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A Thyroidectomy Case with a Surprising Pathologic Result: Three Different Birds in One Nest
A Thyroidectomy Case with a Surprising Pathologic Result: Three Different Birds in One Nest MEHLIKA ISILDAK, MD; DUYGU YAZGAN AKSOY, MD; AYSEN TERZI, MD; GAYE GULER TEZEL, MD, PHD; MIYASE BAYRAKTAR, MD
ABSTRACT: Neoplasms of the thyroid include types that range from indolent, localized papillary carcinomas to lethal anaplastic disease. Hurthle cell neoplasm is a histopathologic subtype that signals poor prognosis. Herein, we present the case of a 72-year-old female patient with multinodular goiter who, although fine needle aspiration biopsy revealed a benign result, underwent thyroid surgery because of the diameter of the largest nodule. Histopathologically, the neoplasm was diagnosed as papillary thyroid microcarcinoma on one lobe and Hurthle cell neoplasm on the other, whereas
the remainder of the thyroid showed a typical pattern of colloidal goiter, all of which are not commonly encountered in one patient. Although multinodular goiter is usually acknowledged as a sign of a benign process, its risk of malignancy is no less than that of a solitary thyroid nodule. The age of the patient, the duration of the disease, or the number of the nodules should not mislead the physician, nor affect the therapeutic approach. KEY INDEXING TERMS: Hurthle cell neoplasm; Papillary thyroid carcinoma; Multinodular goiter; Age. [Am J Med Sci 2006;331(2):97–99.]
T
nodes.4 Herein, we present the case of a patient with Hurthle cell neoplasm who underwent surgery and was diagnosed with a coincidental cancer of the thyroid gland in association with multinodular goiter.
hyroid carcinoma accounts for roughly 1% of all new malignant disease.1 Of these cases, 94% are differentiated thyroid carcinomas that derive from the follicular epithelial cells and are either papillary or follicular thyroid carcinomas. Neoplasms of the thyroid include types that range from indolent, localized papillary carcinomas to lethal anaplastic disease. Cytologic examination is the initial diagnostic procedure to readily diagnose papillary, medullary, and anaplastic carcinomas. This approach, however, is not satisfactory as far as the differentiation of follicular adenoma and follicular carcinoma is concerned, where histolopathogic examination is necessary.2 Hurthle cell neoplasm or oxyphilic variant of the follicular neoplasm is a histopathologic subtype that signals poor prognosis.3 These cells are characterized by a dense, eosinophilic granular cytoplasm and prominent nucleoli. Although nodal metastasis is rare for other types of follicular carcinoma, Hurthle cell neoplasm can spread to regional lymph From the Departments of Internal Medicine (MI, DYA, MB) and Pathology (AT, GGT), Section of Endocrinology and Metabolism, HaceHepe University, Ankara, Turkey. Submitted for publication April 6, 2005; accepted for publication September 25, 2005. Correspondence: Duygu Yazgan Aksoy, Angora Evleri Ruyalar Cad. Masal Sok., E-2 Bl. No:31 06530, Beysukent/Ankara/Turkey (E-mail: [email protected]). THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
Case Report A 72-year-old female patient with a lump on her neck was seen in our outpatient clinic. She had first recognized the mass about 10 years earlier and declined an operation for the lesion at that time. Fine-needle aspiration biopsies of the thyroid were made twice at the time of the diagnosis and both were unable to show any microscopic sign of malignancy. The patient was on L-thyroxine treatment for 10 years. She did not suffer from any symptoms of hypo- or hyperthyroidism. On physical examination, her thyroid gland was visibly large, especially on the right side, where a diffuse mass of 5 cm was palpated. The left lobe of the gland was irregular, with multiple nodules ranging in size from 10 to 20 mm. Other physical findings were unremarkable. Complete blood cell count, serum biochemistry, (including liver transaminases), and renal function test results were normal. Thyroid function test results and autoantibody results were within normal limits. Ultrasonographic examination of the thyroid gland revealed multiple heterogeneous nodules on both sides, the dimensions of the largest being 36 ⫻ 52 mm on the right and 19 ⫻ 20 mm on the left. After application of 2% prilocaine hydrochloride, an experienced endocrinologist aspirated thyroid tissue from both sides, including the largest nodule, with a 0.7 ⫻ 32 mm needle. On-site alcohol-fixed specimens were stained with Papanicolaou stain and were reported to have a small number of follicular epithelial cells, which were not atypical, with some macrophages and colloid material. The patient underwent thyroid surgery, since the nod-
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Thyroidectomy Case with Surprising Pathologic Result
Figure 1. Microscopic findings of the thyroid gland in the present case. The tumor is well encapsulated (A) (H&E, original magnification ⫻100) and characterized by cells with large eosinophilic granular cytoplasm (B) (H&E, original magnification ⫻200) in the right lobe. Papillary microcarcinoma in the left lobe (C) (H&E, original magnification ⫻100). Many of the nuclei showed prominent clearing and overlapping (D) (H&E, original magnification ⫻200).
ule dimension was larger than 3 cm. Total thyroidectomy was performed. Gross examination of the thyroidectomy specimen showed a well-circumscribed 6 cm yellow-brown nodule with a fibrous capsule located within the right lobe. Microscopically, the neoplasm was composed of cells characterized by an eosinophilic, granular cytoplasm and round to oval nuclei with coarse chromatin material. The neoplasm was composed mostly of solid areas with only a few foci of follicles. Secondary changes such as calcification and ischemic necrosis were also observed. Mitotic activity was inconspicuous. However, neoplastic cells pushing the capsule were seen. This nodule was considered to be a Hurthle cell neoplasm. On the other hand, macroscopic examination of the left lobe revealed a 6 mm tan-brown nodule. Histolopathogically, this neoplasm was diagnosed as papillary thyroid microcarcinoma, which had not been clinically suspected. The neoplasm was composed of follicles and papillae, which were lined by cells with nuclear clearing and grooves (Figure 1). Immunohistochemical studies showed that the neoplastic cells were positive for thyroglobulin and cytokeratin 19 (CK 19). The Hurthle cell nodule, on
the other hand, lacked cytokeratin expression. The remainder of the thyroid showed a typical pattern of colloidal goiter (Figure 2). Twenty days after the operation, the patient was recovering well and was receiving levothyroxine replacement treatment. Her serum thyroglobulin level, which was measured for the first time, was greater than 300 ng/mL. Owing to the suspicion of capsular invasion of the Hurthle cell neoplasm, 150 mCi radioactive iodine treatment was given. Six months after the radioactive iodine treatment, a total body scan of radioactive iodine showed no evidence of metastases.
Discussion Differentiated thyroid cancer is a rare disease with an annual prevalence rate ranging from 0.5 to 10 per 100,000 people in most countries. Male gender, history of previous head and neck radiation,
Figure 2. (A) Immunohistochemically, Hurthle cell neoplasm did not show expression of CK19 (IHC, original magnification ⫻100). (B) Cytoplasmic expression of the CK19 in the papillary microcarcinoma (IHC, original magnification ⫻200).
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family history of thyroid cancer or multiple endocrine neoplasia 2, and iodine deficiency are wellknown risk factors for thyroid cancer.5 Traditionally, the presence of multinodular goiter has been acknowledged as sign of a benign process. Nevertheless, it has been shown that malignancy risk in multinodular goiter is the same as the risk in solitary thyroid nodules; therefore, the possibility of malignancy should not be underestimated.6–8 Fine-needle aspiration biopsy is considered very precise for the diagnosis of papillary carcinoma of the thyroid.9 From a series of 10,039 fine needle aspiration biopsies of the thyroid gland, 1330 cases were aspirated involving two or more palpable nodules. In 103 cases (1%), two different pathologic processes were cytologically diagnosed. In 12 of the 103 patients, Hurthle cell neoplasms coincident with nodular goiter were diagnosed, all of which were determined to be adenomas after surgery. This study showed a statistically significant association between multinodularity and neoplasms.10 The coincidence of two different malignancies simultaneously developing in the same gland is not unusual in cases involving anaplastic thyroid cancer, which is usually seen together with foci of papillary or follicular carcinomas. Furthermore, an even closer relationship between papillary carcinoma and Hurthle cell tumors has been reported.11,12 Total thyroidectomy is the preferred surgical procedure for most patients with differentiated thyroid carcinomas. This argument is supported by a study that proved that papillary foci are seen in both lobes in 60% to 85% of the patients.13 In contrast to the rarity of differentiated thyroid cancer, occult thyroid carcinoma, meaning a clinically silent tumor with a diameter of less than 1 cm (mostly the papillary type) is present in as many as 2% to 36% of thyroid glands, according to autopsy studies.14 Although patient age itself is not a contraindication for major surgical procedures, few patients in the geriatric age group undergo thyroid surgery. There are few studies of elderly patients, but chronological age does not add an additional risk of morbidity if individual risk and benefit analysis, as well as careful preoperative evaluations, are properly done. Therefore, patient age should not be considered a factor influencing this therapeutic approach.15,16 Our case was one of the rare patients in the geriatric age group who simultaneously showed three different pathologic processes of the thyroid: multinodular goiter, Hurthle cell neoplasm, and occult focus of papillary thyroid cancer. Although the pathogenesis of these cancers is still obscure (which one developed from the other is debatable and they all may have developed independently), our experience showed
THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
that nesting of one relatively aggressive neoplasm and another silent neoplasm in the same tissue is possible. Total thyroidectomy should be the definitive approach in patients with large nodules regardless of the duration the disease, the age of the patient, and the number of nodules present. References 1. Figge J. Epidemiology of thyroid cancer. In: Wartofsky L, editor. Thyroid cancer: a comprehensive guide to clinical management. Ottawa: Humana Press;1999:77–83. 2. Sherman SI. Thyroid carcinoma. Lancet 2003;361:501–11. 3. Burman KD, Ringel MD, Wartofsky L. Unusual types of thyroid neoplasms. Endocrinol Metab Clin North Am 1996; 25:49–68. 4. Grant CS. Operative and postoperative management of the patient with follicular and Hurthle cell carcinoma. Surg Clin North Am 1995;75:395–403. 5. Jameson JL, Weetman AP. Disorders of the thyroid gland. In: Kasper DL, Wiener C, Fauci AS, editors. Harrison’s principles of internal medicine, 16th ed. New York: McGraw-Hill, 2005. p. 2123. 6. Rios A, Rodriguez JM, Canteras M, et al. Risk factors for malignancy in multinodular goitres. Eur J Surg Oncol 2004; 30:58–62. 7. Gandolfi PP, Frisina A, Raffa M, et al. The incidence of thyroid carcinoma in multinodular goiter: retrospective analysis. Acta Biomed Ateneo Parmense 2004;75:114–7. 8. Tollin SR, Mery GM, Jelveh N, et al. The use of fine needle-aspiration biopsy under ultrasound guidance to assess the risk of malignancy in patients with a multinodular goiter. Thyroid 2000;10:235–41. 9. Schlumberger MJ. Papillary and follicular thyroid carcinoma. N Engl J Med 1998;338:297–306. 10. Zeppa P, Benincasa G, Lucariello A, et al. Association of different pathologic processes of the thyroid gland in fine needle aspiration samples. Acta Cytol 2001;45:347–52. 11. Herrera MF, Hay ID, Wu PS, et al. Hurthle cell (oxyphilic) papillary thyroid carcinoma: a variant with more aggressive biological behavior. World J Surg 1992;16:669–74. 12. Zwi LJ, LiVolsi VA. Hurthle cell carcinoma arising from thyroid papillary carcinoma. Endocr Pathol 2002;13:213–7. 13. Dinneen SF, Valimaki MJ, Bergstrahl EJ, et al. Distant metastasis in papillary thyroid carcinoma: 100 cases observed in one instiution during 5 decades. J Clin Endocrinol Metab 1995;80:2041–5. 14. Ain KB. Papillary thyroid carcinoma: etiology, assessment and therapy. Endocrinol Metab Clin North Am 1995;24:711– 60. 15. van Tol KM, de Vries EG, Dullaart RPF, et al. Differentiated thyroid carcinoma in the elderly. Crit Rev Oncol Hematol 2001;38:79–91. 16. Passler C, Avanessian R, Kaczirek K, et al. Thyroid surgery in the geriatric patient. Arch Surg 2002;137:1243–8.
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ABSTRACT: Neoplasms of the thyroid include types that range from indolent, localized papillary carcinomas to lethal anaplastic disease. Hurthle cell neoplasm is a histopathologic subtype that signals poor prognosis. Herein, we present the case of a 72-year-old female patient with multinodular goiter who, although fine needle aspiration biopsy revealed a benign result, underwent thyroid surgery because of the diameter of the largest nodule. Histopathologically, the neoplasm was diagnosed as papillary thyroid microcarcinoma on one lobe and Hurthle cell neoplasm on the other, whereas
the remainder of the thyroid showed a typical pattern of colloidal goiter, all of which are not commonly encountered in one patient. Although multinodular goiter is usually acknowledged as a sign of a benign process, its risk of malignancy is no less than that of a solitary thyroid nodule. The age of the patient, the duration of the disease, or the number of the nodules should not mislead the physician, nor affect the therapeutic approach. KEY INDEXING TERMS: Hurthle cell neoplasm; Papillary thyroid carcinoma; Multinodular goiter; Age. [Am J Med Sci 2006;331(2):97–99.]
T
nodes.4 Herein, we present the case of a patient with Hurthle cell neoplasm who underwent surgery and was diagnosed with a coincidental cancer of the thyroid gland in association with multinodular goiter.
hyroid carcinoma accounts for roughly 1% of all new malignant disease.1 Of these cases, 94% are differentiated thyroid carcinomas that derive from the follicular epithelial cells and are either papillary or follicular thyroid carcinomas. Neoplasms of the thyroid include types that range from indolent, localized papillary carcinomas to lethal anaplastic disease. Cytologic examination is the initial diagnostic procedure to readily diagnose papillary, medullary, and anaplastic carcinomas. This approach, however, is not satisfactory as far as the differentiation of follicular adenoma and follicular carcinoma is concerned, where histolopathogic examination is necessary.2 Hurthle cell neoplasm or oxyphilic variant of the follicular neoplasm is a histopathologic subtype that signals poor prognosis.3 These cells are characterized by a dense, eosinophilic granular cytoplasm and prominent nucleoli. Although nodal metastasis is rare for other types of follicular carcinoma, Hurthle cell neoplasm can spread to regional lymph From the Departments of Internal Medicine (MI, DYA, MB) and Pathology (AT, GGT), Section of Endocrinology and Metabolism, HaceHepe University, Ankara, Turkey. Submitted for publication April 6, 2005; accepted for publication September 25, 2005. Correspondence: Duygu Yazgan Aksoy, Angora Evleri Ruyalar Cad. Masal Sok., E-2 Bl. No:31 06530, Beysukent/Ankara/Turkey (E-mail: [email protected]). THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
Case Report A 72-year-old female patient with a lump on her neck was seen in our outpatient clinic. She had first recognized the mass about 10 years earlier and declined an operation for the lesion at that time. Fine-needle aspiration biopsies of the thyroid were made twice at the time of the diagnosis and both were unable to show any microscopic sign of malignancy. The patient was on L-thyroxine treatment for 10 years. She did not suffer from any symptoms of hypo- or hyperthyroidism. On physical examination, her thyroid gland was visibly large, especially on the right side, where a diffuse mass of 5 cm was palpated. The left lobe of the gland was irregular, with multiple nodules ranging in size from 10 to 20 mm. Other physical findings were unremarkable. Complete blood cell count, serum biochemistry, (including liver transaminases), and renal function test results were normal. Thyroid function test results and autoantibody results were within normal limits. Ultrasonographic examination of the thyroid gland revealed multiple heterogeneous nodules on both sides, the dimensions of the largest being 36 ⫻ 52 mm on the right and 19 ⫻ 20 mm on the left. After application of 2% prilocaine hydrochloride, an experienced endocrinologist aspirated thyroid tissue from both sides, including the largest nodule, with a 0.7 ⫻ 32 mm needle. On-site alcohol-fixed specimens were stained with Papanicolaou stain and were reported to have a small number of follicular epithelial cells, which were not atypical, with some macrophages and colloid material. The patient underwent thyroid surgery, since the nod-
97
Thyroidectomy Case with Surprising Pathologic Result
Figure 1. Microscopic findings of the thyroid gland in the present case. The tumor is well encapsulated (A) (H&E, original magnification ⫻100) and characterized by cells with large eosinophilic granular cytoplasm (B) (H&E, original magnification ⫻200) in the right lobe. Papillary microcarcinoma in the left lobe (C) (H&E, original magnification ⫻100). Many of the nuclei showed prominent clearing and overlapping (D) (H&E, original magnification ⫻200).
ule dimension was larger than 3 cm. Total thyroidectomy was performed. Gross examination of the thyroidectomy specimen showed a well-circumscribed 6 cm yellow-brown nodule with a fibrous capsule located within the right lobe. Microscopically, the neoplasm was composed of cells characterized by an eosinophilic, granular cytoplasm and round to oval nuclei with coarse chromatin material. The neoplasm was composed mostly of solid areas with only a few foci of follicles. Secondary changes such as calcification and ischemic necrosis were also observed. Mitotic activity was inconspicuous. However, neoplastic cells pushing the capsule were seen. This nodule was considered to be a Hurthle cell neoplasm. On the other hand, macroscopic examination of the left lobe revealed a 6 mm tan-brown nodule. Histolopathogically, this neoplasm was diagnosed as papillary thyroid microcarcinoma, which had not been clinically suspected. The neoplasm was composed of follicles and papillae, which were lined by cells with nuclear clearing and grooves (Figure 1). Immunohistochemical studies showed that the neoplastic cells were positive for thyroglobulin and cytokeratin 19 (CK 19). The Hurthle cell nodule, on
the other hand, lacked cytokeratin expression. The remainder of the thyroid showed a typical pattern of colloidal goiter (Figure 2). Twenty days after the operation, the patient was recovering well and was receiving levothyroxine replacement treatment. Her serum thyroglobulin level, which was measured for the first time, was greater than 300 ng/mL. Owing to the suspicion of capsular invasion of the Hurthle cell neoplasm, 150 mCi radioactive iodine treatment was given. Six months after the radioactive iodine treatment, a total body scan of radioactive iodine showed no evidence of metastases.
Discussion Differentiated thyroid cancer is a rare disease with an annual prevalence rate ranging from 0.5 to 10 per 100,000 people in most countries. Male gender, history of previous head and neck radiation,
Figure 2. (A) Immunohistochemically, Hurthle cell neoplasm did not show expression of CK19 (IHC, original magnification ⫻100). (B) Cytoplasmic expression of the CK19 in the papillary microcarcinoma (IHC, original magnification ⫻200).
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February 2006 Volume 331 Number 2
Isildak et al
family history of thyroid cancer or multiple endocrine neoplasia 2, and iodine deficiency are wellknown risk factors for thyroid cancer.5 Traditionally, the presence of multinodular goiter has been acknowledged as sign of a benign process. Nevertheless, it has been shown that malignancy risk in multinodular goiter is the same as the risk in solitary thyroid nodules; therefore, the possibility of malignancy should not be underestimated.6–8 Fine-needle aspiration biopsy is considered very precise for the diagnosis of papillary carcinoma of the thyroid.9 From a series of 10,039 fine needle aspiration biopsies of the thyroid gland, 1330 cases were aspirated involving two or more palpable nodules. In 103 cases (1%), two different pathologic processes were cytologically diagnosed. In 12 of the 103 patients, Hurthle cell neoplasms coincident with nodular goiter were diagnosed, all of which were determined to be adenomas after surgery. This study showed a statistically significant association between multinodularity and neoplasms.10 The coincidence of two different malignancies simultaneously developing in the same gland is not unusual in cases involving anaplastic thyroid cancer, which is usually seen together with foci of papillary or follicular carcinomas. Furthermore, an even closer relationship between papillary carcinoma and Hurthle cell tumors has been reported.11,12 Total thyroidectomy is the preferred surgical procedure for most patients with differentiated thyroid carcinomas. This argument is supported by a study that proved that papillary foci are seen in both lobes in 60% to 85% of the patients.13 In contrast to the rarity of differentiated thyroid cancer, occult thyroid carcinoma, meaning a clinically silent tumor with a diameter of less than 1 cm (mostly the papillary type) is present in as many as 2% to 36% of thyroid glands, according to autopsy studies.14 Although patient age itself is not a contraindication for major surgical procedures, few patients in the geriatric age group undergo thyroid surgery. There are few studies of elderly patients, but chronological age does not add an additional risk of morbidity if individual risk and benefit analysis, as well as careful preoperative evaluations, are properly done. Therefore, patient age should not be considered a factor influencing this therapeutic approach.15,16 Our case was one of the rare patients in the geriatric age group who simultaneously showed three different pathologic processes of the thyroid: multinodular goiter, Hurthle cell neoplasm, and occult focus of papillary thyroid cancer. Although the pathogenesis of these cancers is still obscure (which one developed from the other is debatable and they all may have developed independently), our experience showed
THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
that nesting of one relatively aggressive neoplasm and another silent neoplasm in the same tissue is possible. Total thyroidectomy should be the definitive approach in patients with large nodules regardless of the duration the disease, the age of the patient, and the number of nodules present. References 1. Figge J. Epidemiology of thyroid cancer. In: Wartofsky L, editor. Thyroid cancer: a comprehensive guide to clinical management. Ottawa: Humana Press;1999:77–83. 2. Sherman SI. Thyroid carcinoma. Lancet 2003;361:501–11. 3. Burman KD, Ringel MD, Wartofsky L. Unusual types of thyroid neoplasms. Endocrinol Metab Clin North Am 1996; 25:49–68. 4. Grant CS. Operative and postoperative management of the patient with follicular and Hurthle cell carcinoma. Surg Clin North Am 1995;75:395–403. 5. Jameson JL, Weetman AP. Disorders of the thyroid gland. In: Kasper DL, Wiener C, Fauci AS, editors. Harrison’s principles of internal medicine, 16th ed. New York: McGraw-Hill, 2005. p. 2123. 6. Rios A, Rodriguez JM, Canteras M, et al. Risk factors for malignancy in multinodular goitres. Eur J Surg Oncol 2004; 30:58–62. 7. Gandolfi PP, Frisina A, Raffa M, et al. The incidence of thyroid carcinoma in multinodular goiter: retrospective analysis. Acta Biomed Ateneo Parmense 2004;75:114–7. 8. Tollin SR, Mery GM, Jelveh N, et al. The use of fine needle-aspiration biopsy under ultrasound guidance to assess the risk of malignancy in patients with a multinodular goiter. Thyroid 2000;10:235–41. 9. Schlumberger MJ. Papillary and follicular thyroid carcinoma. N Engl J Med 1998;338:297–306. 10. Zeppa P, Benincasa G, Lucariello A, et al. Association of different pathologic processes of the thyroid gland in fine needle aspiration samples. Acta Cytol 2001;45:347–52. 11. Herrera MF, Hay ID, Wu PS, et al. Hurthle cell (oxyphilic) papillary thyroid carcinoma: a variant with more aggressive biological behavior. World J Surg 1992;16:669–74. 12. Zwi LJ, LiVolsi VA. Hurthle cell carcinoma arising from thyroid papillary carcinoma. Endocr Pathol 2002;13:213–7. 13. Dinneen SF, Valimaki MJ, Bergstrahl EJ, et al. Distant metastasis in papillary thyroid carcinoma: 100 cases observed in one instiution during 5 decades. J Clin Endocrinol Metab 1995;80:2041–5. 14. Ain KB. Papillary thyroid carcinoma: etiology, assessment and therapy. Endocrinol Metab Clin North Am 1995;24:711– 60. 15. van Tol KM, de Vries EG, Dullaart RPF, et al. Differentiated thyroid carcinoma in the elderly. Crit Rev Oncol Hematol 2001;38:79–91. 16. Passler C, Avanessian R, Kaczirek K, et al. Thyroid surgery in the geriatric patient. Arch Surg 2002;137:1243–8.
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