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Carcinogenesis and Paraneoplastic Syndrome

Some occupational cancers

Arsenic: lung, skin, hemangiosarcoma
Asbestos: lung, mesothelioma, esophagus, stomach
Benzene: leukemia, lymphoma
Berrylium: lung
Cadmium: prostate
Chromium: lung
Ethylene oxide: leukemia
Nickel: nose, lung
Radon and its decay products: lung
Vinyl chloride: angiosarcoma, liver
Chimney sweepers: SCC
Kangari cancer due to hot water container
Mahogany wood: nasopharyngeal cancer
Aniline dyes: bladder cancer

CHEMICAL CARCINOGENS

Direct-Acting Carcinogens
Alkylating Agents like anticancer drugs (cyclophosphamide, chlorambucil, nitrosoureas, and others)
Acylating Agents- dimethyl carbamide chloride
Procarcinogens That Require Metabolic Activation
Polycyclic and Heterocyclic Aromatic Hydrocarbons in smoke like Benz(a)anthracene, Benzo(a)pyrene

Aromatic Amines, Amides, Azo Dyes
2-Naphthylamine (b-naphthylamine), Benzidine

Natural Plant and Microbial Products
Aflatoxin B1
Griseofulvin
Betel nuts

Others

Nitrosamine in barbeque and smoked foods
Vinyl chloride, nickel, chromium
Insecticides, fungicides


Radiation carcinogenesis

Children who underwent radiotherapy for lymphoma might develop papillary carcinoma of thyroid later in life

Viral carcinogenesis
HTLV-1 causing T cell leukemia
EBV causing Burkit’s lymphoma, nasopharyngeal carcinoma and Hodgkin’s lymphoma
HIV causing Kaposi sarcoma and CNS lymphoma
HBV/HCV causing hepatocellular carcinoma
HPV 16/18 causing carcinoma cervix

Helicobacter pylori causes stomach cancer by causing chronic gastritis



PARANEOPLASTIC SYNDROMES

Cushing syndrome: Small cell carcinoma of lung (ACTH )
Syndrome of inappropriate antidiuretic hormone( SIADH): Small cell carcinoma of lung; intracranial neoplasms,
Hypercalcemia: Squamous cell carcinoma of lung:(PTHRP), TGF-a, TNF, IL-1
Hypoglycemia: Fibrosarcoma (Insulin, IGF)
Carcinoid syndrome: Bronchial carcinoid (Serotonin, bradykinin)
Polycythemia: (Erythropoietin) released by Cerebellar hemangioma, Renal carcinoma, Hepatocellular carcinoma

Myasthenia Bronchogenic carcinoma
Acanthosis nigricans Gastric carcinoma
Hypertrophic osteoarthropathy Bronchogenic carcinoma
Migratory thrombophlebitis(Trousseau phenomenon) Pancreatic carcinoma

TUMOR MARKERS
can be hormones, enzymes, glycoproteins

Human chorionic gonadotropin( hCG): choriocarcinoma
Calcitonin: Medullary carcinoma of thyroid
Catecholamine and metabolites Pheochromocytoma , eg vanillyl mandelic acid, metanephrine, homovanillic acid
Ectopic hormones See Paraneoplastic Syndromes
a-Fetoprotein( AFP), eg Liver cell cancer, nonseminomatous germ cell tumors of testis
Carcinoembryonic antigen( CEA) Carcinomas of the colon, pancreas, lung, stomach, and heart

Prostatic acid phosphatase

Neuron-specific enolase( NSE) Small cell cancer of lung, neuroblastoma
Immunoglobulins: Multiple myeloma
Prostate-specific antigen (PSA)
Mucins
CA-125 Ovarian cancer
CA-19-9 Colon cancer, pancreatic cancer
CA-15-3 Breast cancer

Clinical symptoms of cancer

Symptoms occur in cancer due to
(1) location and impingement on adjacent structures,
(2) functional activity such as hormone synthesis or the development of paraneoplastic syndromes,
(3) bleeding and infections when the tumor ulcerates through adjacent surfaces,
(4) symptoms that result from rupture or infarction, and
(5) cachexia or wasting

Staging and grading of cancer

Grading is a histopathological process of grading the differentiation of cancer cells
Staging is a clinical process of determining the extent of the tumor
Eg of grading is Broder’s grading done for squamous cell carcinoma according to the keratin pearls present in the cancer cells
Staging is usually done by TNM staging as advised by AJC
T stands for tumor size and extent
N stands for extent of lymph node involvement
M stands for metastasis
Duke’s staging for colon carcinoma is almost similar to TNM classification

Example: TNM staging of lung cancer

T1 Tumor <3>
T2 Tumor >3 cm or involvement of main stem bronchus 2 cm from carina, visceral pleural involvement, or lobar atelectasis
T3 Tumor with involvement of chest wall (including superior sulcus tumors), diaphragm, mediastinal pleura, pericardium, main stem bronchus 2 cm from carina, or entire lung atelectasis
T4 Tumor with invasion of mediastinum, heart, great vessels, trachea, esophagus, vertebral body, or carina or with a malignant pleural effusion


N0 No demonstrable metastasis to regional lymph nodes
N1 Ipsilateral hilar or peribronchial nodal involvement
N2 Metastasis to ipsilateral mediastinal or subcarinal lymph nodes
N3 Metastasis to contralateral mediastinal or hilar lymph nodes, ipsilateral or contralateral scalene, or supraclavicular lymph nodes
M0 No (known) distant metastasis
M1 Distant metastasis present

staging

Stage Ia T1 N0 M0
Stage Ib T2 N0 M0
Stage IIa T1 N1 M0
Stage IIb T2 N1 M0 / T3 N0 M0
Stage IIIa T1–3 N2 M0 / T3 N1 M0
Stage IIIb Any T N3 M0 / T3 N2 M0T4 / Any N M0
Stage IV Any T Any N M1

Diagnosis of cancer

2 ways of obtaining cells for histological examination: cytology and biopsy
Cytology: eg touch smear, brush smear, bronchoalveolar lavage or exfoliative cytology like Pap smear, FNAC( fine needle aspiration cytology)
Biopsy: incisional or excisional biopsy
Ways of obtaining incisional biopsy: trucut biopsy, punch biopsy, cone biopsy, ring biopsy of cervix, ultrasound guided biopsy, etc

Frozen section is a method of tissue preparation which gives very quick result, within minutes, so that decision can be made intraoperatively as to how much resection is needed, or if the tumor is benign, or is the margin clear, or is the tumor unresectable, etc
Detecting tumor markers in the blood: diagnostic, prognostic, or to check response to therapy
Certain receptors present in the tumor will dictate which anticancer drug to use, eg tamoxifen is used if estrogen receptor is present in the breast cancer tissue.


Normal Papanicolaou smear from the uterine cervix. Large, flat cells with small nuclei. B, Abnormal smear containing a sheet of malignant cells with large hyperchromatic nuclei. There is nuclear pleomorphism, and one cell is in mitosis. There are few interspersed neutrophils with compact lobated nuclei and much smaller size