Pathology Test 2 Review
Pathology Chapter 6 Review: Neoplasia
1. Terminology
Knudson’s Two Hit Hypothesis: Both alleles of a tumor suppressor gene must be mutated for loss of inhibitory function. A classic example of this is Retinoblastoma protein (RB) where both of the normal alleles of the RB locus must be inactivated (two hits) for the development of retinoblastoma.
Neoplasia: It literally means “new growth”. It is a loss of responsiveness to normal growth controls.
Tumor: Swelling and often used to mean neoplasm. All tumors, benign and malignant, have two basic components: Parenchyma (made up of neoplastic cells) and non-neoplastic stroma (the connective tissue and blood vessels which supports it)
Oncology: The study of tumors
Benign Tumor: A localized mass that does not spread to other sites, grows slowly, and is amenable to local surgical removal. Benign neoplasms are composed of well-differentiated cells that closely resemble their normal counterparts. Mitoses are extremely scant in number and are of normal configuration.
Malignant Tumor:
o Collectively referred to as cancers
o In terms of a neoplasm, it implies that the lesion can invade and destroy adjacent structures and spread to distant sites (metastasis) and potentially causing death
Cancer:
o The book basically says that cancer is a malignant tumor (so see above J)
Metastasis:
o Connotes the development of secondary implants (metastases) discontinuous with the primary tumor, possibly in remote tissues
o The properties of invasiveness and, even more so, metastasis more unequivocally identify a neoplasm as malignant than any of the other attributes
Adenoma:
o Benign epithelial neoplasms producing gland patterns and to neoplasms derived from glands but not necessarily exhibiting gland patterns
Chondroma:
o A benign cartilaginous tumor
Papilloma- benign, epithelial neoplasms, growing on any surface that produce microscopic or macroscopic finger-like fronds. (See fig. 6-1)
Fibroma- a benign tumor arising in fibrous tissue.
Polyp- a mass that projects above a mucosal surface to form a macroscopically visible structure. Generally used to describe benign tumors but sometimes used with malignant tumors. Especially in the colon, the term is applied to non-neoplastic growths that form polypoid masses.
Sarcoma- malignant neoplasm arising in mesenchymal tissues. It is designated by its histogenesis. Ex. fibrosarcoma, chondrosarcoma
Carcinoma- malignant neoplasm derived from epithelial tissue. Ex. squamous cell carcinoma. SN: Epithelia can be derived from all 3 germ layers so mesoderm can give rise to both carcinomas (epithelial) and sarcomas (mesenchymal).
Adenocarcinoma: a subdivision of carcinoma; denotes a lesion in which the neoplastic
epithelium cells begin to grow in gland patterns (not new glands)
Differentiation: refers to the extent to which parenchymal cells resemble their normal
forebears both in morphology and function.
Teratoma: contains recognizable mature or immature cells or tissues representative of
more than one germ-cell layer and sometimes all 3; originates from
totipotential cells such as those present in the ovary/testis; have the capacity
to differentiate into any of the cell types found in the adult body (why it is
possible to see bone, epithelial, muscle, teeth, etc strange places;
A well differentiated teratoma is BENIGN
A less well differentiated teratoma is MALIGNANT
Mesothelioma: rare neoplasm of mesothelial cells, usually arising in the parietal
or visceral pleura (although can also occur in the peritoneum and
pericardium)-related to occupational exposure to asbestos in the air
Leiomyoma: benign tumor found in areas of smooth muscle; often associated with the
myometrium of the uterine wall
Rhabdomyosarcoma – a malignant mesenchymal neoplasm that exhibits skeletal muscle differentiation. Has peak incidence in first decade of life and is the most common form of soft tissue sarcoma in the pediatric patient.
Osteogenic sarcoma (Osteosarcoma) – malignant mesenchymal neoplasm in which the neoplastic cells produce osteiod. Excluding multiple myeloma osteosarcoma is most common primary malignant tumor of bone. Two types:
Primary forms: arise de novo. These conventional osteosarcomas occur most often in the second decade of life and the most common site of origin is around the knee, the distal femur, and the tibia.
Secondary forms: usually arise as a complication of a known underlying process, like Paget disease of bone or a history of radiation exposure.
Melanoma – a malignant tumor of melanocytes or the nevus-type cells. Tend to occur on sun-exposed skin, although other less common sites include: the oral and anogenital mucosal surfaces, the esophagus, the meninges, and the eye.
Seminoma – a malignant testicular tumor arising from the germ cell lines. Approximately 5% of the time they arise from Sertoli or Leydig cells (although rarely) and these rare types are benign.
Hamartoma – an excessive but focal overgrowth of cells and tissues native to the organ in which it occurs. The cellular elements are mature and identical to those found in the remainder of the organ, but they do not reproduce the normal architecture of the surrounding tissues. Ex/ may see mass of mature but disorganized hepatic cells, blood vessels, and bile ducts in the liver.
Lymphoma: malignant lymphocytic neoplasm
Choristoma: a heterotopic rest of cells left behind as embryonic structures form; a congenital anomaly; not a true neoplasm; for example, a small nodule of well-developed and normally organized pancreatic substance may be found in the submucosa of the stomach, duodenum, or small intestine. This heterotopic rest may be replete with islets of Langerhans and exocrine glands.
Anaplasia: lack of differentiation; a hallmark of malignancy
Pleomorphism: variation in cell shape and size; signals malignancy
Dysplasia: disorderly, but non-neoplastic proliferation; loss in the uniformity of individual cells and a loss in their architectural orientation; in dysplastic stratified squamous epithelium, mitoses are not confines to the basal layers, where they normally occur, but may appear at all levels and even in surface cells; dysplasias do not necessarily progress to cancer
Encapsulation—the coating or engulfing of particles within a continuous matrix
Oncogenes—mutated forms of proto-oncogenes (DNA), which no longer effectively
regulate cell replication, and promote autonomous cell growth in cancer cells; they have the ability to promote cell growth in the absence of normal growth-promoting signals
Proto-oncogenes—genes which encode products that regulate cell division (growth
factors and growth factor receptors, nuclear regulatory proteins, etc.)
Oncoproteins—products of oncogenes which resemble the normal products of proto-
oncogenes except that oncoproteins are devoid of important regulatory elements,
and their production in the transformed cell does not depend on growth factors or other external signals
Promoters—non-carcinogenic chemicals that augment the actions of chemical
carcinogens (however, many carcinogens do not require the actions of promoters)
Carcinogen - an agent or substance that causes cancer. There are three classes of carcinogenic agents: chemicals, radiant energy, and oncogenic viruses. They can also be classified as direct-acting (requiring no metabolic conversion to become carcinogenic) or indirect-acting (require metabolic conversion before they become active).
Translocation – transfer of a part of one chromosome to another chromosome. The process is usually reciprocal (i.e. fragments are exchanged between two chromosomes).
Philadelphia chromosome – translocation that causes genetic damage, characteristic of chronic myeloid leukemia. A reciprocal translocation between chromosomes 9 and 22 relocates a truncated portion of the protooncogene c-abl (from chromosome 9) to the breakpoint cluster (bcr) locus on chromosome 22. The hybrid c-abl-bcr gene encodes a chimeric protein that, like several other oncoproteins, has potent tyrosine kinase activity.
Suppressor gene – also known as antioncogenes, these encode proteins that inhibit cell proliferation. These are the genes related to Knudsen’s two-hit hypothesis (which is defined earlier).
Paraneoplastic syndrome – a symptom complex other than cachexia (a general wasting away, weakness, and anemia that is seen in cancer patients) that appears in patients with cancer and that cannot be readily explained either by the local or distant spread of the tumor or by the elaboration of hormones indigenous to the tissue of origin of the tumor.
2. Describe characteristics of benign vs. malignant neoplasmas (p. 168-174, Table 6.2)
Benign / MalignantDifferentiation and Anaplasia (refers to parenchymal cells) / Well differentiated; structure may be typical of tissue of origin / Some lack of differentiation with anaplasia; structure is often atypical; anaplastic cells display pleopmorphism, the nuclei are hyperchromatic and large (nuclear-cytoplasmic ratio may be 1:1 instead of 1:4 or 1:6)
Rate of Growth / Usually progressive and slow; may come to a standstill or regress; mitotic figures are rare and normal / Erratic and may be slow to rapid; mitotic figures may be numerous and abnormal
Local Invasion / Usually cohesive and expansile, well-demarcated masses that do not invade or infiltrate the surrounding normal tissues / Locally invasive, infiltrating the surrounding normal tissues; sometimes may seem cohesive and expansile but with microscopic invasion
Metastasis / Absent / Frequently present; the larger and less differentiated the primary, the more likely are metastases
-The better the differentiation of the cell, the more completely it retains the functional capabilities of its normal counterparts.
-The more rapidly growing and anaplastic a tumor, the less likely it is to have specialized functional activity.
-When dysplastic changes are marked and involve the entire thickness of the epithelium, the lesion is referred to as carcinoma in situ, a preinvasive stage of cancer.
-The rate of growth of malignant tumors correlates with their level of differentiation.
-Most cancers take years to develop; very few, if any, develop suddenly (days to months).
-Rapidly growing malignant tumors often contain central areas of ischemic necrosis because the tumor blood supply, derived from the host, fails to keep pace with the oxygen needs of the expanding mass of cells.
-Some benign neoplasms have a fibrous capsule surrounding them but not all do. This capsule involves the stroma when present.
-Next to the development of metastases, local invasiveness is the most reliable feature that distinguishes malignant from benign tumors.
-Approximately 30% of new patients with solid tumors present with clinically evident metastases. Another 20% have occult metastases at the time of diagnosis.
-In general, the more anaplastic and the larger the primary neoplasm, the more likely is metastatic spread
-Cancers grow by progressive infiltration, invasion, destruction, and penetration of the surrounding tissue
3. Describe the 3 pathways for metastatic spread of cancer (p. 172)
1. Seeding
-Neoplasms invade a natural body cavity
-Characteristic of cancers of the ovary, which often cover the peritoneal surfaces
-Can glaze all peritoneal surfaces yet not invade the underlying parenchyma
2. Lymphatic spread
-more typical of carcinomas
-may traverse all of the lymph nodes ultimately to reach the vascular compartment via the thoracic duct
-the necrotic products of the neoplasm and tumor antigens often evoke reactive changes in the nodes, such as enlargement and hyperplasia of the follicles (lymphadenitis) and proliferation of macrophages in the subcapsular sinuses (sinus histiocytosis)
3. Hematogenous spread
-more typical of sarcomas
-most feared consequence of a cancer
-arteries are penetrated less readily than veins
-liver and lungs are the most frequent secondary sites of hematogenous dissemination.
-Renal cell carcinoma often invades the renal vein up to the inferior vena cava reaching the right side of the heart
-prostatic carcinoma preferentially spreads to bone
-bronchogenic carcinomas involve the adrenals and brain
-neuroblastomas spread to the liver and bones
-skeletal muscles are rarely the site of secondary deposits
4. Neoplasia Epidemiology (p. 174-178, Figure 6-13, 6-14)
A. Describe the most common cancers and cancer deaths in men and women.
Ø Top 3 cancers for men: Prostate (30%), Lung and bronchus (14%), and Colon and rectum (11%)
Ø Top 3 cancers for women: Breast (31%), Lung and bronchus and colon and rectum (each 12%)
Ø Top 3 cancer deaths for men: Lung and Bronchus (31%), Prostate (11%), and Colon and rectum (10%)
Ø Top 3 cancer deaths for women: Lung and Bronchus (25%), Breast (15%), and Colon and rectum (11%)
B. Discuss the relative importance of age, occupation, environment, and heredity in the development of cancer.
Age: The frequency of cancer increases with age. Most cancer mortality occurs between the ages 55 and 75 years; the rate declines, along with the population base, after age 75. The rising incidence with age may be attributed to the accumulation of somatic mutations associated with the emergence of malignant neoplasms. The decline in immune competence that accompanies aging also is a factor.
Cancer causes slightly more than 10% of all deaths among children younger than 15 years. The major lethal cancers in children are leukemia, tumors of the CNS, lymphomas, soft tissue sarcomas, and bone sarcomas.
Occupation: Different occupations cause one to be exposed to various harmful agents. See question 5 and table 6-3 for a complete list.
Environment: Environmental factors are the predominant determinant of the most common sporadic cancers. There is no paucity of environmental carcinogens. They lurk in the environment, workplace, food, and personal practices. They can be anything from sunlight, diet, cigarette smoking, alcohol consumption, number of sex partners, etc. Some examples of environmental/geographic cancers: Death rates from breast cancer are about fourfold higher in America compared with Japan. The death rate for stomach carcinoma in men and women is about seven times higher in Japan than in the United States.
Heredity: Heredity forms of cancer can be divided into 3 categories which include the following: Inherited Cancer Syndromes (autosomal dominant), Familial cancers, and Autosomal Recessive Syndromes of Defective DNA Repair.
Ø Examples of Inherited Cancer Syndromes: Familial retinoblastoma, familial adenomatous polyposis, multiple endocrine neoplasia, neurofibromatosis types 1 and 2, von Hippel-Lindau syndrome
Ø Examples of Familial Cancers: Breast cancer, ovarian cancer, colon cancers
Ø Examples of Autosomal Recessive Syndromes of Defective DNA repair: Xeroderma pigmentosom, ataxia telangiectasia, bloom syndrome, and fanconi anemia.
5. Discuss the role of occupation in development of specific types of cancer such as asbestos-induced (mesothelioma). Table 6-3.
Asbestos:
Human Cancer Site for Which Reasonable Evidence is Available: Lung, mesothelioma: gastrointestinal tract (esophagus, stomach, large intestine).
Typical Use of Occurrence: Byproduct of metal smelting. Component of alloys, electrical and semiconductor devices, medications and herbicides, fungicides, and animal dips.