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.
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