Solitary thyroid metastasis from
clear-cell renal carcinoma P. Madore, md,
m
sc, frcs; S.
Lan, mb,
Summary: A 56-year-old woman underwent nephrectomy because of clear-cell renal carcinoma. Seven years later a solitary thyroid metastasis was detected. She is alive and well 17 months after thyroidectomy. The rarity of this manifestation is well known but its explanation is not clear. The long metastasis-free interval, a characteristic shared by other hormonally dependent neoplasms, has been explained in part by the concept of "dormant cells", which do not undergo division. The stimulus that provokes these cells into division is at present not known. Resume: Un cas de metastase solitaire de la thyroide a partir d'un carcinome renal a cellules claires Une femme de 58
ans avait subi une un carcinome renal a cellules claires. ans tard on decela une metastase
nephrectomie pour
Sept
plus thyroidienne solitaire. Apres thyroldectomie
elle a survecu et est bien portante 17 mois apres cette operation. On connait bien la rarete de cette manifestation, mais on ne se I'explique guere. On a bien tente d'expliquer ce long intervalle exempt de metastase, qu'on rencontre du reste dans d'autres
ch
b, ph d
Both lobes of the thyroid gland were sought in the thyroid gland.4 conspicuously enlarged. Over the lower thyroid may be the only biologically active manifes¬ half of the left lobe was a round, 3.5-cm which moved with the thyroid tation of the neoplastic state and there¬ hard mass on swallowing. No other distinct gland fore surgical extirpation is indicated, nodules were detectable. Her temperature as in the following case. was normal, pulse rate 80 beats/min and
posits
are
However,
metastases in the
Case report A
58-year-old obese (97 kg) white wom¬ a right nephrectomy at St. Mary's Hospital, Montreal in 1966 for renal carcinoma. The kidney measured 9 x 5 x 3 cm. When it was sectioned a soft, yellowish-orange area 4 cm in dia¬ meter was noted near the lower pole. The cortex and medulla were well demarcated. Microscopic examination re¬ vealed that normal tissue in the involved area was completely replaced by sheets of cells with clear cytoplasm and a small, central, darkly staining nucleus. The blood vessels were free of tumour cells. The capsule was intact (Fig. 1). During this admission the thyroid gland was noted to be diffusely enlarged. Protein-bound iodine value was 6.1 $xg/dl and total iodine 7.9 mg/dl, both normal values. She remained well until October 1973, when she first discovered that the left side of the "goitre" was becoming larger and that swallowing and turning her head to an
underwent
the left caused discomfort. There
was no
temperature^ intolerance and there were no other signs of thyroid disease. She was admitted to hospital.
regular, blood pressure 150/100 mm Hg. She was still obese, weighing 97 kg. Laboratory investigation on admission revealed the following values: hemoglobin, 12 g/dl; plasma glucose, 235 mg/dl; blood urea nitrogen, 16 mg/dl; serum creatinine, 1.0 mg/dl; serum tetraiodothyronine (T4), 8.7 jjLg/dl (normal, 4 to 11 jxg/dl); triiodothyronine (T3) resin uptake, 29.6% (normal, 23 to 35%). A thyroid scan with iodine 131 revealed a multinodular goitre with a large cold area in the left lobe. The electrocardiogram revealed mild ischemia. The chest radiograph showed emphysema¬ tous changes in the lungs and a slightly enlarged heart. Bone scan and skeletal survey were normal. The patient underwent thyroidectomy with total removal of the left lobe, which extended 2 cm below the level of the suprasternal notch, and subtotal removal of the right lobe. The left lobe contained a well circumscribed lesion (dimensions, 4x3x3 cm); microscopy (Fig. 2) revealed cords of polygonal cells with clear cyto¬ plasm and small, dense nuclei. The tumour was surrounded by a fibrous pseudocapsule, broken in areas by invading tumour. The remainder of the gland was multi-
neoplasmes hormono-dependants, en basant en partie sur le concept des "cellules latents", qui ne se divisent pas automatiquement. On ne connait se
pas presentement la nature du stimulus
qui declenche la division de ces cellules. Metastasis of clear-cell renal carcinoma
the thyroid gland discovered during the lifetime of the patient is relatively rare. Friberg and Kinnman1 in 1969 found only 28 reported cases, to which they added 4 cases of their own, and Alfthan and Michelsson2 added a fur¬ ther case. The incidence of metastasis of renal carcinoma to the thyroid discovered at autopsy is much higher; Shimaoka, Sokal and Pickren3 in 1962 found this to be as high as 12%. The incidence is probably dependent on the thoroughness with which metastatic deto
From the
department of surgery, St. Mary's Hospital, Montreal and McGill University Reprint requests to: Dr. P. Madore, Department of surgery, St. Mary's Hospital, Montreal, Que. H3T 1M5
FIG. 1.Clear-cell carcinoma in
(hematoxylin-eosin; x480).
kidney
FIG. 2.Clear-cell carcinoma. Metastasis
(R) compressing adjacent thyroid
follicles (T) (hematoxylin-eosin x225).
CMA JOURNAL/MARCH 22, 1975/VOL. 112 719
new .Stemetil 'Spansule' Capsules 10 mg for continuous, dependable anti-emetic action Indication: nausea and vomiting due to stimulation of the chemoreceptor trigger zone. Dosage: one or two 10 mg 'Spansule' Capsules every twelve hours. This dosage may be increased as required by increments of 10 mg every 2 or 3 days until symptoms are controlled. For maintenance therapy the dosage should be reduced to the minimum effective dose. Because of the lower pediatric dosage requirements, the 'Spansule' Capsules are not intended for use in children. Contraindications: Comatose or deeply depressed states of the CNS due to hypnotics, analgesics, narcotics, alcohol, etc.; hypersensitivity to phenothiazines; blood dyscrasias; bone marrow depression; liver damage.
Warnings and precautions: etiology of vomiting should be established before using the drug as its antiemetic action may mask symptoms of intracranial pressure or intestinal obstruction. Patients with a history of convulsive disorders should be given an appropriate anticonvulsant while on therapy. Tardive dyskinesia may occur In patients on long-term therapy. If used with CNS depressants, the possibility of an additive effect should be considered. Use with great caution in patients with glaucoma or prostatic hypertrophy. The drug may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery, especially during the first few days of therapy. Keep in mind that all medications should be used cautiously in pregnant patients, especially during the first trimester. Side effects: extrapyramidal reactions, disturbed temperature regulation and seizures have been encountered. Other side effects due to phenothiazine derivatives should be borne in mind; for complete list, see product monograph. Overdosage: no specific antidote; symptomatic treatment. If a pressor agent is required, norepinephrlne may be given (not epinephrine as it may further depress the blood pressure).
nodular in appearance and did not contain tumour. The postoperative course was uneventful and the patient was discharged on levothyroxine, 0.2 mg daily. The diabetes was controlled with appropriate diet. The patient has remained well for 17 months after the operation, with no further evidence of metastasis or local recurrence.
Discussion The reason for the rarity of metastatic deposits in the thyroid gland is not known. Possible contributing factors include (a) the sieve-like action of the lungs; (b) the large blood flow through the thyroid, which prevents seeding; (c) the high oxygen tension in normal thyroid tissue (a low oxygen tension favouring the growth of malignant cells);5 and (d) the high iodine concentration in the gland. In most of the previous cases, as in the present case, deposits were found in abnormal glands.1 This may be related to a change in oxygen tension and blood flow in the abnormal areas of the gland.6 The clinical course of renal adenocarcinoma is frequently one of slow progression with late development of metastases. In the cases recorded with metastasis to the thyroid, for example, the interval between the detection of the primary tumour and the development of clinically manifest metastases ranged from 3 to 23 years.1 In our case the interval was 7 years. The protracted time interval is one of the bizarre characteristics of renal adenocarcinoma, which it shares with neoplasms that
are hormonally dependent, such as those in the breast and prostate. These long metastasis-free intervals have been explained in part by the concept of "dormant cells", which do not undergo division.7 The stimulus that provokes these cells to divide and form rapidly enlarging metastatic deposits is at present not known. References 1. FRIBERO S JE, KINNMAN J: Renal adenocarcinoma with metastases to the thyroid gland. Acta Otolaryngol (Stockh) 67: 552, 1969 2. ALFTHAN 0, MIcHELssoN JE: Late metastases of renal cell carcinoma to the thyroid gland. Ann Chir Gynaecol Fenn 58: 339, 1969 3. SHiMAOKA K, SOKAL JE, PICKREN JW: Meta-
4. 5. 6. 7.
static neoplasms in the thyroid gland: pathological and clinical findings. Cancer 15: 557, 1962 Ricit CO: Microscopic metastases in the thyroid gland. Am J Pathol 10: 407, 1934 WARBURO 0: Versuche an uberlebendem Carcinomgewebe (Methoden). Biochem Ztschr (Berlin) 142: 317, 1923 JOHNSON N: Blood supply of thyroid gland: nodular gland. Aust NZ J Surg 23: 241, 1954 HADF5ELD G: The dormant cancer cell. Br Med J 2: 607, 1954
'Slow-K
tablets are the only satisfactory method of giving potassium by mouth"2 Brief Prescribing information Indications - All circumstances in which potassium supplementation is necessary, and particularly during prolonged or intensive diuretic therapy. Patients at special risk are those with advanced hepatic cirrhosis or renal disease, patients with considerable edema (particularly if urinary output is large), patients on a salt-restricted diet and patients receiving digitalis (a lack of potassium sensitizes the myocardium to the toxic effects of digitalis). The range of indications for SLOW-K may be summarized as follows: As a supplement to diuretics Hypochloremic alkalosis Cushing's Syndrome Steroid therapy Liver cirrhosis Diseases characterized by persistent vomiting or diarrhea
Digitalis therapy Steatorrhea Chronic diarrhea Regional ileitis Ileostomy Neoplasms or obstructions referable to the gastrointestinal tract Ulcerative colitis
Dosage - The dosage is determined according to the needs of the individual patient. When administered as a potassium supplement during diuretic therapy, a dose ratio of one SLOW-K tablet with each diuretic tablet will usually suffice, but may be increased as necessary. In general, a dosage range between 2-6 SLOW-K tablets (approximately 16-48 mEq K +) daily, or on alternate days, will provide adequate supplementary potassium in most cases. Preferably, administer after meals. Warning - A probable association exists between the use of coated tablets containing potassium salts, with or without thiazide diuretics, and the incidence of serious small bowel ulceration. Such preparations should be used only when adequate dietary supplementation is not practical, and should be discontinued if abdominal pain, distention, nausea, vomiting or gastro-intestinal bleeding occurs. Side Effect - To date, only three cases of small bowel ulceration, one of which is of doubtful origin, have been reported. Cautions - Administer cautiously to patients in advanced renal failure to avoid possible hyperkalemia. Slow-K should be used with caution in diseases associated with heart block since increased serum potassium may increase the degree of block. Contraindications - Renal impairment with oliguria or azotemia, untreated Addison's Disease, myotonia congenita, hyperadrenalism associated with adrenogen ital syndrome, acute dehyd ration, heat cramps and hyperkalemia of any etiology; conditions associated with statis of the GI tract. Suppiled - Tablets (pale orange, sugar coated), each containing 600 mg. of potassium chloride in a slow-release, inert wax core; bottles of 100, 1,000 and 5,000.
References 1. Leading Article, Brit. Med. J., 1,191, 1967 (April 22). 2. ODriscoll, B.J.: Potassium Chloride with Diuretics, Br. Med. J., Vol. 11, pg. 348,1966.
Complete information upon request MEMBER
CIBA
DORvAL, OUEBEC H951B1
C-4073
CMA JOURNAL/MARCH 22, 1975/VOL. 112 721
clear-cell renal carcinoma P. Madore, md,
m
sc, frcs; S.
Lan, mb,
Summary: A 56-year-old woman underwent nephrectomy because of clear-cell renal carcinoma. Seven years later a solitary thyroid metastasis was detected. She is alive and well 17 months after thyroidectomy. The rarity of this manifestation is well known but its explanation is not clear. The long metastasis-free interval, a characteristic shared by other hormonally dependent neoplasms, has been explained in part by the concept of "dormant cells", which do not undergo division. The stimulus that provokes these cells into division is at present not known. Resume: Un cas de metastase solitaire de la thyroide a partir d'un carcinome renal a cellules claires Une femme de 58
ans avait subi une un carcinome renal a cellules claires. ans tard on decela une metastase
nephrectomie pour
Sept
plus thyroidienne solitaire. Apres thyroldectomie
elle a survecu et est bien portante 17 mois apres cette operation. On connait bien la rarete de cette manifestation, mais on ne se I'explique guere. On a bien tente d'expliquer ce long intervalle exempt de metastase, qu'on rencontre du reste dans d'autres
ch
b, ph d
Both lobes of the thyroid gland were sought in the thyroid gland.4 conspicuously enlarged. Over the lower thyroid may be the only biologically active manifes¬ half of the left lobe was a round, 3.5-cm which moved with the thyroid tation of the neoplastic state and there¬ hard mass on swallowing. No other distinct gland fore surgical extirpation is indicated, nodules were detectable. Her temperature as in the following case. was normal, pulse rate 80 beats/min and
posits
are
However,
metastases in the
Case report A
58-year-old obese (97 kg) white wom¬ a right nephrectomy at St. Mary's Hospital, Montreal in 1966 for renal carcinoma. The kidney measured 9 x 5 x 3 cm. When it was sectioned a soft, yellowish-orange area 4 cm in dia¬ meter was noted near the lower pole. The cortex and medulla were well demarcated. Microscopic examination re¬ vealed that normal tissue in the involved area was completely replaced by sheets of cells with clear cytoplasm and a small, central, darkly staining nucleus. The blood vessels were free of tumour cells. The capsule was intact (Fig. 1). During this admission the thyroid gland was noted to be diffusely enlarged. Protein-bound iodine value was 6.1 $xg/dl and total iodine 7.9 mg/dl, both normal values. She remained well until October 1973, when she first discovered that the left side of the "goitre" was becoming larger and that swallowing and turning her head to an
underwent
the left caused discomfort. There
was no
temperature^ intolerance and there were no other signs of thyroid disease. She was admitted to hospital.
regular, blood pressure 150/100 mm Hg. She was still obese, weighing 97 kg. Laboratory investigation on admission revealed the following values: hemoglobin, 12 g/dl; plasma glucose, 235 mg/dl; blood urea nitrogen, 16 mg/dl; serum creatinine, 1.0 mg/dl; serum tetraiodothyronine (T4), 8.7 jjLg/dl (normal, 4 to 11 jxg/dl); triiodothyronine (T3) resin uptake, 29.6% (normal, 23 to 35%). A thyroid scan with iodine 131 revealed a multinodular goitre with a large cold area in the left lobe. The electrocardiogram revealed mild ischemia. The chest radiograph showed emphysema¬ tous changes in the lungs and a slightly enlarged heart. Bone scan and skeletal survey were normal. The patient underwent thyroidectomy with total removal of the left lobe, which extended 2 cm below the level of the suprasternal notch, and subtotal removal of the right lobe. The left lobe contained a well circumscribed lesion (dimensions, 4x3x3 cm); microscopy (Fig. 2) revealed cords of polygonal cells with clear cyto¬ plasm and small, dense nuclei. The tumour was surrounded by a fibrous pseudocapsule, broken in areas by invading tumour. The remainder of the gland was multi-
neoplasmes hormono-dependants, en basant en partie sur le concept des "cellules latents", qui ne se divisent pas automatiquement. On ne connait se
pas presentement la nature du stimulus
qui declenche la division de ces cellules. Metastasis of clear-cell renal carcinoma
the thyroid gland discovered during the lifetime of the patient is relatively rare. Friberg and Kinnman1 in 1969 found only 28 reported cases, to which they added 4 cases of their own, and Alfthan and Michelsson2 added a fur¬ ther case. The incidence of metastasis of renal carcinoma to the thyroid discovered at autopsy is much higher; Shimaoka, Sokal and Pickren3 in 1962 found this to be as high as 12%. The incidence is probably dependent on the thoroughness with which metastatic deto
From the
department of surgery, St. Mary's Hospital, Montreal and McGill University Reprint requests to: Dr. P. Madore, Department of surgery, St. Mary's Hospital, Montreal, Que. H3T 1M5
FIG. 1.Clear-cell carcinoma in
(hematoxylin-eosin; x480).
kidney
FIG. 2.Clear-cell carcinoma. Metastasis
(R) compressing adjacent thyroid
follicles (T) (hematoxylin-eosin x225).
CMA JOURNAL/MARCH 22, 1975/VOL. 112 719
new .Stemetil 'Spansule' Capsules 10 mg for continuous, dependable anti-emetic action Indication: nausea and vomiting due to stimulation of the chemoreceptor trigger zone. Dosage: one or two 10 mg 'Spansule' Capsules every twelve hours. This dosage may be increased as required by increments of 10 mg every 2 or 3 days until symptoms are controlled. For maintenance therapy the dosage should be reduced to the minimum effective dose. Because of the lower pediatric dosage requirements, the 'Spansule' Capsules are not intended for use in children. Contraindications: Comatose or deeply depressed states of the CNS due to hypnotics, analgesics, narcotics, alcohol, etc.; hypersensitivity to phenothiazines; blood dyscrasias; bone marrow depression; liver damage.
Warnings and precautions: etiology of vomiting should be established before using the drug as its antiemetic action may mask symptoms of intracranial pressure or intestinal obstruction. Patients with a history of convulsive disorders should be given an appropriate anticonvulsant while on therapy. Tardive dyskinesia may occur In patients on long-term therapy. If used with CNS depressants, the possibility of an additive effect should be considered. Use with great caution in patients with glaucoma or prostatic hypertrophy. The drug may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery, especially during the first few days of therapy. Keep in mind that all medications should be used cautiously in pregnant patients, especially during the first trimester. Side effects: extrapyramidal reactions, disturbed temperature regulation and seizures have been encountered. Other side effects due to phenothiazine derivatives should be borne in mind; for complete list, see product monograph. Overdosage: no specific antidote; symptomatic treatment. If a pressor agent is required, norepinephrlne may be given (not epinephrine as it may further depress the blood pressure).
nodular in appearance and did not contain tumour. The postoperative course was uneventful and the patient was discharged on levothyroxine, 0.2 mg daily. The diabetes was controlled with appropriate diet. The patient has remained well for 17 months after the operation, with no further evidence of metastasis or local recurrence.
Discussion The reason for the rarity of metastatic deposits in the thyroid gland is not known. Possible contributing factors include (a) the sieve-like action of the lungs; (b) the large blood flow through the thyroid, which prevents seeding; (c) the high oxygen tension in normal thyroid tissue (a low oxygen tension favouring the growth of malignant cells);5 and (d) the high iodine concentration in the gland. In most of the previous cases, as in the present case, deposits were found in abnormal glands.1 This may be related to a change in oxygen tension and blood flow in the abnormal areas of the gland.6 The clinical course of renal adenocarcinoma is frequently one of slow progression with late development of metastases. In the cases recorded with metastasis to the thyroid, for example, the interval between the detection of the primary tumour and the development of clinically manifest metastases ranged from 3 to 23 years.1 In our case the interval was 7 years. The protracted time interval is one of the bizarre characteristics of renal adenocarcinoma, which it shares with neoplasms that
are hormonally dependent, such as those in the breast and prostate. These long metastasis-free intervals have been explained in part by the concept of "dormant cells", which do not undergo division.7 The stimulus that provokes these cells to divide and form rapidly enlarging metastatic deposits is at present not known. References 1. FRIBERO S JE, KINNMAN J: Renal adenocarcinoma with metastases to the thyroid gland. Acta Otolaryngol (Stockh) 67: 552, 1969 2. ALFTHAN 0, MIcHELssoN JE: Late metastases of renal cell carcinoma to the thyroid gland. Ann Chir Gynaecol Fenn 58: 339, 1969 3. SHiMAOKA K, SOKAL JE, PICKREN JW: Meta-
4. 5. 6. 7.
static neoplasms in the thyroid gland: pathological and clinical findings. Cancer 15: 557, 1962 Ricit CO: Microscopic metastases in the thyroid gland. Am J Pathol 10: 407, 1934 WARBURO 0: Versuche an uberlebendem Carcinomgewebe (Methoden). Biochem Ztschr (Berlin) 142: 317, 1923 JOHNSON N: Blood supply of thyroid gland: nodular gland. Aust NZ J Surg 23: 241, 1954 HADF5ELD G: The dormant cancer cell. Br Med J 2: 607, 1954
'Slow-K
tablets are the only satisfactory method of giving potassium by mouth"2 Brief Prescribing information Indications - All circumstances in which potassium supplementation is necessary, and particularly during prolonged or intensive diuretic therapy. Patients at special risk are those with advanced hepatic cirrhosis or renal disease, patients with considerable edema (particularly if urinary output is large), patients on a salt-restricted diet and patients receiving digitalis (a lack of potassium sensitizes the myocardium to the toxic effects of digitalis). The range of indications for SLOW-K may be summarized as follows: As a supplement to diuretics Hypochloremic alkalosis Cushing's Syndrome Steroid therapy Liver cirrhosis Diseases characterized by persistent vomiting or diarrhea
Digitalis therapy Steatorrhea Chronic diarrhea Regional ileitis Ileostomy Neoplasms or obstructions referable to the gastrointestinal tract Ulcerative colitis
Dosage - The dosage is determined according to the needs of the individual patient. When administered as a potassium supplement during diuretic therapy, a dose ratio of one SLOW-K tablet with each diuretic tablet will usually suffice, but may be increased as necessary. In general, a dosage range between 2-6 SLOW-K tablets (approximately 16-48 mEq K +) daily, or on alternate days, will provide adequate supplementary potassium in most cases. Preferably, administer after meals. Warning - A probable association exists between the use of coated tablets containing potassium salts, with or without thiazide diuretics, and the incidence of serious small bowel ulceration. Such preparations should be used only when adequate dietary supplementation is not practical, and should be discontinued if abdominal pain, distention, nausea, vomiting or gastro-intestinal bleeding occurs. Side Effect - To date, only three cases of small bowel ulceration, one of which is of doubtful origin, have been reported. Cautions - Administer cautiously to patients in advanced renal failure to avoid possible hyperkalemia. Slow-K should be used with caution in diseases associated with heart block since increased serum potassium may increase the degree of block. Contraindications - Renal impairment with oliguria or azotemia, untreated Addison's Disease, myotonia congenita, hyperadrenalism associated with adrenogen ital syndrome, acute dehyd ration, heat cramps and hyperkalemia of any etiology; conditions associated with statis of the GI tract. Suppiled - Tablets (pale orange, sugar coated), each containing 600 mg. of potassium chloride in a slow-release, inert wax core; bottles of 100, 1,000 and 5,000.
References 1. Leading Article, Brit. Med. J., 1,191, 1967 (April 22). 2. ODriscoll, B.J.: Potassium Chloride with Diuretics, Br. Med. J., Vol. 11, pg. 348,1966.
Complete information upon request MEMBER
CIBA
DORvAL, OUEBEC H951B1
C-4073
CMA JOURNAL/MARCH 22, 1975/VOL. 112 721
