FOLLICULAR CARCINOMA OF THE=THYROiD WITH METASTASIS TOTHE BREASTReginald C. Chisholm, MD, E. B. Chung, MD, PhD, Wayne Tuckson, Tarig Khan, MD, andJack E. White, MDWashington, DC

A 75-year-old woman with two previous neckoperations for follicular carcinoma of thethyroid presented with a breast mass nineyears after diagnosis. The mass recurred onemonth after excisional biopsy. Pathologicalexamination revealed metastatic follicularcarcinoma. The breast tumor was weakly pos-itive for estrogen receptor and positive forprogesterone receptor. Recurrences in theneck and breast were resected. Residual dis-ease in the neck and metastasis to the lungswere resolved by 1311 ablative therapy. Previ-ous reports of thyroid metastasis to the breastwere described as papillary carcinoma. Thisreport describes a rare site of metastasis andbriefly reviews the pathology, diagnosis, andmanagement of thyroid carcinoma.

Carcinoma of the thyroid is a rare disease with agood prognosis and long patient survival. Ninethousand new cases in the United States are esti-mated for 1980 and approximately 1,000 deaths.'In England, the incidence of thyroid cancer is es-timated to be about 0.7 percent of all cancers inwomen and 0.2 percent in men.2 Age-specific ratesincrease with age and the tumor is more commonin women than men. The incidence is less in blacksthan in whites.3 Regional lymph nodes are the

Requests for reprints should be addressed to Dr. ReginaldC. Chisholm, Medical Oncology Section, Department ofMedicine, Howard University, Washington, DC 20059.

most common site of metastasis. Other commonsites are bone, liver, kidneys, and braifl.4 Mostthyroid cancers grow slowly. Recurrences ormetastasis may take several years or even decadesto develop.

Reports in the literature of metastasis of thyroidcarcinoma to the breast are sparse.45 The casepresented here relates the clinical course of a pa-tient with follicular carcinoma of the thyroid, whodeveloped metastasis to the breast seven yearsafter resection of the thyroid tumor. To the au-thors' knowledge this is the first detailed docu-mentation of metastatic follicular carcinoma of thethyroid to the breast.

CASE REPORTA 75-year-old black woman was admitted to

Howard University Hospital in June 1979 with alarge mass in the right breast. A 4 x 5 cm mass inthe upper inner quadrant of the right breast wasfirst detected during a clinic visit in May 1979. Anexcisional biopsy at that time revealed metastaticfollicular carcinoma. The tumor mass recurred onemonth after excision.

The patient's past history revealed that she hada subtotal thyroidectomy for a thyroid mass nineyears previously in July 1970. The diagnosis wasfollicular adenoma of borderline malignancy. Amass in the right lobe of the thyroid, and two pal-pable adjacent right anterior cervical lymph nodeswere detected in December 1976. A near totalthyroidectomy with modified right radical neckdissection was performed. A diagnosis of follicular

JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 72, NO. 11, 1980 1101

METASTATIC THYROID CARCINOMA

Figure 1. Oxyphilic type of follicular carcinoma of thyroid with capsular andvascular invasion

carcihoma was made (Figure 1). Six lymph nodeswere found and all were negative for tumor metas-tasis. Radiotherapy, radioactive iodine therapy,and thyroid replacement or suppressive therapywere not employed.On admission to the hospital in June 1979, the

patient complained of hoarseness, productivecough of whitish sputum, dysphagia, and progres-sive weight loss. Significant findings on physicalexamination included a 1.5 x 2 cm node in the areaof the left lobe of the thyroid and several nodulesin the left anterior cervical lymph chain. Therewas coarse nodularity over the scar from previousthyroid surgery. A firm mass, partially fixed to thechest wall, occupied the entire right breast. Noaxillary nodes were palpated. Examination of thelungs and heart were unremarkable. The remain-der of the physical examination was essentiallynormal. The white blood cell count was 10,000mm3, Hb 9.8 gm/100 ml, Hct 28%. The anemia wasnormochromic normocytic. Thyroid function andliver function studies were normal. Chest x-ray

showed no evidence of metastasis. Xeromammo-gram of the opposite breast demonstrated no ab-normalities. Resection of the thyroid mass, amodified left neck dissection and a simple mastec-tomy were done. Pathologic examination revealeda recurrent follicular carcinoma of the thyroid, in-volving skeletal muscle and skin, and metastaticfollicular carcinoma in the breast (Figure 2). Es-trogen receptor assay on the breast tumor wasweakly positive (7.5 femto-moles/mg protein) andprogesterone receptor assay was positive (42femto-moles/mg protein). One month later, afterthree days of exogenous thyroid stimulating hor-mone (TSH), 10 units intramuscularly daily, a 1311total body scan revealed residual uptake in the neckand significant uptake over both lung fields. Atherapeutic dose ofradioactive iodine, 100 mCi 1311,was administered. Replacement therapy consistedof 0.1 to 0.2 mg of levothyroxine (Synthyroid).

Six months later, repeat 1311 total body scanshowed disappearance of all activity over the lungfields indicating a response of the metastasis to the

1102 JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 72, NO. 11, 1980

METASTATIC THYROID CARCINOMA

. . :~~~~~~~VI

Figure 2. Metastatic follicular carcinoma involving the breast. (A) Atrophic mammary lobule and a dilatedduct are shown on the left. (B) Different area of the breast t4mor depicting follicles containing colloid(arrows)

radioactive iodine therapy. The patient continuesto improve without significant signs of recurrenceof metastasis.

DISCUSSIONThe major histologic types of thyroid carcinoma

are of papillary, follicular, mixed papillary-folli-cular, medullary, and undifferentiated carcinoma.The miscellaneous group includes squamous cell,malignant lymphoma, plasmacytoma, and sar-coma. Pure papillary or follicular carcinomas arerare.4 Most of these tumors are mixed, with onepredominant histologic type making up most of thetumor. Prognosis in thyroid carcinoma is related tothe age of the patient, the histologic type of tumor,and, in most tumors, the size and extent of thelesion. In general, patients under age 35 have a

better prognosis. Patients with papillary carci-noma have a good prognosis.

Follicular carcinoma accounts for about 15 per-cent of all thyroid cancers. The tumor tends to beencapsulated and spread by vascular invasion.The most common sites of metastasis are the lungsand the bones. Unlike papillary carcinoma thistumor rarely spreads to lymph nodes. Metastasisto lymph nodes have been reported to vary from 2to 10 percent in follicular carcino'ma and from 40 to70 percent in papillary carcinoma'.46 In contrast topapillary carcinoma, the size of the primary lesiondoes not influence prognosis.6 The tumor concen-trates 1311 avidly. Soft tissue lesions respond betterthan bone metastasis. Metastases which concen-trate '3'I respond well to ablative doses ofradioactive iodine.

At present, the recommended treatment for fol-licular carcinoma of the thyroid is total thyroidec-

JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 72, NO. 11, 1980 1103

METASTATIC THYROID CARCINOMA

tomy, or near-total thyroidectomy, which consistsof total lobectomy on the side of the cancer andpartial lobectomy, leaving the posterior capsule in-tact, on the contralateral side.7 Retention of theposterior capsule preserves viable thyroid tissueand avoids the risk of recurrent nerve injury.Lymph node dissection is only attempted whennodes are clinically palpable. Residual disease inthe neck, recurrent or metastatic follicular carci-noma, is diagnosed by obtaining a total body scanutilizing 2-5 mCi 131j. Detected disease is treatedwith ablative doses of 100-200 mCi 1311.8,9 How-ever, distant metastasis can only be treated effec-tively if all normal tissue has been ablated. Afterablation, the patient is placed on adequate re-placement therapy, which -also suppresses TSH,an important growth factor for thyroid follicularcells in most cases of differentiated follicular andpapillary carcinoma. Chemotherapy and radio-therapy are usually reserved for disease refractoryto radioiodine or thyroid hormone therapy.Adriamycin appears to be an active agent for pro-gressive metastasis.10

Most target tissues in the endocrine systemhave hormone receptors. Hormone receptors areproteins which contain sites to which hormonescan bind. The binding alters the receptors whichsubsequently mediate various cellular actions.Three types of hormone receptors have been de-scribed.11 One type has specific receptors onplasma membrane surfaces, for peptide hormonesand releasing factors. The receptors for steroidhormones are found in the cytoplasm. The thirdtype is exemplified by thyroid hormones whichhave intracellular binding sites found in the nu-clear chromatin of target cells. TSH interacts withspecific TSH receptors and the cell membrane ofthe thyroid12 activates adenylate cyclase and in-creases cyclic adenosine monophosphate (AMP)formation. TSH also stimulates functioning metas-tatic thyroid lesions. In this patient, estrogen re-ceptor assay was weakly positive and progester-one receptor definitely positive. The role of estro-gen and progesterone receptors in functioningthyroid metastasis is not known. The use of non-thyroid hormone therapy in estrogen positive re-ceptor metastatic thyroid lesions has not beendocumented in the literature.

Breast5 and skin are sites rare for thyroidmetastasis. Metastatic lesions to the thyroid aremore common and most frequently arise from

breast and kidney.4 Reports in the literature ofthyroid metastasis to the breast have all been de-scribed as papillary carcinoma. To the authors'knowledge there are no reports of follicular carci-noma of the thyroid metastasizing to the breast.The rare site described here should alert the phy-sician to include this in the differential diagnosis,especially in an elderly patient with a breast massand a previous history of follicular carcinoma ofthe thyroid.

AcknowledgementsThe authors are grateful to Dr. Suresh Mohla and his

technical staff for the hormonal receptor evaluations.

Literature Cited1. Silverberg E: Cancer statistics, 1979. Ca 29:6-45,

19792. Alagaratnam TT, Ong GB: Carcinoma of the thyroid.

Br J Surg 66:558-561, 19793. Moseley EL, Chung EB, Rogers N, et al: Thyroid

carcinoma in black patients. J NatI Med Assoc 70:915-918,1978

4. del Regato JA, Spjut HJ: Tumors of the thyroidgland. In Ackerman L, del Regato J (eds): Cancer Diag-nosis, Treatment and Prognosis. St. Louis, CV Mosby, 1977,pp 410-424

5. Dailey ME, Mayo SH, Lindsay S: Carcinoma of thethyroid gland: A clinical and pathologic study. Am J Med 9:194-199, 1950

6. Mazzaferri EL, Young RL, Ortell JE, et al: Papillarythyroid carcinoma: The impact of therapy in 576 patients.Medicine 56:171-196, 1977

7. Figg MD, Bratt HJ, VanVilet PD, et al: Thyroidcancer: Diagnosis and management based on review of 142cases. Am J Surg 135:671-674, 1978

8. Blahd WA: Treatment of malignant thyroid disease.Semin Nucl Med 9:95-99, 1979

9. Beierwaltes WH: The treatment of thyroid carci-noma with radioactive iodine. Semin NucI Med 8:79-94,1978

10. Gottlieb JA, Hill CS: Chemotherapy of thy-roid cancer with adriamycin. N EngI J Med 290:193-197,1974

11. Baxter JD, Funder JW: Hormone receptors. N EngI JMed 301 :1149-1160, 1979

12. Ichikawa T, Saito E: Presence of TSH receptor inthyroid neoplasm. J Clin Endocrinol Metabol 42:395-401,1976

1104 JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 72, NO. 11, 1980