"Powered by intellect,Driven by Values..!”

Life motto of Infosys founder and Chairman, Narayana Murthy. INDIA

1

Tip for Success in life….!

T4W1: Week overview:2013 Term 4 CPC 1

Title: MSK

System: RheumatologyAim: To train students in:

History taking + clinical examination of patient with joint pain ; pathology of physiologyof rheumatological diseases; process of care + population health especially in rural and remote areas

Learning Outcomes:

Students will be able

to

1. Demonstrate competency in history taking & clinical examination of patients

presenting with joint pain2. Describe the Pathophysiology of

• Rheumatoid arthritis (RA)• Sero-negative arthritis• Osteoarthritis (OA), • Gout

3 Describe differential diagnoses for patients presenting with joint pains.4 Formulate a first line management plan for patients presenting with joint pains, demonstrating a knowledge of indications and side effects of commonly used medications prescribed for treatment of joint pain.

CPC 4.1 – MSK-Rheumatology– Scenario 1: Ms F.M. 19 year old student – Scenario 2: Mr J.W. 45 year old foot, 1st metatarsal – Scenario 3: Mrs N.M 69y retired Sports teacher.

• Notes to Tutors:– Discuss DD - variety of clinical scenarios.– Remember/revise serious causes of acute joint pain esp.

septic arthritis, rheumatic fever (Jones criteria). – DD to include fibromyalgia, polymyalgia rheumatica, SLE

etc.

• Investigations:– FBC, RFT, ESR/CRP, ALP, Auto Ab.P, RF & Anti-CCP,

HLA B27,

3

Rheumatoid A Gouty Arthritis Osteoarthritis

4

COMMON CLINICAL ARTHRITIS

Differentiating Features:

5

Rheumatoid Arthritis:• Young, small joints• Autoimmune.• Synovial Inflammation• synovium Cartilage

Osteoarthritis:• Old age, Large joints• Degenerative.• Cartilage degeneration.• Cartilage Synovium

Degenerative - Inflammatory• Both sexes equal.• Pain through the day• No morning stiffness.• Stiffness, less pain.• Bony swelling.• No soft tissue swelling• Uni/Bilateral,

Asymmetrical.

• Females more.• Morning stiffness >1h.• Less with movement.• Pain & redness • Inflammation & swelling

of soft tissue.• Late bone swelling.• Bilateral, Symmetrical.

6

Early Destruction of cartilage in RA:

7

Normal -- Femur Head -- OA

8

Normal Osteoarthritis

Osteoarthritis: Ankylosis

9

• varus deformity of the knee and collapse of the joint space with destruction of the medial cartilage and the subchondral cortex (open arrowheads).

OA Hip:

10

RA - Pathophysiology

11

Autoimmune TH1, TH17 & B cellsMMPs, TNF, PGE2

Synovial Inflam & Proliferation withPapillary projections

Chronic Inflam.Lymphocytes &Lymphoid follicles

RA Joint destruction, ankylosis:

12

Gout:• 1%, Males common, • High serum uric acid + monosodium

urate crystals in & around joints.– Primary 90% - congenital– Secondary 10% (malignancies, renal

disesase, high protein diet)– Acute / Chronic.

• Large deposits – Tophi

13

Tophus

Acute Chronic

Degenerative Disc Disease (DDD)

• Ageing / trauma• Low back pain/deformity.• Complication:

– Nerve damage

Common Disc degenerations

Online Animation (Spine Universe.com)

Arthritis Comparison:

15

“To be a great champion you must believe you are the best. If

you’re not, pretend you are….!”

– Muhammad Ali

Fake it until you make it….!

T4W2: Week overview:2013 Term 4 CPC 2

Title: Renal Disease (Glomerulonephritis)

System: Nephrology – Renal DiseaseAim: • Clinical, Pathology & population study of patients with kidney

function disorders.• Pathology & clinical diagnosis of patient with chronic illness—

chronic kidney diseasesLearning

outcomes: The student

will be able to

1. Demonstrate competency in history taking & clinical examination of patients with renal disease.

2. Describe the Investigation and first line management of UTIs, recurrent UTIs, acute and chronic renal failure including chronic kidney disease.

3. Outline the basic sciences relating to fluid balance, kidney function, urine production & urination (including bladder & urethra).

4. Outline the autonomic nervous system + signs of autonomic neuropathy

5. Describe the Pathophysiology & Pathology of renal disease(nephrotic, nephritic & renal failure acute & chronic).

6. Outline the different types of glomerulonephritis.7. Describe the epidemiology, community & rural health issues in

renal disease, renal dialysis & transplantation.

Renal Case Scenarios 1. 35y female, Tired for years, Worsened since

two months. She has noted swelling of her legs and puffiness around eyelids.

2. 2 year old boy presents with sudden onset polyuria, proteinuria following mild fever.

3. 8 year old girl presents with fever, oliguria, smoke coloured urine & hypertension following upper respiratory tract infection.

4. 49y, nephrotic syndrome non-responsive.

5. 18y male recurrent painless hematuria, 3-6 days, usually following fever, URTI.

MGN

MCD

PGN

IgA

FSGS

Anatomy of Renal System

Cortex

Medulla - pyramid

Renal Papilla

Renal calyx

LR

Anatomy of Kidney

Note the positions of Glom, PCT, Loop, DCT, CT

Glom, PCT, DCT

Aldosterone

ADH

Renin

Renal Physiology: Urine, Hormones & Homeostasis

Hypertonic media

Normal Kidney: Histology

DCT

PCT

Gl.Cap

Mesang.

Aff.Art JGA

* Revise: JGA, Renin, Angiotensin, Aldosterone, BP & Electrolyte control.

Filtration Membrane:

Endothelium

Basement Mem

Epithelium

Clinical Presentations of Renal Function Dis.

1. Nephrotic Syndrome:– Massive albuminuria, hypoalbuminemia, edema, hyperlipidemia,

lipiduria.

2. Nephritic Syndrome:– Oliguria, Hematuria, mild Proteinuria, azotemia, Hptn.

3. Painless hematuria / Proteinuria:– Mild forms of glomerulonephritis.

4. Acute Renal Failure (ARF):– Pre-Renal, Renal & Post-Renal.

5. Chronic Renal Failure (CRF): – Chronic progressive kidney damage (Diabetes, Hptn.)

UTI, Nephrolithiasis, Cysts & Neoplasms.

Nephritic

• Oliguria• Hematuria• Non selective Proteinuria.• GFR, Cr, BUN• Edema (salt and water

retention)• Hypertension• RBC & Protein casts.

Nephrotic

• Proteinuria (“nephrotic range” >3.5g/24h)

• Edema (retention+Hypoalbuminemia)

• Hyperlipidemia• Lipiduria• Protein casts.

urineurine

Synonyms:

Incidence:

Etiology:

ClinicalFeatures:

LabFeatures:

Pathology:

ClinicalCourse:

Nil disease, lipoid nephrosis, foot process disease

Idiopathic. Loss of net negative charge destruction of podocyte foot processes.

Nephrotic syndrome. History of recent URI in 30%. Association with Hodgkin’s lymphoma. Overlap with FSGS patients.

Nephrotic urine (polyuria, Selective proteinuria. (albuminuria).

Spontaneous remission in 25-40%. Complete remission in 65-70% of patients. Steroid resistant patients may progress to FSGS.

Normal Microscopy. IF - Negative.EM loss of foot processes.

80% of nephrotic syndrome in children (1-8 yrs.), mostly male. Adults in 2nd-3rd decade.

Minimal Change GN:

Normal Microscopy

Loss of foot process - EM

Focal Segmental GN: Adults

Synonyms:

Incidence:

Etiology:

ClinicalFeatures:

LabFeatures:

Pathology:

ClinicalCourse:

Focal segmental Sclerosis

Idiopathic - ? Auto Immune. No deposits. (Similar to minimal change).

Nephrotic syndrome. History of recent URI in 30%. Association with Hodgkin’s lymphoma. Overlap with MCD patients.

Nephrotic urine (more, clear) Selective proteinuria. No specific laboratory findings.

Spontaneous remission 30% , 50% progression to chronic renal failure, 20% rapid progression.

Podocyte damage, Segmental collapse of glom. increase in matrix (pink).

10 - 35% of nephrotic syndrome in adults.

Synonyms:

Incidence:

Etiology:

Clinical:

Lab:

Path:

ClinicalCourse:

membranous GN

Immune complex deposition. Idiopathic in most patients, associated with infections, drugs, carcinomas, and heavy metals.

Nephrotic syndrome in 80%, asymptomatic proteinuria in 20%. Microscopic hematuria.

Non-selective proteinuria ± hematuria.

Excellent prognosis in children. Some adults develop ESRD. Exclusion of other diseases is required.

Diffuse, uniform BM thickening with subepithelial projections (“spikes”). Diffuse, coarsely granular IgG and C3 deposits along basement membranes. Electron-dense subepithelial deposits.

40-60 Years, 50% of adult nephrotic syndrome.

Membranous GN:

Wireloop

Synonyms:

Incidence:

Etiology:

Clinical:

Lab:

Path:

ClinicalCourse:

Acute proliferative glomerulonephritis, acute post-infectious GN.

Glomerular trapping of circulating immune complexes. (Group A, Beta-hemolytic streptococci, type 12).

Acute nephritic following strep. pharyngitis or pyoderma. (Other infections rare)

Nephritic urine (little, dark, smoky) RBC casts, non selective proteinuria. Decreased serum complement. Evidence of strep inf.

Children - Excellent prognosis. Adults - Worse prognosis, some develop progressive disease.

Enlarged, hypercellular glomeruli with endothelial and mesangial cell proliferation, neutrophils, IgG and C3 in very coarsely granular pattern along GBMs. Discrete, subepithelial “hump-like” deposits.

children (3-14). Sporatic, mostly winter and spring.

Acute Post Strept, Diff, Prol GN:

• Commonest form of GN – Nephritic.• Young 15-30y, males, Asia-Pacific.• IgA deposits in mesangium, High serum

IgA, varied severity• Episodic asymptomatic hematuria • microscopic hematuria (40%)• Bouts of macro hematuria (40%)• Nephritic or Nephrotic (rare). • Renal failure (10%)• Slowly progressive CRF in 1/3

patients.

IgA Nephropathy (Berger’s)

IgA dep.

Normal

IgA dep.

Progression of GN:

Renal Failure

Renal Insufficiency

Endstage

Decreased Renal reserve

GFR

Acute Tubular Necrosis:

• Necrosis of tubular cells – fall of as casts.

• Most common cause of ARF.

• Ischemic (patchy PCT & DCT)– Hypovolemia– Shock

• Toxic (PCT only)– Drugs…– Toxins – Mercury, CCL4,

Radiocontrast.

Acute Tubular Necrosis(ATN): toxic

Glom. Norm

Necrotic PCT(no nuclei)

Normal DCT(Pro. cast inside)

PCT early necrosis

“Look at the sky. We are not alone. The whole universe is friendly to us and conspires only to give the best to those who dream and work.” - Wings of Fire: An Autobiography of Dr. APJ Abdul Kalam.

T4W3: Week overview:2013 Term 4 CPC 3 Title: Male Genitourinary

System:GU + RenalAim: Understanding pathology ,presentation and clinical

diagnosis of patients with urinary obstruction & urinary tract infections.

Learning outcomes:

The student will be able to

1. Demonstrate competency in history taking & clinical examination of patients with urinary symptoms.

2. Demonstrate competency in the clinical examination of the abdomen and pelvis

3. Describe the Laboratory investigations for patients with bladder outflow obstruction and haematuria

4. Demonstrate competency in debating the use of the PSA in

individual patients and as a screening test.5. Describe the first line management of prostate

cancer and BPH6. Describe the anatomy and histology of bladder,

urethra + prostate;

Week Learning outcomes:2013 Term 4 CPC 3 Title: Male Genitourinary

System:GU + RenalAim: Understanding pathology ,presentation and clinical

diagnosis of patients with urinary obstruction & urinary tract infections.

Learning outcomes:

The student will be able to

7. Describe the pathology of BPH, prostate cancer, renal and bladder tumours ,and renal and bladder calculi

8. Outline the Professional, ethical & legal issues in diagnosis & management of patients with benign prostatic hyperplasia (BPH) and prostate cancer

9. Outline the Epidemiology & Public Health issues of BPH and prostate cancer

SAQ: UT Obstruction

• What are differential diagnosis?

• What complication he has? Or he may develop?

• Should PSA be tested for all? Diagnostic levels?

• When is biopsy indicated?

• Does BPH lead to Carcinoma?

• What is the best screening test for Ca?

• What investigations are available?• BPH & Carcinoma – microscopy?• Gleason grading of prostate carcinoma?

Self Assessment:

• Common obstructions of LUT – age• Etiology, pathogenesis, morphology: BPH• PSA levels in diagnosis – debate.• Cystic diseases of Kidney – ADPKD• Urinary Tract Infections – Microbiology.• Nephrolithiasis – common stones

morphology.• Transitional cell carcinoma – brief• U:C ration – significance, diagnosis.

Core Learning Issues: (CLI)

Major:• Disorders of Prostate – Prostatitis, BPH & Ca.• Nephrolithiasis: Features, Types, Pathogenesis.• Tumors of Kidney. – RCC, TCC, Wilms. • Urinary Tract Infection – Common Microbiology.

Minor: • hematuria, strictures, obstructions, polyps.• Tumors of Urinary tract and bladder.• Kidney Cysts, Hydronephrosis, Recurrent UTIs,

Pyelonephritis, renal abscess, Congenital disorders of kidney.

When you lose, don’t lose the lesson!

Lao Tzu

Everyone makes Mistakes, only intelligent learns from it.

Causes of Obstructive Uropathy INTRINSIC:

Calculi - Lithiasis Strictures – congenital,

inflammatory (UTI) Tumors – Transitional cell

papilloma & Carcinoma. Blood clots, necrotic tissue

(Papillary necrosis) EXTRINSIC:

Pregnancy Inflammation- STI / PID,

peritonitis, diverticulitis, salphingitis.

Tumors: Prostate, rectum, bladder, ovaries etc.

Nephrolithiasis:• Usually unilateral, small 1-3 mm, • Flank pain & tenderness – renal

capsule.• Passage marked by Paroxysmal,

intense colicky pain in the back (loin) with radiation to anterior (renal or ureteral "colic“)

• “writhing in pain, pacing about, and unable to lie still”

• Hematuria macro/micro• Larger stones that cannot pass

produce hydronephrosis or hydroureter.

Levels - Clinical symptoms• Ureteropelvic junction - deep flank

pain No radiation. Distension of the renal capsule. (Symp. T11-L2)

• Ureter – Acute, severe, colicky pain in the flank and ipsilateral lower abdomen with radiation to the testes/vulva (ilioinguinal n.). nausea / vomiting.– Upper ureter – cholecystitis.– Middle – appendicitis– Distal ureter – Pelvic Infl. Dis.

• Ureterovesical junction - Cause irritative voiding, urinary frequency and dysuria.

Calcium Oxalate

Calcium Oxalate

Nephrolithiasis: Organic matrix(3%) + salts (97%) ~

• Calcium stones (80%): oxalate/phosphate/urate salts. – Increased gut absorption or defective tubular

reabsorphtion of calcium – Common, high pH.– Hyperparathyroidism (10%)– Hyperuricosuria – high pH

• Struvite Stones (15%) magnesium ammonium phosphate (triple phos). Staghorn stone.– Chronic UTI with gram-negative rods (split urea) pH

>7– Proteus, Pseudomonas, and Klebsiella (not E. coli).

• Uric acid stones (6%): – pH <5.5, high protein (meats), malignancy, 25% have

gout. • Cystine stones (2%)

– Genetic disorder - Failure of reabsorption

Staghorn Calculus:

Male Urogenital System - anatomy

Ca

BPH

Zonal Histology:

BPH

Ca.

Normal Histology: Fibro-Musclular-Gland

Two Layer Ep.

Fibromuscular stroma

Secretions

Benign Prostatic Hyperplasia:

BPH-Bladder Gross – Identify Cues?

Trabeculations Hypertrophy of wall Stone - urolithiasis Inflammation Median lobe- ball valve. Enlarged prostate.

BPH: Nodular, Gland+stromal hyperplasia

Cystic Gl

Nodule of BPH

Secret

ions

BPH-Complications:

1. Obstructive Uropathy2. Bladder hypertrophy3. Trabeculation4. Diverticula formation5. Hydroureter – bilateral6. Hydronephrosis7. Lithiasis / stone.8. Secondary infection.

• Not a risk factor for Carcinoma prostate.

Pathogenesis: PIN & carcinoma

1. Prostatic Intraepithelial Neoplasia (PIN) Multilayered, pleomorphic.

2. Malignancy is single layered, & well differentiated at start…!

Adeno-Ca Prostate

• Posterior Lateral lobes: Carcinoma• Rectal examination.• Solid, hard, adenocarcinoma

Gleason Grading & Scoring of Prostatic Ca.

Summary: BPH/Ca

Benign: Double layer. Secretion (clear cytopl) Uniform cells Papillary folds

Malignant Single/crowded. Less/no secretion. Uniform/Pleomorphic No papillary folds. But

crowding & clustering.

Normal

Ca.

Normal

Ca.

Transitional cell Neoplasms: 90% of bladder ca. Males 3:1 Fem, 50-70y Painless hematuria, Malignant cells in urine Papillary(low gr), Flat / Infiltrative (high gr) Risk F: β-naphthylamine. Cigarette smok,

chronic cystitis, schistosomiasis

“No one who does good work will ever come to a bad end, either here

or in the world to come”

– Bhagavad Gita 6:6

T4W4: Week overview:

2013 Term 4 CPC 4 Title: Epididymo-OrchitisSystem: Male Genital System

Aim: Clinical, Pathology & Population study of patients with male genitalsystem disorders & sexually transmitted disease (STD) using a case of epididymo-orchitis with a differential diagnosis of testicular torsion and testicular tumour.

Learning Outcomes The student will be

able to

1. Demonstrate competency in history taking & the clinical examination of male patients with genital disorders

2. Outline the Laboratory investigations and first line management of common infections including STIs.

3. Outline the Investigations and first line management of testicular torsion and testicular carcinoma

4. Outline the anatomy and histology of male genital system.5. Describe the Microbiology of common STIs; Pathology of

Penis & testicular disorders including torsion and tumours.6. Relate the Professional, Ethical & Legal issues in diagnosis &management of patients with STIs.7. Describe the Epidemiology & Public Health issues of STIs,

testicular torsion, testicular cancer.

CPC4.4:Testes: Common presentations. 12y boy, woke up in the night with sudden

severe scrotal pain. O/E tender, swollen testes high up in the scrotal sac does not allow to touch.

35y man, dragging sensation in scrotum since 6 weeks. O/E enlarged, smooth, non tender, firm testes on one side.

28y man, severe aching pain in the left groin radiating to the scrotum since 3 days with associated fever and rigors. O/E a 4 cm, hot, swollen, tender, (left epididymis & testis).

35y man, smoker, chronic cough, presents with recurrent attacks of sharp pain in right groin with small painful bulge, disappears on laying down.

68y male, erythematous, irregular, raised papule on penis/glans since 6 months.

Torsion

Seminoma

Ep.Orchitis

Hernia

Bowen/EQ

Structure, origin, Lymphatics:

Normal Testes:Leydig Cells

Sperms

Condyloma Accuminatum

• HPV serotypes 6 & 11• Fleshy / warty Papillary

epithelial overgrowth.• Glans & periurethra • Acanthosis & Koilocytes

Bowen’s & Erythroplasia of Queyrat:

• Epithelial hyperplasia & dysplasia.• HPV type 16, 18• On Glans: Erythroplasia of Queyrat• On Shaft : Bowens Disease.• Premalignant Sq. Cell Ca.

Carcinoma Penis: (Sq cell) Hygiene, smegma irritation Smegma carcinogen? Smoking is a risk factor* HPV 16, 18 * Circumcision known to prevent. Phimosis increases risk. Starts as erythroplakia/leukoplakia. Well diff. sq.ca – Epithelial pearls. Slow growth, Good prognosis Inguinal & iliac LN spread. 70% 5 year survival.

Cryptorchidism: “undescended testes” Normal descent: 3m to pelvis, 9m to scrotum. Non descent 5% at birth, 1% at 1y (10% bilateral) Cause: Hormonal, intrinsic & mechanical. Common in Patau, Prader willi sy. etc. Atrophy, - sertoli & Leydig cell hyperplasia. 3-5 fold increase in Germ cell Malignancy – even in the other testes.

(not in other types of atrophy) Orchiopexy – reduces risk of sterility & cancer.

- 9m

- 3mAbdominal

Inguinal

Suprascrotal

Normal

~ 1 yearNormal Atrophy

Testes Atrophy:

Bilateral in Hypopituitarism, Chronic Alcoholism, chemotherapy or radiation.

Hormonal, infection, Cryptorchidism. Mumps – Patchy. Sertoli only, Leydig cell hyperplasia.

high chance of neoplasms.

Normal

Atrophic

Normal SpermatognesisFew Leydig cell cluster outside

AtrophySertoli only inside, Leydig cell Hyperplasia outside

Hydrocele: Common, Clear Fluid in Tunica vaginalis. Cong./Acquired (inflam).

Varicocele: Engorged spermatic cord veins (pampiniform plexus). Common cause of infertility oligospermia.Primary / Secondary

Spermatocele: Epididymis dilatation trauma/infection, multilocular, sperms.

Hematocele:Blood in tunica vaginalis. Trauma, tumours.

To measure the man, measure his heart. -- Malcolm Stevenson Forbes

Epididymo-Orchitis: Symptoms:

• Testicular pain - unilateral• Erythema / oedema of the scrotum• Urethritis, dysuria / urethral discharge.

Etiology:• Gonococcal – Neisseria gonorrhoeae.

Non Gonococcal - (chlamydia, Mycoplasma..)

Gross: swollen, hot, Acute inflammation, edema

Micro: Edema, neutrophils, necrosis.

Investigations:• Exclude torsion/trauma in <30 years, • Microbiology: C/S, Elisa, etc.

Genital herpes: STD - HSV (Herpes Simplex

Virus) type 2. Itching closely grouped

vesicles surrounded by erythema.

Vesicles burst to form painful ulcers.

Multinucleate giant cells with viral inclusion.

Syphilis: Treponema pallidum Primary chancre on penis:

ulcerated nodule inguinal lymphadenitis

Secondary stage: condylomata lata, (2-8w)

Painless, broad, moist Grey white to red plaques. Highly infectious.

Tertiary stage: gumma, often in the testis

Lymphogranuloma venereum Chlamydia trachomatis, serotypes L1-L3 Genital Painless papule - 2-5 days. 1-4 wk. suppurative necrotic Inguinal

lymphadenitis. Suppurative granuloma (neutrophil abscess)

& Chlamydial inclusions in microscopy.

Reiter’s Syndrome: Common Inflammatory

polyarthritis in young men. Chlamydia trachomatis (rarely

salmonella & shigella) HLA-B27 – risk factor in 70% Fever, malaise, myalgia,

asymmetric arthritis & Conjunctivitis.

Knee, ankle & feet common. Chronic, recurrent. Disability in ~ 20% cases.

Sausage toe

Inflammed ankle

Testes Tumors: Features: Commonest tumour of young males. Etiology:

• Idiopathic, Undescended testes, estrogens. Clinical features:

• Adults 40-50y – Seminoma.• Children <10y – NSGT- Yolksac tum.• Painless, enlargement, • unilateral, Hydrocele, Gynaecomastia. • Metastases – Para aortic LN*.

Origin: • 95% Germ cell,

• Seminoma 40-50%• Non seminoma (NSGT)

(Embryonal ca 25%, Terato ca 25%, Teratoma 5%, Chriocarcinoma 1%, 15% mixed.)

• 5% Sertoli/Leydig cell tumours.

Seminoma: Commonest Germ cell tumour, 30-50y, hCG Firm, grey, smooth, painless, (many subtypes:

classical, spermatocytic, anaplastic, etc.) Microscopy: uniform cells, Pale, vacuolated

cytoplasm contains glycogen, plenty lymphocytes. Mixed seminoma Seminoma + Teratoma,

embryonal carcinoma or choriocarcinoma etc.

Embryonal Ca.Children (Yolksac/Endodermal sinus)

• Pink AFP globules in cells.• Schiller-Duvall bodies (embryo like)

Adults: Embryonal Ca.• Primitive, pleomorphic cells in clusters,

embryoid structures.

Pathology: Germ cell tum.Clinical: painless swelling of testes.

malignant, poor prognosis, metastases.

Gross: Hemorrhagic, necrotic tum.Micro: Pleomorphic cells, embryoid

structures.

“Strength does not come from winning,

Struggles & Hardship develop strength.

- - Arnold SchwarzeneggerBodybuilder, Actor & Leader.

T4W5: Week overview:

2013 Term 4 CPC 5 Title: Breast Cancer System: Breast

Aim: Clinical, Pathology & population study of patients breast disease

Learning outcomesThe student will be

able to

1. Demonstrate competency in history taking & the clinical examination of patients with breast disease.

2. Describe the first line investigation and management of patients with breast disease or symptoms.

3. Describe the Pathophysiology of breast disease (benign and malignant)

4. Outline the basic sciences relating to function of the breasts.

5. Describe the Epidemiology and aetiology of breast disease in Australia and world wide.

6. Illustrate the advantages and disadvantages of the breast screening program in Australia

Case studies:• 22year female, noticed small mobile round

lump in her right breast, lower inner quadrant.• 39year female, multiple small lumps, irregular,

firm, tender more during mid cycle.• 41year female, two left axillary LN, no pain, no

breast mass. mild loss of weight.• 34year female, diffuse firm left breast. FNAC

reports abnormal cells. No LN. • 39year female, painful lump, chronic pus

discharge from nipple. • 71year old female. Rough, red scaling pruritic

patch on left nipple and areola.• 26y nurse, right breast lump 5m, firm irregular,

6cm firm, fixed lump.

• Fibroadenoma

• Fibrocystic dis

• Ca breast.

• DCIS

• Duct ectasia

• Paget’s dis

• BRCA Ca.

Self assessment:• Clinical features of benign, malignant & reactive…• Breast cancer screening guidelines.• Hyperplasia / tumour features.• Familial vs Non familial breast Ca features.• Screening Mammogram – policy, procedure &

interpretation.• Fibrocystic disease, fibroadenoma & cancer.• Breast cancer common types & features (gross,

microscopy, complications etc.)• Duct carcinoma, lobular carcinoma, other types.• BRCA testing in familial breast ca.

Anatomy

T4 level

Age changes in breast:

Puberty Adult (Lactating) MenopauseFibrous Fibro-Fatty Fat

Disorders of Breast:

Fibrocystic Disease

FibroCystic Disease: types

A. Simple Fibrocystic change.B. Lobular hyperplaisa without atypica (adenosis)C,D - Ductal hyperplasia without atypia (E. with atypia - cribriform)F. Lobular hyperplasia.

Non prol. / low grade

Prol. / High grade

Breast Neoplasms: Benign: (round, smooth, soft, mobile)

Fibroadenoma Duct Papilloma Others – rare.

Malignant: (irregular, rough, hard, fixed) Ductal carcinoma – classic. Lobular carcinoma Others - rare

Fibrocystic Disease(Not a neoplasm)

Fibroadenoma

Slit like glands

Pathology: Benign tumor of acini tissue (gland & stroma)Clinical: Well demarcated, mobile, round/nod (mouse)Gross: Capsulated, firm grey, nodular tumour, cysts+/-.Micro: Compressed slit like ducts/glands in cellular stroma.

StromaTumour

N. Breast

Capsule

Breast fat

N. Fat

Giant Fibroadenoma

• Pathology: Benign(young) to malignant(adult) tumor of acinii.• Clinical: young (Low grade) /adult (high grade)*, unilateral macromastia,

recurrent, metastasis 15%.• Gross: Large 10-15cm . Giant. With linear “leaf-like” clefts and slits –

Giant/Juvenile in young - Phyllodes tumor in adult.• Micro: Both stroma & glands are hypercellular & pleomorphic. glands

show branching..

Leafy folds

Etiology of Breast Carcinoma:

• Overexposure to oestrogens and underexposure to progesterone • No definite relationship to oral contraceptives • Some tumours contain hormone receptors and respond to hormone manipulation • No good evidence for viral involvement

GeneticsHormone

Environment

• Family history – First degree relative.

• Premenopausal & bilateral.• Early menarche/Late menopause.

• Estrogen therapy.• Alcohol, Smoking.• High fat diet,

Obesity.

• HER2/NEU• RAS & MYC• BRC A1, A2.

Pathogenesis of Breast Cancer.

Hyperplasia Dysplasia DCIS CarcinomaFibrocystic change Cancer

Duct Ca. in-SituDCIS

Pathogenesis:

Infiltrating Duct Carcinoma: Breast Ca.

Note: Fibrotic tumor, radiating fibrous scar around resulting in nipple retraction & skin pulling (puckering)

(NOS or Classic or typical “Schirrhous carcinoma”)

Typical Invasive Ductal Carcinoma / Duct Ca (NOS)

Ca-tubules

collagen stroma

Pagets Disease• Spread of Breast cancer

cells to skin (areola) & resulting in Eczematous reaction.

Ca. Cells

Ca. Cell

Summary:• Anatomy & Physiology.• Congenital, Inflammatory & Neoplastic dis.• Fat Necrosis, Abscess, Duct ectasia.• Proliferative Disorders:

– Fibrocystic Disease – hormonal, benign.• Neoplastic Disorders

– Benign – Fibroadenoma, papilloma– Malignant – Invasive Duct Carcinoma, Lobular

Carcinoma, – DCIS – Ductal carcinoma in-situ.

If through a broken heart you become a better person then,

thank him for breaking your heart!

~ Oswald Chambers

98

T4W6: Week overview:

2013 Term 4 CPC 6 Title: Female Gynaecological 2System: Female genital tract

Aim: Understanding pathology & clinical diagnosis of female patients with abnormal vaginal discharge

Learning Outcomes(The student will be

able to..)

1. Demonstrate competency in History taking & clinical examination of patients with an abnormal vaginal discharge.

2. Demonstrate competency in the Physical examination of abdomen and pelvis.

3. Outline the Investigation and first line treatment of common causes an abnormal vaginal discharge including pelvic inflammatory disease.

4. Outline the anatomy and histology of female genital tract5. Describe the difference in presentation in STIs in women and men6. Discuss the screening program for cervical cancer in Australia7. Construct a management plan for patients with normal and

abnormal PAP smears8. Relate the Professional, ethical & legal issues in diagnosis &

management of victims of violent crime.9. Describe the Epidemiology & Public Health issues of cervical cancer and

STIs.

Case studies:• 8year girl, vaginal bleeding and discharge.• 21year female, itchy vaginal discharge foul

smelling.• 26 year old thick white cheesy discharge.• 25 year old, whitish yellow pus discharge.• 31year female, irregular heavy bleeding. • 34year female, irregular & post coital bleeding.• 28y G2 P1, second trimester vaginal bleed.• 69year female, vaginal bleeding

Trauma

Chlamy..

Candida

Gonoco..

DUB

CaCx

Molar preg.

Endo.. Ca

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CPC4.5- Female Genital System-1 - CLI

• Pathology Major Core Learning Issues: – Sexually Transmitted Infections – Microbiology*– Pathology of  Cervical disorders, cervical cancer. – Pap smear, biopsy & CIN, Ca Cx grading & staging. – Endometrial - hyperplasia, polyps, cancer.

• Pathology Minor Core Learning Issues: – Pelvic Inflammatory Disease (PID)*– Disorders of Vulva & Vagina.– Infections & inflammations – vulvovaginitis, cervicitis, – Endometriosis & Adenomyosis.

101

Vaginal disorders:Sarcoma Botryoides

Sarcoma, 1-5 year children

102

Pelvic Inflammatory Disease (PID):

Infertility

Pain & Fever

Mass

103

HPV: Condyloma acuminatum

Ano-genital wart, soft, HPV 6 & 11, STI, Benign,

A. Small, warty, Cauliflower-like growth.

B. Koilocytes: peri nuclear halo + viral particles

C. Mild Dysplasia. (Cx. CIN-1)

A B C

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Transformation Zone:

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Colposclopy & Acetic acid test

mosaic pattern resembling inlaid woodwork. (LSIL)

Erythematous patch in the transformation zone.

Before acetic acid After acetic acid

http://www.operationalmedicine.org/ed2/images/Cervix/Cervix.htm

106

Normal Ectocervix :Strt. Sq. Ep

SUPERFICIAL

INTERMEDIATE

BASAL

107

PAP: CIN I-III Comparison (note nuclei)

Normal CIN I (LSIL)

CIN II (HSIL) CIN III

PAP Smear

CINPathogenesis & Features

25y 30y 35y 45y

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Low Risk

– 6,

11.

High Risk 16, 18

HPV - Pathogenesis:

Vulva, Vagina, Cx

Benign Wart(CIN1/LSIL)

???

Cx-Transition Zone - HPV

Smoking, Estrogens, Genetics..E6, E7 protein Rb & p53

Carcinoma

CIN1/LSIL

CINII-III/HSIL

LSIL: Lowgrade Squamous Intraepithelial Lesion (CIN1)HSIL: Highgrade Squamous Intraepithelial Lesion (CIN II, III)

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CIN Progression: • CIN (Stage 0)

– CIN I – LSIL, HPV 6,11.– CIN II & III – HSIL, HPV 16, 18.

• Stage 1: Limited to Cervix.– Ia. Preclinical by microscopy

• Ia1. Microinvasive <3 mm x <7 mm.• Ia2. <5mm x <7mm wide.

– Ib Larger - Confined to cervix.• Stage 2: Beyond Cx.• Stage 3: To pelvic wall/lower vagina.• Stage 4a: Bladder, Rectum• Stage 4b: Beyond pelvis.

LSIL / CIN-1 is virtually a transient HPV infection and not a cancer precursor.

111

Cervical Dysplasia: HSIL margin

HSIL/DysplasiaNormal

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Cervical Dysplasia: HSIL

?

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HSIL early invasion: Ca

Invasion

“We choose our joys and sorrows long before we experience them!”

--Khalil Gibran

115

• Myometrium: – Benign – Leiomyoma– Malignant – Leiomyosarcoma

• Endometrium:– Endometritis.– Endometrial Hyperplasia – polyp, diffuse, atypical.– Endometriosis, Adenomyosis.Endometrial tumor:– Malignant – Endometrial Carcinoma.

Disorders of Uterus & Endo..

116

Endometrial Hyperplasia & Polyp:• Hyper-estrogenemia.• Hyperplasia of endometrium, may form

polyp.• Common cause of uterine bleeding - DUB• Risk of malignancy – more with

atypical/dysplasia.

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Uterus Adenomyosis:

Endometrial Cavity

Cervix

Adenomyosis

118

Endometriosis:• Definition: Endometrial spread

beyond uterus.– Spread through Fallopian tube– Pelvic veins or Lymphatic spread.– Metaplasia of coelomic epithelium.

• Cause: Hyper Oestrogenemia.• Sites:

– Endometriosis Interna – Adenomyosis.– Endometriosis Externa

• Clinical: Periodic Pain, pelvic inflammation, fibrosis,

• Complications: infertility,

119

Endometrial Ca:• Adenocarcinoma (not HPV)• Estrogen – risk factor.• Post-menopausal bleeding.• Irregular, polypoid, bleeding.• Dysplastic back to back glands• Little/no stroma. Adenocarcinoma

Hyperplasia

We are responsible for what we are…

You are the stone, You are the chisel, and You are the sculpture….!

www.akshardham.com

LAST LECTURE !CPC47-Ovary

T4W7: Week overview:Term4 CPC 7 Title: Female Gynaecological 2

System Female genital tract

Aim: Understanding pathology & clinical diagnosis of female patients with abnormal vaginal bleeding

Learning Outcomes:

The student will be able to

1. Demonstrate competency in History taking & the clinical examination of patients with abnormal vaginal bleeding.

2. Demonstrate competency in history taking and clinical examination ofpatients with menopausal symptoms3. Outline the Investigation and first line management of patients

with abnormal vaginal bleeding: menopausal symptoms.4. Illustrate the advantages and disadvantages of HRT

5. Outline the anatomy and histology of the female genital tract; the physiology of menstrual cycle and menopause including anovulatory menstrual cycles and polycystic ovarian syndrome

6. Describe the pathology of common disorders of the uterus and ovaries including polyps, tumours -both benign and malignant.

7. Relate the Professional, ethical & legal issues in diagnosis & management of patients with abnormal vaginal bleeding.

8. Describe the Epidemiology & Public Health issues of menopause, ovarian

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Core Learning Issues:Pathology Major CLI:• Ovary – disorders overview.• PolyCystic Ovary Syndrome (PCOS)• Tumors of Ovary – overview (common: Cystadenoma,

dermoid cyst)• Gestational Pathology – Overview

Pathology Minor CLI:• Ectopic pregnancy. • Eclampsia & Pre-Eclampsia, Gestational tumours.• Disorders of placenta, Hydatidiform mole,choriocarcinoma.• Other tumours of ovary – teratocarcinoma,

124

Polycystic Ovary Sy: PCOS• Arrested follicle development, anovulation.• Teens/young adults, acne, oligemenorrhoea,

hirsutism, obesity, HPTN, DM2. • Multiple subcortical follicular cysts.• Excess androgens & estrogens.• Stromal hyperplasia & anovulation. • Complications: – Important cause of infertility, – Endometrial hyperplasia.

125

Endometriosis: chocolate cysts

Frozen Pelvis - adhesions

126

Classification of Ovarian Tumours

Cystadenoma: • Serous more common, 75% benign.• Serous frequently bilateral • Multi-loculated / single cyst.• Benign cystic Malignant solid.• Single layer ep papillary.• CA125 Tum marker (epithelial) followup.

Germ Cell Tumours: Teratoma• Many types of tissues inside.• Benign/mature Teratoma mature

tissues. (common Dermoid cyst)• Malignant/solid Teratoma multiple

cancers on microscopy.

128

Tooth..!

FatHair

Dermoid Cyst

Dermoid Cyst

Dermoid Cyst

Immature Teratoma

Chorioamnionitis:• Infection & inflammation of

chorionic membrane & villi.– 1-4% of normal births, – 40-70% of premature births.

• Risk factors: Early rupture of membranes, nulliparity, prolonged labour, race/ethnicity.

• Local: Vaginal flora, genital mycoplasma, Candida.

• Systemic: TB, Syphilis, Toxo, Rubella, CME (TORCH).

• Inflammation, WBC, infarctions.• Neonatal sepsis, asphyxia, death..

129

130

Eclampsia & pre-eclampsia

• Diagnosis: HPTN, proteinuria, edema in 3rd trimester (pre-Ecl.) + Seizures, DIC (Eclamp.)

• 5-10% pregnancies.• Etiology: Unknown/genetic/immune.• Risk Factors: Primi / molar preg, later age.• Pathogenesis: Placental Ischemia. – Abnormal

spiral arteries Decreased placental vasodilators and Renin Angiotensin inhibition Hypertension & Glomerulonephritis.

• Placental infarction or hemorrhage. • Chorionic villi underperfusion, cytotrophoblast

hyperplasia.• Complications: DIC, CCF, fatal.

Ectopic Pregnancy:• Implantation outside uterus. • 1% pregnancy, • 90% in fallopian tubes.• Ovary, abdomen, etc. rare.• Risk factors: Obstruction, PID,

stricture, IUD, tumours, endometriosis etc. in 50%, rest idiopathic (50%).

• Embryo / placental tissue within dilated tube filled with hemorrhage.

• Complications: Abortion, bleeding, chorioamnitis, Choriocarcinoma (rare).

131

132

Mole/Molar pregnancy1. Gestational Trophoblastic Disease:

2. Spectrum of trophoblast neoplasms.

3. Benign to malignant: – Partial mole – Benign, fetal parts+

Ovum+2 sperms. (triploid) – βHCG– Complete mole – no fetal parts, 2%

ChorioCa. 2 sperms (diploid)– Invasive mole. aggressive.– Choriocarcinoma. Malignant.

βHCG High grade Poor prognosis.

133

Complete Mole Partial• All villi cystic, no BV• No fetal parts• Diffuse trophoblastic

hyperplasia• Diploid (2 sperms)• Choriocarcinoma 2%• High βHCG levels.

• Partially cystic, few BV.• Fetal parts +• Focal hyperplasia of

trophoblasts• Triploid (ovum+2 sperms)• Rare carcinoma• Relatively less βHCG.

134

Core Learning Issues:Pathology Major CLI:• PolyCystic Ovary Syndrome (PCOS)• Tumors of Ovary – overview (Common: Cystadenoma,

dermoid cyst, carcinoma)• Gestational Pathology – chorioamnionitis, mole/Ch.Ca.

Pathology Minor CLI:• Ectopic pregnancy. • Eclampsia & Pre-Eclampsia, Gestational tumours.• Hydatidiform mole, invasive mole, choriocarcinoma.• Other tumours of ovary – Teratoma / Teratocarcinoma,

Remember the Challenge….!Dec 2011:

4th Year Students at JCU School of Medicine set new record.…!!!100% Pass & Class Average over 70%

Yes We Can…!

136

Asking quality questions is the key!

“Identifying your Goal is like identifying the North Star, you fix your compass on it and then

use it as the means of getting back on track when you tend to stray”

-- Marshall Dimock

What am I doing? - Where am I going?(Where I want to be in 5 years?)

"I learned that good judgment comes from experience and that experience grows out of mistakes!"

– Omar Bradley

Education is what remains after we have forgotten all the facts taught in the class!--

“A man must be big enough to admit his mistakes, smart enough to profit from them, and strong enough to correct them!”

--John C. Maxwell

Wish you all Success, Health,

& Happiness in life.

Need help for exams? You can still contact me..