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Microscopic slides:
1. Atherosclerosis of aorta
2. Arteriolosclerotic nephrosclerosis
3. Myocardial infarction
4. Rheumatic myocarditis.
5. Fibrous endocarditis
6. Subcutaneous rheumatoid/ rheumatic nodule
7. Acute bronchitis
8. Chronic bronchitis
9. Lung emphysema
10. Abscessing bronchopneumonia (lobular pneumonia)
11. Lobar pneumonia (croup)
12. Interstitial pneumonia
13. Silicosis
14. Squamous cell carcinoma (SCC) lung
15. Undifferentiated small cell lung cancer
16. Chronic lymphogenic Leukemia (in liver)
17. Chronic myelogenous Leukemia (in liver)
18. NHL – 4 of the more common types
19. Hodgkin's lymphoma – all four types
20. Plasmacytoma
21. Leucoplakia
22. Giant cell epulis
23. Amelloblastoma (adamantinoma)
Micro continued..
24. Chronic tonsillitis
25. Atrophic gastritis
26. Acute duodenal ulcer
27. Chronic peptic ulcer
28. Massive acute necrosis liver
29. Micronodular cirrhosis of liver
30. Chronic cholecystitis
31. Crescentic GN (semilunar or subacute)
32. Mesangiocapillary GN
33. Nephrosclerotic glomerulonephritis
34. Acute pyelonephritis
35. Chronic pyelonephritis
36. Renal cell carcinoma
37. Carcinoma urinary bladder
38. Adenocarcinoma of prostate
39. Seminoma testis
40. Abortion
41. Molar pregnancy
42. Choriocarcinoma
43. In situ SSC uterine cervix
44. Adenocarcinoma of endometrium
45. Papillary cystadenoma of ovary
46. Papillary cystadenocarcinoma ovary
Micro continued…
47. Fibrocystic disease of breast
48. Fibroadenoma
49. Breast cancer
50. Nodular goitre
51. Graves disease (hyperthyroidism)
52. Diabetic Glomerulosclerosis
53. Acute polio encephalitis
54. Acute poliomyelitis
55. Tuberculous leptomeningitis
56. Astrocytoma
57. Glioblastoma multiforme
58. Neurinoma (schwannoma)
59. Meningioma
60. Miliary TB lungs
33. Nephrosclerosis (glomerulonephritic type - micro):
• Nephrosclerosis indicates end-stage Renal failure and
is the singular end result of myriad renal disease
processes
• It can occur due to vascular pathologies
(Arteriosclerotic and arteriolosclerotic), Inflammatory
conditions such as GN, pyelonephritis, renal TB,
metabolic disorders; diabetes, gout, amyloidosis as
well as due to obstructive nephropathies.
• GN nephrosclerosis (diffuse sclerosing GN) – most
glomeruli are hyalinized and obliterated .
• There is loss of glomerular capillaries.
• Arterioles are thickened
• Tubules are dilated and atrophied, epithelium is flat
and lumens are filled with debris/ pink colloidal
substance - Thyroidization
• Interstitium is fibrosed with diffusely scattered
chronic inflammatory infiltrate
• In patients on dialysis, calcium oxalate precipitates
may be observed in tubules and the interstitium.
Above:
obliteration of
virtually all visible
glomeruli, tubules
are destroyed.
Left: normal
healthy glomeruli
and tubules
34. Acute pyelonephritis – microscopic:
• Tubulointerstitial disease caused by infection with pyogenic –
“pus forming” - bacteria (eg. E. coli, Enterobacter, Klebsiella,
Proteus as well as Staph epidermidis, Strep pyogenes and
pneumoniae).
• Numerous neutrophils invading tubules from interstitium.
• Abscess formation sometimes with central bacteria colony.
• WBC casts in tubules.
• Hemorrhages.
• Glomeruli and capillaries are spared. Neutrophils
35. Chronic
pyelonephritis –
Microscopic:
• Eosinophilic material/
pink globules in
tubules =
proteinaceous casts of
“thyroidization”
• Basophilic highly
cellular interstitium –
chronic inflammatory
cells (mostly plasma
cells but also
lymphocytes).
• Peri-glomerular
fibrosis.
• Tubular atrophy,
dilation and necrosis
• Retracted fibro-
encased capillaries/
cicatrices.
36. Renal Cell Carcinoma - micro:
• Clear cell carcinoma is the most
common type: Large cells with
abundant clear cytoplasm that
doesn’t stain. Nuclei are
irregular; more prominent,
ovoid and with clear nucleoli.
• Neoplastic cells are arranged in
nests/ clusters and sheets with
intervening delicate vessels and
stromal network.
• There is a clear, well defined
border between healthy and
neoplastic tissue.
• Clinically patients are often
asymptomatic until a late stage.
The classic triad of symptoms is
flank pain, haematuria and a
palpable mass.
37. Carcinoma of bladder – microscopic:
 90% arise from Urothelium (transitional epithelium)
but can also arise out of squamous metaplasia (5%),
glandular, small cell or can be mixed type.
 Most common location is the lateral walls followed by
the posterior wall and region of the trigone.
 In situ forms have cellular atypism throughout the full
thickness of the urothelium but do not penetrate the
basement membrane.
 Most common form is papillary carcinoma; it is frond/
fern like with multiple anastomosing and branching
exophytic papillary projections into the bladder lumen.
 Papillae are slender when well differentiated and wide,
short and irregular when poorly differentiated. Each
has a fibrovascular core.
 Usually cells are well-differentiated enough to
resemble normal epithelium but still with some
atypism; hyperchromatic nuclei, variable nuclear size,
round and oval shape.
 Low grade tumours have organised layers
 High grade tumours have increased mitosis, more
branching and thicker layering/ stratification, cells are
larger with increased variability and more prominent
nucleoli.
38. Adenocarcinoma of prostate - microscopic:
 Second most common cancer in men
 More common in apical and peripheral zones of the
prostate rather than the bladder base, transitional
and central zones.
 Some glands may be with papillary, solid or
cribriform (punched with small holes) structure.
 Irregular tumour glands – small, crowded or “Back-
to-Back” and with abnormal shape/ structure.
 Little to no intervening stroma, cytoplasm may be
finely granular, clear or foamy do to lipid inclusions
 Basement membrane is frequently penetrated.
 Prominent nucleoli, nuclei are large and
hyperchromatic.
 Perineural invasion
 In poorly differentiated cases no glandular structure
is observed.
 Most common site of metastasis is to pelvic
lymphnodes and bones where they show as
osteoblastic/ sclerotic lesions. Most common bones
affected are the vertebrae causing long standing
back pain, Mets to the lungs and lover are also seen
in some cases.
39. Seminoma testis – micro:
• Most common testicular germ cell
tumour (45%). Origin = transformed
gonocytes.
• Uniform tumour cells - well defined
borders, pale watery clear cytoplasm
and large/ prominent, central,
vesicular/ round to polygonal nuclei,
prominent nucleoli.
• Peak incidence from 15 -30s. Never
occurs in infants.
• Separated into nests or lobules by
delicate fibrous stromal tissue.
• Usually there is lymphocytic/
plasmocytic infiltration into stroma.
• Multinucleated giant cells may be
seen.
• Granulomatous inflammation can be
seen in one third of cases.
• Sensitive to chemotherapy/ radiation
with good prognosis.
• Neoplastic tissue stains more densely
basophilic than healthy tissue
Normal testis above
40. Abortion - microscopic:
 Defined as termination of pregnancy before the 28th week of gestation
with expulsion of an embryo/ foetus incapable of surviving.
 After 28 weeks the term used is premature delivery
 Spontaneous abortions occur in the first trimester (up to 12th week)
 Stromal cells are rich in glycogen deposits (decidual reaction – occurs
during pregnancy).
 Trophoblasts(arrowheads) infiltrate uterine decidua (D).
 Focal areas of decidual necrosis (death of uterine mucosa stromal cells)
 Intense neutrophil infiltration
 Thrombi and hemorrhages of maternal blood (B).
 Edematous chorionic villi devoid of blood vessels (arrows), many are
immature, variable sizes.
 Fetal remains may be visualised, umbilical cord etc
41. Molar pregnancy – microscopic:
• Abnormal product of conception in which there is no foetus.
• Uterus is filled with cystically dilated chorionic villi
• Diffuse, Edematous, enlarged villi are seen that contain no foetal blood
vessels
• There is overgrowth of trophoblastic tissue – trophoblastic columns.
• Remarkable cytological atypia and frequent mitosis are often seen
• Fibrillar material
• HCG is usually elevated 100X fold.
42. Choriocarcinoma – microscopic:
 Chorionic villi are not present in a choriocarcinoma
 This tumour is one of the only tumours to completely lack
stroma.
 Most severe tumour that arises from trophoblast epithelium.
 Grows very aggressively, invading myometrium and rapidly
metastasizing to other organs, usually to the vagina first but also
the liver, lungs and brain.
 Tumour is associated with very markedly elevated levels of HCG.
 Cavitation and hemorrhage throughout the tissue. Bloody mess.
 Consists of monstrously large atypical and bizarre
cytotrophoblasts (pre-cursor to syncytiotrophoblasts, produce
hcg) and abnormal syncytiotrophoblasts (form the placental-
maternal blood barrier)
43. In situ SSC Uterine cervix – microscopic:
 70% = moderately differentiated large cell non-keratinizing
type – has best prognosis
 25% = well differentiated keratinizing, 5% = small cell
undifferentiated – rare but poor prognosis.
 Cancer pearls – keratin secretions at the centre of tumour
nests in highly differentiated forms of scc.
 Stratification and cellular atypia, polygonal cells with oblong
nuclei.
 Stroma is fibrous tissue with stromal reaction -
inflammatory response with plasma cell, eosinophil and
lymphocyte infiltration.
 HPV 16 + 18 are etiological factors
 In situ – has all cellular features but has not invaded the
basement membrane.
Left: normal
cervical mucosa
Right: increased
number of layers,
hyperchromatic
and enlarged
nuclei.
44. Adenocarcinoma of endometrium – microscopic:
 Peak incidence 55-65 years, rare before the age of 40.
 Post-menopausal bleeding should always raise suspicion of this pathology.
 Strongly associated with obesity and any condition that increases exposure to
estrogen.
 exophytic polyploid-papillary structure. Sometimes endophytic – infiltrating
underlying stroma and uterine muscle.
 Closely packed neoplastic glands “Back-to-back” with irregular shape, covered in
cuboidal of cylindrical cells in one to several layers thickness.
 Marked atypia
 Mitotic figures
 As the basal membrane is destroyed the glands collapse and merge forming
“punched out” elongated spindle shaped vacuolar spaces
 Squamous metaplasia may be seen in some
areas – this can occasionally transform into
a simultaneous squamous cell carcinoma
(adenosquamous carcinoma).
 Well differentiated tumours secrete mucous
at the centre of tumour nests.
Genital tumour
classification
Tumours of the surface
epithelium (Female
only)
Germ cell tumours
(M&F)
Sex cord-stromal
tumours
(M&F)
Mixed/ miscellaneous
tumours
(M&F)
OTHER: Metastatic
(krukenberg tumour in
females)
Lymphoma in males.
A). Serous (serous cystadenomas and cystadenocarcinomas)
B). Mucinous (mucinous cystadenoma/ cystadenocarcinoma)
C). Endometrioid
D). Clear cell
E). Brenner A). Teratomas (immature, mature
and malignant types)
B). Dysgerminomas (seminoma in
Male)
C) Spermatocytic seminoma (M)
D). Endodermal Yolk-Sac tumour
E). Choriocarcinoma
A). Granulosa Cell tumour
B). Theca cell tumour
(female mostly, rare in
males)
C). Sertoli – Leydig
D). Mixed granulosa- Theca
(mostly female)
E). Fibroma
F). Gynandroblastoma
A). Lipid cell tumour
B). Gonadoblastomas
45. Papillary Cystadenoma – microscopic structure:
• Tumour of the ovarian epithelium class
• Benign form, tend to occur in younger women, can be serous or mucinous
• Large variability in size from small cystic inclusions to large multilocular cysts greater than 40cm.
• Internal lining is papillary with cuboidal or flattened epithelium.
• Sometimes taller ciliated columnar epithelium is seen which resemble that of the fallopian
tubes.
• No infiltration into stroma or capsule is seen and only slight cellular atypia.
• Borderline/ low-grade malignant forms are differentiated due to their increased papillary
ingrowth and more complex pattern as well as stratification (more than 3 cell layers) and
moderate cellular atypia.
Serous form - Ciliated
columnar epithelium
resembling fallopian tubes
Mucinous form (below) resembles
endocervical mucosa – secretes mucoid fluid
46. Papillary cystadenocarcinoma of ovary:
• A tumour of the ovarian surface
epithelium; serous type (most common
type of ovarian tumour = 40% of all
cases).
• Cyst epithelium has pronounced papillary
growth pattern with complex infoldings.
• Cellular stratification is present (more
than three cell layers).
• Mitotic figures and marked cellular
atypia.
• Hyperchromatism
• Pleomorphic
• Invasion is common into underlying
stroma or ovarian capsule.
• Calcification in the form of small round
psammoma bodies is sometimes present
• Lymphnode and peritoneal involvement
occurs relatively early in the disease
course.
• 70% of serous malignancies are bilateral.
Severely atypical nucleus
Micropapillary structure
47. Fibrocystic disease of the breast – microscopic:
• Non-proliferative process, usually affecting terminal duct-lobular unit
(TDLU).
• Many of the ducts are dilated. Some are so dilated they form irregular
cysts.
• There is fibrosis interweaving between cysts
• Cysts are lined by benign uniform cuboidal or columnar epithelium
• Hydro-adenoid metaplasia may occur – development of glands that
resemble sweat glands.
• Lumens of the glands may be filled with homogenous pink substance.
• Some cysts may rupture leading to mild chronic inflammation and
there may be scanty infiltration with lymphocytes and plasma cells.
• Most commonly
develops between 30
and menopause in 10-
25% women.
• Most common cause for
benign breast lumps
which are often bilateral
but not always
symmetrical.
48. Fibroadenoma of the breast – microscopic:
• Most common tumour of the breast.
• Occurs in young women
• Can be peri-canalicular (upper image) or
intracanalicular (lower image).
• fibro-epithelial composition; fibrinoid
element = immature fibrose tissue with
scanty collagen, epithelioid element =
glandular like formations covered with
tubular epithelium.
• Intracanicular fibroadenomas cause “slit-
like” distorted and compressed ducts due to
displacement inward by stromal fibrose
tissue.
• Peri-canalicular fibroadenomas present as
stroma that grows concentrically around
round or elongated dilated duct lumena.
49. Breast Carcinoma – Microscopic:
Breast cancer
classification
Non-invasive/
in-situ types
Ductal carcinoma
in situ (DCIS)
Comedocarcinoma
Cribiform DCIS
Solid DCIS
Papillary DCIS
Micropapillary
DCIs
Lobular carcinoma
in situ (LCIS)
Invasive types
Invasive ductal
carcinomas
Medullary
carcinoma
Mucinous/
colloid
carcinoma
Tubular
carcinoma
Invasive papillary
Inflammatory
carcinoma
Invasive lobular
carcinomas
A). Invasive ductal carcinoma - microscopic:
 The most common type of breast cancer constituting 70-80% of
all cases.
 Multiple structural patterns are seen; tubules, solid nests and
strands of tumour cells
 The lumen may be partially or fully occluded by proliferating
tumour cells
 The tumour cells infiltrate adjacent structures and as it does the
stroma gets progressively more fibrose and dense producing
the characteristic “Scirrhous” or scarred appearance.
 The stroma is rich in collagen and elastic fibers, hyaline
deposition occurs in places.
 There is no capsule
 peri-neural invasion is frequent = trademark dull, constant
neoplastic pain from the affected breast.
B). DCIS – Microscopic:
• Classic cribriform pattern (lower image) shows fenestrations –
intraepithelial “punched-out” clear vacuolar spaces
• Regular in shape (monomorphic) and evenly distributed with
minimal hyperchromatism or pleomorphism.
• Lacks periductal fibrosis
• Excision is curative in 95% of cases.
Comedo form (upper image):
• More hyperchromatic and pleomorphic
• Rapidly proliferating
• Central necrosis is clearly visible
• Periductal fibrosis
• High grade but prognosis is still relatively good.
50. Nodular Goiter (endemic hypothyroidism) – microscopic:
• Caused most often by iodine deficiency and used to affect whole
communities in areas where there was poor levels of iodine in soil and
water.
• Thyroid follicles are lined with inactive, flattened epithelium
• There is abundant eosinophilic colloid, these are the early stages and is
defined as simple goiter.
• Over time, complicated or nodular goiter occurs - interstitial fibrosis
slowly develops forming nodules.
• Hemorrhages, microcysts and calcifications are also seen.
• Follicles are variable in size from small to very large
• Nodules are poorly or incompletely encapsulated.
51. Graves disease (autoimmune hyperthyroidism, Basedow’s disease) –
microscopic:
 Thyroid hyperplasia with many papillary infoldings within the follicles
– this is because autoantibodies to TSH receptors stimulate
overgrowth of the follicular epithelium.
 Epithelium has increased height and the lumena are smaller than
normal.
 Colloid is diminished/ pale and diluted or even absent in some
follicles.
 Colloid contains many interspersed empty bubbles.
 Clear spaces/ vacuolar “haloes” around the centrally placed colloid
indicates its resorption and release into systemic circulation
(thyrotoxicosis).
 Pre-tibial myxedematous infiltrate as well as exophthalmos are
classical features of the disease.
 Graves is most common
around 30-40 years of age
with female predominance.
 Stroma shows inflammatory
infiltrate with lymphocytes
and we also see increased
vascularity.
52. Diabetic Glomerulosclerosis –
microscopic:
 Hyalinosis of afferent arteriolar
wall.
 Expansive sclerosis of mesangium
of glomeruli leads to their
enlargement.
 Interpapillary hyaline globules (PAS
stain pink) are seen in the
glomeruli, some glomeruli are
completely sclerosed.
 There may be slightly increased
mesangial cellularity and capillary
basement membrane thickening.
 Tubular atrophy with vacuolar
degeneration of the epithelium.
 These changes may progressively
worsen if diabetes is not well
controlled and results in chronic
renal failure.
53. Polioencephalitis – microscopic:
• Vascular hyperaemia
• Perivascular edema
• Lymphocytic infiltration, some neutrophils
• Micro-abscesses, petechial or pin-point hemorrhages and glial hyperplasia around blood vessels – “cuffing” of
arterioles and injured cells by inflammatory reaction.
• Changes are seen mostly in the spinal cord and rarely in the cerebellum and brainstem.
• Tigrolysis – loss of Nissl substance/ bodies (rough endoplasmic reticulum) in the motor neurons that accompanies
neurodegenerative processes.
• Intranuclear eosinophilic inclusions are seen
54. Acute poliomyelitis – microscopic:
- Polio is a disabling, life-threatening central
nervous system disease caused by poliovirus
(an RNA enterovirus which only infects
humans.)
- It causes flu-like symptoms and less often
paraesthesia, meningitis and paralysis (in 1%
of cases).
- Poliovirus destroys motor neurons in the
anterior horn gray matter of the spinal cord as
well as in the brainstem.
- Flaccid paralysis and progressive muscle
wasting/ atrophy may occur leading to
respiratory failure. Milder cases of weakness
may last for several years – post-polio
syndrome.
- Hyperaemia and edema can be seen in the
anterior horn.
- Lymphocytic infiltrate is present
- “Reactive” microglial cells (CNS macrophages)
are seen surrounding the remnants of
ruptured anterior horn motor neurons and
consuming the debris – Neurophagia.
55. Tuberculous leptomeningitis –
microscopic:
 Granulomas are usually not seen
 Usually manifests in the meninges
covering the base of the brain.
 Fibrinous exudate with numerous
lymphocytes and plasma cells is seen
 Sometimes local microscopic granulomas
are seen in only peri-vascular areas
accompanied by caseating necrosis and
giant Langhan cells.
 Acid-fast or “Ziehl-Neelson” staining can
be used to identify the mycobacterium
which appear as red rods. The specimen is
not decolourised upon addition of the
acid.
 Commonly affects children, elderly and
immunocompromised patients
 Workup demonstrates profoundly low CSF
glucose, high CSF protein.
56. Astrocytoma:
 A type of low-grade benign glioma
 Star- shaped cells
 Diffuse and fine, multiple, fibrillary, tangled
meshwork is seen in the background.
 Increased cellularity and slight pleomorphism
compared to the normal healthy brain tissue.
 Some cells are hyperchromatic/ dark blueish- purple
staining
 The stroma is rich in blood vessels
 Though low grade this tumour isn’t very discrete or
well circumscribed and tend slowly invade over the
course of many years.
 Astrocytoma's tend to accumulate more and more
mutations over time, becoming ever increasingly
anaplastic and may eventually transform into the
higher grade, aggressive glioblastomas.
 Astrocytoma’s may occur anywhere in the brain from
the cerebral hemispheres and cerebellum to the
brainstem and spinal cord but are most frequent in
the central portions of the cerebrum.
57. Glioblastoma multiforme – microscopic:
 Malignant tumour with poor prognosis
 Highly cellular
 Many cellular shapes (pleomorphism) are seen hence the
name “multiforme”
 Cells are hyperchromatic and very atypical.
 The stroma is a fine fibrillary meshwork
 There is prominent vascularity – the stroma is rich in
blood vessels and hemorrhages are frequently seen
 Pale areas of necrosis are visible with concentrations of
tumour cells around their circumference giving a
pseudopallisading necrosis pattern that is very
characteristic for glioblastomas.
 Monstrous multinucleated cells may be seen
 The anaplastic atypical cells favour invading white matter
tracts and often spread across the brain to the opposite
hemisphere via the corpus callosum.
 This tumour is most commonly found in the frontal and
temporal lobes making it a common cause of new onset
epilepsy/ seizures and these symptoms tend to rapidly
progress.
58. Neurinoma – microscopic
 tumour stroma has fascicular structure (arranged
together in “fascicles” or “bundles/clusters”)
 Tumour cells are spindle shaped (wide in the middle
and tapered at both ends)
 Borders between cells are difficult to visualise and
indistinct
 Pathognomonic feature= Verocay bodies – these are
pink areas surrounded by a palisade/ fence of nuclei
 Nuclei are elongated and slender and look like cigars
 Recent and old hemorrhages may be seen.
 When the connective tissue component is very
abundant the tumour is called a neurofibroma.
 These tumours have one of two specific patterns:
Antoni A pattern (left side fig.1) – alternating rows of
nuclei (pseudopallisades) with pink acellular areas in-
between giving a striped appearance.
Antoni B pattern( R. side fig 1.) – less cellular, with
more loosely organised stroma and myxoid change
(metachromatic or more blueish purple connective
tissue).
FIG.1
59. Meningioma – Microscopic
• Benign tumour
• Pathognomonic feature = “Psammoma body”.
• Psammoma bodies are pink or dark violet hyalinized
globules or fibroblastic elements, sometimes with calcium
deposits, found at the centre of concentrically layered
tumour cells. They have the characteristic appearances of
a rosebud.
• Meningiomas are variable in microscopic pattern
• A tight whorled pattern is commonly seen with oval
nuclei.
• Nuclei appear open or vesicular/ semi-empty due to
dispersed chromatin.
• Tumour cells are elongated and spindle-shaped and tend
to be layered in concentric circles
• Meningiomas are rich in blood vessels with abnormally
thick hyalinized walls
• They are uncommon in children
• Slightly more common in females than males (3:2)
• More aggressive or atypical meningiomas can be
identified by a few key characteristics; higher mitotic
index/ more mitotic figures seen, increased number of
tumour cells and larger nuclei (increased nuclear to
cytoplasmic ratio).
60. Miliary TB - Microscopic:
• Multiple irregularly spread “millet seed” sized granulomas
• Central caseous necrosis
• Granulomas are well-defined with discrete borders
• Macrophages transform into "epithelioid” cells – they appear like
epithelium due to the way their nuclei change into bean
shaped/long pale vesicular form as do they palisade or make a
fence-like barricade around the outer rim of the granuloma.
• Other macrophages stimulated by cytokines form giant Langhan
cells – multinucleated cells formed by Mafs that fused together.
• Langhan cells form horseshoe shapes around the central necrosis
with their nuclei lining up on the inner edge closest to the
necrosis.
• Plasma cells, fibroblasts and occasional polymorphonuclear cells
can also be seen.
• Acid fast staining can be utilised to visualise mycobacteria. They
stain as reddish-purple rods within granulomas
• PCR is much more sensitive than microscopy for detecting
mycobacteria

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PMU third/fourth year Clinical pathoanatomy Part 2

  • 1. Microscopic slides: 1. Atherosclerosis of aorta 2. Arteriolosclerotic nephrosclerosis 3. Myocardial infarction 4. Rheumatic myocarditis. 5. Fibrous endocarditis 6. Subcutaneous rheumatoid/ rheumatic nodule 7. Acute bronchitis 8. Chronic bronchitis 9. Lung emphysema 10. Abscessing bronchopneumonia (lobular pneumonia) 11. Lobar pneumonia (croup) 12. Interstitial pneumonia 13. Silicosis 14. Squamous cell carcinoma (SCC) lung 15. Undifferentiated small cell lung cancer 16. Chronic lymphogenic Leukemia (in liver) 17. Chronic myelogenous Leukemia (in liver) 18. NHL – 4 of the more common types 19. Hodgkin's lymphoma – all four types 20. Plasmacytoma 21. Leucoplakia 22. Giant cell epulis 23. Amelloblastoma (adamantinoma) Micro continued.. 24. Chronic tonsillitis 25. Atrophic gastritis 26. Acute duodenal ulcer 27. Chronic peptic ulcer 28. Massive acute necrosis liver 29. Micronodular cirrhosis of liver 30. Chronic cholecystitis 31. Crescentic GN (semilunar or subacute) 32. Mesangiocapillary GN 33. Nephrosclerotic glomerulonephritis 34. Acute pyelonephritis 35. Chronic pyelonephritis 36. Renal cell carcinoma 37. Carcinoma urinary bladder 38. Adenocarcinoma of prostate 39. Seminoma testis 40. Abortion 41. Molar pregnancy 42. Choriocarcinoma 43. In situ SSC uterine cervix 44. Adenocarcinoma of endometrium 45. Papillary cystadenoma of ovary 46. Papillary cystadenocarcinoma ovary
  • 2. Micro continued… 47. Fibrocystic disease of breast 48. Fibroadenoma 49. Breast cancer 50. Nodular goitre 51. Graves disease (hyperthyroidism) 52. Diabetic Glomerulosclerosis 53. Acute polio encephalitis 54. Acute poliomyelitis 55. Tuberculous leptomeningitis 56. Astrocytoma 57. Glioblastoma multiforme 58. Neurinoma (schwannoma) 59. Meningioma 60. Miliary TB lungs
  • 3. 33. Nephrosclerosis (glomerulonephritic type - micro): • Nephrosclerosis indicates end-stage Renal failure and is the singular end result of myriad renal disease processes • It can occur due to vascular pathologies (Arteriosclerotic and arteriolosclerotic), Inflammatory conditions such as GN, pyelonephritis, renal TB, metabolic disorders; diabetes, gout, amyloidosis as well as due to obstructive nephropathies. • GN nephrosclerosis (diffuse sclerosing GN) – most glomeruli are hyalinized and obliterated . • There is loss of glomerular capillaries. • Arterioles are thickened • Tubules are dilated and atrophied, epithelium is flat and lumens are filled with debris/ pink colloidal substance - Thyroidization • Interstitium is fibrosed with diffusely scattered chronic inflammatory infiltrate • In patients on dialysis, calcium oxalate precipitates may be observed in tubules and the interstitium. Above: obliteration of virtually all visible glomeruli, tubules are destroyed. Left: normal healthy glomeruli and tubules
  • 4. 34. Acute pyelonephritis – microscopic: • Tubulointerstitial disease caused by infection with pyogenic – “pus forming” - bacteria (eg. E. coli, Enterobacter, Klebsiella, Proteus as well as Staph epidermidis, Strep pyogenes and pneumoniae). • Numerous neutrophils invading tubules from interstitium. • Abscess formation sometimes with central bacteria colony. • WBC casts in tubules. • Hemorrhages. • Glomeruli and capillaries are spared. Neutrophils
  • 5. 35. Chronic pyelonephritis – Microscopic: • Eosinophilic material/ pink globules in tubules = proteinaceous casts of “thyroidization” • Basophilic highly cellular interstitium – chronic inflammatory cells (mostly plasma cells but also lymphocytes). • Peri-glomerular fibrosis. • Tubular atrophy, dilation and necrosis • Retracted fibro- encased capillaries/ cicatrices.
  • 6. 36. Renal Cell Carcinoma - micro: • Clear cell carcinoma is the most common type: Large cells with abundant clear cytoplasm that doesn’t stain. Nuclei are irregular; more prominent, ovoid and with clear nucleoli. • Neoplastic cells are arranged in nests/ clusters and sheets with intervening delicate vessels and stromal network. • There is a clear, well defined border between healthy and neoplastic tissue. • Clinically patients are often asymptomatic until a late stage. The classic triad of symptoms is flank pain, haematuria and a palpable mass.
  • 7. 37. Carcinoma of bladder – microscopic:  90% arise from Urothelium (transitional epithelium) but can also arise out of squamous metaplasia (5%), glandular, small cell or can be mixed type.  Most common location is the lateral walls followed by the posterior wall and region of the trigone.  In situ forms have cellular atypism throughout the full thickness of the urothelium but do not penetrate the basement membrane.  Most common form is papillary carcinoma; it is frond/ fern like with multiple anastomosing and branching exophytic papillary projections into the bladder lumen.  Papillae are slender when well differentiated and wide, short and irregular when poorly differentiated. Each has a fibrovascular core.  Usually cells are well-differentiated enough to resemble normal epithelium but still with some atypism; hyperchromatic nuclei, variable nuclear size, round and oval shape.  Low grade tumours have organised layers  High grade tumours have increased mitosis, more branching and thicker layering/ stratification, cells are larger with increased variability and more prominent nucleoli.
  • 8. 38. Adenocarcinoma of prostate - microscopic:  Second most common cancer in men  More common in apical and peripheral zones of the prostate rather than the bladder base, transitional and central zones.  Some glands may be with papillary, solid or cribriform (punched with small holes) structure.  Irregular tumour glands – small, crowded or “Back- to-Back” and with abnormal shape/ structure.  Little to no intervening stroma, cytoplasm may be finely granular, clear or foamy do to lipid inclusions  Basement membrane is frequently penetrated.  Prominent nucleoli, nuclei are large and hyperchromatic.  Perineural invasion  In poorly differentiated cases no glandular structure is observed.  Most common site of metastasis is to pelvic lymphnodes and bones where they show as osteoblastic/ sclerotic lesions. Most common bones affected are the vertebrae causing long standing back pain, Mets to the lungs and lover are also seen in some cases.
  • 9. 39. Seminoma testis – micro: • Most common testicular germ cell tumour (45%). Origin = transformed gonocytes. • Uniform tumour cells - well defined borders, pale watery clear cytoplasm and large/ prominent, central, vesicular/ round to polygonal nuclei, prominent nucleoli. • Peak incidence from 15 -30s. Never occurs in infants. • Separated into nests or lobules by delicate fibrous stromal tissue. • Usually there is lymphocytic/ plasmocytic infiltration into stroma. • Multinucleated giant cells may be seen. • Granulomatous inflammation can be seen in one third of cases. • Sensitive to chemotherapy/ radiation with good prognosis. • Neoplastic tissue stains more densely basophilic than healthy tissue Normal testis above
  • 10. 40. Abortion - microscopic:  Defined as termination of pregnancy before the 28th week of gestation with expulsion of an embryo/ foetus incapable of surviving.  After 28 weeks the term used is premature delivery  Spontaneous abortions occur in the first trimester (up to 12th week)  Stromal cells are rich in glycogen deposits (decidual reaction – occurs during pregnancy).  Trophoblasts(arrowheads) infiltrate uterine decidua (D).  Focal areas of decidual necrosis (death of uterine mucosa stromal cells)  Intense neutrophil infiltration  Thrombi and hemorrhages of maternal blood (B).  Edematous chorionic villi devoid of blood vessels (arrows), many are immature, variable sizes.  Fetal remains may be visualised, umbilical cord etc
  • 11. 41. Molar pregnancy – microscopic: • Abnormal product of conception in which there is no foetus. • Uterus is filled with cystically dilated chorionic villi • Diffuse, Edematous, enlarged villi are seen that contain no foetal blood vessels • There is overgrowth of trophoblastic tissue – trophoblastic columns. • Remarkable cytological atypia and frequent mitosis are often seen • Fibrillar material • HCG is usually elevated 100X fold.
  • 12. 42. Choriocarcinoma – microscopic:  Chorionic villi are not present in a choriocarcinoma  This tumour is one of the only tumours to completely lack stroma.  Most severe tumour that arises from trophoblast epithelium.  Grows very aggressively, invading myometrium and rapidly metastasizing to other organs, usually to the vagina first but also the liver, lungs and brain.  Tumour is associated with very markedly elevated levels of HCG.  Cavitation and hemorrhage throughout the tissue. Bloody mess.  Consists of monstrously large atypical and bizarre cytotrophoblasts (pre-cursor to syncytiotrophoblasts, produce hcg) and abnormal syncytiotrophoblasts (form the placental- maternal blood barrier)
  • 13. 43. In situ SSC Uterine cervix – microscopic:  70% = moderately differentiated large cell non-keratinizing type – has best prognosis  25% = well differentiated keratinizing, 5% = small cell undifferentiated – rare but poor prognosis.  Cancer pearls – keratin secretions at the centre of tumour nests in highly differentiated forms of scc.  Stratification and cellular atypia, polygonal cells with oblong nuclei.  Stroma is fibrous tissue with stromal reaction - inflammatory response with plasma cell, eosinophil and lymphocyte infiltration.  HPV 16 + 18 are etiological factors  In situ – has all cellular features but has not invaded the basement membrane. Left: normal cervical mucosa Right: increased number of layers, hyperchromatic and enlarged nuclei.
  • 14. 44. Adenocarcinoma of endometrium – microscopic:  Peak incidence 55-65 years, rare before the age of 40.  Post-menopausal bleeding should always raise suspicion of this pathology.  Strongly associated with obesity and any condition that increases exposure to estrogen.  exophytic polyploid-papillary structure. Sometimes endophytic – infiltrating underlying stroma and uterine muscle.  Closely packed neoplastic glands “Back-to-back” with irregular shape, covered in cuboidal of cylindrical cells in one to several layers thickness.  Marked atypia  Mitotic figures  As the basal membrane is destroyed the glands collapse and merge forming “punched out” elongated spindle shaped vacuolar spaces  Squamous metaplasia may be seen in some areas – this can occasionally transform into a simultaneous squamous cell carcinoma (adenosquamous carcinoma).  Well differentiated tumours secrete mucous at the centre of tumour nests.
  • 15. Genital tumour classification Tumours of the surface epithelium (Female only) Germ cell tumours (M&F) Sex cord-stromal tumours (M&F) Mixed/ miscellaneous tumours (M&F) OTHER: Metastatic (krukenberg tumour in females) Lymphoma in males. A). Serous (serous cystadenomas and cystadenocarcinomas) B). Mucinous (mucinous cystadenoma/ cystadenocarcinoma) C). Endometrioid D). Clear cell E). Brenner A). Teratomas (immature, mature and malignant types) B). Dysgerminomas (seminoma in Male) C) Spermatocytic seminoma (M) D). Endodermal Yolk-Sac tumour E). Choriocarcinoma A). Granulosa Cell tumour B). Theca cell tumour (female mostly, rare in males) C). Sertoli – Leydig D). Mixed granulosa- Theca (mostly female) E). Fibroma F). Gynandroblastoma A). Lipid cell tumour B). Gonadoblastomas
  • 16. 45. Papillary Cystadenoma – microscopic structure: • Tumour of the ovarian epithelium class • Benign form, tend to occur in younger women, can be serous or mucinous • Large variability in size from small cystic inclusions to large multilocular cysts greater than 40cm. • Internal lining is papillary with cuboidal or flattened epithelium. • Sometimes taller ciliated columnar epithelium is seen which resemble that of the fallopian tubes. • No infiltration into stroma or capsule is seen and only slight cellular atypia. • Borderline/ low-grade malignant forms are differentiated due to their increased papillary ingrowth and more complex pattern as well as stratification (more than 3 cell layers) and moderate cellular atypia. Serous form - Ciliated columnar epithelium resembling fallopian tubes Mucinous form (below) resembles endocervical mucosa – secretes mucoid fluid
  • 17. 46. Papillary cystadenocarcinoma of ovary: • A tumour of the ovarian surface epithelium; serous type (most common type of ovarian tumour = 40% of all cases). • Cyst epithelium has pronounced papillary growth pattern with complex infoldings. • Cellular stratification is present (more than three cell layers). • Mitotic figures and marked cellular atypia. • Hyperchromatism • Pleomorphic • Invasion is common into underlying stroma or ovarian capsule. • Calcification in the form of small round psammoma bodies is sometimes present • Lymphnode and peritoneal involvement occurs relatively early in the disease course. • 70% of serous malignancies are bilateral. Severely atypical nucleus Micropapillary structure
  • 18. 47. Fibrocystic disease of the breast – microscopic: • Non-proliferative process, usually affecting terminal duct-lobular unit (TDLU). • Many of the ducts are dilated. Some are so dilated they form irregular cysts. • There is fibrosis interweaving between cysts • Cysts are lined by benign uniform cuboidal or columnar epithelium • Hydro-adenoid metaplasia may occur – development of glands that resemble sweat glands. • Lumens of the glands may be filled with homogenous pink substance. • Some cysts may rupture leading to mild chronic inflammation and there may be scanty infiltration with lymphocytes and plasma cells. • Most commonly develops between 30 and menopause in 10- 25% women. • Most common cause for benign breast lumps which are often bilateral but not always symmetrical.
  • 19. 48. Fibroadenoma of the breast – microscopic: • Most common tumour of the breast. • Occurs in young women • Can be peri-canalicular (upper image) or intracanalicular (lower image). • fibro-epithelial composition; fibrinoid element = immature fibrose tissue with scanty collagen, epithelioid element = glandular like formations covered with tubular epithelium. • Intracanicular fibroadenomas cause “slit- like” distorted and compressed ducts due to displacement inward by stromal fibrose tissue. • Peri-canalicular fibroadenomas present as stroma that grows concentrically around round or elongated dilated duct lumena.
  • 20. 49. Breast Carcinoma – Microscopic: Breast cancer classification Non-invasive/ in-situ types Ductal carcinoma in situ (DCIS) Comedocarcinoma Cribiform DCIS Solid DCIS Papillary DCIS Micropapillary DCIs Lobular carcinoma in situ (LCIS) Invasive types Invasive ductal carcinomas Medullary carcinoma Mucinous/ colloid carcinoma Tubular carcinoma Invasive papillary Inflammatory carcinoma Invasive lobular carcinomas
  • 21. A). Invasive ductal carcinoma - microscopic:  The most common type of breast cancer constituting 70-80% of all cases.  Multiple structural patterns are seen; tubules, solid nests and strands of tumour cells  The lumen may be partially or fully occluded by proliferating tumour cells  The tumour cells infiltrate adjacent structures and as it does the stroma gets progressively more fibrose and dense producing the characteristic “Scirrhous” or scarred appearance.  The stroma is rich in collagen and elastic fibers, hyaline deposition occurs in places.  There is no capsule  peri-neural invasion is frequent = trademark dull, constant neoplastic pain from the affected breast.
  • 22. B). DCIS – Microscopic: • Classic cribriform pattern (lower image) shows fenestrations – intraepithelial “punched-out” clear vacuolar spaces • Regular in shape (monomorphic) and evenly distributed with minimal hyperchromatism or pleomorphism. • Lacks periductal fibrosis • Excision is curative in 95% of cases. Comedo form (upper image): • More hyperchromatic and pleomorphic • Rapidly proliferating • Central necrosis is clearly visible • Periductal fibrosis • High grade but prognosis is still relatively good.
  • 23. 50. Nodular Goiter (endemic hypothyroidism) – microscopic: • Caused most often by iodine deficiency and used to affect whole communities in areas where there was poor levels of iodine in soil and water. • Thyroid follicles are lined with inactive, flattened epithelium • There is abundant eosinophilic colloid, these are the early stages and is defined as simple goiter. • Over time, complicated or nodular goiter occurs - interstitial fibrosis slowly develops forming nodules. • Hemorrhages, microcysts and calcifications are also seen. • Follicles are variable in size from small to very large • Nodules are poorly or incompletely encapsulated.
  • 24. 51. Graves disease (autoimmune hyperthyroidism, Basedow’s disease) – microscopic:  Thyroid hyperplasia with many papillary infoldings within the follicles – this is because autoantibodies to TSH receptors stimulate overgrowth of the follicular epithelium.  Epithelium has increased height and the lumena are smaller than normal.  Colloid is diminished/ pale and diluted or even absent in some follicles.  Colloid contains many interspersed empty bubbles.  Clear spaces/ vacuolar “haloes” around the centrally placed colloid indicates its resorption and release into systemic circulation (thyrotoxicosis).  Pre-tibial myxedematous infiltrate as well as exophthalmos are classical features of the disease.  Graves is most common around 30-40 years of age with female predominance.  Stroma shows inflammatory infiltrate with lymphocytes and we also see increased vascularity.
  • 25. 52. Diabetic Glomerulosclerosis – microscopic:  Hyalinosis of afferent arteriolar wall.  Expansive sclerosis of mesangium of glomeruli leads to their enlargement.  Interpapillary hyaline globules (PAS stain pink) are seen in the glomeruli, some glomeruli are completely sclerosed.  There may be slightly increased mesangial cellularity and capillary basement membrane thickening.  Tubular atrophy with vacuolar degeneration of the epithelium.  These changes may progressively worsen if diabetes is not well controlled and results in chronic renal failure.
  • 26. 53. Polioencephalitis – microscopic: • Vascular hyperaemia • Perivascular edema • Lymphocytic infiltration, some neutrophils • Micro-abscesses, petechial or pin-point hemorrhages and glial hyperplasia around blood vessels – “cuffing” of arterioles and injured cells by inflammatory reaction. • Changes are seen mostly in the spinal cord and rarely in the cerebellum and brainstem. • Tigrolysis – loss of Nissl substance/ bodies (rough endoplasmic reticulum) in the motor neurons that accompanies neurodegenerative processes. • Intranuclear eosinophilic inclusions are seen
  • 27. 54. Acute poliomyelitis – microscopic: - Polio is a disabling, life-threatening central nervous system disease caused by poliovirus (an RNA enterovirus which only infects humans.) - It causes flu-like symptoms and less often paraesthesia, meningitis and paralysis (in 1% of cases). - Poliovirus destroys motor neurons in the anterior horn gray matter of the spinal cord as well as in the brainstem. - Flaccid paralysis and progressive muscle wasting/ atrophy may occur leading to respiratory failure. Milder cases of weakness may last for several years – post-polio syndrome. - Hyperaemia and edema can be seen in the anterior horn. - Lymphocytic infiltrate is present - “Reactive” microglial cells (CNS macrophages) are seen surrounding the remnants of ruptured anterior horn motor neurons and consuming the debris – Neurophagia.
  • 28. 55. Tuberculous leptomeningitis – microscopic:  Granulomas are usually not seen  Usually manifests in the meninges covering the base of the brain.  Fibrinous exudate with numerous lymphocytes and plasma cells is seen  Sometimes local microscopic granulomas are seen in only peri-vascular areas accompanied by caseating necrosis and giant Langhan cells.  Acid-fast or “Ziehl-Neelson” staining can be used to identify the mycobacterium which appear as red rods. The specimen is not decolourised upon addition of the acid.  Commonly affects children, elderly and immunocompromised patients  Workup demonstrates profoundly low CSF glucose, high CSF protein.
  • 29. 56. Astrocytoma:  A type of low-grade benign glioma  Star- shaped cells  Diffuse and fine, multiple, fibrillary, tangled meshwork is seen in the background.  Increased cellularity and slight pleomorphism compared to the normal healthy brain tissue.  Some cells are hyperchromatic/ dark blueish- purple staining  The stroma is rich in blood vessels  Though low grade this tumour isn’t very discrete or well circumscribed and tend slowly invade over the course of many years.  Astrocytoma's tend to accumulate more and more mutations over time, becoming ever increasingly anaplastic and may eventually transform into the higher grade, aggressive glioblastomas.  Astrocytoma’s may occur anywhere in the brain from the cerebral hemispheres and cerebellum to the brainstem and spinal cord but are most frequent in the central portions of the cerebrum.
  • 30. 57. Glioblastoma multiforme – microscopic:  Malignant tumour with poor prognosis  Highly cellular  Many cellular shapes (pleomorphism) are seen hence the name “multiforme”  Cells are hyperchromatic and very atypical.  The stroma is a fine fibrillary meshwork  There is prominent vascularity – the stroma is rich in blood vessels and hemorrhages are frequently seen  Pale areas of necrosis are visible with concentrations of tumour cells around their circumference giving a pseudopallisading necrosis pattern that is very characteristic for glioblastomas.  Monstrous multinucleated cells may be seen  The anaplastic atypical cells favour invading white matter tracts and often spread across the brain to the opposite hemisphere via the corpus callosum.  This tumour is most commonly found in the frontal and temporal lobes making it a common cause of new onset epilepsy/ seizures and these symptoms tend to rapidly progress.
  • 31. 58. Neurinoma – microscopic  tumour stroma has fascicular structure (arranged together in “fascicles” or “bundles/clusters”)  Tumour cells are spindle shaped (wide in the middle and tapered at both ends)  Borders between cells are difficult to visualise and indistinct  Pathognomonic feature= Verocay bodies – these are pink areas surrounded by a palisade/ fence of nuclei  Nuclei are elongated and slender and look like cigars  Recent and old hemorrhages may be seen.  When the connective tissue component is very abundant the tumour is called a neurofibroma.  These tumours have one of two specific patterns: Antoni A pattern (left side fig.1) – alternating rows of nuclei (pseudopallisades) with pink acellular areas in- between giving a striped appearance. Antoni B pattern( R. side fig 1.) – less cellular, with more loosely organised stroma and myxoid change (metachromatic or more blueish purple connective tissue). FIG.1
  • 32. 59. Meningioma – Microscopic • Benign tumour • Pathognomonic feature = “Psammoma body”. • Psammoma bodies are pink or dark violet hyalinized globules or fibroblastic elements, sometimes with calcium deposits, found at the centre of concentrically layered tumour cells. They have the characteristic appearances of a rosebud. • Meningiomas are variable in microscopic pattern • A tight whorled pattern is commonly seen with oval nuclei. • Nuclei appear open or vesicular/ semi-empty due to dispersed chromatin. • Tumour cells are elongated and spindle-shaped and tend to be layered in concentric circles • Meningiomas are rich in blood vessels with abnormally thick hyalinized walls • They are uncommon in children • Slightly more common in females than males (3:2) • More aggressive or atypical meningiomas can be identified by a few key characteristics; higher mitotic index/ more mitotic figures seen, increased number of tumour cells and larger nuclei (increased nuclear to cytoplasmic ratio).
  • 33. 60. Miliary TB - Microscopic: • Multiple irregularly spread “millet seed” sized granulomas • Central caseous necrosis • Granulomas are well-defined with discrete borders • Macrophages transform into "epithelioid” cells – they appear like epithelium due to the way their nuclei change into bean shaped/long pale vesicular form as do they palisade or make a fence-like barricade around the outer rim of the granuloma. • Other macrophages stimulated by cytokines form giant Langhan cells – multinucleated cells formed by Mafs that fused together. • Langhan cells form horseshoe shapes around the central necrosis with their nuclei lining up on the inner edge closest to the necrosis. • Plasma cells, fibroblasts and occasional polymorphonuclear cells can also be seen. • Acid fast staining can be utilised to visualise mycobacteria. They stain as reddish-purple rods within granulomas • PCR is much more sensitive than microscopy for detecting mycobacteria