p065 Artifacts, Anatomical and Physiological Variants, and Unrelated Diseases That Might Cause...

Artifacts, Anatomical and Physiological Variants, and Unrelated Diseases That Might Cause False-Positive

Whole-Body 131-I Scans in Patients With Thyroid Cancer

Brahm Shapiro, Vittoria Rufini, Ayman Jarwan, Onelio Geatti, Kimberlee J. Kearfott, Lorraine M. Fig, lan D. Kirkwood, and Milton D. Gross

The whole body 131-1 scan remains an important component in the postoperative t reatment of patients with well-differentiated thyroid cancer, Because normal thyroid tissue remnants and residual or metastatic loci of well-differentiated thyroid cancer have the unique abil i ty to concentrate, orgsnify, and store 131-1, the whole body scan provides a depiction of those tissues that can be ablated w i th therapeutic doses of 131-1. Over t ime, it has become obvious that the whole body scan may also reveal foci of 131-1 uptake owing to a wide variety of other causes. We provide a detailed pathophysiological classification of the artifacts, anatomic and physiological variants, and nonthyroidal diseases that may give rise to false-

positive whole body scans in postoperative patients w i th thyroid cancer. These include ectopic foci of normal thyroid tissue; nonthyroidal physiological sites (eg, choroid plexus, salivary glands, gastric mucosa, urinary tract); contamination by physiological sec- tions; ectopic gastric mucosa; other gastrointestinal abnormalit ies; urinary tract abnormalit ies; mammary abnormalit ies; serous cavities and cysts; inf lammation and infection; nonthyroidal neoplasms; and currently unexplained causes. This article also provides a detailed review of the widely scattered English language literature in which these phenomena were originally described. Copyright �9 2000 by W.B. Saunders Company

W rHOLE BODY 131-1 scanning of patients with thyroid cancer after a thyroidectomy

has been widely accepted as a central component of the treatment of this disease for over 4 decades. 1-12 The value of the technique lies in its ability to detect loci of residual normal thyroid tissue and tumor and metastatic spread to remote sites. The modality may depict disease that is otherwise undetectable by any other modality. 6,8-1~ Further- more, uptake of 13 I-I on diagnostic studies permits the selection of patients for whom 131-I therapy is appropriate. 6,8,9,13

All of this rests on the unique property of thyroid tissue to concentrate, organify, and retain 131-I. 2,7-9,11-17 Many thyroid cancers retain this characteristic property and, thus, foci of uptake on postthyroidectomy scans are considered highly specific for thyroid tissue, be it residual remnant, normal, or cancerous tissue in the neck or elsewhere in metastatic foc i . 2'7"9'11"17 This specificity is unfortunately degraded by uptake in other tissues that can concentrate 131-I but do not retain it in organic form (Fig 1). These include the choroid plexus, salivary glands, nasopharynx, and stomach; furthermore, excretion via the kidney, liver, and gut may depict these organs and the bladder, z,6-9,II,14,I5,17 The literature is replete with an ever-growing collection of reports of uptake in these organs and tissues and their associated diseases, as well as other pathological processes. 1,4,6,8,12-14,18-21

The accurate interpretation of postthyroidec-

tomy whole body 131-I images requires a thorough knowledge and understanding of all these potential confounding phenomena. 1,2,4,6-9,13,18,19,21 Imaging after the therapeutic administration of large activities of 131-I permits verification of the biodistribution of the therapeutic dose and may depict an otherwise greater extent of disease. 6-9 The same problem of interpretation applies in this posttherapeutic situa- tion as in the diagnostic images. Unfortunately the literature is widely scattered and consists primarily of isolated case reports, very small series, or it is hidden within larger works as anecdotal descrip- tions. 1'3,4'6'8'12,14J8-21 We have sought to approach this daunting problem by means of a detailed review with the available data organized according to first principles based on the underlying physiological principles governing the biodistribution of radioactive iodine. This permits a logical classification and pathophysiological interpretation of

From the University of Michigan, Department of Veterans' Affairs Health Systems, Department of Internal Medicine, Division of Nuclear Medicine, Ann Arbor, MI; Instituto di Medicina Nucleate, Universita Cattolica del Sacro Cuote, Rome, Italy; Department of Nuclear Engineering and Radiological Sciences, University of Michigan, Ann Arbor, MI; and Servizio di Medicina Nucleate, Ospedale Maggiore, Trieste, Italy.

Address reprint requests to Brahm Shapiro, MB, ChB, PhD, Division of Nuclear Medicine, University of Michigan Medical Center, 1500 East Medical Center Drive, Ann Arbor, M148109-0028.

Copyright �9 2000 by W.B. Saunders Company 0001-2998/00/3002-00065 l 0.00/0 doi: 10.1053/nm. 2000.5414

Seminars in Nuclear Medicine, Vol XXX, No 2 (April), 2000: pp 115-132 115

116 SHAPIRO ET AL

Feces I Sweat I" Expired breath I"

> Inorganic iodine pathways

D O ~ c iodine pathways

the disparate literature of the host of artifacts, anatomical and physiological variants, and nonthyroidal diseases that are responsible for false- positive whole body 131-1 scans in thyroid cancer. In the references, we provide a comprehensive compilation of the primary sources of the literature on this subject.

The administration of large activities of 131-I for the treatment of residual or metastatic well-differentiated thyroid cancer is a uniquely effective systemic therapy when applied to appropriate patients. 3,5-9,11 Recognition of the multiple causes of false-positive diagnostic studies will prevent the inappropriate delivery of this therapy. Similarly the correct interpretation of posttherapy images will prevent incorrect prognostic inferences from being drawn.

ARTIFACTS RELATED TO ECTOPIC NORMAL THYROID TISSUE

The embryological origin of the thyroid gland from the foramen cecum at the junction between the anterior two thirds and the posterior one third of

Milk I" Uri .e I"

Fig 1. A schematic represen- tation of iodine metabolism.

the tongue, with its subsequent descent and bifurca- tion in the neck, gives rise to a wide variety of abnormalities owing to embryological maldevelop- ment (Table 1). 4,22-56 Thus, complete failure to migrate leads to a lingual thyroid (Fig 2) and incomplete migration leads to a high cervical thyroid, whereas excessive migration causes a superior mediastinal thyroid or even a paracardiac gland. 4,22-4~ Foci of functioning tissue may remain anywhere along the embryological thyroglossal d u c t tract. 4,22-24,29,39-41 Abnormal migration results in widely divergent ectopic foci (eg, esophageal, intratracheal, and intrahepatic). 4,22-24,31,32,42,43,57-59 The so-called lateral aberrant thyroid tissue is highly controversial and many believe that it is, in fact, well-differentiated thyroid cancer metastatic to and completely replacing cervical lymph nodes, with the thyroidal primary being completely oc- cult. 4'23,24,52,5456 Finally, normally differentiated thyroid tissue may occur in the ovary (struma ovari i) . 4,23,24,44"53 This may represent the thyroidal

131-1 SCAN ARTIFACTS 117

Table 1. Ectopic Normal Thyroid Tissue

Comments Regarding Abnormal Embryonic Ectopic Normal Thyroid 13ssue Sites Mechanism for 131-1 Uptake Thyroid Migration/Development

Lingual thyroid 4,23-2s,4~ Owing to normal processes Failure to migrate (descend) of thyroidal 131-1 uptake and organificetion

" Incomplete migration Excessive migration Excessive migration

High cervical thyroid ~,~3,=3,~4,~7,2a,30,3~.4~

Thoracic superior mediastinal thyroid ".zz,z4,~-z> Paracardiac thyroid ~,2~,33,3",37,3s

Intracardiac ( S t ruma cordis) Pericardial

Functioning thyroid tissue in the thyroglossal tract 4̀~3'z~,2~,39,40's9

Esophageal thyroid 4,23,24,32,4~ Intratracheal thyroid 4.23,32,42

Ovarian thyroid ( St ruma ovarit~ ~,~3,2~,~

Lateral aberrant thyroid tissue rests 4.14,z3,24,54-56

lntrahepatic thyroid tissue 4.~3.~4̀31's'/'ss

Small foci of functioning thyroid tissue along route of migration may be stimulated by high TSH levels after thyroidectomy

Abnormal migration Abnormal migration Differentiation of thyroid tissue in a benign ovarian

teratoma Current knowledge suggests many or all are owing to

metastases to cervical lymph nodes Need to be distinguished from biliary tract

component of a teratoma or it may exist in isola- tion.

ARTIFACTS RELATED TO PHYSIOLOGICAL SITES OF NONTHYROIDAL UPTAKE OR

BIODISTRIBUTION

Although thyroid tissue is unique in its ability to organify iodide and synthesize thyroid hormones, a variety of glandular tissues share with the thyroid gland the ability to actively transport 131-I against a chemical gradient from the plasma into their

secretory lumen (Table 2). 2'16'60 Concentration gradients of up to 20:1 can be achieved. Tissues that share this property include gastric mucosa, nasal mucosa, salivary glands, lachrymal gland, and the lactating or nonlactating breast (Fig 3). 2'4"~3"16'60"90

The choroid plexus, although not a glandular epithelium, is nevertheless a site of secretory function for the formation of cerebrospinal fluid (CSF) and also shows 13 I-I uptake. 4

Iodide, being a small ion, is readily cleared by glomerular filtration and subsequently subject to a

< =

, , ~',, ~., .~, ~ ,. �9 ~ '., , .,.~.,, .., ' ~ - , ,

Fig 2. (A) Anterior and (B) lateral views of the head, neck, and upper chest, 24 hours after 2 mCi of 131-1 after a total thyroidectomy for papillary thyroid cancer. There w a s a small thyroid bed remnant (arrowhead) and normal uptake of 131-1 in the N, nose; M, mouth; and P, parotid glands. The intense midline focus of uptake below the floor of the mouth was owing to s lingual thyroid remnant in the base of the tongue (arrow).

118 SHAPIRO ET AL

Table 2. Physiological Sites of Nonthyroidal Uptake or Biodistribution

Physiological Sites of Nonthyroidal Mechanism for 131-1 Uptake (owing to Uptake/Distribution Normal Processes of 131-1Biodistribution) Comments Regarding Normal Biodistdbutien

Normal cardiac blood pool displaced by pectus excavatum 4,1~

Carotid ectasia 4Js,7~176

Salivary gland uptake 4.6,16.26,6~

Gastric mucosal uptake 4A6,69 Nasal mucosal uptake 4,63,69,70,73,74,82

Gut activity 4,69

Urinary tract excret ion 4,21,91,92

Choroid plexus uptake 4

Cardiac and great vessel blood pool may persist 2,4,7~

Nonlactating breast uptake 4,16,sT,el,83,84

Lactating breast uptake (see Figure 3) 4'13'16'61'64-66'68'69'72'77-79'82'84'90

Liver uptake 4,73,98,99,1~

Gallbladder uptake 4,73,91,1~

Swallowed saliva in pharynx and esophagus 4,62,8~

Lacrimal gland 4,s8

131-1 transported from site of absorption Activity fades as blood pool clears with via circulation time (not to be confused with lung

lesions) 131-1 transported from site of absorption Activity fades as blood pool clears with

via circulation time (not to be confused with tumor

Site of active 131-1 transport

Site of active 131-1 tra nsport Site of active 131-1 transport Translocation of activity secreted by

gastric mucosa Major route of clearance Site of active 131-1 transport

Slow renal clearance in renal disease or absent renal clearance in renal failure and on dialysis



Hepatic u pta ke of 131-1-1a beled thyroid hormones synthesized by functioning normal or neoplastic thyroid tissue

Enterohepatic excretion of 131-1 thyroid hormone and metabolites

Activity translated from site of secretion in salivary glands


spread to cervical lymph nodes) Knowledge of normal biodistribution

required for image interpretation n

Notto be confused with brain or skull metastases

Slow or absent renal clearance from blood pool owing to kidney disease

Usually faint but intensity may be quite variable (not to be confused with lung metastases)

Uptake may be intense, breast feeding must cease before scintigraphy as signifi- cant 131-1 may be transferred to the infant

The uptake by normal residual thyroid tissue or functioning thyroid cancer deposits is usually very obvious

Unusual cause for focal uptake in right upper quadrant may be discharged into gut by gallbladder contraction

Knowledge of normal biodiatribution required for image interpretation, restudy after swallow of water

Secretion in tears

balance between tubular secretion and reabsorption such that the urine is the principal route of 131-1 excretion. 2,4,2],91-93 Clearance of 131-I is delayed in patients on dialysis. 93-97 Urinary iodide concentration or excretion rates are a good index of the state of iodine nutrition.

Thyroid hormones undergo metabolic degradation and excretion in conjugated form into the gut. 4,69 Hence, 131-1 uptake by the liver several days after 131-1 administration is an index of the amount of functioning (hormone synthesizing) tissue present. 4,69,73,91,98-101 The gallbladder may occa- sionally be depicted when biliary excretion is extensive. 4,73,91,1~ The majority of the various iodine-containing compounds excreted via the liver undergo further metabolism and reabsorption with reutilization in an enterohepatic circulation. 4,73,91,98-1~

After the prompt and efficient absorption of 131-I in the upper gastrointestinal tract, the anion is carried to all tissues of the body via the circulation and, particularly at earlier imaging time points, 131-I within the vascular compartment may be visualized. ~,a~ Examples of artifactual cardiovascu- lar depictions include the heart and great vessels, particularly in the presence of pectus excavatum and carotid ectasia. 2,4,18,7~176 In the face of renal insufficiency, clearance from the vascular compartment will be delayed.

ARTIFACTS RELATED TO CONTAMINATION BY PHYSIOLOGICAL SECRETIONS

A wide variety of potentially misleading artifacts can arise from contamination by physiological or pathological secretions derived from those organs that


A �9 -.c ~

C , . , . . : .

Fig 3. Diagnostic scan of 2 mCi of 131-1 in a patient 1 week after weaning after 18 months of lactation. Some milk could sti l l be expressed from the breasts. (A) Anterior, (B) lef t lateral, and (C) right lateral images of the neck and chest, showing {B) intense bilateral breast uptake, and ST, normal gastric uptake. This clearly showed that a delay of much longer than 1 week after weaning is required for resolution of breast uptake of 131-1.

are capable of uptake and excretion of 131-1 (Table 3). These include urine, saliva (Fig 4), nasal secretions, other respiratory tract secretions, sweat, vomit, and breast milk. 1,10,19,61,63-65,68-70,72-75,77,79,82,87,88,90,92,105-123 Any

focus of 131-I uptake for which there is not an obvious physiological or pathological causation must be sus- pected as arising from contamination by secretions. The patient should always be imaged in a clean gown and, if necessary, this should be replaced after an attempt is made to wash away any unexplained 131-I foci. 92'106'113'124"126

Irritants or foreign bodies may exaggerate this phenomenon such as tracheostomy tubes, bronchitis, nose rings, ocular prosthesis, chewing gum, or chewing tobacco, tt,88,112,t13:t8,119 Unless sweating is excessive and owing to fever or high environmental temperature, this route of excretion is seldom prominent but may be increased in cystic fibrosis. 1~176176176

ARTIFACTS RELATED TO ECTOPIC GASTRIC MUCOSA

The ability of gastric mucosa to concentrate 131-1 is a prominent feature on whole body 131-1 scintigraphy and this property is retained by ectopic gastric mucosa (Table 4). 4'16'18'69'86'127"138 Ectopic

gastric mucosa may arise de novo as an abnormal- ity of embryological development in diverticuli (eg, Meckel's), or in duplication cysts almost anywhere along the foregut and midgut, or as a component of ovarian or other teratomas.41.86,127,129 Chronic inflammatory changes may cause meta- plastic transformation of gastrointestinal epithelium of various types to gastric mucosa (eg, squamous to gastric mucosa in Barrett's esophagus and gastric metaplasia in chronic colitis). 138 Finally, normal gastric mucosa may be anatomically displaced to abnormal anatomic sites. Mechanisms for this phenomenon include a hiatus hernia (Fig 5A and B) and surgeries such as a gastric pull- through.4,16,18,86A29-133,135-137

ARTIFACTS RELATED TO ABNORMALITIES OF GASTROINTESTINAL UPTAKE OTHER THAN

ECTOPIC GASTRIC MUCOSA

A variety of pathophysiological processes other than active gastric transport of 131-1 may result in altered 131-I biodistribution (Table 5). These include active concentration by salivary glands with secretion into saliva with subsequent abnormal transfer of the radioactivity into upper gastrointestinal diverticuli, delay by mechanical esophageal stricture, or dysmotility. 4,14,16,28,62,69,80,86,113,119,126,139-142 When

131-I is used in capsule form rather than in solu- tion, poorly dissolved capsules may be retained

120 SHAPIRO ET AL

Table 3. Contamination by Physiological Secretions

Mechanism for 131-1 Uptake (Consequence Sources of Contamination by of Normal Physiological Concentration Comments Regarding

Physiological Secretions or Route of Excretion) Normal 131-1 Biodistribution

Urine (see Figure 1 )19,92,105-115 Major route of 131-1 excretion Clothing must be changed just before scanning, attempts to wash away unexplained foci should always be made if there is any suspicion of contamination (not to be confused with pathological uptake)

Typically onto hair, skin, clothing; may be seen on neurosurgical immobilization frame

Saliva (see Figure 1 )60,75,90,112,113,115-117

Nasal secretions 63,70,73,74,82,90,110,111,113"115

Nasal secretions on nose ring TM

Respiratory secretions (especially if there is a tracheostomy) (see Figure 9)113.~1s.119

Sweat 105,108.109,113,120

Vomit89.113

Breast mi l k 1,61,64,65,68,69,72,77,87,88,121"123

Lacrimal, on artificial eye ss.9~ Chewing gum and chewing tobacco 1~2

External contamination (source unknown) 92,1~

Active 131-1 transport into saliva

Active 131-1 transport by mucus glands Active 131-1 transport by mucus glands

and drying on ring Active 131-1 transport by mucus glands

Active 131-1 transport into sweat

Active 131-1 transport into gastric secretions

Active 131-1 transport into milk (iodine is an essential micronutrient for the infant)

Active 131-1 transport into tears Stimulate salivation with transport of 131-1

saliva Origin of skin or clothing contamination not

always obvious

Sweat iodide excretion may be greater in cystic fibrosis

Vomiting may occur as a side effect of 131-1 therapy

Activity may be transmitted to infant

Could be washed off prosthesis Gum, tobacco quid, and expectorated saliva

may cause extensive contamination Contamination above the waist usually

saliva or nasal secretion, below waist often urine

in the esophagus under these circumstances. 143 Asymmetrical depiction of the salivary glands them- selves may follow ductal obstruction owing to stone (Fig 6), stricture, or tUlTIOr. 4'6'8'14'16'28'60'69,71,143-148 Prior

surgery or radiotherapy may reduce salivary gland 13 1-I uptake and this may be asymmetrical, lntralumi-

nal 13 1-I within the upper gastrointestinal tract is derived from swallowed saliva or active gastric secretion and can be refluxed into the esophagus. 4'16'62'69'80'86'127'142'144'145 This phenomenon is ex-

tremely common and to distinguish esophageal reflux activity from mediastinal nodal metastases,

Fig 4. (A) Anterior and (B) posterior views of the neck and chest in a patient 6 weeks after a near-total thyroidectomy for papillary thyroid cancer obtained 24 hours after 2 mCi 131-1 tracer dose shows (s) normal salivary gland uptake and (M) mouth activity. There was extensive salivary contamination of the shirt over the patient's shoulder (arrowhead) and a prominent halo around the heart owing to a pericardial effusion caused by hypothyroidism (small arrows).


Table 4. Uptake by Ectopic Gastric Mucosa

Comments Regarding Normal Function of Gastric Sites of Uptake by Mucosal (Normal Gastric Mucosal Uptake Is One of the

Ectopic Gastric Mucosa Mechanism for 131-1 Uptake Most Prominent Features on the Postthyroidectomy 131-1 Scan)

Meckel's diverticulum 4,1z7 Owing to normal active 131-I Gastric mucosa at abnormal site

transport into gastric

secretions n Gastric duplication cysts (may occur in

esophagus, duodenum, small bowel)4,86,129

Normal stomach in abnormal locations (hiatus hernia, gastric pull through) (see Figure 5A and [3) 4"1e.18,e6A2~'137

Ba rrett's esophagus 13s

Gastric mucosa at abnormal site

Displacement of stomach from normal site

Gastric mucosa present at abnormal site in esophagus

studies must be performed after a drink of water. 3'4'6'8'14'86'138 In resistant cases, the patient may have to be studied while sitting upright.

Radioiodine secreted by the stomach, 131-I- labeled metabolites of thyroxine metabolism excreted into the bile, and possible direct secretion by colonic mucosa together will often result in prominent depicti on of the col on. 1,3,4,7,8,14,91,98,99, i 01,102,149.150

When extensive, this degrades the quality of images owing to possible masking of metastatic sites and decreasing information density elsewhere in

the scan, as well as increasing colonic radiation exposure. 150 The decreased colonic motility, which almost always accompanies the hypothyroidism required for whole body 131-I studies is a major contributing factor. 15o The appropriate use of laxa- tives will remedy this phenomenon. Is~

ARTIFACTS RELATED TO URINARY TRACT ABNORMALITIES

The urinary tract is the principal route of iodide excretion after glomerular filtration of the small

Fig 5. (A) Whole body anterior image obtained 24 hours after a dose of 2 mCi of 131-1 in a patient wi th papillary thyroid carcinoma after a total thyro idectomy and radioiodine ablation of thyroid remnants. There is normal uptake of 131-1 in the nasopharynx and salivary glands, stomach (s), and gut (G), and excretion via the bladder (B) as well as a focus above the stomach (arrow) owing to a hiatus hernia_ (This was con- f irmed by a barium study, see Figure 5B.) (B) Barium study showing the presence of a small hiatus hernia.

122 SHAPIRO ET AL

Table 5. Abnormalities of Gastrointestinal Uptake Other Than Ectopic Gastric Mucosa

Mechanism for 131-1 Uptake Sites of Other Abnormalities (Owing to Normal Active 131-1 Comments Regarding Abnormal of Gastrointestinal Uptake Transport Into Secretions) Motility or Structure

Zenker's diverticulum ~39,~4~ Active 131-1 transport into saliva Owing to retention of activity in swallowed saliva in diverticulum

Retention of saliva above stricture Delayed clearance from esophagus

Stricture of esophagus 8~176 Achalasia and other causes of esopha-

geal dysmotil ity zs,s2,~ 2s,~4~,~ 4s,147

Poorly dissolved 131-] capsule ~43

Colonic bypass graft of the esopha- gus131,13 7

Gastroesophageal reflux 14,sg,ss,13s

Abnormal location of bowel with normal 131-1 content (eg, diaphragmatic or other hernias) 69,128,133

Constipation 150

Parotid gland uptake 148

Asymmetrical retention of saliva in salivary glands 1'~

Active 131-1 transport into saliva Active 131-1 transport into saliva

Lack of absorption and retention in the esophagus

Active 131-1 transport into saliva and gastric secretions

Active 131-1 transport into gastric secretions

Active 13%1 transport into gastric secretions and translocation by luminal transport

Active 131-1 transport into gastric secretions and translocation by luminal transport to small bowel and colon

Active 131-1 secreted into the lumen in patients with ectasia

Active 131-1 transport into saliva

Often combined with retention of saliva above stricture and delayed clearance from esophagus

Delayed clearance and reflux from stomach

Reflux of gastric activity into esophagus is very common, always rescan after drink of water if mediastinal activity is present

Luminal 131-1 activity observed at abnormal location

Delayed transport of luminal 131-1 activity owing to abnormal colonic motility (may be a result of hypothyroidism)

Pooling of activity in dilated duct as dis- tinct from diffuse uptake in gland

Owing to obstruction of salivary duct by stone, stricture, or tumor (or absence of normal gland owing to prior sur- gical removal or injury by radiation therapy)

Fig 6. Anterior view of head, neck, and chest 24 hours after a dose of 2 mCi of 131-I after a near-total thyroidectomy for papillary thyroid cancer. There was a large thyroid remnant (large arrow), normal 131-I uptake in the nose (N), mouth (M), parotid glands (P), and right submendibu- lar gland (s). There was increased 131-1 uptake in the left suhman- dibular gland owing to an ob- structing stone (small arrow).


Table 6. Urinary Tract Abnormalities

Comments Regarding Slow Clearance From Urinary Tract Sites of Urinary Tract Abnormalities Mechanism for 131-1 Uptake or Abnormal Structures in Communication With Urinary Tract*

Hydronephrosis, extrarenal pelvis, and calyectasis 3̀4,6,e,~s,2L24

Renal cysts 2Llsl

Urinary tract diverticuli (eg, affecting renal pelvis, ureter, and bladder) 4,s,s.ls,2~,z4

Urinary tract f istulae ",s,s.ls.2~,9~

Atonic or dilated bladder 4,6's,~s,21,24

Ectopic kidney or transplanted kidney ~.4,s,z~,z4,s~

Renal clearance of 131-1

into the urine as the

major route of

excretion e

Slow clearance from dilated and/or obstructed renal col- lecting system

Cyst communicates with urinary tract or nephrons

Delayed clearance from diverticuli

131-1 in urine transferred to abnormal locations by fistu-

lous communications

Delayed clearance from bladder owing to obstruction or abnormal moti l i ty

Normal renal handling of 131-1 at abnormal location

*Simultaneous imaging of urinary tract with suitable radiopharmaceutical (eg, Tc-99m-DTPA or Tc-99m MAG3) may be helpful.

anion and a balance between tubular secretion and reabsorpfion (Table 6). 2-4J5'~7"21"86 Thus, the urine within the bladder is often the most radioactive site on the whole body 131-I scan, particularly at 24 and 48 hours postadministration. 2,3,~-8,14,18,2L86J16 As a consequence of this, all dilations, diverticuli, and fistulae of the kidney, ureter, and bladder may show focal 131-I retention.3,4,6-8,14.21:24,86,116 The same is true of ectopic, horseshoe and transplanted kidneys. 21 Renal cysts may show 131-I uptake if they communicate with the urinary tract or if the epithelium, which lines them, has the capacity to concentrate and secrete iodide. 21,151 The simultaneous depiction of the urinary tract with a suitable renal tract-imaging agent such as 99mTc-DTPA or 99mTc-MAG3 may be useful in characterizing the nature of these urinary tract abnormalities.

ARTIFACTS RELATED TO MAMMARY VARIATIONS AND ABNORMALITIES

The glandular epithelium of the breast during lactation is capable of actively transporting the

essential micronutrient iodide from plasma into milk with an efficiency of 20 to 1 (Table 7) . 15,16,61,64.65,68,69,72,77,79,87,88,12 I- 123,156-158 The lactat-

ing breast shows intense 131-I uptake. 4,13, i 6,61,64- 66,68,69,72,77-79,82,84,90 This is under systemic hormonal

influence including priming by estrogens, secretory stimulation by prolactin, and milk ejection by oxytocin, which acts on both breasts. In addition, local reflex secretory stimulation occurs in that 131-I uptake is greater in the breast which is stimulated in asymmetrical or unilateral suckling. The phenomenon of breast uptake persists for weeks or even months after lactation ceases, Faint to moderate 13 I-I uptake is also seen in nonlactating breast tissue presumably owing to the same epithelial mechanism that operates in lactation.4,]6.67.st,83,84 This phenomenon may be symmetri-

cal or asymmetrical and may also be seen in unilateral mammary hypertrophy, supernumery breasts, and lactational duct cysts (Figs 7 and 8).81,83.89.152-155

Table 7. Mammary Abnormalities

Mechanism for 131-1 Uptake Sites of (Breast Duct Epithelium Actively Comments Regarding Related

Mammary Abnormalities Transports 131-1 Into the Lumen) Abnormalities of Location or Structure

Unilateral mammary hyper- Site of active 131-1 transport Asymmetrical exaggeration of normal breast uptake t rophySLSS.ls2.1ss

Supernumerary breast s9 Site of active 131-1 transport



Asymmetrical lactation sS,ls2.1~

Lactational duct cyst ls5

Additional foci of breast tissue may be found from axilla

to groin

Asymmetrical suckling may stimulate 131-1 uptake into

breast with greatest milk secretion Cyst may be lined with epithelium able to transport 131-1

into cyst lumen

124 SHAPIRO ET AL

B

Fig 7, Diagnostic 131-1 scans. of the chest performed 24 hours after a 2 mCi tracer dose in a pat ient w i th a previously re- sected papil lary thyroid carcinoma (A, anterior, B, left lateral). There is a small intense focus of activity that corresponded to a palpable breast cyst. After aspira- t ion of the cyst f luid contents the uptake disappeared as shown in C (anterior) and D (left lateral}, which are images obtained for lesser total counts. This indi- cates that the vast majori ty of the 131-1 activity was in the cyst fluid. Normal gastric uptake (s).

ARTIFACTS RELATED TO UPTAKE IN SEROUS CAVITIES AND CYSTS

The epithelia lining pleura, peritoneum, and pericar- dium are not able to actively transport 131-I but may be permeable to passive diffusion even in the absence of

inflammation (Table 8). This leads to the accumulation of 131-I in pleural, peritoneal and pericardial effusions, scrotal hydroceles, and pleuropericardial cystS. 19'159-163

Similar processes appear to operate in ovarian cysts and lymphoepithelial cysts. 161'162

Fig 8. (A) Anter ior and (B) poster ior head, neck, and chest views 24 hours after administrat ion of a dose of 2 mCi of 131-1 in a patient wi th papil lary thyroid cancer after a prior thyroidectomy. Note thyroidal bed 131-1 uptake (arrow) and normal stomach (ST), salivary gland (s), and mouth (M) uptake. There is intense 131-1 uptake in the right breast (B) (note clear visualization anteriorly and not posteriorly). The patient had ceased breast feeding just before tracer administrat ion but for months had only been feeding her infant on the r ight breast, Thus, al though the hormonal miiMu of both breasts was the same (eg, prolactin levels) the local effect of suckling was important in 131-1 uptake by the lactating breast.


Table 8. Uptake in Serous Cavities and Cysts

Sites of Uptake in Comments Regarding Diverse Locations and Serous Cavities or Cysts Mechanism for 131-1 Uptake Factors That May Be Involved

Pericardial effusion (not associated with Cysts are lined by epithelia not able to May be associated with hypothyroidism inflammation; also see Table 9) ~6,~69,~6~ actively transport 131-1; passive diffu-

sion into cyst fluid with subsequent slow c l e a r a n c e

Scrotal hydrocele ls~

Lymphoepithelial cysts 161 Ovarian cysts ~62

Pleuropericardial cysts ~63

Must be distinguished from urinary contamination

This does not include lesions (teratomas) with ectopic gastric, salivary gland, or thyroid epithelium

ARTIFACTS RELATED TO UPTAKE IN SITES OF INFLAMMATION OR INFECTION

Inflammation, whether it be sterile (autoimmune, traumatic, or ischemic) or owing to infection, results in increased blood flow caused by vasodilation, increased capillary permeability owing to the complex interplay of various inflammatory cells, immune mediators, lymphokines, and other systemic and paracrine mediatory factors (Table 9).

This results in the accumulation of 131-1 at the sites of a wide variety of inflammatory and infectious processes in which increased blood flow delivers increased levels of 131-1 to the site, which then diffuses through the capillaries that are rendered highly permeable and then accumulates in the increased extracellular water space (edema fluid) (Fig 9). 1.6,12,19,20,90,117,145,160,161,164"175 These pro-

cesses seem to be independent of the active iodide

Table 9. Uptake in Sites of Inflammation or Infection

Comments Regarding Diverse Uptake in Sites of Locations Possible (Inflammatory

Inflammation/Infection Mechanism for 131-1 Uptake Process Need Not Be Infectious in Cause)

Pulmonary (eg, rheumatoid lung, Inflammation results in increased perfu- Increased production of mucus may be an bronchiectasis, fungal infection, sion, vasodilation, end capillary perme- additional factor or acute respiratory tract infec- ability tion)2O,9O,164-1s6

Perica rditislg, llT,lSo,~s~ Skin burns ~61 "

Dental disease/peridontal surgery ~z.167"169 ArthrRis (eg, rheumatoid) ~ss Chronic sinusitis 1,9~176

Dacryocystitis ~,90

Psoriatic plaques s Acute or chronic cholecystitis ~7~ Scalp folliculitis ~72 Sialoadenitis 14s Recent myocardial infarct ~v3

Infected sebaceous cyst 171,174

Frontal sinus mucocele 17~

Site of needle biopsy 175

r

Increased capillary permeability and inflammation in region of infarcted myo- cardium implies coronary redistribution

Inflammation results in increased perfu- sion, vasodilation, and capillary permeability

Frequently autoimmune in cause Need not be infected to show 131-1 uptake May not be clinically evident Usually noninfected inflammatory lesion Increased production of mucus may be an

additional factor Increased uptake in gland beyond that

owing to concentration in tears Noninfected inflammatory lesion Biliary excretion may also occur

Should not be confused with normal gastric uptake of 131-1 or activity in a hiatus hernia

Sebaceous glands may also concentrate 131-1

Sinus mucosa capable of iodide transport To be distinguished from acute or chronic sinusitis

Inflammation at site of trauma Uninfected inflammation

126 SHAPIRO ET AL

Fig 9. (A) Anterior and (B) posterior head, neck, and chest views obtained 3 days after a 175-mCi therapy dose of 131-1 6 weeks after a total thyroidectomy and tracheostomy for an invasive papillary carcinoma that had infiltrated the larynx. There was normal uptake of 131-1 in the salivary glands (s) and nasopharynx (N). There was intense uptake of 131-1 in the region of the thyroid bed and tracheostomy (large arrowheads) and faint abnormal uptake of 131-1 throughout the tracheobronchial tree, which had the appearance of an inverted Y (small arrows). This was caused by tracheobronchitis associated with the tracheostomy.

transport seen in thyroid, gastric, salivary, and other �9 " 16 specialized epltheha.

ARTIFACTS RELATED TO UPTAKE BY NONTHYROIDAL NEOPLASMS

A wide variety of nonthyroidal neoplasms have been shown to have 131-1 uptake, albeit per-

haps only in a minority of such lesions (Table 1 0 ) . 44-51'53'64'67'161"162"t76-19! The mechanisms for this

uptake are probably diverse and include (1) the increased vascularity and capillary permeability similar to that seen in inflammation and infection (these include meningiomas, ovarian adenocarcinoma and cystadenoma, uterine fibroma [Fig 10],

Table 10. Uptake by Nonthyroidal Neoplasms

Comments Regarding Both Primary and Sites of Nonthyroidal Neoplasms Mechanism for 131-1 Uptake* Metastatic Tumors

Gastric adenocarcinoma 67,~76,177 Gastric mucosa actively transports 131-1 Probably owing to preservation of

Meningioma17S, 17~ Lung cancer (adenocarcinoma, oat cell

carcinoma, and squamous cell carcinoma)iS1.176,180-183

Salivary adenocarcinoma (Warthin's tumor} 184

Ovarian adenocarcinoma and ovarian cystadenoma 162

Ovarian teratoma (benign or malignant)44-s1.53.185-188

normal gastric mucosal active iodide uptake mechanisms

This would explain uptake in adenocarcinoma but not squamous or oat cell cancers

Other salivary tumors are less likely to show 131-1 uptake; must be distinguished from uptake owing to ductal obstruction

Mechanism differs from that in ovarian teratomas

"nssues that normally take up 131-1 may differentiate in such tumors

Teratomas at other sites (benign or malignant) 189

Uterine f ibromyoma (see Figure 10)

Abdominal neurilemoma 67,19~

Mechanism unclear (highly vascular) Bronchial mucus glands actively trans-

port 131-1

Salivary glands actively transport 131-1

Mechanism unclear

Owing to uptake of 131-1 into salivary gland, gastric mucosa, or thyroid gland tissue present in tumor

Owing to uptake of 131-1 into salivary gland, gastric mucosa, or thyroid gland tissue present

Mechanism unclear

Mechanism unclear

33ssues that normally take up 131-1 may differentiate in such tumors

May be difficult to separate from bladder and bowel activity

May be difficult to separate from bladder and bowel activity

*Some, by no means all, of these tumors are derived from tissues that can normally concentrate 131-1,


B C

Fig 10. Diagnostic studies performed 24 hours after a dose of 2 mCi of 131-1 as part of a metastatic survey in a patient after a total thyroidectomy for papillary thyroid cancer. There was intense and extensive gut radioactivity (G) owing to the constipation caused by the hypothyroidism required in preparation for the scan. There was normal urinary excretion of 131-1 through the bladder (B) and urinary contamination of the vulva. There was also a large abnormal focus of 131-1 uptake in the anterior pelvis (T), which was quite separate from the gut and bladder and best seen on the (A) anterior and (C) right anterior oblique projections. On the (B) posterior projection the focus was much fainter, indicating a relatively anterior location. The abnormal 131-1 uptake was in a large fibroid uterus, which rose out of the pelvis.

neurilemoma)67,162,179,187,19~ and (2) many of the

tumors are derived from epithelia that show normal physiological iodide transportJ 6 These include gastric adenocarcinoma, bronchial adenocarcinoma, salivary adenocarcinoma, ovarian and other teratomas containing gastric, salivary, thyroid, and similar tissues.44-51,53,65,161,176,177,180-184,186-189

CURRENTLY UNEXPLAINED SITES OF ARTIFACTUAL UPTAKE

There remain a few reports of focal 131-I uptake in postthyroidectomy patients for which there remains no obvious physiological or pathophysiological explanation (Table 11). The uptake of 131-I in normal or hyperplastic thymic tissue remains unexplained because there does not seem to be a well-defined iodine uptake mechanism in the thymus. 192-2~176 Focal uptake of 131-I at sites of porencephaly and cerebral malacia occurring up to 25 years after the original cerebral injury remain

unexplained but may relate to ongoing chronic inflammation.2~176176

CONCLUSIONS

This classification and organization of artifacts, anatomic and physiological variants, and nonthyroidal d i seases caus ing f a l s e - p o s i t i v e whole body 131-I scans in thyroid cancer patients and in the correct interpretation of both diagnostic and posttherapeutic 131-I studies gives access to an extensive and scattered literature. This provides a single compendium of the available English language literature on the subject at the millenium. This organizational schema is offered as a means to interpret and clarify additional future observations in this area, which will undoubtedly continue to accrue.

Acknowledgement: The authors wish to thank Judith A. Csoka for assistance in the preparation of the text.

Table 11, Currently Unexplained Sites of Uptake

Factors to Be Considered in Other Sites and Causes Mechanisms for 131-1 Uptake Otherwise Unexplained Thoracic 131-1

Unexplained thymic uptake 192-2~176 Currently unexplained May be associated with a mediastinal mass at CT scan owing to thymic hyperplasia

" To be considered in otherwise unexplained thoracic 131-1

Trauma occurred 25 years earlier

Unexplained mediastinal uptake (? normal variant) 19s,197

Unexplained uptake at site of porencephaly TM

Posttraumatic cerebral malacia 2~176 Possible chronic inflammation of cerebral or overlying tissues

Prior surgery for cerebral abscess 25 years earlier

128 SHAPIRO ET AL

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