7.1 about 22 minDeep Learning viewL7 p.2–3, 5–7

What a tumor is and what it is called

A neoplasm is a clone of cells that keeps growing after the stimulus is gone. Its name records two things: the tissue it imitates and whether it behaves benignly or malignantly.

Neoplasia: one clone, growing without a reason

L7 p.2

The lecture defines neoplasia as new tissue growth that is unregulated, irreversible and monoclonal. Each word separates it from the adaptations in Chapter 1. Hyperplasia and repair also add cells, but they answer a stimulus (a hormone, a wound) and stop when the stimulus stops, and they are built by many different cells dividing together: they are polyclonal. A neoplasm keeps growing when the stimulus is gone, because its cells carry mutations that switched growth on permanently, and all of its cells descend from one mother cell.

Teaching schematic

Normal tissue or hyperplasia

Each cell silenced one X at random, so both G6PD isoforms appear, about 1:1. Many cells are dividing: polyclonal.

Neoplasia

Every cell copies the X-inactivation of one mother cell, so only one isoform is found: monoclonal. The B-cell version is κ or λ light-chain restriction.

How clonality is proven with an X-linked marker. In a woman heterozygous for G6PD (or the androgen-receptor gene), each cell has silenced one X at random, so normal and hyperplastic tissue is a mosaic of both isoforms. A neoplasm descends from one cell and shows only one.L7 p.2

That is how clonality was first demonstrated. Glucose-6-phosphate dehydrogenase (G6PD) is encoded on the X chromosome. Early in female development each cell inactivates one X at random (lyonization), so in a woman who inherited two different G6PD isoforms, any normal or hyperplastic tissue contains both, roughly 1:1. A tumor from the same woman contains only one isoform, because all of its cells copy the X-inactivation pattern of their single ancestor. The androgen-receptor gene, also on the X, is used the same way today. For B cells there is a neater marker: each B cell commits to a κ or λ light chain. A reactive lymph node mixes both; a B-cell lymphoma shows only one (light-chain restriction).

Hyperplasia versus neoplasia

Hyperplasia (adaptation)

  • Driven by a stimulus (hormone, growth factor, injury)
  • Stops or regresses when the stimulus is removed
  • Polyclonal: both G6PD isoforms, κ and λ B cells
  • Normal maturation and architecture

Neoplasia

  • Growth continues without the stimulus (unregulated)
  • Irreversible: the change is in the cell's DNA
  • Monoclonal: one isoform, one light chain
  • Benign or malignant depending on how far the clone has escaped control
L7 p.2

Every tumor has two parts. The parenchyma is the neoplastic clone itself; it decides the tumor's name and behavior. The stroma is the host's supporting tissue: connective tissue, vessels and inflammatory cells, recruited by the tumor. Some carcinomas provoke abundant dense collagen, called desmoplasia; such tumors are stony hard (scirrhous), which is why an invasive breast or pancreatic carcinoma feels firm and gritty when cut.

Lecture slide

Lecture diagram: a row of normal cells, one transformed cell, and its expanding progeny forming a malignancy with subclones that all derive from one progenitor.
The lecture's diagram of the same idea over time: one transformed cell expands into a mass whose cells all descend from it. The colored segments are subclones, daughter populations that have picked up further mutations. A tumor is monoclonal in origin and still genetically heterogeneous, which is why parts of it can differ in growth, invasiveness and drug response.L7 p.2

Naming rules: -oma, carcinoma, sarcoma

L7 p.3, 5–6

A tumor's name answers two questions. Which tissue does it imitate? That is its lineage of differentiation. Benign or malignant? That is its behavior. A benign tumor usually takes the tissue name plus -oma (lipoma, adenoma, leiomyoma). A malignant tumor of epithelial origin is a carcinoma; a malignant tumor of mesenchymal (connective tissue, mesoderm) origin is a sarcoma. Carcinomas are named by the epithelium they imitate: squamous, glandular (adeno-) or transitional (urothelial).

Lineage plus behavior gives the nameL7 p.3, 5

  • Glandular epithelium

    Benign
    Adenoma
    Malignant
    Adenocarcinoma

  • Surface epithelium in fronds

    Benign
    Papilloma
    Malignant
    Papillary carcinoma

  • Squamous epithelium

    Benign
    Squamous papilloma
    Malignant
    Squamous cell carcinoma

  • Urothelium (transitional epithelium)

    Benign
    Urothelial papilloma
    Malignant
    Urothelial (transitional cell) carcinoma

  • Fat

    Benign
    Lipoma
    Malignant
    Liposarcoma

  • Smooth muscle

    Benign
    Leiomyoma
    Malignant
    Leiomyosarcoma

  • Skeletal muscle

    Benign
    Rhabdomyoma
    Malignant
    Rhabdomyosarcoma

  • Bone

    Benign
    Osteoma
    Malignant
    Osteosarcoma

  • Melanocytes

    Benign
    Nevus (mole)
    Malignant
    Melanoma

  • Lymphocytes

    Benign
    No benign counterpart
    Malignant
    Lymphoma / leukemia

Lecture image

Three panels: soft subcutaneous lumps on a back; a yellow, lobulated, encapsulated fatty mass; and a micrograph of mature fat cells.
Lipoma, a benign mesenchymal tumor: soft subcutaneous lumps on the back, a yellow, lobulated mass with a thin capsule, and mature fat cells under the microscope that look almost exactly like normal fat. Benign tumors resemble their tissue of origin.L7 p.5

Lecture image

Bisected uterus with two round, sharply demarcated, firm white-tan whorled nodules in the wall.
Leiomyoma of the uterus: sharply demarcated, firm, white, whorled nodules in the myometrium. The tumor imitates smooth muscle and does not invade. As the lecture notes, a uterine leiomyoma is well circumscribed even though it has no true fibrous capsule.L7 p.6

Lecture image

Longitudinally cut distal femur: a tan, gritty tumor fills the metaphysis, destroys the cortex and pushes into the surrounding soft tissue (arrow).
Osteosarcoma of the distal femur, a malignant mesenchymal tumor: a tan, gritty, bone-forming mass fills the metaphysis, destroys the cortex and extends into soft tissue (arrow). Compare its ragged edge with the smooth border of the leiomyoma.L7 p.6

The lineage also predicts behavior. Carcinomas usually spread first through lymphatics to regional nodes; sarcomas usually spread through the blood (section 7.3). The lecture adds that about 40% of sarcomas arise in the lower extremity; osteosarcoma (bone) and rhabdomyosarcoma (skeletal muscle) are its examples.

Reading lineage under the microscope

L7 p.3, 6

A tumor betrays its lineage by what its cells try to make. Squamous cells make keratin; glandular cells make glands and mucin; mesenchymal cells make spindle-shaped cells and their matrix (osteoid in osteosarcoma, cartilage in chondrosarcoma). The better differentiated the tumor, the more clearly it still makes these products.

Lecture image

Micrograph of squamous cell carcinoma: nests of large pink squamous cells, several with concentric whorls of keratin (keratin pearls), separated by stroma with lymphocytes.
Squamous cell carcinoma: nests of large squamous cells in the stroma. At their centers the cells have made concentric layers of keratin (asterisk), the keratin pearls that stain bright pink with H&E. Keratin production marks squamous differentiation.L7 p.6

Lecture image

Micrograph of adenocarcinoma: crowded, irregular glands lined by tall columnar cells with elongated dark nuclei; rounder crypts rich in goblet cells at the right.
Adenocarcinoma: crowded, irregular glands lined by tall columnar cells with elongated, dark, stacked nuclei. The goblet-cell-rich crypts at the right are closer to normal colonic mucosa. Gland formation marks glandular differentiation.L7 p.6

What the cells make tells you the lineageL7 p.3, 6

  • Keratin pearls, intercellular bridges

    Lineage
    Squamous epithelium
    Example
    Squamous cell carcinoma of lung, cervix, esophagus, skin

  • Glands, mucin in the lumen

    Lineage
    Glandular epithelium
    Example
    Adenocarcinoma of colon, stomach, pancreas, lung

  • Spindle cells with osteoid

    Lineage
    Mesenchyme (bone)
    Example
    Osteosarcoma

  • Sheets of discohesive round cells

    Lineage
    Lymphoid (or other small round cell tumors)
    Example
    Lymphoma

Tumor-like masses: hamartoma, choristoma, teratoma

L7 p.7

Not every lump is a neoplasm in the lecture's sense. Two tumor-like conditions are made of mature tissue that is not growing autonomously, and the question that separates them is simple: is the tissue native to that site?

Hamartoma

  • Disorganized overgrowth of tissue that belongs at that site
  • Pulmonary hamartoma: cartilage, fat, fibrous tissue and bronchial epithelium in a lung 'coin lesion'
  • Peutz–Jeghers polyp: native glands and smooth muscle of the gut, arranged chaotically

Choristoma (heterotopic rest)

  • Normal tissue in a foreign place
  • Pancreatic tissue in the wall of the stomach
  • Brain tissue in the nasal cavity; functioning thyroid tissue in the liver

Teratoma (a true neoplasm)

  • Arises from totipotent germ cells
  • Contains tissues of more than one germ layer (skin, hair, teeth, neural tissue, gut)
  • Mature cystic teratoma of the ovary (dermoid) is benign; immature teratomas and most postpubertal testicular teratomas are malignant
L7 p.7

Lecture image

Cut surface of a well-circumscribed, glistening white nodule with islands that look like cartilage: a pulmonary hamartoma.
Pulmonary hamartoma: a well-circumscribed, glistening white nodule whose bulk is cartilage, with clefts of fat and connective tissue. Every component is native to the bronchial wall; only the arrangement is wrong.L7 p.7

Core activity · Almost Twins

Almost Twins

Two look-alikes side by side. Decide what they share, then pick the clue that separates them and say why it works.

Look-alike A

Hamartoma

Lungcartilage, fat, bronchial glands: all native to lung
A nodule in the lung (schematic).
  • Made of mature, cytologically normal tissue
  • The tissue belongs at this site (cartilage, fat, bronchial glands in lung); only its arrangement is disorganized
  • Forms a discrete, well-circumscribed mass
  • Pulmonary 'coin lesion'; the polyps of Peutz–Jeghers syndrome

Step 1 · What they share

What do they share?

Select every feature that both show.

Peutz–Jeghers syndrome

L7 p.7

Peutz–Jeghers syndrome is an autosomal dominant disorder (germline mutation of the STK11/LKB1 tumor-suppressor gene) with two visible features: hamartomatous polyps throughout the gastrointestinal tract, most numerous in the small intestine, and hyperpigmented macules on the lips, buccal mucosa, hands and genitalia. The polyps themselves are not premalignant in the usual sense, but they can bleed or lead an intussusception, and patients carry a markedly increased risk of cancers of the colon, stomach, small bowel, pancreas and breast.

Lecture image

Open mouth with multiple small dark-brown macules on the lips and buccal mucosa.
Peutz–Jeghers syndrome: dark-brown macules on the lips and buccal mucosa. Freckles do not occur inside the mouth, so oral pigmentation is the visible clue to the polyps.L7 p.7

Knowledge check · 7.1

Answer, read why, and try again whenever you like. Answers are kept in both study modes.

0 of 6 correct
  1. Q1Naming a benign mesenchymal tumorCh. VII cases p.8L7 p.4, 6

    A 45-year-old woman has abdominal pain and heavy vaginal bleeding. A hysterectomy shows a benign tumor of the uterus derived from smooth muscle cells.

    What is the appropriate diagnosis?

  2. Q2Lineage from morphology: glandsL7 p.3, 6

    A 67-year-old man has a colonic mass that, on resection, has grown into the muscular wall of the bowel. A section of the tumor is shown.

    Micrograph: irregular, back-to-back glands lined by crowded tall columnar cells with dark elongated nuclei.

    Which term fits this tumor?

  3. Q3Hamartoma vs choristomaL7 p.7

    Endoscopy for dyspepsia in a 38-year-old woman finds a 1-cm smooth submucosal nodule in the gastric antrum. Biopsy shows normal pancreatic acini and ducts with no atypia.

    What is the best term for this nodule?

  4. Q4Clonality by light-chain restrictionL7 p.2

    A 59-year-old woman has painless, enlarging cervical lymph nodes. In an excised node, flow cytometry shows that 97% of the B cells express λ light chain and almost none express κ.

    What does this result indicate?

  5. Q5Peutz–Jeghers syndromeL7 p.7

    A 16-year-old boy has colicky abdominal pain from an intussusception. The lead point is a small-bowel polyp made of disorganized but normal-looking glands and branching smooth muscle. He has dark macules on his lips and buccal mucosa; his father had similar spots.

    Open mouth with multiple small dark-brown macules on the lips and buccal mucosa.

    Which statement about his condition is correct?

  6. Q6Exceptions to the -oma ruleL7 p.3

    Which of these tumors is malignant even though its name ends in -oma?

Chapter startNext7.2 Dysplasia and invasion