THYROID DISEASE
Ed Friedlander, M.D., Pathologist
scalpel_blade@yahoo.com

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Welcome to Ed's Pathology Notes, placed here originally for the convenience of medical students at my school. You need to check the accuracy of any information, from any source, against other credible sources. I cannot diagnose or treat over the web, I cannot comment on the health care you have already received, and these notes cannot substitute for your own doctor's care. I am good at helping people find resources and answers. If you need me, send me an E-mail at scalpel_blade@yahoo.com Your confidentiality is completely respected. No texting or chat messages, please. Ordinary e-mails are welcome.

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Pathology's modern founder, Rudolf Virchow M.D., left a legacy of realism and social conscience for the discipline. I am a mainstream Christian, a man of science, and a proponent of common sense and common kindness. I am an outspoken enemy of all the make-believe and bunk that interfere with peoples' health, reasonable freedom, and happiness. I talk and write straight, and without apology.

Throughout these notes, I am speaking only for myself, and not for any employer, organization, or associate.

Special thanks to my friend and colleague, Charles Wheeler M.D., pathologist and former Kansas City mayor. Thanks also to the real Patch Adams M.D., who wrote me encouragement when we were both beginning our unusual medical careers.

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Especially if you're looking for information on a disease with a name that you know, here are a couple of great places for you to go right now and use Medline, which will allow you to find every relevant current scientific publication. You owe it to yourself to learn to use this invaluable internet resource. Not only will you find some information immediately, but you'll have references to journal articles that you can obtain by interlibrary loan, plus the names of the world's foremost experts and their institutions.

Alternative (complementary) medicine has made real progress since my generally-unfavorable 1983 review. If you are interested in complementary medicine, then I would urge you to visit my new Alternative Medicine page. If you are looking for something on complementary medicine, please go first to the American Association of Naturopathic Physicians. And for your enjoyment... here are some of my old pathology exams for medical school undergraduates.

I cannot examine every claim that my correspondents share with me. Sometimes the independent thinkers prove to be correct, and paradigms shift as a result. You also know that extraordinary claims require extraordinary evidence. When a discovery proves to square with the observable world, scientists make reputations by confirming it, and corporations are soon making profits from it. When a decades-old claim by a "persecuted genius" finds no acceptance from mainstream science, it probably failed some basic experimental tests designed to eliminate self-deception. If you ask me about something like this, I will simply invite you to do some tests yourself, perhaps as a high-school science project. Who knows? Perhaps it'll be you who makes the next great discovery!

Our world is full of people who have found peace, fulfillment, and friendship by suspending their own reasoning and simply accepting a single authority that seems wise and good. I've learned that they leave the movements when, and only when, they discover they have been maliciously deceived. In the meantime, nothing that I can say or do will convince such people that I am a decent human being. I no longer answer my crank mail.

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More of Ed's Notes: Ed's Medical Terminology Page

Perspectives on Disease
Cell Injury and Death
Accumulations and Deposits
Inflammation
Fluids
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What is Cancer?
Cancer: Causes and Effects
Immune Injury
Autoimmunity
Other Immune
HIV infections
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Environmental Lung Disease
Violence, Accidents, Poisoning
Heart
Vessels
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Red Cells
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Men
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Ear
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Alternative Medicine (current)
Preventing "F"'s: For Teachers!
Medical Dictionary

Courtesy of CancerWEB

OBJECTIVES

KCUMB Students
"Big Robbins" -- Endocrine
Lectures follow Textbook

QUIZBANK

Endocrine
Taiwanese pathology site
Good place to go to practice

Endocrine
Photo Library of Pathology
U. of Tokushima

Goiter
From Chile
In Spanish

Endocrine
Brown Digital Pathology
Some nice cases

Endocrine
Utah cases for path students
Juliana Szakacs MD

Endocrine
Iowa Virtual Microscopy
Have fun

Thyroid Exhibit
Virtual Pathology Museum
University of Connecticut

Endocrine
Photos, explanations, and quiz
Indiana U.

Normal thyroid

WebPath Photo

Normal thyroid

WebPath Photo

Normal thyroid

WebPath Photo

Normal thyroid
C-cells stained
WebPath Photo

Thyroid
"Pathology Outlines"
Nat Pernick MD

Thyroid Histology
Ed's Histology Notes

{11803}    normal thyroid, gross
{00135}    normal thyroid, histology
{11755}    normal thyroid, histology
{00138}    goiter
{24613}    goiter
{39460}    goiter


Endemic goiter

    Mountaineers dew-lapped like bulls, whose throats had hanging at 'em wallets of flesh...

          -- Shakespeare, "The Tempest"

INTRODUCTION

{08959}    propylthiouracil effect
{24718}    propylthiouracil effect

{24719}    high-dose iodine effect

{09362}    normal scan
{09363}    cold nodule, right upper pole

CRETINISM

{49456}    cretin, age 4 months

Cretin
Classic drawing
Adami & McCrae, 1914

ACQUIRED HYPOTHYROIDISM (Lancet 363: 793, 2004 -- it's often missed even though this should never happen)

{24611}    myxedema
{25468}    myxedema
{25469}    myxedema

Iodine deficiency
Epidemic goiter
KU Collection

BIRTH DEFECTS

Thyroid Malformations
From Chile
In Spanish

{49471}    thyroglossal duct cyst, patient
{09245}    thyroglossal duct cyst, histology

{21529}    lingual thyroid

HASHIMOTO'S THYROIDITIS ("chronic autoimmune thyroiditis": NEJM 335: 99, 1996)

{09241}    Hashimoto's, gross
{08960}    Hashimoto's, histology
{08961}    Hashimoto's, histology
{09242}    Hashimoto's, histology
{37881}    Dr. Hashimoto
{37882}    Dr. Hashimoto "after 40 years of teaching"

Hashimoto's
From Chile
In Spanish

Hashimoto's Disease
Text and photomicrographs. Nice.
Human Pathology Digital Image Gallery

Hashimoto's
Anti-thyroglobulin antibodies
WebPath Photo

Hashimoto's thyroiditis
Germinal centers, damaged parenchyma
KU Collection

Hashimoto's

WebPath Photo

Hashimoto's

WebPath Photo

Hashimoto's

WebPath Photo

Hashimoto's
Anti-microsomal antibodies
WebPath Photo

NON-HASHIMOTO LYMPHOCYTIC THYROIDITIS

DEQUERVAIN'S SUBACUTE GRANULOMATOUS THYROIDITIS ("thyroid virus infection")

{09247}    DeQuervain's
{24721}    DeQuervain's

DeQuervain's

WebPath Photo

RIEDEL'S THYROIDITIS ("Riedel's struma"; review J. Clin. Endo. Metab. 87: 3545, 2002; Am. J. Clin. Path. 121: 550, 2004)

{49460}    Riedel's

HYPERTHYROIDISM (Lancet 379: 1155, 2012; Am. Fam. Phys. 72: 635, 2005)

GRAVES'S DISEASE (NEJM 358: 2704, 2008)

{09235}    Graves's
{09237}    Graves's

Graves's

WebPath Photo

Graves's

WebPath Photo

{09355}    Graves's exophthalmos
{09356}    Graves's exophthalmos

{09360}    pretibial myxedema
{25470}    pretibial myxedema
{25471}    pretibial myxedema
{25472}    pretibial myxedema

{24717}    Graves's with scalloping

ATROPHY OF THE THYROID

Thyroid Atrophy
From Chile
In Spanish

{17447}    burned-out thyroid; this could be anything from old I131 injury to old Hashimoto's to Riedel's to a really gone patch in a nodular goiter.

Burned out thyroid
No history -- surprise at autopsy
KCUMB Team

* Future pathologists: the rare AMYLOID GOITER features amyloid AA and often extensive fatty ingrowth. It remains a minor mystery of medicine. See Arch. Pathol. Lab Med. 124: 281, 2000.

DIFFUSE NONTOXIC GOITER ("colloid goiter") / (MULTI)NODULAR GOITER

{21053}    colloid goiter
{21054}    colloid goiter
{19502}    colloid goiter, around 100 gm
{09354}    colloid goiter, gross
{19505}    colloid goiter, histology
{19511}    colloid goiter, histology
{10825}    nodular goiter
{12710}    nodular goiter (this was billed as "Hashimoto's"; I doubt it)
{39052}    nodular goiter (dominant nodule was called "adenoma", heh heh)
{09238}    nodular goiter, gross
{49451}    nodular goiter, gross
{09240}    nodular goiter, histology
{49465}    nodular goiter, they decided to operate

Nodular goiter

WebPath Photo

Nodular goiter

WebPath Photo

Thyroid gland with diffuse hyperplasia
What could this be?
Wikimedia Commons

Big inactive follicles
Nodular goiter / Could be other things too
WebPath Photo

* Let us worry about "dyshormonogenetic goiter" a genetic syndrome with difficulty synthesizing thyroid hormones, deafness, hypothyroidism, an enormous thyroid composed mostly of fibrous tissue, very pleomorphic nuclei, and no cancer risk.

Thyroid Tumors I
From Chile
In Spanish

Thyroid Tumors II
From Chile
In Spanish

Thyroid Tumors
Histopathology and essay
For pathologists

THYROID ADENOMAS

{24724}    thyroid adenoma, gross
{13363}    thyroid adenoma, gross
{09248}    thyroid adenoma, gross
{09250}    thyroid adenoma, gross
{09777}    thyroid adenoma, gross
{39965}    thyroid adenoma, gross
{49453}    thyroid adenoma (center has liquefied)
{49454}    thyroid adenoma
{19523}    thyroid adenoma, histology
{19529}    thyroid adenoma, histology

Thyroid, follicular adenoma
Ed Uthman MD
Wikimedia Commons

Adenoma

WebPath Photo

Adenoma

WebPath Photo

Adenoma

WebPath Photo

PAPILLARY ADENOCARCINOMA ("Orphan Annie's Tumor"; Arch. Path. Lab. Med. 130: 1057, 2006)

{24725}    papillary carcinoma, gross
{24723}    papillary carcinoma, histology
{26792}    papillary carcinoma, histology
{26795}    papillary carcinoma, histology
{26798}    papillary carcinoma, histology
{20291}    world's smallest papillary thyroid cancer

Papillary carcinoma

WebPath Photo

Follicular carcinoma
Orphan Annie Eyes
WebPath Photo

Orphan Annie, psammoma bodies

WebPath Photo

Papillary Thyroid Cancer
Dino Laporte's PathosWeb

    "Orphan Annie's tumor" reminds us of papillary carcinoma of the thyroid:

    • It most often affects younger women;
    • It tends to stay around for years without getting any bigger;
    • It is usually well-behaved and seldom kills people;
    • Its nuclei exhibit marginated chromatin, producing the "Orphan Annie's eye" appearance
    • The psammoma bodies (Greek psammos means "sand") recall the name of Orphan Annie's faithful dog, Sandy.

FOLLICULAR ADENOCARCINOMA (pathologists see Cancer 100: 1123, 2004)

{09255}    follicular carcinoma of thyroid, histology. Trust me, this was invading a vessel
{39838}    follicular carcinoma of thyroid, histology. Trust me, this was invading a vessel

MEDULLARY ADENOCARCINOMA (Surg. Clin. N.A. 75: 405, 1995; Am. J. Med. 103: 60, 1997).

{49355}    medullary carcinoma of thyroid, gross
{49356}    medullary carcinoma of thyroid, gross
{49366}    medullary carcinoma of thyroid, gross. Of course, you couldn't diagnose any of these four without histology.
{09265}    medullary carcinoma of thyroid, histology
{09266}    medullary carcinoma of thyroid, histology
{37160}    medullary carcinoma of thyroid, histology; Congo Red stain
{37163}    medullary carcinoma of thyroid, histology; crystal violet stain (amyloid is scarlet, all else is Navy Blue)

Medullary carcinoma

WebPath Photo

Medullary carcinoma
Congo red
WebPath Photo

POORLY DIFFERENTIATED THYROID CANCER is a new category convincingly defined in 2006 (Cancer 106: 1286, 2006).

ANAPLASTIC ADENOCARCINOMA ("undifferentiated carcinoma")

{09264}    anaplastic carcinoma of thyroid, histology
{37004}    anaplastic carcinoma of thyroid, cytology

Anaplastic carcinoma of the thyroid
Clear vascular invasion
Pittsburgh Pathology Cases

{10934}    lymphoma of the thyroid
{10937}    lymphoma of the thyroid

THYROID TESTING (see Lancet 357: 619, 2001)

In suspected Graves's disease and Hashimoto's disease, you can order a battery of anti-TSH receptor autoantibodies. The first is "thyroid stimulating antibody" / "long-acting thyroid stimulator" / "LATS" / "TSH receptor antibody" / now TRAb. The second is "anti-thyroglobulin antibodies" / now TgAb. The third is "anti-microsomal antibodies" / anti-peroxidase antibodies" / now TPOAb. Interpretation is rather cloudy, though TRAb causes Graves's, and very high titers of anti-microsomal antibodies is pretty specific for Hashimoto's.

If you've got a bump in your thyroid, a pathologist will be happy to FINE-NEEDLE ASPIRATE it, and look at the cells on a slide. Unless the nodule is under 4 cm AND is free of calcifications AND has a perfectly smooth border, you'll probably want to get tissue (Surgery 150: 436, 2011). Review of 4700 cases from Galveston: Cancer 111: 306, 2007 (it's accurate). How to do it right: J. Cln. End. Metab. 79: 335, 1994; Mayo Clin. Proc. 69: 44, 1994; some sub-subspecialty training is advised for pathologists who want to do this (Cancer 107: 406, 2006). Using it with ultrasound to be sure you hit the itty-bitty nodules: Otolar. 123: 700, 2000. The procedure is not perfect, and there are still plenty of false-positives and false negatives; the most common problem is the all-too-human attempt to interpret an unsatisfactory specimen (Am. J. Clin. Path. 125: 873, 2006). Nowadays, we generally operate the tough calls, and this is a good thing as a lot of them are cancer (J. Am. College. Surg. 213: 188, 2011). Bethesda (2007) offered a six-category sytem that was a baffler for me; the feeling afterwards seems to have been to send anybody with a follicular thyroid lesion that wasn't obviously just a nodular goiter to see a surgeon. The Royal College of Pathologists's system seems to be the most popular and reproducible among observers (Thy1, nondiagnostic; Thy2 nonneoplastic; Thy3a atypia probably benign, Thy3f follicular lesion infamously difficult to tell benign from malignant; Thy4 suspicious for cancer; Thy5 cancer.) See Am. J. Clin. Path. 135: 852, 2011; two "nondiagnostic" needlings means "almost certainly no cancer": Am. J. Clin. Path. 135: 750, 2011. In the meantime, molecular diagnostics are now being applied to thyroid fine needle aspirates (BRAF, RAS, RET/PTC, PAX8/PPAR gammma) and this seems to help greatly (Arch. Path. Lab. Med. 135: 569, 2011.) Patients may be concerned that the needling will spread the cancer; this is very rare but does happen (J. Laryn. Otol. 121: 268, 2007.) This is really a screening technique to find out which bumps to cut out, and it is the one instance in which a decision to perform such serious surgery may be based on a few cells in a cytology smear. The practice is now standard, and has greatly reduced the number of people who need to be operated for diagnosis. Update on this now-huge field: CA 59(2): 99, 2009. "The Bethesda System for Reporting Thyroid Cytopathology": Am. J. Clin. Path. 132: 658, 2009; Am. J. Clin. Path. 134: 45, 2010.

Please remember that we CANNOT tell benign from low-grade-malignant follicular lesions of the thyroid using fine-needle aspiration.

Once a thyroid needle biopsy shows something worrisome, there's no reason to "repeat the biopsy" -- the mass comes out (Am. J. Clin. Path. 134: 788, 2010). And if the pathologists are "uncertain", the best rule seems to be, "When in doubt, cut the lobe out" (Surgery 148: 516, 2010 -- today there is very little morbidity from this surgery, which is now done on outpatients.) A surgeon should remove the bump if the fine needle aspirate shows:

Oxalate crytsals in the thyroid
Curiosity of no significance
KCUMB Team

Oxalate crytsals in the thyroid
Polarized shot
KCUMB Team

BIBLIOGRAPHY / FURTHER READING

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