Neoplasia

Chapter 5 Neoplasia



Ivan Damjanov, MD, PhD




1 Define neoplasia


Neoplasia means “new growth.” British pathologist Sir Rupert Willis defined it as follows: A neoplasm is an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of normal tissues and persists in the same excessive manner after cessation of the stimuli that evoke the change.


In contrast to normal cells, the growth of neoplastic cells is:


image Autonomous: The growth of neoplastic cells is independent of growth factors and regulatory mechanisms operating inside the normal tissues.

image Excessive: This excess may be evident in the size of the outgrowths and the duration of the proliferation.

image Disorganized: The structures formed by tumor cells differ from normal tissues and do not fit into the general organization scheme of the normal body.


2 Define other key words used in the study of neoplasia



image Tumor literally a swelling (tumefaction): This term is used as a synonym for neoplasm. Clinically, tumors are classified as benign (good natured, innocuous) or malignant (bad, ominous, potentially lethal).

image Cancer: This is a synonym for malignant tumors.

image Oncology: This is the science dealing with the study of tumors (Greek term oncos is equivalent to the Latin term tumor, meaning “a swelling”).


3 What are hamartomas and choristomas?



image Hamartoma is a mass composed of cells and tissues native to the organ in which structures arose, usually during fetal development. Examples include the following:
image Mole (melanocytic nevus): This skin hamartoma represents an aggregate of pigment cells that are normally dispersed in the skin.

image Pulmonary hamartoma: This presents as a nodule composed of cartilage, bronchial epithelium, and smooth muscle cells.

image Choristoma is a mass composed of normal cells or tissues found in a wrong location. It is also called ectopia. Examples include the following:
image Pancreatic choristoma in the stomach or in the liver

image Ectopic brain tissue in the nasal cavity


4 Define dysplasia


Dysplasia means abnormal growth and differentiation. The term may have a developmental pathology or oncologic meaning. In developmental pathology, it is used to describe morphogenetic abnormalities (e.g., dysplastic kidneys). In oncology, it is used to describe disorderly growth and maturation of cells that are not normal but that are not obviously malignant. This kind of dysplasia is a premalignant condition, a precursor of invasive neoplasia. Dysplasia can also be considered as a transitional stage linking neoplasia to hyperplasia or metaplasia. Examples include:


image Squamous dysplasia of the cervix: Dysplasia may be graded as mild, moderate, or severe (grade I, II, or III). Severe dysplasia cannot be reliably distinguished from carcinoma in situ. To avoid misunderstanding, dysplasia and carcinoma of the cervix are grouped together under the name cervical intraepithelial neoplasia (CIN), which is then graded as mild, moderate, or severe.

image Liver cell dysplasia: It is well known that liver cell carcinomas arise at an increased rate in cirrhosis caused by viral hepatitis B and C. Such pathologically altered liver may contain preneoplastic cells that can be recognized in histologic sections. Such cells have irregularly enlarged nuclei with prominent nucleoli.


5 What is anaplasia?


Adult somatic cells are differentiated—that is, they express genes in a tissue-specific manner. Anaplasia of tumor cells is defined as lack of differentiation. Anaplastic tumor cells differ from normal cells and pathologists can recognize them as “atypical.” Common features of anaplasia include:


image Pleomorphism: variation in size and shape of nuclei

image Hyperchromatic nuclei: the chromatin in the nuclei is increased in amount and irregularly distributed (“clumped”)

image Atypical mitoses: may be tripolar (“Mercedes logo like”) or multipolar, in contrast to bipolar normal mitoses

image High nuclear cytoplasmic ratio: thus resembling embryonic cells

image Bizarre cells: including giant cells


Key Points: Neoplasia



1. Tumors are classified and named on the basis of their clinical and pathologic features, which must be correlated to determine the prognosis and the mode of therapy for each tumor.

2. Most tumors can be classified as either benign or malignant.

3. Metastasis, a unique feature of malignant tumors, is a complex process resulting in the transfer of tumor cells from the site of origin to distant organs.


6 How are neoplasms classified clinically?


Neoplasms can be classified as benign or malignant on the basis of their clinical behavior. Benign tumors have a good prognosis, whereas malignant tumors have an unfavorable prognosis and are potentially lethal. A third category can be recognized for some tumor types, such as ovarian tumors. These tumors are called borderline malignant or low-grade malignant tumors. If recognized early and surgically resected, such borderline tumors have an excellent prognosis (>95% 5-year survival), but if untreated, they metastasize and will result in death.



7 What is the basis of histologic or histogenetic classification of tumors?


Tumors often retain many of the histologic features of their tissue of origin. For example, a squamous cell carcinoma resembles normal squamous epithelium, whereas a transitional cell papilloma of the urinary bladder is lined by transitional epithelium resembling normal transitional epithelium. On the basis of such microscopic data, one can determine the composition of the tumors and in many instances theoretically reconstruct the histogenesis of most tumors (from Greco-Latin words histo, meaning “tissue,” and genesis, meaning “development”). The histologic–histogenetic classification of tumors is widely used to amplify the clinical classification. It serves as a basis for selecting treatment and for formulating the prognosis of the neoplastic disease in each particular case.



8 What is the difference between carcinoma and sarcoma?


Most human organs (except for the nervous system) are composed of epithelial cells, connective tissue cells, or both. Malignant tumors of epithelial origin are called carcinomas. Sarcomas are malignant tumors of connective tissue origin. Epithelial cells of carcinomas form nests surrounded by nonneoplastic connective tissue stroma. In sarcomas, the tumor cells are intermixed with the nonneoplastic stromal cells.


See Fig. 5-1.


image

Figure 5-1 Carcinoma and sarcoma. Carcinoma (CA) is composed of epithelial malignant cells surrounded by stroma that contains fibroblasts, collagen, and blood vessels. Because the epithelial cells form glands, this tumor is classified as an adenocarcinoma. Sarcoma (SA) is composed of malignant connective tissue (mesenchymal) cells that merge imperceptibly with other nonneoplastic mesenchymal cells that form the stroma of the tumor. The blood vessels are included in the stroma of this sarcoma but are not as visible as in the loose stroma of the carcinoma.



9 Are there any benign equivalents of carcinomas and sarcomas?


Yes. The names for benign tumors are formed by adding the suffix -oma to the cell of their origin. Thus a benign tumor originating from fibroblasts is called fibroma, a tumor of fat cells is called lipoma, a tumor of smooth muscle cells is called leiomyoma, a tumor of striated muscles is called rhabdomyoma, a tumor of bone is called osteoma, and so on.


Benign epithelial tumors could be called epitheliomas, but this term is not specific enough and is not used. Instead, benign epithelial tumors are known under a number of other names, such as:


image Adenoma: This tumor is composed of cells forming glands or tubules. Benign endocrine gland tumors are also called adenomas.

image Papilloma: This descriptive term is derived from the Latin word for the nipple. Papillomas appear as nipple-like protrusions on the surface of the skin or a hollow organ (e.g., urinary bladder). The surface of some papillomas may branch into smaller fronds, which give such tumors a cauliflower appearance.

image Polyp: This term is derived from the Greek term meaning “numerous feet” as seen in the octopus. These tumors may be attached to the surface of the skin or mucosa of hollow organs by a stalk. Other tumors form fingerlike epithelial protrusions broadly attached to the surface of their origin. Such tumors are called sessile polyps.

See Fig. 5-2.


image

Figure 5-2 Benign epithelial tumors. A, Adenoma is composed of glands. B, Papilloma is a nipplelike protrusion on the surface of the skin or mucosa of an internal organ, such as the urinary bladder. C, Polyp consists of fingerlike protrusions. Such a polyp is called sessile because it has a broad base and does not have a stalk. D, Pedunculated polyp has a stalk.



10 List the main histologic–histogenetic categories of human neoplasms


On the basis of their histologic features and presumed cell or tissue of origin, neoplasms can be classified as:


image Epithelial tumors: More than 80% of all human tumors are of epithelial origin. They can be benign or malignant. Depending on the type of epithelium, these tumors are classified as:
image Squamous cell tumors: benign—squamous cell papilloma; malignant—squamous cell carcinoma

image Glandular tumors: benign—adenoma; malignant—adenocarcinoma

image Transitional cell tumors: benign—transitional cell papilloma; malignant—transitional cell carcinoma

image Connective tissue tumors: Benign tumors include fibromas, lipomas, and osteomas, and so on; their malignant equivalents include fibrosarcomas, liposarcomas, osteosarcomas, and so on.

image Tumors of blood cells and lymphocytes: All tumors in this category are malignant. They include entities such as lymphomas, leukemias, multiple myeloma, polycythemia rubra vera, Hodgkin disease, and others.

image Tumors of neural and glial cells and neural support structures: This category includes tumors such as neuroblastoma, gliomas, and meningiomas.

image Germ cell tumors: This category includes tumors such as seminoma, teratoma, teratocarcinoma, and choriocarcinoma.


11 What are mixed tumors?


Mixed tumors are composed of both epithelial and connective tissue tumor cells. Benign mixed tumors composed of epithelial and myoepithelial cells and cells resembling cartilage cells are commonly found in the salivary glands. Malignant mixed tumors are called carcinosarcomas. Carcinosarcomas composed of adenocarcinoma and various sarcoma cells are most often found in the uterus. These uterine tumors are also called malignant mixed Müllerian tumors.



12 What are teratomas?


Teratomas are tumors of germ cell origin. They are composed of tissues derived from three germinal layers: ectoderm, endoderm, and mesoderm. Thus in a teratoma one may find ectodermal derivatives such as skin and neural tissue, endodermal derivatives such as intestine-like and bronchial-like structures, and mesodermal tissues such as bone or cartilage all intermixed in a haphazard manner. Malignant teratomas are called teratocarcinomas. These tumors consist of differentiated somatic tissues and malignant stem cells. These stem cells are developmentally equivalent to early embryonic cells and are called embryonal carcinoma cells.



13 What is the difference between leiomyoma and rhabdomyoma?


Leiomyomas are tumors composed of smooth muscle cells. Rhabdomyomas are tumors of striated muscle cells (i.e., cells forming the skeletal or heart muscle). Malignant tumors composed of the same cells are called leiomyosarcomas and rhabdomyosarcomas, respectively.



14 What are blastomas?


Blastomas are tumors composed of immature cells resembling those that form the fetal anlage or primordia of adult organs. Retinoblastoma is a tumor of the eye, neuroblastoma is a tumor composed of nerve precursors cells (neuroblasts), and a hepatoblastoma is a tumor composed of fetal hepatocytes.



15 List the most well-known tumor eponyms


Eponyms (i.e., proper names used as designations) are applied to tumors that cannot be properly classified or whose histogenesis is controversial. The best-known tumor eponyms are:


image Hodgkin disease: a special form of malignant lymphoma

image Ewing sarcoma: a malignant bone tumor

image Wilms tumor: a malignant kidney tumor of childhood, also known as nephroblastoma

image Kaposi sarcoma: a blood vessel tumor of the skin and internal organs

image Burkitt lymphoma: a form of malignant lymphoma


16 Is seminoma a benign tumor?


The suffix -oma attached to the cell or tissue of origin of a specific tumor is commonly used to name benign tumors (e.g., osteoma and fibroma). There are, however, some important exceptions to this rule, and seminoma is one of them. Seminoma is a malignant tumor of the seminal epithelium in the testis. The equivalent tumor originating from the female germ cells in the ovary is called dysgerminoma.



17 Give some other examples of malignant tumors ending in -oma



image Glioma: Almost all tumors derived from glia cells are malignant. This group includes tumors such as astrocytoma, oligodendroglioma, and ependymoma, all of which are actually malignant.

image Lymphoma: All lymphoid neoplasms are malignant. To emphasize this fact, it is customary to add an adjective and call these tumors malignant lymphomas.

image Insulinoma, gastrinoma, somatostatinoma, and glucagonoma: These endocrine pancreatic tumors originating from the islets of Langerhans may be either malignant or benign. Histologically, it is not possible to distinguish benign from malignant endocrine tumors.


18 Is meningioma a benign tumor?


Most meningiomas (96%) are biologically benign intracranial tumors of limited growth potential. Because of their intracranial location and the proximity to vital centers, meningiomas must be removed surgically because they can increase the intracranial pressure and compress the vital centers. Although biologically benign, such meningiomas may kill the host (i.e., act in a clinically “malignant” manner).



19 What are the main differences between benign and malignant tumors?


See Table 5-1.


TABLE 5-1 Major Differences between Benign and Malignant Tumors
















































Feature Benign Malignant
Growth Slow Fast
Expansive Invasive
Gross appearance
External surface Smooth Irregular
Capsule Present Not obvious
Cross section Homogeneous Variable
Color Uniform Variable
Microscopic
Differentiation Resembles tissue of origin Anaplastic, does not resemble tissue of origin
Nuclei Normal size and shape Atypical, pleomorphic
Hyperchromatic
Mitoses Few Numerous, often abnormal


20 How are benign tumors distinguished from malignant tumors in practice?


During the past 150 years, clinicians and pathologists have been correlating the clinical behavior of various neoplasms with the histologic features of these tumors. Empirical clinicopathologic criteria have been formulated on the basis of such studies and are used to predict whether a tumor is benign or malignant. These criteria include:


image Clinical findings: Benign tumors tend to grow slowly and remain localized. Malignant tumors tend to develop fast, disseminate through the body, and kill the patient.

image Radiologic findings: Benign tumors are circumscribed, whereas malignant tumors have irregular outlines and invade the surrounding tissues. For example, mammographic examination of the breast provides valuable data about breast tumors.

image Gross features: During surgery, one may assess tumors by direct inspection or palpation. Surgeons can determine in many instances whether a tumor is most likely benign or malignant.

image Gross pathologic examination: The previously mentioned criteria are often used by pathologists to predict whether a tumor is benign or malignant.

image Cytopathologic features: Tumors can be examined by fine needle aspiration biopsy. A needle is inserted, and a small sample of single cells is obtained by aspiration. These cells can be examined microscopically and the diagnosis established in most cases.

image Histologic examination: Microscopic examination of tumors in most instances provides the final proof that a tumor is malignant. In some instances, even the histologic examination cannot indicate whether a tumor is benign or malignant. The best example of such tumors is endocrine tumors, such as pituitary, thyroid follicular neoplasms, and parathyroid tumors. In such cases, the diagnosis of malignancy can be made only if the tumor is found to be clinically malignant (i.e., has metastasized, extensively invaded, and destroyed tissue or killed the patient).


21 What is the difference between tumor invasion and metastasis?


Malignant tumors invade locally and extend into the surrounding normal tissues. In contrast, metastasis is a spread of tumors to sites that are anatomically separate from their site of origin.



22 How do tumors metastasize?


Tumors can metastasize three ways:


image Lymphatic spread: Tumor cells invade the lymphatics and spread to local lymph nodes.

image Hematogenous spread: Tumor cells invade the blood vessels and are carried by blood to distant sites.

image Seeding of body cavities: Tumor cells enter the cavities and float in the serous fluid to attach on the surface of the peritoneal or pleural cavity.


23 Which tumors metastasize through the lymphatics, and which ones metastasize hematogenously?


Previously, it was thought that carcinomas metastasize through the lymphatics and sarcomas through blood vessels. This rule is only partially correct, and there are many exceptions. Tumors of organs that are rich in lymphatics, such as the breast and the large intestine, metastasize preferentially through the lymphatics. Such tumors may metastasize hematogenously as well, but blood-borne metastases usually occur in later stages of the disease. Tumors originating in organs that are well vascularized but contain few lymphatics, such as bones, tend to metastasize hematogenously. This fact accounts for the high rate of hematogenous metastases of bone sarcomas.



24 Which carcinomas metastasize more often hematogenously than through the lymphatics?


Carcinomas of the liver and the kidney, two organs that have more blood vessels than lymphatics, metastasize more often hematogenously than lymphogenously.



25 Do all malignant tumors metastasize?


No. Malignant tumors of the brain usually kill the patient before the tumor has the chance to metastasize. The fact that brain tumors do not have metastases does not automatically mean that the cells of these tumors cannot metastasize. Evidence that brain tumors can metastasize includes the following:


image Drop metastases in the spinal cord: These metastases develop occasionally from cerebellar medulloblastoma cells carried to distant sites by the cerebrospinal fluid.

image Lymph node metastases in patients who have had brain surgery: It is assumed that the surgery has breached the blood–brain barrier and thus allowed the tumors to metastasize.

image Metastases through shunts: Some brain cancer patients whose cerebrospinal fluid is drained into the abdominal cavity by a tube have developed distant metastases. Such metastases arise from tumor cells carried by the cerebrospinal fluid through the manmade shunt.


26 Which tumors spread primarily by seeding of body cavities?


Peritoneal seeding is common in patients with ovarian cancer. Malignant tumors originating from the surface epithelium of the ovary tend to detach and float away in the peritoneal fluid. Such floating cells may attach to the serosal surfaces covering the abdominal wall or abdominal organs.



27 What is the difference between staging and grading of tumors?


Staging is used to determine the extent of spread of a tumor. It is based on correlating all the available clinical data with the pathologic findings. For example, the size of the tumor is assessed radiologically and on gross examination during surgery and in the pathology laboratory. The lymph nodes are examined to establish whether the tumor has spread to local and distant lymph nodes. Radiologic and radioisotope studies can be used to establish whether there are distant metastases.


Grading of tumors is based on microscopic examination of tumor tissues obtained at the time of operation or by biopsy. Tumors are graded on a scale from I to III, or descriptively as well differentiated, moderately well differentiated, or poorly differentiated. Although grading is important, overall, staging is much more predictive of the tumor behavior and is thus more valuable for prognosis.



28 What is the TNM system?


The TNM system is used for staging of tumors. T stands for the size of the tumor, which is expressed according to defined criteria for each anatomic site on a scale from 1 to 4. N (from 0 to 3) stands for lymph node involvement, and M (0 negative, 1 positive) stands for distant metastases. Thus a small tumor that has not metastasized is designated as T1, N0, M0. A small tumor that has metastasized to lymph nodes and distant sites is designated as T1, N1, M1.



29 Are there other staging systems besides the TNM system?


Yes. TNM is not a perfect system, and many other systems have been developed by cancer societies and even major medical centers. Some tumor staging systems were devised even before the TNM system was proposed and are still used in clinical practice. Probably the best-known staging system is the Dukes system for staging colon cancer.



CANCER EPIDEMIOLOGY



30 Define cancer epidemiology


Cancer epidemiology deals with the occurrence of tumors in human populations. By studying cancer incidence, prevalence, and specific mortality, epidemiologists try to identify environmental and genetic causes of cancer and thus contribute to better diagnosis, treatment, and prevention.



31 Define epidemiologic terms: incidence, prevalence, and mortality



image Incidence of cancer is the number of new cases of a specific cancer registered over a specified period in a defined population. For example, the yearly incidence of cancer of the thyroid has increased in Japan since the atomic bomb explosions in 1945.

image Prevalence of cancer is the number of all cases of cancer—both new and old—registered within a defined population at a given point in time. For example, the prevalence of cancer may have increased because of an environmental carcinogen but also because of improved treatment and longer survival of cancer patients.

image Mortality of cancer is the number of deaths from a given form of cancer during a specified period of time in a defined population.


32 How are epidemiologic data used to detect environmental carcinogens?


Epidemiologic data may point to a cause-and-effect relationship between a cancer and a potential carcinogen. For example, a high incidence of lung cancer among smokers provided the first indication that lung cancer may be related to tobacco smoking. These initial data were corroborated by showing that there is a dose–response relationship and that the risk of cancer is directly proportional to the number of years and the number of cigarettes smoked (“pack years”). Finally, it was shown that tobacco tar contains carcinogenic polycyclic hydrocarbons. These carcinogens can produce malignant tumors in experimental animals and are the most likely cause of cancer in tobacco smokers.



Key Points: Cancer Epidemiology



1. Tumor incidence, prevalence, and mortality vary among populations and in different areas of the world.
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Jul 23, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Neoplasia

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