By Crystal Walker,2014-06-26 20:16
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    Parathyroid Pathology Review Page 1

    Neoplasia Background


    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

    connective tissue).



     “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.

    Malignant Tumors

     “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

    malignant tumor.”

    Table 7-1.

    Nomenclature of


    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

     Lipoma Liposarcoma

     Chondroma Chondrosarcoma

     Osteoma Osteogenic sarcoma Endothelial and related tissues

     Blood vessels Hemangioma Angiosarcoma

     Lymph vessels Lymphangioma Lymphangiosarcoma

     Synovium Synovial sarcoma

     Mesothelium Mesothelioma

     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

    epidermoid carcinoma

     Basal cells of skin or adnexa Basal cell carcinoma

     Epithelial lining of glands or ducts Adenoma Adenocarcinoma

     Papilloma Papillary carcinomas

     Cystadenoma Cystadenocarcinoma

     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

    (transitional) carcinoma

     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

    Cell Layer

    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.




    Both the cells and the nuclei

    characteristically display

    pleomorphism-variation in

    size and shape. Cells may

    be found that are many

    times larger than their

    neighbors, and other cells

    may be extremely small and

    primitive appearing.

    Abnormal nuclear


    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-

    differentiated malignant

    neoplasms, undifferentiated

    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.

Other changes

    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-

    dependent kinases.

    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.

    Sustained angiogenesis:

    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 blood.


    The amount by which a tumor has spread determines its staging:


    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.




    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

    paraneoplastic syndromes.



    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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    Radiation therapy

    General chemotherapy (cytotoxic)

    Targeted therapy

    Treatment will consist of some combination of the above, depending on the stage and nature of

    the tumor.


    Robbins and Cotran

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