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Neoplasm: “new growth”; an abnormal mass of tissue whose growth is not coordinated with the
growth of normal tissue and which persists despite removal of the stimuli which evoked the
Neoplasms consist of parenchymal cells and stroma (support cells, i.e. blood vessels and
“In general, benign tumors are designated by attaching the suffix -oma to the cell of
origin. Tumors of mesenchymal cells generally follow this rule. For example, a benign
tumor arising from fibroblastic cells is called a fibroma, a cartilaginous tumor is a
chondroma, and a tumor of osteoblasts is an osteoma. In contrast, nomenclature of benign
epithelial tumors is more complex. They are variously classified, some based on their
cells of origin, others on microscopic architecture, and still others on their macroscopic
Adenoma is the term applied to a benign epithelial neoplasm that forms glandular patterns
as well as to tumors derived from glands but not necessarily reproducing glandular
patterns. On this basis, a benign epithelial neoplasm that arises from renal tubular cells
growing in the form of numerous tightly clustered small glands would be termed an
adenoma, as would a heterogeneous mass of adrenal cortical cells growing in no
distinctive pattern. Benign epithelial neoplasms producing microscopically or
macroscopically visible finger-like or warty projections from epithelial surfaces are
referred to as papillomas
Those that form large cystic masses, as in the ovary, are referred to as cystadenomas.
Some tumors produce papillary patterns that protrude into cystic spaces and are called
papillary cystadenomas. When a neoplasm, benign or malignant, produces a
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macroscopically visible projection above a mucosal surface and projects, for example, into the gastric or colonic lumen, it is termed a polyp.
The term polyp is preferably restricted to benign tumors. Malignant polyps are better
designated polypoid cancers.”
“The nomenclature of malignant tumors essentially follows the same schema used for
benign neoplasms, with certain additions. Malignant tumors arising in mesenchymal tissue are usually called sarcomas (Greek sar = fleshy) because they have little connective tissue stroma and so are fleshy (e.g., fibrosarcoma, liposarcoma,
leiomyosarcoma for smooth muscle cancer, and rhabdomyosarcoma for a cancer that
differentiates toward striated muscle). Malignant neoplasms of epithelial cell origin,
derived from any of the three germ layers, are called carcinomas. Thus, cancer arising in
the epidermis of ectodermal origin is a carcinoma, as is a cancer arising in the
mesodermally derived cells of the renal tubules and the endodermally derived cells of the
lining of the gastrointestinal tract. Carcinomas may be further qualified. One with a
glandular growth pattern microscopically is termed an adenocarcinoma, and one
producing recognizable squamous cells arising in any epithelium of the body is termed a
squamous cell carcinoma. It is common practice to specify, when possible, the organ of
origin (e.g., a renal cell adenocarcinoma or bronchogenic squamous cell carcinoma). Not
infrequently, however, a cancer is composed of undifferentiated cells of unknown tissue
origin, and must be designated merely as a poorly differentiated or undifferentiated
Tissue of Origin Benign Malignant
Composed of One Parenchymal Cell Type
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Tumors of mesenchymal origin
Connective tissue and derivatives Fibroma Fibrosarcoma
Osteoma Osteogenic sarcoma Endothelial and related tissues
Blood vessels Hemangioma Angiosarcoma
Lymph vessels Lymphangioma Lymphangiosarcoma
Synovium Synovial sarcoma
Brain coverings Meningioma Invasive meningioma Blood cells and related cells
Hematopoietic cells Leukemias
Lymphoid tissue Lymphomas Muscle
Smooth Leiomyoma Leiomyosarcoma
Striated Rhabdomyoma Rhabdomyosarcoma Tumors of epithelial origin
Stratified squamous Squamous cell papilloma Squamous cell or
Basal cells of skin or adnexa Basal cell carcinoma
Epithelial lining of glands or ducts Adenoma Adenocarcinoma
Papilloma Papillary carcinomas
Respiratory passages Bronchial adenoma Bronchogenic carcinoma
Renal epithelium Renal tubular adenoma Renal cell carcinoma
Liver cells Liver cell adenoma Hepatocellular carcinoma
Urinary tract epithelium Transitional cell papilloma Transitional cell
Placental epithelium Hydatidiform mole Choriocarcinoma
Testicular epithelium (germ cells) Seminoma
Embryonal carcinoma Tumors of melanocytes Nevus Malignant melanoma More Than One Neoplastic Cell Type-Mixed Tumors, Usually Derived from One Germ
Salivary glands Pleomorphic adenoma Malignant mixed tumor of
(mixed tumor of salivary salivary gland origin
Renal anlage Wilms tumor More Than One Neoplastic Cell Type Derived from More Than One Germ Cell Layer-Teratogenous
Totipotential cells in gonads or in Mature teratoma, dermoid Immature teratoma,
embryonic rests cyst teratocarcinoma
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Differentiation refers to the extent to which neoplastic cells resemble comparable normal cells, both morphologically and functionally; lack of differentiation is called anaplasia (“to form backwards”). Cancerous cells that are undifferentiated are said to be anaplastic.
Grading of a cancer is based on the degree of differentiation of the tumor cells and the number of mitoses within the tumor as presumed correlates of the neoplasm's aggressiveness. Thus, cancers are classified as grades I to IV with increasing anaplasia.
In general, benign tumors are well-differentiated and therefore look and act like their tissue of origin, for the most part.
Cancerous cells may range from differentiated to undifferentiated.
ACK OF DIFFERENTIATION, ANAPLASIA, IS MARKED BY MANY MORPHOLOGIC CHANGES:
Both the cells and the nuclei
size and shape. Cells may
be found that are many
times larger than their
neighbors, and other cells
may be extremely small and
Characteristically the nuclei
contain an abundance of DNA and are extremely dark staining (hyperchromatic). The
nuclei are disproportionately large for the cell, and the nucleus-to-cytoplasm ratio may
approach 1:1 instead of the normal 1:4 or 1:6. The nuclear shape is very variable, and the
chromatin is often coarsely clumped and distributed along the nuclear membrane. Large
nucleoli are usually present in these nuclei.
As compared with benign
tumors and some well-
tumors usually possess large
numbers of mitoses, reflecting
the higher proliferative activity
of the parenchymal cells. The
presence of mitoses, however,
does not necessarily indicate
that a tumor is malignant or
that the tissue is neoplastic.
Many normal tissues exhibiting
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rapid turnover, such as bone marrow, have numerous mitoses, and non-neoplastic
proliferations such as hyperplasias contain many cells in mitosis. More important as a
morphologic feature of malignant neoplasia are atypical, bizarre mitotic figures,
sometimes producing tripolar, quadripolar, or multipolar spindles
Loss of polarity
In addition to the cytologic abnormalities, the orientation of anaplastic cells is markedly
disturbed (i.e., they lose normal polarity). Sheets or large masses of tumor cells grow in
an anarchic, disorganized fashion.
Another feature of anaplasia is the formation of tumor giant cells, some possessing only a
single huge polymorphic nucleus and others having two or more nuclei. These giant cells
are not to be confused with inflammatory Langhans or foreign body giant cells, which are
derived from macrophages and contain many small, normal-appearing nuclei. In the
cancer giant cell, the nuclei are hyperchromatic and large in relation to the cell. Although
growing tumor cells obviously require a blood supply, often the vascular stroma is scant,
and in many anaplastic tumors, large central areas undergo ischemic necrosis.
Table 7-2. Comparisons Between Benign and Malignant Tumors Characteristics Benign Malignant
Differentiation/anaplasia Well differentiated; structure may be Some lack of differentiation
typical of tissue of origin with anaplasia; structure is often
atypical Rate of growth Usually progressive and slow; may Erratic and may be slow to
come to a standstill or regress; rapid; mitotic figures may be
mitotic figures are rare and normal numerous and abnormal
Local invasion Usually cohesive and expansile well-Locally invasive, infiltrating the
demarcated masses that do not invade surrounding normal tissues;
or infiltrate surrounding normal sometimes may be seemingly
tissues cohesive and expansile
Metastasis Absent Frequently present; the larger
and more undifferentiated the
primary, the more likely are
How a cell becomes cancerous:
Self-sufficiency in growth signals:
Tumors have the capacity to proliferate without external stimuli, usually as a
consequence of oncogene activation.
Insensitivity to growth-inhibitory signals:
Tumors may not respond to molecules that are inhibitory to the proliferation of normal
cells such as transforming growth factor-β (TGF-β), and direct inhibitors of cyclin-
Evasion of apoptosis:
Tumors may be resistant to programmed cell death, as a consequence of inactivation of
p53 or other changes.
Defects in DNA repair: Tumors may fail to repair DNA damage caused by carcinogens or
unregulated cellular proliferation.
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Limitless replicative potential:
Tumor cells have unrestricted proliferative capacity, associated with maintenance of
telomere length and function.
Tumors are not able to grow without formation of a vascular supply, which is induced by
various factors, the most important being vascular endothelial growth factor (VEGF).
Ability to invade and metastasize:
Tumor metastases are the cause of the vast majority of cancer deaths and depend on
processes that are intrinsic to the cell or are initiated by signals from the tissue
Once a cell has become metastatic, it can invade other tissues by traveling through the lymph or
The amount by which a tumor has spread determines its staging:
PRIMARY TUMOR (T):
TX: Primary tumor cannot be assessed.
T0: No evidence of primary tumor (this sometimes happens).
Tis: Pure carcinoma in situ; intraductal carcinoma, lobular carcinoma in situ, or Paget disease of
the nipple with no associated tumor mass.
T1: Tumor 2 cm (about ? of an inch) or less in greatest dimension.
T2: Tumor more than 2 cm but not more than 5 cm (2 inches) in greatest dimension.
T3: Tumor more than 5 cm in greatest dimension.
T4: Tumor of any size growing into the chest wall or skin.
EGIONAL (NEARBY) LYMPH NODES (N) PATHOLOGIC STAGING (BASED ON LOOKING AT THEM
UNDER A MICROSCOPE):
NX: Regional lymph nodes cannot be assessed (for example, removed previously).
N0: Cancer has not spread to regional lymph nodes.
N1: Cancer has spread to 1 to 3 lymph node(s) under the arm
N2: Cancer has spread to 4 to 9 lymph nodes under the arm
N3: Cancer has spread to 10 or more lymph nodes under the arm or also involves lymph nodes
in other areas around the breast.
METASTASIS (M): MX: Presence of distant spread (metastasis) cannot be assessed.
M0: No distant spread.
M1: Spread to distant organs is present.
Stage 0: Tis, N0, M0: (DCIS. LCIS is sometimes classified as stage 0 breast cancer, but most oncologists believe it is not a true breast cancer).
Stage I: T1, N0, M0
Stage IIA: T0, N1, M0 / T1, N1, M0 / T2, N0, M0 Stage IIB: T2, N1, M0 / T3, N0, M0
Stage IIIA: T0-2, N2, M0 / T3, N1-2, M0
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Stage IIIB: T4, N0-2, M0 Stage IIIC: T0-4, N3, M0: Stage IV: T0-4, N0-3, M1
Cancer and the host:
Obviously, cancers are far more threatening
to the host than benign tumors are.
Nonetheless, both types of neoplasia may
cause problems because of (1) location and
impingement on adjacent structures, (2)
functional activity such as hormone
synthesis, (3) bleeding and secondary
infections when they ulcerate through
adjacent natural surfaces, and (4) initiation
of acute symptoms caused by either rupture
or infarction. Any metastasis has the
potential to produce these same
consequences. Cancers may also be
responsible for cachexia (wasting) or
Patients with cancer commonly suffer
progressive loss of body fat and lean body
mass accompanied by profound weakness,
anorexia, and anemia. This wasting
syndrome is referred to as cachexia. The
origins of cancer cachexia are obscure.
There is little doubt, however, that cachexia
is not caused by the nutritional demands of
the tumor. Current evidence indicates that
cachexia results from the action of soluble
factors such as cytokines produced by the
tumor and by the host in response to the
Symptom complexes in cancer-bearing
patients that cannot readily be explained,
either by the local or distant spread of the
tumor or by the elaboration of hormones indigenous to the tissue from which the tumor arose, are known as paraneoplastic syndromes. These occur in about 10% of patients with malignant
disease. Despite their relative infrequency, paraneoplastic syndromes are important to recognize, for several reasons:
• They may represent the earliest manifestation of an occult neoplasm.
• In affected patients, they may represent significant clinical problems and may even be lethal.
• They may mimic metastatic disease and therefore confound treatment.
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General chemotherapy (cytotoxic)
Treatment will consist of some combination of the above, depending on the stage and nature of
Robbins and Cotran