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Non-Infectious Diseases of RatsPathology of Lab Animals

June 2010

Brett H. Saladino, DVM, Diplomate ACVP

"All rats are not created equal""All rats are not created equal"

Wistar:Wistar: The original outbred albino The original outbred albino laboratory rat. Commonly used in Europe. laboratory rat. Commonly used in Europe. Relatively small, long lived.Relatively small, long lived.

SpragueSprague--Dawley Dawley (Crl:CD(Crl:CD®®BR & Hsd: BR & Hsd: S D lS D l ®®SDSD®®) D i d f) D i d fSprague DawleySprague Dawley®®SDSD®®): Derived from ): Derived from Wistar stock around 1930; rapid weight Wistar stock around 1930; rapid weight gain, early sexual maturity, large.gain, early sexual maturity, large.

F344F344: Commonly used by the NIH. Small : Commonly used by the NIH. Small and long lived.and long lived.

Choose your animal model wellChoose your animal model well

Use industry standard diagnostic criteriaUse industry standard diagnostic criteria

In toxicologic pathology, most hyperplasias are In toxicologic pathology, most hyperplasias are considered preconsidered pre--neoplastic; criteria for diagnosis neoplastic; criteria for diagnosis of hyperplasia vs adenoma is often based on of hyperplasia vs adenoma is often based on size or expansile growthsize or expansile growth

When an uncommon finding occurs in a treated When an uncommon finding occurs in a treated animal, knowledge of spontaneous background animal, knowledge of spontaneous background findings in the same strain of rat and/or good findings in the same strain of rat and/or good historical data is essential for interpretation and historical data is essential for interpretation and assessmentassessment

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REFERENCESREFERENCES Boorman, Eustis, Elwell, Montgomery & Boorman, Eustis, Elwell, Montgomery &

MacKenzie (eds.): MacKenzie (eds.): Pathology of the Fischer Pathology of the Fischer RatRat

Greaves:Greaves: Histopathology of Preclinical Histopathology of Preclinical Toxicity StudiesToxicity Studies

Jones Mohr & Hunt: Monographs onJones Mohr & Hunt: Monographs on Jones, Mohr & Hunt: Monographs on Jones, Mohr & Hunt: Monographs on Pathology of Laboratory AnimalsPathology of Laboratory Animals

The Standardized System of Nomenclature The Standardized System of Nomenclature and Diagnostic Criteria: and Diagnostic Criteria: Guides for Guides for Toxicologic PathologyToxicologic Pathology

Cardiovascular SystemCardiovascular System

CardiomyopathyCardiomyopathy

Spontaneous, idiopathic, degenerativeSpontaneous, idiopathic, degenerative Incidence, severity, and age of onset Incidence, severity, and age of onset

affected by diet & stress.affected by diet & stress. Males > femalesMales > females Males > females Males > females SD SD –– early lesions by 3 months of ageearly lesions by 3 months of age Gross: pale or tan streaksGross: pale or tan streaks Micro: mononuclear infiltrates or Micro: mononuclear infiltrates or

inflammation, myofiber degeneration & inflammation, myofiber degeneration & necrosis, fibrosisnecrosis, fibrosis

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Atrial Atrial ThrombosisThrombosis

Dilated auricleDilated auricle

Organised Organised ggthrombusthrombus

+/+/-- emboli in emboli in other tissuesother tissues

Endocardial HyperplasiaEndocardial Hyperplasia/ Schwannoma/ Schwannoma

Endocardial spindle cell proliferationEndocardial spindle cell proliferation

May infiltrate myocardium & bulge into May infiltrate myocardium & bulge into the ventricular lumenthe ventricular lumenthe ventricular lumen the ventricular lumen

Size & extent of lesion dictates Size & extent of lesion dictates hyperplasia vs schwannoma hyperplasia vs schwannoma

PolyarteritisPolyarteritis

Gross: nodular arterial thickeningGross: nodular arterial thickening

Micro: segmental fibrinoid necrosis of Micro: segmental fibrinoid necrosis of muscular arteries with fibrosis, mixed cell muscular arteries with fibrosis, mixed cell inflammation +/inflammation +/ stenosis & thrombosisstenosis & thrombosisinflammation, +/inflammation, +/-- stenosis & thrombosisstenosis & thrombosis

Common in mesentery, heart base, testes, Common in mesentery, heart base, testes, epididymidesepididymides

Wistar > F344 or SD Wistar > F344 or SD

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Respiratory SystemRespiratory System

Alveolar HistiocytosisAlveolar Histiocytosis

Prevalence: seen occasionally in young Prevalence: seen occasionally in young animals, but very common in older ratsanimals, but very common in older rats

Cause unknown, not infectious or Cause unknown, not infectious or contagiouscontagiouscontagiouscontagious

White to pale tan 1White to pale tan 1--3mm areas on the 3mm areas on the pleural surfacepleural surface

Clusters of foamy macrophages in alveoli Clusters of foamy macrophages in alveoli and terminal airwaysand terminal airways

Digestive System & LiverDigestive System & Liver

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MalocclusionMalocclusion

Incisors grow throughout lifeIncisors grow throughout life

Malocclusion prevents normal wearMalocclusion prevents normal wear

Can interfere with food intake and cause Can interfere with food intake and cause i ht li ht lweight loss weight loss

Low incidenceLow incidence

Occurs more often when rats are fed Occurs more often when rats are fed powdered diets, not pelleted foodpowdered diets, not pelleted food

Stomach Erosion / UlcerationStomach Erosion / Ulceration

Gross: red or black areas on the Gross: red or black areas on the nonglandular or glandular mucosanonglandular or glandular mucosa

Histo: necrosis / loss of epithelium with Histo: necrosis / loss of epithelium with ffinflammation, granulation tissue inflammation, granulation tissue

Multifactorial; related to stress, irritating Multifactorial; related to stress, irritating test articles, or powdered dietstest articles, or powdered diets

Normal LiverNormal Liver

Occasional mitotic figures & multinucleate Occasional mitotic figures & multinucleate hepatocytes are normal, increased hepatocytes are normal, increased numbers indicate pathology numbers indicate pathology

"Streamlining”"Streamlining” blood from differentblood from different Streamlining Streamlining -- blood from different blood from different segments of GI tract concentrates in segments of GI tract concentrates in different liver lobes; toxins with segmental different liver lobes; toxins with segmental absorption may cause lesions in only one absorption may cause lesions in only one lobe; must examine multiple lobes. lobe; must examine multiple lobes.

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Foci of Cellular AlterationFoci of Cellular Alteration

Common in old ratsCommon in old rats Distinct areas in which hepatocytes differ Distinct areas in which hepatocytes differ

in size & staining quality from surrounding in size & staining quality from surrounding hepatocytes, usu no compression hepatocytes, usu no compression p y , pp y , p

Basophilic, eosinophilic, clear, vacuolated, Basophilic, eosinophilic, clear, vacuolated, or mixed or mixed

Significance is somewhat controversialSignificance is somewhat controversial Increased incidence, esp basophilic foci, Increased incidence, esp basophilic foci,

can be considered precan be considered pre--neoplasticneoplastic

Hepatocellular Adenoma / Hepatocellular Adenoma / CarcinomaCarcinoma

Adenoma:Adenoma: Larger than one liver lobule, expansileLarger than one liver lobule, expansile

Loss of normal architectureLoss of normal architecture

C iC i Carcinoma:Carcinoma: Loss of normal architecture; trabecular pattern Loss of normal architecture; trabecular pattern

with irregular cords is most common with irregular cords is most common

Cells can be fairly normal to pleomorphicCells can be fairly normal to pleomorphic

Invasive growth, metsInvasive growth, mets

Bile Duct HyperplasiaBile Duct Hyperplasia

Common; 20Common; 20--50% incidence in older rats50% incidence in older rats

Not considered preneoplastic; bile duct Not considered preneoplastic; bile duct neoplasms are rareneoplasms are rare

N l iN l i No gross lesionsNo gross lesions

Micro: proliferation of wellMicro: proliferation of well--differentiated differentiated bile ductules, +/bile ductules, +/-- fibrosis fibrosis

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Liver Lobe TorsionLiver Lobe Torsion

Acute: hemorrhagic coagulative Acute: hemorrhagic coagulative necrosis +/necrosis +/-- neutrophilic inflammationneutrophilic inflammation

Chronic: fibrosis, variable necrosis & Chronic: fibrosis, variable necrosis & neutrophilic inflammationneutrophilic inflammation

May occur in any lobe; usually the May occur in any lobe; usually the papillary process of the caudate lobepapillary process of the caudate lobe

Hepatodiaphragmatic noduleHepatodiaphragmatic nodule

Nodule on anterior surface associated Nodule on anterior surface associated with small diaphragmatic herniawith small diaphragmatic hernia

Microscopically normal hepatic tissueMicroscopically normal hepatic tissue

F344 > SDF344 > SD

Differentiate from hepatic neoplasiaDifferentiate from hepatic neoplasia

Pancreatic Lobular AtrophyPancreatic Lobular Atrophy

No gross lesionsNo gross lesions

Micro: atrophy / loss of acini with Micro: atrophy / loss of acini with retained ducts mononuclearretained ducts mononuclearretained ducts, mononuclear retained ducts, mononuclear inflammation, +/inflammation, +/-- fibrosisfibrosis

Common finding; increases with age Common finding; increases with age

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Urogenital SystemUrogenital System

Chronic Progressive Nephropathy Chronic Progressive Nephropathy (CPN)(CPN)

Most important disease of rat kidneyMost important disease of rat kidney

Incidence & severity higher in malesIncidence & severity higher in males

C f l d thC f l d th Common cause of early death on Common cause of early death on carcinogenicity studiescarcinogenicity studies

Cause unknown; progressive: causes Cause unknown; progressive: causes renal malfunction or renal failurerenal malfunction or renal failure

Chronic Progressive Nephropathy Chronic Progressive Nephropathy (CPN)(CPN)

Incidence varies with strain; SD may Incidence varies with strain; SD may have early lesions by 3 months of agehave early lesions by 3 months of age

Calorie & protein restriction lowersCalorie & protein restriction lowers Calorie & protein restriction lowers Calorie & protein restriction lowers incidence & severityincidence & severity

Difficult to distinguish from drugDifficult to distinguish from drug--related related effects in toxicity or carcinogenicity effects in toxicity or carcinogenicity studiesstudies

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Chronic Progressive Nephropathy Chronic Progressive Nephropathy (CPN)(CPN)

Gross: Shrunken, pale, and irregularlyGross: Shrunken, pale, and irregularly--shaped kidneys; surface pitted +/shaped kidneys; surface pitted +/-- small small cystscystscystscysts

Micro: Basement membrane thickening, Micro: Basement membrane thickening, ectatic tubules, protein casts, interstitial ectatic tubules, protein casts, interstitial inflammation, fibrosis, tubular inflammation, fibrosis, tubular degeneration / regeneration, glomerular degeneration / regeneration, glomerular crescents, glomerulosclerosis crescents, glomerulosclerosis

CPN related lesionsCPN related lesions

Tubular hyperplasia Tubular hyperplasia

Soft tissue mineralization Soft tissue mineralization (stomach, lung, blood vessels)(stomach, lung, blood vessels)(stomach, lung, blood vessels)(stomach, lung, blood vessels)

Fibrous osteodystrophyFibrous osteodystrophy

Renal MineralizationRenal Mineralization

Distribution can be random or zonal Distribution can be random or zonal

Basement membranes, tubules, Basement membranes, tubules, interstitium, pelvisinterstitium, pelvisinterstitium, pelvis interstitium, pelvis

Background finding, significance? Background finding, significance?

Females > malesFemales > males

F344 > SD & WistarF344 > SD & Wistar

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Hyaline DropletsHyaline Droplets

Protein resorption droplets in lysosomes of the tubule epitheliumα2µ globulin in male rats (normal inα2µ globulin in male rats (normal in

P2 segment of PCT, more extensive with protein overload)

Lysozyme in animals with histiocytic sarcoma

NephroblastomaNephroblastoma

Multilobular tumor, usually at one pole of the kidney

C d f i iti b l Composed of primitive embryonal blastema with tubular and glomeruloid structures

Renal Mesenchymal TumorRenal Mesenchymal Tumor

Arise near corticomedullary junction

Composed of mesenchymal cells with differentiation into musclewith differentiation into muscle, nervous tissue, cartilage or bone

May entrap epithelial elements

Rat specific

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Genitourinary InflammationGenitourinary Inflammation

Nonspecific chronic ongoing inflammationNonspecific chronic ongoing inflammation

Common in old rats, esp malesCommon in old rats, esp males

Caused by bacteria, but bacteria are Caused by bacteria, but bacteria are llrarely seenrarely seen

+/+/-- calculi, epithelial hyperplasiacalculi, epithelial hyperplasia

May involve secondary sex glands May involve secondary sex glands (prostate, seminal vesicles)(prostate, seminal vesicles)

Transitional Cell Papilloma / Transitional Cell Papilloma / CarcinomaCarcinoma

May arise within hyperplastic lesions due to chronic inflammation

Complex branching fibrovascular corep g May see deep growth of epithelial nests; do

not confuse this with infiltrative growth Transitional cell carcinomas have atypia &

pleomorphism True invasive growth is rare

Testicular Atrophy Testicular Atrophy (Hypospermatogenesis)(Hypospermatogenesis)

Primary aging change or secondary to Primary aging change or secondary to polyarteritispolyarteritis

Also around interstitial cell tumorsAlso around interstitial cell tumors

Multinucleated spermatids can occur in Multinucleated spermatids can occur in association or independentlyassociation or independently

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Sperm GranulomaSperm Granuloma

Foreign body reaction to extravasated Foreign body reaction to extravasated spermsperm

Not uncommon in older ratsNot uncommon in older rats

Interstitial Cell TumorInterstitial Cell Tumor

Very common in F344 (~90% at 2 yrs), Very common in F344 (~90% at 2 yrs), uncommon in SD & Wistar (<5%) uncommon in SD & Wistar (<5%)

Expansile mass of foamy polygonal Expansile mass of foamy polygonal ll +/ll +/ h h ih h icells, +/cells, +/-- hemorrhage, necrosis. hemorrhage, necrosis.

Hyperplasia progresses to ICTHyperplasia progresses to ICT

Hyperplasia < 3 tubules diameter < ICTHyperplasia < 3 tubules diameter < ICT

Nearly always benign Nearly always benign

Ovarian Ovarian CystsCysts

IntraovarianIntraovarian FollicularFollicular

LutealLuteal

GlandularGlandular

ParaovarianParaovarian BursaBursa

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TeratomaTeratoma

Tumor of germ cell origin, usually in Tumor of germ cell origin, usually in ovary or testesovary or testes

2 or more germ cell layers present2 or more germ cell layers present

Neural tissue & epithelium often most Neural tissue & epithelium often most prominentprominent

May also see muscle, fat or other May also see muscle, fat or other tissues.tissues.

Endometrial Stromal PolypEndometrial Stromal Polyp

Polypoid mass of endometrial stromaPolypoid mass of endometrial stroma

Very common; F334 > SDVery common; F334 > SD

May undergo torsion / infarction May undergo torsion / infarction

Atypia & invasive growth Atypia & invasive growth sarcomasarcoma

Endocrine SystemEndocrine System

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Pituitary HyperplasiaPituitary Hyperplasia

Nonexpansile (distinguish from Nonexpansile (distinguish from adenoma)adenoma)

Very commonVery common

Cannot determine cell of origin Cannot determine cell of origin without IHCwithout IHC

Pituitary AdenomaPituitary AdenomaPituitary CarcinomaPituitary Carcinoma

Expansile mass in pars distalis +/Expansile mass in pars distalis +/--hemorrhagehemorrhage

Often compresses ventral brain Often compresses ventral brain Usually sharply demarcated (someUsually sharply demarcated (some Usually sharply demarcated (some Usually sharply demarcated (some

diagnose carcinoma if infiltrative growth) diagnose carcinoma if infiltrative growth) Very common in SD (~80% in females, Very common in SD (~80% in females,

60% in males). Slightly less common in 60% in males). Slightly less common in F344 & Wistar.F344 & Wistar.

Nearly all are prolactin + with IHCNearly all are prolactin + with IHC

Islet Fibrosis / PigmentationIslet Fibrosis / Pigmentation

IdiopathicIdiopathic

Occurs sporadicallyOccurs sporadically

Affected islets are admixed with Affected islets are admixed with normal islets in the same sectionnormal islets in the same section

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Islet Cell Hyperplasia Islet Cell Hyperplasia Islet Cell Adenoma / CarcinomaIslet Cell Adenoma / Carcinoma

Criteria is not clear cut, continuum of Criteria is not clear cut, continuum of diagnosesdiagnoses

Size, compression, cellular and nuclear Size, compression, cellular and nuclear , p ,, p ,atypiaatypia

Carcinomas may be well encapsulated Carcinomas may be well encapsulated +/+/-- evidence of breaking through the evidence of breaking through the capsulecapsule

Rarely metastasizeRarely metastasize

Adrenocortical Cystic DegenerationAdrenocortical Cystic Degeneration

Aging change in ratsAging change in rats

Females > malesFemales > males

SD > F344 & WistarSD > F344 & Wistar

Affected adrenal glands are enlarged, soft, Affected adrenal glands are enlarged, soft, dark red, and massdark red, and mass--likelike

Cell vacuolation & loss; dilated, cystic Cell vacuolation & loss; dilated, cystic spaces that contain blood +/spaces that contain blood +/-- thrombi.thrombi.

PheochromocytomaPheochromocytoma

Males > femalesMales > females

F344 > SD > WistarF344 > SD > Wistar

Discrete expansile clusters of basophilic Discrete expansile clusters of basophilic d ll ll /d ll ll / t it imedullary cells +/medullary cells +/-- atypiaatypia

If no compression, may be medullary If no compression, may be medullary hyperplasiahyperplasia

Malignant if capsular invasion or metsMalignant if capsular invasion or mets

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CC--Cell HyperplasiaCell HyperplasiaAdenoma / CarcinomaAdenoma / Carcinoma

Expansile mass of wellExpansile mass of well--differentiated Cdifferentiated C--cellscells

If >5 avg follicles in diam → adenomaIf >5 avg follicles in diam → adenoma

C i i i ith t i itC i i i ith t i it Carcinoma: invasive with atypia, mitoses, Carcinoma: invasive with atypia, mitoses, or mets (lungs), +/or mets (lungs), +/-- hemorrhage, hemorrhage, mineralization or necrosismineralization or necrosis

Incidence low (<5%), but still more Incidence low (<5%), but still more common than follicular tumorscommon than follicular tumors

Lymphoreticular & Lymphoreticular & Hematopoietic SystemsHematopoietic Systems

Thymic Atrophy / InvolutionThymic Atrophy / Involution

Normal, ageNormal, age--related process related process –– 100% 100% incidence in old ratsincidence in old rats

Identifying and collecting thymus in aged Identifying and collecting thymus in aged rats is difficult due to small sizerats is difficult due to small sizerats is difficult due to small size rats is difficult due to small size

Microscopically, lymphocyte population is Microscopically, lymphocyte population is decreased, epithelial cells are more decreased, epithelial cells are more prominent and may form cysts.prominent and may form cysts.

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Mononuclear Cell (LGL) LeukemiaMononuclear Cell (LGL) Leukemia

Common in F344 (~25%), rare in SD & Common in F344 (~25%), rare in SD & WistarWistar

Monomorphic round cell infiltrates in any Monomorphic round cell infiltrates in any organ (esp spleen liver lymph nodesorgan (esp spleen liver lymph nodesorgan (esp. spleen, liver, lymph nodes, organ (esp. spleen, liver, lymph nodes, bone marrow)bone marrow)

May not see cytoplasmic granulesMay not see cytoplasmic granules

Histiocytic SarcomaHistiocytic Sarcoma

Monomorphic histiocytic infiltrates in any Monomorphic histiocytic infiltrates in any organ, often with spindle cell morphologyorgan, often with spindle cell morphology

Mulitnucleate giant cellsMulitnucleate giant cells

L t d t i idL t d t i id Low to moderate incidenceLow to moderate incidence

Lysozyme & EDLysozyme & ED--1+ by IHC1+ by IHC

May see hyaline droplets (lysozyme) in May see hyaline droplets (lysozyme) in renal tubulesrenal tubules

LymphomaLymphoma

Monomorphic lymphocytic infiltrates Monomorphic lymphocytic infiltrates in any organin any organ

Low incidenceLow incidence

R l t d b t t t dR l t d b t t t d Rarely typed, but most are reported Rarely typed, but most are reported to be B cell origin to be B cell origin

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Nervous SystemNervous System

AstrocytomaAstrocytomaOligodendrogliomaOligodendroglioma

Expansile mass with indistinct margins, Expansile mass with indistinct margins, blend with surrounding neuropilblend with surrounding neuropil

RareRare

Oligodendrogliomas tend to have more Oligodendrogliomas tend to have more round nuclei, clear cytoplasmround nuclei, clear cytoplasm

Granular Cell TumorGranular Cell Tumor

Discrete, expansile mass of polygonal Discrete, expansile mass of polygonal cells with PAS+ cytoplasmic granulescells with PAS+ cytoplasmic granules

Uncommon, benignUncommon, benign, g, g

Arise in meningesArise in meninges

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Degenerative MyelopathyDegenerative Myelopathy

Common in old rats (15% in SD)Common in old rats (15% in SD)

May see posterior paresis or ataxiaMay see posterior paresis or ataxia

Also see sciatic nerve degenerationAlso see sciatic nerve degeneration Also see sciatic nerve degenerationAlso see sciatic nerve degeneration

Demyelinization, axonal swelling & Demyelinization, axonal swelling & loss, Gitter cells, reactive gliosis in the loss, Gitter cells, reactive gliosis in the ventral & lateral tracts from T4 ventral & lateral tracts from T4 –– L4 L4

Special Sense OrgansSpecial Sense Organs

Retinal DegenerationRetinal Degeneration

Thinning / loss of the outer nuclear Thinning / loss of the outer nuclear layer, rods & cones layer, rods & cones

More common in old rats, esp albinoMore common in old rats, esp albino

Light induced retinopathy; minimize Light induced retinopathy; minimize by rotating cages in animal rooms or by rotating cages in animal rooms or putting a solid “roof” on the cage putting a solid “roof” on the cage racksracks

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Corneal DystrophyCorneal Dystrophy

Early: basophilic granules along Early: basophilic granules along epithelial basement membraneepithelial basement membrane

Later: mineralization plaque along Later: mineralization plaque along basement membrane and intobasement membrane and intobasement membrane and into basement membrane and into superficial corneal stromasuperficial corneal stroma

CataractCataract Degenerate, swollen lens fibersDegenerate, swollen lens fibers

Displacement of nuclei of lens epitheliumDisplacement of nuclei of lens epithelium

Common in aged ratsCommon in aged rats

Zymbal’s Gland TumorsZymbal’s Gland Tumors

External auditory sebaceous glandExternal auditory sebaceous gland

Gross: Look like abcesses, express Gross: Look like abcesses, express caseous material caseous material

Mi lif ti b &Mi lif ti b & Micro: proliferative sebaceous & Micro: proliferative sebaceous & squamous elements squamous elements

Can grow very large very quickly, Can grow very large very quickly, may invade into brainmay invade into brain

Mets to lungs may occurMets to lungs may occur

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Integumentary SystemIntegumentary System& Mammary Gland& Mammary Gland

GalactocelesGalactoceles

Very common in older rats, esp femalesVery common in older rats, esp females

Gross: cysts or massesGross: cysts or masses

Micro: affected ducts and glands are Micro: affected ducts and glands are dil t d fill d ith t t i l /dil t d fill d ith t t i l /dilated, filled with secretory material, +/dilated, filled with secretory material, +/--cellular debris & inflammatory cellscellular debris & inflammatory cells

If ruptured, inflammation is more severe If ruptured, inflammation is more severe and extends into adjacent tissuesand extends into adjacent tissues

Mammary FibroadenomaMammary Fibroadenoma

SD > F344 & Wistar SD > F344 & Wistar

Females > malesFemales > males

Calorie restriction decreases incidence Calorie restriction decreases incidence

Occur anywhere except head, tail, & Occur anywhere except head, tail, & distal extremitiesdistal extremities

Well circumscribed, firm, lobular mass Well circumscribed, firm, lobular mass with variable amounts of mature collagen with variable amounts of mature collagen & ductular / glandular elements& ductular / glandular elements

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Ulcerative PododermatitisUlcerative Pododermatitis

VariablyVariably--sized ulcers on soles of feetsized ulcers on soles of feet

More common with wire cages & More common with wire cages & ad ad libitumlibitum feedingfeeding

SD F344 & Wi tSD F344 & Wi t SD > F344 & WistarSD > F344 & Wistar

Males > femalesMales > females

Micro: epidermal ulceration, chronic Micro: epidermal ulceration, chronic inflammation; +/inflammation; +/-- hyperostosis of hyperostosis of underlying boneunderlying bone

Auricular ChondritisAuricular Chondritis

Trauma related (ear tags, bites); may Trauma related (ear tags, bites); may be immunebe immune--mediated reaction to Type mediated reaction to Type II collagenII collagen

Low to moderate incidence in group Low to moderate incidence in group g pg phoused animals of certain strainshoused animals of certain strains

Gross: distorted thickened pinnaeGross: distorted thickened pinnae Micro: cartilage degeneration with Micro: cartilage degeneration with

hemorrhage & granulomatous hemorrhage & granulomatous inflammation inflammation

Squamous PapillomaSquamous Papilloma

Exophytic, squamous epithelium Exophytic, squamous epithelium overlying fibrovascular core overlying fibrovascular core

Low incidenceLow incidence

NN i li l NonNon--viralviral

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KeratoacanthomaKeratoacanthoma

Multilocular / cystic invaginations lined by Multilocular / cystic invaginations lined by squamous epithelium & filled with keratin squamous epithelium & filled with keratin debrisdebris

Incidence lowIncidence low Incidence lowIncidence low

May progress to squamous cell carcinomaMay progress to squamous cell carcinoma

Preputial / Clitoral Gland AbscessPreputial / Clitoral Gland Abscess

Specialized sebaceous glands (paired) Specialized sebaceous glands (paired) near the base of the penis or clitorisnear the base of the penis or clitoris

Gross: abcessed glands may be mistaken Gross: abcessed glands may be mistaken for skin or mammary neoplasmsfor skin or mammary neoplasmsfor skin or mammary neoplasmsfor skin or mammary neoplasms

Micro: inflammation is generally chronic Micro: inflammation is generally chronic and ongoing, with marked dilatation of and ongoing, with marked dilatation of main ductsmain ducts

Preputial / Clitoral Gland Preputial / Clitoral Gland Adenoma / CarcinomaAdenoma / Carcinoma

Acinar or squamous differentiationAcinar or squamous differentiation

Acinar tumors have brightly eosinophilic Acinar tumors have brightly eosinophilic cytoplasmic granules (rats only)cytoplasmic granules (rats only)y p g ( y)y p g ( y)

UncommonUncommon

Carcinoma may met to lungs Carcinoma may met to lungs

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Miscellaneous & Miscellaneous & Systemic LesionsSystemic Lesions

ChordomaChordoma

Multilobular tumor of primitive notochord Multilobular tumor of primitive notochord elements (physaliferous cells)elements (physaliferous cells)

May have chondroid or osseous May have chondroid or osseous yydifferentiationdifferentiation

Uncommon, usually located along the Uncommon, usually located along the cervical or anterior thoracic spinecervical or anterior thoracic spine

HibernomaHibernoma

Multilobular tumor of microvesculate Multilobular tumor of microvesculate round to spindloid cells round to spindloid cells

Originate in brown fat; usually on midline Originate in brown fat; usually on midline (intrascapular periaortic)(intrascapular periaortic)(intrascapular, periaortic) (intrascapular, periaortic)

Historically rare; recent reports of Historically rare; recent reports of moderate incidence in SD, Wistarmoderate incidence in SD, Wistar

Distinctive ultrastructural appearance, Distinctive ultrastructural appearance, positive for uncoupling protein by IHCpositive for uncoupling protein by IHC

Mets to lungs are not uncommonMets to lungs are not uncommon

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MesotheliomaMesothelioma

F344 & Wistar (3F344 & Wistar (3--4%), SD (<1%)4%), SD (<1%)

Gross: pale tan nodules on testis, Gross: pale tan nodules on testis, peritoneumperitoneum

Mi l ill f d fMi l ill f d f Micro: complex papillary fronds of Micro: complex papillary fronds of stroma covered by mesothelial cells stroma covered by mesothelial cells

All are considered malignantAll are considered malignant

Distinguish from simple mesothelial Distinguish from simple mesothelial hyperplasiahyperplasia

Special thanks to:Jim NoldCharlie CliffordPaul StrombergPaul StrombergJohn KingBruce WilliamsSteve Van Adestine