Neoplasia

Chapter 8 Neoplasia



I. Nomenclature

A. Benign tumors

1. Suffix “oma” generally indicates a benign tumor.



Benign tumors: epithelial or connective tissue origin


2. Benign tumors of epithelial origin

a. Arise from ectoderm or endoderm



Epithelial tissue origin: ectoderm, endoderm


b. Example—tubular adenoma (adenomatous polyp) arising from glands in the colon (Fig. 8-1A; see Fig. 17-37)


3. Benign tumors of connective tissue origin arise from mesoderm.

image

8-1: A, Tubular adenoma (adenomatous polyp) of the colon. Note the fibrovascular stalk (arrow) lined by normal colonic mucosa and a branching head surfaced by dysplastic (blue-staining) epithelial glands. B, Lipoma showing a well-circumscribed yellow tumor. C, Cystic teratoma of the ovary, showing the cystic nature of the tumor. Hair is present, and a tooth is visible (arrow). D, Squamous cell carcinoma. The many well-differentiated foci of eosinophilic-staining neoplastic cells produce keratin in layers (keratin pearls). E, Adenocarcinoma. Irregular glands infiltrate the stroma. The nuclei lining the gland lumens are cuboidal and contain nuclei with hyperchromatic nuclear chromatin. Many of the gland lumens contain secretory material (arrow). F, Osteogenic sarcoma of the distal femur. The light-colored mass of tumor in the metaphysis abuts the epiphyseal plate (arrow) and has spread laterally out through the cortex and into the surrounding tissue.


(A from Kumar V, Fausto N, Abbas A: Robbins and Cotran’s Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 860, Fig. 17-57A; B and C from Damjanov I: Pathology for the Health-Related Professions, 2nd ed. Philadelphia, WB Saunders, 2000, pp 77, 79, Figs. 4-7, 4-11, respectively; D from Klatt E: Robbins and Cotran’s Atlas of Pathology. Philadelphia, WB Saunders, 2006, p 302, Fig. 13-35; E and F from Damjanov I, Linder J: Pathology: A Color Atlas. St. Louis, Mosby, 2000, pp 139, 369, Figs. 7-59, 17-35B, respectively.)



Connective tissue origin: mesoderm


• Example—lipoma from adipose (Fig. 8-1B)

4. Tumors that are usually benign

a. Mixed tumors

(1) Neoplastic cells have two different morphologic patterns but derive from the same germ cell layer.

(2) Example—pleomorphic adenoma of the parotid gland

b. Teratomas

(1) Tumors that derive from more than one germ cell layer



Teratoma: derives from ectoderm, endoderm, mesoderm


• Contain tissue derived from ectoderm, endoderm, and mesoderm (Fig. 8-1C)

(2) Sites

• Ovaries, testes, anterior mediastinum, and pineal gland

B. Malignant tumors (cancer)

1. Carcinomas

a. Derive from epithelial tissue—squamous, glandular, transitional



Carcinomas: derive from squamous, glandular (adenocarcinoma), transitional epithelium


b. Sites of squamous cell carcinoma (Fig. 8-1D)

• Oropharynx, larynx, upper/middle esophagus, lung, cervix, skin

c. Sites of adenocarcinoma (glandular epithelium; Fig. 8-1E)

• Lung, distal esophagus to rectum, pancreas, liver, breast, endometrium, ovaries, kidneys, prostate

d. Sites of transitional cell carcinoma

• Urinary bladder, ureter, renal pelvis

2. Sarcomas

a. Derive from connective tissue



Sarcomas: derive from connective tissue


b. Example—osteogenic sarcoma in bone (Fig. 8-1F)

C. Tumor-like conditions

1. Hamartoma

a. Non-neoplastic overgrowth of disorganized tissue indigenous to a particular site



Hamartoma: non-neoplastic overgrowth of tissue


b. Examples—bronchial hamartoma (contains cartilage), Peutz-Jeghers polyp

2. Choristoma (heterotopic rest)

a. Non-neoplastic normal tissue in a foreign location



Choristoma: normal tissue where it should not be


b. Examples—pancreatic tissue in the stomach wall; parietal cells in Meckel diverticulum

II. Properties of Benign and Malignant Tumors

A. Components of benign and malignant tumors

1. Parenchyma


Parenchyma: neoplastic component


• Neoplastic component that determines the tumor’s biologic behavior

2. Stroma

a. Non-neoplastic supportive tissue

b. Most infiltrating carcinomas induce production of a dense, fibrous stroma

B. Differentiation

1. Benign tumors

• Usually well differentiated (resemble parent tissue)

2. Malignant tumors

a. Well differentiated or low grade



Grade of cancer: does the cancer resemble its parent tissue or not?


(1) Resemble parent tissue

(2) Example—produce keratin pearls or glandular lumens with secretions (see Fig. 8-1D and E)

b. Poorly differentiated, high grade, or anaplastic

• No differentiating features

c. Intermediate grade

• Features are between low- and high-grade cancer.

C. Nuclear features

1. Benign tumors

a. Nuclear/cytoplasmic ratio is close to normal.

b. Mitoses have normal mitotic spindles.



Malignant tumors: ↑ nuclear/cytoplasmic ratio; abnormal mitotic spindles


2. Malignant tumors

a. Nuclear/cytoplasmic ratio is increased, and nucleoli are prominent.

b. Mitoses have normal and atypical mitotic spindles.

D. Growth rate

1. Benign tumors usually have a slow growth rate.

2. Malignant tumors have a variable growth rate.

a. Correlates with the degree of differentiation

b. Anaplastic (high-grade) cancers have an increased growth rate.

3. Thirty doubling times are required for a tumor to be clinically evident.



Malignant tumors: 30 doubling times before detected


• Equivalent to 109 cells, 1 g of tissue, volume of 1 mL

4. Malignant cells in the cell cycle are primarily targeted by chemotherapy.

a. DNA is exposed and is susceptible to damage by drugs and radiation causing the cells to die.

b. Loss of the cells causes more cancer cells to go into the cell cycle; hence debulking the tumor as these cells also get destroyed.

E. Monoclonality

1. Benign and malignant tumors derive from a single precursor cell.

2. Non-neoplastic proliferations derive from multiple cells (polyclonal).



The monoclonal origin of neoplasms has been shown by studying glucose-6-phosphate dehydrogenase (G6PD) isoenzymes A and B in selected neoplasms (e.g., leiomyoma of the uterus). All the neoplastic smooth muscle cells in uterine leiomyomas have either the A or the B G6PD isoenzyme. Non-neoplastic smooth muscle proliferations in the uterus (e.g., pregnant uterus) have some cells with the A isoenzyme and others with the B isoenzyme, indicating their polyclonal origin.




Benign and malignant tumors: monoclonal


F. Telomerase activity

1. Telomerase function

a. Preserves length of telomeres

• Sequences of nontranscribed DNA at the ends of chromosomes

b. Prevents gene loss after multiple cell divisions

2. Benign tumors have normal telomerase activity.



Malignant tumors: upregulation telomerase activity


3. Malignant tumors have upregulation of telomerase activity.

• They do not lose genetic material after multiple cell divisions.

G. Local invasion

1. Benign tumors

a. They do not invade.

b. They are usually enclosed by a fibrous capsule.

• Exception—uterine leiomyomas do not have a fibrous tissue capsule.

2. Malignant tumors invade tissue.



Basal cell carcinomas of the skin: invade tissue but do not metastasize


3. Some tissues resist invasion.

• Examples—mature cartilage, elastic tissue in arteries

4. Sequence of invasion by malignant tumors



Invasion: second most important criterion for malignancy


a. Loss of intercellular adherence

• E-cadherin (intercellular adhesion agent) is not produced.

b. Cell invasion occurs.

(1) Cell receptors attach to laminin (glycoprotein in the basement membrane).



Resist invasion: cartilage, elastic tissue


(2) Cells release type IV collagenase (metalloproteinase containing zinc).

• Dissolves the basement membrane

(3) Cell receptors attach to fibronectin in the extracellular matrix.



Loss of intercellular adherence → cell invasion


(4) Cells produce cytokines (stimulate locomotion) and proteases (dissolve connective tissue).

(5) Cells produce factors that stimulate angiogenesis.

• Secrete vascular endothelial growth factor and basic fibroblast growth factor

H. Metastasis

1. Benign tumors do not metastasize.

2. Malignant tumors metastasize.

3. Pathways of dissemination

a. Lymphatic spread to lymph nodes

• Usual mechanism of dissemination of carcinomas



Extranodal metastasis (e.g., liver) has greater prognostic significance than nodal metastasis.




Regional lymph nodes are the first line of defense against the spread of a carcinoma. However, if the nodal architecture is destroyed, malignant cells enter the efferent lymphatics, which empty into the bloodstream. In the bloodstream, malignant cells metastasize to distant organ sites (e.g., liver, lungs, bone).


b. Hematogenous spread


Lymph nodes: first line of defense in carcinomas


(1) Usual mechanism of dissemination for sarcomas

(2) Cells entering the portal vein metastasize to the liver.

(3) Cells entering the vena cava metastasize to the lungs.



Some carcinomas have both lymphatic and hematogenous spread. Renal cell carcinomas commonly invade the renal vein, where the tumor has the potential for extending into the vena cava to as far as the right side of the heart. Hepatocellular carcinomas invade the portal and hepatic veins. Tumor obstruction of either vein produces portal hypertension, splenomegaly, and ascites.


c. Seeding



Routes of metastasis: lymphatic, hematogenous, seeding of body cavities


• Malignant cells exfoliate from a surface and implant and invade tissue in a body cavity.

(1) Primary surface-derived ovarian cancers (e.g., serous cystadenocarcinoma) commonly seed the omentum.



Seeding: common with surface-derived ovarian cancers


(2) Peripherally located lung cancers commonly seed the parietal and visceral pleurae.

(3) Glioblastoma multiforme commonly seeds the cerebrospinal fluid causing spread to the brain and spinal cord.

4. Bone metastasis

a. Vertebral column

(1) Most common metastatic site in bone (Fig. 8-2A)

(2) Due to the Batson paravertebral venous plexus

image

8-2: A, Radionuclide scan. Radionuclide uptake is increased throughout the skeleton, with a very heavy uptake in the vertebral column. The patient had a primary breast cancer, which is the most common cancer metastatic to bone. B, Prostate cancer metastatic to the vertebral column. Multiple white foci of metastatic prostate cancer produce an osteoblastic response in the bone. C, Radiograph showing osteoblastic metastases. Note the increased density of bone in the lower lumbar vertebra and pelvic bone in metastatic prostate cancer. D, Radiograph showing osteolytic lesions. Note the radiolucent areas in the midshaft of the femur (arrow) in metastatic breast cancer. E, Metastasis to the liver. The liver contains multiple nodules that have a depressed central area (“umbilicated”) and stellate-shaped borders.


(A from Bouloux P: Self-Assessment Picture Tests: Medicine, Vol. 1. London, Mosby-Wolfe, 1997, p 70, Fig. 140; B from Kumar V, Fausto N, Abbas A: Robbins and Cotran’s Pathologic Basis of Disease, 7th ed. Philadelphia, WB Saunders, 2004, p 1052, Fig. 21-35; C from Bouloux P: Self-Assessment Picture Tests: Medicine, Vol. 3. London, Mosby-Wolfe, 1997, p 11, Fig. 21; D from Rosai J, Ackerman LV: Surgical Pathology, 9th ed. St. Louis, Mosby, 2004, p 2187, Fig. 24-92; E from Damjanov I: Pathology for the Health-Related Professions, 2nd ed. Philadelphia, WB Saunders, 2000, p 303, Fig. 11-18.)

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Jun 25, 2017 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Neoplasia

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