Neoplasia

Introduction to Neoplasia

Metaplasia, Dysplasia, and Neoplasia

• Metaplasia:

  • Replacement of one differentiated cell type with another mature differentiated cell type not normally present in that specific tissue.

  • Why: To adapt to environmental changes by changing the identity of original cells.

  • Outcome:

    • Removal of stimulus → tissues may return to normal differentiation or not.

    • Persistence of stimulus → metaplasia can progress to dysplasia or malignancy.

  • How: Reprogramming of stem cells/progenitor cells or even differentiated cells.

Types of Metaplasia

• Epithelial

  • Squamous

  • Glandular

• Mesenchymal

  • Connective tissue

Squamous Metaplasia

• Change of any type of epithelium into the more resistant stratified squamous epithelium.

• Cause: Chronic irritation.

• Examples of chronic irritation:

  • Cigarette smoking

  • Bilharzia ova

• Examples:

  • Pseudostratified columnar ciliated epithelium (bronchi) in chronic smokers transforms into more resistant stratified squamous epithelium.

  • Transitional epithelium of urinary bladder transforms into stratified squamous epithelium due to Bilharzial ova or stones.

• Mechanism:

  • Small cuboidal reserve cells develop beneath the columnar epithelium.

  • Proliferation and differentiation of these cells into immature squamous epithelium.

  • Loss of the overlying columnar cells, leaving stratified squamous mucosa.

Glandular Metaplasia

• Esophageal epithelium changes to gastric or intestinal type epithelium due to acid reflux.

• Intestinal metaplasia of the oesophagus is characterized by:

  • Squamous cell differentiation.

  • Goblet cells.

  • Columnar cells

  • Basement membrane

  • Luminal surface

Mesenchymal (CT) Metaplasia

• Traumatic myositis ossificans:

  1. Trauma (repeated) leads to hematoma.

  2. Granulation tissue (BV & fibroblasts) invades.

  3. Fibroblasts transform into osteoblasts, leading to osteoid tissue formation.

• Scars and atheromas may also show osseous metaplasia.

• Skeletal muscle develops bone formation secondary to injury and hemorrhage.

• Bony trabeculae and muscle fibers are observed.

Dysplasia

• Non-neoplastic, disordered epithelial cell proliferation.

  • Loss of uniformity in a population of cells and disorder of their normal architecture.

• Low-grade changes may be reversible.

• High-grade dysplasia is premalignant.

• Why: Chronic irritation

• Examples:

  • Chronic cervicitis → cervical dysplasia

  • Bilharzial Cystitis → urothelial dysplasia

• Microscopic features:

  1. Pleomorphism

  2. Hyperchromatism

  3. Increased N/C ratio (nuclear/cytoplasmic ratio)

  4. Increased mitosis

  5. Loss of normal orientation "polarity".

Features of Atypia

1. Pleomorphism: Variation in size and shape of cells.

2. Hyperchromatism: Dark nuclei.

3. Increased N/C ratio.

4. Increased mitosis.

Grades of Dysplasia (Cervical Mucosa Example)

• Mild: Atypia & loss of polarity in the epidermal lower 1/3.

• Moderate: Involvement of 2/3 of the epidermis.

• Severe: Involvement of more than 2/3 of the epidermis.

• Full thickness epidermis involvement = Carcinoma in situ (not invading basement membrane).

Neoplasia

• An acquired abnormality with abnormal, uncoordinated, and excessive cell growth.

• Growth persists after the initiating stimulus has been removed (autonomous).

• Involves genetic alterations in the neoplastic cells.

Neoplasm (Tumor)

• Definition:

  • Neoplasm = new growth

  • Oncology = Study of tumors

• A persistent, abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissue and persists after cessation of the stimulus that evoked it.

• The suffix "…oma" = neoplasm.

Characteristics of Neoplasms

1. No response to normal growth control.

2. Behave like parasites, competing with normal cells for their metabolic needs.

3. Enjoy self-control; they increase steadily regardless of the local environment and the nutritional status of the host.

Role of Histopathology in Neoplasia

• Predictive

• The base of evidence-based pathology

• The gold standard for diagnosis

Main Components of Neoplasms

1. Transformed, neoplastic cells.

2. Supporting stroma: connective tissue & blood vessels.

   • Tumor vascularization is affected by tumor cells (tumor-associated angiogenic factors) and inflammatory cells.

   • The parenchyma of the neoplasm determines its behavior and is the component from which the neoplasm derives its name.

   • The stroma carries the blood supply to the neoplasm, thus is important for its growth.

Classification of Neoplasms

1. According to clinical behavior:

   • Benign

     • Non-invasive

     • Remain localized

     • Slow growth rate

     • Closely resemble parent tissue histology

   • Malignant

     • Invasive

     • Spread directly and metastasize

     • Relatively rapid rate of growth

     • Variable degree of resemblance to parent tissue

   • Locally malignant

2. According to tissue of origin:

   • Tumors of one parenchymal cell type

     • Epithelial tumors

     • Mesenchymal tumors

   • Tumors from one germ layer (mixed tumors)

     • Salivary gland (mixed tumor)

     • Breast (fibroadenoma)

   • Tumors from more than one germ layer (Teratoma)

     • The three germ layers & some of their derivatives

       • Endoderm: GIT with liver and pancreas, pulmonary

       • Mesoderm: Heart and muscles, bone, cartilage, genitourinary

       • Ectoderm: Skin & glands, nervous system

Benign Tumors: --oma

1. Benign mesenchymal tumors:

   • Cartilage → chondroma

   • Fibrous tissue → fibroma

   • Adipose tissue → lipoma

2. Benign epithelial tumors:

   • Named either according to cell of origin, microscopic or macroscopic patterns.

Benign Epithelial Tumors

1. Adenoma: benign epithelial tumor producing glandular pattern.

2. Papilloma: benign epithelial tumor growing on any surface and producing macroscopic or microscopic finger-like projections.

3. Polyp: A mass projecting above the surface; it can be non-neoplastic or neoplastic benign or malignant

Adenomatous Polyp Diagnosis

Description: A projecting mass above the colon surface (polyp) composed of glandular formations (adenoma-like).

Characteristics of Benign Tumors

• Growth:

  1. Rate of growth: usually slow

  2. Mode of growth: Expansile growth from center outwards or Project outwards→ papillary growth

     • Tumor within a solid tissue

     • Tumor growing from a surface

Benign Tumors, Gross Picture

• Tumor encapsulation: Fibrous capsule = compressed CT +/- surrounding atrophic tissue.

• Non-encapsulated benign tumors include: leiomyomas, hemangiomas, lymphangiomas, nevi, benign surface epithelial tumors.

• Shape:

  • From solid organs: Round, oval, sessile.

  • From surface epithelium: Simple or compound pedunculated, polypoid mass.

Benign Tumors, Microscopic Picture

1. Cell morphology:

   • Tumor cells mimic cells of original tissue.

   • Cells are small, uniform in size and shape.

   • N/C ratio is preserved.

   • Mitotic figures are minimal and normal.

2. Tumor architecture (structure):

   • Same histological pattern as tissue of origin.

   • Well-developed, vascular stroma.

Benign Tumors, Behavior

• Rate of growth: slow

• Mode of growth: by expansion → compress neighboring tissue → atrophy

• Localized at site of origin (no spread)

• No recurrence if totally excised

• Effect on host: not dangerous, except if:

  • Compresses on vital organs (Brain, spinal cord,…)

  • Obstructs a tubular organ (intestine, esophagus,…)

  • Secretes hormones (tumors of endocrine glands)

  • Undergoes malignant transformation

Diagnosing Malignant Transformation of a Benign Tumor

• Increased rate of growth

• Loss of cellular differentiation

• Invasion of capsule or surrounding tissue.

Malignant Tumors (Malignant Neoplasms)

• Names usually follow benign ones with some additions.

• Malignant tumors of mesenchymal origin are SARCOMAS

  • They are termed according to their cell of origin [From fibrous tissue → fibrosarcoma, bony tissue→ osteosarcoma,…]

• Malignant tumors of epithelial cell origin are CARCINOMAS

Characters of Malignant Tumors

• Arise de novo or on top of precancerous lesions

• Growth

  1. Rate of growth: rapid

  2. Mode of growth: invasive

Malignant Tumors, Gross Picture

• Size: may reach a large size.

• Shape: depends on the site

  • Hard

  • Fixed

  • Irregular

  • Ill-defined

• Within solid organs Mass

• On a surface

  1. Polypoid mass

  2. Ulcerative mass

  3. Infiltrative mass

Ulcerative vs. Infiltrative Tumors

• Ulcerative tumor

  • Edge: raised, everted

  • Floor: hemorrhage & necrosis

  • Base: fixed, indurated (becomes hard/firm)

• Infiltrative tumor

  • Infiltrates underlying tissue

  • Annular

  • Diffuse

Malignant Tumors, Cut Section

• Usually solid with areas of hemorrhage and necrosis

• No capsule

Malignant Tumors, Microscopic Picture

• Cellular anaplasia: Anaplasia from Greek: ana: no, plasia: formation

  • A. Cell morphology:

    1. Cells: variable in size & shape (pleomorphism)

    2. Nuclei:

       • Large ↑ N/C ratio (nucleocytoplasmic ratio)

       • Hyperchromatic (duplication of DNA)

    3. Nucleoli: large, prominent

    4. Mitosis: increased both normal and abnormal

    5. Tumor giant cells

  • B. Loss of polarity

• Stroma:

  1. Highly vascular

  2. Areas of hemorrhage & necrosis

Malignant Tumors: Characteristic Cellular Features

1. Pleomorphic cells

2. Increased N/C

3. Prominent nucleoli

4. Tumor giant cells

5. Hyperchromatic nuclei

Malignant Tumors, Microscopic Picture: Differentiation

• The extent to which neoplastic cells resemble comparable normal cells

  • Well-differentiated cells resemble the tissue of origin

  • Undifferentiated cells “Anaplasia” = lack of differentiation

• Malignant tumors are thus graded as:

  1. Well-differentiated (grade I)

  2. Moderately-differentiated (grade II)

  3. Poorly-differentiated (grade III)

  4. Undifferentiated “anaplastic” (grade IV)

Squamous Cell Carcinoma

• Grade I: ‘well-differentiated’ great resemblance to parent cells

• Grade II: ’moderately differentiated’ moderately simulating parent cells

• Grade III: ‘poorly differentiated

• Grade IV: ‘undifferentiated” no similarity to parent cell