Faculty of Medicine and Surgery

Department of Pathology
TISSUE REACTIONS TO INJURY

Environmental Pathology

Prepared by

Emmanuel R. de la Fuente, M.D.

 Objectives
2. To create an awareness of the
common lesions associated with
environmental pathology
3. To apply the principles of basic
pathology to these common lesions
4. To promote changes in attitudes and
behavior towards the environment
Lesions associated with radiation
Sun exposure damages
the skin, primarily as the
result of ultraviolet light
exposure. This actinic
damage manifests itself
as a collection of
abnormal collagen fibers
in the upper dermis,
seen here with a pale
bluish appearance
(basophilic
degeneration) as
indicated by double
headed arrow. The
result is increased
wrinkling of the skin and
an increase risk for skin
cancer.
Actinic damage is seen above at medium power, with the
damaged collagen and elastic fibers appearing as a
homogenous pale blue area. With more extensive solar
damage, inflammation occurs as seen above. Fair-
skinned persons are at greater risk. This actinic damage
is cumulative and non-reversible.
1. Using the basic principles of
pathology that you have learned,
discuss the probable pathogenesis
of this dermal lesion
2. How does this lesion increase the
risk of skin cancer?
This is a basal cell carcinoma (BCC). A BCC is probably the most
common skin malignancy. A BCC can grow quite large and invade
surrounding tissues but it virtually never metastasizes. The cells of a
basal cell carcinoma are dark blue and oblong with scant cytoplasm.
They resemble the cells along the basal layer of normal epidermis.
The typical nest has a pallisaded arrangement of cells around the
periphery.
1. Using the principles of neoplasia,
discuss the pathogenesis of the lesion.
2. Hypothesize as to why this malignancy
virtually never metastasizes.
Above at low power magnification is a squamous cell carcinoma
in situ, i.e., confined within the basement membrane. Note the
normal skin to the carcinoma at the left. There is extensive solar
damage of dermal collagen similar to that seen in actinic
keratosis.
Invasive squamous
cell carcinoma seen at
medium power. The
neoplastic cells extend
downward into the
dermis. Note the
pleomorphism of the
cells, and there is little
keratinization.
Compare with the
normal skin above and
at the right. An intense
inflammatory infiltrate
is present.
Discuss the following:
2. Selective clonal theory in the
pathogenesis of in-situ to invasive
carcinoma.
3. Presence of lymphocytic infiltrates
around the tumor cells.
A malignant melanoma of the skin is shown above. The lesion is
larger than a centimeter with irregular borders and irregular
pigmentation. A very dark area is indicated by the arrow. The
prognosis of a melanoma correlates best with the depth of
invasion. Sun exposure is a high-risk factor in the development of
melanoma in light-skinned persons.
This is the microscopic appearance of a malignant melanoma.
The neoplasm is making brown melanin pigment. A Fontana-
Masson stain for melanin may help to detect small amounts of
cytoplasmic melanin which may not be readily visible.
1. Describe the morphologic features of
the tumor that indicate malignancy.
2. Discuss the biologic meaning of these
morphologic features.
Leukemia is the uncontrolled proliferation of a bone marrow cell
component resulting in a highly cellular marrow as seen above.
The normal fat cells have been obliterated. Normal hematopoiesis
is suppressed.
Explain why patients with leukemia are anemic,
highly susceptible to infections, and often develop
hemorrhage during the course of the disease.
 Lesions associated with cigarette
smoking

(Only the common malignant lesions associated

with smoking are presented here. The other
lesions/diseases will be taken up in their respective
organ/system).
This is a squamous cell
(SCC) carcinoma of the lung
arising from a main bronchus
(as most SCC do). It is
obstructing the right main
bronchus (arrow). Describe
the lesion. What gross
features do you see that
indicate it is malignant?
This is the microscopic appearance of squamous cell
carcinoma with nests of polygonal cells with pink cytoplasm
and distinct cell borders. The nuclei are hyperchromatic
and angular. We suppose that by now you can easily
recognize the essential features.
This irregular reddish, ulcerated exophytic mid-esophageal mass
as seen on the mucosal surface is a squamous cell carcinoma.
Risk factors for esophageal squamous carcinoma include mainly
smoking and alcoholism in developed countries. In other parts of
the world dietary factors may play a role.
Pneumoconiosis
Anthracotic pigment ordinarily is not fibrogenic, but in massive
amounts (as in "black lung disease" in coal miners) a fibrogenic
response can be elicited to produce the "coal worker's
pneumoconiosis" seen here.
This is the causative agent for asbestosis. This long, thin object is an
asbestos fiber. Some houses, business locations, and ships still contain
building products with asbestos, particularly insulation materials. In
some countries, use of asbestos has been banned. In the Philippines,
asbestos is still being used for construction materials, so care must be
taken when remodelling or constructing houses or buildings.
The asbestos fiber becomes coated with iron and calcium and
referred to as a "ferruginous body" as seen here with an iron
stain. Ingestion of these fibers by macrophages sets off a
fibrogenic response via release of growth factors that promote
collagen deposition by fibroblasts.
The white tumor mass encircling
and arising from the visceral
pleura is a mesothelioma. These
are big bulky tumors that can fill
the chest cavity. The risk factor
for mesothelioma is asbestos
exposure. Asbestosis more
commonly predisposes to
bronchogenic carcinomas,
increasing the risk by a factor of
five. Smoking increases the risk
for lung cancer by a factor of
ten. Thus, smokers with a
history of asbestos exposure
have a risk 50 fold greater
likelihood of for developing
bronchogenic lung cancer.
Mesotheliomas have either spindle cells (sarcomatous) or
plump rounded cells forming gland-like configurations
(epithelial), as seen above. They are very difficult to
differentiate from other epithelial and mesenchymal tumors.
Immunohistochemistry is often necessary.
In the above, the mesothelioma appears epithelial. Mesotheliomas
are rare, even in persons with asbestos exposure, and are virtually
never seen in persons without a history of asbestos exposure.
A silicotic nodule (above) is composed mainly of bundles of
interlacing pink collagen. There is minimal inflammatory reaction.
The greater the degree of exposure to silica and increasing length
of exposure determine the amount of silicotic nodule formation
and the degree of restrictive lung disease. Silicosis increases the
risk for lung carcinoma only about 2-fold.
Silica crystals (and other crystals that induce pneumoconiosis)
can be visualized by polarized light microscopy seen above as
bright white crystals of varying sizes. When macrophages ingest
the crystals, they secrete cytokines to induce a predominantly
fibrogenic response. The result is the production of many
scattered nodular foci of collagen deposition in the lung.
A gross lesion typical for pneumoconioses (asbestosis in
particular) is a fibrous pleural plaque. Seen above on the
pleural side of the diaphragmatic leaves are several tan-
white pleural plaques.
Microscopically, the fibrous pleural plaque is
composed of dense layers of collagen that give a pink
appearance with H&E staining.
Hypersensitivity pneumonitis (also known as extrinsic allergic
alveolitis) occurs when there is an inhaled organic dust that
produces a localized Type III Hypersensitivity (Arthus) reaction
from antigen-antibody complexes. Indicate and describe the
lesion.
Hypersensitivity pneumonitis often becomes chronic because
the diagnosis is difficult to make and the offending antigen not
easily identifiable. A granulomatous type of inflammation is
then seen indicating the transformation of the previous Type III
into a Type IV hypersensitivity reaction. Progression to fibrosis,
however, is not common.
Hepatic lesions associated with
alcohol abuse
(In its chronological occurrence)
This liver is slightly enlarged and has a pale yellow appearance.
This uniform change is consistent with fatty metamorphosis (fatty
change).
This is the histologic appearance of hepatic fatty change. The lipid
accumulates in the hepatocytes as vacuoles. These vacuoles have
a clear appearance with H&E staining due to the removal of the lipid
contents by the organic solvents during processing of the tissue.
The most common cause of fatty change is alcoholism.
Acute alcoholic hepatitis is characterized by the presence of
Mallory's hyaline, neutrophils, necrosis of hepatocytes, collagen
deposition, and fatty change. Such inflammation can occur in a
person with a history of alcoholism who goes on a drinking
"binge" and consumes large quantities of alcohol over a short
time. Identify these changes as described above.
This is an example of a micronodular cirrhosis. The
regenerative nodules are quite small, averaging less
than 3 mm in size. The most common cause for this is
chronic alcoholism. The process of cirrhosis develops
over many years.
Hepatocellular carcinomas arise in the setting of cirrhosis.
Worldwide, viral hepatitis is the most common cause, but in the
U.S., chronic alcoholism is the most common cause. Identify
and describe the lesion. What are the gross features indicating
the malignancy of the above lesion?
Drug Abuse
This is the lung of a patient with a long history of intravenous
drug use. Bright white collections of polarizable crystals are
primarily seen centered around vascular spaces. The crystals
represent talc that is used to dilute the injected drug. Only about
1% of such persons get a significant degree of pulmonary
fibrosis.
LOVE AND PROTECT THE
ENVIRONMENT. IT IS THE ONLY
ONE WE HAVE.