8.3 Types & Characteristics of Cancer: Benign vs. Malignant, Tumor Families, Spread & Precursors
Key Takeaways
Malignant neoplasms invade surrounding tissue and can metastasize; benign neoplasms grow locally, are usually encapsulated and well differentiated, and do not metastasize.
Registries code behavior as /0 benign, /1 uncertain or borderline, /2 in situ, or /3 malignant; /6 (metastatic site) and /9 (uncertain whether primary or metastatic) are not used in registry abstracts.
Cancer spreads by direct extension to adjacent tissue, through lymphatics to lymph nodes, through the bloodstream to distant organs, and by seeding across body cavities such as the peritoneum.
Oncogenes (such as KRAS and ERBB2/HER2) drive growth when activated, while tumor suppressor genes (such as TP53, RB1, APC and BRCA1/2) promote cancer when inactivated.
Precursor lesions such as colon adenomas, Barrett esophagus and MGUS are not reportable on their own, but they explain multiple primary and histology rules.
Why this topic matters
"Types and characteristics of cancer" is a Domain 3 knowledge area. It lets a registrar recognize a malignancy described in unfamiliar words, choose the right coding manual (solid tumor or hematopoietic), and understand why the staging and multiple primary rules work the way they do.
Benign versus malignant
| Characteristic | Benign neoplasm | Malignant neoplasm |
|---|---|---|
| Growth | Usually slow and expansive | Often rapid; invasive and infiltrating |
| Borders | Usually well circumscribed or encapsulated | Poorly defined; invades neighboring tissue |
| Differentiation | Well differentiated; resembles the tissue of origin | Ranges from well differentiated to anaplastic |
| Invasion of the basement membrane | No | Yes (in situ lesions have malignant cells that have not yet invaded) |
| Metastasis | Never | Possible, and the defining feature of malignancy |
| Recurrence after excision | Uncommon | Common |
Behavior codes (the fifth digit of the ICD-O morphology code) capture this spectrum: /0 benign, /1 uncertain whether benign or malignant (borderline or low malignant potential), /2 in situ (intraepithelial, noninvasive), and /3 malignant, primary site. ICD-O also has /6 (metastatic site) and /9 (uncertain whether primary or metastatic), but registries do not use them. A primary tumor is always coded /3 even when the only biopsy came from a metastasis.
Families of cancer by cell of origin
| Family | Origin | Examples |
|---|---|---|
| Carcinoma | Epithelium; about 80–90% of cancers | Squamous cell carcinoma, adenocarcinoma, urothelial carcinoma, neuroendocrine carcinoma |
| Sarcoma | Mesenchymal (connective) tissue | Osteosarcoma, leiomyosarcoma, liposarcoma, GIST |
| Lymphoma | Lymphocytes, usually in lymph nodes or lymphoid tissue | Hodgkin lymphoma, diffuse large B-cell lymphoma, follicular lymphoma |
| Leukemia | Blood-forming cells in the bone marrow | AML, ALL, CML, CLL |
| Plasma cell neoplasms | Plasma cells | Plasma cell myeloma, plasmacytoma |
| Melanoma | Melanocytes | Cutaneous, mucosal and uveal melanoma |
| Germ cell tumors | Germ cells | Seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, teratoma |
| CNS tumors | Glial and neuronal cells, meninges | Glioblastoma, astrocytoma, oligodendroglioma, meningioma |
| Embryonal tumors (-blastomas) | Immature precursor cells, mostly in children | Neuroblastoma, nephroblastoma (Wilms), retinoblastoma, medulloblastoma |
| Mixed tumors | More than one cell line | Adenosquamous carcinoma, carcinosarcoma, mixed germ cell tumor |
Hematopoietic and lymphoid neoplasms (ICD-O codes 9590–9993) follow the Hematopoietic Manual and Database. All other malignancies follow the Solid Tumor Rules.
How cancer develops
- Genetic damage accumulates in a cell line: from inherited (germline) mutations and from acquired (somatic) damage caused by carcinogens or random copying errors.
- Oncogenes are normal growth-promoting genes (proto-oncogenes) that become overactive through mutation, amplification or translocation. Examples are KRAS and NRAS (colorectal and lung cancer), ERBB2 (HER2) amplification (breast and gastric cancer), BCR::ABL1 (CML), and EGFR and ALK rearrangements (lung cancer).
- Tumor suppressor genes normally restrain growth or repair DNA. Cancer develops when both copies are lost. Examples are TP53, RB1 (retinoblastoma), APC (familial adenomatous polyposis) and BRCA1/BRCA2 (hereditary breast and ovarian cancer).
- DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2): their loss causes microsatellite instability (MSI-H/dMMR). When inherited, this is Lynch syndrome (colorectal, endometrial and other cancers).
- Carcinogenesis is often described in stages: initiation (DNA damage), promotion (clonal expansion) and progression (invasion and metastasis).
Major risk factors
- Tobacco, alcohol, obesity and inactivity, ultraviolet radiation, and ionizing radiation.
- Infections: HPV (cervical, oropharyngeal and anal cancer), hepatitis B and C (liver), Helicobacter pylori (stomach cancer and gastric MALT lymphoma), EBV (nasopharyngeal carcinoma and some lymphomas), HHV-8 (Kaposi sarcoma).
- Occupational and environmental exposures: asbestos (mesothelioma), benzene (leukemia), aromatic amines (bladder cancer).
- Inherited syndromes: Lynch, HBOC (BRCA1/2), FAP, Li-Fraumeni (TP53), von Hippel-Lindau, and the multiple endocrine neoplasias.
How cancer spreads
| Route | Mechanism | Registry relevance |
|---|---|---|
| Direct extension | Continuous growth into adjacent tissue or organs | Raises the T category; Summary Stage "regional by direct extension" |
| Lymphatic | Tumor cells travel to regional, then distant, lymph nodes | N category; distant nodes are M1 |
| Hematogenous (bloodstream) | Tumor cells enter blood vessels and seed distant organs | M1. GI cancers commonly spread to the liver through the portal vein; breast, lung and prostate cancers often go to bone; lung and breast cancers to the brain |
| Implantation (seeding) | Tumor cells shed across body cavities or along a biopsy or surgical tract | Peritoneal carcinomatosis in ovarian and gastric cancer; malignant effusions |
Tumor deposits, satellite nodules and in-transit metastases (in melanoma) are discontinuous spread through lymphatics. Staging systems assign them specifically; for example, melanoma satellites are counted as nodal disease in Summary Stage 2018.
Precursor and borderline lesions
| Lesion | Meaning | Registry status (CoC) |
|---|---|---|
| Colon adenoma with high-grade dysplasia (8210/2, 8211/2, 8261/2, 8263/2) | Precursor to adenocarcinoma | Not required by CoC for diagnoses on or after January 1, 2022; check state rules |
| Barrett esophagus | Metaplasia that predisposes to adenocarcinoma | Not reportable |
| CIN III / cervical carcinoma in situ, PIN III | Intraepithelial neoplasia | Not reportable |
| VIN III, VAIN III, AIN III | Intraepithelial neoplasia of the vulva, vagina and anus | Not required by CoC, but reportable to SEER and NPCR central registries |
| LCIS (8520/2) | Lobular carcinoma in situ of the breast | Not required by CoC; required by SEER and NPCR |
| MGUS | Monoclonal gammopathy that precedes myeloma | Not reportable |
| Borderline ovarian tumor (/1) | Low malignant potential | Not reportable |
(Reportability details are in Section 9.3.)
Grade versus stage
Grade describes how abnormal the cells look under the microscope, or their biology (for example, the Gleason Grade Group). Stage describes how far the tumor has spread in the body. A small tumor can be high grade, and a large tumor can be low grade. The two are recorded separately: grade in the Grade Clinical and Grade Pathological items, stage in AJCC and Summary Stage.
Which feature, when present, establishes that a neoplasm is malignant rather than benign?
A well-circumscribed border
Close resemblance to the tissue of origin
Slow growth over many years
Metastasis to a distant site
A patient's colon adenocarcinoma is found to have deficient mismatch repair (dMMR/MSI-H), and germline testing confirms an inherited MLH1 mutation. Which syndrome is present?
Familial adenomatous polyposis
Li-Fraumeni syndrome
Lynch syndrome
Hereditary breast and ovarian cancer syndrome
A 68-year-old with known colon adenocarcinoma is found to have multiple liver metastases. Which route of spread does this most typically represent?
Implantation along a biopsy tract
Direct extension through the bowel wall
Lymphatic spread to regional mesenteric nodes
Hematogenous spread through the portal venous system
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