Pathohistology

Semester II. 2016

By: Botond Vitzy

Slide 51: Meningioma

Meningioma is a benign tumor of meningothelial cells generally
found on the surface, or in the ventricles of the brain. It usually
presents as a single lesion, but in some cases, such as
neurofibromatosis, it can be multiple lesions

It is an encircled, whitish, non-infiltrating mass, which can compress several regions of

the brain that, depending on the region compressed, can cause symptoms such as:
headache and profuse vomiting.

The higher the grading of the lesion, the more malignant the tumor. Meningiomas are
usually benign, however malignant forms (eg: papillary meningioma) exist.
Imaging: CT, MRI to confirm the meningioma. Biopsy is only used as a method if we
cannot confirm that its a meningioma based on imaging, and to rule out glioblastoma or
other malignant types of cancer.
Treatment: Remove it surgically if the patient shows symptoms.
Slide:
The slide doesnt provide healthy tissue for easy
recognition. The most notable structures are the
psamomma bodies for easier orientation.
Frequently, the tumor cells form crescent shaped,
onion skin-like nests, which have the
psamomma bodies in their center. There are no
mitotic figures, necrosis or atypia present.

Slide 52: Schwannoma

Schwannoma is a benign encapsulated tumor of peripheral nerves
and nerve roots, soft tissues or internal organs originating from
Schwann cells. It is generally an extracranial lesion found usually in
the extremities, however if it is in the skill, then it is most likely
affecting the hearing.
It is usually solitary but also neurofibromatosis can occur in some
cases.
An schwannoma is a rounded and encapsulated lesion with sharp borders. The growing
pattern is typical with two types: Antoni type A and Antoni type B. Antoni type A is
easier to recognize since it has distinctive Verocay bodies which make a palisading
structure formation.
Imaging: Ultrasound, CT, MRI
Slide: The slide doesnt provide healthy tissue for easy recognition. Two types of
schwannoma can be distinguished: Antoni type A (organoid +Verocay Body) and Antoni
type B (patternless area) schwannomas.

Type A

Type B

Verocay bodies have fascicular architecture and form compact bundles by their spindle
cells. Antoni type B schwannomas have a network like architecture, where macrophages
with foamy cytoplasm can be seen in small groups.

Slide 53: Glioblastoma

Glioblastoma is one of the most aggressive malignant tumors of
the CNS. It generally affects the frontal lobe of the cerebral
hemispheres, but can be found anywhere on the brain or spinal cord.
In the brain the most common malignancy is usually metastasis
arriving from the lung or breast or lymphoma.

(Hortobgyi + Molnr love their WHO grading)

WHO grading - grade 1: Pilocytic astrocytoma
Grade 2 - Diffuse astrocytoma
Grade 3- Anaplastic astrocytoma
Grade 4 (highest grade) - Glioblastoma itself
Slide:
Normal brain parenchyma is present for the easer recognition of the slide.

General necrosis can be observed. Pseudopalisading architecture around it.

Key words for description: hypercellularity, pleomorphism, mitotic figures, necrosis

abnormal blood vessels - glomeruloid vascular proliferation.

The complex aggregates of focally anastomosing capillaries with narrow lumina, which
compose the glomeruloid vascular structure. Endothelial cells are hyperplastic, varied in
size and shape, overlap focally, and contain numerous cytoplasmic filaments.

Slide 54: Retinoblastoma

Retinoblastoma is the most common primary intraocular malignancy
in children. It affects children between the ages of 1-5 years.
40% are related with the germline mutation of RB1 gene. 60% is
sporadic, which is caused by the somatic RB1 gene mutation. Cats
eye appearance due to light reflection.
Origin: Immature cells of the retina

Slide: Nodular mass in the posterior retina. It is an undifferentiated tumor with huge area
of necrosis, mitotic figures and pleomorphism. Among undifferentiated areas the most
recognizable differentiated points of orientation are the Flexner-Wintersteiner rosettes
and Homer Wright rosettes.

Treatment methods include enucleation, chemotherapy and irradiation. It is irrelevant

which method we use, since all of these methods destroy the eye, but can save the
patients life.

Slide 55a: Alzheimers disease

Alzheimers is a chronic neurodegenerative disease that
accounts for 60-70% of cases of dementia. It is generally sporadic
but some cases are familiar. The disease presents with amyloid
deposits (extracellular) and tau protein aggregation
(intracellular), and general brain atrophy (simple cortical atrophy)
Hydrocephalus ex vacuo

Slide: The slide contains sections of the hippocampus, specifically the cornu ammonis,
which is part of the neocortex. The corresponding contour is seahorse shaped. At the left
end of the slide, the choroid plexus can be seen. Within the choroid plexus a calcified
center is apparent where a psamomma body is visible. This can also be found in papillary
thyroid body cancer.

In most of the cases, the karyoplasm, nucleus and nucleolus can be seen in their
respective bodies, however some neurons are different because they are dark and the
nucleus is difficult to find. These are called red neurons.

Its color change is not due to Tau

accumulation, but due to degradation
of eosinophilic products (RNA, DNA,
etc.)

Red neuron

Amyloid containing plaques can be seen as extracellular eosinophilic spots

Amyloid containing plaque, not amyloidosis (!)

Slide 55b: Alzheimers disease (Tau Immune Stain)

Slide: With immunohistochemistry, anything that is stained in brown
is positive. This recognizes abnormal Tau proteins, especially in the
hippocampal area, since many neurons bind this very strongly.
The neurons on this slide become flame-like due to the stained
neurofibrinoid tangles.

Only Molnr or Hortobgyi give a shit

which part of the brain it is. If you just
say brain to anyone else then they say:
Yaaay high five go home.

Slide 56: Parkinsons disease +

Slide 56b: Parkinsons Disease (Alpha-synuclein immune staining)

Parkinsons disease is a degenerative disorder of the CNS mainly affecting the motor
system. The motor symptoms result from the death of the dopamine generating cells in
the substantia nigra.
Slide: A significant mechanism of disease progression consists of an abnormal
accumulation of the protein alpha-synuclein bound to ubiquitin in the damaged cells.
This insoluble protein accumulates inside neurons forming inclusions called Lewy bodies

Lower amount of neurons with Lewy body

alpha-synuclein IC accumulation

Symptoms: Tremor, muscle rigidity, bradykinasia

Treatment: DOPA agonist drugs, dose has to be increased with time, intracranial
stimulation

Slide 57: Lipoma

A lipoma is one of the most common benign soft tissue tumors,
hence the end oma. Its malignant version is the liposarcoma. It is
usually under the skin directly, but deeper or retroperitoneal versions
also exist. Can be single or multiple and in women it can have a
genetic background.

Macroscopically is it painless, mobile and slow growing. The symptoms are not really
present, except for the palpable mass. A lipoma usually has a connecting tissue around
it, and truly thats the only characteristic feature, which helps in differentiating lipoma
from normal fat tissue.
Slide: Normal fat tissue present, but in H-E staining most of it is removed due to the
presence of alcohol.
The shape of excision with a sharp border is visible on the slide and thats how we can
tell its a lipoma since a CT capsule surrounds the lesion.
No lipoblasts, no necrosis, no mitotic figures, no infiltration.
Immunohistochemistry cant help to differentiate between lipoma and liposarcoma, since
the phenotype is the same; only the architecture of the lipoblast can help.
Subtypes: The subtypes such as fibrolypoma, angiolypoma, myxolipoma mean that
next to the fat tissue other components of the tumor are present. They dont change the
behavior of the tumor. Most commonly only fat persists.

Diagnosis: Physical examination is enough, if in a deep location (e.g wall of stomach)

ultrasound is used. A biopsy is usually not performed, only to differentiate from another
conditions, like metastasis or other soft tissue tumors. It is surgically removed if deemed
necessary. No malignant potential, rare for this form of lesion to turn into a liposarcoma.

Slide 58: Embryonal Rhabdomyosarcoma

The name helps: rhabdo skeletal muscle, sarcoma malignant,
therefore it is a malignant type soft tissue lesion. The embryonal is
a subtype of it.
The embryonal doesnt define age, only the level of differentiation,
but generally occurs before the age of 20 (1-5 years). Usually
present in the head and neck region.
3 subtypes exist: alveolar, embryonal, pleomorphic

The tumor cells are of the embryonal type, since the cells are not longitudinal, but more
circular with dense cytoplasm and big nuclei. We can see tadpole cells, or strep cells,
which have a longitudinal shape, where striations might be observed. They are more
differentiated than embryonal cells.
Significance of immunohistochemistry - lots of soft tissue tumors look the same in the
H-E slide, and to check the origin of them we perform IHC (e.g in lymphoma for
subtypes) for soft tissue tumors.
Diagnosis: Imaging + biopsy is obligatory. The age of the patient, and the location of the
mass helps, but doesnt confirm what it is.
The lesion is removed if possible; otherwise chemotherapy and irradiation is applied,
since up to 70% can be saved with the combination of chemotherapy and irradiation. If
the patient is older the prognosis is worse.

Slide: 70% of the slide is blurry (yay!). To identify, 3 things are important:
1. Region is covered by normal squamous epithelium, and it can help in narrowing
down the possibilities

Most helpful features of the slide for

identification are the tumor cells, the
rhabdomyoblast cells (2.). It is evident that
they are embryonal, since a normal skeletal
muscle cells are not rounded. They possess a
huge cytoplasm and a huge nucleus and
nucleolus, and they could even be
multinucleated.
The nucleus of strep cells/tadpole cells (3.)
(longitudinal cells) is spindle shaped and the
cytoplasm is stretchy. These cells might possess
striations.

To avoid confusion - All previously listed cell types are tumor

cells. The main cell type is the rhabdomyoblast, which can be the
most helpful for identification. Tadpole/strep cells are also
rhabdomyoblasts, they just have variable shape for which we give a
unique name.

Slide 59: Basal Cell Cancer - Basalioma

Basalioma is the most common malignant epithelial tumor. The

type of epithelial origin grows slowly, but doesnt bring metastasis
usually. Screening has to be repeated frequently in a patient who
had one previously removed, since the lesion likes to reoccur, due
to the several types of mutations, which occur in the background.

Macroscopically: Pearl-shaped lesion, similar to many others, but the dilated blood
vessels are typical for basalioma.
3 important factors for easier recognition:
1. The cells are basal like cells.
2. On the periphery of the tumor nests, cells show a palisading architecture
(located next to one another)
3. In the slide you can see a separation artifact between the tumor cell nest and the
connecting tissue surrounding it.
Immunohistochemistry Not usually needed, but EMA and BERep4+ can be used to
differentiate basalioma from squamous cell cancer.
Diagnosis: Easy to recognize, but biopsy is not really used since the lesion is not big
enough for a biopsy, we rather just remove it surgically. It only gives metastasis in very
rare cases.

Slide:
Check the healthy tissue in the slide, such as the
epithelium, sebaceous glands and hair follicles. The
squamous epithelium is intact, healthy, and the
sebaceous glands and the hair follicle are normal.

In the dermis, big and dark tumor cell nests are

visible.

We call it basalioma, since as the basal layer proliferates towards the surface, the nucleus
is supposed to shrink and the cytoplasm should become bigger and the cell should change
to a lighter shade, however here it is not characteristic. Tumor cells have a large nucleus
and small amount of cytoplasm. Basal like cells are a clue, the second is the periphery
itself, and the palisading structure being one by the other, which is a typical sign for BSC.
Lastly there is variable shape and size, irregular CM, chromatic mitotic figures; no
melanin production and the squamous epithelium is intact.

Zoomed in tumor nest

with palisading basal cellular
architecture

Slide 60: Compound Nevus

The cause is unknown, no dysplasia, or maturation is present.
The compound nevus is a small lesion, of which the border is
sharp and the color is uniform. It is usually brown but not
always.
Dermoepidermal type is the one in our slide. None of the types
of compound nevus have malignant potential.

Diagnosis/Control: Check whether the lesion is growing or changing. A dermatoscope

can prove useful in diagnosis
Biopsy: No, it would only unnecessarily damage the tissue, which could trigger a
malignant transformation. Instead of a biopsy removal
Slide:
Differences between the basalioma slide: Here there are no basal tumor cell nests in the
dermis, all visible points of interest are healthy features of the skin (eg: hair follicles)
The lesion is on the surface. No mitotic figures, no necrosis, NO ATYPIA.

Characteristic tissue for

orientation

Slide 61: Superficial spreading malignant melanoma (of the skin)

Melanoma is the malignant tumor of the melanocytes of the

skin and the eye. It is usually sporadic, but it could be
hereditary.
This form of malignant tumor is very dangerous; it kills almost
everyone.

Macroscopically: It has irregular color and irregular border. Melanoma in the eye is
inside on the choroid layer of the eye, and macroscopically looks discolored.
Melanocytic Melanoma + Amelanocytic melanoma exist.
Histologically: No maturation is present, no ABCs, only A type cells, mitotic figures are
present with typical appearance. The nuclei are always big and inside the nucleus a
nucleolus (magenta color) can be observed - Macronucleolus.
This is a very typical histological sign of melanoma

Magenta colored
macronucleolus.

ATYPIA, active nucleoli and

mitotic figures

Infiltrating tumor cell nests

The horizontal phase of growing for

melanoma follows the epithelial surface so it
takes more time to reach blood vessels, which
decreases the chance of metastasis.
Control: Always observe the change of the
lesion; follow- up is obligatory.
Diagnosis: With dermatoscope, but cut out the
lesion if possible, and check for sentinel
lymph node metastasis.
Target therapy exists for melanoma which is
similar to normal chemo, but more targeted,
but either way the tumor most likely will
come back years later in a more aggressive
fashion

Staging: Breslow - surface to deep and Clarke.

For differentiation:
Slide: It could look like the compound nevus, what could help in differentiation is that
deep infiltration is an important malignancy sign in melanoma therefore check the dermis
and the epidermis.
The size, shape, melanin production is not different, same large cells with melanin
production, however there are mitotic figures and atypia in melanoma, and thats an
important sign for differentiation.
Do not forget the huge macronucleolus, which is NOT PRESENT in the nevus.

You are my favorite

group not true, the other
one is my favorite group,
but I tell them the same
thing.
Just so you can all see that

I hate you all.

Slide 62: Malignant melanoma in the eye

Symptoms: Blurred vision, however it is usually a late symptom in metastasis,

ophthalmoscopy is the best way to check.
The color can help in recognition since it is generally black, but amelanocytic types
could also exist.
Eye metastasis is not common, however the GI or the lung can give metastasis to the eye.
A possible way of spreading from the eye is through the optic nerve, where the melanoma
can leave the eye. The distance between the tumor and the optic nerve has to be
measured. If the optic nerve is tumor free, it gives the patient a better prognosis, and the
method of enucleation could have worked.
Treatment: Enucleation, if its not possible, then chemotherapy, target therapy or
irradiation.

Slide 63: Diabetic nephropathy

The cause of diabetic nephropathy is longstanding

diabetes mellitus. Diabetes mellitus has type 1 and 2
forms where in type 1 no insulin secretion exists and in
type 2 where insulin resistance occurs.

Symptoms: tiredness, excessive thirst, vaginal infection, and sexual problems

Diagnosis: Checking the insulin function or glucose tolerability by oral glucose tolerance
test.
The cause of diabetic nephropathy is not well understood, but it is thought that high blood
sugar, and cytokines may me involved in the development. It attacks almost all organs
through blood vessels causing: nephropathy,
retinopathy, gangrene of the leg and liver
problems.
Nephrosclerosis: surface irregular due to
excessive granulations.
Histologically: Vascular changes showing a
thickening and hyaline degeneration of the
vessel wall, which can form Kimmelstiel
Wilson nodules (homogenous pinkish
nodule inside the glomeruli). It is typical for
diagnosing diabetes after kidney biopsy.

Treatment: Type 1: insulin; type 2: depending on how severe it is, if its in the beginning
a lifestyle change can help, if its not enough then oral diabetics, and then later on we
give insulin. Diabetes is manageable but incurable.
The cause of death is because of the consequences of diabetes.
Slide: Recognize renal features. Check the medulla in the center and peripelvic fat tissue.
Lesions are present in the cortex. Blood vessels outside the glomeruli have to be
observed. Their diameter is smaller, and the wall thickness is much thicker than it should
be.
No crescent formation, no inflammation, no tumor

Slide 64: Rapidly progressive (crescentic) glomerulonephritis (RPGN)

RPGN is an autoimmune disease, which is the deadliest type

of glomerulonephritis. Based on urine samples we can tell
whether it is a nephritic or nephrotic syndrome.

Symptoms are not specific: edema, fever, weight gain, and urine changes (proteinuria)

Diffusely on the surface or cortex we see reddish dots everywhere.

3 autoimune mechanisms can be listed behind RPGN:
- Immune complex type
- Anti GBM (antibody in blood,)
- pauci-immune (unknown cause) with intraglomerular crescent formation.
Diagnosis: Check urine and blood - blood for the antibodies or immune complexes, and
BIOPSY:
It is irrelevant which type of glomerulonephritis it is, we ALWAYS BIOPSY.

Treatment: Dialysis + transplant. The problem is that the kidneys shuts down temporarily
Slide: PAS (Periodic acid-Schiff) slide, which stains polysaccharides such as glycogen
and mucosubstances such as glycoproteins, glycolipids and mucins in tissues. Its distinct
color can help with identification.

Crescent shaped cell proliferation, destroying the glomeruli

Lesion exists in the cortex, no blood vessel damage or inflammation in the interstitium.

Slide 65. Acute pyelonephritis

Pyelonephritis is an inflammation/ infection of the

kidney which can be classified as a UTI which
ascends as an inflammation from urethra, bladder,
ureter which eventually reaches the kidney.
Pyelonephritis doesnt mean the infection of the
pelvis alone, as it spreads to the parenchyma also.

Obstruction, pregnancy and diabetes all predispose to it.

Pyelonephritis can be acute or chronic.
In acute PN the size can be larger with abscesses and the cut surface can be yellow and
could contain pus. Healing leads to scarring which then causes the surface to become
irregular.
Histologically: How to differentiate it from RPGN: the GLOMERULI are INTACT
and no Kimmelstein-Wilson nodules, acute inflammation, neutrophils and macrophages
can be seen. The interstitial acute inflammation with intact glomeruli is the most
important feature.

Symptoms: flank pain, fever, urinary problems, the patient doesnt want to pee, because it
hurts.
Imaging: not needed, since the urine test is enough for diagnosis
No biopsy
Treatment: Treat the cause, such as a blockage, sepsis and give oral antibiotics.
Slide: No tumor in the kidney. No glomerular problems, No Kimmelstiel nodules

Huge interstitial inflammatory reaction, and when checked we can see neutrophils and
some macrophages. Dilated hyperemic blood vessels due to inflammation.

Intact glomeruli

Dilated blood vessels

Neutrophil casts

Slide 66. Clear cell kidney carcinoma

Kidney cancer - One of the main groups of kidney cancer is
renal cell carcinoma, coming from kidney parenchyma cells.
It has 4 main subtypes:
- Clear cell
- Papillary
- Chromophobe
- Collecting duct carcinoma.
The most common is sporadic clear cell kidney carcinoma
with roughly 80%

Macroscopically: Primary kidney cancers, except for transitional cell, have a sharp
border. The cut surface of clear cell is yellow due to fat content, where also necrosis and
hemorrhage is common.
As the carcinoma is growing it grows into the renal vein and it can grow into the IVC,
which can cause edema. Unfortunately at this point it is usually too late because the
patient will likely die within a week.
It is called clear cell carcinoma, because during the making of the slide the alcohol
removes the lipid from the cut making the cells look clear
To avoid lipid removal, Oil Red O staining is used and then the fat is preserved.
Grading: The Fuhrmann nuclear grading system.
Based on how the nuclei look like this slide could be Fuhrmann grade II or III
Diagnosis: Blood in urine is present + flank pain
Ultrasound used and if cancer is suggested an MRI performed, biopsy if needed.
It has good prognosis but requires thorough follow up
Slide:
Find the healthy
parenchyma to
recognize that
we are in the
kidney, since
almost the
whole slide is
the tumor itself

The tumor itself can have hemorrhage, necrosis and fibrotic areas in the center.

Cell borders are very sharp and show atypia and large cell nuclei with empty cells.
The way to tell that these are not fat cells is that then the nucleus would be much smaller
and wouldnt be located in the center of the cell.
They show variable size and shape, some being almost spindle shaped.

Blood vessels must be checked. If tumor cells are located inside the lumen, the patient
will have metastasis.

Slide 67. Transitional cell carcinoma of the urinary bladder

The most common bladder cancer is transitional cell carcinoma

and the other forms are much more rare. Old men are the ones
usually affected.
Risk factors: being a man, age, but the most COMMON
predisposing factor is smoking.

Macroscopically: The lesion looks papillary, similar to the architecture of a polyp.

There are 2 main groups:
- Flat lesion (rare)
- Papillary lesion (more common)
Symptoms: Flank pain, obstruction if the lesion is big enough. The most common
symptom is blood in the urine. Since it is not a cancer specific symptom a cystoscopy has
to be performed.
In most cases these tumors are small and we can catch them while they are still small
(around 2cm)
It has to be checked how deep the lesion goes, and if it doesnt reach muscle, then it is
enough to just remove the lesion, otherwise we have to remove the whole bladder.
If the bladder is removed the urine goes into the small intestine which is not hygienic,
since it is not sterile.
Avoid cystectomy if possible.

Slide:
Help to recognize bladder:
Fat + peritoneum is visible
and also the epithelial
surface which is
transitional epithelium

Lesion itself

Mitotic figures +
variable shape and
size, definite atypia.

Superficially - tumor nodule

Deeper - also a tumor nodule can be found therefore the bladder muscle was infiltrated,
and the whole bladder was removed.

Slide 68. Prostatic adenocarcinoma

Even if some students question it during the exams,
prostate cancer affects men. If you are a man and you
want to have cancer then have prostate cancer.
For girls, go have thyroid cancer.
(Best prognosis)
The tumor usually affects the periphery of the prostate.
If the prostate gives metastasis then it gives it to the
bone.
A 5 level grading system exists for the prostate, the
1-5 Gleason grading system.
From the grading we calculate a scoring system. The
differentiation level of all tumor cells is usually the
same.

Above the age of 70 or 80, studies suggest

all men have prostate cancer.
Tumor markers are prostate specific, but
not tumor specific.
After the tumor is removed regular follow
up (rectal digital examination) is
recommended.
PSA levels drop to 0 after removal, so if
the PSA elevates after the surgery then
something is wrong - PSA is coming
from something else.
Biopsy: AT LEAST 6 in the SAME
TIME due to the size of the prostate and
the fact that a sample is less than 1mm.
To tell whether it is benign or malignant the cell layers have to be checked.
A healthy gland has 2 cell layers (myoepithelial + epithelial), on the other hand a
malignant prostate gland has no myoepithelial layer, only an epithelial.
HMWCK (high molecular weight cytokeratin) stains the myoepithelial layer only.
If no positivity exists, then the glands dont have a myoepithelial layer, which makes it
malignant.

Treatment: Do nothing if it is low grade, however in high-grade use chemotherapy: TAB

(total androgen block), or remove the prostate.
Slide: Periprostatic fat tissue with a capsule, strictly speaking light is good, the dark
isnt

Periprostatic fat tissue

The corpora amylacea can help in identifying that it is a prostate.

Slide 69. Hyaline membrane disease (IRDS) - Infant respiratory distress

syndrome
The adult version - ARDS looks the same as IRDS
histologically, only the pathomechanism is different. In
adulthood the trigger could be aggressive pneumonia.
Red and firm lung everywhere, it is not fibrosis since it
would make it white, and not red.
The other name is hyaline membrane disease because
in the inner surface of the alveolar structure a small
membrane is visible, the hyaline membrane, which
comes from damaged inflammatory cells. It interferes
with gas exchange.
Diagnosis: based not enough lung function, premature birth
Phospholipid levels correlate with lung function.
Treatment: Delay the labor, usually by hours or days. Apply high dose steroid to the
mother, which then goes to the fetus, which then matures the lung, and increases
surfactant production. After birth only surfactant and oxygen can be given.
Slide: Hilar structures can help in recognition

Bronchi + cartilage +
ciliary epithelium
And lymph nodes
WITHOUT
anthracosis

No normal alveolar structure is present since they are all collapsed.

In the inner surface the

red hyaline membrane
is visible

Slide 70. Bronchial asthma

Bronchial asthma has atopic or extrinsic asthma types.

Atopic is almost exclusively young patients.
This form is an identified allergic reaction, and there is a
chance to outgrow it since with aging the immune system
also matures.
In extrinsic asthma we cannot specifically identify a
pollen or causative agent for it, and the skin test is
negative. This subtype will not go away with age.
The bronchi tree is the usual location of
the allergic reaction.
All the layers of the bronchi are reacting to
hypersensitivity, the muscle is
constricting, and the epithelium is
thickening and secreting mucus, which
causes a narrowing of the airways, which
is called an asthma attack.
Goblet cells are responsible for secreting
the mucus during the attack.

Way too many Goblet cells and the basement membrane is

much thicker than normal

Diagnosis by anamnesis: Allergy test if we can identify a causative agent which triggers
the asthma.
Treatment: An inhaler is used during the attack (antihistamine). Oral drugs,
immunosuppressing drugs, or corticosteroids
Slide: Normal alveolar structure for easier recognition

Normal alveoli +
anthracosis and
lymph node

Mucus plug within

bronchi(contains:
inflammatory cells
(eosinophils mostly))

Slide 71. Boecks Sarcoidosis

Sarcoidosis itself is a multisystemic disease, which can

affect any organ, but it is usually found in the lung or
affects the lymph nodes around the lung. The reasons are
unknown.
Boecks Sarcoidosis is the only lung disease, which is
more common in non-smokers than smokers.

Histology: It is a granulomatous disease, several granulomas are visible in the lung. It is

very similar to a tuberculosis lung, but in granulomatous diseases no necrosis is present,
also there is no specific location like in TB.
The beginning stage has no real symptoms present.
Prognosis is good with proper drugs (around 70% can be healed)
Stages:
0 - no lesion
1 - small lesion
4- lung destroyed by fibrosis
Diagnosis: Biopsy is unique since it is not usually taken from the lung, but the
surrounding lymph node, so the whole lymph node is removed.
Important differential diagnosis:
Whether the patient has sarcoidosis or tuberculosis, it has to be 100% determined since
the treatment of sarcoidosis is steroids!
If we give steroids to a patient with tuberculosis then it will turn into miliary
tuberculosis and it will kill the patient.
Ziehl Neelsen staining can be used to rule out TB
Slide: Epitheloid cells and giant cells build up the granuloma itself (one cytoplasm and
several nuclei)
Langhans type giant cells
are important to recognize
No necrosis!

Fibrosis in the center + Lymphocytic infiltration under it

Slide 72. Bronchial squamous carcinoma

Lung cancer is the most common, with men and now

also with women.
Risk factors are smoking (most common), air pollution,
Radon exposure, family history (lots of mutations exist in
the background)

2 main types of lung cancers:

non small cell and small cell
Non small cell has 4 types -
- adenocarcinoma
- squamous cell carcinoma
- large cell carcinoma
- carcinoid tumor
The treatment is different between the two thats why it has to be separated between
small and non-small cell lung cancer.
Ciliary epithelia damage - metaplasia - dysplasia - in situ cancer
It is centrally located since it comes from the bronchi.
Macroscopically: The location could help, since squamous and small cell are in the
center, all of them are firm and white and no sharp borders are in the lung.
Grade 1 or grade 2 they still can produce keratin, therefore in the center keratin pearls can
still be seen.
In grade 3, this is no longer visible.
Diagnosis: X ray for screening, CT MRI, bronchoscopy (tumor can be seen in the
bronchi)
Treatment: non-small cell - surgery if possible, afterwards chemotherapy and
irradiation. If its small cell then chemo has to be started as soon as possible. By the
diagnosis small cell is very likely to have already metastasized.

Center of lymph node, encircled sharp border lesion, squamous cells with centralized
keratin production

Signs of metastasis in the center

Normal epithelium would never have keratin

pearls!

Slide 73. Intrabronchial carcinoid tumor +

Slide 74. Small cell cancer

73 and 74 are called neuroendocrine tumors.

In the lung the cell origin is the Kulchitsky cell which lives in the wall of the central
bronchi. The old classification is typical carcinoid and atypical carcinoid and small cell
carcinoma.
Atypical - more aggressive
Small cell - the most aggressive
New classification: Grade 1, 2 ,3 for neuroendocrine tumors.
The cells of the lesion look almost exactly the same. There is a lack of necrotic area.
Differences/Comparison: Neuroendocrine cells (small blue cells) the nuclei are big with
a special architecture, and the cytoplasm isnt too big.
The number of mitotic figures is different with typical carcinoid it is less than 2, with
atypical is between 2-10, and with small cell is over 10.
Necrosis is only visible in atypical and small cell carcinoma. This helps with telling
which type of neuroendocrine tumor it is.
Typical carcinoid is well demarcated with intact normal ciliary epithelium.

The small cell cancer infiltrates and destroys everything.

Salt and pepper chromatin shows a neuroendocrine cell in general
Histologically:
In carcinoid the cells are uniform, forming nests separated with fine CT fibers. No
necrosis and no mitotic figures.
Treatment of carcinoid is surgery, for small cell it is chemotherapy.
Carcinoid tumor doesnt give metastasis - only around 1%.
Slide:
Carcinoid: check surface, nests of cells, salt and pepper chromatin of neuroendocrine
cells, nucleus is big and dark, and monomorphic, no variable shape or size.
Count the mitotic figures - 40x magnification
Bronchi - normal ciliary epithelium

Kulchinsky cell nests with salt and pepper appearance

Small cell:

Normal parenchyma on peripheral area

No sharp borders and no seeds of tumor cell nests can be seen.

Dark areas visible and if counting for mitotic figures, hundreds of them can be seen with
prominent necrotic areas.

Slide 75. A and B Barretts esophagus

(2 slides) 1 HE 1 PAS
Barrett metaplasia
Reason - Gastroesophageal reflux disease, causing the acid from the stomach to go back
into the esophagus which leads to a metaplastic change.
Risks: Hernia, obesity, h. pylori, and smoking can lead to acid reflux. It either damages
the function of the sphincter or increases acidity within the stomach.
In the squamous epithelium the damage occurs into columnar epithelium.
10% of patients with reflux have this form of metaplasia.
Squamous epithelium in the slide is grayish white normally of the mucosa, but if the
acid leads it to metaplasia, it turns reddish, pinkish. More and more glands appear due to
columnar epithelium.
The lower third of the esophagus is normally affected, and thats where the color
change can be seen in the slide due to the cell type change.
Goblet cells produce acidic mucin in Barretts metaplasia, however if neutral then it is
another form of intestinal metaplasia.
In hematoxylin, we cannot tell the pH of the mucin, thats why we use PAS-A/B staining.
A/b stains the acidic mucin BLUE. This special staining is used if we think its this
condition.
Barretts esophagus increases the chance for adenocarcinoma formation.
Symptoms: Heartburn - burning pain in the chest, which mimics a heart attack, trouble
swallowing and weight loss
Diagnosis: Symptoms are usually enough, endoscopy into the esophagus + biopsy.
Over 30% of primary esophageal cancers are adenocarcinoma.

Treatment: Classic metaplasia without problems - drugs against acidity or surgery and
since Barretts is a premalignant condition, follow up is required.
Slide: 2 slides - Only biopsy slides this semester.
Next to squamous epithelium, glands are present; normally their number should be very
low. Here their number is much higher.

If we see blue stained mucus in the goblet cells, then we can conclude that it is Barretts
metaplasia
PAS

Slide 76. Ulcus pepticum ventriculi - Chronic peptic ulcer in the

stomach

Chronic peptic ulcer of the stomach is most commonly

due to: H. Pylori infection, or NSAIDs (such as
Aspirin), smoking, alcohol, Zollinger Ellison
syndrome, ischemia, and other conditions which
destroy the mucosal surface.

H. Pylori loves to reside in the antrum and the corpus of the stomach and as it goes into
the mucosa, it also neutralizes the stomach acid thereby changing the stomachs normal
environment. It releases cytokines and enzymes, which trigger an inflammatory
reaction and then ulceration.
Acute ulceration - usually large, red and bloody.
Chronic ulcers are usually white due to the scar tissue formation.
Ulcers macroscopically can mimic cancer
An ulcers border is sharp and it makes the wall thinner.
In cancer the border is not as sharp and since its a cell proliferation it makes the wall
THICKER and not thinner.

To localize the ulcer the pain has to be observed. If there is pain before eating then it is in
the stomach, or if its after eating, then its in the duodenum.
Treatment: Surgery - partial resection, nowadays drugs: antiacidic drugs and antibiotics
against H Pylori.
Adenocarcinoma or MALT lymphoma can be a risk, since H Pylori triggers the
immune system, which causes chronic inflammation, which can lead to these conditions.
Slide:
Stomach epithelium, chief
cells + parietal cells
Normal epithelium in upper
and lower level, in-between
them no epithelium exists.

Since there is no blood it is a chronic ulcer. The inflammatory response contains some
lymphocytes and eosinophilic cells.

Slide 77. Crohns disease + Slide 78. Ulcerative colitis

Learning them together can help to differentiate the two slides.
They are both IBDs (inflammatory bowel diseases).
Ulcerative colitis only affects the colon, but Crohns disease is a systemic disease, which
affects the intestine segmentally (one healthy and one damaged part, one by the other)
Ulcerative colitis only affects the large intestine starting at the anus, and continuously
grows upwards towards the large intestine.
Both lesions lead to multiple ulcerations, but in Crohns disease the ulcers are always
deep which reach the serosal surface. In UC it only affects the mucosa and the
submucosal surface.
Symptoms: Non specific - bloody stool, pain, diarrhea
Histologically: Always biopsy should be used to differentiate. Common histologic
features - ulcers
Problems with the biopsy - only one layer is representative which is the mucosal
surface. Due to this fact, the depth of the ulcer cannot be determined.
Cryptitis - the gland is built up by columnar epithelial cells.
Granuloma formation is visible in Crohns disease, but UC never has it.
Diagnosis: Anamnesis - family history, Biopsy
Treatment: Steroids

How to differentiate between the two slides: Crohn is from the small intestine, UC is
from the large. Surface of the small intestine has finger like protrusions, then we can say
its Crohn.
Ulcerative Colitis:

Crohns disease:

Granuloma formation is visible with

deep ulceration

Based on Hematoxylin it is hard to find the granulomas, so immune staining is used.

Cryptitis neutrophil between epithelial cells and crypt abscesses. In the lumen we see
lots of neutrophil cells.

Slide 79. High grade adenoma in the colon

Adenoma - type of polyp, most commonly intestinal and

most commonly occuring in the large intestine.
Polyp types:
- Inflammatory
- Hyperplastic
- Hamartomatous
- Adenomatous
The most common and most dangerous is the
Adenomatous polyp.

Hyperplastic is common, but it doesnt have malignant potential.

As an adenoma is growing it gathers more and more mutations in its cells, first getting
low and then high-grade dysplasia (in situ cancer) then it can turn to adenocarcinoma.
Tubular adenoma, villous adenoma, and tubule-villous adenoma exist histologically.
Grading: (dysplasia)
Low grade: gland or epithelial cells are present, but the nuclei are bigger and higher and
the amount of mucus production is less than normal
High grade: cells dont produce mucus, and the nuclei are very variable, the chromatin
shows clearing, and nucleolus is visible in the nucleus.
It is possible to see one than more polyp in a patient. If its not familiar then more can be
2-10, if its more like hundreds or thousands, then it is most likely genetic.
Imaging/Treatment: Colonoscopy (treatment too) polyps are small and during endoscopy
we can remove them.
Slide: Large intestine epithelium helps
Light glandular structure is healthy, if its dark then its damaged.
Normal colon gland has normal cytoplasm with mucus production and the nuclei rest on
the basement membrane.
If dysplastic - the darker areas are damaged and the lighter are healthy mucosa:

Healthy vs Damaged epithelium

Light vs dark applies
Polyp with high grade dysplasia
Hyperchromatic nuclei
Chromatin is lighter than it should be and in the center a big nucleolus is present - high
grade dysplasia

Biopsy issues - we cant always tell how grade the dysplasia is since it usually doesnt
involve all layers.
Basal layer of the glands has to be checked for infiltration.
In this slide there
Tubulovillous adenoma with high grade dysplasia.
Villous and tubular structure will be present on the exam slide.

Slide 80. Malignant transformation of adenoma +

Slide 81. Mucinous adenocarcinoma

Risks: Smoking + alcohol + obesity + low fiber intake
IBDs and polypous syndromes increase the chance of malignancy
Key feature: p53 mutation in the polyp is an invasive cancer, which can be checked in
the biopsy
Napkin ring structure - growing in the wall and narrowing the lumen as its growing.

Mucinous type: Mucus producing so on the cross section a light jelly-like structure is
present in the tumor. Inside and outside the cells mucus (signet ring cell- mucus inside
the cell)
Increased mucus production is at least Grade 3.
Symptoms: 2 important symptoms: fresh blood in the stool and diarrhea/constipation
because when the tumor grows its narrowing the lumen which increases the pressure,
and feces comes out in intervals, causing inconsistent defecation.
Must look for lymph node metastasis therefore a large segment of the colon has to be
removed. As a pathologist at least 15 lymph nodes have to be found for a report to be
valid.
Malignant transformation slide: Typical mushroom shape with stalk

Decreased mucus production in deeper layers, at least until the submucosa or the muscle
layer.

Between muscle layers glands can be seen which means its classified as a polypoadenocarcinoma since its a sign of invasiveness!

Infiltration

Mucinous type slide:

The rule of dark vs light doesnt apply here since if the
gland is light here its the lesion itself
Signet ring cell, where nucleus is on the periphery and the
mucus is in the cytoplasm

Huge amount of mucus

Normal epithelium on the right,

and to the left is a huge amount
of mucus.
Most likely ttage 3 or 4 already
due to infiltration.

Slide 82. Liver cirrhosis with HCC (Hepatocellular Carcinoma)

The liver has a well-known healing capacity but if the

damage is intense a different method of healing may occur,
such as scarring, which is irreversible. This form of healing
leads to liver cirrhosis.

Risk: Alcohol, Drugs, Chemicals, Viruses (Hepatitis), Autoimmune diseases.

Macroscopically: its firmer and nodular, and the color can be variable depending on the
reason of the cirrhosis.
The functional unit is the lobe of the liver. Lobular structural is preserved - Autopsy
description, however
cirrhosis is considered a
pseudilobular structure,
which is not a real lobule
Symptoms: Jaundice,
Varices, Hemorrhoids,
change in mental state, the
cirrhosis alone can kill the
patient with time.
Hepatocellular carcinoma is a
risk (95% have liver cirrhosis
before)
Usually the border is sharp
(pushing border) and as it
grows it doesnt infiltrate, it
compresses the neighboring
parenchyma.
Encircled nodules are
visible in the liver - the first
guess would be metastasis

To differentiate: If the patient has cirrhosis, then it is most likely hepatocellular

carcinoma, or if the patient already has malignancy elsewhere.
Histologically: Several growing patterns exist (eg. Trabecular)
The presence of dysplasia is important for diagnosis.
Bile can more likely be seen in the tumor than in the normal liver since normally the liver
doesnt store bile, just produces it.
Biopsy is not taken from the cirrhosis, only if we dont know the cause of the cirrhosis.
If its hepatocellular carcinoma, biopsy is taken only if there is metastasis.
Treatment: Transplant (if the cause is not systemic), special treatment for carcinoma:
Chemoembolization (blocking the blood vessel which supplies the tumor)
Slide:
Nodules on the lower part - typical cirrhotic sign

Distinct differences can be observed between the morphology of the nuclei, nucleoli and
cell membranes.
Trabecular growing pattern - the lesion turned malignant
Lack of nodules - already a malignant lesion

Slide 83. Hashimotos thyroiditis

In Hashimotos thyroiditis the thyroid gland is
destroyed which leads to
HYPOTHYROIDISM.
TSA antibodies, which bind to follicular cells,
trigger the inflammation, which in a chronic
stage leads to the destruction of the thyroid.
Hashimoto itself increases the chance for
malignancy, for example - papillary cancer,
primary lymphoma (non Hodgkin)
There is a bilateral enlargement of the thyroid gland. Usually malignant lesions are
unilateral. It is painless, because almost all thyroid diseases are painless.
2 important signs of Hashimotos:
1. Huge lymphocytic infiltration - germinal centers
2. Hrthle cell - a normal follicular cell is changed by the persistent inflammation
into a Hrthle cell. It becomes enlarged and with a wider cytoplasm and the
appearance of fine granulation inside is visible.
Symptoms: Hypothyroidism, bilateral enlargement
Imaging/Diagnosis: US, Blood test (antibody test), Radioiodine uptake test - only organ
which uptakes this is the thyroid gland
Treatment: Steroids, Hormone substitution, Surgery (only in the end stage)
Slide:
Thyroid gland with huge amount of lymphocytes and well formed secondary follicles.
Find normal remaining thyroid tissue:

Relatively distinct thyroid

tissue with colloids + follicular
cells

No atypia, just enlarged cells which

rules out malignancy.

Slide 84. Graves disease

Graves disease also presents with bilateral

enlargement. On the other hand, Gravess
doesnt destroy tissue; it only forces the organ to
work much harder. The antibody found in Graves
mimics the normal TSH, which binds to the
thyroid forcing the hormone secretion causing
HYPERTHYROIDISM

Macroscopically: Exophthalmos the muscle and the fat around the patients eye has
edema which forces the eye out of the socket.
Histologically:
Nuclei lie on the basement membrane, and cytoplasm is normal sized
Graves - hypertrophy + hyperplasia - cuboidal and columnar cells
Inflammation is also visible, but no secondary follicles
Diagnosis: Anti TSH test in the blood
Treatment: Drugs to control symptoms (beta
blockers + calcium channel blockers),
Irradiation (radioactive iodine which only
goes to the thyroid and then destroys thyroid
cells making the organ smaller), or surgery.
Slide: Small dark areas diffused by lymphoid
cells but do not form germinal centers
Follicular changes - variable size and shape
and function of the cells is increased. Cells are
at least cuboidal but also columnar. Inner
surface of the follicles is not smooth (should
be rounded), but because of the cell
proliferation.
The amount of colloid is decreased since the
body cannot catch up with its production
since the cells work in a much higher rate
than normal

Cells eat away the colloid.

Features of Graves disease affecting the whole thyroid gland:
1. Patchy or small amount of inflammation
2. Cuboidal or columnar cells
3. Overproliferation - irregular inner layer
4. Lack of colloid in the cells

Slide 85. Papillary carcinoma of the thyroid

The cancers of the thyroid in general are not very

common, but among all the endocrine organs it is the
most common.
Papillary carcinoma is the most frequent.
It is unilateral usually, but multinodular forms also exist.

This nodule is painless and doesnt produce hormone. It is a cold nodule

It is considered a malignant lesion but the 10 year prognosis is very good - around 95 %,
even if the patient has metastasis by the time of diagnosis.
Most important mutation - BRAF mutation
Macroscopically: Sharp bordered white lesion within the thyroid.
Histologically:
10 variances of papillary cancer exist:
Some examples are the: Papillary type, Toll cell type, Sclerosing type etc
Papillary cancer has a papillary-growing pattern.

The nuclear changes always show specific features such as:

- nuclear overlapping (nuclei ON each other in cancer)
- nuclear grooves - border of the nucleus is very sharp but inside nothing is
visible, thats why it has a ground glass appearance
- Intranuclear pseudoinclusion - In the nucleus center a bubble is seen. The color
of it is the same as the color of the cytoplasm.
Recap:
Overlapping
Groove
Ground glass
Intranuclear pseudoinclusion
These 4 things are always in a papillary cancer, irrelevant which subtype it is.
To make sure: immunohistochemical staining is performed - CK19, Galectin-3
In case of malignancy, a fine needle aspiration has to be performed
Treatment: Surgery - remove the whole thyroid gland, since its possible that the
malignancy is multinodular and then irradiation to remove the left-over traces of the
thyroid gland.
Slide:

Classic variant of papillary cancer - papillary growing pattern (like a tree)

Tree-like:

Intranuclear pseudoinclusion:

Slide 86. Follicular carcinoma of the thyroid

It is the second most common form of

malignancy.
It is unilateral, cold nodule, higher chance of
metastasis than papillary, but the prognosis is
also good - 80% for next 10 years

Mimics follicular adenoma, therefore its hard to distinguish the malignant with the
benign kind.
Atypia here doesnt qualify as adenoma or carcinoma. The cellular architecture
doesnt matter if the capsule is damaged or if there is vascular invasion because then it is
definitely cancer.
2 things that matter between adenoma vs carcinoma:
1. If the capsule is intact - adenoma, if not - carcinoma
2. Vascular invasion - carcinoma
Papillary cancer has a subtype follicular
which can mimic follicular carcinoma,
however papillary cancer always has
cellular changes, but follicular carcinoma
doesnt or only rarely does.
Diagnosis: Radioiodine uptake test, fine
needle aspiration
Treatment: Surgery, Irradiation, with
follow up
Slide: The dark areas are the problem
once again
Lesion vs normal parenchyma -----

Slide 87. Pure seminoma

Pure seminoma is a member of the germ cell tumor family,

which is a tumor of the testis
It is the most common germ cell tumor.
Elevated HCG level is detected in the blood.
Grossly the tumor is white, firm and encircled.
The cut surface is homogenous, no necrosis or hemorrhage
exists
Histologically:
3 things to see:
Cells are monomorphic, no variable shape or size, only a few mitotic figures are visible.
Among septae we see lymphocytic infiltration.

Symptoms: Only leads to symptoms if the lesion starts invading other tissues.
Diagnosis: Physical examination, Blood test for HCG levels (tumor marker; not
seminoma specific), US, CT (only for metastasis)
Treatment: Surgical removal, usually only one is removed

Slide: We have 2 testicular slides this semester.

Darker areas are affected, but we can also see healthy parenchyma.
There is no special growing pattern in the lesion; it is quite monomorphic, with only
minor cellular variability.

Huge amount of lymphocytes are visible next to the tumor at the connective tissue.
The lack of aggressiveness - no necrosis or hemorrhage helps in diagnosing seminoma.

Slide 88. Embryonal carcinoma with choriocarcinoma

Germ cell tumors: 5 main types:

- Seminoma
- Teratoma
- Yolk Sack tumor
- Choriocarcinoma
- Embryonal carcinoma

The seminoma likes to grow alone, however the other types could have other tumor
types mixed in; therefore they are classified as mixed type germ cell tumors.
The embryonal is growing fast and there is high frequency of mitotic figures, necrosis
and hemorrhage is present.
CD30 immune staining helps in diagnosing embryonal carcinoma .
Histologically: Strange growing pattern with huge areas of necrosis

The HCG elevation is typical for choriocarcinoma, but finding high HCG in a man can
help in identifying testicular carcinoma.

Trophoblastic cells are found in the tumor, which happen to be multinucleated giant cells.
HCG Immune staining helps in finding this component.

Diagnosis: US, Physical exam, blood test (HCG levels)

Slide: The second testicular slide. The hemorrhage alone should be enough to
differentiate between seminoma and this mixed type germ cell tumor.
The growing pattern is variable and also the cellular appearance.
Chromatin distribution is irregular and almost all nuclei have visible nucleoli.

Slide 89. Tubal abortion

Tubal abortion (Ectopic pregnancy) means that

the egg didnt stop where it should have. The
most common place for an ectopic pregnancy is
the ovarian tube, but it can also end up in the
abdominal cavity as well. The problem occurs
when the body tries to supply this ectopic fetus
and damage occurs to the supplying vessels.

Location - almost always in the middle of the Fallopian tube, most likely caused by a
damage of the tube itself (surgery, infection, inflammation etc)
Macroscopically: Hemorrhage with Chorionic villi and blood vessels inside HAVE to be
identified, since there is a tumor mimicking a pregnant endometrium, which can be
confused with pregnancy since it produces HCG.
Symptoms: Irregular bleeding and intense pain as the fetus start to grow.
Treatment: Abortion - removal either by drugs or surgery.
Slide:
Have to recognize the Fallopian tube - luminal organ and a wall and an inner epithelial
surface.

Tree-like fimbriae
help with recognition

Also hemorrhage:

Chorionic villi (bubbles inside the lumen)

Slide 90. Fibroadenoma

Fibroadenoma is the most common benign tumor of the

breast affecting women around 30 years of age.
Characteristics: Solitary + rounded, moderately firm and
mobile. It is caused by increased estrogen levels.

There is a fibro- CT component and a glandular epithelial component, only the stromal
cells are neoplastic (not malignant!)
The border is very sharp.
Histologically: Intracanalicular and pericanalicular growing pattern compressing the
lumen.
Symptoms: Not common, until it reaches extreme sizes.

Diagnosis: Self-examination, which directs the patient to the doctor and Mammography
Treatment: Surgery since its not pre-malignant
Slide: Recognize the breast based on fat tissue with ducts and lobules.
Sharp border by the lesion.
The CT is loose CT, not firm, not dense, no atypia, no mitotic figures, no necrosis are
present.

Slide 91. Invasive ductal carcinoma with DCIS

+ Slide 92. Invasive lobular carcinoma

Breast cancer in general is very common among women. It competes with lung cancer to
be the most common.
Risk: Old age, obesity, mutations, high breast tissue density, lack of pregnancy in lifetime
Consistency is firm and NOT mobile
4 Quadrants of the breast exists artificially, which are important for surgical resection.
The most common location is the upper lateral quadrant for the malignant lesion.
The non-encircled white lesion within the breast without experience can be mixed with
simple aging or fibrosis of the breast.
Main forms: Ductal and Lobular cancer, ductal being 80-90% of all cancers
Ductal meaning, the functioning part of the breast is the origin of the cancer (ducts)
The malignant glands lack the myoepithelial layer but if the cancer happens to be
in situ, they still retain their myoepithelial layer.
P63 stains the myoepithelial layer, so it can also help in finding in situ cancer.
Subclassifications:
Subtypes of in situ cancer: comedo, cribriform, solid, micropapillary, papillary etc
This helps in the grading of the tumor

The growth forms cell chains (indian file

growing pattern) and it NEVER FORMS
GLANDS

To differentiate between ductal or lobular pattern an immunohistological staining

method is used called: E-CADHERIN
E-cadherin is + in ductal and lobular cancer, which helps in differentiation.
The Nottingham grading system is used in the breast
Symptoms: Self-examination, Mammography (X-ray technique to find a lesion), Biopsy
Treatment:
Surgery: In case of BRCA mutation detection - bilateral mastectomy is performed, but
nowadays total mastectomy is not recommended.
A sentinel lymph node (closest lymph node to the tumor) is removed and is checked for
malignancy, if it is clean then no other lymph nodes are removed, if it has cancer the
axillary lymph nodes are also removed.
New study: Around 30-60% of cases the sentinel lymph node is clean, but the lymph
node next to it has a tumor - skip metastasis occurred which increases chance for
false negative diagnosis

Slide: Fat helps in recognition that its a breast. Normal structures - some CT within the
fat. The cancer is the darker part, the in situ part grows with tumor cell nests (bubbles)
and it is always surrounded with the myoepithelial flat cells (the nests themselves)
Mostly comedo type, moderate cribriform type is present in the slide.
The invasive part of the tumor - gland like growing pattern with high frequency of
atypia (shape and size of nuclei is variable, nucleolus within nuclei)
In LOBULAR cancer severe atypia is NOT present.
Ductal Carcinoma:

Lobular Carcinoma:

Slide 93. Adenocarcinoma of the endometrium

The spectrum from benign to malignant starts with

hyperplasia and ends in carcinoma. It is irrelevant
whichever it is since it usually affects post-menopausal
patients.
The main reason of adenocarcinoma formation is the
high estrogen level of the patient.

Osteoporosis is very common and the treatment for it is estrogen, however high estrogen
treatments can increase the chance of formation of adenocarcinoma in the endometrium.
Hyperplasia - 4 stages:
Circular growth - simplex hyperplasia
Strange variable growth - complex hyperplasia
Check cells within glands, if healthy - typical hyperplasia
If they are irregular - atypical hyperplasia
Typical simplex, typical complex, atypical simplex, atypical complex (worst type)

Symptoms: Post menopausal bleeding - always a bad sign

Slide: Serosal surface - single cell layer and the myometrial layer helps
Small atrophic endometrial gland with small amount of stroma.
Invasiveness on the bottom, the border is not sharp as it eats the myometrium and thats
and thats a distinct feature of endometrial cancer.

Slide 94. Perineal endometriosis

Endometrium where it shouldnt be

There are two classifications:
endometriosis interna and externa
If it is internal it is still inside the uterus - adenomyosis
The external is the endometriosis

Symptoms: Pain, bowel symptoms, depression

It can be found anywhere in the body, but most commonly it is in the ovaries and the
Fallopian tube.
It is classified as a Chocolate cyst since it is filled with dead blood cells, shows such an
appearance.
Histologically:
4 criteria to see to identify:
1. Endometrial stroma,
2. Endometrial glands
3. Blood
4. Siderophages
Treatment: Drugs (contraceptives),
Surgery
Slide:
It is located under the skin; therefore
normal stratified keratinized squamous
epithelium is visible in the slide.
Features, which should be found:
- Pools of blood and siderophages
inside the blood and also in the
surrounding tissue
- Around the epithelium endometrial
stroma
- Cuboidal epithelium due to
increased pressure
- Lack of atypia

Slide 95. Papillary cystadenocarcinoma of the ovary

The ovary has several tumor groups, one of them

being epithelial tumors and one type of it is the
serous-papillary lesion, which can by cystadenoma (benign) or border-line (dont know if
benign or malignant), and malignant version: the
cystadenocarcinoma.

Adenoma - several cysts in the ovary, outer and inner surface of the cysts is smooth
everywhere.
Borderline - Inner surface has papillary polyp like lesions which are usually small
(couple mms), with no solid areas.
Carcinoma - Malignant version of the lesion, the tumor itself can overgrow the cysts. Its
outer and inner surface is filled with tumor tissue, which we called solid areas of the
tumor.
Symptoms: Usually it doesnt break the capsule of the ovary, when it infiltrates flank
pain can occur with general tumor symptoms.
A biopsy shouldnt be taken because rupturing the capsule can release the fluid of the
cyst which has free tumor cells which helps the tumor to spread.
Diagnosis + Treatment: Surgery, in late stage do chemotherapy.
Slide: Try to recognize the ovary itself:

Preserved stroma
with follicles

The tumor is growing in the papillary structures

To see if its malignant: papillary growing structure, the severe atypia, and mitotic
figures, however if no infiltration is found, the lesion is still considered border-line
(check the CT of the cyst)

Slide 96. Acute osteomyelitis

Acute osteomyelitis is an infection-based inflammation of

the bone. It is usually a primary lesion of the bone, caused
by trauma or peripheral tissue inflammation. It most
commonly occurs in the leg.

Symptoms: Symptoms of inflammation, localized pain

Diagnosis: X-ray to check for necrotic bone tissue (sequestrum seen on the X-ray), Blood
test to check for infection

Treatment: Use antibiotics by applying them directly into the bone. Drainage of pus can
be done before applying the antibiotics.
Slide: Recognize a the bone itself - the bone trabeculae are preserved, around the space
where the fat should be are huge cellular inflammatory cell populations which are signs
of inflammation - Acute inflammation

The slide is dark blue due to huge amounts of neutrophils

Slide 97. Chondroma

Benign tumor of bone or cartilage, usually affecting

the hands and feet in middle aged patients. It is
usually solitary but about in 30% it could have
multiple lesions, which likely has another illness in
the background such as Ollier disease or Maffucci
syndrome.

The patient has several chondromas, and therefore there is a higher chance for mutation,
which increases the chance for malignancy, so it can turn to chondrosarcoma.
If it is inside the bone is it called an enchondroma; if its on the surface of the bone it is
periosteal or juxtacortical chondroma.

Histologically: Almost like the lipoma in the sense that you see normal cartilage. It has a
sharp border and the chondrocytes are benign.
Symptoms: Not painful, only physical signs, only in larger size
Treatment: Surgery (removal) In multiple chondroma - amputation
Slide: Only slide with cartilage
Normal bone in the center, without inflammatory cells and benign sharp bordered
growing cartilage.

Slide 98. Osteosarcoma

Bone tumors - to diagnose them we need to
know:
- The age of the patient
- Location of the tumor (bone and part of
bone)
- X ray (!!)

Radiologically the Codmans

triangle can be used.
Between the two lines a triangle
shaped lesion can be seen. Its
almost enough to definitely say it
is osteosarcoma.
The location is usually around
the knee.

Osteoid production - the cells

try to produce bone how they
should, but since they are
damaged, they produce bone
with a different pinkish
structure which we call
osteoid.

Damaged osteoid meshwork:

Symptoms: Painful pathological structures.

Treatment: Amputation

REFERENCES: Some pictures were taken and labeled by Yair Eynath and taken from
the Histo 2nd Eyal powerpoint.