Rubin's Chapter 5 Flashcards
25 yo M presents 1 week after discovering that his left testicle is twice normal size. Physical: non-tender, testicular mass. Histological exam shows embryonal carcinoma. Compared to normal adult somatic cells, this germ cell neoplasm would show high levels of which protein?
Telomerase. Somatic cells don’t normally express telomerase, which is an enzyme that adds repetitive sequences to maintain the length of the telomere. Normally, with each round of somatic cell replication, the telomere shortens, governing the lifespan of replicating cells. Cancer cells and embryonic cells express high levels of telomerase, by activating the gene for the catalytic subunit of telomerase: human telomerase reverse transcriptase.
25 yo F presents for gyno exam. Cervical pap smear shows koilocytic atypia characterized by perinuclear halos and wrinkled nuclei. She has invasive squamous cell carcinoma. Molecular tests for HPV in the tumor cells are positive. What mechanism of disease explains the role of HPV in the pathogenesis of neoplasia in this patient?
Inactivation of tumor suppressor proteins. Unlike RNA tumor viruses whose oncogenes have normal cellular counterparts, the transforming genes of DNA viruses are not homogenous with any cellular genes. The gene products of oncogenic DNA viruses inactivate tumor suppressor proteins. Ex: proteins encoded by the E6 and E7 genes of HPV16, bind p53 and rRb.
A pathological exam reveals dysplastic squamous cells occupying the entire thickness of the cervical epithelium with no evidence of epithelial maturation. The basal membrane is intact. What term describes this lesion?
Carcinoma in situ. Most carcinomas begin as localized growths confined to the epithelium n which they arise. As long as they don’t penetrate the basal membrane that the epithelium rests on, they’re considered in situ.
62 yo F presents w/ breast lump that she discovered 6 days ago. Breast biopsy shows lobular carcinoma in situ. Compared to normal epithelial cells of the breast lobule, these malignant cells would most likely show decreased expression of which protein?
E-cadherin. Cadherins are Ca2+ dependent transmembrane glycoproteins that mediate cell-cell adhesion They suppress invasion and metastasis.
80 y M complains of lower abdominal pain, increasing weakness and fatigue. He has lost 16 lb in the past 6 months. The prostate specific antigen test is elevated and rectal exam reveals an enlarged prostate. Needle biopsy discloses prostatic adenocarcinoma. Histological grading of the carcinoma is based on what criteria?
Resemblance to normal tissue of origin. To establish criteria for therapy, many cancers are classified according to histological grading schemes or by staging protocols that describe the extent of the spread. Cancer grading reflects cellular characteristics. Low-grade tumors are well differenti- ated, whereas high-grade tumors lack differentiated features (anaplasia).
A 50 yo F presents with lump in her breast. A 4 cm firm and fixed mass is noted on exam. Excision biopsy reveals malignant cells that form gland-like structures and solid nests, surrounded by dense collagenous stroma. A CT stain, trichrome, shows blue areas. What would describe these blue areas?
Desmeoplastic. Secondary descriptors are used to classify tumors:
medullary = soft cellular
scirrhous/desmplastic = dense, fibrous stroma
colloid carcinomas = abundant mucus secretion
comedocarcinoma = intraductal neoplasm w/ necrotic material expressed from ducts
65 yo M complains of muscle weakness and a dry cough for 4 months. He has smoked 2 ppd for 45 years. CXR shows 4 cm central, left lung mass. Labs show hyperglycemia and hypertension. Transbronchial biopsy shows small cell carcinoma. Metastases to the liver are detected by CT scan. What accounts for the development of hyperglycemia and hypertension?
Paraneoplastic syndrome – collective term for remote effects that cancers produce. This is Cushing Syndrome: hyperglycemia and hypertension due to secretion of ACTH, corticotropin. This is most often seen with small cell carcinoma of the lung.
60 yo M w/ 4 month history of weight loss, wheezing and SOB. Smoked 2 ppd for 40 yrs. PMH: emphaysema and chronic bronchitis. CXR: 10 cm mass on left lung. Bronchoscopy shows obstruction of left main stem bronchus. Immunohistochemical stains of biopsy would show expression of which tumor markers?
Cytokeratins. Tumor markers are products of malignant neoplasms that can be detected in cells or body fluids. Useful tumor markers include immunoglobulins, fetal proteins, enzymes, hormones and cytoskeletal proteins. Carcinomas uniformly express cytokeratins, which are intermediate filaments.
Alpha-fetoprotein - marker for yolk cell carcinoma and hepatocellular carcinoma.
Calretinin - marker for mesothelioma
Carcinoembryonic antigen - colon carcinoma and others
Synaptophysin - neuroendocrine tumors, and small cell carcinoma of the lung.
What potent carcinogen may be involved in the lung cancer pathogenesis of this patient:
60 yo M w/ 4 month history of weight loss, wheezing and SOB. Smoked 2 ppd for 40 yrs. PMH: emphaysema and chronic bronchitis. CXR: 10 cm mass on left lung.
Polycyclic aromatic hydrocarbons - derived from coal tar - very well-studied carcinogens. Often produce cancer at the site of application and have been identified in cigarette smoke.
Aflatoxin B = liver carcinogen
Abestos = mesothelioma and adenocarcinoma of the lung
Vinyl Chlrodie = angiosarcoma of the liver
33 yo F discovers lump in left breast on self-exam. Mom and sister both had breast cancer. Mammogram shows ill-defined density in the outer quadrant of the left breast with microcalcifications. Needle aspiration reveals the presence of malignant, ductal epithelial cells. Genetic screening identifies the BRCA 1 mutation. BRAC1 protein provides cell cycle control and what other cellular function?
DNA Repair. Breast cancer susceptibility genes (BRCA 1 and 2) encode tumor suppressor proteins involved in checkpoint functions related to progression of the cell cycle into S phase. BRCA 1 and 2 proteins also promote DNA repair by binding to RAD51, which mediates DNA double-strand repair breaks.
A 60-year-old man who worked for 30 years in a chemical factory complains of blood in his urine. Urine cytology discloses dysplastic cells. A bladder biopsy demonstrates transitional cell carcinoma. Which carcinogen was most likely involved in the pathogenesis of bladder cancer in this patient?
Aniline dyes. Transitional cell carcinoma is the most common malignant tumor of the urinary bladder, and the incidence of bladder cancer is increased in aniline dye workers. These azo dyes are converted to water-soluble car- cinogens in the liver. They are excreted in the urine, where they primarily affect the transitional epithelium of the bladder.
Benzene exposure - leukemia.
Vinyl chloride exposure - hepatic angiosarcomas.
60 yo M presents w/ ulcerated, encrusted and infiltrating lesion on the sun-exposed dorsal aspect of a finger. Biopsy shows squamous cell carcinoma. The metastatic potential of this neoplasm would be enhanced by up regulation of the gene for which protein?
Plasminogen Activator - malignant cells and stream cells associated with cancers use proteases that degrade basement membrane components. These enzymes include urokinase-type plasminogen activator u-PA, and matrix metalloproteinases. u-PA converts serum plasminogen to plasmin, a serine protease that degrades laminin and activates type 4 procollagenase. Changes in the u-PA or its receptor or inhibitors are seen in cancer.
45 yo M presents with a 9 month history of a red nodule on his foot. Biopsy of the nodule discloses a poorly demarcated lesion composed of fibroblasts and endothelial-like cells lining vascular spaces. Similar lesions are found in the lymph nodes and liver. The tumor cells contain sequences of human herpes virus 8. The patient most likely has what disease?
Acquired Immunodeficiency. He has Kaposi sarcoma associated with AIDS. The cancer cells contain HHV-8 which is also known as Kaposi-sarcome associated herpes virus. In addition to infecting the spindle cells of Kaposi sarcoma, HHV-8 is lymphotropic and has been implicated in two uncommon B-cell lymphoid malignancies, namely, primary effusion lymphoma and multicentric Castleman disease. Like other DNA viruses, the HHV-8 genome encodes pro- teins that interfere with the p53 and pRb tumor suppressor pathways.
During a routine checkup, a 50-year-old man is found to have blood in his urine. He is otherwise in excellent health. Abdominal CT scan shows 2 cm renal mass. You inform the patient that the key to prognosis and selecting treatment is the staging of this tumor. What’s the most important factor in staging for this patient?
Metastases to regional lymph nodes. The choice of surgery or other treatment depends on the stage of a cancer. The criteria for staging includes: 1) tumor size, 2) extent of local growth, 3) presence of lymph node metastases, and 4) presence of distant metastases.
A 68 year old man who worked in a shipyard and manufacturing plant his whole life complains of a 4 month history of chest discomfort, malaise, fever, night sweats and weight loss. CXR shows large pleural effusion. 5 months later the patient dies of cardiorespiratory failure due to a malignant neoplasm found on the lung at autopsy. This is associated with which environmental carcinogen?
Asbestos. The characteristic tumor associated with asbestos exposure is mesothelioma of the pleural and peritoneal cavities. This cancer is reported in 2-3% of exposed workers.
Afloxin B – liver carcinogen
Beryllium and silica – lung disease but not cancer.
