Neoplasia: Review

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:

• Collectively referred to as cancers

• 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

Metastasis:

• Connotes the development of secondary implants (metastases) discontinuous with the primary tumor, possibly in remote tissues

• The properties of invasiveness and, even more so, metastasis more unequivocally identify a neoplasm as malignant than any of the other attributes

Adenoma:

• Benign epithelial neoplasms producing gland patterns and to neoplasms derived from glands but not necessarily exhibiting gland patterns

Chondroma:

• A benign cartilaginous tumor

Papilloma- benign, epithelial neoplasms, growing on any surface that produce microscopic or macroscopic finger-like fronds.

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.

Category: Pathology Notes