• Clinical science

General oncology


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 the article on paraneoplastic syndromes for more information.

For more details about tumor markers and immunohistochemical markers, see the article on tumor markers.



Term Definition
Normal cell
  • Abnormal growth of cells. Can be either malignant or benign.
  • Abnormal growth of cells or edema that leads to swelling of tissue
  • 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). Has a low potential to undergo malignant transformation.
  • Presence of pleomorphism: cells of different shape and size
  • Loss of cell orientation
  • Increased nuclear:cytoplasmic ratio
  • No invasion of the basement membrane
Carcinoma in situ (CIS)
Invasive carcinoma
  • Spread of malignant cells to distant organs, tissues (e.g., colorectal cancer spreading to the liver)
    • Lymphatic spread
    • Hematogenous spread

Benign and malignant tumors

Benign tumor Malignant tumor
Differentiation (grading)
  • Well differentiated (low grade)
  • Poorly differentiated (high grade)
  • Rapid with high rate of cell division (high mitotic rate)
  • Locally destructive and invasive
  • Well demarcated from surrounding tissue
  • Possible necrosis (e.g., squamous cell carcinoma of the lung)
  • Usually no tumor capsule
  • Infiltration (invasion) into surrounding tissue
  • Bleeding
  • Almost no irregularities of cellular structures
  • Detection and confirmation of cellular atypia
    • Nuclei: enlargement , polymorphism , increased cell count and/or enlarged nucleoli are all signs of increased activity of nuclei, polychromasia
    • Numerous mitotic figures

Metastasis and relapse

Tumor origin

Cell origin Benign tumor Malignant tumor
Epithelial tumors
  • Papilloma

Mesenchymal tumors

  • Blood vessels
  • Lymphatic vessels
  • Rhabdomyocytes (striated muscle cells)
  • Leiomyocytes (smooth muscle cells)
Special variants of mesenchymal tumors
Neuroectodermal tumors
Germ cell tumors
  • Germ cells
Embryonal tumors


General epidemiology (United States)

In 2018, approximately 1.7 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.

Epidemiology of common cancer types in 2018

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


(Sorted by total incidence)

Incidence/year in men Incidence/year in women Mortality/year
Breast 2,550 266,120 41,400
Lung and bronchus 121,680 112,350 154,050
Prostate 164,690 N/A 29,430
Colorectal 75,610 64,640 50,630
Bladder 62,380 18,810 17,240
Kidney 42,680 22,660 14,970
Uterus N/A 63,230 11,350
Pancreas 29,200 26,240 44,330
Thyroid 13,090 40,900 2,060
Non-Hodgkin lymphoma 41,730 32,950 19,910
Leukemia 35,030 25,270 24,370



  • 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 is passed on
    3. Latency: time between promotion and progression
    4. Progression: The neoplastic cell line proliferates with the acquired DNA damage, leading to malignant transformation.

DNA damage

Key genes involved in carcinogenesis

Properties of malignant cells

  • Uncontrolled cell proliferation
  • Failure to differentiate
  • Failure of normal apoptotic pathways
  • Defective DNA repair pathways
  • Lack of response to external growth inhibiting signals
  • Increased angiogenesis
  • Shift in cellular metabolism (e.g., Warburg effect)



Proto-oncogene Chromosome Gene product Associated malignancies
  • 7q34
Serine/threonine kinase
  • t(9;22) (q34.1;q11.21)
Tyrosine kinase
  • 9p24.1

HER2/neu (c-erbB2)

  • 17q12
Receptor tyrosine kinase
  • 2p23.2-p23.1
  • Lung adenocarcinoma
  • 10q11.21
  • 4q12
Cytokine receptor
L-myc-1 (MYCL1)
  • 1p34.2
Transcription factors
N-myc (MYCN)
  • 2p24.3
  • 8q24.21
  • Burkitt lymphoma t(8;14)
  • 12p12.1
  • 18q21.33

Antiapoptotic molecule
  • 12q14.1
Cyclin-dependent kinase
  • 11q13.3
Cyclin D protein (regulatory protein of the cell cycle)
  • Mantle cell lymphoma t(11;14)
  • 7p11.2
Epidermal growth factor receptor
  • Squamous cell carcinoma of the lung

Tumor suppressor genes

  • Definition: A gene that normally controls and suppresses cell proliferation. Loss of function or inactivation leads to an increased risk of developing cancer. Both alleles need to be mutated in order for complete loss of function of the gene.
Gene Chromosome Gene product Associated malignancy
  • 17p13.1
  • Most human cancers
  • LiFraumeni syndrome
  • 13q14.2
  • 9p21.3

APC gene
  • 5q22.2
  • A protein that prevents unregulated cell proliferation by inhibiting β-catenin synthesis
  • 17q21.31
  • DNA repair protein
  • 13q13.1
  • DNA repair protein
MMR gene family
  • Varies depending on the mutated protein+
  • 18q21.2

  • Transmembrane receptor involved in cell apoptosis
  • 18q21.2
  • 11q13.1
  • 17q11.2

  • 22q12.2

  • Merlin (schwannomin)
  • 9q34.13
  • 16p13.3
  • 3p25.3
  • 11p13
  • 11p15.5


Chemical carcinogens

Substance Occurrence Malignancy
Benzene, Benzol
  • Gasoline
  • Cigarette smoke
Vinyl chloride
  • Cured meat, fish, bacon
Aromatic amines (β-Naphthylamine)
  • Rubber
  • Insulation material (formerly used in construction and shipbuilding)
Wood dust
  • Woodworking (e.g., sawing, drilling, sanding)
  • Alcoholic beverages
Alkylating agents
Cigarette smoke
  • Accumulates in basements, and byproduct of uranium decay
  • Stored nuts and grains
  • Contaminated groundwater (esp. in developing countries)
  • Pesticides, herbicides
  • Metal smelting


Type Occurrence Malignacy
Nonionizing radiation
  • UV-B
Ionizing radiation

Oncogenic infections

Infective agent Associated malignancies
DNA viruses
HPV 16
HPV 18
RNA viruses
Nonviral pathogens
Schistosoma haematobium
Clonorchis sinensis (Chinese liver fluke)
H. pylori

Grading and staging

Tumor grading

  • Definition: Process of classifying tumors based on their histological appearance (degree of differentiation).
  • Indicators of poor differentiation
    • High-proliferation index
    • Presence of nucleoli
    • Giant cells with multiple nuclei
    • Hyperchromasia and heterogenous chromatin distribution
    • Abnormal shape of cell or nucleus (nuclear atypia, enlarged nucleoli)
    • Different cell polarity
    • Different orientation of nuclei belonging to the same group of cells
    • Increase in mitotic figures
  • 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 Moderate differentiation (intermediate grade)
G3 Poor differentiation (high grade)
G4 Undifferentiated/anaplastic (high grade)
GX Differentiation cannot be assessed

Cancer-specific grading systems

Tumor staging

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

Staging systems

  • TNM and AJCC systems are most commonly used

TNM classification

  • T: size or direct extent of the primary tumor
    • Tcis: Carcinoma in situ (no basement membrane penetration - no infiltration of submucosa)
    • T1-4 based on the size and/or extent of the primary tumor
      • T4 refers to infiltration of neighboring organs
  • N: Involvement of regional lymph nodes
  • M: Presence of distant metastasis
  • By adding a "C" to any category, it's 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's 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

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



Most carcinomas spread lymphatically. However, renal cell carcinoma, follicular thyroid carcinoma, hepatocellular carcinoma, choriocarcinoma primarily spread hematogenously!

Mechanisms of Metastasis

Common sites for cancer metastasis

Organ with metastasis Primary tumor located in

Generally, tumors in the brain (approximately 50%) and in the bone are most often metastatic rather than primary tumors!


Cancer anorexia-cachexia syndrome

  • Definition: A syndrome characterized by progressive wasting of skeletal muscle mass with or without loss of body fat that occurs in patients with advanced cancer.
  • Pathophysiology
  • Clinical features: weight loss, poor appetite, ↓ adipose tissue, muscle wasting, fatigue
  • Diagnosis: no formal diagnostic criteria available, but some features for diagnosis include
  • Treatment
  • Prognosis: poor prognostic indicator


Antineoplastic therapy


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 the patient's wishes when choosing a treatment option.

Treatment evaluation

Assessing resection

Resection margin Definition Examined by
  • Complete removal: resection margins are macro- and microscopically free of tumor tissue
  • Microscopically visible tumor tissue in resection margins
  • Macroscopically visible tumor tissue remains
    • Size/extent of residual tumor tissue is indicated in operative report

Assessing response

Complete response


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

Partial response


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


Increase of all lesions/tumor volume