a = new Array(298);
var f = "<FONT FACE=ARIAL SIZE=2>"
a[0] = ""
a[1] = f + "(A) Incorrect. Many breast cancers are estrogen receptor positive, which suggests that hormonal therapy will be helpful."
a[2] = f + "(B) CORRECT. The lack of metastases suggests a lower stage and a better prognosis."
a[3] = f + "(C) Incorrect. Both aneuploidy and a high S-phase are characteristic for malignancies and suggest a worse prognosis."
a[4] = f + "(D) Incorrect. A history of breast cancer suggests a greater risk for breast cancer, but does not predict prognosis."
a[5] = f + "(E) Incorrect. A higher grade suggests a worse prognosis."
a[6] = f + "(A) CORRECT. Many human carcinomas are associated with RAS mutations that contribute to oncogenesis."
a[7] = f + "(B) Incorrect. Vimentin is a more typically marker for soft tissue malignancies (sarcomas). Carcinomas are positive for cytokeratin by immunohistochemistry."
a[8] = f + "(C) Incorrect. Bacterial infections do not tend to increase the risk for adenocarcinoma."
a[9] = f + "(D) Incorrect. Adenocarcinomas of the colon are generally not seen with significantly increased frequency in persons with immunodeficiency diseases."
a[10] = f + "(E) Incorrect. Adenocarcinomas of the colon are generally not seen with significantly increased frequency in persons with collagen vascular diseases."
a[11] = f + "(A) Incorrect. Either a neoplasm or a granuloma could recur. It is not just neoplasms that can recur. Many inflammatory processes go on and on."
a[12] = f + "(B) Incorrect. Some neoplasms can increase in size quickly, but so can granulomas with some infections."
a[13] = f + "(C) Incorrect. Response to therapy is not always a reliable indicator that the presumed disease was actually present. The natural course of the disease may be waning while therapy is being given, with actual no cause-effect relationship."
a[14] = f + "(D) CORRECT. A neoplasm is new, uncontrolled growth of cells."
a[15] = f + "(E) Incorrect. Any mass lesion can undergo necrosis, particularly if it is large and outgrows the blood supply."
a[16] = f + "(A) Incorrect. Breast cancer incidence is highest for women from Europe and North America."
a[17] = f + "(B) Incorrect. Colon cancers are most prevalent in developed nations and when diets are low in fiber."
a[18] = f + "(C) Incorrect. Lung cancer is most related to smoking."
a[19] = f + "(D) CORRECT. Gastric cancers are more prevalent in Japan. Is this genetics or environment? The risk goes down with emigration and subsequent generations living outside of Japan. The prevlance of <I>H. pylori</I> infection may play a role. Incidence of gastric cancer has diminished in the U.S."
a[20] = f + "(E) Incorrect. Uterine cancers include endometrium and cervix. The latter is related to HPV infection, and Pap smear screening has markedly reduced the risk for development of fatal cervical cancers."
a[21] = f + "(A) Incorrect. This classification is for a small primary cancer with nodal metastases but no distant metastases."
a[22] = f + "(B) Incorrect. This classification is for a small primary cancer with no lymph node metastases but with distant metastases."
a[23] = f + "(C) Incorrect. This classification is for a larger primary cancer with nodal metastases but no distant metastases."
a[24] = f + "(D) Incorrect. This classification is for a larger primary cancer with no metastases to either lymph nodes or to distant sites."
a[25] = f + "(E) CORRECT. She has a large invasive (high T) primary tumor mass with axillary node (N > 0) and lung metastases (M1)."
a[26] = f + "(A) Incorrect. While this feature is more prominent in malignant neoplasms, it may be present in benign neoplasms, too."
a[27] = f + "(B) Incorrect. Atypia can be part of benign or dysplastic processes that are not malignant."
a[28] = f + "(C) CORRECT. Metastasis would be an even better indicator, but invasion suggests malignancy more than the other items listed here."
a[29] = f + "(D) Incorrect. A high N/C ratio is one feature of malignancy, but is not the best indicator."
a[30] = f + "(E) Incorrect. Necrosis may occur for many reasons. Even a benign tumor could cause pressure necrosis or outgrow its blood supply."
a[31] = f + "(A) Incorrect. Criteria for malignancy must be satisfied first, then grading and staging follow."
a[32] = f + "(B) Incorrect. Grading and staging are most useful for epithelial malignancies, but are not reserved specifically for them."
a[33] = f + "(C) Incorrect. It may indeed spread to lymph nodes, particularly if it is a carcinoma, or distant sites, but is less likely to do so if it has a low grade and it remains small and localized."
a[34] = f + "(D) Incorrect. It may have an in situ component, but the behavior of most neoplasms is judged by the worst part of it, and stage I puts it beyond in situ."
a[35] = f + "(E) CORRECT. A well-differentiated and localized neoplasm usually has both a low grade and low stage. In such cases surgery is more likely to be curative."
a[36] = f + "(A) Incorrect. Hydrocarbon exposure can predispose to development of leukemias."
a[37] = f + "(B) Incorrect. Radon gas exposure can increase the risk for lung cancer."
a[38] = f + "(C) Incorrect. Cyclophosphamide is an alkylating agent used for chemotherapy, but this drug can promote leukemia, lymphoma, and carcinoma."
a[39] = f + "(D) Incorrect. Asbestos exposure can increase the risk for lung cancer particularly in persons who smoke. It is also associated with the rare neoplasm known as mesothelioma."
a[40] = f + "(E) CORRECT. This is a rare cause of cancer. However, this causal relationship is easy to demonstrate, because hepatic angiosarcoma is a rare neoplasm. What else could happen? At least a hundred new chemical compounds are dumped into the environment each year."
a[41] = f + "(A) Incorrect. Most breast carcinomas are sporadic, though some are related to BRCA1 and BRCA2 or other gene mutations which can be inherited, though the onset of disease occurs in young adults."
a[42] = f + "(B) Incorrect. Most small cell carcinomas of the lung are related to smoking."
a[43] = f + "(C) CORRECT. The RB gene is the classic example of the 'two hit' mechanism for loss of tumor suppression. About 60% of these tumors are sporadic, while others are familial, and there is inheritance of a mutated copy of the RB gene. Loss of the second copy in retinoblasts leads to the occurrence of retinoblastoma in childhood."
a[44] = f + "(D) Incorrect. Gliomas of the brain are mostly sporadic."
a[45] = f + "(E) Incorrect. CML is most often associated with the 'Philadelphia chromosome'."
a[46] = f + "(A) Incorrect. Chronic alcoholism can lead to micronodular cirrhosis, and in this setting hepatocellular carcinomas can arise."
a[47] = f + "(B) CORRECT. Radiation is oncogenic. Cancers of thyroid and bone often develop in children with radiation exposure. Leukemias can occur as well."
a[48] = f + "(C) Incorrect. This is a disorder of DNA instability in which leukemias, lymphomas, and breast cancers may arise."
a[49] = f + "(D) Incorrect. Trauma is not a risk for neoplasia."
a[50] = f + "(E) Incorrect. Arsenic exposure can increase the risk for skin cancer. For years, pressure-treated lumber to prevent wood rot has relied upon use of arsenical compounds. There is a lot of that treated wood out in the environment."
a[51] = f + "(A) Incorrect. Melanomas arise on the skin in most cases and are rarely visceral or in soft tissue."
a[52] = f + "(B) Incorrect. A hamartoma is a peculiar small benign neoplasm composed of tissues normal to a site, but just in a jumbled mass. A pulmonary hamartoma is the most common of these."
a[53] = f + "(C) Incorrect. Adenocarcinomas do not arise in soft tissues. Sarcomas arise in soft tissues."
a[54] = f + "(D) Incorrect. It is unlikely that matted nodes with lymphoma would reach this size."
a[55] = f + "(E) CORRECT. Sarcomas are big and bad. They arise in soft tissues derived from mesenchymal (connective) tissues. Retroperitoneum is a typical location."
a[56] = f + "(A) Incorrect. p53 is a tumor suppressor gene, and mutations can be found in a variety of human carcinomas."
a[57] = f + "(B) Incorrect. RB is a tumor suppressor gene best known for association with retinoblastomas of the eye."
a[58] = f + "(C) CORRECT. This is the 'Philadelphia chromosome' of chronic myelogenous leukemia (CML). Therapy with a biologic agent such as imatinib that targets the abnormal protein produced by the BCR-ABL fusion gene is often effective."
a[59] = f + "(D) Incorrect NF-1 is a tumor suppressor gene associated with neurofibromatosis.."
a[60] = f + "(E) Incorrect. RAS is an oncogene found in many human carcinomas."
a[61] = f + "(A) Incorrect. Retinoblastomas occur with loss of alleles for a suppressor oncogene on chromosome 13."
a[62] = f + "(B) Incorrect. Most of these cancers are related to smoking."
a[63] = f + "(C) CORRECT. Human T-lymphocytotropic virus (HTLV) infection can lead to T-cell leukemia. However, few human cancers arise as a result of viral oncogenesis."
a[64] = f + "(D) Incorrect. Adenocarcinomas of the prostate are common, but are not associated with preceding viral infection."
a[65] = f + "(E) Incorrect. Hepatic angiosarcoma is causally related to vinyl chloride exposure."
a[66] = f + "(A) Incorrect. FISH is useful to identify abnormal expression of known genes, because a specific marker is needed. The best example is detection of HER2/neu amplification in breast cancers."
a[67] = f + "(B) Incorrect. Flow cytometry analyzes DNA content and can use markers for known components of cells."
a[68] = f + "(C) Incorrect. Immunohistochemistry identifies protein products of gene expression, and is most useful to determine the cell of origin of a cancer, or identify a characteristic of that cancer, such as estrogen receptor expression."
a[69] = f + "(D) CORRECT. SNPs can be analyzed to find alterations present in cancer cells. One could analyze multiple histologically similar cancers to determine what gene(s) alteration(s) such as deletions and amplifications may underlie carcinogenesis. Using millions of SNPs can produce a virtual karyotype down to the gene level."
a[70] = f + "(E) Incorrect. Serum tumor markers, such as prostate specific antigen, utilize known characteristics of cancer protein expression. Tumor markers tend to be insensitive for early detection of cancer."
a[71] = f + "(A) Incorrect. Dysplasias should not be ignored, because they can progress to carcinomas."
a[72] = f + "(B) Incorrect. Cervical dysplasias are associated with human papillomavirus infection, but HPV is cannot be treated with antibiotic therapy. In general, most women will clear the virus. However, it is a sexually transmitted disease, and further infections can occur."
a[73] = f + "(C) Incorrect. Dysplasias are confined to the epithelium, so there is no benefit to chemotherapy."
a[74] = f + "(D) CORRECT. Cervical dysplasia is a pre-neoplastic condition that has the potential to develop into a carcinoma if not treated. Epithelia subjected to initiators and promoters of carcinogenesis tend to undergo progression from metaplasia to dysplasia to carcinoma. Even a carcinoma is essentially 100% curable when it is limited to the epithelium (in situ). That is why you try to diagnose the lesion as early as possible."
a[75] = f + "(E) Incorrect. Dysplasias are confined to the epithelium, and there is no benefit to radiation therapy."
a[76] = f + "(A) CORRECT. He has an adenocarcinoma of the colon. Such lesions are often associated with blood loss from mucosal erosion and necrosis. Cancer cells are less differentiated and less functional than their normal cell of origin and thus less functional. With poor construction come many problems."
a[77] = f + "(B) Incorrect. Colonic adenocarcinoma is not typically associated with autoimmune diseases."
a[78] = f + "(C) Incorrect. Hyperglycemia is unlikely, though inanition with hypoglycemia is possible."
a[79] = f + "(D) Incorrect. Elevation of the AFP in association with neoplasia most often occurs with testicular and liver cancers."
a[80] = f + "(E) Incorrect. The LDH is elevated in a variety of disease conditions and never decreased. In this case, metastatic disease and tissue necrosis may have elevated the LDH."
a[81] = f + "(A) CORRECT. Hemangiomas, teratomas, and fibromatoses are common pediatric neoplasms which are benign."
a[82] = f + "(B) Incorrect. Melanomas are unlikely to appear in the first two decades. They are malignancies that are characterized by change-growth and differences in coloration."
a[83] = f + "(C) Incorrect. Carcinomas are generally uncommon in children. Carcinomas tend to enlarge and invade over time."
a[84] = f + "(D) Incorrect. Lymphomas are never benign. Leukemias and lymphomas are malignancies that can occur in childhood, but they rarely involve skin."
a[85] = f + "(E) Incorrect. Gliomas are not benign. They are one of the common childhood malignancies and occur in the posterior fossa of the brain most often."
a[85.1] = f + "(F) Incorrect. Sarcomas can arise in soft tissues such as the dermis, but this is not a common site for such a neoplasm in children. Sarcomas comprise a larger percentage of malignancies in children than in adults, but only because carcinomas are far less common in children than adults. Cancers in general are not common in children, but the ones that do occur can be aggressive."
a[86] = f + "(A) Incorrect. Asbestos exposure is a risk for bronchogenic carcinoma in persons who are smokers. It is rare."
a[87] = f + "(B) CORRECT. Radon gas is considered to be the second most common cause for lung cancer following tobacco smoking. However, most persons with radon exposure who develop lung cancer are also smokers. A small amount of radon gas naturally seeps up from the soil."
a[88] = f + "(C) Incorrect. The risk for lung cancer is only slightly increased with silica dust exposure. Silica is more likely to produce a restrictive lung disease."
a[89] = f + "(D) Incorrect. Benzene, as are other hydrocarbon compounds, is more likely to affect the bone marrow."
a[90] = f + "(E) Incorrect. Formaldehyde is unpleasant but not a major risk for lung cancer."
a[91] = f + "(A) Incorrect. Epithelial malignancies spread late via the bloodstream. Sarcomas spread early via bloodstream."
a[92] = f + "(B) Incorrect. Seeding through body cavities is possible for a cancer, but more of a late finding for a squamous cell carcinoma."
a[93] = f + "(C) Incorrect. Direct spread to chest wall is a late finding with a central squamous cell carcinoma. Contiguous spread is a form of invasion, which is technically not a metastasis, but still bad."
a[94] = f + "(D) CORRECT. Epithelial malignancies such as a squamous cell carcinoma of the lung often have non-contiguous (metastatic) spread initially to regional lymph nodes. This is important to determine for staging, because the treatment and prognosis depend upon accurate staging."
a[95] = f + "(E) Incorrect. This is a very unlikely mode of spread for a squamous cell carcinoma; however, the cells can be shed into the bronchial tree and that is how they are picked up in a sputum specimen."
a[96] = f + "(A) Incorrect. Necrosis is unlikely to be a feature of a benign neoplasm. The liver is not a common site for multiple benign masses. A primary hepatocellular carcinoma could be multicentric, but arises in the context of chronic hepatitis/cirrhosis, not normal liver."
a[97] = f + "(B) Incorrect. The grade of a tumor is a microscopic diagnosis and indicates the degree of differentiation."
a[98] = f + "(C) Incorrect. The primary neoplasm could be in the stomach, but any number of primary sites could exist for such an appearance."
a[99] = f + "(D) Incorrect. It is not possible to state this with certainty from gross appearance alone."
a[100] = f + "(E) CORRECT. The most likely possibility is that these masses represent metastases from a primary site elsewhere in the body. Thus, this is a malignant neoplasm that has an advanced stage (M1). The umbilication is the result of tumor necrosis with collapse of a tumor nodule."
a[101] = f + "(A) Incorrect. Mutations occuring in some irradiated cells would have no significant immediate effect. Exposure to environmental radiation has this effect, which increases the risk for cancer."
a[102] = f + "(B) CORRECT. The purpose of therapeutic radiotherapy is to try and kill more neoplastic cells than normal cells. This is mediated mainly through generation of oxidant free radicals."
a[103] = f + "(C) Incorrect. Vascular changes do occur following radiation, but are not a desired effect."
a[104] = f + "(D) Incorrect. Necrosis with inflammation will occur following radiation, but the desired effect is to kill neoplastic cells directly Inflammation by itself does not have diagnostic or prognostic value in neoplasia. The immune system may play a role in tumor surveillance to prevent malignancies from occurring, but once a malignancy is established, the immune system is unlikely to eliminate it unaided."
a[105] = f + "(E) Incorrect. ATP depletion may occur as the neoplastic cells die, but this is not the main effect of radiotherapy."
a[106] = f + "(A) Incorrect. Flow cytometry does not distinguish individual chromosomes or count them."
a[107] = f + "(B) Incorrect. Flow cytometry cannot be used to analyze individual genes."
a[108] = f + "(C) CORRECT. Flow cytometry can detect the degree of aneuploidy from the DNA content. Aneuploidy implies that the neoplasm is worse than if it were not aneuploid."
a[109] = f + "(D) Incorrect. Flow cytometry cannot distinguish the cell of origin of neoplasms."
a[110] = f + "(E) Incorrect. Flow cytometry is used to measure DNA content, not RNA content."
a[111] = f + "(A) Incorrect. Adenocarcinomas of the uterus would arise in the endomtrium and are often accompanied by hemorrhage."
a[112] = f + "(B) Incorrect. The slow growth and her asymptomatic condition suggest a benign neoplasm. Leiomyosarcomas of the uterus do occur, but are not common."
a[113] = f + "(C) Incorrect. This is an unusual place for a hematoma, or a collection of blood. Hematomas tend to resolve in days to weeks."
a[114] = f + "(D) CORRECT. The slow growth of the nodule and the lack of symptoms suggests a benign course. Leiomyomas of the uterus are quite common (up to 50% of women have at least one)."
a[115] = f + "(E) Incorrect. Solitary slow-growing metastases are quite rare."
a[116] = f + "(A) Incorrect. Staining with LCA will only tell you that cells are of leukocyte origin, not whether they are part of a neoplastic proliferation."
a[117] = f + "(B) CORRECT. Clonality is a key characteristic of neoplastic cellular proliferations that distinguishes them from reactive proliferations (such as inflammation)."
a[118] = f + "(C) Incorrect. Flow cytometry cannot tell you with certainty that a neoplasm is present."
a[119] = f + "(D) Incorrect. Inflammation could lead to lymphocytosis. Lymphomas are unlikely to have a lymphocytosis."
a[120] = f + "(E) Incorrect. Fibrosis is a feature of inflammation as well as neoplasia."
a[121] = f + "(A) Incorrect. Smoking is associated with many malignancies, including those of lung and the urinary tract, but it is not a risk for skin cancers."
a[122] = f + "(B) Incorrect. Allergies do not give rise to malignancies."
a[123] = f + "(C) Incorrect. The Rb gene is a tumor suppressor gene that can be involved with retinoblastomas and osteosarcomas when a mutation is inherited."
a[124] = f + "(D) Incorrect. Asbestos exposure can increase the risk for bronchogenic carcinomas, mesothelioma, and gastrointestinal adenocarcinomas."
a[125] = f + "(E) CORRECT. Worldwide, more and more skin cancers, including melanoma, are occurring because of sun exposure. The UV light damages the skin and damages cellular DNA, leading to mutations that escape cellular repair mechanisms. Depletion of the earth's protective upper atmospheric ozone layer has not helped, either."
a[126] = f + "(A) Incorrect. A patient with widely disseminated cancer would not be in excellent health, and there would likely be many other masses."
a[127] = f + "(B) Incorrect. Melanomas arise in epidermis and are typically visible on the skin surface. They may infiltrate downward."
a[128] = f + "(C) Incorrect. Such a small, unchanging mass in a young person is unlikely to be a sarcoma."
a[129] = f + "(D) CORRECT. The small size of the lesion, the relatively young age of the patient, and the lack of other findings suggests a benign process."
a[130] = f + "(E) Incorrect. Leiomyomas can theoretically arise in any location with smooth muscle, but in a woman they are most likely to be found in the myometrium."
a[131] = f + "(A) CORRECT. HPV infection, a sexually transmitted disease (STD), is highly associated with cervical dysplasias and malignancies, particularly high risk subtypes 16 and 18 that are now covered by the HPV vaccine. Syphilis is not a risk for epithelial dysplasias or carcinomas, but if one STD is present, others can be present as well."
a[132] = f + "(B) Incorrect. Diabetes mellitus increases the risk for bacterial infections, but does not increase cancer risk."
a[133] = f + "(C) Incorrect. Cigarette smoking is a risk for many cancers, particularly of the lung, but not for cervical carcinoma."
a[134] = f + "(D) Incorrect. PID is most often the result of gonorrheal or chlamydial infections and is not a risk for cancer."
a[135] = f + "(E) Incorrect. Previous chemotherapy can increase the risk for malignancies in general, but not significantly for cervical carcinoma."
a[136] = f + "(A) Incorrect. Prp can be secreted as part of a paraneoplastic syndrome and leads to hypercalcemia. Of lung neoplasms, the one most likely to do this is a squamous cell carcinoma."
a[137] = f + "(B) Incorrect. Erythropoietin secretion leads to increased production of red blood cells. Renal cell carcinomas can do this."
a[138] = f + "(C) CORRECT. He has findings of Cushing syndrome from ectopic ACTH production by the lung tumor, a form of paraneoplastic syndrome common to 'oat cell' carcinomas of the lung."
a[139] = f + "(D) Incorrect. Insulin can be secreted by neuroendocrine neoplasms, such as islet cell tumors and carcinoids."
a[140] = f + "(E) Incorrect. Gastrin can be secreted by neuroendocrine neoplasms, such as islet cell tumors and carcinoids."
a[141] = f + "(A) Incorrect. Gliomas are primary malignant brain neoplasms that rarely metastasize outside the cranial cavity."
a[142] = f + "(B) CORRECT. Lymph node metastases are typical of spread from carcinomas. The first stop along the way is regional nodes, but spread to more distant lymphatic sites is possible."
a[143] = f + "(C) Incorrect. A fibroadenoma is a benign lesion that does not metastasize."
a[144] = f + "(D) Incorrect. Sarcomas typically do not spread via lymphatics."
a[145] = f + "(E) Incorrect. A papilloma is a benign lesion. Laryngeal papillomas may recur locally, but do not spread elsewhere."
a[146] = f + "(A) Incorrect. The PTCH genes are involved in encoding cell membrane 'patched' protein functioning as a receptor for hedgehog proteins involved in cell proliferation. Many basal cell carcinomas of skin have PTCH mutations."
a[147] = f + "(B) CORRECT. Cancers must elaborate growth factors in order to produce an environment for continued growth. VEGF promotes angiogenesis that will keep the neoplasm supplied with blood. VEGF increases the expression of ligands that active the Notch signaling pathway. Biotherapies with monoclonal antibodies can specifically target protein components of cancers."
a[148] = f + "(C) Incorrect. The JAK-STAT pathway promotes neoplastic cell proliferation."
a[149] = f + "(D) Incorrect. TGF-beta signaling represses several cyclins and CDKs, as well as C-MYC, to reduce cell proliferation."
a[150] = f + "(E) Incorrect. The WNT signaling pathway is involved in cell proliferation and adhesion."
a[151] = f + "(A) Incorrect. ADP is released from platelets to signal activation and aggregation of surrounding platelets."
a[152] = f + "(B) Incorrect. The BCR-ABL fusion gene product is the Philadelphia chromosome of chronic myelogenous leukemia that has tyrosine kinase activity."
a[153] = f + "(C) Incorrect. Cyclic AMP is not generally considered part of neoplastic processes. cAMP is a second messenger from activation of G-protein coupled cell surface receptors."
a[154] = f + "(D) Incorrect. Cyclin D appears in the mid G1 phase of the cell cycle and is part of the cell cycle machinery that is influenced by oncogenes."
a[155] = f + "(E) CORRECT. The mechanism described is that of RAS oncogene activation in which the active RAS is permanently turned on and through the MAP kinase pathway activates transcription that drives abnormal, uncontrolled cellular proliferation that leads to neoplasia."
a[155.1] = f + "(F) Incorrect. The p53 gene product is a tumor suppressor, and loss of both p53 alleles results in loss of control over cell proliferation when DNA damage occurs."
a[156] = f + "(A) Incorrect. G0 cells are quiescent and not participating in the cell cycle. This includes most cells in the body."
a[157] = f + "(B) Incorrect. G1 cells have just entered into the cell cycle."
a[158] = f + "(C) CORRECT. A high S-phase, as well as aneuploidy, are features often seen in cancers. The hyperchromatism indicates active DNA synthesis. The estrogen receptor positivity suggests that this breast cancer will respond to hormonal therapy with tamoxifen."
a[159] = f + "(D) Incorrect. G2 is the part of the cell cycle just before division."
a[160] = f + "(E) Incorrect. M is the part of the cell cycle in which cells are dividing. Although more mitoses can be seen in cancers than in normal tissues, the number of cells in mitosis is still not high."
a[161] = f + "(A) Incorrect. Amplification of gene expression typically occurs when there is reduplication of DNA sequences, often with hundreds of copies, greatly increasing the amount of protein produced, which drives cellular proliferation."
a[162] = f + "(B) CORRECT. Epigenetic changes are common in cancers. The DNA is not altered, but methylation occurs to silence DNA expression. If selective hypermethylation of a DNA sequence encoding a tumor suppressor occurred, then the result would be similar to loss of the tumor suppressor gene itself. Genomic imprinting works the same way."
a[163] = f + "(C) Incorrect. Binding of growth factors is one way to control cell signaling, but this does not affect DNA methylation directly."
a[164] = f + "(D) Incorrect. Point mutations alter the DNA directly; methylation affects expression of normal DNA."
a[165] = f + "(E) Incorrect. Micro RNAs often act to inhibit oncogene translation. Hence, reduced miRNA expression has the same effect as loss of a tumor suppressor gene."
a[166] = f + "(A) Incorrect. The RAS oncogene 'turns on' cells to promote carcinogenesis."
a[167] = f + "(B) CORRECT. Abnormal p53 has been identified in many carcinomas. This loss of normal tumor suppression leads to development of carcinomas."
a[168] = f + "(C) Incorrect. The MYC oncogene 'turns on' cells to promote carcinogenesis."
a[169] = f + "(D) Incorrect. The BCR-ABL fusion gene results from a 9:22 translocation (Philadelphia chromosome of chronic myelogenous leukemia) that promotes cellular transformation via protein kinases."
a[170] = f + "(E) Incorrect. The BCL-2 gene acts by decreasing apoptosis (cell death) to cause accumulation of cells, as with follicular lymphomas."
a[171] = f + "(A) CORRECT. Aneuploidy is a bad prognostic finding because such neoplastic cells tend to be much less differentiated and much more aggressive."
a[172] = f + "(B) Incorrect. The presence of estrogen receptor suggests better differentiation and the possibility of treatment with hormonal agents."
a[173] = f + "(C) Incorrect. Well-differentiated tumors usually have a better prognosis."
a[174] = f + "(D) Incorrect. Intraductal growth suggests that this carcinoma remains in situ; infiltration indicates a more aggressive behaviour."
a[175] = f + "(E) Incorrect. The stage of T1 N0 M0 is the lowest possible stage. Neoplasms with a low stage tend to be less agressive and have a better prognosis."
a[176] = f + "(A) Incorrect. Endometrial adenocarcinomas are more frequent in persons who have endometrial hyperplasia."
a[177] = f + "(B) Incorrect. Cirrhosis of the liver from any cause predisposes the patient to development of hepatocellular carcinoma."
a[178] = f + "(C) Incorrect. Dysplastic cervical lesions must be treated because they have a tendency to progress to carcinoma."
a[179] = f + "(D) Incorrect. Adenocarcinoma of the colon is more frequent in persons with chronic ulcerative colitis."
a[180] = f + "(E) CORRECT. Many women have multiple uterine leiomyomas. Leiomyosarcomas of the myometrium are rare and develop de novo."
a[181] = f + "(A) Incorrect. <I>Candida</I> infection is not a risk for malignancy, but persons with malignancies treated with chemotherapy are more likely to get candidal infections."
a[182] = f + "(B) CORRECT. These plaque-like reddish lesions are characteristic for Kaposi sarcoma. HHV8 (KSHV) is the agent that promotes angiogenesis from which the KS arises in persons with HIV infection. This is an example of viral oncogenesis."
a[183] = f + "(C) Incorrect. Mycobacterial infections are not related to malignancies."
a[184] = f + "(D) Incorrect. Bacterial infections do not predispose to neoplasia, but persons with neoplasms may have more infections."
a[185] = f + "(E) Incorrect. <I>Pneumocystis jiroveci (carinii)</I> can be seen in persons with AIDS, but it is not related to the AIDS-associated malignancies."
a[186] = f + "(A) Incorrect. The doubling time indicates how quickly the neoplastic cells are dividing, and if no other factors affected growth, then a palpable 1 cm mass of a billion cells would be present in just 90 days (30 doublings), but in reality, there are limits to cell growth as well as cell loss, so this generally takes years. In general, a rapidly proliferating mass will have a fast doubling time and be more responsive to chemotherapy, but this does not give the best indication of why chemotherapy effectiveness diminishes."
a[187] = f + "(B) Incorrect. Apoptosis determines cell loss. In general, apoptosis is slowed in cancers. If one could turn on apoptosis in cancer, then the cancer would self-destruct. However, this does not predict diminished response to chemotherapy."
a[188] = f + "(C) Incorrect. Gene amplification is one way cell proliferation is promoted for carcinogenesis, but this does not predict diminished response to chemotherapy."
a[189] = f + "(D) CORRECT. The proportion of cancer cells that are actively proliferating will predict response to chemotherapy. Cells not actively proliferating are generally unresponsive to chemotherapeutic agents. As cancers increase in size, more cancer cells exit the replicative pool. During the course of chemotherapy, the cells in replication are selectively killed, leaving behind the cells out of the pool that can continue on. If one were to completely surgically excise the mass, then that would solve this issue, but even if the mass cannot be removed, then at least one can debulk it, or use radiation therapy to kill more cells. Chemotherapy protocols can be designed to include more agents, thereby reducing cancer cell resistance, or by giving cycles of chemotherapy that get more cancer cells into the replicative pool."
a[190] = f + "(E) Incorrect. Cancer cells tend to express telomerase that makes them survive longer, but this does not predict diminishing response to chemotherapy."
a[191] = f + "(A) Incorrect. The history suggests a sarcoma arising in soft tissue. Cytokeratin is a marker for epithelial malignancies (carcinomas)."
a[192] = f + "(B) Incorrect. Factor VIII as a marker is found in endothelium. It is possible that this mass is an angiosarcoma, but other sarcomas at this site are more common."
a[193] = f + "(C) Incorrect. Alpha fetoprotein is a marker that is found in hepatocellular carcinomas and in some testicular carcinomas."
a[194] = f + "(D) Incorrect. This component of immunoglobulin would be a marker for multiple myeloma."
a[195] = f + "(E) CORRECT. The location and size and histologic characteristics suggest a sarcoma. Vimentin is an intermediate filament often found in neoplasms of mesenchymal (connective tissue) origin."
a[196] = f + "(A) Incorrect. The expression of laminin receptors is a characteristic of neoplasia that implies the tumor can more readily attach to basement membranes and invade."
a[197] = f + "(B) Incorrect. Increased cathepsin, an enzyme that aids in matrix degradation, implies a worse prognosis because the neoplasm can more easily spread."
a[198] = f + "(C) Incorrect. Neoplastic cells can switch their metabolism to aerobic glycolysis (the Warburg effect) to give them a selective advantage when actively proliferating in the poorly vascularized environment. Positron emission tomography (PET) scans make use of increased glucose uptake to identify the cancer cells."
a[199] = f + "(D) Incorrect. Decreased programmed cell death allows cells to accumulate. By inducing apoptosis, neoplasms can be made to self-destruct."
a[200] = f + "(E) Incorrect. Neoplasms that have an shorter doubling time are growing faster, which implies a worse prognosis."
a[200.1] = f + "(F) CORRECT. An increased N/C ratio is a feature of malignancy, but a normal to decreased N/C ratio is a feature more like normal cells, and hence better differentiation."
a[201] = f + "(A) Incorrect. This is part of the BCR-ABL fusion gene of the 'Philadelphia chromosome' in which the oncogene BL is spliced onto the BCR region of chromosome 22, resulting in increased tyrosine kinase activity. It is associated with chronic myelogenous leukemia."
a[202] = f + "(B) Incorrect. This oncogene is one of many epidermal growth factor (EGF) receptors and appears to be activated by overexpression and is best associated with breast cancers (HER2/neu)."
a[203] = f + "(C) Incorrect. Overexpression appears to be the mechanism behind the action of this oncogene, one form of platelet-derived growth factor (PBDGF) beta chain receptor, associated with brain and bone tumors."
a[204] = f + "(D) CORRECT. The RAS gene can be turned on by a point mutation to make it an oncogene. It occurs in a wide variety of carcinomas."
a[205] = f + "(E) Incorrect. This oncogene appears to be activated by amplification and it has been associated with neuroblastomas."
a[206] = f + "(A) CORRECT. HPV infection leads to squamous epithelial dysplasias and carcinomas involving the uterine cervix. HPV is a sexually transmitted infection. HPV produces an E7 protein that binds to the RB gene product that normally suppresses cell prolferation. It produces an E6 protein that binds to the p53 protein to degrade it, so that the cell cycle is not stopped. Neoplasia can arise in the setting of abnormal cell proliferation."
a[207] = f + "(B) Incorrect. Lymphomas are malignant proliferations of lymphoid cells. They are rare in the female genital tract."
a[208] = f + "(C) Incorrect. Kaposi sarcoma is a rare condition outside of HIV infection. It is associated with human herpesvirus 8 infection."
a[209] = f + "(D) Incorrect. Adenocarcinomas may arise in the endocervix, but they are not associated with HPV infection."
a[210] = f + "(E) Incorrect. Leiomyomas are benign smooth muscle neoplasms. They are most frequent in the uterine myometrium."
a[211] = f + "(A) Incorrect. The epidemic form of this malignancy is nowadays most often seen in homosexual men with HIV infection and AIDS."
a[212] = f + "(B) Incorrect. This lung cancer is nearly always seen in smokers."
a[213] = f + "(C) CORRECT. The fallout includes Strontium-90, an isotope that can be taken up into bone just like calcium, but promotes neoplastic transformation."
a[214] = f + "(D) Incorrect. Epstein-Barr virus (EBV) infection is most often linked to nasopharyngeal carcinoma and to Burkitt's lymphoma."
a[215] = f + "(E) Incorrect. Endometrial adenocarcinoma is increased with prolonged estrogen hormonal imbalance."
a[216] = f + "(A) Incorrect. The presence of the intermediate filament vimentin in a neoplasm suggests a mesenchymal origin -- a sarcoma."
a[217] = f + "(B) Incorrect. LCA identified in a neoplasm suggests a leukocytic differentiation -- such as a lymphoma."
a[218] = f + "(C) Incorrect. Laminin receptors allow neoplastic cells to attach more readily to basement membranes."
a[219] = f + "(D) Incorrect. Actin is a 'thin' filament found not only in muscle, but a wide variety of other cell types."
a[220] = f + "(E) CORRECT. This topo II is a nuclear enzyme which untangles DNA at the end of mitosis. The drugs that target topoisomerase II freeze the enzyme as it is cutting DNA strands. This leads to DNA strand breakage and cell death. Resistant cells in culture show alterations in the topoisomerase II protein."
a[221] = f + "(A) Incorrect. This is the enzyme used by retroviruses, such as human immunodeficiency virus, to transcribe their RNA into proviral DNA that is incorporated into the host cell."
a[222] = f + "(B) Incorrect. DNA polymerase generates copies of DNA strands, and it is found in normal cells."
a[223] = f + "(C) CORRECT. The telomerase synthesizes telomeric chromosomal ends. The so-called 'immortal' neoplastic cell lines may result from the presence of this enzyme. Interfering with it may promise a new cancer therapy. Of normal human cells, stem cells have significant telomerase activity."
a[224] = f + "(D) Incorrect. Protein kinases are often the 'second messengers' in cells that control cell growth, and their function may be altered by oncogenic activity."
a[225] = f + "(E) Incorrect. DNA topoisomerase is an enzyme that untangles DNA at the end of mitosis. Antineoplastic drugs that target topoisomerase interfere with this enzyme to produce DNA strand breakage and cell death."
a[226] = f + "(A) Incorrect. A change of one type of epithelium for another, called metaplasia, may be the first step in the process leading to neoplasia, but it is reversible."
a[227] = f + "(B) Incorrect. Minimal dysplasia involves only a portion of the epithelium, not the full thickness."
a[228] = f + "(C) Incorrect. A microinvasive neoplasm penetrates only a short distance (a few millimeters) beneath the basement membrane."
a[229] = f + "(D) Incorrect. Hyperplastic epithelium is increased in thickness, and atypical hyperplasia may be a precursor to a neoplastic process, but it is reversible."
a[230] = f + "(E) CORRECT. Malignancy confined to the epithelium is CIS, and such lesions when excised have essentially a 100% cure rate."
a[231] = f + "(A) Incorrect. A choristoma is a mass composed of tissues that appear histologically normal, but not found at the site in which it is located, such as a salivary gland choristoma of the middle ear."
a[232] = f + "(B) Incorrect. A hamartoma is a mass composed of tissues that are normally found at the site in which it is located, but the tissues do not form normal structure, such as a pulmonary hamartoma."
a[233] = f + "(C) Incorrect. A myxoma is a mass composed of stellate cells in a gelatinous (myxomatous) matrix of connective tissue, such as a left atrial myxoma."
a[234] = f + "(D) CORRECT. A teratoma is a neoplasm derived from totipotential germ cells that differentiate into tissues that represent all three germ layersÑectoderm, endoderm, and mesoderm. When the elements are all well differentiated, the neoplasm is 'mature' (benign)."
a[235] = f + "(E) Incorrect. A mesothelioma is a neoplasm that arises from a mesothelial surface, such as a pleural mesothelioma."
a[236] = f + "(A) Incorrect. p53 that is mutated may not function effectively in suppressing the appearance of neoplasms by inhibiting the cell cycle. It is the single most common genetic alteration in cancers."
a[237] = f + "(B) Incorrect. Viral oncogenesis, such as the relationsship of human papillomavirus infection and squamous cell carcinomas, does not predict resistance to chemotherapy."
a[238] = f + "(C) Incorrect. The RAS oncogene, activated by a point mutation, is common in carcinomas, playing a role in development of neoplasia, but does not affect resistance to chemotherapy."
a[239] = f + "(D) CORRECT. The increase in P-glycoprotein allows the cells to pump out any toxin, including any chemotherapy agent."
a[240] = f + "(E) Incorrect. Though a second, separate primary, may be possible, it is not the most likely reason for this phenomenon."
a[241] = f + "(A) Incorrect. Though a sporadic APC mutation may be present at his age, persons with an inherited faulty APC gene present with polyposis (hundreds of polyps) by the second decade, with high risk for malignant transformation."
a[242] = f + "(B) Incorrect. The t(9;22) producing the BCR-ABL fusion gene is seen with chronic myelogenous leukemia."
a[243] = f + "(C) CORRECT. He has an adenocarcinoma of the colon. At his age, a sporadic colon cancer is more likely, and inherited APC and HNPCC are very unlikely. It takes many years for multiple sporadic mutations to have occurred that contribute to development of most malignancies. p53 mutations are found in many carcinomas."
a[244] = f + "(D) Incorrect. HNPCC is a condition with many polyps that typically presents in young to middle age adults. There are faulty DNA mismatch repair genes."
a[245] = f + "(E) Incorrect. EBV infection can be associated with a variety of neoplasms including lymphomas and nasopharyngeal carcinomas. It is not typically associated with colon cancers."
a[246] = f + "(E) Incorrect. A Wilms tumor, a common childhood neoplasm, arises in the kidney."
a[247] = f + "(E) CORRECT. This is one of the more common childhood tumors of soft tissue. Sarcomas tend to be vimentin positive, while carcinomas are cytokeratin positive and lymphomas CD45 positive."
a[248] = f + "(E) Incorrect. Neuroblastomas are childhood tumors but typically arise in the retroperitoneum in adrenal gland."
a[249] = f + "(E) Incorrect. Ewing's sarcomas are childhood neoplasms arising in bone."
a[250] = f + "(E) Incorrect. A malignant lymphoma is likely to arise within a lymph node in children, rarely reaching this size. There should be CD45 positivity."
a[251] = f + "(A) Incorrect. Anaplasia is a characteristic of malignant neoplasms in which there is no differentiation to suggest a particular cell type."
a[252] = f + "(B) Incorrect. Aplasia refers to the absence of growth or development."
a[253] = f + "(C) CORRECT. Neoplasms, and malignant neoplasms in particular, can form a fibrous stroma that gives the tumor a characteristic firm or hard feel on palpation. This connective tissue can fix the tumor to surrounding structures. An infiltrating ductal carcinoma of the breast will often have this appearance."
a[254] = f + "(D) Incorrect. Dysplasia refers to disordered growth of cells in epithelia. It is considered a premalignant change."
a[255] = f + "(E) Incorrect. Metaplasia refers to the exchange of one epithelial cell type for another, typically in response to some form of injury. It may be the first step toward neoplasia."
a[256] = f + "(A) Incorrect. The presence of the intermediate filament vimentin in a neoplasm suggests a mesenchymal origin -- a sarcoma."
a[257] = f + "(B) Incorrect. LCA identified in a neoplasm suggests a leukocytic differentiation -- such as a lymphoma."
a[258] = f + "(C) CORRECT. Beta-catenin can locate to the nucleus to drive cellular proliferation, Mutations of the beta-catenin gene, or in genes such as APC that produce proteins that downregulate beta-catenin, will favor carcinogenesis. In addition, there is loss of normal cell surface e-cadherin expression that maintains attachement of cells to each other. Loss of contact inhibition allows neoplastic cells to invade and metastasize."
a[259] = f + "(D) Incorrect. Telomerase expressed by neoplastic cells allows them to continue division and growth."
a[260] = f + "(E) Incorrect. This is a nuclear enzyme which untangles DNA at the end of mitosis. The drugs that target topoisomerase II freeze the enzyme as it is cutting DNA strands. This leads to DNA strand breakage and cell death. Resistant cells in culture show alterations in the topoisomerase II protein. This may explain cancer chemotherapy resistance."
a[261] = f + "(A) Incorrect. Lipomas can be found in a variety of locations, but in the breast tumors arising from ductular structures are more common."
a[262] = f + "(B) Incorrect. Ductal carcinomas, either confined to the duct or invasive, are the most common primary breast cancer. They are quite uncommon at age 22. They are unlikely to be such a discrete a mass."
a[263] = f + "(C) Incorrect. Lymphomas are malignant proliferations of lymphoid cells. They are quite rare in the breast."
a[264] = f + "(D) CORRECT. The description is that of a benign neoplasm. Fibroadenoma is the most common benign neoplasm of the breast. As the name implies, there are glandular and stromal elements in this neoplasm. The naming of its malignant counterpart is quite odd - phyllodes tumor."
a[265] = f + "(E) Incorrect. Leiomyomas are benign smooth muscle neoplasms. They are most frequent in the uterine myometrium."
a[266] = f + "(A) Incorrect. The epidemic form of this malignancy is nowadays most often seen in homosexual men with HIV infection and AIDS."
a[267] = f + "(B) Incorrect. This lung cancer is nearly always seen in smokers."
a[268] = f + "(C) Incorrect. Radioactive fallout includes Strontium-90, an isotope that can be taken up into bone just like calcium, but promotes neoplastic transformation."
a[269] = f + "(D) CORRECT. EBV infection is most often linked to nasopharyngeal carcinoma in Asia and to Burkitt lymphoma in Africa."
a[270] = f + "(E) Incorrect. Endometrial adenocarcinoma is increased with prolonged estrogen hormonal imbalance."
a[271] = f + "(A) Incorrect. The APC gene is associated with familial polyposis of the colon that can lead to colon carcinomas at a young age, sometimes by the 2nd decade."
a[272] = f + "(B) Incorrect. BRCA1 and BRCA2 mutations are associated with breast cancers, and other cancers including those in ovary. Inherited mutations can lead to breast cancers in young adulthood."
a[273] = f + "(C) Incorrect. MSH2 mutations are associated with the hereditary nonpolyposis colon cancer (HNPCC) syndrome, with the appearance of colon cancers from abnormal DNA mismatch repair in young adulthood."
a[274] = f + "(D) Incorrect. NF1 mutations are associated with neurofibromatosis type I, with the appearance of many neural tumors, particularly neurofibromas."
a[275] = f + "(E) Incorrect. p53 mutations are best known as part of carcinogenesis in many adult sporadic cancers. The rare LiFraumeni syndrome results from inheritance of a faulty p53 gene."
a[275.1] = f + "(F) CORRECT. There are multiple xeroderma pigmentosa (XP) genes, from XPA to XPG and XPV. Sunlight exposure with ultraviolet radiation induces pyrimidine dimer formation that is ordinarily countered through the action of excision repair gene products. Mutation greatly increases the risk for skin cancer formation, and affected persons must avoid sunlight."
a[275.2] = f + "(G) Incorrect. The WT1 gene is associated with Wilms tumor in children."
a[276] = f + "(A) Incorrect. The pattern here is not that of the 50% recurrence risk for autosomal dominant conditions. Most autosomal dominant cancer syndroms involve one or two specific tissue sites."
a[277] = f + "(B) Incorrect. Most defective DNA repair syndromes are inherited in an autosomal recessive fashion and are rare. The most common is the hereditary non-polyposis colon cancer (HNPCC) syndrome, which involves colon."
a[278] = f + "(C) Incorrect. Germline mosaicism can account for a cluster of findings within siblings of a single generation. Cancer syndromes are generally not inherited in this fashion."
a[279] = f + "(D) CORRECT. Cancer that runs in families often does not have a clearly defined pattern of inheritance and does not have a specific genetic marker. Familial cancers should be suspected when cancers occur at a younger age, multiple family members are involved, and multiple sites are involved. The sites of involvement (breast, colon, thyroid, kidney, ovary) are similar to those for sporadic cancers."
a[280] = f + "(E) Incorrect. Teratogens produce congenital anomalies via their effects upon the developing embryo. Cancers are unlikely to occur in this manner."
a[280.1] = f + "(F) Incorrect. Few viruses are associated with human malignancies. Some persistent viruses such as hepatitis B virus, may lead to precancerous conditions such as hepatic cirrhosis in which neoplasia is more likely to occur."
a[281] = f + "(A) CORRECT.  Beta-catenin binds to the intracellular portion of cadherins, which anchor cells together, and the loss of this function results in less cell adhesiveness that favors tumor cell infiltration and metastases. Beta-catenin also binds to a nuclear transcription factor that increases cell proliferation, and loss of normal beta-catenin function leads to cell proliferation."
a[282] = f + "(B) Incorrect. BRCA-2 and BRCA-1 act as tumor suppressors."
a[283] = f + "(C) Incorrect. Cyclin D operates within the cell cycle machinery."
a[284] = f + "(D) Incorrect. NF-1 codes for the protein neurofibromin, which acts in the RAS pathway and promotes GTPase activating factors which facilitate conversion of RAS from active to inactive. The loss of normal NF-1 leads to loss of cell control."
a[285] = f + "(E) Incorrect. RAS oncogene mutations result in loss of control of cell proliferation; there is no direct effect upon cell surface proteins."
a[285.1] = f + "(F) Incorrect. RB acts as a tumor suppressor gene."
a[285.2] = f + "(G) Incorrect. RET codes for a protein that acts as a cell surface receptor for growth factors. Mutations lead to loss of cell control because the receptor remains active even without binding of the growth factor."
a[286] = f + "(A) Incorrect. This represents entry into the cell cycle from the resting, non-proliferating state. Connective tissue cells and hepatocytes can be stimulated to enter the cell cycle, but others such as neurons are terminally differentiated and cannot."
a[287] = f + "(B) Incorrect. This is the cell cycle checkpoint at which defects in DNA are detected to prevent replication with mutations or chromosomal breaks. ."
a[288] = f + "(C) Incorrect. This is the synthesis phase in which there is no checkpoint."
a[289] = f + "(D) CORRECT. This is the second checkpoint in the cell cycle; ionizing radiation activates this checkpoint, resulting in chromosomal abnormalities in mitosis."
a[290] = f + "(E) Incorrect. This is the point at which a cell goes back to a resting state."