Neoplasia: Carcinogenesis, Clinical Effects, Staging, and Diagnosis

Comprehensive flashcards covering carcinogen classifications, chemical and radiant carcinogenesis, viral and microbial oncogenesis, paraneoplastic syndromes, tumor spread, staging, and diagnostic laboratory techniques.

How does the International Agency for Research on Cancer (IARC) define a Group 1 carcinogen, and what are common examples?

Group 1 agents have sufficient evidence of carcinogenicity in humans. Examples include tobacco smoke, alcoholic beverages, Chinese-style salted fish, and consumption of processed meat.

What evidence defines an IARC Group 2A carcinogen, and what are notable examples?

Group 2A agents are probably carcinogenic to humans, having limited evidence in humans and sufficient evidence in experimental animals. Examples include emissions from high-temperature frying of food, occupational exposures as a hairdresser or barber, consumption of red meat, and night shift work.

How does the IARC define Group 2B carcinogens, and what exposures fall into this category?

Group 2B agents are possibly carcinogenic to humans, having limited evidence in humans and less than sufficient evidence in experimental animals. Examples include occupational exposures in textile manufacturing, printing processes, traditional Asian pickled vegetables, and radiofrequency electromagnetic fields.

What defines an IARC Group 3 agent, and what proportion of evaluated substances fall into this class?

Group 3 agents are not classifiable as to their carcinogenicity to humans because evidence is inadequate in humans and inadequate or limited in experimental animals. Roughly $50\%$ of all substances analyzed by IARC fall into this category.

What characterizes an IARC Group 4 agent, and which substance was the only one in this category as of 2018?

Group 4 agents are probably not carcinogenic to humans, supported by evidence suggesting a lack of carcinogenicity in humans and animals. As of 2018, only caprolactam falls under Group 4.

What are the three general classes of carcinogenic agents that promote cancer development?

1. Chemicals
2. Radiant energy
3. Microbial agents

Which malignancy is associated with Aflatoxin from Aspergillus?

Hepatocellular carcinoma in association with hepatitis B virus.

What cancers are linked to alcohol consumption?

Squamous cell carcinoma of the oropharynx and upper/middle esophagus, pancreatic carcinoma, and hepatocellular carcinoma.

Which cancers are associated with arsenic exposure?

Squamous cell carcinoma of the skin, lung cancer, and liver angiosarcoma.

What malignancies are associated with exposure to asbestos?

Bronchogenic carcinoma and pleural mesothelioma.

Which malignancy is characteristically associated with benzene exposure?

Acute leukemia.

Which inorganic chemical carcinogens primarily cause bronchogenic carcinoma?

Beryllium, chromium, nickel, and silica.

Which chemical carcinogens are specifically associated with transitional cell carcinoma of the urinary bladder?

Cyclophosphamide and $\beta$-Naphthylamine (aniline dyes).

What malignancy is associated with prenatal exposure to Diethylstilbestrol?

Clear cell carcinoma of the vagina.

Which chemical carcinogen is linked specifically to stomach carcinoma?

Nitrosamines.

Which hepatic malignancy is associated with exposure to polyvinyl chloride (PVC)?

Liver angiosarcoma.

What three steps constitute the sequence of chemical carcinogenesis?

1. Initiation
2. Promotion
3. Progression

What cellular events must occur during the initiation phase of chemical carcinogenesis for a mutation to become fixed and heritable?

Non-lethal irreversible mutations must occur, and carcinogen-altered cells must undergo at least one cycle of proliferation so that the damaged DNA template is replicated and the mutation becomes fixed.

What is the function of promoters during the promotion phase of chemical carcinogenesis?

Promoters stimulate mutated cells to enter the cell cycle. Cell proliferation can also be induced by concurrent exposure to biologic agents (viruses, parasites), dietary factors, or hormonal influences (e.g., estrogen).

What defines the progression phase in chemical carcinogenesis?

Development of tumor heterogeneity, producing cells that have the capability to invade or metastasize.

What is the carcinogenic mechanism of ionizing radiation, and what are typical cancers caused by it?

Mechanism: Hydroxyl free radical injury to DNA. Associated cancers: Acute or chronic myelogenous leukemia, papillary thyroid carcinoma, lung cancer, breast cancer, bone cancer, and liver angiosarcoma (from radioactive thorium dioxide).

What is the mechanism of UV light-induced carcinogenesis, and which neoplasms does it cause?

Mechanism: Formation of pyrimidine dimers that distort DNA. Associated neoplasms: Basal cell carcinoma, squamous cell carcinoma, and malignant melanoma.

Which bacterium is linked to stomach cancer and low-grade malignant lymphoma?

Helicobacter pylori.

Which malignancies are associated with the parasitic infections Schistosoma hematobium and Clonorchis sinensis / Opisthorchis viverrini?

• Schistosoma hematobium: Squamous cell carcinoma of the urinary bladder.
• Clonorchis sinensis and Opisthorchis viverrini: Cholangiocarcinoma of the bile ducts.

Which RNA viruses are oncogenic, and what cancers do they cause?

• Human T-cell leukemia virus type I (HTLV-I): T-cell leukemia/lymphoma.
• Hepatitis C virus (HCV): Primary hepatocellular carcinoma.

Which oncogenic DNA viruses correspond to cervical carcinoma, hepatocellular carcinoma, nasopharyngeal carcinoma, and Kaposi sarcoma?

• HPV: Carcinoma of the cervix
• Hepatitis B virus (HBV): Hepatocellular carcinoma
• Epstein-Barr virus (EBV): Certain forms of lymphoma and nasopharyngeal carcinoma
• HHV 8: Kaposi sarcoma

What is cancer cachexia, and what is its underlying mechanism?

Cancer cachexia is an irreversible wasting disease characterized by a catabolic state mediated by tumor necrosis factor-alpha ($\text{TNF-}\alpha$) secreted by macrophages and cancer cells. $\text{TNF-}\alpha$ suppresses the hypothalamic appetite center and decreases $\beta$-oxidation of fatty acids.

What are the common causes of iron deficiency anemia and macrocytic anemia in cancer patients?

• Iron deficiency anemia: Gastrointestinal blood loss (e.g., from colorectal cancer).
• Macrocytic anemia: Folate deficiency resulting from rapid tumor cell growth.

What is myelophthisic anemia, and what peripheral blood smear findings characterize it?

Anemia resulting from bone metastasis. It causes a leukoerythroblastic smear containing nucleated RBCs, immature neutrophils (e.g., myeloblasts, metamyelocytes), and teardrop RBCs indicating myelofibrosis secondary to bone involvement.

What mechanisms cause vessel thrombosis and disseminated intravascular coagulation (DIC) in cancer patients?

• Vessel thrombosis: Thrombocytosis, increased synthesis of coagulation factors (fibrinogen, factors V and VIII), and procoagulant release from tumor cells (e.g., pancreatic carcinoma).
• DIC: Release of tissue thromboplastin from cancer cells.

What are paraneoplastic syndromes, and what percentage of cancer patients do they affect?

Distant clinical effects of a tumor that are unrelated to direct metastasis or local spread. They occur in $10\%$ to $15\%$ of cancer patients, may predate the onset of metastatic disease, mimic metastasis, and often involve ectopic hormone production.

Which cancers and ectopic hormones are associated with paraneoplastic Cushing syndrome and gynecomastia?

• Cushing syndrome: Small cell carcinoma of the lung and medullary carcinoma of the thyroid via ectopic ACTH.
• Gynecomastia: Choriocarcinoma (testis) via ectopic hCG.

Which paraneoplastic hormone causes hypercalcemia, and what tumors commonly secrete it?

PTH-related protein (PTHrP), secreted by renal cell carcinoma, primary squamous cell carcinoma of the lung, and breast carcinoma.

Which cancers and ectopic hormones are associated with paraneoplastic hyponatremia and secondary polycythemia?

• Hyponatremia: Small cell carcinoma of the lung via antidiuretic hormone (ADH).
• Secondary polycythemia: Renal cell carcinoma and hepatocellular carcinoma via erythropoietin.

What are the five major pathways of cancer spread?

1. Direct spread
2. Lymphatics
3. Vascular
4. Transcoelomic spread
5. Perineural

What are transcoelomic spread and perineural spread, and what are classic examples of each?

• Transcoelomic spread: Seeding across peritoneal, pleural, or pericardial cavities causing malignant ascites, pleural effusions, or Krukenberg tumour.
• Perineural spread: Tumor growth along nerve bundles, commonly seen in prostate cancers and adenoid cystic carcinomas.

What criteria are used to determine the grade of a cancer?

Degree of differentiation (low, intermediate, or high grade), nuclear features, and invasiveness.

What do T, N, and M stand for in the TNM staging system, and what tumor size correlates with metastatic potential?

• T: Tumor size ($\ge 2\text{ cm}$ correlates with metastatic ability)
• N: Regional lymph node involvement
• M: Extranodal distant metastases (e.g., liver, lung)

What are the primary clinical utilities of tumor markers?

1. Identifying tumors
2. Estimating tumor burden
3. Detecting tumor recurrence

Which neoplasms are associated with the tumor markers AFP, CEA, and Bence Jones protein?

• AFP: Hepatocellular carcinoma, yolk sac tumor (endodermal sinus tumor) of ovary or testis
• CEA: Colorectal and pancreatic carcinomas
• Bence Jones protein: Multiple myeloma, Waldenström's macroglobulinemia (representing free light chains in urine)

Which cancers are monitored using the glycoprotein markers CA 15-3, CA 19-9, CA 125, and PSA?

• CA 15-3: Breast carcinoma
• CA 19-9: Pancreatic carcinoma
• CA 125: Surface-derived ovarian cancer (e.g., serous cystadenocarcinoma)
• PSA: Prostate carcinoma (also elevated in prostate hyperplasia)

What sampling approaches are employed in histologic and cytologic diagnosis of cancer?

1. Excision and incisional biopsy
2. Fine needle aspiration (FNA)
3. Cytologic smears (Pap smears and other fluid smears, from which cell blocks can be prepared)

What are the three main clinical applications of immunohistochemistry in oncology?

1. Categorization of undifferentiated malignant tumors (distinguishing anaplastic carcinomas, lymphomas, melanomas, and sarcomas)
2. Determination of the site of origin of metastatic tumors
3. Detection of molecules with prognostic or therapeutic significance (e.g., ER and PR in breast cancer)

What does flow cytometry measure, and what neoplasms is it particularly helpful in evaluating?

It rapidly and quantitatively measures individual cell characteristics, including membrane antigens and tumor cell DNA content. It is particularly useful for identifying and classifying neoplasms of T and B lymphocytes and mononuclear-phagocytic cells.

What are the four primary diagnostic applications of molecular diagnosis in oncology?

1. Differentiating benign polyclonal from malignant monoclonal T or B cell proliferations
2. Determining prognosis of neoplasms (e.g., N-MYC amplification and 1p deletion in neuroblastoma)
3. Detecting minimal residual disease
4. Diagnosing hereditary cancer predispositions (e.g., germline mutations in BRCA1, BRCA2, RET proto-oncogene)