Neoplastic and Non-neoplastic Rodent Thyroid Lesions and Their Relevance

Thyroid presentation

Neoplastic and Non-neoplastic Rodent Thyroid Lesions and Their RelevanceBob MaronpotRTP Rodent Pathology Course - 2014

AcknowledgmentThe majority of the photomicrographs in this presentation were provided courtesy of the National Toxicology Program Archives

http://ntp.niehs.nih.gov/nnl/

Toxicologic Pathology Vol 22 (2): 179-186, 1994Haschek and Rousseauxs Handbook of Toxicologic Pathology, 3rd Edition (2013)

HypothalamusPit

TRH

ThyroidTSH

BloodT3T4T3/T4Negative feedback

Liver

Elimination

T4

T3

TSH

Basics of Thyroid Hormone PhysiologyFigure courtesy of Doug Wolf

55

Rat-Human Species Differences

Effects of Xenobiotics on the Thyroid

Toxicologic Pathology Vol 22 (2): 179-186, 1994

Effects of Xenobiotics on the Thyroid

Toxicologic Pathology Vol 22 (2): 179-186, 1994

NomenclatureThyroid changes affecting the thyroid in general (e.g., inflammation)Follicles changes restricted to the follicles (e.g., secretory depletion)Follicular epithelium - effect is specific to the follicular epithelium (e.g., hypertrophy)C-Cells changes specifically affecting the C-cells (e.g., hyperplasia)

Thyroid LesionsNon-ProliferativeCystsEnlarged/dilated folliclesSecretory depletion/colloid depletionColloid alterationDegenerationInflammationMineralizationHypertrophy

ProliferativeFollicular epitheliumHyperplasiaGeneralizedCysticAdenomaAdenocarcinomaC-cellsHyperplasiaDiffuseFocalAdenomaCarcinoma

Parathyroid LesionsNon-ProliferativeCystsSyncytial giant cells/cytomegalyAngiectasisProliferativeHyperplasiaAdenomaCarcinoma

Rat Thyroid - Normal

A49050 Vehicle male F344 Cresol Normal. C-cells normal13


A50388 Subchronic F344 Normal14


A49766 Subchronic Vehicle male F344 Normal15


A49051 Cresol Vehicle male F344 Normal16

Mouse Thyroid - Normal

A45151 Female normal FVB/N17


A47139 Ginko F344 control Normal18

Mouse Thyroid - Normal

A40629 mouse B6C3F1 Untreated male Normal19

Rat versus Mouse

Rat Thyroid - Mineral

A40749 methyjlimidazole F344 dx= follicular cell hyperplasia and mineral21

Embryonal Cyst

A08337 Aminonotrophenol F344 dx= cystic duct22

Embryonal Cyst

A05288 Vehicle female F344 dx=23

Embryonal Cyst

A24178 p-Nitroaniline B6C3F1 dx= thyroglossal cyst24

Embryonal Cyst

A24180 p-Nitroaniline B6C3F1 dx= thyroglossal cyst

25

Ectopic Thymus

A12939 B6C3F1 Ectopic thymus26



Enlarged Follicles

F344

A05294 4-vinylcyclohexane F344 dx= enlarged follicles28

Follicular Degeneration

A51381 Milk thistle extract B6C3F1 follicular degeneration29


B6C3F1 Control Female

A48961 B6C3F1 control female Follicular degeneration 30


degeneration31


Ciliated Vehicle female32

Pigment

Vehicle control. Male F344

A07951 pigment Vehicle Male F34433

Pigment

High dose methoxypsoralen male F344

A07961 Pigment Methoxypsoralen High dose male F34434

Pigment

1 of 3

A10435 pigment Trinitrofluorenone F344 minocycline semisynthetic tetracycline derivative; dark brown resembles melanin35

Pigment

2 of 3

A10436 pigment Trinitrofluorenone F344minocycline semisynthetic tetracycline derivative; dark brown resembles melanin36

Pigment

3 of 3Subchronic trinitrofluorenone study in F344 rats

A10437 pigment Trinitrofluorenone F344 minocycline semisynthetic tetracycline derivative; dark brown resembles melanin

37

Follicular Cell Hypertrophy

A40643 B6C3F1 control male dx=hypertrophy 2-methylimidazole38

Concurrent Control

A40629 to cf to A40643 2-methylimidazole normal B6C3F1 control male39


1 of 3Female SD Rat

A52749 PCB 118 SD Female TEF 2 yr gavage dx= hypertrophy41


2 of 3



3 of 3



Subchronic study. SD Rat

A47461 PCN subchronic dx = hypertrophy Sprague Dawley Female

44

Hypertrophy

Subchronic study. F344 Rat

A49763 Tetrachlorobenzene Subchronic dx=hypertrophy F34445

Hypertrophy

Harlan SD Rat.

A66377 Harlan SD Indole-3-carbinol Marked follicular cell hypertrophy46

Hypertrophy & Hyperplasia

1 of 4Subchronic study. F344 Rat

A49772 Pentachlorobenzene Subchronic dx = hypertrophy Some hyperplasia present F344 47


2 of 4



3 of 4

A4977449


4 of 4


Hypertrophy

A44355 dx follicular cell hypertrophy PCB mixture Female SD 2 yr gavage51

Hypertrophy

A40345 dx follicle atrophy?? Really is hypertrophy dioxin mixture Female SD 2 yr gavage52

Secretory Depletion

Subchronic study. F344 Rat

A50379 Pentabromophenyloxide Subchronic Fischer 344 dx secretory depletion Flame retardant. Still under study and no pathology findings yet available on NTP web site. 53

Secretory Depletion



Secretory Depletion



Secretory Depletion

Chronic study. F344 Rat

A11171 secretory depletion F344 CI Acid Red 11456

Lymphoid Infiltrate, Secretory Depletion and Hypertrophy

1 of 2Subchronic study. FVB/N Mouse.

A45156 Sodium bromate subchronic study in FVB/N mouse Lymphoid infiltrate, secretory depletion, follicular cell hypertrophy57


2 of 2

A45157 Sodium bromate subchronic study in FVB/N mouse Lymphoid infiltrate, secretory depletion, follicular cell hypertrophy58


1 of 2Female SD Rat

A51536 A51537 Tetrachloroazobenzene Female SD Inflammation and hypertrophy

59

Lymphoid Infiltrate, Secretory Depletion, Pigment, and Hypertrophy

2 of 2

A51537 Tetrachloroazobenzene Female SD Inflammation and hypertrophy

60

Periarteritis

1 of 2B6C3F1 Mouse

A23377 B6C3F1 Mouse tetrafluoroethylene chronic dx=periarteritis 61

Periarteritis

2 of 2

A23378 B6C3F1 Mouse tetrafluoroethylene chronic dx=periarteritis 62



Take away 1. Hypertrophy often with hyperplasia. 2. Concurrent control 3. dx the primary change63

Follicular Cell Proliferative LesionsHyperplasiaFollicular cell hyperplasiaDiffuseFocal (simple papillary infoldings)Cystic hyperplasiaMinimal compressionAdenomaCircumscribed, compressiveGrowth pattern complex papillary or follicularCells well differentiated and hyperchromaticCarcinomaCapsular invasionInfiltrative, disorganized, varied growth patternCellular pleomorphism and atypiaVarying sized folliclesScirrhous reaction

Usually unilateral64

Diffuse Hyperplasia

1 of 2F344 Rat Chronic Study

A08048 F344 Mercaptobenzimidazole Chronic study65

Diffuse Hyperplasia

2 of 2

A8049 F344 Mercaptobenzimidazole Chronic study

66

Focal Hyperplasia

B6C3F1 Mouse Sodium Chlorate Study

A40905 B6C3F1 Sodium chlorate dx= follicular cell hyperplasia67

Follicular Cell Hyperplasia

1 of 2B6C3F1 Mouse

A40646 2-methylimidazole B6C3F1 dx= hyperplasia and hypertrophy?68

Follicular Cell Hyperplasia

2 of 2

A40647 2-methylimidazole B6C3F1 dx= hyperplasia and hypertrophy?69

Hyperplasia vs. Adenoma

1 of 2B6C3F1 Mouse. Original dx = Adenoma

A57552 ginkgo biloba extract B6C3F1 dx= adenoma70


2 of 2

A57553 ginkgo biloba extract B6C3F1 dx= adenoma

71


1 of 2B6C3F1 Mouse Original dx = Hyperplasia

A43866 Methylisobutylketone B6C3F1 dx=hyperplasia72


2 of 2

A4386773

Follicular Cell Adenoma

F344 Rat

A09478 Tris chloroethylphosphate F344 dx follicular cell adenoma74

Cystic Follicular Cell Adenoma

A03709 F344 75


F344 Rat

A57079 ginko biloba extract F344 dx=adenoma76


1 of 4F344 Rat

A54750 Kava kava Follicular adenoma F34477


2 of 4

A5475178


3 of 4

A5475279


4 of 4

A54753 Kavakava Follicular adenoma

80


1 of 3SD Female Rat

A44360 PCB SD Follicular adenoma81


2 of 3

A4436182


3 of 3

A4436283

Follicular Cell Carcinoma

1 of 2Wistar Han Rat

P3273459 Han Wistar Follicular Carcinoma

84


2 of 2

P3273461 Han Wistar Follicular Carcinoma

85


B6C3F1 Mouse

A24203 methyl bromide B6C3F1 control female dx= carcinoma and follicular degeneration86


F344 Rat

A29499 Isobutene F344 dx= follicular cell CA87


A30974 Isobutene F344 dx=carcinoma, invasion88


1 of 2F344 Rat

A46141 Methylene blue trihydrate F344 Follicular cell CA89


2 of 2

A46143 Methylene blue trihydrate F344 Follicular cell CA90

Macrofollicular Carcinoma

A0553691

Squamous Cell Carcinoma

1 of 2F344 Rat

A07405 Dibromopropanol SCC F34492

Squamous Cell Carcinoma

2 of 2

A4740693

Follicular Cell Proliferative LesionsHyperplasiaFollicular cell hyperplasiaDiffuseFocal (simple papillary infoldings)Cystic hyperplasiaMinimal compressionAdenomaCircumscribed, compressiveGrowth pattern complex papillary or follicularCells well differentiated and hyperchromaticCarcinomaCapsular invasionInfiltrative, disorganized, varied growth patternCellular pleomorphism and atypiaVarying sized folliclesScirrhous reaction


C-Cell Proliferative LesionsHyperplasiaDiffuse, focal, bothMaximum diameter less than 5 average colloid-filled folliclesAdenomaMaximum diameter greater than 5 average colloid-filled folliclesDiscrete, circumscribedMay compress adjacent folliclesCarcinomaInfiltrative, local & capsular invasionPleomorphism & atypia may be present


C-Cell Hyperplasia, Diffuse

1 of 2

A42474 F344 2-methylimidazole dx= c-cell hyperplasia, diffuse

96

C-Cell Hyperplasia, Diffuse

2 of 2

A42475 F344 2-methylimidazole dx= c-cell hyperplasia, diffuse

97

C-Cell Hyperplasia, Focal

1 of 2

A42478 F344 2-methylimidazole dx= c-cell hyperplasia, focal98

C-Cell Hyperplasia, Focal

2 of 2

A42482 F344 2-methylimidazole dx= c-cell hyperplasia, focal99

C Cell Hyperplasia

Female SD Rat

A45816 Female SD rat, vehicle control dx= c-cell hyperplasia100

Hyperplasia vs Adenoma

1 of 2F344 Rat

A42486 F344 Untreated female dx=c-cell adenoma101

2 of 2Original dx = Adenoma

A42488 F344 Untreated female dx=c-cell adenoma102

C-Cell Adenoma

A10075 F344 Trichlorfon dx=c-cell adenoma103

C-cell Adenoma

A05541 Nalidixic Acid F344 dx= c-cell tumor with amyloid104

C-Cell Carcinoma

1 of 3F344 Rat

A46215 F344 Methylene blue trihydrate dx=C-cell carcinoma105

C-Cell Carcinoma

2 of 3

A46216 F344 Methylene blue trihydrate dx=C-cell carcinoma

106

C-Cell Carcinoma

3 of 3

A46217 F344 Methylene blue trihydrate dx=C-cell carcinoma

107

C-Cell Carcinoma

1 of 3

A47948 Formamide F344 dx=c-cell carcinoma108

C-Cell Carcinoma

2 of 3


C-Cell Carcinoma

3 of 3


C-Cell Proliferative LesionsHyperplasiaDiffuse, focal, bothMaximum diameter less than 5 average colloid-filled folliclesAdenomaMaximum diameter greater than 5 average colloid-filled folliclesDiscrete, circumscribedMay compress adjacent folliclesCarcinomaInfiltrative, local & capsular invasionPleomorphism & atypia may be present


If I have more time..

112


Normal Parathyroid

A54698 KavaKava Extract F344 Normal114

Cyst, NOS

A05286 Phenol F344 dx= cyst, NOS115

Embryonal Cyst

1 of 2

A23383 Aminodibromoanthraquinone B6C3F1 dx=thyroglossal duct cyst116

Embryonal Cyst

2 of 2

A23385 Aminodibromoanthraquinone B6C3F1 dx=thyroglossal duct cyst

117

Ectopic Thymus & Embryonal Cyst

1 of 2

A59824 BALB/c adenoviral vector subchronic study dx - = cyst, ectopic thymus118

Embryonal Cyst

2 of 2

A59825 BALB/c adenoviral vector subchronic study dx - = cyst119

Angiectasis

1 of 2

A49628 Mouse (MW)_ Viral vector, subchronic dx= angiectasis120

Angiectasis

2 of 2

A49629 Mouse (MW)_ Viral vector, subchronic dx= angiectasis121

Cytomegaly

A05290 Propylene oxide F344 dx= cyjtomegaly122

Syncytial Giant Cells

A06101 F344 rat dx= syncytial giant cells123

Parathyroid Fibrosis

Downloaded from NTP Non-Neoplastic Lesion Atlas 1 of 2

A28149 Chloroprene F344 dx=fibrosis124

Parathyroid Fibrosis

Downloaded from NTP Non-Neoplastic Lesion Atlas 2 of 2

A28151 Chloroprene F344 dx=fibrosis

125

Ectopic Thymus

A26251 B6C3F1 Subchronic Ectopic thymus126


Parathyroid Hyperplasia, Diffuse

1 of 3

A03511 F344 Asbestos study dx= diffuse hyperplasia128

Parathyroid Hyperplasia, Diffuse

2 of 3

A03513 F344 Asbestos study dx= diffuse hyperplasia & C-cell proliferative lesion (dx=adenoma)

129

Parathyroid Hyperplasia

3 of 3

A03514 F344 Asbestos study dx= diffuse hyperplasia & C-cell proliferative lesion (dx=adenoma)130


A02622 naphthyl ethyldiamine F344 dx- focal hyperplasia131


1 of 2


2 of 2

A54695133

Parathyroid Adenoma

1 of 2

A14777 F344 Benzylchlorophenol dx= adenoma134

Parathyroid Adenoma

2 of 2

A14778 F344 Benzylchlorophenol dx= adenoma

135

Parathyroid Adenoma

1 of 2

A22217 F344 Vehicle male Nickel subsulfide dx= adenoma136

Parathyroid Adenoma

2 of 2

A22218 F344 Vehicle male Nickel subsulfide dx= adenoma

137

Parathyroid Adenoma

1 of 2

A02310n Rotenone F344 dx=adenoma138

Parathyroid Adenoma

2 of 2

A02311 Rotenone F344 dx=adenoma

139

Parathyroid Carcinoma

1 of 2

A05300 Telone II F344 dx= carcinoma140

Parathyroid Carcinoma

2 of 2

A05301 Telone II F344 dx= carcinoma

141

Thank you for your attention

142

ParameterHumanRat

Thyroxine-binding globulinPresentEssentially absent

T4 Half-life5-9 days0.5-1 days

T3 Half-life1 day0.25 days

T4 production rate/kg BW1X10 x that in humans

TSH1X6-60 x that in humans

Follicular morphologyLow cuboidalCuboidal

Sex differences

Serum TSHSexes equalM 2 x F

Cancer sensitivityF = 2.5 x MM>F

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Neoplastic and Non-neoplastic Rodent Thyroid Lesions and Their Relevance