13 In our case, the conventional FNA did not disclose the nature of the tumor and since suspicious cold nodules of the thyroid are routinely excised," the patient underwent thyroidectomy. The workup of our case included light microscopy, immunohistochemical staining, and ultramicroscopy. Our case was negative for both thyroglobulin and calcitonin, whereas cytokeratin and CEA positivity suggested the possibility of colon adenocarcinoma." It is worth remembering that primary mucinous carcinoma of the thyroid is a recognized entity," and has to be distinguished from a secondary mucinous carcinoma. Ultrastructurally, primary mucinous thyroid carcinoma shows evidence of both colloid and mucin secretion by the same neoplastic cell," in contrast to the case presented here, in which only mucin granules were found. Metastasis to the thyroid gland may appear many years after the removal of the primary tumor,":" as happened in our case 8 years after resection of the primary. In these cases, the thyroid nodules may be the only remains of the primary malignant disease. Prompt di-
468 Case Reports
agnosis of a secondary thyroid tumor and its surgical removal may render some degree of palliation to the patient. 4,8 The prolonged history in our patient with metastasis to various organs demonstrate how common cancer can behave in an unpredictable way. In summary, metastatic disease must be considered in the differential diagnosis of solitary cold nodules of the thyroid. In cases in which primary tumor can not be differentiated from a primary one by FNA alone, excisional biopsy and meticulous histologic study, including light microscopy, immunohistochemical staining and electron microscopy, will be required to establish the correct diagnosis. REFERENCES
I, Rosen Y, Rosenblatt P, Saltzman E. Intraoperative pathologic diagnosis of thyroid neoplasms. Report on experience with 504 specimens. Cancer 1990;66:2001-6. 2. Katsutaro S, Sokal JE, Pickren JW. Metastatic neoplasms in the thyroid gland: pathological and clinical findings. Cancer 1962;15:557-65. 3. Meissner W, Warren S. Tumors of the thyroid gland. In: Firminger H, ed. Atlas of tumor pathology. 2nd series. Washington D.C.: Armed Forces Institute of Pathology, 1969:127-9. 4. Schroder S, Burk CG, de-Heer K. Metastases to the thyroid gland-morphology and clinical aspects of 25 secondary thyroid neoplasms. Langenbecks Arch Chir 1987;370:25-35. 5. Schroder S, Boeker W. Clear-cell carcinomas of thyroid gland: a clinicopathological study of 13 cases. Histopathology 1986;10:75-89. 6. Takashima S, Saeki H, Moriwaki S, Yamamoto Y. An autopsy case of metastatic thyroid tumor. Gan No Rinsho 1984;30: 880-4.
OlolaryngologyHead and Neck Surgery
7. Cruickshank Je. Leiomyosarcoma metastatic to the thyroid gland. Ear Nose Throat J 1988;67:899-900,902,904. 8. Yoshida A, Imamura A, Tanaka H, et al. A case of metastatis from gastric cancer to the thyroid gland. J Jpn Surg 1989;19: 480-4. 9. Cristal1ini EG, Balis GB, Francucci M. Diagnosis of thyroid metastasis of colonic adenocarcinoma by fine needle aspiration biopsy. Acta Cytol 1990;34:363-5. 10. Lertprasertsuke N, Kakudo K, Satoh S, Tada N, Osamura Y. Rectal carcinoid tumor metastasizing to the thyroid and pancreas. An autopsy case exploiting immunohistochemistry for differentiation from tumors involving multiple endocrine organs. Acta Pathol Jpn 1990;40:352-60. II. Lester JW Jr, Carter MP, Berens SV, Long RF, Caplan GE. Colon carcinoma metastatic to the thyroid gland. Clin Nucl Med 1986;11:634-5. 12. Watts NB. Carcinoma metastatic to the thyroid: prevalence and diagnosis by fine-needle aspiration cytology. Am J Med Sci 1987;293:13-7. 13. Smith SA, Gharib H, Goellner JR. Fine-needle aspiration. Usefulness for diagnosis and management of metastatic carcinoma to the thyroid. Arch Int Med 1987;147:311-2. 14. Mazzaferri EL. Management of thyroid neoplasms. In: Cummings CW, Fredrickson JM, Harker LA, Krause CJ, Schuller DE, eds. Otolaryngology-head and neck surgery. Update 2. SI. Louis: The C.Y. Mosby Co., 1990:224-60. 15. Primus FJ, Clark CA, Goldenberg OM. Immunohistochemical detection of carcinoembryonic antigen. In: Delellis RA, ed. Diagnostic immunohistochemistry. Masson monographs in diagnostic pathology. New York: Masson Publishing USA Inc., 1981:263-76. 16. Deligdisch L, Subhani Z, Gordon RE. Primary mucinous carcinoma of the thyroid gland. Report of a case and ultrastructural study. Cancer 1980;45:2564-7.
