Neoplasia LAQs Flashcards
A 40-year-old man has a positive stool guaiac test during a routine physical examination. A colonoscopy is performed and a 0.9-cm, circumscribed, pedunculated mass on a short stalk is found in the upper rectum. Which of the following terms best describes this lesion?
A Adenoma B Carcinoma C Choristoma D Hamartoma E Hyperplasia F Sarcoma
A A discrete small mass such as that described is probably benign. Adenomas arise from epithelial surfaces. Though adenocarcinoma may arise from a colonic adenoma, such malignant lesions tend to be larger and more irregular. A choristoma is a benign mass composed of tissues not found at the site of origin. A hamartoma is a rare benign mass composed of tissues usually found at the site of origin. A hyperplastic colonic lesion tends to be smaller and flatter. A sarcoma is a malignant neoplasm arising in mesenchymal tissues, not in epithelium.
A 32-year-old woman has experienced dull pelvic pain
for the past 2 months. Physical examination shows a right adnexal mass. An abdominal ultrasound scan shows a 7.5-cm cystic ovarian mass. The mass is surgically excised. The surface of the mass is smooth, and it is not adherent to surrounding pelvic structures. On gross examination, the cystic mass is filled with hair. Microscopically, squamous epithelium, tall columnar glandular epithelium, cartilage, and fibrous connective tissue are present and resemble normal tissue counterparts. Which of the following is the most likely diagnosis?
A Adenocarcinoma B Fibroadenoma C Glioma D Hamartoma E Mesothelioma F Rhabdomyosarcoma G Teratoma
G A teratoma is a neoplasm derived from totipotential germ cells that differentiate into tissues that represent all three germ layers: ectoderm, endoderm, and mesoderm. When the elements all are well differentiated, the neoplasm is “mature” (benign). Adenocarcinomas have malignant-appearing glandular elements. Fibroadenomas have a benign glandular and stromal component; they are common in the breast. Gliomas are found in the central nervous system. Hamartomas contain a mixture of cell types common to a tissue site; the lung is one site for this uncommon lesion. A mesothelioma arises from the lining of thoracic and abdominal body cavities. A rhabdomyosarcoma comprises cells that poorly resemble striated muscle; most arise in soft tissues.
A 62-year-old man has had several episodes of hematuria in the past week. He has a 48 pack-year history of smoking cigarettes. On physical examination, there are no abnormal findings. A urinalysis shows 4+ hematuria, and cytologic examination of the urine shows that atypical cells are present. A cystoscopy is performed and a 4-cm sessile mass with a nodular, ulcerated surface is seen in the dome of the bladder. Which of the following terms best describes this lesion?
A Adenoma B Carcinoma C Fibroma D Papilloma E Sarcoma
B A large, irregular, ulcerated mass such as that described is most likely malignant, and the epithelium of the bladder gives rise to carcinomas. Urothelial carcinomas are associated with smoking. An adenoma is a benign epithelial neoplasm of glandular tissues. A fibroma is a benign mesenchymal neoplasm. A papilloma is a benign, localized mass that has an exophytic growth pattern. A sarcoma is derived from cells of mesenchymal origin; sarcomas are much less common than carcinomas.
A 23-year-old woman has noted a nodule on the skin of her upper chest. She reports that the nodule has been present for many years and has not changed in size. It is excised, and the microscopic appearance is shown in the figure. Which of the following neoplasms is this lesion most likely to be?
A Fibroadenoma B Hemangioma C Leiomyoma D Lipoma E Melanoma F Nevus
B The small, discrete nature of this mass and its slow growth with nearly unchanged size suggest a benign neoplasm. The red color is consistent with vascularity. A hemangioma is a common benign lesion of the skin. Fibroadenomas arise in the breast. Leiomyomas, which are white, arise from smooth muscle and are most common in the uterus. Lipomas are yellow fatty tumors that can occur beneath the epidermis. Melanomas are malignant and tend to increase in size quickly; many are darkly pigmented. The benign counterpart to the melanoma is the nevus, which is quite common, but nevi are usually light to dark brown.
A 50-year-old woman undergoes screening colonoscopy as part of a routine health maintenance work-up. An isolated 1-cm pedunculated polyp is found in the sigmoid colon. The excised polyp histologically shows well differentiated glands with no invasion of the stalk. Which of the following investigational research procedures can distinguish most clearly whether the polyp represents hyperplasia of the colonic mucosa or a tubular adenoma?
A Flow cytometry to quantitate cells in the S phase
B Histochemical staining for mucin
C Immunohistochemical staining for keratin
D Molecular marker of clonality
D A true neoplasm is a monoclonal proliferation of cells, whereas a reactive proliferation of cells is not monoclonal. Molecular genetic analysis, such as allelotype analysis with microsatellite markers, shows clonality. Reactive and neoplastic cellular proliferations may have similar histochemical and immunohistochemical staining patterns based on the type of cells and proteins that are present. Flow cytometry is effective at indicating the DNA content, aneuploidy, and growth fraction, but does not indicate clonality.
A 39-year-old woman underwent a routine health maintenance examination for the first time in many years. A Pap smear was obtained, and the result reported was abnormal. On pelvic examination, a red, slightly raised, 1 cm lesion on the anterior ectocervix at the 2 o’clock position was excised and biopsied. The microscopic appearance on medium-power magnification is shown in the figure. Which of the following is most characteristic of this patient’s condition?
A Primary neoplasm in the endometrium
B Elevated CA-125 level in the serum
C Positive HSV-2 molecular test in the lesion
D Pulmonary nodules on a chest radiograph
E No recurrence following local excision
E The figure shows an in situ carcinoma of the squamous cervical epithelium with neoplastic growth only above the basement membrane. Tissue damage with repair and regeneration may give rise to metaplasia, which may progress to dysplasia, considered premalignant. In situ cancers, limited to the epithelium, are noninvasive, and local excision has a 100% cure rate. In situ lesions do not give rise to metastases and have not arisen elsewhere. This lesion is related to human papillomavirus (HPV) infection, not herpes simplex virus (HSV). CA-125 is most often a tumor marker for ovarian cancer.
A 53-year-old woman has noticed increasing malaise. On physical examination, there are no abnormal findings, but a stool guaiac test is positive. Her hemoglobin level is 7.9 g/dL. A colonoscopy is performed, and a 3-cm sessile mass is found in the cecum. A biopsy specimen of the mass shows a moderately differentiated adenocarcinoma confined to the mucosa. An abdominal CT scan shows no lymphadenopathy or hepatic lesions. Given this information, which of the following is the best course of action?
A Administer a multiagent chemotherapeutic regimen
B Observe the lesion for further increase in size
C Remove the entire colon to prevent a recurrence
D Resect the tumor and some normal surrounding
tissue
E Search for a primary malignancy in another organ
D A malignant epithelial neoplasm arises in the mucosa but has a tendency to invade locally. A benign neoplasm is often well circumscribed, and compressed normal surrounding tissue appears to form a discrete border. This localized lesion can be resected easily, with adequate margins. Without evidence for spread outside the colon, chemotherapy is unlikely to be of benefit. The biopsy specimen shows a malignant lesion; it must be removed before it increases in size and invades locally or metastasizes. If there is no family history, a familial cancer with high risk of recurrence from multiple polyps is unlikely; local excision is adequate. Such a solitary mucosal lesion is unlikely to represent a metastasis.
A 57-year-old woman has experienced an increasing feeling of fullness in her neck along with a 3-kg (7-lb) weight loss over the past 3 months. On physical examination, there is a firm, fixed mass in a 3 × 5 cm area in the right side of the neck. A CT scan shows a solid infiltrating mass in the region of the right lobe of the thyroid gland. A biopsy of the mass is performed and the microscopic appearance is shown in the figure. All areas of the tumor have similar morphology. Which of the following terms best describes this neoplasm?
A Anaplastic B Apoptotic C Dysplastic D Metaplastic E Well-differentiated
A The cells shown in the figure show marked pleomorphism and hyperchromatism (anaplasia), and it is difficult to discern the cell of origin because no differentiation is noted. A bizarre tripolar mitotic figure is present. This degree of anaplasia is consistent with an aggressive, high-grade malignancy called anaplastic carcinoma. Apoptosis is single cell necrosis, but the cells shown appear viable and not fragmented. Dysplasia refers to changes within an epithelium that presage a neoplasm. Metaplasia with one epithelial cell type substituted for another may presage dysplasia and malignancy. Well differentiated neoplasms tend to be less aggressive and slower growing and resemble the cell of origin.
A Pap smear obtained from a 29-year-old woman during a routine health maintenance examination is abnormal. She is currently asymptomatic. She has a history of multiple sexual partners. Cervical biopsy specimens are obtained and the microscopic appearance is shown in the figure. Which of the following is the most likely diagnosis?
A Adenocarcinoma B Carcinoma in situ C Dysplasia D Hamartoma E Metaplastic transformation F Squamous cell carcinoma
F In the figure the disorderly, atypical epithelial cells involve the entire thickness of the epithelium. They extend through the underlying basement membrane and into the underlying stroma as rounded nests at the right, a process known as invasion. The ectocervix and the squamous metaplasia of endocervix give rise to dysplasia from which squamous cell carcinoma can arise. Carcinoma in situ is confined to the epithelium; if the basement membrane is breached, the lesion is no longer in situ, but rather invasive. An adenocarcinoma is a malignant neoplasm arising from glandular epithelium, such as the endocervix or endometrium, not the ectocervix. A dysplastic process could precede development of carcinoma in situ and squamous carcinoma; dysplasia involves only part of the thickness of the epithelium. A hamartoma contains a mixture of cell types common to a tissue site. Metaplasia can occur in response to persistent infection with human papillomavirus (HPV) and other inflammatory conditions. Metaplasia can be the precursor to dysplasia.
A 44-year-old woman feels painless lumps in her armpit, which were not present a month ago. On examination, right axillary lymphadenopathy is present. The nodes are painless but firm. Which of the following is the most likely lesion in her right breast?
A Acute mastitis with abscess B Fibroadenoma C Infiltrating lobular carcinoma D Intraductal carcinoma E Leiomyosarcoma
C Lymphatic spread, especially to regional lymph nodes draining from the primary site, is typical of a carcinoma. An intraductal carcinoma has not extended beyond the basement membrane, but an infiltrating carcinoma has acquired the ability to invade and spread via metastasis. The primary site may be difficult to detect if small or deep, and hence the need for radiologic imaging, such as mammography.A fibroadenoma is a benign neoplasm and cannot invade or metastasize. Infection from a breast abscess canspread to the lymph nodes, but the resultin nodal enlargement is typically associated with pain—a cardinal sign of acute inflammation. Sarcomas uncommonly metastasize to lymph nodes, and a leiomyosarcoma of breast is rare.
A 69-year-old woman has experienced increasing malaise and a 10-kg weight loss over the past year. She dies of massive pulmonary thromboembolism. The gross appearance of the liver at autopsy is shown in the figure. Which of the following best describes the lesions seen in her liver?
A Invasive angiosarcoma B Hepatocellular carcinoma C Leukemic infiltration D Metastatic adenocarcinoma E Multifocal hepatic adenomas
D The figure shows the appearance of multiple variably sized tan metastatic lesions in the liver from hematogenous spread of carcinoma. Adenocarcinomas from abdominal primary sites such as colon, pancreas, and stomach are most likely. Thromboembolism suggests a hypercoagulable state such as a paraneoplastic syndrome. Angiosarcomas of the liver are uncommon. A primary malignancy typically appears as a dominant mass, not multiple masses. Although some benign tumors, such as leiomyomas of the uterus, can be multiple, this is not the rule in the liver, and hepatic adenomas are rare. Although hepatocellular carcinomas can have “satellite” nodules, widespread nodules such as those seen in the figure are more characteristic of metastases. Leukemic infiltrates typically do not produce large mass lesions, though some lymphomas may do so. Resection of multiple metastases is usually futile.
A 66-year-old man with chronic cough has an episode of hemoptysis. On physical examination, there are no abnormal findings. A chest radiograph shows a 6-cm mass in the right lung. A sputum cytologic analysis shows neoplastic squamous cells. Metastases from his lung lesion are most likely to be found at which of the following sites?
A Cerebral hemisphere B Chest wall muscle C Hilar lymph nodes D Splenic red pulp E Vertebral bone marrow
C Carcinomas metastasize through lymphatics most often, usually to regional nodes first. Hematogenous metastases are possible, however, to sites such as bone marrow, liver, or the opposite lung. About half of all cerebral metastases arise from lung primary carcinomas. Soft-tissue metastases to muscle, fat, and connective tissues are rare, as are splenic metastases.
An epidemiologic study of cancer deaths recorded in the last half of the 20th century is conducted. The number of deaths for one particular type of cancer had been decreasing in developed nations, despite the absence of widespread screening and prevention programs. Which of the following neoplasms was most likely to be identified by this study?
A Cerebral glioma B Gastric adenocarcinoma C Hepatic angiosarcoma D Leukemia E Pulmonary small cell carcinoma
B The decrease in the number of gastric cancers may be related to reduced numbers of dietary carcinogens or a decrease in the prevalence of Helicobacter pylori infection; however, the exact reason is obscure. Cerebral gliomas are not as common as carcinomas; an urban legend links them to cell phone use, but legitimate epidemiologic studies have not made this link. Angiosarcomas of the liver are quite rare; they are epidemiologically linked to vinyl chloride exposure. Leukemias and lymphomas are not as common as carcinomas. Pulmonary small cell carcinomas are related to smoking, and the numbers have decreased in many countries with campaigns to reduce smoking; the death rate is typically high because the prognosis for lung cancer is so poor.
An epidemiologic study of cancer deaths recorded in the last half of the 20th century is conducted. The number of deaths for one particular cancer had increased markedly in developed nations. More than 30% of cancer deaths in men, and more than 24% of cancer deaths in women, were caused by this neoplasm in 1998. In some nations, prevention strategies reduced deaths from this cancer. Which of the following neoplasms was most likely identified by this study?
A Cerebral glioma B Bronchogenic carcinoma C Hepatocellular carcinoma D Colonic adenocarcinoma E Pancreatic adenocarcinoma F Skin melanoma
B Incidence of lung cancers increased dramatically in the 20th century because of the popularity of cigarette smoking. As the number of individuals in a population who smoke increases, so do the number of lung cancers. Some cancers of the urinary tract, oral cavity, esophagus, and pancreas also are causally related to smoking. Breast, prostate, and colon cancers remain common in developed nations, but the number of cases has not increased sharply. Pap smear screening and human papillomavirus (HPV) vaccination markedly decreases numbers of cervical cancers. There has been an increase in the incidence of melanomas worldwide, but there are still far fewer cases of melanomas than of lung cancers. Hepatic and intracranial neoplasms in adults are far less common than lung cancers.
An epidemiologic study analyzes health care benefits of cancer screening techniques applied to persons more than 50 years of age. Which of the following diagnostic screening techniques used in health care is most likely to have the greatest impact on reduction in cancer deaths in Europe and North America?
A Chest radiograph B Mammography C Pap smear D Serum tumor markers E Stool guaiac F Urine cytology
B A screening program should reliably detect early cancers with higher incidence. Breast cancer affects up to 1 in 9 women in these regions. Mammography may aid in detection of small cancers that have a better prognosis. A chest radiograph is an insensitive technique for detecting early lung cancers. Because Pap smear screening can detect dysplasias and in situ carcinomas that can be treated before progression to invasive lesions, deaths from cervical carcinoma have steadily decreased since this screening method became widely available in the last half of the 20th century. The introduction of human papillomavirus (HPV) vaccination will diminish the numbers of cervical cancers even further. Serum tumor markers have not proved useful as general screening techniques, although they are useful in selected circumstances. Use of stool guaiac has had a minimal effect on rates of death from colorectal carcinomas, but physicians are cautioned not to indicate “rectal deferred” on the physical examination report, and hence contribute to the problem. Urine cytology is better than urinalysis for detection of urothelial malignancies, but it does not have a high sensitivity.
A 38-year-old woman has abdominal distention that has been worsening for the past 6 weeks. An abdominal CT scan shows bowel obstruction caused by a 6-cm mass in the jejunum. At laparotomy, a portion of the small bowel is resected. Flow cytometric analysis of a portion of the tumor shows a clonal population of B lymphocytes with high S phase. Translocation with activation of which of the following nuclear oncogenes is most likely to be present in this tumor?
A APC B EGF C MYC D p53 E RAS
C The MYC oncogene is commonly activated in Burkitt lymphoma because of a t(8;14) translocation. The MYC gene binds DNA to cause transcriptional activation of growth related genes such as that for cyclin D1, resulting in activation of the cell cycle. EGF (such as HER2 in breast cancers) encodes the epithelial growth factor receptor located on the cell surface. p53 and APC are tumor suppressor genes that are inactivated in many cancers, including colon cancer. RAS oncogene encodes a GTP binding protein that is located under the cell membrane.
A 50-year-old woman has had easy fatigability and noted a dragging sensation in her abdomen for the past 5 months. Physical examination reveals that she is afebrile. She has marked splenomegaly, but no lymphadenopathy. Laboratory studies show her total WBC count is 250,000/mm3 with WBC differential count showing 64% segmented neutrophils, 11% band neutrophils, 7% metamyelocytes, 5% myelocytes, 4% myeloblasts, 3% lymphocytes, 2% basophils, 2% eosinophils, and 2% monocytes. A bone marrow biopsy is performed, and karyotypic analysis of the cells reveals a t(9;22) translocation. Medical treatment with a drug having which of the following modes of action is most likely to produce a complete remission in this patient?
A Activating cellular caspases
B Antibody binding to EGF receptors
C Delivering normal p53 into cells with viral vectors
D Inhibiting tyrosine kinase activity
E Preventing translocation of β-catenin to the nucleus
D This patient has a classic history and t(9;22) translocation with chronic myelogenous leukemia. The translocation causes uncontrolled nonreceptor tyrosine kinase activity of the BCR-ABL fusion gene. These patients undergo remission with drugs such as imatinib that inhibit tyrosine kinases. Agents that activate caspases theoretically may help in many cases, especially when apoptosis is blocked as in tumors with BCL2 over expression. Antibodies to epithelial growth factor receptors, such as ERBB2 (HER2) receptors, are beneficial in certain breast tumors with amplification of this gene. Delivery of p53 into cells by viral vectors has not yet been proven to be valuable in cancer treatment, and it is not used in chronic myelogenous leukemia. Translocation of β-catenin to the nucleus occurs in colon cancers when there is mutational loss of APC genes.
A 54-year-old woman notes a lump in her right breast. Physical examination shows a 2-cm mass fixed to the underlying tissues beneath the areola and three firm, nontender, lymph nodes palpable in the right axilla. There is no family history of cancer. An excisional breast biopsy is performed, and microscopic examination shows the findings in the figure. Over the next 6 months, additional lymph nodes become enlarged, and CT scans show nodules in the lung, liver, and brain. Which of the following molecular abnormalities is most likely to be found in her carcinoma cells?
A Amplification of the ERBB2 (HER2) gene B Deletion of one RB gene copy C Fusion of BCR and C-ABL genes D Inactivation of one BRCA1 gene copy E Mutation of one p53 gene copy
A Infiltrating ductal and intraductal carcinoma are present in the figure. Increased expression of ERBB2 (HER2) can be detected immunohistochemically and by fluorescence in situ hybridization (FISH) in the biopsy specimen. One third of breast cancers may show this change. Such amplification is associated with a poorer prognosis. Detection of a specific gene product in the tissue has value for determination of treatment and prognosis. BRCA1 and p53 mutations, if inherited in the germ line, can predispose the patient to breast cancer and other tumors. With BRCA1, there is family history of breast cancer, often at a young age. The tumor suppressor gene p53 mutations predispose to many types of cancers. An inherited deletion of RB gene predisposes to retinoblastoma. The BCR-ABL fusion product, seen in chronic myeloid leukemia, often results from t(9;22).
The mother of a 5-year-old boy notices that his abdomen has enlarged in the past 6 months. On physical examination there is an ill-defined abdominal mass. An abdominal CT scan shows a 9-cm mass in the region of the right adrenal gland. The mass is removed and microscopically shows primitive hyperchromatic cells. Cytogenetic analysis of tumor cells shows many double minutes and homogeneously staining regions. Which of the following genes is most likely to have undergone alterations to produce these findings?
A BCL1 (cyclin gene) B BCL2 (anti-apoptosis gene) C IL2 (growth factor gene) D K-RAS (GTP-binding protein gene) E Lyn (tyrosine kinase gene) F N-MYC (transcription factor gene)
F Double minutes and homogeneously staining regions seen on a karyotype represent gene amplifications. Amplification of the N-MYC gene occurs in 30% to 40% of neuroblastomas, and this change is associated with a poor prognosis. The BCL1 and BCL2 genes are mutated in some non-Hodgkin lymphomas. The IL2 mutation may be present in some T cell neoplasms. K-RAS mutations are present in many cancers, but not typically childhood neoplasms. The Lyn mutation is seen in some immunodeficiency states.
A 34-year-old sexually active woman undergoes a routine physical examination. There are no abnormal findings. A Pap smear is obtained as part of the pelvic examination. Cytologically, the cells obtained on the smear from the cervix show severe epithelial dysplasia (high-grade squamous intraepithelial lesion). Which of the following therapeutic options is most appropriate for this woman?
A Antibiotic therapy B Excision C Ovarian removal D Screening of family members E Watchful waiting
B Epithelial dysplasias, especially severe dysplasias, can be precursors of carcinomas. This is a key reason for Pap smear screening. The incidence of cervical carcinoma decreases when routine Pap smears are performed. Colposcopy with biopsy is indicated to determine the extent of the lesion for removal. Though related to human papillomavirus (HPV) infection, severe dysplasias are not amenable to antibiotic therapy. Ovarian neoplasms are not related to cervical dysplasias or carcinomas. In general, cervical cancers are not related to hereditary syndromes, and cervical dysplasias are not hereditary. Screening of family members is appropriate for those who have risk factors, such as multiple sexual partners. Regression of a severe dysplasia is unlikely.
An epidemiologic study investigates the potential morphologic and molecular alterations that may contribute to the development of cancers in a population. Data analyzed from resected colonic lesions show changes that suggest the evolution of a sporadic colonic adenoma into an invasive carcinoma. Which of the following best describes the mechanism producing these changes leading to colonic malignancies?
A Activation of proto-oncogenes by chromosomal
translocation
B Extensive regeneration of tissues increasing the
mutation rate in regenerating cells
C Inheritance of defects in TP53 genes that increase
the susceptibility to develop cancer
D Overexpression of growth factor receptor genes
E Stepwise accumulation of multiple proto-oncogene
and tumor suppressor gene mutations
E Development of colonic adenocarcinoma typically takes years, during which time multiple mutations occur within the mucosa, including mutations involving such genes as APC (adenomatous polyposis coli), K-RAS, and p53. The accumulation of mutations, rather than their occurrence in a specific order, is most important in the development of a carcinoma. Activation of proto-oncogenes, extensive regeneration, faulty TP53 genes, and amplification of growth factor receptor genes all contribute to the development of malignancies, but they are not sufficient by themselves alone to produce a carcinoma from an adenoma of the colon. Inherited loss of wild-type TP53 contributes to multiple cancers, but not to sporadic adenomas.
A 61-year-old woman has noted a feeling of pelvic heaviness for the past 6 months. On physical examination, there is a palpable nontender lower abdominal mass. An abdominal ultrasound scan shows a 12-cm solid mass in the uterine wall. A total abdominal hysterectomy is performed. The mass has the microscopic appearance of a well-differentiated leiomyosarcoma. One year later, a chest radiograph shows a 4-cm nodule in her right lower lung. Cytologic analysis of a fine-needle biopsy specimen of the nodule shows a poorly differentiated sarcoma. The patient’s medical history indicates that she has smoked cigarettes most of her adult life. Which of the following mechanisms best explains these findings?
A Continued cigarette smoking by the patient
B Development of a second primary neoplasm
C Inheritance of a defective RB gene
D Immunodeficiency with HIV infection
E Metastasis from an aggressive tumor subclone
E Although neoplasms begin as monoclonal proliferations, additional mutations occur over time, leading to subclones of neoplastic cells with various aggressive properties. This subcloning may allow metastases, greater invasiveness, resistance to chemotherapy, and morphologic differences to occur. Because sarcomas of the lung are rare, the lung mass is statistically a metastasis. Though second primary malignancies do arise, particularly in persons who have already had a malignancy, the odds favor a metastasis in a person with a prior malignancy. Sarcomas are not related to smoking tobacco. Inheritance of a mutant RB gene is most likely to lead to childhood retinoblastomas and osteosarcomas. Kaposi sarcoma is the sarcoma most often associated with AIDS from HIV infection.
A 70-year-old woman reported a 4-month history of a 4-kg weight loss and increasing generalized icterus. On physical examination, she has midepigastric tenderness on palpation. An abdominal CT scan shows a 5-cm mass in the head of the pancreas. Fine-needle aspiration of the mass is performed. On biochemical analysis, the neoplastic cells show continued activation of cytoplasmic kinases. Which of the following genes is most likely to be involved in this process?
A APC B MYC C p53 D RAS E RET F sis
D The RAS oncogene is the most common oncogene involved in the development of human cancers. Mutations of the RAS oncogene reduce GTPase activity, and RAS is trapped in an activated GTP-bound state. RAS then signals the nucleus through cytoplasmic kinases. The APC gene can cause activation of the WNT signaling pathway. The MYC oncogene is a transcriptional activator that is overexpressed in many tumors. The p53 tumor suppressor gene encodes a protein involved in cell cycle control. The RET proto-oncogene encodes a receptor tyrosine kinase involved in neuroendocrine cells of the thyroid, adrenal medulla, and parathyroids. The sis oncogene encodes platelet-derived growth factor receptor-β, which is over expressed in certain astrocytomas.
A 22-year-old man has a raised, pigmented lesion on his forearm that has increased in size and become more irregular in color over the past 4 months. Physical examination shows a 0.5 × 1.2 cm black-to-brown asymmetric lesion with irregular borders. An excisional biopsy specimen shows clusters of pleomorphic pigmented cells that extend into the reticular dermis. Family history indicates that the patient’s maternal uncle died from a similar tumor. His grandfather required enucleation of the left eye because of a “dark brown” retinal mass. Which of the following genes is most likely to have undergone mutation to produce these findings in this family?
A BCL2 (anti-apoptosis gene) B c-MYC (transcription factor gene) C IL2 (growth factor gene) D Lyn (tyrosine kinase gene) E p16 (cell cycle inhibition) F p53 (DNA damage response gene)
E A family history of malignant melanoma is present. Familial tumors often are associated with inheritance of a defective copy of one of several tumor suppressor genes. In the case of melanomas, the implicated gene is called p16, or INK4a. The product of the p16 gene is an inhibitor of cyclin- dependent kinases. Germline mutations in CDKN2A may also underlie familial melanomas. With loss of control over cyclin-dependent kinases, the cell cycle cannot be regulated, favoring neoplastic transformation. BCL2 is present in some lymphoid neoplasms. The c-MYC gene is mutated in various carcinomas, but is not known to be specifically associated with melanomas. The IL2 mutation is associated with some T cell neoplasms. The Lyn mutation is seen in some immunodeficiency states. p53 mutations occur in many cancers, but not specifically in familial melanomas.
