Pathogenesis of each disease!

1. Definition2. Aetiology3. Epidemiology4. Pathogenesis5. Pathological features6. Clinical features/manifestations/presentation7. Investigations8. Management9. Complications10. Prognosis11. Prevention

Direct cause: there wont be a disease without this cause. – not RISK FACTORS!!!

Eg: hypertension- primary: essential hypertension. Secondary: tumor to … gland, but not DM- because not ALL.

Aetiology:all patients must have. Include: primary and secondary.

Epidemiology: indirect causes: help to lead to the disease- but not the casue of it.

Pathogenesis: natural- include complications… not casued by stop or altered. Unless UNDERGOING TREATMENT. Include pathological features: ante& post mortem. ** other findings: eg: TB: grossly, microscopy-H&E stain(usually), but in this case is Zeihl Neelson- include all these.

Oil-red-o??- stains fat. Not antigen antibody.

Immunofluorescence: dark slide, but it will shine.

Symptoms: what patients complain to you, signs: what you get out of the patient.

Write on the clinical features who has this disease: important- give history in the past: eg: rheumatic heart disease: in adults, happens because when they were teenager, strep phryngitis? – body- produce antibodies, but after bacteria being cleared, the antibody attacks the body- because- some of the body parts(heart valves) have the same structure- weaker- therefore prone to endocarditis.

Weakened heart valve, heart murmur… infection by.. in childhood- CLINICAL FEATURES

Polyuria, polydypsia(thirsty), polyphagia(hungry): in DM, include complications: diabetic retinopathy: include clinical features as well

Bedside test: glucometer: to see glucose level- interpretation is needed.

ERCP- endograde..

Histopath: a piece of tissue: biopsy is also a piece of tissue

Cyto: use aspiration- peritoneal fluid etc. also body fluids. But if u want to quantify, you send to others: this is just: malignant? Typical cell. Send to haematology and chemical pathology.

Electrolytes: sodium, potassium…

Microbiology anything to do with infections.

Biopsy: need to know where to send it.

Normally: one for histopath and another one is microb. Containers will be different!

Ziehl Neelson: acid fast bacilli- cannot be sure is it MTB, leprosy… can be others. (for histopath), only know it is mycobacterium. – “consistent” with tuberculosis. But it could be atypical –if want species: need culture.

Major surgery: only surgeons

Minor: all doctors.

*** non- pharmacological treatment: esp : DM, hyprtention.

Notification: for public health people: trace the contact.

After treated: follow-up.

Prognosis: usually for malignant tumors. – but DM also can-healthy life etc.

Biomarkers*: cd7,20… antigens on the cells. – sometimes better, sometimes worse prognosis;

Benign-cells look like normal, but in a mass

Malignant: invasive, irregular

From benign to malignant is uncommon except: polyps adenoma.

VEGF is produced by malignant : to obtain blood vessel.

The one in purple: basement membrane:- wont invade down or up.

Has to separate from the primary tumor- metastasized cell. – if still not yet- it is direct spread- from one organ to another adjacent- have to write in exam too!- surgical interventions differ

To invade: (NEED TO KNOW THE FACTORS)

1. Proteolysis2. Migration3. Adhesion- Cadherin- loss of e-cadherin- causes metastasis

Malignant: not always poorly differentiated!

Well-differentiated – follicular adenoma and carcinoma of thyroid- looks the same- search at the capsules for invasion, if invasion, then carcinoma. – difficult to differentiate benign and malignant

Necorsis*- malignant.

Readily removed: easy to scoop up- because encapsulated

No recurrence after removal: only if COMPLETELY REMOVED;

Recurrent: is it left something a bit and grows back, or remove all, new one grow there, and exactly the same thing- both are recurrent. Relapse: actually second, but for tumor, use only the word recurrent.

Seldom causes death: but need to see where is it.

Eg:Secondary Hypertension**

Disrupted architecture: some books say it is disrupted, some books say it is intact- because it depends what u are comparing it with, if compare with healthy, then distorted, if compared to malignant: it would be disrupted. – thus we normally say disrupted- because we normally compare it with normal.

What can cause bleeding: can be injury: malignant mass- undergo necrosis, benign tumors(sometimes bleed, depending on the location), hormonal effect(pituitary, LH, FSH), if tumor in there, it will increase the surface of the uterus- therefore it will bleed more. Some tumor feeds on the hormone to grow.

Abnormal per-vaginal bleed. – how many pads per day for how many days- normally- how much =sometimes bleed more than normal. 2 pads- 5 pads- something is wrong. Sometimes intermenstrual bleed- stop and on.

1. Quantity2. Timing

Any surgery done? Abortion? Sometimes due to abortion. For malignant: have to ask: loss of appetite, cachaxic, etc.. ANY MEDICATION???!!!! Wad medication? Have they stopped or started any medication recently.

Benign: round and smooth: usually fibroid: leimyoma – very common in uterus- smooth muscle of uterus. Sometimes if at the margin: become sub-serosal, middle: middle-appear thicker-intramural,submucosal fibroid(projecting into the lumen-abnormality in bleeding).

Expected findings: well, look like other people. But she may be pallor- because anemia (check conjunctiva), depending on how long, do pelvic examination: vaginal examination- if abnormally enlarged, can feel. Speculum(metal), looks like duck’s mouth- to open up to see- any injury/ tumor.

Or colposcopy , ultrasound(most common, because wont be that uncomfortable)

Spindle cells are from mesenchyme: any mesenchyme tumor(smooth muscle, nerve, blood vessels), they are all spindle , except fat. Either fibrous or smooth muscle: because skeletal will be thicker. Sometimes can be vascular , but you will see blood even if tiny(RBC).

Middle: compressed the tumor.

The right: intramural

Left: sub-serosa

Longitudinal and transverse cutting. – normal arrangement of smooth muscle cells- the cells in the uterus jiao cha, thus showing both. In benign tumor, the mix will be round- therefore, whorling pattern(leiyomymo , benign tumor)

Outcome: good: just remove it.

Case2:

Malignant: LOSS OF APPETITE AND WEIGHT(>10% OF WEIGHT WITHIN 6 MONTHS)!!!!

Bimanual examination: can felel the mass there, it extends up to suprapubic region and umbilical. –lymph nodes in inguinal region, thus, metastasized to the inguinal lymph nodes.

Investigation: ultrasound(first thing obs and gyne, ALWAYS), CT scan to see how far it has gone, how many lymph nodes…

Uterus is being cut into two halfs(reflected)

Lobullated, and discoloration(due to bleeding).

Left top

right top- mitosis unlike benign, just one or two , but hardly see(esp, mesenchyme, epithelial still okay)

Below.: pleomorphism- highly pleomorphic,

1. Gall bladder: cut opened, gall stones, inside: lumen, trace the edge, malignant tumor, -irregular, invasive; it is supposed to be empty- adenocarcinoma with gall stones**- glandular lining of it. Cholenytisis , haemorrhagic(black area- old- digested blood) yellowish or whitish- necrosis, look closely, very soft, like going to crumble. If whitish, then firbrosis(top)

2. Periosteum is very tough, thus, the malignant will take the round shape in beginning- this is malignant, lower part invading to the muscles. Cant really tell the muscle. – osteosarcoma. Not much haemorrhage and necrosis- butlook out for invasion and edges

3. Breast tissue: breast ducts, well surcumscirbed, layering(pushed edges), therefore, not invade, benign. But tumor comprosed of fibrous connecting tissue and the ducts( fibroadenoma- fibrous+adenoma), usual ducts are the small one on top, but it

became tumor, so bigger)- mixed tumor- the fibrous tissue is more too- but will see fibrous tissue because NO TISSUE WILL SURVIVE WITHOUT THE CONNECTIVE TISSUE.

4. Ovary, looks malignant, but NOT! So many diff component, hard, whitish, yellow, cystic change, teratoma. – benign tumor but a lot of tissue components: usually from epidermis. Yellow: sebaceous gland, then the white is the sebaceous fat. Sometimes there will be hair too(exam will have), bony structure too. Microscopy: lung, liver, brain… eyes….

5. Breast: normal fat is beside, malignant, not really smooth edges, surface is of diff colour, the middle whitish is fibrosis.

6. Bone.the purplpe ones. Malignant: pleomorphic. It is producing bone, not inside the bone. This is hap-hazardly arranged. Osteosarcoma.

7. Bluish on top- looks gelatinous(looks pinkish), they are cartilage tissues- malignant. Edges are not well defined.- growing into the bone marrow- chondrosarcoma. – of the cartilage. – bluish also under microscope

8. Left: breast tissue, malignantRight: axilla : lymph node: involved in malignancy- blue is the dye- sentinel node)Metastasized breast cancer.

9. From bone: purplish-bluish- cartilage-cartilagenous cell. Benign- have these cells too, but well defined clear cell. So this is malignant

10. Bone tumor: x-ray: tumor is on the right:can remove the tumor: easy to remove: how much of the tumor removed: benign here. If malignant: will have whole leg .

11. Breast section: normal breast: arranged in lobule, inside, ascini , sometimes will have smaller lobules outside. If u see the margin, don’t think the lobules outside is the invasion:This is malignant: ducts are malignant: not in lobules, and irregular, all over the place.

12. Breast: malignant, they are everywhere this time, and nucleus is very very clear. 13. Skull: benign: menignioma, even though benign, but can compress on brain, thus can cause

damages. 14. Menignes: like fibrous tissue, almost the same size, benign, meningioma.15. Fibrous, glial processes- cytoplasmic processes of glial tissue- typical brain tissue. But they

are not glands, glands have lumen, this is rosecting arrangement. Small cells are almost the same cells, but this is in brain, cerebellum, in malignant: medulloblastoma. Blastic cells: small round blue cell tumor(blast)- have to know where is their location. Usually is from childhood- from in-utero, present in early childhood. BUT IF OTHERS; EPITHELIUM ETC, they are benign. EXCEPT THIS, small, round, blue! Differential diagnosis: all the blastomas and lymphoma, including retinoblastoma etc.

16. Gross for medulla blastoma, down part: malignant17. Benign, sometimes might have a bit of haemorrhhage, if removed, and very nice, then it is

benign. Shiny- smooth surface. 18. Pleomorphic and hyperchromatic, - low grade malignancy. 19. Malignant: brain tumor, in between is the brain tissue: glioblastoma multiforming

Pelliciding of the tumor- around the necrotic area???Pleomorphism, mitosis.

20. Malignant: because: surface is rough: also glioblastoma: midline shift. Obstruct csf flow by invasion. On the left might be from the same,-cutting point different.

21. Skin: mole or nirvus?-normally one colour, but if it changes colour like this, it is atypical. May not be malignant yet, but atypical

22. Malignant: microscopy of that. Cells: pleomorphic and big. Brown: melanin: melanoma.23. Malignant, pleomorphic, epithelial tumor, squamous shape. Look for keratin. Intercellular

ridges, bridging in the cell. But poorly differentiated: differentiation depends on the production of keratin. Mitosis is obvious. Squamous cell carcinoma.

24. Malignant: basal cell carcinoma25. Margins are quite well defined, but invading therefore irregular margin.- but not

widespread- around epidermis. It is a slow growing tumor.26. Basal later, invade, peripheral pelliciding, basal cell carcinoma, because its arrangement, it is

rarely metastasis, but it malignant- invasive27. Benign- from thyroid28. Thyroid: malignant: irregular, mass is cystic, forms a cyst, but the growth in the cyst is

irregular- papillary growth: when cut, look circle. Papillary carcinoma(most common in thyroid)

29. Thyroid follicles(below), it is not capsulated, it is malignant, growing all over the place30. Carcinoma of thyroid: pleomorphic ones: the darker brown: the pinkish mass, is the

amyloid(abnormal protein)-deposited anywhere, certain organs, certain tumors, systemic amyloid will deposite in everywhere. Some people says amyloid is invasive, disrupting the functions of the tissues: very typical. 4 types of thyroid tumor, only MEDULLARY TYPE HAS AMYLOID. – medullary carcinoma. Follicular, …

31. This is congo red– immunefluorescence- shining.32. Malignant: on the right: margins are not clear

Outside on the left, cant see.33. Pituitary adenoma. Stalk is on top – round, big, smooth34. Same size: pituitary adenoma, benign35. Adrenal gland: very small only, usually flat, the mass: zona granulosa..(check(, this is benign,

adrenal adenoma36. Kidney, the one on top is the mass, from adrenal. Adrenal carcinoma, round, but surface is

rough!!!!! LOOK AT SURFACE!37. Benign: microscopy, not the gross! So look at the edges. Inside: glandular

proliferation:adenoma38. Edge, higher power, same thing, nucleus akmost same size, no pleoorphism39. Same pict40. Intestinal mucosa: glandular tissue: the one on right. Underneath is submucossa, muscularis.

The dark purple is malignant: irregular … not normally there, need higher power to see which type

41. Benign: look at the nucleus42. they are different cells: cartilage tissue: chondroma: benign43. skin: there is inflammation down there: dysplasia: because basement membrane is intact.44. Dysplasia: mild- moderate dysplasia45. Cytology: pap smear- normal squamous cell- on top – nucleus is small. Bluish0 bigger, but

cytoplasm still a lot, it is dyskariotic ( moderate)dysplasia)46. Skin: invasive: pinkish – keratin pearls – well-diff squamous cell carcinoma

47. Uterus: tilt it- showing cervix. Speculum examination, can see sometimes, malignant, usually smooth, round at the opening.

48. Carcinoma of cervix. Normal is the white area, whole round. The one down there, irregular is the mass

49. Carcinoma of cervix. (down), rough looking. Top is uterus. 50. VERY COMMON-UTERUS. Uterus51. Endometrial glands. Normal – SECRETORY PHASE. Gland become bigger, and convoluted.

The secretion is below the nucleus, later, migrate to the lumen. Mucin- secretory phase- to secrete the mucin. – normal proliferative phase

52. Uterus: no cervix: malignant: carcinoma of the endometrium53. Endometrium, normal endometrium: secretory phase: like snake, proliferative phase:

round(glands), no cytoplasmic…, a lot of stroma, under surface, endometrium gland- GROW ANYWHERE IN ENDOMETRIUM, myometrium is below, unlike the colon-(invasive). This is malignant: it’s still one gland one gland, this one is together, clumps. Irregular, going everywhere

54. Ovary: benignon top: not irregular, just extra buble, cyst. Therefore, if cut, there will be fluid.55. More cystic. – ovary. Space inside, cut, fluid come out56. Benign cystic tumor: cut opened: yellowish fluid inside. Wall is very thin57. Benign: ovarian tumor: but hard: this is fibroma of ovary: white and hard. 58. Benign59. Malignant ovary- adenocarcinoma60. Cystic tumor of ovary: borderline tumor: projections , but there is basement membrane,

does not invade into stroma, thus, borderline61. Papillary tumors: in thyoroid: calcification: psammoma(the rounded spheres of calcification)-

thyroid or ovary… - PAPILLARY!!!62. Benign: it’s a whole thing(rare)63. Nodular pattern64. Ovary, teratoma: like bone, yellow like fat65. Higher power in teratoma: fat (empty), cartilage, on right top: nucleus small, bluish, circular.

Glandular below(right), resp. Left:thyroid follicles66. Malignant- pleomorphic67. Scope: yellowish throat68. Malignant: invading: glands are invasive, squamous has turned into glandular: a

transformation zone: cervix, esophagus to stomach, adenocarcinoma of lower esophagus is more common than cervix. Cervix is more to squamous cell .. – glandular turn into squamous, thus squamous metaplasia. (terbalik), transforming area are the prone ones, unstable

69. Esophagus. Right: stomach. Lower esophagus- a bit black. Barrots is metaplasia, NOT MALIGNANT!!!.

70. GIT71. Malignant, masses invading down72. Malignant(nucleus)73. Dermis: malignant74. Malignant- pleomorphism, signet ring: no gland (poorly, there is signet ring- ion right- poorly

diff adenocarcinoma; signet ring formed because accumulate mucin, mucin formed inside.

75. More obvious ring76. Staining: marker- to identify signet ring(brown)77. Colonic polyp: down: colon- grow up. Proliferation of gland, from mucosa, but no invasion,

normal glands: light;dark is dysplastic(adenoma)dangerous part(on top)78. …79. …80. Malignancy- polyps- malignant. Because it is big. Sometimes not malignant yet- need

microscopy. 81. Squamous on skin- rare- squamous papilloma, intact basement, just proliferation82. Malignant(middle)- irregular, in pharynx83. Lymph node: lymphoid tissue-blue; metastatic adenocarcinoma: because not supposed to

have the glands. – which organ did it come from?84. Benign of kidney85. Kidney: round. Renal adenoma86. Although round, but surface, malignant, 87. Rough surface- some area- necrosis- then drop out.(due to necrosis).

Around mass: nodules=satellite nodules88. So many rounds, liver, metastasis, if primary, benign, only one. If a lot, unless

leiomyoma(but not in liver), will be metastasis LIVER VERY COMMON89. Metastasis of liver90. Malignant: mitosis.. pleomorphic91. Stain: identify: immunomarker- brown92. Testes: epididymis –NOT BENIGN!!! It is seminoma- it is malignant!! But good prognosis

tumor. Because [refer next slide]93. Normal seminoferous tubules, on left, mature into sperm, middle: spermatozoa, when they

turn tumorous, they are invasive, on the right- can invade and metastasis, lymphocytes surrounding it(classic), immune respond is good. Don’t look malignant, well differentiated

94. Malignant: 95. Small, blue, round, rosac – if from neural tissue, form rosac, not lumen! It is the brain tissue.

It is a blastoma96. Lung: trachea. Bifurcation: malignant, edges: irregular(typical bronchogenic carcinoma- not

really lung carcinoma although they use the name)97. Irregular- later- involves the lung has bronchus inside the lung- the mass come from there.

Bronchogenic carcinoma. 98. Bronchial lining- bronchogenic carcinoma- pleomorphic99. Lung: nodule below: bronchogenic carcinoma: irregular100. Lung: metastasis 101. Metastasis to the lung.102. Cystic lesion: mass inside. Mass is malignant- should be ovary- irregular surface103. Bladder: a mass inside: malignant104. Malignant: uterus105. Malignant: kidney- mass from renal pelvis, fills up renal pelvis, not affecting the

parenchyma, 2 types in kidney: from proximal and distal collecting duct- parenchyma –renal cell carcinoma ; renal pelvis: lined by transitional cell, thus transitional cell carcinoma.