Cellular Pathology

Histopathology Lab #1
(web)

Paul Hanna Jan 2011

Case #167

Clinical History:

• Sheltie, 4 years, spayed female

• chronic bilateral alopecic skin condition with hyperpigmentation and mild seborrhea.

• skin is very thin.

Note bilaterally symmetric
alopecia; owner indicated dog
was not pruritic (ie not itchy)
Drawing of human skin to show overall 3-D arrangement of structures.
(note sweat glands show difference between primates and other haired mammals)
Normal haired skin (low power); note dermis,
hair follicles, subcutaneous fat and underlying
cutaneous muscles.
Normal haired skin (medium power); note epidermis is about 2-4 cell layers thick and
the walls of the hair follicles are several cell layers thick.
Normal haired skin (high power); note epidermis is about 2-4 cell layers thick and the
walls of the hair follicles are several cell layers thick.
Epidermis / dermis
(which is much thinner than normal

Subcutaneous
fat

Cutaneous
muscle
 Case #167

Epidermis / dermis
(which is much thinner than normal

Subcutis
 Case #167

Epidermis and follicle wall often

reduced to 1 nucleated cell layer
 Case #167

Note also the sebaceous

gland atrophy
Case #167

Description:
• on low-power exam, the dermis is very thin and many follicles are inactive and
follicular lumina are dilated and filled with keratin.
• on higher power, there is excess surface keratin (hyperkeratosis) and follicular
keratin (follicular keratosis), the epidermis is only 1 to 2 cell layers thick (epidermal
atrophy) and follicles are in an inactive phase (telogen) with the follicle walls being
only 1 or a few layers thick (marked follicular atrophy).

Morphologic
Diagnosis: Dermatosis, atrophic, marked
(Epidermal, dermal & follicular atrophy, diffuse, marked)

Comment:
• clinical history, gross and microscopic findings are most consistent with an
endocrine dermatosis.
Hyperadrenocorticism

• One of the more common causes of endocrine dermatosis, especially those with
marked dermal atrophy, is due to excess glucocorticoid hormone.

• This can be the result of abnormal overproduction of glucocorticoids by the body

(endogenous hyperadrenocorticism) or when excess glucocorticoids are given for
medical reasons (exogenous or iatrogenic hyperadrenocorticism).

• There are a few different pathologic mechanisms by which the body can produce
excess amounts of corticosteroids, but one of the most common in dogs is a neoplasm
of ACTH secreting cells of the pituitary gland; which because of altered genetic
control are producing excess amounts of ACTH.

• This excess ACTH stimulates the target adrenal cortical cells with a resultant increase
in the number (hyperplasia), and to a mild degree size (hypertrophy) of the adrenal
cortical cells which produce the corticosteroids (ie cells in the zona fasiculata).
Hyperadrenocorticism

Various routes for increased levels of corticosteroids (glucocorticoids)

Hyperadrenocorticism

Pituitary adenoma (corticotroph adenoma) in a dog

secreting excess ACTH leading to bilateral Canine, normal adrenals, note
hyperplasia of the adrenal cortex. ratio of cortex to medulla (on
cut surface of upper section).
Pituitary adenomas in the adenohypophysis (arrows) which in this
case are neoplasms of corticotroph cells secreting excess ACTH
 Affected dog with sections
of adrenal gland showing
Normal adrenal cortical hyperplasia
gland
 Subgross of adrenal gland with marked cortical
hyperplasia (note cortical to medullary ratio).

Subgross of normal adrenal

(note normal cortical to medullary ratio)
Hyperadrenocorticism

Normal adrenal gland Affected adrenal gland

Hyperadrenocorticism

Normal adrenal gland Affected adrenal gland

Hyperadrenocorticism

Normal adrenal gland - cortex Affected adrenal gland - cortex

 Affected adrenal gland – note cortical cells are
Normal adrenal gland - cortex similar in size or only mild enlarged; so the
marked increase in thickness of the cortex must
be due mostly to increased numbers of cells.
Description:
• on low-power exam, note the marked enlargement of the cortex in the affected adrenal
compared to the cortex in the control animal; ie at 2.5X you can only see a portion of
the adrenal cortex in the affected animal, while in the control animal you can almost
see the whole gland!
• you can see that the enlarged cortex is due to a marked increase in the number
(hyperplasia) of cortical cells and to a much lesser degree an increase in the size
(hypertrophy) of the cells as well. Note, the enlarged cortical cells have vacuolated
cytoplasm and are somewhat compressing the cortical capillaries.

Morphologic Diagnosis: Adrenal cortical hyperplasia, diffuse, marked

Comment:
• adequate levels of corticosteroids are necessary for normal body function, however
excess corticosteroids can have deleterious effects on many body systems, eg
bilaterally symmetric alopecia, ↑ susceptibility to bacterial infections, “steroid”
hepatopathy, dystrophic mineralization, hypercoagulability, etc.
Slide #159

History:
• a 1.5 year old, male, domestic long haired cat presented comatose.

• for humane reasons, the cat was euthanized before a complete diagnostic work up.
• at necropsy: - liver was swollen & hepatic parenchyma bulged from the cut surface.
- on cut surface the hepatic parenchyma showed a mottled appearance.
Hepatic cords

Sinusoids
Slide #159
Loss of most hepatocytes from periportal Centrolobular (zone 3) hepatocytes
(zone 1) and mid zonal (zone 2) regions are swollen

Portal region with with

proliferation of bile ducts
Note hepatocytes in zone 3 show marked swelling which is due to mostly poorly
delineated cytoplasmic vacuoles (which is typical of hydropic degeneration)
Note hepatocytes in zone 3 show marked swelling which is due to mostly poorly
delineated cytoplasmic vacuoles (which is typical of hydropic degeneration)
Slide #159

Description:
• there is extentsive loss of hepatocytes from periportal / midzonal regions.
(additionally there is proliferation of bile ducts in portal regions).
• the majority of recognizable hepatocytes (in centrolobular region) are swollen and
have abundant vacuolated cytoplasm.
• most of the cytoplasmic vacuoles are poorly delineated (likely water = hydropic
degeneration), while a few are well delineated (likely lipid).

Morphologic Diagnosis: Hepatopathy, vacuolar (& necrotizing), severe

Comment:
• these hepatic lesions (necrosis and marked vacuolar / hydropic degeneration) are
most consistent with toxic damage.
• (a specific toxin was not identified in this case).
 Slide #46

Clinical History:
• necropsy of a ewe with the following history: lambed 3-weeks-ago, steadily losing
condition, poor appetite.

Necropsy examination revealed:

• a decrease in muscle mass and body fat stores.
• liver enlarged, diffusely yellow, greasy texture and sections floated in formalin.
• no other lesions were observed at the time of gross pathology examination.
Slide #46
At this magnification we can see that most hepatocytes, in all 3 acinar zones, are enlarged
due to clear well-delineated cytoplasmic vacuoles (typical of lipid accumulation)
At this magnification we can see that most hepatocytes, in all 3 acinar zones, are enlarged
due to clear well-delineated cytoplasmic vacuoles (typical of lipid accumulation)
At high magnification we can see that clear well-delineated cytoplasmic vacuoles (typical of
lipid accumulation). The nuclei are usually pushed to the periphery (although often not in
the plane of section). Note, the vacuoles are either single and large or multiple and small.
Slide #46

Description:
• the hepatocytes are swollen (note narrow sinusoids) and most contain a single large
or multiple small, clear, well-delineated cytoplasmic vacuoles.
• the vacuoles expand the cytoplasm and most nuclei are pushed to the periphery.

Morphologic diagnosis: Hepatic lipidosis (fatty liver), diffuse, severe.

Comment:
• to confirm the nature of the material in the hepatocellular cytoplasm (fat vs H20 vs
glycogen) special stains can be done, eg Oil-Red-O (for fat) or PAS (for glycogen).
• for pathogenesis read about pregnancy toxemia of sheep and cattle and fatty liver
syndrome in cattle and cats and diabetes mellitus (www.merckvetmanual.com)