NEOPLASIA

Department of Pathology
Chang Gung Memorial Hospital

DEFINITION

Neoplasia: the process of new growth

Neoplasm (tumor): new growth
Oncology: the study of tumors
Cancer: malignant tumors
Genetic alterations excessive and unregulated
proliferation that becomes autonomous
Arising from a single cell --- tumors are clonal

NOMENCLATURE
Tumors are composed of:
1. Parenchyma: neoplastic cells
Determines the behavior and pathologic consequences

2. Stroma: connective tissue and blood vessels

The growth and evolution of tumors depend on the
stroma
Abundant collagenous stroma desmoplasia

NOMENCLATURE
Benign tumors:
Mesenchymal tumors: attaching -oma to the
cell of origin
Fibroblastic cells Fibroma
Cartilage Chondroma
Osteoblasts Osteoma

NOMENCLATURE
Benign tumors:
Epithelial tumors: based on the cells of origin,
microscopic architecture, or macroscopic pattern
Adenoma: forming glandular patterns or deriving from
glands
Papilloma: forming papillary projections
Cystadenoma: forming large cystic cavities
Polyp: projecting into the lumen

NOMENCLATURE
Malignant tumors:
Mesenchymal tumors: sarcoma
Fibroblasts Fibrosarcoma
Fat cells Liposarcoma
Smooth muscle cells Leiomyosarcoma
Striated muscle cells Rhabdomyosarcoma

NOMENCLATURE
Malignant tumors:
Epithelial tumors: carcinoma
Adenocarcinoma: with a glandular pattern
microscopically
Squamous cell carcinoma: producing recognizable
squamous cells

NOMENCLATURE
Mixed tumor: with divergent differentiation
Mixed tumor of salivary gland: epithelial
components + myxoid stroma resembling
cartilage pleomorphic adenoma

Teratoma: composed of cell types of more

than one germ layer
Arising from totipotent cells
Principally encountered in the gonads

NOMENCLATURE
Melanoma: malignant melanocytic tumor
Hepatoma: malignant hepatocellular tumor
(hepatocellular carcinoma)
Seminoma: one of the malignant germ cell
tumors
Choristoma: ectopic tissue
Hamartoma: disorganized tissue indigenous
to the particular site

NOMENCLATURE
The nomenclature is important because specific
designation have specific clinical implications.
For example, cancer of the testis tells little of its
clinical significance
Seminoma: tends to spread to lymph nodes; extremely
radiosensitive
Embryonal carcinoma: Not radiosensitive; tends to
invade locally and spread throughout the body

BIOLOGY OF TUMOR GROWTH

Natural history of malignant tumors:
1. Malignant change of the target cell
(transformation)
2. Growth of the transformed cell
3. Local invasion
4. Distant metastases

DIFFERENTIATION AND
ANAPLASIA
Differentiation: how much the tumor cells
resemble comparable normal cells (both
morphologically and functionally)
Benign tumors: well differentiated
Malignant tumors: ranging from well
differentiated to undifferentiated
Anaplasia: lack of differentiation --- a
hallmark of malignant transformation

MORPHOLOGICAL CHANGES
OF ANAPLASIA
Pleomorphism (of the cells and the nuclei):
variation in size and shape
Abnormal nuclear morphology

Hyperchromatic nuclei
Increased nucleus-to-cytoplasm (N/C) ratio
Variable nuclear shape
Coarsely clumped chromatin
Large nucleoli

MORPHOLOGICAL CHANGES
OF ANAPLASIA
Mitoses: atypical, bizarre mitotic figures
(tripolar, quadripolar, or multipolar)
Loss of polarity: growing in a disorganized
fashion
Other changes:
Forming tumor giant cells
Central areas of ischemic necrosis

DYSPLASIA
Dysplasia:
1. Loss in the uniformity of individual cells
2. Loss in architectural orientation

Carcinoma in situ: severe dysplasia involving the

entire thickness of the epithelium without stromal
invasion (a preinvasive neoplasm)
Dysplasia does not necessarily progress to cancer.

RATES OF GROWTH
The growth rate of a tumor:
1. Doubling time of tumor cells
2. Fraction of tumor cells that are in the
replicative pool
3. Rate at which cells are shed and lost

The growth fraction of tumor cells has a

profound effect on their susceptibility to
chemotherapy.

CANCER STEM CELLS

A rare population of tumor stem cells
exists among the heterogeneous group of
cells that constitute a tumour.
Have been found in breast cancer and acute
myeloid leukemia
Have a low rate of replication

LOCAL INVASION
Benign tumors: grow as cohesive expansile masses
Fibrous capsule

Malignant tumors: progressive infiltration, invasion,

and destruction of the surrounding tissue
Carcinoma in situ: malignant cytologic features
without invasion of the basement membrane

METASTASIS
Metastasis: tumor implants discontinuous with the
primary tumor
Benign tumors do not metastasize, whereas
malignant tumors can metastasize
Pathways of spreading
Seeding of body cavities and surfaces
Lymphatic spread: common in carcinomas
Hematogenous spread: common in sarcomas

EPIDEMIOLOGY
Cancer is the #1 cause of death in Taiwan
(27.3%, 2008)
Cancer deaths In Taiwan (2008)
Male: Liver (39.3%) > Lung (36.5%) >
Colorectum (17.1%) > Oral cavity (14.8%) >
Stomach (10.2%)
Female: Lung (16.5%) > Liver (14.7%) >
Colorectum 11.8%) > Breast (10.7%) > Stomach
(5.1%)

AGE
Most carcinomas occur in the later years of life (
55 years)
Common neoplasms of infancy and childhood:

Neuroblastoma
Wilms tumor
Retinoblastoma
Acute leukemia
Rhabdomyosarcoma

GENETIC PREDISPOSITION TO
CANCER
Autosomal dominant inherited cancer
syndromes:
Childhood retinoblastoma: RB gene
10,000-fold increased risk of developing
retinoblastoma, usually bilateral

Familial adenomatous polyposis: APC gene

Fated to develop colorectal carcinoma by age 50

GENETIC PREDISPOSITION TO
CANCER
Defective DNA repair syndromes
Hereditary non-polyposis colorectal cancer
(HNPCC): DNA mismatch repair gene

Familial cancers

NON-HEREDITARY PREDISPOSING
CONDITIONS
Chronic inflammation and cancer
Ulcerative colitis, Crohn disease, Helicobacter
pylori gastritis, viral hepatitis

Precancerous conditions
Chronic atrophic gastritis, actinic keratosis of the
skin, leukoplakia of the oral cavity

MOLECULAR BASIS OF
CANCER
Non-lethal genetic damage carcinogenesis
Clonal expansion of a transformed cell
Principal targets of genetic damage:

Growth-promoting protooncogene
Growth-inhibiting tumor suppressor genes
Genes regulating apoptosis
Genes involved in DNA repair

MOLECULAR BASIS OF
CANCER
Carcinogenesis is a multi-step process (tumor
progression): accumulation of genetic
alterations stepwise acquirement of
phenotypic attributes, such as excessive
growth, local invasiveness, and the ability to
form distant metastases

CHEMICAL CARCINOGENESIS
Initiation: induction of certain irreversible
changes (mutations) in the genome of cells
Promotion: tumor induction in previously
initiated cells
The effect of promoters is relatively shortlived and reversible

RADIATION CARCINOGENESIS
Ultraviolet rays (especially UVB):
Damage to DNA
Induce an increased incidence of skin cancers

Ionizing radiation:
To induce mutations
Most frequent induced cancers:
Leukemias (except for chronic lymphocytic leukemia)
Thyroid cancer in children

MICROBIAL CARCINOGENESIS
Oncogenic DNA viruses:
Human papillomavirus (HPV): uterine cervical cancer
Epstein-Barr virus (EBV): endemic Burkitt lymphoma;
nasopharyngeal carcinoma
Hepatitis B virus (HBV): hepatocellular carcinoma

Oncogenic RNA virus:

Human T-cell leukemia virus type 1 (HTLV-1): adult Tcell leukemia/lymphoma

MICROBIAL CARCINOGENESIS
Helicobacter pylori:
Gastric adenocarcinoma, intestinal type
Gastric extranodal marginal zone B-cell
lymphoma, mucosa-associated lymphoid tisse
(MALT) type (so called MALToma)

EFFECT OF TUMORS ON THE

HOST
Location and impingement on adjacent
structures
Functional activity such as hormone
synthesis
Bleeding and secondary infections when they
ulcerate
Initiation of acute symptoms caused by
rupture or infarction

LOCAL AND HORMONE

EFFECTS
Pituitary adenoma: destroy the remaining
pituitary and lead to endocrinopathy
Intestinal tumors: intestinal obstruction
-cell adenoma of the pancreatic islets:
insulin production fatal hypoglycemia
Intestinal tumors: melena
Urinary tract tumors: hematuria

CANCER CACHEXIA
Cachexia: progressive loss of body fat,
wasting, and profound weakness in cancer
patients
Possible causes:
Loss of appetite
Reduced synthesis and storage of fat and
increased mobilization of fatty acids from
adipocytes
Cytokines

PARANEOPLASTIC
SYNDROMES
Symptoms not directly related to the spread of
tumor or elaboration of hormones indigenous to the
tissue from which the tumor arose
Common paraneoplastic syndromes:

Endocrinopathies
Hypercalcemia
Acanthosis nigricans
Clubbing of fingers; hypertrophic osteoarthropathy
Thrombotic diathesis

GRADING AND STAGING OF

TUMORS
Grading:
The degree of differentiation (higher grade = less
differentiation)
Presumably reflects the aggressiveness of the tumor

Staging:
Based on the size of the primary tumor, the extent of
spread to regional lymph node, and the presence or
absence of blood-borne metastases (TNM system)

Staging is of greater clinical value than grading.

LABORATORY DIAGNOSIS OF
CANCER
Histologic and cytologic methods
Sampling approaches:
1. Excision or biopsy
2. Fine needle aspiration
3. Cytologic smears

Frozen section
Histologic evaluation within minutes

LABORATORY DIAGNOSIS OF
CANCER
Immunohistochemistry
To classify poorly differentiated malignant
tumors
To classify leukemias and lymphomas
To determine the primary site of metastatic
tumors
To detect molecules that have prognostic or
therapeutic significance

LABORATORY DIAGNOSIS OF
CANCER
Molecular diagnosis

Diagnosis of malignant tumors

Prognosis of malignant tumors
Detection of minimal residual disease
Diagnosis of hereditary predisposition to cancer
DNA microarray analysis and proteomics

LABORATORY DIAGNOSIS OF
CANCER
Flow cytometry
To identify cell-surface antigens of tumor cells
classification of leukemias and lymphomas
To measure the DNA content (ploidy) of tumor
cells a prognostic factor in certain
malignancies

LABORATORY DIAGNOSIS OF
CANCER
Tumor markers
Tumor-derived or tumor-associated molecules
that can be detected in blood or other body fluids
They are not primary methods of diagnosis.
Main utilities
To support the diagnosis
To determine the response of therapy
To indicate relapse during follow-up