PATHOLOGY

Lecture 4

Anna Skórczewska, M.D.

NEOPLASIA

DEFINITION

NEOPLASIA

"A neoplasm is an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues and persist in the same excessive manner after cessation of

the stimuli which evoked the change.”

(by Sir Rupert Willis, XIX century)

NEOPLASIA

=

1. Abnormal tissue

2. Derived from one cell

3. As a result of: + disorders in normal cell cycle

+ abnormalities in differentiaton of cells

+ disorders in intracellular, intercellular and extracellular communication of neoplastic cells/tissues

NOMENCLATURE

NEOPLASIA

BENIGN MALIGNANT

EPITHELIAL MESENCHYMAL

BENIGN NEOPLASIA

EPITHELIAL MESENCHYMAL

Adenoma Cystadenoma Papilloma

Lipoma Fibroma Angioma Haemangioma Lymphangioma

Chondroma Myoma Leiomyoma Rhabdomyoma

MALIGNANT NEOPLASIA

EPITHELIAL MESENCHYMAL

= CARCINOMA Adenocarcinoma Squamous cell carcinoma Basal cell carcinoma Anaplastic carcinoma Urothelial carcinoma

= SARCOMA

Liposarcoma Fibrosarcoma Angiosarcoma Chondrosarcoma Osteosarcoma Rhabdomyosarcoma Leiomyosarcoma

2 CONFUSING STRANGERS

1. Hamartoma

• = a mass of mature, but disorganized tissue normal to the particular site

• in: – Liver: hepatic cells, blood vessels and bile ducts

– Lung: a nodule with islands of cartilage, bronchi and blood vessels

• traditionally have been considered as a developmental malformations, but some genetic studies suggests a neoplastic origin.

This non-encapsulated, rounded hamartoma is surrounded by lung (bottom and left). Lobules of cartilage (upper right) and loose connective tissue (arrow) are separated by low, cuboid epithelium.

2 CONFUSING STRANGERS

2. Choristoma

• = a congenital anomaly consisting of a heterotopic rest of cells.

• e.g. a small nodule of well-developed and normally organized pancreatic tissue (islets of Langerhans and exocrine glands) in the submucosa of: – the stomach,

– the duodenum

– the small intestine

Heterotopic pancreas in Meckel's diverticulum

CANCER INCIDENCE

INCIDENCE

= the number of new cases diagnosed during one year in a country or other well-defined population.

• the differences between the incidence of tumors in different countries may vary due to:

(a) the average life span,

(b) race,

(c) culture,

(d) habits and

(e) environmental differences.

INCIDENCE

• Incidence rate is the ratio of cases per 100 000 population.

• There are also sex-specific rates, age-specific rates, ect.

CANCER RISK FACTORS

• Agents, mixture, circumstancce

Viruses

Tumor type

• Papilloma

• Sarcoma

• HSV – 1

• HSV – 2

• CMV

• EBV

Virus (common name)

• BK

• JC

• Adenocarcinoma, sarcoma

• Adenocarcinoma, fibrosarcoma

• Kaposi’s sarcoma

• Nasopharyngeal carcinoma

Inherited Predisposition to Cancer

HYPERPLASIA & NEOPLASIA

• HYPERPLASIA = adaptative change

• = an increase in the amount of organic tissue that results from cell proliferation

• reversible if damaging agents stops working,

BUT

• If NOT progress to DYSPLASIA NEOPLASIA

• e.g. endometrial hyperplasia

HYPERPLASIA & NEOPLASIA

• Responsiveness to normal regulatory control mechanisms

• Growth control mechanisms become dysregulated or ineffective

METAPLASIA

• = adaptative change

• = one adult cell type (epthelial/mesenchymal) is replaced by another adult cell type in tissue

• reversible if damaging agents stops working

METAPLASIA

• adaptive substitution – chronic irritation – smoking – chemicals – vitamins – growth factors (TGF- - bone macrophogenic

factor) – cytostatic drugs (disruption of DNA metylation)

METAPLASIA

• epithelial tissue – collumnar epithelium squamous epithelium ( squamous cell ca.)

– respiratory tract – salivary glands – pancreas – bile ducts – squamo-collumnar junction of the cervix

• SQUAMOUS METAPLASIA

• BARRETT’S ESOPHAGUS

DYSPLASIA

= INTRAEPITHELIAL NEOPLASIA = a LOSS in: 1. the uniformity of the individual cells + 2. their architectural orientation

DYSPLASIA/INTRAEPITHELIAL NEOPLASIA

• irreversible change

• often precedes malignancy

DYSPLASIA/INTRAEPITHELIAL NEOPLASIA

SQUAMOUS

INTRAEPITHELIAL NEOPLASIA SIN

CIN = cervical IN VIN = vulvar IN

VaIN = vaginal IN LaIN = laryngeal IN

OIN = oral IN BIN = bronchial IN

EIN = esophageal IN

GLANDULAR

INTRAEPITHELIAL NEOPLASIA GIN

EIN = endometrial IN CaIN = colorectal IN

PIN = prostatic IN MIN = mammary IN

- Ductal (DIN) - Lobular (LIN)

PaIN = pancreatic IN GaIN = gastric IN

UROTHELIAL

INTRAEPITHELIAL NEOPLASIA

UIN

DYSPLASIA/INTRAEPITHELIAL NEOPLASIA – morphology

1. a LOSS in the uniformity of the individual cells - Cytologic polymorphism - Nuclear enlargement - Normal N/C ratio - Irregular shape of cell - 2 or more nuclei - Hyperchromasia - Higher mitotic rate

DYSPLASIA/INTRAEPITHELIAL NEOPLASIA – morphology

2. a LOSS in epithelium architectural orientation

- Impaired cell maturation

- Abnormal axial arrangement of cells in the epithelium

- Abnormal stratification of epithelium

- Mitotic figures higher than usually

1/3 2/3

CIN III = CARCINOMA IN SITU

CARCINOMA IN SITU

• Cancer which appears only in layers of epithelium and does not break through the basement membrane

• No angioinvasion, no metastases

• Important early diagnosis => 100% curable

= INTRAEPITHELIAL NEOPLASIA III°

(e.g. CIN III)

ANAPLASIA

• = lack of differentiation (dedifferentiation or loss of the structural and functional differentiation of normal cells)

• cell/nuclei pleomorphism

• abundance of DNA (hyperchromatic)

• nuclear-cytoplasmic ratio 1:1 (normally: 1:4, 1:6)

• large nucleoli

• proliferative activity

• tumor giant cells

• markedly disturbed orientation of anaplastic cells

NEOPLASMS

BENIGN MALIGNANT

CLINICAL FEATURES

Slow GROWTH Rapid

Unusual ULCERATION Frequent

Unusual HAEMORRHAGE Frequent

No EVIDENCE OF METASTASIS Frequent

GROSS APPEARANCE

Smooth, due to expansile growth TUMOUR EDGE Irregular, due to infiltrative growth

Bland, homogenous CUT SURFACE Variegated, due to haemorrhage and necrosis within tumour

No EVIDENCE OF SECONDARY SPREAD Draining lymph nodes or adjacent structures may obviously be infiltrated

MICROSCOPICAL FEATURES

Good RESEMBLANCE TO TISSUE ORIGIN Often poor

Fairly uniform CELL SIZE AND SHAPE Highly variable (pleomorphic)

Very few, all normal MITOTIC FIGURES Often numerous, frequently abnormal, e.g. tripolar mitoses

No INVASION OF BLOOD VESSELS/LYMPHATICS/

PERINEURAL SPACE

Often present

No DYSPLASIA IN ADJACENT TISSUES Sometimes (e.g. cervix, skin, stomach)

Malignant MICROSCOPIC FEATURES

1. ↑ N/C rate 2. Polymorphism of nuclei (size, shape, color) 3. Hyperchromasia of nuclei 4. Heterochromasia of nuclei 5. Irregular shape of nuclei 6. Irregular shape of chromatin 7. Irregular thickening of nuclear membrane 8. Numerous pathologic mitoses 9. Architectural anarchy 10.Invasion of stroma

TUMOR – HOST INTERACTIONS

GRADE

GRADING

= level of histopathologic aggressiveness or malignancy of tumor cells + No. of mitoses within tumor

• G1 = well – differentiated

• G4 = poorly – differentiated/undifferentiated

STAGE

STAGING

= level of clinical advance

• TNM:

– T = tumor (size or depth of invasion)

– N = lumph nodes (number or size)

– M = metastases

DIAGNOSTIC METHODS IN PATHOLOGY

DIAGNOSTIC METHODS

• Postoperative specimen in H&E stains • Intraoperative frozen section • Fine needle aspiration biopsy • Cytologic (Papanicolaou) smears • Immunocytochemistry/Immunohistochemistry • Flow cytometry

• Tumor markers

• Molecular diagnosis

PARANEOPLASTIC SYNDROMES

PARANEOPLASTIC SYNDROME

= a syndrome (a set of signs and symptoms) that is the consequence of cancer in the body but that is not due to the local presence of cancer

cells

PARANEOPLASTIC SYNDROME

Etc. …. … … Table in Robbins Basic Pathology, 2014