The Table of Frequent Questions: Pathology

5th session

- Sidharth R
Please contribute by making comments

Kidney
Disorder Pathogenesis Gross Microscopy Clinical Genetics Special Notes

Membranoproliferative ● Immune mediated ● Glomerular cells : Large ● Nephrotic syndrome Secondary to:
Glomerulonephritis ● IgG hypercellular ● Progressive ● SLE
● Complement activation ● Deposits in mesangial regions deterioration ● Alpha 1
& glomerular capillary wall ● May end in Rapid antitrypsin
● Infiltrating leukocytes Progressive deficiency
● Splitting of basement Glomerulonephritis ● Malignancies
membrane

Diabetic Nephropathy ● AGE - RAGE pathway - ● Thinning of cortical ● Capillary Basement membrane ● Microalbuminuria More prevalent in non
Microangiopathy, tissue thickening ● Hypertension whites - Niggas, Latinos,
Basement membrane ● Diffuse granular ● Diffuse mesangial sclerosis ● Some progress to and Red Indians
collagen cross-linking. nodules on surface ● Nodular Glomerulosclerosis end-stage requiring
● Protein Kinase C (Kimmelstiel-Wilson disease) dialysis
activation ● Renal atherosclerosis
● Oxidative stress

Minimal change ● Degeneration of foot ● Normal with Light microscopy ● Massive proteinuria May occur
disease process of podocytes ● Visceral epithelial cells: uniform (90% albumin) secondary to
● Immune mediated. loss of foot processes ● Excellent prognosis - NSAID therapy,
● No Ig/complement deposits Steroids, or growth to Hodgkin
puberty. lymphoma

Post-streptococcal ● 1-4 weeks after strep ● Enlarged, Hypercellular ● Malaise, fever, nausea
Glomerulonephritis infection (sore throat, glomeruli and endothelium ● Oliguria, mild
impetigo) ● Infiltration of leukocytes Hematuria, mild
● Immune complex ● Subepithelial “hump” Proteinuria
containing streptococcal ● Granular deposits of Ig and ● Most recover with
antigens complement supportive therapy
Adult Polycystic Kidney ● Autosomal dominant ● Kidneys - Bilaterally ● Functional nephrons found ● Asymptomatic until ● Mutated APDK Most dies of
disease mutation enlarged between cysts renal insufficiency gene (PKD1 or Polycystic liver,
● Mutation of gene ● Composed of masses ● Bowman capsule occasionally ● Associated colicy Pain PKD2) valve prolapse,
responsible for altered of cysts involved ● Insidious hematuria, berry aneurysms
tubular cilia sensation/ ● No parenchyma progressive kidney
calcium flux disease, hypertension
● This causes altered ● Other extrarenal
tubular epithelial growth - congenital anomalies
causing cysts

Childhood Polycystic ● Autosomal recessive ● Kidneys - Bilaterally ● Survivors have ● Mutated PKHD1 -
Kidney Disease mutation enlarged associated hepatic fibrocystin
● ● Smooth external fibrosis
appearance
● Small cysts on c.s -
Sponge like
● Dilated elongated
channels replaces
medulla and cortex

Chronic Pyelonephritis ● Reflux nephropathy: ● Irregular scarring ● Variable Tubular ● Silent onset or
○ Early childhood ● Coarse, discrete, atrophy/hypertrophy ● Back pain, fever,
○ UTI + Reflux Corticomedullary scars ● Thyroidization : Casts fill pyuria, bacteriuria
(Vesico-ureteral, ● Dilated, blunted, tubules, like thyroid colloid ● Renal insufficiency
intrarenal) deformed calyces ● Inflammation and fibrosis in ● Hypertension
● Chronic obstructive ● Flattening of papillae cortex and medulla ● Polyuria, nocturia
nephropathy: ● Secondary focal
○ UTI + Obstruction segmental
○ Inflammation and glomerulosclerosis
scarring ● Progress to End-Stage
○ Parenchymal Renal Disease
atrophy

Lupus Nephritis ● Autoimmune mediated Stages: ● Hematuria ● MHC associated

● Deposition of immune ● Class I - Minimal mesangial: ● Nephritic syndrome genes
complexes in the Immune deposits in mesangium ● Progressive ● HLA linked gene
mesangium and ● Class II - Mesangial glomerulonephropathy mutation
basement membrane proliferative: Mesangial cell ● Acute and chronic renal
proliferation, mesangial matrix failure
accumulation ● Hypertension
● Class III - Focal : <50%
glomeruli affected (swelling,
proliferation of endothelial cells,
inflammation)
● Class IV - Diffuse: Most
common, >50% glomeruli
affected
● Class V - Membranous : Diffuse
thickening of capillary walls,
increased production of
basement membrane like
material
● Class VI - Advanced sclerosing:
 >90% glomeruli involved

Renal Cell Carcinoma ● Smoking, Obesity, ● Bright yellow Clear cell ● Costovertebral pain ● VHL gene
Hypertension grey-white spherical ● PCT origin ● Palpable mass deletion
● Hereditary predisposition masses ● Polygonal clear cells - clear or ● Hematuria
○ VHL syndrome ● Large areas of granular cytoplasm ● General weakness,
○ H. necrosis and ● Delicate vasculature fever, weight loss
leiomyomatosis haemorrhagic ● Invades renal vein ● “Great mimic” of other
○ H. Papillary discoloration systemic illness
carcinoma ● May grow in the ● Mets before any clinical
inferior vena cava up sign
to the heart! ● Prognosis good if
without mets
Papillary ● MET - proto
● DCT origin oncogene
● Cuboidal cells in papillary
formation
● Interstitial foam cells
Other:
● Chromophobe renal carcinoma
● Collecting duct carcinoma

Wilms Tumor ● WAGR syndrome - ● Large, solitary, well ● Triphasic combination of cell ● Large abdominal mass ● WAGR : WT1
○ Wilms circumscribed mass types: in children (after second hit) -
○ Aniridia(no iris) ● Soft, homogenous ○ Blastemal (blue sheets) ● Hematuria, Pain, ● Denys-Drash:
○ Genital tan-grey on c.s ○ Stromal (fibro-cytic) Intestinal obstruction, Inactivated
abnormalities ● Occasional ○ Epithelial (tubules, Hypertension inactivation of
○ Retardation haemorrhage, cyst, glomeruli) ● Good prognosis mostly WT1
● Denys-Drash syndrome - and necrosis ● Anaplastic cells found rarely ● High risk of developing ● BWS: WT2 with
also develop (bad prognosis) other primary tumors genomic
gonadoblastoma due to mutation or imprinting
● Beckwith-Wiedemann radiation
Syndrome (BWS)
● Beta-catenin gain of
function mediated

Acute Tubular Injury ● Caused by Ischemia, ● Focal tubular epithelial necrosis Initiation:
Direct toxic injury along the nephron with skip ● Decreased Urine output
● Causes areas ● Increased BUN
○ Tubular cell injury, ● Occlusion of tubular lumen by ● Due to decreased GFR
○ Persistent eosinophilic hyaline casts Maintenance
disturbances in ● Sustained salt, water
blood flow overload
● Raising BUN
● Uremia
Recovery
● Hypokalemea is
problematic
● Vulnerable to infection

Female Genital Tract

Disorder Pathogenesis Gross Microscopy Clinical Genetics Special Notes

Ovarian Epithelial tumours Serous: ● Mass projecting from ● Cysts lined by columnar ● Lower abdominal pain, Low grade:
● Nulliparity, family ovarian surface epithelium with cilia (in benign) enlargement ● KRAS
Classification for each: history, Heritable ● Multicystic - papillary ● Increased complexity and ● GI complains, urinary ● BRAF
● Benign: Well mutations play a role epithelium within stratification of papillae in frequency, dysuria ● ERBB2
defined epithelium ● High grade tumors fibrous walled cysts borderline ● Benign lesions easily High grade:
with originates from ● Malignant: Papillary ● High infiltration and nuclear resected ● TP53
● Borderline: fallopian tube tumour mass increases atypia in Malignant ● Malignant Progressive ● BRCA1/2
Increased ● Psammoma bodies : concentric weakness, cachexia
proliferation calcifications ● Massive Ascites (fluid
● Malignant: Invade filled with tumor cells)
stroma, high Mucinous: Genetic mutation ● Large cystic masses ● Lined by tall columnar epithelial ● Poor prognosis - Mostly Mutation of KRAS
nuclear atypia with other collaborating ● Filled with sticky cells present with high stage proto-oncogene
mutations gelatinous fluid (rich in ● Excessive glandular growth disease
glycoprotein) ● Intraepithelial carcinoma until it
● Multiloculated invades the stroma
● Surface rarely involved

Endometrioid: Solid and cystic areas of Glandular pattern resembles Mutation in:
● Arise in setting of growth endometrial tissue ● PTEN
endometriosis ● CTNNB1 (beta
● Might be associated catenin)
with areas of ● KRAS
borderline tumor
● Increased PI3K/ AKT
signalling

Dysgerminoma ● Counterpart of ● Highly variable in size ● Large vesicular cells ● Might produce elevated ● OCT3/4
seminoma ● Soft, fleshy ● Clear watery cytoplasm chorionic gonadotropin ● NANOG
● May occur in patients yellow-white to greyish ● Well defined cell boundaries ● Malignant, but varies in
with Gonadal pink on c.s ● Sheets of cells separated by aggressiveness
dysgenesis scant fibrous stroma ● Good prognosis if not
● Lymphocytic infiltration, broken through the
granulomas capsule
● Dysgerminoma might also be
present
● KIT immunofluorescence

Teratoma Mature : Dermoid cyst, arises ● Bulky, smooth external ● Immature neuroepithelium, ● Younger women during Karyotype - 46XX
from ovum after meiotic surface cartilage, bone, muscle tissues active reproductive
division ● Hair, sebaceous ● Immature neuroepithelium tend years
material, cartilage, to spread ● Paraneoplastic
bone, calcifications syndrome:
● Areas of haemorrhage Inflammatory limbic
and necrosis encephalitis

Immature: Resemble Occurs in Prepubertal

embryonal foetal cells adolescents

Monodermal/ Specialized: ● Spread fast

● Resemble thyroid - ● Stage I - Good
hyperthyroidism prognosis
● Intestinal - Carcinoid ● Recurrence mostly
within 2 years

Cervical Intraepithelial ● Mostly caused by SIL: ● Peaks in active Viral gene insertion -
Neoplasia (CIN) high risk HPV(16,18) ● Nuclear atypia, enlargement reproductive age Dysregulation of MYC
● Viral protein E6 and ● Hyperchromasia ● LSIL - benign; some gene
E7 interfere with ● Coarse chromatin granules transform into HSIL.
tumour suppressors ● Variation in nuclear size and Monitoring and
and growth regulators shape conservative therapy
(p53, MYC) ● Perinuclear halo : koilocytic ● HSIL - high risk of
atypia progression into
LSIL: Immature cells confined to lower carcinoma
⅓ of epidermis
HSIL: Immature cells invade upper ⅔
of epidermis

Cervical Carcinoma ● High risk HPV ● Fungating(exophytic) Squamous cell carcinoma - ● PAP smear helps in
● May develop from or infiltrative mass ● Nests of malignant squamous early diagnosis
adenocarcinoma in Stages: epithelium (may or may not ● Cervical cone excision
situ or HSIL ● Stage 0 - HSIL (CIN III) keratinize) in early cases
● Stage I - Carcinoma ● Invade underlying strome ● Hysterectomy with
confined to cervix Adenocarcinoma - lymph node dissection
● Stage II - Extends ● Proliferation of glandular in malignant cases with
beyond cervix epithelium radiation and chemo
● Stage III - Extends to ● Large, hyperchromatic nuclei ● Neuroendocrine - very
the pelvic wall and dark appearance of glands bad prognosis
● Stage IV - Extends Neuroendocrine - like small cell
beyond pelvis carcinoma of lungs

Endometrial Hyperplasia ● Prolonged estrogenic Non- atypical: Abnormal vaginal bleeding Inactivation of PTEN in
stimulation ● Increased gland-to-stroma ratio some cases
● Inactivated PTEN ● Glands dilated
cause PI3K/ AKT Atypical:
pathway amplification ● Complex patterns, nuclear
atypia
● Cells not oriented to basement
membrane
● Premalignant lesion

Endometrial carcinoma Type 1 (Endometrioid ● Localized polypoid or ● Glandular growth pattern ● Occurs > 40 yrs ● PTEN mutation
carcinoma): diffusely infiltrative ● Asymptomatic for a ● Loss of function
● Endometrial ● Spreads by myometrial Glandular tissue may be: long time ARID1A
hyperplasia precedes invasion ● Well differentiated ● Irregular ● TP53 loss of
● Assn with Obesity, Stages: ● Moderately differentiated - Solid postmenopausal function
Diabetes, ● Stage I - Confined to sheets of cells seen vaginal bleeding
Hypertension, uterine body ● Poorly differentiated - Mostly ● Leukorrhea
Infertility, Estrogen ● Stage II - Involved solis cells ● Type 2 is highly
stimulation cervix invasive
● PI3K/ AKT pathway ● Stage III - Outside ● Prognosis depends on
amplification uterus, within true stage of identification
pelvis ● Resection, Radiation,
● Stage IV - Beyond true Chemotherapy
pelvis

Type 2 (Serous Carcinoma): ● Occurs in small ● Serous Endometrial ● TP53 Mutations

● Endometrial atrophy atrophic uterus Intraepithelial Carcinoma lacks
● Precursor - Serous ● Large bulky tumours invasion
Endometrial ● Deeply invades ● Papillary growth pattern
Intraepithelial myometrium ● High atypia
 Carcinoma ● May also be glandular

Hydatidiform mole Complete mole: ● Delicate mass of ● Enlarged chorionic tissue ● High risk in teenagers Complete mole: 46XX or
Fertilization of egg without thin-walled translucent ● Cisterns present and 40-50 yrs 46XY
chromosomes by 1 grape like structures ● Trophoblastic proliferation ● Abnormally high HCG
(homozygous) or 2 sperms ● Swollen hydropic villi involves the circumference of levels Partial mole: 69XXX,
(heterozygous) the villi ● Spontaneous 69XXY, 69XYY
miscarriage
Partial mole: Fertilization of ● Removed by curettage
normal egg with 2 sperms ● Invasive mole:
Penetrates uterine wall,
Invasive mole: may embolize.
Regresses without
chemotherapy

Male Genital Tract

Disorder Pathogenesis Gross Microscopy Clinical Genetics Special Notes

Seminoma ● From precursor lesion ● Bulky masses ● Sheets of uniform cells divided ● 30 - 40 yrs old male ● Isochromosome
- Intratubular germ ● Homogenous, grey into lobules 12p
cell neoplasia white lobulated on c.s ● Large, round polyhedral cells ● Express OCT3/4
(ITGCN) ● Tunica albuginea ● Watery cytoplasm and NANOG
● Growth activating usually not penetrated ● Large central nucleus ● KIT activation
mutations ● May extend to ● Anaplastic in some tumours
epididymis, spermatic ● Expression of KIT, OCT4 in
cord, scrotal sac. immunohistochemistry

Teratoma ● Heterogenous with ● Different organ type like tissues Isochromosome 12p
solid, cartilaginous, found- Squamous epithelium,
cystic areas Thyroid gland, Bronchiolar
● Hemorrhage and epithelium, brain structures
necrosis ● Fibrous stroma
● One tissue may change into
into teratoma with malignant
transformation (mostly
squamous)

Choriocarcinoma ● Mostly occurs mixed ● Syncytiotrophoblasts:

with other germ cell ○ Large, multinucleated
tumours ○ Contain HCG
● No testicular ● Cytotrophoblasts:
enlargement ○ Regular, polygonal
● Small palpable nodules ○ Distinct borders, clear
cytoplasm

Benign Prostatic The androgen DHT might ● Nodular hyperplasia ● Dilated glands with two layers - ● Men, > 50 years
Hyperplasia induce: ● Mostly inner aspect inner columnar, outer flattened ● Urinary obstruction
● Stromal Growth (transition zone) ● Reactive squamous metaplasia ● Risk of infection and
 ● Retard cell death ● Compresses urethra sometimes seen UTI
leading to senescent ● Median lobe ● Polyuria, nocturia.
cells hypertrophy - on floor ● Difficulty starting and
of urethra stopping urine
● Glandular nodules- Treatment:
yellow-pink, soft, ● Alter fluid intake
exude milky prostatic behavior
fluid ● alpha - blockers
● Fibrous nodules - pale ● Surgery - Transurethral
grey, tough. Creates a resection of prostate
pseudo capsule (TURP)
● Ultrasound, laser
therapy

Urinary Bladder tumour ● Smoking, Papilloma - ● Identical to normal urothelium ● Painless hematuria ● FGFR3 - Gain of
● Exposure to ● Small, delicate ● Benign ● Tumour cells can be function
arylamines, attached to mucosa by found in urine (FISH) ● TP53, RB loss -
● Schistosoma stalk only in high grade aggressive
haematobium ● Inverted papillomas neoplasms tumour
● Heavy use of extend into lamina ● High recurrence rate ● CDKN2A deletion,
Cyclophosphamide propria ● Infiltrative tumour had PTCH
● Irradiation bad prognosis,
Papillary urothelial cancer ● Discohesive cells, ● Deadly, mostly due to
hyperchromatic nuclei late diagnosis
● Highly anaplastic
● Loss of polarity
● Invasion into muscular layer

Carcinoma in situ: Lack of cohesiveness

● Malignant cells within
flat urothelium.
● Shedding of cells in
urine

Invasive Urothelial cancer ● Extends into muscularis

mucosae

Breast
Disorder Pathogenesis Gross Microscopy Clinical Genetics Special Notes

Carcinoma Breast ER +ve, HER2 -ve: ● Calcifications on mammogram ● Well differentiated to ● Common in ● BRCA2 mutation
Risk factors: ● PI3K signalling ● Grating sound on cutting poorly differentiated menopausal estrogen ● PIK3CA activation
● Germline mutation, pathway enhanced ● Invasion into the pectoralis ● Mucinous, papillary, therapy in older
relatives with Types: ● Dimpling of the skin, retraction cribriform, lobar women, men
cancer, ● High proliferation of nipple patterns seen ● Detected by
race/ethnicity ● Low proliferation ● Usually detected in breast mammographic
● Age - > 70 before axillary lymph node screening
● Age at menarche - presentation ● Long survival possible
<11 General Microscopy: with metastases
● Age at first live Nottingham Histologic Score: tubule (mostly to bone)
 birth - >20 HER2+ve: formation, nuclear pleomorphism, ● Poorly differentiated ● Metastasize early ● TP53 mutations
● High estrogen ● HER2 is tyrosine mitotic rate ● Apocrine and (mostly to bone, brain, (Li-Fraumeni syn.)
exposure kinase receptor ● Grade I : micropapillary types viscera) ● Amplification of
● High breast density ● Progesterone ○ Tubular pattern ● HER2 receptor HER2 (on
● Radiation exposure receptor absent ○ Small round nuclei antibodies is effective chromosome 17q)
● Bad Diet, obesity, ○ Low proliferation rate treatment
no exercise ● Grade II : ● Survival with mets rare
● Less breast feeding ○ Some tubule formation
ER-ve HER2-ve: ○ Clusters or single ● Poorly differentiated ● Common in young BRCA1 mutation
Least understood pathway infiltrating cells ● Special histological premenopausal
○ High nuclear patterns recognized women, African
pleomorphism (incl. Carcinoma with Americans
● Grade III: medullary features) ● Presents as palpable
○ Ragged nests mass
○ Large irregular nuclei ● Prognosis after mets is
bad

Medullary carcinoma ● ER-ve HER2 -ve with Softer in consistency due to minimal ● Solid syncytium like Relatively good prognosis BRCA1 - downregulation
BRCA1 desmoplasia sheets of large cells (might be due to host
● A special histological with prominent nuclei immunity)
type ● Frequent mitotic
figures
● Lymphocytic
infiltration

Fibroadenoma (benign) ● Polyclonal ● Small to large enough to replace ● Stroma resembles ● 20 - 30 years old
hyperplasia of lobular most of breast normal interlobular ● Multiple and bilateral
strom ● Well circumscribed, rubbery stroma ● Palpable mass with
● Cytogenetic ● Greyish white nodules bulge out ● Epithelium mammographic density
aberrations confined of the tissue surrounded, ● Complications with
to stromal component compressed by inflammation may
● Cyclosporin A after stroma resemble carcinoma
renal transplant ● Dense hyalinized
stroma, atrophic
epithelium in older
patients

Cystosarcoma phyllodes/ Arise from intralobular ● Very small to very large ● Bulbous leaf like ● Detected mostly as ● Gain in
Phyllodes tumor stroma protrusions palpable masses chromosome 1q
● Higher cellularity, ● HOXB13
mitotic rate than overexpression
fibroadenomas ● Low grade mostly,
don’t metastasize
often

Skin
Disorder Pathogenesis Gross Microscopy Clinical Genetics Special Notes

Basal Cell carcinoma ● Mutation in hedgehog ● Pearly papules ● Origin from epidermis, follicular ● Blockage in Hedgehog ● PTCH mutation - Nevoid Basal
pathway : Excessive ● Telangiectasis : epithelium pathway might be Hedgehog cell carcinoma
 stimulation of growth Prominent dilated ● Multifocal : Spreads over large area possible therapy signalling syndrome
pathway subepidermal ● Nodular : Grows downwards deeply pathway
● Immunosuppression vessels ● Basophilic cells, Hyperchromatic
● Lesions ulcerate - nuclei
Rodent ulcers ● Surrounded by fibroblasts and
lymphocytes
● Palisading arrangement at edges

Squamous cell carcinoma ● UV induced DNA In situ: In situ: ● TP53 mutation:

damage ● Sharply defined, ● Cells with atypia DNA Repair with
● Immunosuppression red scaling ● Found in all levels of epidermis errors
(caused by HPV) plaques Invasive: ● Increased RAS
Infiltrative: ● Variable degree of differentiation signalling
● Nodular ○ Polygonal cells in lobules mutations
● Hyperkeratotic ○ Large areas of keratinization
plaques ○ Highly anaplastic cells
● May ulcerate

Melanoma ● Acquired mutations ● High variation in General: ● Asymmetry ● CDKN2A

with UV exposure colour - black, ● Large cells with irregular contours ● Borders : irregular mutation : CDK4
effect: brown, red, blue, ● Large nuclei, clumped chromatin ● Colour : variegated mediated cell
○ Pro-growth grey Radial growth: ● Diameter : increased cycle stopper
pathway ● Irregular and ● Horizontal spread ● Evolution over time ● BRAF activation
○ Cell cycle notched borders ● Within epidermis and superficial ● Associated itching, pain : Increased RAS,
○ Telomerase dermis ● Breslow thickness is PI3K signalling
● Inherited: Autosomal ● Lack ability to metastasize prognostic ● TERT :
dominant mutation ● Lentigo maligna, superficial spreading ● Resistant to conventional Telomerase
Vertical growth: chemotherapy and activation
● Metastatic potential radiation
● Appearance of nodules ● Antibody therapy to
● Breslow thickness : Superficial stimulate T-cells to kill the
epidermis to infiltration level tumour

Bone
Disorder Pathogenesis Gross Microscopy Clinical Genetics Special Notes

Ewings ● Primitive ● Involves cortex, ● Small uniform round cells ● Younger than 20 Fusion of EWS gene on
neuroectodermal periosteum and soft (lymphocyte like) without ● Aggressive tumours, 22 to FLI1 gene
tumour tissues obvious differentiation treated with
● Genetic disorder ● Soft, tan white ● Clear, scant cytoplasm ○ neoadjuvant
● Maybe transcription, ● Areas of haemorrhage ● Neuroectodermal differentiation chemotherapy
RNA splicing and necrosis - Homer-Wright rosettes ○ Surgical
mediated ● Fibrous septa in little stroma excision

Osteoclastoma/ Giant cell ● High osteoclastic ● Arise in epiphysis but ● Uniform oval mononuclear cells ● Treated with curettage ● RANKL highly Mostly around the
tumour proliferation, absence may extend to ● Osteoclast type giant cells with ● Recurrence likely expressed knee
of feedback metaphysis 100 or more nuclei! ● Metastasize to lungs
● Localized, destructive ● Destruction of cortex, ● Prominent necrosis and mitotic ● RANKL inhibitor in trials
bone resorption soft bulging tumour activity
mass

Osteosarcoma ● Genetic origin ● Bulk, gritty, gray-white ● Tumour cells - Hyperchromatic ● Neoadjuvant ● RB mutation Mostly around the
● Peak during ● Hemorrhage and cystic nuclei, form bone tissue chemotherapy ● TP53 knee
adolescent growth degeneration (diagnostic) ● Surgery ● INK4a inactivation
spurt ● Infiltrate medullary ● Fine lace like neoplastic bone ● Metastasize to lungs ● MDM2 and CDK
canal, replacing hematogenously - bad overexpression
hematopoietic marrow prognosis

Mycobacterial ● Caused by M. ● Caseous necrosis ● Granulomas ● Tuberculous spondylitis

Osteomyelitis tuberculosis ● Other typical tb findings is very destructive -
● Haematogenous Pott disease
spread from ● Spine involvement -
pulmonary TB Fracture of vertebral
disks, kyphosis
● Neurological defects

Pyogenic Osteomyelitis ● Bacterial infection ● Necrosis of bone and ● Neutrophilic inflammatory ● Acute systemic -
from mucosal injury, marrow reaction Malaise, fever, chills
fractures, surgeries ● Sub periosteal abscess ● Infection spreads longitudinally ● Throbbing pain
● Strep. aureus most can drain into skin as a along the Haversian system ● Lytic focus in bone
common other. Also sinus radiograph
by E. coli, ● Dead bone - ● May persist as chronic
Pseudomonas, Sequestrum infection
Klebsiella ● Reactive bone ● Acute flare-ups
● Cell wall protein binds deposition - Involucrum
to bone matrix ●
● Vasculature plays a
vital role in spread

Rheumatoid arthritis ● Chronic inflammatory Joints Joints Fever, fatigue, generalized ● HLA-DRB1 -
Autoimmune disease ● Small joints of hand ● Synovial cell hyperplasia pain Antigen binding
● CD4+ Helper T and feet ● Dense inflammatory cell ● Joint pain - small joints part
secrete cytokines to ● Synovium is infiltration first ● PTPN22
autoantigens or edematous, thickened, ● Increased vascularity (Metacarpophalangeal
microbial antigens villous and proximal
● TNF mediated ● Formation of pannus interphalangeal)
proteolytic destruction (mass of synovial, ● Upper spine
inflammatory tissue) involvement
and fibrous/bony ● Stiff, warm, swollen
ankylosis joints in the morning
Skin - Rheumatoid ● Baker cyst in knee
subcutaneous nodules ● Treat with steroids,
Blood vessels - high risk of anti-TNF agents
vasculitis

Gout ● Crystallization of Acute arthritis : ● Asymptomatic HGPRT deficiency

monosodium urate ● Neutrophilic infiltration hyperuricemia
● Hyperuricemia: ● MSU crystals in neutrophils and ● Acute arthritis
○ increased synovium ● Asymptomatic
production Chronic tophaceous: resolution period
○ Decreased ● MSU encrusts articular surface ● Complications: Chronic
 excretion] ● Synovium becomes tophaceous gout
● Inflammation hyperplastic - pannus
triggered by Tophi
precipitation of ● Aggregation of Urate crystals
Monosodium urate ● Foreign body giant cells
(MSU)
● Gouty nephropathy
● MSU in renal medulla,
interstitium and tubules

Endocrine
Disorder Pathogenesis Gross Microscopy Clinical Genetics Special Notes

Hashimoto Thyroiditis ● Auto-immune disease ● Diffusely enlarged ● Infiltration of parenchyma by ● Painless enlargement Associated with:
● Breakdown of self ● Intact capsule and well mononuclear inflammatory cells of thyroid ● CTLA4 (T-
tolerance to thyroid demarcated from other ● Germinal centres of leukocytes ● More common in lymphocyte
antigens structures seen women 45+ and associated
● Abnormalities in ● Pale, yellow- tan, firm, ● Atrophic thyroid follicles children antigen)
Regulatory T cells nodular surface surrounded by eosinophilic - ● Hypothyroidism ● PTPN22 (Protein
● Thyroid cell death by - Hurthle cells ● May cause tyrosine
CD8+ cytotoxic cells, ● Metaplastic response of thyrotoxicosis due to phosphatase)
Cytokine mediated, cuboidal epithelium disruption of follicles
Antibody mediated (hashitoxicosis)
● May develop other
autoimmune disorders
too

Papillary carcinoma ● RET/PTC mutation ● Solitary or multifocal ● Branching papillae with ● Female preponderance ● RET/PTC
Thyroid causes receptor with ● Well circumscribed or fibrovascular stalk ● Mass in the cervical translocation or
tyrosine kinase activity infiltrating ● Covered by cuboidal epithelium lymph nodes inversion
● Activation of BRAF arm ● Fibrosis and ● Anaplastic changes seen ● Mass moves with the ● BRAF mutation
of the signalling pathway calcification seen ● Optically clear, ground glass thyroid gland during
● Papillary foci on c.s appearance of nuclei swallowing
● Psammoma bodies : ● Hoarseness,
Concentrically calcified dysphagia, cough,
structures in core of papillae dyspnea in advanced
● Lymphocytic infiltrate may be disease
seen ● Excellent prognosis
● Variants:
○ Tall cell
○ Diffuse sclerosing
○ Papillary
microcarcinoma

Grave’s ● Autoimmune ● Symmetrically ● Hypertrophy and hyperplasia of ● Hyperthyroidism Immune function genes:
● Antibodies against TSH enlarged follicles ● Infiltrative ● CLTA4
receptor, and other ● Parenchyma is soft ● Crowding results in papillae Ophthalmopathy ● PTP22
thyroid proteins and meaty like muscle formation ● Dermopathy, pretibial ● HLA-DR3
 ● Inflammation mediated ● Lymphoid infiltrates myxedema
ophthalmopathy ● Elevated T3 and T4,
Decreased TSH
● Preoperative Iodine
therapy

Multinodular Goitre ● Response by follicular ● Multilobular, enlarged ● Follicular hyperplasia: colloid ● Mistaken for neoplasms
cells to Trophic hormone glands rich follicles Mass effect
● TSH signalling pathway ● Asymmetric and may ● Surrounded by inactivated ● Airway obstruction
becomes autonomous in cause pressure on one flattened epithelium ● Nerve
some nodules side ● Artery/Vein : Superior
● Intra-thoracic or vena cava syndrome
plunging goiter if
extends beyond ● Hyperthyroidism: Toxic
sternum multinodular goitre
● Irregular nodules with ● FNAC helpful in
brown gelatinous diagnosis
material on c.s

Diabetes Mellitus Type 1 ● Reduction in number ● Polyuria HLA cluster on

● Autoimmune Destruction and size of islets in ● Polydipsia chromosome 6p21
of pancreatic islets pancreas ● Polyphagia
● Failure of self tolerance ● Leukocytic infiltrates in Acute complications:
in T cells specific for Beta islets ● Diabetic ketoacidosis
cells of islets (fatigue, nausea,
● Viral - molecular vomiting, Kussmaul
mimicry? breathing)
● Hypoglycemia

Type 2 ● Reduction in islet cell Acute complications: Monogenic diabetes:

● Insulin resistance, Beta mass ● Hyperosmolar ● Glocokinase
cell dysfunction ● Amyloid deposition in Hyperosmotic mutaion - GCK
● Obesity contributes by: islets Syndrome ● Insulin receptor
○ Adipokines ● Hypoglycemia gene
○ Free fatty acids
○ Inflammation

Chronic Complications Macrovascular disease: ● Macrovascular:

● AGE-RAGE: ● Endothelial injury ○ Myocardial
● Activation of Protein ● Atherosclerosis infarction
Kinase C ● Myocardial infarction ○ Renal vascular
● Oxidative Stress ● Hyaline arteriosclerosis insufficiency
Microangiopathy: ○ Cerebrovascular
● Diffuse thickening of accident
basement membrane ● Diabetic Nephropathy
● Capillaries more leaky ● Visual impairment
Nephropathy ● Diabetic Neuropathy
● Enhanced susceptibility
Ocular complications: to TB, pneumonia,
● Opacification of lens - pyelonephritis
cataract
● Glaucoma
● Retinopathy
Neuropathy

Pheochromocytoma Rule of 10s: ● Small well ● Highly variable ● Hypertension Increased Growth:
 10% extra-adrenal circumscribed lesions ● Clusters of chromaffin cells ● Paroxysmal episodes ● RET, NF1
10% bilateral ● Might also be large ● Surrounded by supporting ● May precipitate acute ● HIF1alpha
10% not associated with HTN and hemorrhagic sustentacular cells creating heart failure due to
25% genetic ● Richly vascular alveoli(zellballen) sudden increase
● Remnants of adrenals ● Richly vascular ● Tumour may also
can be seen ● Salt and pepper nuclei secrete ACTH and
● Chromaffin: ● Definitive diagnosis of somatostatin
Incubation with malignancy based only on
Potassium dichromate metastases.
turns it brown due to
oxidation of stored
catecholamines

CNS
Disorder Pathogenesis Gross Microscopy Clinical Genetics Special Notes

Chronic Meningitis(TB) ● M. tuberculosis in ● Subarachnoid space ● Inflammatory infiltration ● Headache, malaise,

CNS along with has gelatinous or ● Granulomas with caseous confusion, vomiting
active disease fibrous exudate necrosis ● Pleocytosis, elevated
● Haematogenous ● Discrete white areas of ● Giant cells protein level in CSF
spread inflammation over ● Acid fast bacilli ● Complication:
leptomeninges Arachnoid fibrosis -
● Discrete white areas of causes hydrocephalus,
inflammation scattered infarction
over ● Tuberculomas
leptomeninges(pia + resemble tumours
arachnoid) ● AIDS patients M.
● Tuberculomas : Well avium-intracellulare
circumscribed
intraparenchymal
masses

Pyogenic meningitis ● Bacterial - E. coli, L. ● Exudate on the surface ● Neutrophils fill the ● Systemic signs of
monocytogenes, S. of the brain subarachnoid space infection with
pneumoniae, ● Pus follows along ● Gram stain reveals bacteria neurological
Neisseria meningitidis blood vessels of the ● Inflammatory cells may infiltrate involvement, headache,
● Immunosuppressed brain leptomeninges and go into the neck stiffness
people at high risk ● Hydrocephalus after brain (cerebritis) ● CSF cloudy or purulent.
Leptomeningeal Increased
fibrosis - chronic ● Treated with antibiotics
adhesive arachnoiditis ● Infection symptoms
● Neurological
involvement:
● CSF cloudy, purulent
● Treat with antibiotics

Meningioma Molecular mechanisms ● Round masses, well Various types: ● Mass effect of tumour ● Gene loss in
defined dural base ● Syncytial Common spots: chromosome 22
● Extension into bone ● Fibroblastic ● Parasagittal ● NF2 gene - merlin
 ● Sheet like growth - en ● Transitional ● Dura over convexity protein
plaque ● Psammomatous ● Wing of Sphenoid ● TNF-receptor
● Secretary ● Foramen magnum associated factor
Atypical: (TRAF 7)
● More mitotic bodies
● Other atypical structures
Anaplastic:
● Highly aggressive
● Papillary growth or
Rhabdoid(sheet like)

Oligodendroglioma Molecular mechanisms ● Well circumscribed ● Sheets of cells resembling ● Neurological complaints ● Isocitrate
● Gelatinous, grey white oligodendrocytes like seizures Dehydrogenase
● Focal haemorrhage, ● Finely granular chromatin ● (IDH1, IDH2)
calcification surrounded by halo of ● Loss of 9q, 10q
vacuolated cytoplasm ● CDKN2A
● Anaplastic oligodendrogliomas :
More mitotic bodies, anaplasia,
necrosis

Infiltrating Astrocytoma Molecular mechanisms Diffuse Diffuse ● Progress slowly ● PTEN, deletion in
● Poorly defined gray ● High cellular density ● Mass effect of tumour chromosome 10,
infiltrative ● GFAP positive astrocytes ● DNA alkylating drugs EGFR oncogenes
● Distorts the brain Anaplastic ● Treatment: Resection ● TP53
● Soft or hard gelatinous ● Greater nuclear pleomorphism followed by ● NELF, GABRA1
on c.s ● Eosinophilic cell bodies radiotherapy ● NF1 on
Gliblastoma (Gemistocytic astrocytoma) chromosome 17
● Firm/white or Glioblastoma
Soft/Yellow due to ● Pseudo palisading - tumour
necrosis cells along the necrotic regions
● Cystic degeneration
and Haemorrhage