3. CLINICAL ASPECTS OF NEOPLASIA
• Local and Hormonal Effects
• Cancer Cachexia
• Paraneoplastic Syndromes
• Grading and Staging of Tumors
4. LABORATORY DIAGNOSIS OF CANCER
• Prognosis of malignant neoplasms.
• Detection of minimal residual disease
• Diagnosis of hereditary predisposition to cancer.
• Guiding therapy with oncoprotein directed drugs
• Molecular Profiles of Tumors: The Future of Cancer Diagnostics
5. LOCAL AND HORMONAL EFFECTS
• Tumors may impinge upon vital tissues and impair their functions, cause death of
involved tissues, and provide a nidus for infection.
• Cancers arising within or metastatic to an endocrine gland may cause an
endocrine
• insufciency by destroying the gland.
• may cause obstruction as they enlarge.
• A benign beta-cell adenoma of the pancreatic islets less than 1 cm in diameter
may produce suficient insulin to cause fatal hypogly-cemia.
6. • Melena (blood in the stool) and hematuria, for example, are characteristic of
neoplasms of the gut and urinary tract.
7. CANCER CACHEXIA
Equal loss of both fat and lean muscle
Elevated basal metabolic rate
Evidence of systemic in ammation
9. • They may be the earliest manifestation of an occult neoplasm.
• In affected patients they can cause significant clinical problems and may even be
lethal.
• They may mimic metastatic disease and therefore con- found treatment.
10. ENDOCRINOPATHIES
• The responsible cancers are not of endocrine origin.
• Secretory activity of such tumors is referred to as ectopic hormone production.
Cushing syndrome is the most common endocrinopathy.
• Approximately 50% of individuals with this endocrinopathy have carcinoma of the
lung, chiefly the small-cell type. It is caused by excessive production of
corticotropin or corticotropin- like peptides.
• Lung cancer patients with Cushing syndrome have elevated serum levels of both
proopio melanocortin and corticotropin.
11. HYPERCALCEMIA
The most common paraneoplastic syndrome;
• (1) osteolysis induced by cancer, whether primary in bone, such as multiple
myeloma, or metastatic to bone from any primary lesion.
• (2) the production of calcemic humoral substances by extraosseous neoplasms.
Only the second mechanism is considered to be paraneoplastic; hypercalcemia
due to primary or secondary involvement of the skeleton by tumor is not a
paraneoplastic syndrome.
12. • The most important, parathyroid hormone-related protein (PTHRP), is a molecule
related to, but distinct from, parathyroid hormone (PTH). PTHRP resembles the
native hormone only in its N terminus.
• Some biologic actions similar to those of PTH, and both hormones
13. NEUROMYOPATHIC PARANEOPLASTIC
SYNDROMES
• A neurological syndrome can affect the brain
and/or spinal cord and/or the peripheral nervous
system.
• peripheral neuropathies, cortical cerebellar
degeneration, a polymyopathy resembling
polymyositis, and a myasthenic syndrome similar
to myasthenia gravis
• antibodies, presumably induced against tumor cell
antigens
• S
15. HYPERTROPHIC OSTEOARTHROPATHY
• This disorder is characterized by
• (1) periosteal new bone formation, primarily at the distal ends of long bones,
metatarsals, metacarpals, and proximal phalanges;
• (2) arthritis of the adjacent joints; and
• (3) clubbing of the digits
16. • migratory thrombophlebitis (Trousseau syndrome) may be encountered in
association with deep-seated cancers, most often carcinomas of the pancreas or
lung. Disseminated intravascular coagulation
• nonbacterial thrombotic endocarditis,
17. GRADING AND STAGING OF TUMORS
Grading. based on the
• degree of differentiation of the tumor cells
• and, in some cancers, the number of mitoses
• or architectural features
18. • Staging. The staging of solid cancers is 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.
19. LABORATORY DIAGNOSIS OF CANCER
Histologic and Cytologic Methods
• 1) excision or biopsy,
• (2) needle aspiration, and
• (3) cytologic smears
24. IMMUNOHISTOCHEMISTRY.
• Categorization of undifferentiated malignant
tumors.
• Determination of site of origin of metastatic
tumors.
• Detection of molecules that have prognostic or
therapeutic significance
26. CIRCULATING TUMOR CELLS.
• Instrumentation that permits detection, quanti cation, and characterization of
rare solid tumors cells (e.g., carcinoma, melanoma) circulating in the blood is
being explored as a diagnostic modality.
27.
28. MOLECULAR AND CYTOGENETIC DIAGNOSTICS.
• Diagnosis of malignant neoplasms.
• Prognosis of malignant neoplasms.
• Detection of minimal residual disease.
• Diagnosis of hereditary predisposition to cancer.
• Guiding therapy with oncoprotein directed drugs.
BCR-ABL fusion gene in chronic myelogenous leukemia and acute lymphoblastic
leukemia; ERBB1 (EGFR) mutations and ALK gene rearrangements in lung cancer;
and BRAF mutations in melanoma.
29. MOLECULAR PRO LES OF TUMORS: THE FUTURE
OF CANCER DIAGNOSTICS
• The most common method for large-scale analysis of RNA expression in use
today in research laboratories is based on DNA microarrays
