Neoplasia 2

Dr Suvarna Nalapat

Immunology of Neoplasia Persons with congenital immunodeficiencies increased risk (200 times normal) for malignancies, Immune surveillance must play some role in preventing neoplasia. Viral and chemical-induced cancers in animals associated with "tumor-specific antigens" This is equivocal in humans. Such antigens could evoke host defenses in the form of sensitized cytotoxic T lymphcytes, natural killer (NK) cells, macrophages. Such antigens evoke humoral immunity (antibody formation), but could "block" antigens and prevent recognition and attack through cellular immunity.

Diagnostic Methods for Neoplasia

History and Physical Examination What the health care worker learns from talking to the patient and through direct examination may give clues to the presence of a neoplasm. Signs and symptoms such as weight loss, fatigue, and pain may be present. A mass may be palpable or visible.

Radiographic Techniques
The use of plain films (x-rays), computed tomography (CT), magnetic resonance imaging (MRI), mammography, and ultrasonography (US) may be very helpful to detect the presence and location of mass lesions. The findings from these methods may aid in staging and determination of therapy.

Laboratory Analyses
General findings such as anemia, enzyme abnormalities (increased alkaline phosphatase), hematuria or positive stool occult blood helpful to suggest further workup. More specific testing, such as measurement of p sa levels, may help to determine the presence of specific neoplasms, but such tests are not perfect screening tools in a general population. Detection of specific genes (such as BRCA-1 for breast cancer) suggest an increased risk for some malignancies

Diagnosis of Neoplasia
Cytology: fastest and simplest with least morbidtity, but yield few cells. Techniques include fine needle aspiration, brushings through endoscope, tapping of fluid collections through needle, direct scrapings such as pap smear. Biopsy: take a bite of tissue, either a small piece through endoscope or larger piece as excision. more preparation and skill required, the potential for complications greater, but more diagnostic tissue obtained.

Cytology
Methods that sample cells can be simple and cost-effective and minimally invasive. A good example is the Pap smear for diagnosis of cervical dysplasias and neoplasms. Cells exfoliated into body fluids may also be examined. Fine needle aspiration (FNA) can be used to sample a variety of mass lesions

Tissue Biopsy and Surgery

Methods that sample small pieces of tissue (biopsy) from a particular site, often via endoscopic techniques (such as colonoscopy, upper endoscopy, or bronchoscopy) can often yield a specific diagnosis of malignancy. At surgery, portions of an organ or tissue can be sampled, or the diseased tissue(s) removed and examined in surgical pathology to determine the stage and grade of the neoplasm

Autopsy
Sometimes neoplasms are not detected or completely diagnosed during life. The autopsy serves as a means of quality assurance for clinical diagnostic methods, as a way of confirming diagnoses helpful in establishing risks for family members, as a means for gathering statistics for decision making about how to approach diagnosis and treatment of neoplasms, and to provide material for future research

Autopsy: some neoplasms are discovered only at autopsy, either because they had not yet manifested an effect, because diagnostic techniques did not work, or because the patient died before a diagnosis could be obtained

Limitations of diagnosis:
Sampling error: not all neoplasms are uniform, material obtained may be the desmoplastic reaction, area of necrosis, inflammation around neoplasm, or not representative of the neoplasm. Improper handling: allowing the sample to dry, crushing material, using wrong fixative, delay in sending to laboratory. Lack of correlation betweeen histologic appearance and actual biologic behavior of the neoplasm

Adjuncts to histologic diagnosis:

Flow cytometry: more aneuploid tumors worse prognosis, still an experimental technique. DNA probes recognize oncogenes or clonal gene rearrangements . Immunohistochemistry identify tumorspecific products or markers (such as p s a, common leukocyte antigen, keratin). Tumor markers in serum carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), prostatic acid phosphatase (PAP).

They are not all that specific or sensitive, particularly when applied as screening tests to a general population

Treatment for Neoplasia

Surgery: the most effective method, but not all primary sites are accessible or resectable with a clear margin. Once metastasis has occurred, surgery is no longer primary curative therapy. Radiation: effectiveness depends upon radiosensitivty of tumor and the body's ability to tolerate the dose without serious sequelae from necrosis, fibrosis, or radiation sickness. Chemotherapy: effectiveness depends upon ability of the drug to selectively poison the neoplastic cells and not normal cells.

Combination chemotherapy (multiple drugs)

allows lower doses of each drug with potentially less tumor resistance. Some neoplasms -hormonal therapy (estrogens inhibit prostatic adenocarcinoma, antiestrogen therapy inhibits breast adenocarcinoma). Immunotherapy: either tries to promote the body's own immune surveillance (activating T lymphocytes) or tries to direct antibodies against tumor antigens. Physical agents: hyperthermia ,cryotherapy attempt to selectively kill more thermally sensitive neoplastic cells

The problem with all treatments other than surgery is that they are never 100% selective for the neoplastic cells, and normal cells are injured. Patients with a positive attitude or who have something to live for and have emotional support from family, friends, or a caring physician will tend to do better with treatment and/or live longer.