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General oncology

Last updated: September 21, 2021

Summarytoggle arrow icon

Oncology is the science of tumors. This article explains basic concepts relevant to the development, progression, spread, complications, diagnosis, and management of cancer. Histological analysis helps to determine tumor type and grade, whereas the TNM classification system is used to assess staging. Because it is standardized and used internationally, the TNM classification helps unify oncological research and therapy protocols. Metastasis occurs via different pathways mainly by hematogenous or lymphatic spreading. Therapy can be curative (mostly in early tumor stages) or palliative (mostly later stages). In addition to surgically removing a tumor, it can be beneficial to perform neoadjuvant (before surgery) and/or adjuvant (after surgery) radiation, chemotherapy, or both. Response rates to these forms of treatment are highly variable.

In addition to local effects, such as compression or infiltration of neighboring structures, malignant tumors can also cause systemic complications such as paraneoplastic syndromes and cancer anorexia-cachexia syndrome. See “Paraneoplastic syndromes” article for more information.

For more details about tumor markers and immunohistochemical markers, see “Tumor markers”.

Terminology

Basic terminology in oncology
Term Definition
Normal cell
Neoplasia
Tumor
Adenoma
Carcinoma
Sarcoma

Hamartoma

  • A benign mass composed of mature cells that are native to the tissue of origin but have abnormal tissue organization (e.g., Peutz-Jeghers syndrome, pulmonary hamartoma, iris hamartoma)
  • Low potential to undergo malignant transformation
Choristoma
  • Presence of normal tissue at a site where this type of tissue is not normally found (e.g., the presence of gastric tissue in the ileum, as is sometimes seen in Meckel diverticulum)
Dysplasia
Carcinoma in situ (CIS)
Invasive carcinoma
Metastasis
  • Spread of malignant cells to distant organs, tissues (e.g., colorectal cancer spreading to the liver)
    • Lymphatic spread
    • Hematogenous spread

Benign and malignant tumors

Overview of benign and malignant tumors
Benign tumor Malignant tumor
Differentiation (grading)
  • Well-differentiated (low grade)
  • Poorly differentiated (high grade)
Growth
  • Slow growth with a low rate of cell division (low mitotic rate)
  • Mass effect with compression of non-tumor tissue
  • Unpredictable growth, high rate of cell division (high mitotic rate)
  • Suppressed cellular apoptosis
  • Locally destructive and invasive
Macroscopy
  • Necrosis is rare.
  • Well-demarcated from surrounding tissue
Microscopy
  • Almost no irregularities of cellular structures
  • Detection and confirmation of cellular atypia

Metastasis and relapse

Tumor origin

Types of tumors based on cell origin
Type of tumors Cell origin Benign tumor Malignant tumor
Epithelial tumors
  • Papilloma

Mesenchymal tumors

  • Fibrosarcoma
  • Blood vessels
  • Lymphatic vessels
  • N/A
Special variants of mesenchymal tumors
  • N/A
  • N/A
Neuroectodermal tumors
Germ cell tumors
  • Germ cells
Embryonal tumors
  • N/A

In 2020, approximately 1.8 million people will be diagnosed with cancer in the United States. Cancer is the 2nd leading cause of death; after heart disease. The most common type of cancer in both men and women is skin cancer, with basal cell carcinoma being more common than squamous cell carcinoma and melanoma. [1]

Epidemiology of common cancer types in 2020 [2]

The following numbers are an estimation of new cancer cases and their mortality in the United States (excluding skin cancer ).

Epidemiology of most common cancer types

Type

Incidence/year in men Incidence/year in women Mortality/year
Breast cancer 2,620 276,480 42,690
Lung and bronchus cancer 116,300 112,520 135,720
Prostate cancer 191,930 N/A 33,330
Colorectal cancer 78,300 69,650 53,200
Bladder cancer 62,100 19,300 17,980
Kidney cancer 45,520 28,230 14,830
Uterine cancer N/A 65,620 12,590
Pancreatic cancer 30,400 27,200 47,050
Thyroid cancer 12,720 40,170 2,180
Non-Hodgkin lymphoma 42,380 34,860 19,940
Leukemia 35,470 25,060 23,100

Overview

  • Definition: a multistep process by which normal cells develop and accumulate genetic mutations (inherited or acquired), resulting in a monoclonal expansion of mutated cells that can progress to the development of neoplasia
  • Process
    1. Initiation: DNA damage
    2. Promotion: DNA damage passed on
    3. Latency: the time between promotion and progression
    4. Progression: proliferation of the neoplastic cell line with the acquired DNA damage, leading to malignant transformation

Properties of malignant cells

Defense mechanisms of malignant cells [7]

Adenocarcinoma of Lung Kinase”: Cancer (adenocarcinoma of lung) and the gene product (tyrosine kinase) are associated with ALK mutations.

L-myc is associated with lung cancer and n-myc with neuroblastoma.

c-KIT mutations affect CytoKIne recepTor production.

BCL-2 mutations are associated with diffuse large B-cell lymphoma.

  • Tumor suppressor gene: a gene that normally controls and suppresses cell proliferation
    • Loss of function or inactivation leads to an increased risk of developing cancer.
    • Both alleles must be mutated in order for complete loss of function of the gene.
Overview of tumor suppressor genes
Gene Chromosome Gene product Associated malignancy
TP53
  • 17p13.1
Rb
  • 13q14.2
CDKN2A
  • 9p21.3

APC gene
  • 5q22.2

PTEN [12]

  • 10q23
  • Negatively regulates the PI3k/AKT pathway
BRCA1
  • 17q21.31
  • DNA repair protein
BRCA2
  • 13q13.1
MMR gene family
  • Varies depending on the mutated protein
DCC (Deleted in colorectal cancer)
  • 18q21.2

  • Transmembrane receptor involved in cell apoptosis
SMAD4 (DPC4) (Deleted in pancreatic cancer)
  • 18q21.2
MEN 1
  • 11q13.1
NF1
  • 17q11.2

NF2
  • 22q12.2

  • Merlin (schwannomin)
TSC1 (Tuberous sclerosis complex 1)
  • 9q34.13
TSC2 (Tuberous sclerosis complex 2)
  • 16p13.3
VHL
  • 3p25.3
WT1 (Wilms Tumor 1)
  • 11p13
WT2 (Wilms Tumor 2)
  • 11p15.5

Mutations of the Rb (retinoblastoma) gene mutations cause Retinoblastomas and bone cancer (osteosarcoma).

PTEN mutation is associated with cancers of the Prostate, breasT, and ENdometrium.

Mutations in MEN 1 affect its gene product: MENin.

Chemical carcinogens

Examples of chemical carcinogens
Substance Sources of exposure Malignancy
Aflatoxin
Alkylating agents
Aromatic amines (β-naphthylamine, benzidine)
  • Tobacco smoke
  • Dyes (occupational exposure in the textile industry)
  • Rubber
Arsenic
  • Contaminated groundwater (esp. in developing countries)
  • Pesticides, herbicides (e.g., vineyard workers)
  • Metal smelting
Asbestos
  • Insulation material (formerly used in construction and shipbuilding)
  • Asbestos cement (fibrolite), roofing, and siding
Benzene, benzol
Beryllium
  • Occupations that involve beryllium production and processing, esp.: [13][14]
    • Smelting and founding
    • Welding
    • Manufacturing
      • Industrial ceramics
      • Electronics
      • Automotive, aerospace, and defense components
      • Dental supplies and prostheses
  • See also “Beryllium” in “Rare pneumoconioses”.
Chromium
  • Significant in workers exposed to:
    • Galvanization (chrome plating)
    • Paint and glass manufacturing
    • Tanning leather
    • Building materials
Cigarette smoke
  • First-hand smoke: smoke inhaled by the smoker
  • Second-hand smoke: exhaled smoke that is inhaled by others in the vicinity of the smoker
  • Third-hand smoke: smoke particles that adhere to surfaces in the surroundings of the smoker
  • All three have been proven to be carcinogenic.
Ethanol
  • Alcoholic beverages
Nickel
  • Occupations that involve mining, smelting, welding, and casting of alloys (e.g., in coins, jewelry)
Nitrosamines
  • Cured meats (e.g. bacon) and fish
  • Cold-smoked foods
  • Tobacco [15]
Radon
  • Accumulation in basements
  • Uranium mining (extraction of uranium ore from the ground): miners are exposed to radon gas, which is emitted during natural radioactive decay of uranium ore
Silica
  • Occupations that involve cutting, drilling, chipping, or grinding crystalline silica (e.g., quartz) or materials that contain it (e.g., sand, granite), esp.: [17]
    • Sandblasting
    • Glass manufacturing
    • Construction work
  • See also “Etiology” in “Silicosis.”

Vinyl chloride

Wood dust
  • Woodworking (e.g., sawing, drilling, sanding)

Radiation

Overview of radiation
Type Occurrence Malignancy
Nonionizing radiation
  • UV-B
Ionizing radiation

Oncogenic infections

Tumor grading

  • Definition: the process of classifying tumors based on their histological appearance (degree of cell differentiation)
  • Indicators of poor differentiation
  • Anaplasia: loss of morphological features of malignant cells so that resemblance to normal cells of a particular tissue where tumor cell originated from is lost

Grading systems

  • AJCC grading system
    • Most commonly used grading system for nonhematological malignancies
    • Can be applied to a wide range of tumors
Grading Differentiation of malignant tissue
G1 Well differentiated (low grade)
G2 Moderately differentiated (intermediate grade)
G3 Poorly differentiated (high grade)
G4 Undifferentiated/anaplastic (high grade)
GX Differentiation cannot be assessed.

Tumor staging [18]

  • Definition: a method of determining and classifying a tumor according to its spread throughout the body
  • Prognosis: The stage of the tumor is typically more important than the grade in determining the prognosis.

Spread determines Stage, and Stage determines Survival more than grade.

TNM classification

  • T: size or direct extent of the primary tumor
  • N: involvement of regional lymph nodes
  • M: presence of distant metastasis
  • By adding a "C" to any category, it is possible to express the certainty of the diagnosis:
    • C1: routine procedure (clinical examination, x-ray)
    • C2: special procedure (e.g. ERCP, CT)
    • C3: based on biopsy, cytology or surgical exploration
    • C4: based on surgery and additional histopathological workup
    • C5: based on autopsy and histopathological workup
  • By adding a prefix to TNM it is possible to indicate additional diagnostic or clinical information:
    • cTNM: staging based on clinical criteria
    • pTNM: histopathological staging

T, N, and M have independent prognostic values. N and M are typically the most important determinants of prognosis.

AJCC staging system

  • Stage 0 (carcinoma-in-situ)
  • Stage I–III: Tumor spread into nearby tissues.
  • Stage IV: Tumor spread to distant parts of the body.

Cancer-specific staging systems

Definition

  • Metastasis: the spread of malignant cells to distant organs, tissues (e.g., colorectal cancer spreads to the liver)

Types of metastasis [19]

Four Carcinomas Route Hematogenously”: Follicular thyroid carcinoma, Choriocarcinoma, Renal cell carcinoma, and Hepatocellular carcinoma spread via the blood, compared to most carcinomas which spread lymphatically.

Mechanisms of metastasis

Common sites for cancer metastasis [24]

Common sites for cancer metastasis
Organ with metastasis

Associated features

Primary tumor location
Liver
Bone
Brain
  • Approximately 50% of brain tumors result from metastases.
  • Appear in the white-gray matter junction as multiple well-circumscribed lesions

Approximately 50% of brain tumors and most bone tumors are not primary tumors but rather result from metastases.

Cancers spread progressively to the liver”: Colon, Stomach, and Pancreas cancers metastasize to the liver.

BLT with a kosher pickle and mayo on the bun”: Breast, Lung, Thyroid, Kidney, Prostate cancers, and Multiple myeloma metastasize to the bone.

Definitions

Modalities of antineoplastic therapy

Besides tumor grade and stage, it is important to consider the patient's performance status (Karnofsky score), general well-being, comorbidities, and personal wishes regarding treatment options.

Assessing resection

Resection margin Definition Examined by
R0
  • Complete removal: Resection margins are macro- and microscopically free of tumor tissue.
  • Pathologist
R1
  • Microscopically visible tumor tissue in resection margins
R2
  • Macroscopically visible tumor tissue remains.
  • The size/extent of residual tumor tissue is indicated in the operative report.

Assessing response

Response Characteristics

Complete response (CR)

  • No clinical or radiological evidence of tumor disease over a certain amount of time (depends on tumor type)

Partial response (PR)

  • A decrease in tumor volume by a certain percentage (depends on tumor type)

Stable disease (SD)/(NC )

  • Minimal decrease or increase of all lesions/tumor volume

Progressive disease (PD)

  • Increase of all lesions/tumor volume

Definition: Substances produced by cancer cells that are found in increased amount in the bloodstream, urine, or body tissues.

For more details for each tumor marker see the article on tumor markers.

Neurocutaneous syndromes associated with neoplasms

Skin conditions associated with neoplasms

Overview of skin conditions associated with neoplasms
Condition Key features Neoplasms
Actinic keratosis
  • Small lesion with sandpaper-like texture
  • Lesions grow and become brown or erythematous and scaly
Leukoplakia
  • Persistent white plaques that usually cannot be scraped off (predominantly affects oral cavity)
Bowen disease
  • Erythematous and scaly
  • Irregularly shaped with sharply defined borders
Erythroplasia of Queyrat
  • Single or multiple sharply demarcated, non-healing lesions
  • Ulcerate and bleed easily
Lentigo maligna
  • Darkly pigmented macule with irregular borders on sun exposed skin
  • Gradual growth, color irregularities, surrounding "island-like" speckling
Dysplastic nevi
Xeroderma pigmentosum

Gastrointestinal conditions associated with neoplasms

Overview of gastrointestinal conditions associated with neoplasms
Condition Key features Neoplasms
Inflammatory bowel disease Ulcerative colitis
Crohn disease
Plummer-Vinson syndrome
Barrett esophagus
Atrophic gastritis Autoimmune metaplastic atrophic gastritis (AMAG)
Environmental metaplastic atrophic gastritis (EMAG)
Liver cirrhosis

Infectious conditions associated with neoplasms

Overview of infectious conditions associated with neoplasms
Condition Key features Neoplasms
DNA virus infections EBV infection
HBV infection
HHV-8 infection
  • Infects endothelial cells causing malignant, multifocal, highly vascularized tumors
HPV 16
HPV 18
RNA virus infections HTLV-1 infection
HIV infection
HCV infection
Nonviral pathogen infections Schistosoma haematobium
Clonorchis sinensis (Chinese liver fluke)
Streptococcus bovis

Miscellaneous conditions associated with neoplasms

Miscellaneous conditions associated with neoplasms
Condition Key features Neoplasms
Down syndrome
Paget disease of the bone

Paraneoplastic conditions

Overview of paraneoplastic conditions
Condition Key features Neoplasms
Neuromuscular Lambert-Eaton myasthenic syndrome
Myasthenia gravis
Polymyositis
  • Proximal muscle weakness affecting both sides
Dermatomyositis
Neurological Paraneoplastic encephalomyelitis
  • Immune reaction against neural antigens
Paraneoplastic cerebellar degeneration
Opsoclonus-myoclonus syndrome
Endocrine Cushing syndrome
Syndrome of inappropriate ADH secretion
  • Ectopically produced ADHanorexia, nausea, vomiting
Hypercalcemia of malignancy
Mucocutaneous Malignant acanthosis nigricans
Necrolytic migratory erythema
  • Multiple areas of centrifugally spreading erythema that develop into develop into painful and pruritic crusty patches with central areas of bronze-colored induration
Paraneoplastic seborrheic keratosis (Leser-Trélat sign)
Skeletal Hypertrophic pulmonary osteoarthropathy (Bamberger-Marie syndrome)
  • Ectopically produced growth factors (e.g., VEGF, PDG) → clubbing, joint pain, thickening of tubular bones
Hematological Polycythemia
Pure red cell aplasia
  • Absence of red cell precursor cells → anemia
Good syndrome
Trousseau syndrome (thrombophlebitis migrans)
Nonbacterial thrombotic endocarditis
Miscellaneous

Neoplastic fever

  • Most cancers

Membranous glomerulonephritis
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