PATHOLOGY OF THE EYES AND EARS

Dr. Jared Billena

Nov 25, 2022
1:30-3:30 PM
4.1
OUTLINE DERMOID CYST OF THE UPPER EYELID

I. Non-Neoplastic Lesions of the Eye

a. Dermoid cyst of the upper eyelid
b. Limbal Dermoid
c. Chalazion
d. Pterygium
e. Eyelid Cyst
f. Nevus of Margin of Lower Eyelid
g. Sturge-Weber Syndrome
h. Xanthelasma
i. Mucocele
II. Neoplastic Lesions of the Eye
a. Recklinghausen’s Neurofibromatosis
b. Benign Mixed Tumor of Left Lacrimal
Gland Dermoid cyst of right upper eyelid.
c. Extensive Papilloma of Bulbar
Conjunctiva All dermoid cysts elsewhere will look the same
d. Papilloma of Conjunctiva
e. Meningioma of Orbit It can have mature components of ectoderm,
f. Carcinoma In Situ of Conjunctiva And mesoderm, and endoderm
Cornea
g. Leukoplakia (SCCA-In-Situ)
h. Squamous Cell Carcinoma of
Conjunctiva
i. Basal Cell Carcinoma of the Eyelid
j. Sebaceous Gland Carcinoma of the
Eyelid
k. Adenocarcinoma of Meibomian Gland
l. Melanoma of the Eyelid
m. Choroidal Melanoma
n. Retinoblastoma
o. Secondary Metastasis to the Globe
III. Lesions of the Ear
a. Inflammatory Lesions
b. Otosclerosis
c. Tumors
i. Ceruminous Adenoma
ii. Meningioma of The Ear Excised dermoid cyst
iii. Squamous Cell Carcinoma
iv. Adenoid Cystic Carcinoma If you excise it, there will be derivatives of the
v. Embryonal Rhabdomyosarcoma ectoderm, some instances mesoderm, but rarely you
vi. Yolk Sac Tumor can find endoderm.
Many instances you can find ectoderm, for example
the stratified squamous epithelium and the
sebaceous glands which are embedded in
I. NON-NEOPLASTIC LESIONS OF THE EYE fibrocollageous tissue which are mesodermal
derivatives.
When we say non-neoplastic, there are still
polyclonal cells that are yet to develop. They look exactly the same as the dermoid cyst of
the ovary and testes.
They can be inflammatory, developmental

Assessor: Gangoso and Dalida

Group 9: Barbasa, Cabalo, Fabila Page | 1
Notes:

LIMBAL DERMOID

Limbal dermoid in a child

This can occur in the limbus with the same
histopathologic findings and diagnosis as you will
see in the upper eyelid.
CHALAZION
Multiple foci of granulomatous inflammation with
micro abscesses and multinucleated giant cells in
chalazion
Remember that not all granulomatous is tuberculosis
especially if the giant cells are not Langhan’s type.
But in Filipinos, granulomatous lesions is
tuberculosis until proven otherwise.
Chalazion is not neoplastic, it is inflammatory.

Chalazion of right upper eyelid

Looks the same with the dermoid cyst in PE. If you
have mass on the upper eyelid, you have so many There will be splattering of acute and chronic
diagnoses to consider. inflammation in the background of necrosis. There
“Mass, right upper eyelid to consider the following: are scattered multinucleated giant cells present.
“amo ni dapat mag refer or send specimen sa
pathology department. When you list down your
differentials we will look for characteristic
histopathologic findings of the things you
enumerated. If you did not give your differentials, it
will take time for us to diagnose especially if the case
is difficult.

Assessor: Gangoso
Group 16: Barbasa, Cabalo, Fabila Page | 2
Notes:

Few layers of squamous cells that is keratinized

resting on an edematous and focally necrotic stroma
The presence of pools of fat in the center of many of
the granulomas is characteristic of chalazion EYELID CYST
They tend to involve the subcutaneous fat and will
cause subsequent necrosis of adjacent fatty lobule

PTERYGIUM

Simple cyst of the eyelid margin believed to be

secondary to obstruction of duct of Moll’s gland
(sudoriferous cyst)
Seen a lot in OPD. Pterygium tissues are not usually Lined by a layer of mucinous cells with basally
sent in the laboratory. located nuclei and apically oriented cytoplasm

NEVUS OF MARGIN OF LOWER EYELID

Pterygium that has grown over the pupillary axis and

has interfered with vision How do you differentiate nevus from melanoma?

Assessor: Gangoso
Group 16: Barbasa, Cabalo, Fabila Page | 3
Notes:

When there is neurotization. When you see that the Not really abnormal because as we grow old,
nevocytes from the superficial are ovoid and they cholesterol deposits in every part of the body. When
become elongated as they go deeper, it is an it deposits around the eye, it is called xanthelasma
indication that they undergone maturity

STURGE-WEBER SYNDROME

● The patient, a 42-year-old man, had had facial Xanthelasma of eyelid

hemangioma all his life and was blind in the Clusters of foamy macrophages are seen in the
ipsilateral eye because of retinal degeneration, dermis in association with few lymphocytes
glaucoma, and cataract. Foamy macrophages engulf the fats
● Choroidal hemangioma was found in the
enucleated eye, but clinical study failed to MUCOCELE
disclose evidence of an intracranial lesion.
Hemangioma in the eye is hemangioma elsewhere

XANTHELASMA

Mucocele producing downward and lateral

displacement of left eye
Mucocele is just a cyst with no lining that has
accumulated extravasated mucin. Usually fluctuant
(movable) in PE

Xanthelasma of upper eyelids in a patient who had

no other systemic findings (arrows)

Assessor: Gangoso
Group 16: Barbasa, Cabalo, Fabila Page | 4
Notes:
II. NEOPLASTIC LESIONS OF THE EYE
RECKLINGHAUSEN NEUROFIBROMATOSIS
Several unilateral deformity of face in a patient with
Recklinghausen’s neurofibromatosis
When the nerve in the eye is affected, there is ptosis
of the eyelid.
BENIGN MIXED TUMOR OF LEFT LACRIMAL
GLAND
Benign mixed tumor of left lacrimal gland in a 38-
year-old man.
● Proptosis was accompanied by severe visual
loss.
Assessor: Gangoso
Group 16: Barbasa, Cabalo, Fabila
● It can cause proptosis accompanied by severe
visual loss
● In parotid gland this is what we call your
pleomorphic adenoma
Common name: Pleomorphic Adenoma
Alternate name is BMT (Benign Mixed Tumor)
Where do we encounter this one? Parotid Gland
There is primary BMT associated with glands around
the eyes. When they undergo neoplasia, they
become such entity. It is associated with severe
visual loss, if it is going to impinge the structures
related to ectoderms.
Benign mixed tumor of lacrimal gland largely
composed of so-called “hyaline cells”:
Low-power view showing encapsulated quality.
There will be sheets of hyaline cells that are
monoclonal associated with fatty stroma and
encapsulated just like what you see in the picture.
The goal of neoplasia is encapsulation.
Why is it called Mixed?
Because it is a mixture of epithelial elements, those
hyaline (pinkish to reddish cell formations) immersed
in fatty stroma.
You have an epithelium and mesenchychymal
component, thus, the name mixed.
Something benign? It is when it impinge on important
structures that will cause visual loss. But when once
removed, vision will be restored.
Page | 5
Notes:
High power view of benign mixed tumor of lacrimal
gland largely composed of so-called “hyaline cells”
with diffuse eosinophilic appearance of the
cytoplasm.
Hyaline is used to describe as cells that appear
glassy and eosinophilic. Something that is basophilic
cannot be a hyaline.
It has to be red or pink (but not all the time), must be
glassy in appearance. Nuclei are round, can be
center or off-center. But basically, not malignant
nuclei.
EXTENSIVE PAPILLOMA OF BULBAR
CONJUNCTIVA
● Blood supply will be engorged due to exophytic
growth
Assessor: Gangoso
Group 16: Barbasa, Cabalo, Fabila
This is somewhat a sign of poverty, because if
someone can a doctor, it will not reach up to this point
(Due to lack of access).
PAPILLOMA OF CONJUNCTIVA
An exophytic growth of well-differentiated epithelial
cells is supported by a prominent central
fibrovascular core.
● The complex pattern of growth may simulate a
carcinoma.
● The papillary structures is lined by several layers
of cuboidal to columnar cells with blunt nuclei,
dense chromatin and inconspicuous nucleoli and
ample cytoplasm
● They are branching and you will think that it is
carcinoma because the pattern is complex but if
you look at the individual cells, these are benign
cells, and it’s just that there is extuberant
papillomatous development.
Papilloma is benign.
There will be finger-like projections or papillae, ample
eosinophilic cytoplasm, and well-defined cell
borders, supported by fibrovascular core.
Page | 6
Notes:
Papilloma in the bulbar area is the same papilloma
elsewhere.
The complex pattern may simulate carcinoma. If it is
benign, the rule is, it is up to secondary branching.
But sometimes, secondary will branch again into
tertiary or quarternary, then it becomes complex.
It is a little difficulty for us to ascertain if it is benign
or malignant. Hence, this is a pass around case.
Meaning, it will have implications on the patient.
Of course! Something that is a papilloma, the lesion
should be removed, but something that is a papillary
carcinoma, the eye has to go. That is why we need
to be very, very careful!
MENINGIOMA OF ORBIT
Meningioma of orbit.
● The tumor has a typical meningothelial
appearance.
● Radiographic finding would be a well defined
mass attached to the falx cerebri
● Composed of whorls of meningoepithelial cells
Meningioma arises from the meninges.
What is the prototypical radiologic finding in the
meningioma? Dural attachment. The mass is
attached to the dura.
However, in orbital meningioma, this does not
happen. The dura can extend to the orbit and
become neoplastic in itself.
So how will we know it is a meningioma? Look for
meningiothelial whirls.
Assessor: Gangoso
Group 16: Barbasa, Cabalo, Fabila
Meniongiothelial cells are squamoid in appearance,
large, with abundant eosinophilic patterns. They can
do whirls on themselves, giving rise to specific
pathognomonic findings called meningothelial swirls.
Can be big or small, composed of squamous cells
that turn around in itself.
CARCINOMA IN SITU OF CONJUNCTIVA AND
CORNEA
Carcinoma in situ of conjunctiva and cornea
● You will see here a cream white ill-defined mass
that encroaches our pupil. You will notice that the
blood vessels are very obvious and congested.
Perhaps these are neovascularization
associated with malignant degeneration.
● Without undergoing biopsy, you will have a hard
time ascertaining that this is malignant
● May be misdiagnosed as pterygium.
This one is a little difficult to diagnose.
We know that is a cancer, but is has not invaded yet.
So if we diagnose this, the burden is on the
ophthalmologists. To have a nucleation or not to
prevent potential spread. It can be preventive which
is to remove the eyes before it spreads. OR. It can
be delayed. Let it invade first with the risk of
metastasis before removing the eyes.
Page | 7
Notes:
LEUKOPLAKIA (SCCA-IN-SITU)
Leukoplakia (SCCA-in-situ)
● Can appear cream white, firm and irregular.
● Only clue that this is carcinoma in situ is its
irregularity, but definite proof has to have this
submitted to the department of pathology and
taken a look at a microscope.
This picture, it’s a little complex and fleshy. It can be
papillary in nature just like in orbital papilloma. But in
PE, it appears white; clinically, leukoplakia.
Carcinoma of conjunctiva with pagetoid pattern of
growth.
● You will notice that there is full-thickness atypia
from the basement membrane downwards to the
surface, these are malignant cells already. So,
there is pleomorphism and hyperchromasia, it’s
Assessor: Gangoso
Group 16: Barbasa, Cabalo, Fabila
just that they haven’t invaded the stroma, yet. So
the supporting membrane tries to limit them.
● Just by looking at it this is squamous cell
carcinoma in situ which is actually leukoplakia,
clinically.
There is the stroma and epithelium. Basement
membrane up to the surface is full thickness
malignancy. All cells are hyperchromatic, has
pleomorphic nuclei, coarse chromatin, scanty
cytoplasm with well-defined cell borders.
Why is it carcinoma in situ? Notice that it has not yet
invaded the basement membrane.
SQUAMOUS CELL CARCINOMA OF
CONJUNCTIVA
Squamous cell carcinoma of conjunctiva.
● The tumor grew rapidly over a 4- month period.
● Malignant
● It is large, fast growing, ill-defined
● It has already misshapen the lower eyelid and
now is involving the lateral canthus of the eye.
● If you have masses that have the same size for
years, chances are, that is benign.
● If it’s fast growing → higher chances that its
malignant
● Conjunctival squamous cell carcinoma may be
preceded by intraepithelial neoplastic changes
analogous to those seen in the evolution of
cervical squamous cell carcinoma. In the
conjunctiva the spectrum of changes from mild
Page | 8
Notes:
dysplasia through carcinoma in situ is designated
as conjunctival intraepithelial neoplasia.
● Squamous papillomas and conjunctival
intraepithelial neoplasia may be associated with
the presence of human papillomavirus types 16
and 18.
When it becomes invasive, we call it “Squamous cell
carcinoma, invasive, primary to the eye”
Squamous cell carcinoma of conjunctiva may look
like squamous cell carcinoma of the skin,
esophagus, urinary bladder, etc.
It can be as large as this… (Upper picture)
Gross photomicrograph of malignant lesions of upper
eyelid
Or it can be as small but a little disturbing or more
well-defined as this lesion. (Upper picture)
Squamous cell carcinoma of conjunctiva growing
extensively inside the orbit and compressing the
ocular globe.
Assessor: Gangoso
Group 16: Barbasa, Cabalo, Fabila
● You will notice that we ink all together because
that’s going to be our margin.
● You will notice that a cream white, ill-defined
infiltrating mass is very near the (inaudible)
The mass is already impounding on the globe,
perhaps the patient is already experiencing pain and
vision loss.
It can even surround the orbit.
Squamous Cell Carcinoma of the Eye, Upper Eyelid,
of the Globe are histologically similar to SCC
elsewhere.
● There is individual cell keratinization, there are
intercellular bridges or desmosomes.
● Desmosomes connect each individual
neighboring squamous cell
● This is a well-differentiated form of SCC
Sheets of malignant squamous cells, with
hyperchomatic and pleomorphic nuclei, abundant
eosinophilic cytoplasm, coarse chromatin, and well-
defined cell borders.
There is one entity in that will give out its squamous
origin. (Yellow circle in upper picture)
When you see this individual cell keratinization
forming into keratin pearls, then it is an indication that
it is squamous cell carcinoma.
Page | 9
Notes:

Basal cell carcinoma of the eyelid

● 2nd most common malignancy (accdg to doc)
● In your textbook, it is ulcerative. As if a rodent has
bitten on it. “RODENT ULCER”
● Locally invasive, malignant but rarely
metastasize

Why is it a BCC and not a SCC? Ulcerations

In PE (and a very important characteristic) there is
the presence of ulcer.
Ulceration in a skin lesion is BCC, unless proven
otherwise.

● You will see that in between malignant cells there

will be the presence of desmosomal attachments
here, so these are your intracellular bridges
(black arrow)
● This is obviously malignant because you can see
that these malignant nucleus have two nucleoli
● The greater number of nucleoli, the higher the
chance of malignancy.
● It is very mitotic too, there is pleomorphism and
hyperchromicity
So why is this squamous cell carcinoma?
Intercellular bridges (Black arrow)
Intercellular bridges + individual keratinization + ● As opposed to SCC that is eosinophilic, this is
keratin pearls = Squamous Cell Carcinoma intensely basophilic and you will notice that the
cells towards the periphery are oriented 90
If you see these things in the board exams, hands on degrees to the cells at the center, that is what we
your waist, squamous cell carcinoma! My God, very call “peripheral palisading”
easy! It can be in the eyes, in the esophagus, in the
skin, they all f__ look the same! (HAHAHA) Cells in BCC are basophilic as opposed to SCC
which are eosinophilic.
BASAL CELL CARCINOMA OF THE EYELID

Assessor: Gangoso
Group 16: Barbasa, Cabalo, Fabila Page | 10
Notes:

● In some areas, the discs detach from the

surrounding stroma
● In SCC, the desmosomes are intact to the well-
differentiated phase, but in BCC the
hemidesmosomes that will ideally attach the
lowermost cell to the cell at the stroma is lost.
● Giving rise to tumor retraction or retraction
spaces, which is another characteristic of BCC

SEBACEOUS GLAND CARCINOMA OF THE

EYELID

Whole mount of sebaceous gland carcinoma

compressing but not infiltrating the ocular globe. The
tumor is sharply circumscribed and very cellular and
has areas of necrosis.
● Hallmark: There are as much areas of necrosis
as there are viable cells

Microscopically, you see glands with necrotic areas

associated with it especially around the center of the
glands.
● This is quite common
● If we see something that is disfiguring, that is wet. Central necrosis + glandular formation = Sebaceous
Squamous CC tends to be dry on PE. carcinoma
● In Sebaceous CC, because it is a sebum
producing tumor, we expect it to be a little wet. ADENOCARCINOMA OF MEIBOMIAN GLAND
Just like what you see here in the PE findings
● Sebaceous carcinoma may form a local mass
that mimics chalazion or may diffusely thicken the
eyelid.
● Tends to spread first to the parotid and
submandibular nodes
● Sebaceous carcinoma of the eyelid is less likely
to be associated with the Muir-Torre syndrome
than sebaceous neoplasms developing
elsewhere

It could be seen in the eyelid which is a little

disfiguring.

Adenocarcinoma of meibomian gland.

Assessor: Gangoso
Group 16: Barbasa, Cabalo, Fabila Page | 11
Notes:

● Plugs of necrotic tumor fill central portions of Melanoma in the eyes looks like melanoma
duct-like tubular masses of neoplastic tissue. elsewhere
The necrotic areas are at the center of this
You know it’s melanoma due to the presence of
malignant nest. Sebaceous carcinoma, arise
melanin
from the meibomian gland.

MELANOMA OF THE EYELID

ABCDE of melanoma (Bates):

A – Asymmetry
B – Border irregularity
C – Color variations/variegation Microscopically: prominent cherry red nucleoli
D – Diameter >6 mm Melanoma: “the great mimic” – it can mimic anything
E – Elevated (Evolution accdg to Doc)
+ F – Firm to palpation If you do not know anything about a tumor and you
+ G – Growing progressively over the weeks see spots of melanin associated with it, it must be
melanoma
CHOROIDAL MELANOMA

Very rare
Uveal and choroidal melanoma have propensity to
metastasize

Assessor: Gangoso
Group 16: Barbasa, Cabalo, Fabila Page | 12
Notes:

Cream-white, irregular, may occupy a small to large

portion of the ocular cavity

Commonly-used IHC stains:

● Melan-A
● HMB-45
● S100
Low-power view of retinoblastoma
RETINOBLASTOMA ● There is a collar of viable cells about nutrient
vessels. The normal retina is seen on the left.

Bilateral retinoblastoma showing a white mass

consisting of detached retina and neoplastic tissue
immediately behind the lens in each eye.
The most common intraocular malignancy of
childhood
PE findings: absence of Red Orange Reflex (ROR),
mass on fundoscopy
● The appearance is that of a malignant small
round cell tumor.
Composed of sheets of very embryonal cells
Small round blue cells with nuclei adjacent to each
other – “nuclear(?) molding”

Assessor: Gangoso
Group 16: Barbasa, Cabalo, Fabila Page | 13
Notes:

Retinoblastoma has a characteristic mutation located

in the gene 13
Deletion of retinoblastoma gene on the sub-band 4
band 1 on the long arm of chromosome 13
● Retinoblastoma is the classic example of the
neoplasm arising from the "two hit" genetic
defect.
● If the patient inherits one bad tumor suppressor
gene (the Rb gene on chromosome 13), either by
a point mutation or by deletion of the locus q14
on chromosome 13 as pictured here, then the
They can be associated with calcifications other is typically lost in childhood and a
retinoblastoma develops.
Embryonal character, poorly differentiated
SECONDARY METASTASIS TO THE GLOBE

If lucky, you get to see its pathognomonic finding:

Homer Wright rosettes
Metastatic carcinoma from breast producing diffuse
thickening of the choroid posteriorly.
Eyes can be a site of metastasis to, but rarely

Assessor: Gangoso
Group 16: Barbasa, Cabalo, Fabila Page | 14
Notes:

III. LESIONS OF THE EAR CHOLEASTOMAS

● associated with chronic otitis media • non-
● The most common aural disorders in descending
neoplastic, cystic lesions 1 to 4 cm in diameter
order of frequency are:
● lined by:
1. Acute and chronic otitis
o keratinizing squamous epithelium or
o most often involving the middle ear
metaplastic mucus-secreting
and mastoid)
epithelium
o sometimes leading to a
● filled with:
cholesteatoma
o amorphous debris (derived largely
2. Symptomatic otosclerosis
from desquamated epithelium)
3. Aural polyps
● Sometimes they contain spicules of cholesterol
4. Labyrinthitis
● A chronic inflammatory reaction surrounds the
5. Carcinomas
keratinous cyst.
o largely of the external ear 6.
6. Paragangliomas
OTOSCLEROSIS
o found mostly in the middle ear
● Abnormal bone deposition in the middle ear
INFLAMMATORY LESIONS about the rim of the oval window into which the
● Inflammations of the ear—otitis media, acute or footplate of the stapes fits
chronic— occur mostly in infants and children. ● Usually affects both ears
● Typically viral in nature and produce a serous ● Usually begins in the early decades of life
exudate, but may become suppurative with ● In most instances it is familial, following an
superimposed bacterial infection. autosomal dominant transmission with variable
penetrance
ACUTE INFECTION ● In most instances the process is slowly
● The most common bacteria in the acute progressive over the span of decades, leading
infection are: eventually to marked hearing loss.
o Streptococcus pneumoniae
o non-typeable H. influenzae TUMORS
o Moraxella catarrhalis ● Basal cell and squamous cell lesions of the
● Repeated bouts of acute otitis media with failure pinna are locally invasive but they rarely spread.
of resolution lead to chronic disease. ● Squamous cell carcinomas arising in the
● The most common bacteria in the chronic external canal may invade the cranial cavity or
infection are: metastasize to regional nodes, accounting for a
o Pseudomonas aeruginosa 5- year mortality of about 50%.
o Staphylococcus aureus
o Fungus CERUMINOUS ADENOMA
o Sometimes, a mixed flora The ceruminous glands in the eyes become
neoplastic. They produce a mass that protrude into
CHRONIC INFECTION the ear canal.
● Chronic infection has the potential to perforate
the eardrum, encroach on the ossicles or
labyrinth, spread into the mastoid spaces, and
even penetrate into the cranial vault to produce a
temporal cerebritis or abscess.
● Otitis media in diabetic person, when caused by
P. aeruginosa, is aggressive and spreads widely,
causing destructive necrotizing otitis media.

Assessor: Gangoso
Group 16: Barbasa, Cabalo, Fabila Page | 15
Notes:

The cytoplasm of the tumor cells has an apocrine

appearance.
Once excised, we see sheets of neoplastic cells with
blunt nuclei and abundant eosinophilic cytoplasm
Fine to clear chromatin pattern
MENINGIOMA OF THE EAR
This squamous cell carcinoma required the removal
of the entire external ear by wide excision.
Most important prognostic histopathologic finding:
margin clearance – if the margins are clear, the
patient will have higher chance of survival
But if the edge of the tumor is very near from the
surgical margin, you need to go back again and have
ample clearance

ADENOID CYSTIC CARCINOMA

Just like what we see in the eyes/orbits

Microscopically: Whorls
● The appearance is identical to that of its
counterpart in the central nervous system.
Adenoid cystic carcinoma growing beneath the
SQUAMOUS CELL CARCINOMA epidermis of the external ear canal.
SCC in the eye will look the same as SCC in the ear They can be in tubules, they can be in glands

Assessor: Gangoso
Group 16: Barbasa, Cabalo, Fabila Page | 16
Notes:

● Neoplastic tumor cells are seen growing beneath

a flattened epithelium. Most of the cell population
is small, but there are larger elements with more
abundant fibrillary acidophilic cytoplasm.
o “Fibrillary” means there are fine fibers
that go through in all directions in the
cytoplasm

YOLK SAC TUMOR

ACC of the ear is ACC of the parotid gland because

the most common histologic finding of this tumor is the
cookie cutter appearance of the tumor or “an island
of cells with punched out lesions”

EMBRYONAL RHABDOMYOSARCOMA

Yolk sac tumor of the middle ear immunostained for

α- fetoprotein.
● Rare, case reportable
● YST is seen in the ovary, also in testes, but can
be seen in the ear too
● Alpha feto protein (AFP) positive
● An embryonal kind of lesion

Red: Doc lecture

Gray: MSM Trans

Embryonal rhabdomyosarcoma of the middle ear

is not common but it will look the same as
embryonal carcinoma
● Microscopically: rhabdomyoblasts with
hyperchromatic pleomorphic nuclei and abundant
eosinophilic cytoplasm, the cell tapers towards the
end (just like the tail of the tadpole)

Assessor: Gangoso
Group 16: Barbasa, Cabalo, Fabila Page | 17
 FORENSIC PATHOLOGY
Dr. Billena
Dec 3, 2022
1:30-3:30 PM 4.2
OUTLINE 3
I. GENERALITIES OF DEATH
II. GUNSHOT WOUNDS
III. SHARP FORCE TRAUMA
IV. BLUNT FORCE TRAUMA
V. SPECIAL SCENARIOS
VI. CASES

FORENSIC SCIENCE
● Autopsy (MD) ●  Assault is in the top 10 causes of death in
● Serology (RMT) the Philippines
● Chemistry (RC)
● Ballistic (POLICE) REPORTABLE DEATHS
● CSI (POLICE) ● Alleged malpractice
● Associated with or as a result of diagnostic,
FORENSIC SCIENCE DISCIPLINES therapeutic or anesthetic procedures
● Maternal deaths from abortion
● Unattended by a physician
● Stillbirth 20 weeks or more unattended by a
physician
● Infant or child whose medical history does not
establish a pre-existing medical condition
● Neglect
● Possibly directly or indirectly attributable to
environmental exposure or workplace factors
● Infectious or contagious illness that may
represent an epidemic disease
NATURAL DEATH
● When cremation is to be performed
● Caused by the interruption and failure of body CERTIFIER
functions resulting from age or disease. The ● The physician/coroner/medical examiner who
most common cause of death indicates the cause of death on a death
certificate.
ACCIDENTAL DEATH ● He/She signs and attests that in his/her opinion
● Caused by unplanned events (car accidents) death resulted from the causes stated to the
best of his/her knowledge.
SUICIDE AUTOPSY PROCEDURE
● When a person kills themselves on purpose ● External examination
(hanging myself) ● Internal examination
● Organs are weighed and dissected
HOMICIDE ● Tissue samples taken by MDs and processed
● The death of one person by another person by MTs
(shooting someone) ● Disease processes, malformations,
deformations, infections, injuries

Assessor: Gangoso and Dalida

Group 17: Capacio, Gicos, Sia Page | 1
 ●  The time of death is very crucial in criminal
investigation because it can temporize the
events in the crime seen

●  Livor Mortis.
This is what you
should always
remember. The
moment you see
this, the person
is already dead

●  Cadavers are really labelled, when you die,

you are not a person anymore. You become a ●  Putrefaction is
personal property. So, when you dissect also a finding in
someone without consent from the family you death, notice the
are destroying a personal property cadaver is bloated
because of the
TIME SINCE DEATH AND BODY CONDITION production of gas
and the tissue
starts to
decompose
already.
Recognition
maybe difficult.

●  Still
putrefaction

Assessor: Gangoso & Dalida

Group 17: Capacio, Gicos, Sia Page | 2
●  This can be
found in humid
environments,
where the humidity
will have a
significant impact
on the body's
preservation in a
parchment-like
state.
●  mummification

●  An abrasion ring, formed when the force of

the gases entering below the skin blow the skin
surface back against the muzzle of the gun, is
seen here in this contact range gunshot wound
to the right temple.
●  You need to establish if its contact,
immediate, or long range

●  Stiffening of the body atleast 12 hours after

death. This is rigor mortis.
●  When oxygen is depleted the actin and
myosin filaments lock in together giving rise to
this.
●  when tissue lysis sets in, rigor mortis actually
disappears.
●  If you move the body from one place to
another after death, contortions of the body is
not in conjunction with the surroundings
chances are the body has been moved from the
place of death, to where it has been found.
 The important application of rigor mortis.
● The abrasion ring, and a very clear muzzle
imprint, are seen in this contact range gunshot
●  “Tache noire” wound.
French term for ●  You will notice that the muzzle imprints
that reddish brown perfectly coincide with the wound. You need to
strip running from describe them properly
the lateral to the
medial canthus

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Group 17: Capacio, Gicos, Sia Page | 3
● This is a contact range gunshot entrance wound
with grey-black discoloration from the burned
powder and hair (singeing).
●  It may not be contact anymore
● Powder tattooing is seen in this intermediate
range gunshot wound.
● Histologic examination of the entrance wound
site on the skin demonstrates black gunshot
residue and coagulative necrosis.
Assessor: Gangoso & Dalida
Group 17: Capacio, Gicos, Sia
●  Some gunshot wounds are perfectly round
you can easily establish them as either exit or
entry, as the case may be.
●  You need to measure it’s diameter. There is
a direct proportion in the diameter of wound
entry to the caliber of the pistol of interest.
●  the entry is a little more disheveled
compared to the exit wound. You want to place
the suspect properly, in relation to the patient.
 If the entry wound is in front and the exit
wound at the back, the suspect is in front -
that is homicide.
 If the suspect is at the back, chances are the
case of murder may be applied.
Page | 4
● The appearance of the wounding characteristics
in the skull is shown in the lower diagram in
which there is bevelling of the skull outward
away from the direction of origin of the bullet.
●  Bevelling is very much noticed in the
trabecular bone in the calvarium , when you ●  They maybe a
have a thin plate of bone surrounding your head, little disheveled
the enrty point is a little small. As it exits the first like in this case.
calvarium it will enlarge goes to the opposite
side, with a small entry and exit again with a
larger exit point.
 That is what we call bevelling because the
bullet has to pass through two bone tables,
there will be two sets of entry and exit points
funneling from the entry to the exit in each
bone table.
● Here is a slit-like
●  The direction of
exit wound. Note
the bullet: from the
that there is no
board going to the
powder or soot
viewer.
visible.
● You don’t have
bevelling in soft
tissues. Like the
femur
● Bevelling is strictly
observed in flat
bones specifically
the calvarium.

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Group 17: Capacio, Gicos, Sia Page | 5
● The actual
entrance site is
somewhat
irregular,
because the
bullet can tumble
in flight.
●  this is an
intermediate
gunshot wound
because of
tattooing
●  The ballistic
weapon has a a
very rough path. ●  Unless there’ a convincing set of evidence
gunshot wounds are considered

SHARP WOUNDS

● Seen in this clay

model is the
pattern of a stab
wound from a
double edge
knife on the left
and a single
edge knife on
the right.

●  This is a one
sided sharp
weapon.

●  This is a
single-edge
●  The entry and the exit are almost in the blade stab
same location. So this is a grazing bullet. wound in which
● It entered from the right and exited in the left. there is a "hilt"
mark at the left.
The sharp blade
edge is at the
right.

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Group 17: Capacio, Gicos, Sia Page | 6
 ●  In crush injuries secondary to vehicular
accidents.
 The passenger will usually die differently
than the driver.
●  Complete sign out of the case:
 Sudden crushing deceleration injury
secondary to vehicular accident

WHY DO PASSENGERS DIE IN A CAR

ACCIDENT?
DEFENSE WOUNDS
●  you may want
to document these
in order to claim
something is
homicidal.

ABRASIONS
●  Superficial
linear marks on the ● Sometimes a sudden deceleration injury in a
skin vehicular accident produces a tear in the aorta.
  The This usually happens just distal to the great
directions of vessels.
which are very ● The tear leads to sudden loss of blood and
important in the shock.
investigation of ●  Complete sign out of the case:
crime scenes  Hypovolemic shock secondary to aortic tear
secondary to sudden deceleration injury

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Group 17: Capacio, Gicos, Sia Page | 7

● Damage to abdominal organs with lacerations,
crush injuries, and rupture can lead to bleeding
into the peritoneal cavity known as
hemoperitoneum.
●  They can also die secondary to rupture of
solid organs
●  But acute blood loss first and then second is
this one
SUBMERSION INJURY
●  Do not sign out as drowning
●  For example, person died in salt water, (right
photo) you will see microphyto and zoo
planktons in the froth in the mouth and nostrils
 Sometimes we need to open the trachea
and fish this out and look it up on a
microscope
●  Complete sign out of the case:
 Asphyxia secondary to submersion injury
Assessor: Gangoso & Dalida
Group 17: Capacio, Gicos, Sia
BURN INJURY
●  characteristic
pustulates in these
victims
● Dies in angular
formations
● No one dies in
straight cadaveric
apperance
●  In burn victims, you remember manny
pacquiao, because burn victims die protecting
their faces from the smoke, and that is the last
posture they have
● Boxer’s attitude
● Pugilistic attitude
●  Immediate cause of death:
 Asphyxia secondary to inhalation injury
secondary to fire, this is how you sign this
out
Case 1
● A 56 year old physician, together with other
physicians, went on a summer outing fully-
sponsored by a drug company. While snorkeling,
the patient complained of chest pain and
eventually lost consciousness. Despite several
attempts of resuscitation, the patient died.
● His wife, who happens to be a doctor as well, is
suing the drug company for negligence. She
claims that the company did not provide life
guards for the participants.
Page | 8
 ●  Should your myocytes die, it will be replaced
by fibrosis
●  That is old MI, nobody dies from old MI

●  Heart attack followed by drowning? Or

drowning followed by heart attack?
● If, heart attack followed by drowning- there is no
negligence from the company
● If, drowning followed by heart attack- the drug
company is negligent
● (Above photo) we see old infarcts- whitish ●  There is also old atherosclerosis of coronary
discoloration in the myocardium, indicates long arteries
standing healed infarct ●  Complete Sign out of the case:
 Cardiac arrythmia secondary to chronic
myocardial infarction secondary to
atherosclerosis
●  Drug company has no liability

Case 2
● A 65 year old lady, known hypertensive, was
with her son on a long haul flight from South
America to the Philippines. After several hours
of flight and the plane was about to land at NAIA,
the lady suddenly stood up and went to the
bathroom where she lost consciousness and
●  In the areas of the infarct, we can see it is was found dead minutes later.
● The son is planning to sue the plane company
substituted by fibrosis
for not having an onboard physician for the flight.
●  Muscles are non replaceable, you will die
with that particular muscle already

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Group 17: Capacio, Gicos, Sia Page | 9
THE REST OF THE CASES WERE NOT DISCUSSED.
Case 3
● A 26 year old woman is on labor for her first
pregnancy. Her pre-natal history was
unremarkable. Right after delivering the baby,
the woman died.
● The family requested for autopsy to look for
possible legal reasons for medical malpractice.
Case 5
● A 32 year old seaman, fresh from finishing a
contract, had a drinking binge with his high
school classmate. At 2 am, they decided to go
home. He was found dead at 10 am.
● The wife requested for an autopsy to look for
possible work-related injuries for possible
compensation from the company.

● In acute pancreatitis, Cullens or Turners sign

occurs in approximately 3 percent of patients
Case 4 and is associated with a mortality of 37 percent.
● A 26 year old male was riding a motorcycle
when it hit a lamp post. He sustained a femoral
fracture and was brought to the ER. He was
conscious and coherent at that time. At the OR,
right before anesthesia was induced, the patient
died.
● The family is requesting for autopsy to rule out
medical negligence.

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Group 17: Capacio, Gicos, Sia Page | 10
 aggressive therapy, the seizures were relentless
and he eventually died.
● The daughter requested for an autopsy to rule
out any possible of a genetically-acquired
disease.

Case 6
● 2 year old boy, being watched over by a newly-
hired yaya and known to incessantly cry, was
brought to the ER unconscious and limp.
Twenty minutes later, he was pronounced dead.
● The mother is suspected that the newly-hired
yaya physically assaulted the child, thus an
autopsy was performed.

Case 7 References:
● A 68 year old male, a month after returning from Dr. Billena’s presentation and audio recording
a dream vacation in the tropics, presented to the
emergency room with seizures. Despite

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Group 17: Capacio, Gicos, Sia Page | 11
 MOLECULAR PATHOLOGY Dr. Billena
Dec 3, 2022
1:30-3:30 PM
4.3
OUTLINE
I. CORE PRINCIPLES OF MOLECULAR
BIOLOGY
II. BIOLOGY OF INFECTIOUS DISEASE
AGENTS
III. MOLECULAR METHODS IN INFECTIOUS
DISEASE DIAGNOSTICS
IV. GENERAL PCR TESTING

MOLECULAR DIAGNOSTICS
● Molecular diagnostics was described as the ●  Karyogram
detection of variations in the genome in order to
detect, diagnose, and monitor response to THE HUMAN GENOME
therapy. It stems from the collaboration between ● the human genome consists of ~3 billion bp and
laboratory medicine, genomics, and the 30,000-35,000 genes (haploid state)
technology in the field of molecular genetics, ● it would fill about 150,000 phone book pages
which contribute to the identification and with A's, T's, G's, and C's
characterization of various diseases that is vital ● a disorder can be caused by variation in one or
for accurate diagnosis, response, and treatment more base pairs (among the 3
(Patrinos et al., 2017). ● billion)
● The discovery of the duplex structure of the ● the challenge is partly one of scale (needle in a
DNA in 1953 as well as the mechanism to haystack)
replicate, transcribe, and translate itself opened
several doors the revolutionized not only the THE CENTRAL DOGMA
area of medicine, but all of biology. This would
lead to advances in recombinant DNA
technology, diagnotic assays, and sequencing.
● And since 1989, as more of the human genome
was being discovered due to the efforts to
sequence the entire human genome, new
technologies were developed to better decode
the biological mechanisms that are increasingly
made available.
● Laboratories began to adapt better technologies
for accurate diagnostics, risk assessment,
therapeutics, response to outbreaks, and
preventative and personalized medicine
(Demidov, 2003).

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Group 17: Sia, Capacio, Gicos Page | 1
 DNA REPLICATION FORK

* Succeeding topics have been skipped by doc.

REVIEW: (from Harper’s llustrated Biochemistry)

● A replication fork consists of four components
that form in the following sequence:
(1) the DNA helicase unwinds a short segment of
the parental duplex DNA;
(2) SSBs bind to ssDNA and prevent premature
reannealing of ssDNA to dsDNA;
(3) a primase initiates synthesis of an RNA
molecule that is essential for priming DNA
synthesis; and
(4) the DNA polymerase initiates nascent, daughter-
strand synthesis.
● DNA polymerases only synthesize DNA in the 5′
to 3′ direction, and only one of the several
different types of polymerases is involved at the
replication fork. Because the DNA strands are
antiparallel, the polymerase functions
asymmetrically.
● On the leading (forward) strand, the DNA is
synthesized continuously. On the lagging
(retrograde) strand, the DNA is synthesized in
short fragments, the so-called Okazaki
fragments, so named after the scientist who
discovered them.
● Several Okazaki fragments (up to 1000) must
be sequentially synthesized for each replication
fork.
● To ensure that this happens, the helicase acts
on the lagging strand to unwind dsDNA in a 5′ to
3′ direction. The helicase associates with the
primase to afford the latter proper access to the
template. This allows the RNA primer to be
made and, in turn, the polymerase to begin
replicating the DNA. This is an important
reaction sequence since DNA polymerases
cannot initiate DNA synthesis de novo.

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Group 17: Capacio, Gicos, Sia Page | 2
● The mobile complex between helicase and
primase has been called aprimosome. As the
synthesis of an Okazaki fragment is completed
and the polymerase is released, a new primer
has been synthesized. The same polymerase
molecule remains associated with the replication
fork and proceeds to synthesize the next
Okazaki fragment.

●  AUG signals the start of translation

●  UAA, UAG, UGA
 Signals to stop translation
●  Translation starts in AUGust and it will stop
when you hear the baby crying.

●  the biggest of them all is mRNA- massive

●  The most common is rRNA - rampant
●  The smallest tRNA - tiny
●  The linear arrangement of the amino acid is
the primary structure of the protein
●  When the primary structure interacts with
itself forming alpha helices and beta pleated
sheets that’s secondary structure.
●  When secondary structures aggregate
together they become tertiary structures and so
on.

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Group 17: Capacio, Gicos, Sia Page | 3
●  when you request for hormone assay, TSH
for example, that is a quarternary protein
structure

TYPES OF PROTEINS:
TYPE EXAMPLES
Structural Tendons, cartilage, hair
nails
Contractile muscles
Transport Hemoglobin, myoglobin
Storage Milk, nuts, seeds
Hormonal Insulin, growth hormone
Enzyme Catalyzes reactions in
cells
Protection Immune response

BELOW ARE JUST SOME OF THE

MOLECULAR BASIS OF PATHOGEN
IDENTIFICATION AND SUBTYPING
● Molecular methods seek to detect and visualize
DNA/RNA unique to the target pathogen.
● The ultimate discriminatory test would be to
sequence the entire genome of every organism,
but this is not practical or economical.
● The detection of nucleotide differences among
shared and uniquely present genomic regions is
the more practical and economical way.
ADVANTAGES BROUGHT ABOUT BY
MOLECULAR DIAGNOSTICS:
1. Rapid
 Shorter turn-around time (TAT) is needed to
complete the whole process.
 Results can be generated in real-time
and/or as little as 1-2 hours
2. Highly-specific
 Only the gene or region of interest is
targeted in pathogen detection
  The moment we positively identify viral
genes solely specific for Covid, we are sure
that it is Covid an not anything else.
3. More sensitive
 Can detect pathogens present at very low
concentrations
4. High throughput
 Can process large numbers of samples in
one run

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Group 17: Capacio, Gicos, Sia Page | 4
●  Polymerase chain reaction is the process,
the machine is called the thermal cycler.
●  There are viruses, wherein the genetic
element is a DNA.
 While Corona Virus, is an RNA virus
●  what can you do to circumvent the central
dogma of molecular biology?
 When we talk about molecular methods in
the detection of pathogens or the
identification of a cancer type, we talk about
specificity.
 Because we talk about the arrangements of
codons.
 There may be commonalities among them,
like the commonalities seen in Influenza and
Covid-19.
○ Although it is specific, there can be ●  if you have a segment of DNA that you want
overlaps among members of the
to amplify, you have to open it first. The only
same pathogen belonging to the
same class. way fr you to do that is to denature it using high
●  we can do serotype classification. temperature. Specifically 94˚C -94˚C
 Dengue  You want to anneal, meaning the primer to
attach to that particular direction in a 5’ to 3’
 Leptorspirosis
manner.
●  Phenotype Classification ● The reason why it’s called a thermal cycler is
 The end result really is there, as opposed to that per cycle the machine has three
serotyping which is for epidemiologic temperature settings
purposes  The number of copies of DNA = 2n
 Can be used to direct therapy for a  With n= the number of cycles
causative agent
 After 6 cycles, how many copies of DNA is
●  In molecular classification we can positively present?
identify the pathogen. ○ 26
○ in PCR the number of DNA copies
rises logarithmically

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Group 17: Capacio, Gicos, Sia Page | 5

● Reverse transcription polymerase chain reaction
(RT-PCR) is a variation of standard PCR that
involves the amplification of specific mRNA
obtained from small samples.
● The reaction mixture is heated to 37 ˚C, which
enables the production of complimentary DNA
from the RNA sample by reverse transcription.
● This complimentary DNA anneals to one of the
primers leading to first-strand synthesis.
Standard PCR proceeds and dsDNA is
produced.
Assessor: Gangoso, Dalida
Group 17: Capacio, Gicos, Sia
●  the y-axis: the number of fluorescence which
is directly proprtional to the copies of the DNA
●  there is a particular threshold that the
logarithmic line has to pass through in order for
us to claim that the sigmoid curve is valid. We
peg it at 20.
●  Anything above 40 is already invalid,
meaning if your sample has risen logarithmically
at around 20, you’re a fast riser. Chances are
you are in the early stage of the disease.
PCR SAMPLE IS VALID IF:
1. The controls are valid
 Negative control
 No template control ( water)
 Positive control
2. The internal control has to be amplified.
 The only way for us to know that a specimen
has been collected properly is if you can
identify that the gene related to the nasal
mucosa is present in the sample.
Page | 6
 Reference:
Dr. Billena’s lecture and audio recording

●  As seen on the graph the one that’s a little

bit faint is the internal control. It amplified
●  What does a legitimate internal control mean?
 The sample was collected properly, because
the gene being amplified here is the
nasopharyngeal mucosal gene present in
humans. The other three, are viral genes
specific for Covid
 This one in you sign out: COVID-19 RNA
DETECTED.
 If you see so many lines: positive
 Just one line: Negative

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Group 17: Capacio, Gicos, Sia Page | 7