bleeding and secondary infections when tumors ulcerate through adjacent natural surfaces
breast cancer carcinoma – pushes through skin causing ulceration
initiation of acute symptoms caused by either rupture or infarction of tumors
when the blood supply to a tumor is cut-off it can infarct and necrose, and then embolize to block the coronary arteries.
paraneoplastic syndromes – symptoms in cancer patients that cannot be explained by the tumor or by hormones indigenous to the tissue from which the tumor arose
Paraneoplastic syndromes are important to recognize because:
(1) may be the earliest manifestations of a neoplasm.
(2) in affected patients, may represent significant clinical probs which may be lethal.
(3) may mimic metastatic disease thus confounding treatment.
Ex.: Cushing’s Syndrome – small cell cancer of the lung produces and secretes ACTH (or POMC) which is normally made by an endocrine gland. Syndromes include hyperpigmentation, enlargement of stomach and face, and gynecomastia (growth of male mammary glands).
cachexia in cancer patients – cachexia = "wasting"
cancer patients commonly suffer progressive loss of body fat and lean body mass accompanied by profound weakness, anorexia, and anemia. Cachexia is not caused by the nutritional demands of the tumor, it results from the action of soluble factors such as cytokines produced either by the tumor or by the host in response to the tumor. The cytokine involved may be TNF-
a (produced by macrophages or maybe tumor) which synergizes with IL-1 and IFN-g .
Grading vs. Staging
Grading
(histological) – of cancers is based on the degree of differentiation of the tumor cells and the number of mitoses within the tumor
criteria for grading varies with different forms of neoplasia to judge the extent to which the cells resemble their normal counterparts
in general tumor differentiation, evaluated on basis of
cellularity
degree of nuclear atypia
presence of malignant giant cells
mitoses count
cancers are classified as grades I to IV with increasing anaplasia
I = well differentiated
II = moderately differentiated
III = poorly differentiated
IV = very poorly differentiated
Staging
(clinical) – based on the size of the primary lesion, its extent of spread to regional lymph nodes, and the presence or absence of blood-borne metastases
UICC Staging System
T = primary tumor (T0-T4)
N = regional lymph node involvement (N0-N3)
M = metastasis (M0-M2)
AJC Staging System
Stage 0 to IV incorporating within each stage the size of the primary lesion as well as the presence of nodal spread and distant metastases.
Staging plays a greater role than grading in the prognosis and treatment of neoplasms.
example: In a patient with a stage III cancer the grade doesn’t really matter because the cancer has already metastasized out of control. Who cares how differentiated it is at this point?
Laboratory Diagnosis of Neoplasms
Cytologic Methods
Histologic Methods
Needle core biopsy
Open biopsy/excisional biopsy/excision biopsy/radical resection
Frozen section
– tissue is removed in operating room, frozen, sliced, stained, and viewed within 10-15 minutes.
Immunochemistry
- (~8 hrs) use Abs to identify certain neoplasms (keratin Abs in carcinoma, B/T cell Abs in lymphomas, etc)
Flow cytometry –
rapidly measures several cell characteristics, such as membrane Ags and the DNA content of tumor cells.
Electron microscopy
– rarely used today. Use electron microscope to view histological details of cells.
Molecular biology
– for example cytogenetics is used to study the tumor’s screwed up DNA (gels, etc).
Tumor markers
– biochemical indicators of the presence of a tumor. Include cell surface Ags, cytoplasmic proteins, enzymes, and hormones. Though tumor markers cannot be used as primary modalities for the dx of cancer, their main use has been in support of the diagnosis.