PA6.1-7 | Neoplasia — Glossary

Velvety, hyperpigmented thickening of skin in body folds (axilla, groin); a paraneoplastic sign most strongly associated with gastric carcinoma and other adenocarcinomas.

A mycotoxin produced by Aspergillus flavus that, after CYP3A4 activation, causes a specific G→T transversion at codon 249 of TP53, strongly associated with hepatocellular carcinoma in sub-Saharan Africa and Asia.

A serum tumour marker produced by hepatocellular carcinoma and non-seminomatous germ cell tumours; also elevated in hepatitis, cirrhosis, and normal pregnancy.

Lack of differentiation in a neoplasm, manifested by pleomorphism, abnormal nuclear features, atypical mitoses, and loss of polarity; hallmark of malignancy.

A structurally abnormal cell division (tripolar spindle, ring-form, asymmetric distribution of chromosomes) that never occurs in normal tissue and is specific for malignancy.

The thin extracellular matrix lamina separating epithelium from stroma; its breach by carcinoma cells marks the transition from in situ to invasive disease.

A valveless vertebral venous network connecting pelvic veins to vertebral veins, allowing retrograde haematogenous spread of prostate, breast, and thyroid carcinomas to vertebral bodies.

An anti-apoptotic protein on the outer mitochondrial membrane that prevents cytochrome-c release; overexpressed in follicular lymphoma via t(14;18) translocation.

Tumour suppressor genes encoding proteins essential for homologous recombination repair of DNA double-strand breaks; germline loss predisposes to hereditary breast and ovarian cancer.

A serum tumour marker elevated in ovarian carcinoma; also elevated in endometriosis, PID, and liver disease; used primarily for monitoring treatment response.

A complex metabolic syndrome in cancer characterised by anorexia, progressive muscle wasting, and fatigue, driven by cytokines (TNF-α, IL-1, IL-6) rather than simple caloric deprivation.

Adoptive immunotherapy in which a patient's T cells are genetically engineered to express a chimeric antigen receptor (CAR) targeting a specific tumour antigen (e.g., CD19 in B-cell malignancies).

A malignant neoplasm arising from epithelial cells (e.g., adenocarcinoma from glandular epithelium, squamous cell carcinoma from squamous epithelium).

A malignant transformation with full cytological features of carcinoma but no penetration through the basement membrane; fully curable by excision.

A serum tumour marker associated with colorectal, gastric, and pancreatic carcinomas; used for monitoring post-resection recurrence rather than screening.

A monoclonal antibody that blocks inhibitory checkpoint molecules (PD-1, PD-L1, CTLA-4) on T cells, releasing immune suppression and restoring anti-tumour killing.

A congenital rest of histologically normal tissue in an abnormal anatomical location (e.g., pancreatic tissue within the stomach wall).

The Darwinian process by which a single initiated cell accumulates progressive mutations, each conferring a growth advantage, giving rise to increasingly malignant subclones.

A laboratory test that identifies patients whose tumours harbour a specific molecular alteration, making them eligible for a paired targeted therapy (e.g., HER2 FISH for trastuzumab eligibility).

An intermediate filament protein expressed by epithelial cells; IHC positivity for cytokeratin identifies a tumour as a carcinoma (epithelial origin).

Excessive fibrous connective tissue (collagen) deposition stimulated by tumour cells within the stroma; gives carcinomas their characteristic hard texture.

The degree to which a neoplasm resembles its tissue of origin morphologically and functionally; quantified by grading (G1–G4).

Malignant proliferation of epithelial cells filling and distending breast ducts without breaking through the basement membrane; Grade 3 DCIS has high nuclear grade.

Secretion of a hormone by a tumour arising from tissue that does not normally produce that hormone (e.g., ACTH from small-cell lung carcinoma).

A cytogenetic technique using fluorescent DNA probes to detect chromosomal translocations, gene amplifications, or deletions in tumour cells (e.g., HER2 amplification, BCR-ABL).

A diagnostic technique using a fine needle to aspirate cells from a lesion for cytological examination; provides cellular morphology but not tissue architecture.

An intraoperative technique in which tissue is snap-frozen and rapidly sectioned for H&E staining, providing a diagnosis within ~20 minutes to guide surgical decisions.

A malignant surface tumour with cauliflower-like exophytic projections resulting from outgrowth of the blood supply, typically seen in advanced surface carcinomas.

Histological assessment of tumour differentiation — how closely the tumour resembles its tissue of origin; Grade 1 (well-differentiated) to Grade 3/4 (poorly differentiated/anaplastic).

The proportion of tumour cells actively cycling at any given time; a better predictor of tumour aggressiveness than mitotic count alone.

Ten biological capabilities acquired during multistep tumour development (Hanahan & Weinberg) that collectively enable a cell to become malignant.

A disorganised but non-neoplastic overgrowth of normal tissue elements indigenous to a given organ (e.g., pulmonary hamartoma); not a true tumour.

Periosteal new bone formation in long bones + digital clubbing, a paraneoplastic finding most commonly associated with bronchogenic carcinoma.

Oncoproteins of high-risk HPV (types 16, 18): E6 targets p53 for proteasomal degradation; E7 binds and inactivates pRB, together disabling the two cardinal TSG pathways.

Dark staining of nuclei due to increased chromatin content or coarse clumping; a nuclear feature of anaplasia.

The continuous process by which the immune system (CTLs, NK cells) recognises and destroys nascent tumour cells before they establish clinically apparent neoplasms.

A laboratory technique using specific antibodies applied to tissue sections to detect antigens in situ, identifying tumour lineage, receptor status, and predictive markers.

The first irreversible step in chemical carcinogenesis in which a carcinogen induces a heritable DNA mutation in a stem cell, rendering it 'initiated'.

Carcinogenesis caused by integration of viral DNA near a proto-oncogene or tumour suppressor, altering its expression; mechanism of HBV in hepatocellular carcinoma.

The most common form of breast carcinoma; defined by BM breach and stromal invasion; graded by Scarff–Bloom–Richardson criteria and staged by TNM.

Bilateral ovarian metastases classically from gastric (or occasionally colonic) carcinoma; the ovaries are involved via transcoelomic or haematogenous route and show signet-ring cells on histology.

A pan-haematopoietic surface marker; IHC positivity establishes lymphoid origin of a tumour, distinguishing lymphoma from carcinoma and melanoma.

Malignant tumour of smooth muscle characterised grossly by necrosis and haemorrhage and microscopically by atypia, high mitotic count, and coagulative necrosis.

The presence of cohesive carcinoma cell clusters within endothelium-lined lymphatic or vascular spaces, the direct anatomical correlate of metastatic dissemination.

An autosomal dominant hereditary cancer syndrome caused by germline mutations in MMR genes (MLH1, MSH2, MSH6, PMS2), predisposing to colorectal, endometrial, and other cancers.

Dissemination of tumour cells from the primary site to establish secondary growths at a distant site; the most reliable indicator of malignancy.

Small non-coding RNA (~22 nt) that post-transcriptionally silences target mRNAs; oncomiRs suppress TSGs, while tumour-suppressor miRNAs target oncoproteins; dysregulation is a recognised carcinogenic mechanism.

A mutational signature caused by defective DNA mismatch repair, in which short tandem repeat sequences throughout the genome accumulate insertion/deletion errors; a hallmark of Lynch syndrome tumours.

The sequential acquisition of multiple driver mutations over years to decades required to convert a normal cell into a fully malignant one, as exemplified by the Fearon–Vogelstein colorectal sequence.

Nuclear-to-cytoplasmic ratio; increased in malignant cells (approaching 1:1) compared to normal cells (1:4 to 1:6).

An abnormal mass of tissue exhibiting autonomous, uncoordinated, persistent growth that exceeds and is unrelated to normal tissue growth (Willis, 1952).

A DNA repair pathway that recognises and removes bulky DNA adducts including UV-induced pyrimidine dimers; defective in xeroderma pigmentosum.

A mutated or amplified proto-oncogene whose product is constitutively active, driving uncontrolled cell proliferation; acts in a dominant gain-of-function manner.

A clinical effect caused by tumour-derived products (hormones, cytokines, antibodies) acting at a site remote from the tumour or its metastases, not due to direct invasion.

The proliferating neoplastic cells of a tumour that determine its biological behaviour and classification.

A checkpoint molecule up-regulated on many tumour cells; binding to PD-1 on T cells delivers an inhibitory signal causing T-cell exhaustion — the primary target of checkpoint inhibitor immunotherapy.

Extension of tumour cells along or around nerve sheaths, a key adverse prognostic and staging feature in pancreatic, prostate, and head-and-neck carcinomas.

Marked variation in cell and nuclear size and shape within a tumour, a key feature of anaplasia.

A chemical precursor that requires metabolic activation by cytochrome P450 enzymes to form the ultimate carcinogen, the reactive electrophile that attacks DNA.

The reversible phase following initiation in which a promoter agent (not itself mutagenic) causes clonal expansion of the initiated cell by stimulating proliferation.

A normal cellular gene encoding proteins that promote cell growth, differentiation, or survival; becomes an oncogene when mutated or overexpressed.

A serine protease produced by prostate epithelium; organ-specific (not cancer-specific); elevated in prostate cancer, BPH, and prostatitis; used for prostate cancer monitoring.

Parathyroid Hormone-related Protein — secreted by squamous cell carcinomas (particularly lung) causing humoral hypercalcaemia of malignancy without bone metastases.

A UV-induced covalent bond between adjacent thymine (or cytosine) residues on the same DNA strand, forming a bulky adduct that blocks replication and causes C→T signature mutations if unrepaired.

A membrane-bound GTPase signal transducer; point mutations (e.g., Gly12Val) prevent GTP hydrolysis, locking it in the constitutively active GTP-bound ON state.

Clear spaces around tumour nests in histologic sections created by tissue processing shrinkage, mimicking LVI; distinguished from true LVI by absent endothelial lining.

A malignant neoplasm arising from mesenchymal (connective tissue) cells such as fibroblasts, lipocytes, smooth muscle, striated muscle, or bone.

Describing a carcinoma (classically breast) with abundant desmoplastic stroma that renders the cut surface hard and gritty; from Greek 'skirrhos' (hard tumour).

Paget's (1889) concept that metastatic spread is not random — tumour cells ('seeds') preferentially grow in specific organ microenvironments ('soil') that are permissive for their survival and proliferation.

The first lymph node encountered in the regional drainage of a tumour; biopsy of this node determines whether lymphatic metastasis has occurred (clinically applied in breast cancer and melanoma).

Clinical/pathological assessment of the anatomical extent of disease using the TNM system (T=primary tumour size/invasion, N=regional nodes, M=distant metastasis); Stage I–IV.

The non-neoplastic supportive framework of a tumour, comprising fibroblasts, blood vessels, and inflammatory cells induced by the tumour from host tissue.

A situation in which loss of two genes/pathways is lethal to the cell, but loss of either alone is tolerated; exploited therapeutically (e.g., PARP inhibitors in BRCA-deficient tumours).

An antigen over-expressed or aberrantly expressed on tumour cells but also present at lower levels on normal cells (e.g., AFP, PSA, CEA, HER2).

A germ cell tumour containing tissues derived from all three embryonic germ layers; mature teratomas are benign (ovary), immature teratomas are malignant, and testicular teratomas are malignant regardless of maturity.

The international tumour staging framework (AJCC/UICC) classifying cancers by primary Tumour extent (T), regional Node involvement (N), and distant Metastasis (M), grouping into Stages I–IV.

The most commonly mutated tumour suppressor gene in human cancer; p53 protein is a transcription factor that, when activated by DNA damage, induces cell-cycle arrest, DNA repair, or apoptosis — hence 'guardian of the genome'.

Metastasis via seeding of tumour cells across a body cavity (peritoneal, pleural, pericardial, or CSF); characteristic of ovarian carcinoma and medulloblastoma.

Recurrent thrombophlebitis migrating to different veins; a paraneoplastic phenomenon of mucin-secreting adenocarcinomas (especially pancreatic) due to tumour procoagulant factors.

An antigen present exclusively on tumour cells, absent from normal cells; usually arising from somatic mutations creating neo-antigens unique to that tumour.

An enlarged mononucleate or multinucleate cell with bizarre hyperchromatic nuclei arising from fusion or failed cytokinesis of anaplastic tumour cells.

A histologic classification (G1 well-differentiated to G4 undifferentiated) based on resemblance to normal tissue, mitotic activity, and degree of anaplasia.

An anatomical extent classification (I–IV) based on tumour size, local invasion, nodal involvement (N), and distant metastasis (M); distinct from grade.

A gene whose protein product restrains cell division, promotes apoptosis, or maintains genomic integrity; must lose both alleles to lose function (recessive at cell level).

Knudson's model stating that both alleles of a tumour suppressor gene must be inactivated for tumour development; in hereditary cancers the first hit is germline, the second is somatic.

Grade 4 tumour with no recognisable tissue architecture or lineage markers on routine H&E; requires immunohistochemistry for classification.

An enlarged left supraclavicular lymph node (Troisier's sign) representing metastasis from an intra-abdominal malignancy (classically gastric carcinoma) via the thoracic duct.

The tendency of cancer cells to rely on aerobic glycolysis (lactate production even in oxygen) rather than oxidative phosphorylation, providing biosynthetic intermediates for rapid growth.

A gross cut-surface appearance of interlacing smooth-muscle fascicles in leiomyoma; the archetypal benign pattern helping distinguish leiomyoma from leiomyosarcoma.

A rare autosomal recessive disorder of nucleotide excision repair in which UV-induced pyrimidine dimers cannot be removed, leading to ~1000-fold increased skin cancer risk and photosensitivity.