Introduction to Histopathology

HISTOLOGY:

THE MICROSCOPIC STUDY OF BIOLOGICAL MATERIAL

PATHOLOGY: THE STUDY OF DISEASE and THE MORPHOLOGIC CHANGES THAT OCCUR IN

INJURY, DEATH,

REPAIR, ADAPTATION:

ACCUMULATIONS, ATROPHY, HYPERTROPHY,

HYPERPLASIA, METAPLASIA

INFLAMMATION

NEOPLASIA

HISTOLOGY:

THE MICROSCOPIC STUDY OF BIOLOGICAL MATERIAL

Derivatives of the three germ layers:

Endoderm, Mesoderm, Ectoderm

---Epithelium

---Connective Tissue

---Neural

EPITHELIUM:

comprised of cells that cover the exterior surface of the body,

and line both the internal closed cavities of the body,

and those body tubes that communicate with the exterior

--alimentary, respiratory, genitourinary

Can be impervious (epidermis or bladder) , secretory (stomach),

absorptive (intestines), be a transport system(trachea),

or receive sensory stimuli (taste buds of the tongue)

Epithelium is attached to its underlying connective tissue by

basement membrane

SQUAMOUS AND TRANSITIONAL EPITHELIUM

BLADDER

Human skin Mouse skin

Mouse skin

GLANDULAR EPITHELIUM

Small intestine with villiMucin stain showing goblet cells

Colon with NO villiMucin stain showing goblet cells

Epithelial cells (continued--mouse tissues)

LiverKidney glomerulus/tubules

PancreasLung

CONNECTIVE TISSUES:

---CELLS:

-fibroblasts

-adipose cells

-undifferentiated mesenchymal cells

-cells of the hematopoietic system

---EXTRACELLULAR MATRIX:

-EXTRACELLULAR FIBERS:

-collagen fibers

-reticular fibers

-elastic fibers

-GROUND SUBSTANCE :

-proteoglycans

-hyaluronic acids

- TISSUE FLUIDMUSCLE, CARTILAGE AND BONE

Trichrome stain for collagen

Silver stain for supporting reticulin fibers

TYPES OF MUSCLE: Cardiac, Smooth, Skeletal

Cardiac: striations + central nuclei

Skeletal: striations + eccentric nuclei

Smooth: central nuclei

Non-epithelial tissues (continued)

Bone/cartilage

Spleen

Brain-hippocampus and ventricle Cerebellum

HISTOCHEMISTRY

IMMUNOHISTOCHEMISTRY

IN SITU HYBRIDIZATION

USE OF HISTOCHEMISTRY TO DETECT DIFFERENCES IN BONE AND CARTILAGE FORMATION

USE OF HISTOCHEMISTRY TO DETECT DIFFERENCES DETECTED ON ROUTINE H&E STAINS

H&E

TRAP stain for osteoclasts

Use of AlcianBlue/PAS to detect differences in Mucin content within Brunner’s glands of duodenum

Silver stain (GMS) to detect presence of fungal hyphae in tissue x200

Gram’s stain to detect bacteria in tissue (oil immersion x1000)

USE OF HISTOCHEMISTRY TO DETECT INFECTIOUS ORGANISMS

Luxol Fast Blue for myelinFontana-Masson for melanocytes

MORE EXAMPLES OF HISTOCHEMISTRY

Folded artefact Cracked tissue artefact

Knife mark + folded arterfact

HISTOLOGY:

THE MICROSCOPIC STUDY OF BIOLOGICAL MATERIAL

PATHOLOGY: THE STUDY OF DISEASE and THE MORPHOLOGIC CHANGES THAT OCCUR IN

INJURY, DEATH,

REPAIR, ADAPTATION:

ACCUMULATIONS, ATROPHY, HYPERTROPHY,

HYPERPLASIA, METAPLASIA

INFLAMMATION

NEOPLASIA

METAPLASIA: (one cell type is replaced by another cell type: cigarette smoking induced change of bronchial epithlelial cells to squamous, Barrett’s esophagitis--where the squamous epithelium of the esophagus is replaced by columnar epithelium)

CELL INJURY: reversible or irreversible if prolonged

Due to: oxygen deprivation--ischemic ( no blood flow) , mechanical trauma (burns), chemical agents (acetaminophen) , infectious agents, immunologic reactions, genetic defects, nutritional imbalances etc.

INTRACELLULAR ACCUMULATIONS: fatty change of liver cells in alcoholism or obesity, glycogen deposits in diabetes, accumulation of pigments like iron after hemorrhage

CELL DEATH: necrosis (occurs from the progressive degradative action of

enzymes on the lethally injured cells) apoptosis: -programmed destruction of cells

during embryogenesis-hormone dependent involution in the adult - cell deletion in proliferating cell populations,

immune cells, tumors, etc.

HYPERPLASIA: An increase in the number of cells in an organ or tissue, which may then have an increased volume.

Physiologic hyperplasia: Proliferation of mammary glandular epithelium at pregnancy, compensatory hyperplasia of the liver after partial hepatectomy

HYPERTROPHY: An increase in size of cells and thus an increase in the size of the organ

eg: physiologic hypertrophy of uterus during pregnancy, hypertrophy of the cardiac muscle in hypertension or valvular disease, hypertrophy of skeletal muscles due to heavy exercise

ATROPHY: a shrinkage in the size of the cells due to

-a decreased work load ( when a limb is immobilized in a plaster cast)

-loss of innervation

-diminished blood supply

-loss of endocrine stimulation

-aging

INFLAMMATION AND REPAIR

Is a protective response, where the goal is to rid the body of the initial cause of injury and the consequences

ACUTE: relatively short duration. There is an alteration of blood vesels such that there is an exudation of fluid and plasma proteins, with an emigration of leukocytes, predominantly neutrophils, into the focus of injury.

CHRONIC: is of longer duration and is associated with the accumulation of lymphocytes and macrophages and allowing the repair process to occur, using angiogenesis and/ or fibrosis.

Red blood cells

(rbcs)

Hematopoietic cells

Erythroid MegakaryocytesLeukocytes

platelets

mast cells

Granulocytes

Neutrophils Eosinophils Basophils

(polymorphonuclear PMNs)

Myeloid

Monocytes

dendritic cells macrophages

B cells T cells NK cells

Plasma cells

Myelo-monocytic Lymphoid

Gr-1

F480

Mac-1

CD41

CD3B220

NEOPLASIA: new abnormal growth

A neoplasm “ is a abnormal purposeless mass of tissue, the growth of which exceeds and is uncoordinated with that of normal tissues, and which persists in the same excessive manner after cessation fo the stimuli which evoked the change”

Tumor= swelling. Benign tumor -- no infiltration into surrounding tissue. Malignant tumor = cancer

Cancer is the common term for all malignant tumors. Cancer derives from the Latin term crab presumably because it “ adheres to any part that it seizes in an obstinate manner like the crab”

Robbins and Kumar textbook of Pathology description of the process of malignant progression and metastasis

Benign tumors: fibroadenomas, polyps of the colon, lipomas

CARCINOMAS:

-Malignant tumors of epithelial cells

-well differentiated, moderately differentiated, poorly differentiated

-squamous carcinomas

- adeno-carcinomas

alveolar

papillary

tubular

(anaplastic, undifferentiated, large cell, small cell)

(hepatocellular carcinoma, cholangiocarcinoma)

SARCOMAS: Malignant tumors of supporting tissue

-chondrosarcomas--cartilage

-osteosarcomas--bone

-hemagiosarcomas--blood vessel

-gliomas (astrocytoma, glioblastoma)

-lymphomas

-melanomas

-rhabdomyosarcomas

-leiomyosarcomas

-fibrosarcomas

-seminoma, teratoma, etc.

Teratoma has multiple tissue types

IMMUNOHISTOCHEMISTRY is an important adjunct to histopathologic evaluation

Epithelium: Keratins

--pan-keratin

and antibodies to keratins of different molecular weights

Supporting connective tissues:

--Vimentin--fibroblasts, blood vessels

--vWF, CD31 (PECAM)-- endothelial cells of blood vessels

Hematopoeitic tissues: CD45, B220, CD3, F480, Mac-1, Gr-1, CD41

Muscle: desmin, smooth muscle actin

Neural: GFAP, NeuN, F480/Mac-1, MBP, NSE, S100

Hormones: specific antibodies--insulin, casein, etc.

Germ cells: alpha-feto protein (teratomas)

Proliferation markers-Ki-67