Patho5 Cdsa Environmental

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. Fairskinned 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 FontanaMasson 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 tanwhite 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.