CLINICAL FEATURESOF TUMORS:
LOCAL AND HORMONAL EFFECTSLocal effects of the tumor or its metastasis can be due to pressure or destruction by direct infiltration, and bleeding from ulceration.
Endocrine tumors may produce hormones (commoner in benign than malignant tumors), e-g. adrenocortical adenoma can cause Cushings syndrome and pheochromocytoma can cause hypertension.
CANCER CACHEXIA
Loss of body fat, wasting, and profound weakness is referred to as cancer cachexia.The basis for cachexia is multifactorial:
Loss of appetite.Metabolic changes leading to reduced synthesis and storage of fats and increased mobilization of fatty acids from adipocytes.
Production of cachectin (TNF-alpha) by macrophages, and some tumor cells and possibly other humoral factors can produce the metabolic effects of cachexia.
PARANEOPLASTIC SYNDROMES:
DefinitionSymptoms not directly related to the primary tumor or its metastasis or elaboration of hormones indigenous to the tissue from which the tumor arose.
Paraneoplastic syndromes may be the earliest manifestation of a tumor and may mimic distant spread.
The commonest syndromes include:
Endocrinopathies: Ectopic hormone or hormone-like factors production by nonendocrine cancers e.g., parathormone by squamous cell carcinoma of the lung, inappropriate ACTH or ADH release by small cell cancers of the lung, polycythaemia due to erythropoetin production by renal cell carcinoma , hypoglycemia due to production of insulin or a like factor by hepatocellular carcinoma .
Myopathy, neuropathy, encephalopathy or myesthenic syndromes as in lung cancers possibly due to immunological mechanisms.
Hypertrophic osteoarthropathy and finger clubbing in lung cancer (unknown cause).
Vascular and hematological changes:Non-bacterial thrombotic endocarditis and DIC, in advanced cancers due to hypercagulibility.
Nephrotic syndrome in various cancers mediated by tumor antigens and immune complexes.
Grading and Staging of CancerMethods to quantify the probable clinical aggressiveness of a given neoplasm and its apparent extent and spread in the individual patient are necessary for arriving at an accurate prognosis and for comparing end results of various treatment protocols. For instance, the results of treating well-differentiated thyroid adenocarcinomas localized to the thyroid gland will on average be very different from those obtained from treating highly anaplastic thyroid cancers that have invaded the neck organs.
Grading: grading of a cancer is based on the degree of differentiation of the tumor cells, generally range from two categories (low grade and high grade) to four categories, Although histologic grading is useful, the correlation between histologic appearance and biologic behavior is less than perfect. In recognition of this problem and to avoid spurious quantification, it is common practice to characterize a particular neoplasm in descriptive terms, for example, well-differentiated, mucin-secreting adenocarcinoma of the stomach, or poorly differentiated pancreatic adenocarcinoma.
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 bloodborne metastases. The major staging system currently in use is the American Joint Committee on Cancer Staging. This system uses a classification called the TNM systemT for primary tumor, N for regional lymph node involvement, and M for metastases. TNM staging varies for specific forms of cancer, but there are general principles. The primary lesion is characterized as T1 to T4 based on increasing size. T0 is used to indicate an in situ lesion. N0 would mean no nodal involvement, whereas N1 to N3 would denote involvement of an increasing number and range of nodes. M0 signifies no distant metastases, whereas M1 or sometimes M2 reflects the presence and estimated number of metastases. In modern practice, grading and staging of tumors are being supplemented by molecular characterization.
LABORATORY DIAGNOSIS OF CANCER:
I. HISTOLOGICAL AND CYTOLOGICAL METHODSA. Histological methods
Histological examination is the most important method of diagnosis.Proper diagnosis is aided by:
Availability of all relevant clinical data.
Adequate preservation and sampling of the specimen.
Frozen specimens are sometimes required for hormone or cell surface receptor study.
A-Routine (H&E)
staining is the corner stone of tissue-based diagnosis. The process stains thin tissue sections so that pathologists can visualize tissue morphology. The process uses a haematoxylin dye to stain cell nuclei (and other parts) blue and an eosin dye to stain other structures pink or red. Properly applied, this technique provides exceptional detail of tissue structure and the makeup of the cells. This detail is required for tissue-based diagnosis, particularly in the detection and classification of cancer.
The hematoxylin and eosin stain (H&E) is the most widely used stain in histology and histopathology laboratories. When it is properly performed it has the ability to demonstrate a wide range of normal and abnormal cell and tissue components and yet it is a relatively simple stain to carry out on paraffin or frozen sections. In histopathology a high proportion of cases can be diagnosed by an experienced pathologist using an H&E stain alone.
Quick frozen section
Quick frozen section is valuable tool used to rapidly prepare slide for microscopical examination, frozen section is used in clinical and research settings, in surgical pathology frozen sections are routinely used for rapid interoperative diagnosis, the slides prepared by frozen section can be utilized for morphological, immunohistochemical and molecular method.
Clinical application of frozen section teqnique:
1-Rapid diagnosis e.g., of breast cancer2- Define free margin of excision as in CA colon.