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M1 FMK > Neoplasia > Flashcards

Neoplasia Flashcards

1
Q

Lipomas

A

Common, benign tumors that arise from the subcutaneous fat and present as soft, mobile masses that are stable or enlarge slowly over time

Biopsy shows well-differentiated mature adipocytes with a fibrous capsule

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2
Q

Liposarcomas

A

Malignant tumors that originate from adipose tissue

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3
Q

Adenocarcinomas

A

Originate from glandular epithelium and consist of a disorganized mass of malignant cells that form glandular structures that may stain positive for mucin

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4
Q

Where is keratin production seen in metastatic disease?

A

Squamous cell carcinomas - arise in organs that are normally lined by stratified squamous epithelium

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5
Q

Anaplasia

A

An extreme degree of peomorphism - usually associated with aggresive malignant tumors

Undifferentiated (anaplastic) thyroid cells lose their ability to produce thyroglobulin, so a stain for thyroglobulin would be negative.

Histology of anaplasia may show undifferentiated cells with abnormal mitoses and possibly giant
cells.

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6
Q

Carcinoma in situ is characterized by what?

A

Irreversible nuclear changes and lack of invasion (aka stage 0)

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7
Q

E-cadherin in metastatic processes

A

Plays an important role in cellular adhesion

Acts to oppose metastatic processes

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8
Q

Metalloproteinase

A

Zinc-containing enzyme that degrades the extracellular matrix, participates in normal tissue remodeling and in tumor invasion through the basement membrane and connective tissue

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9
Q

Key GF that promotes angiogenesis in neoplastic and granulation tissue

A

Vascular endothelial growth factor (VEGF) and fibroblast growth factor (lesser extent)

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10
Q

Most common cause of cancer death for men and women in US

A

Lung cancer

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11
Q

Top three cancers in men and women

A

Men - prostate>lung>colon

Women - breast>lung>colon

After skin cancer in both sexes

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12
Q

Lynch syndrome

A

Associated with gastric, endometrial and ovarian cancers

Germline mutations in DNA mismatch repair genes (i.e. MLH1, MSH2, and MSH6) result in microsatellite instability and are the underlying cause of hereditary nonpolyposis cancer syndrome.

familial disorder that is characterized by development at a younger age of right-sided colon mucinous adenocarcinomas, gastric cancer, endometrial cancer, and ovarian cancer.

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13
Q

Li-Fraumeni Syndrome

A

Mutation of the TP53 gene - associated with multiple cancers at early age

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14
Q

Xeroderma pigmentosa

A

Characterized by exessive freckling and keratosis when exposed to sunlight and increased risk of developing multiple skin cancers in sun-exposed skin at early ag

Results from NER defect caused by decreased endonuclease activity (mutations in excision endonuclease) - an enzyme that normally repairs pyrimidine (thymidine) dimers found in DNA damaged by UVB

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15
Q

Ataxia-telangiectasia

A

Defective DNA break repair

Decreased IgA/G/E levels lead to recurrent sinopulmonary infections

Also characterized by cerebellar ataxia, conjunctival telangiectasia

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16
Q

Fanconi anemia

A

Mutation in genes encoding proteins responsible for DNA interstrand crosslink repair

Characterized by hypoplasia of the thumbs and radii, pancytopenia, and increased risk of developing acute leukemia

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17
Q

Epstein-Barr virus

Can lead to what cancers?

A
  1. Burkitt lymphoma
  2. Nasopharyngeal carcinoma
  3. Pirmary CNS lymphoma
  4. Some types of Hodgkin lymphoma
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18
Q

HPV E7 protein

A

Binds to pRb and stops it from binding to E2F, resulting in activation of E2F transcription factors

The mechanism of HPV-induced carcinogenesis involves inhibition of cell cycle regulatory proteins p53 and Rb, which regulate the G1 restriction point of the cell cycle.

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19
Q

HPV E6 protein

A

Responsible for the inactivation of TP53 gene by degradation in proteosomes

The mechanism of HPV-induced carcinogenesis involves inhibition of cell cycle regulatory proteins p53 and Rb, which regulate the G1 restriction point of the cell cycle.

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20
Q

HPV infection

A
  1. Skin warts (verruca vulgaris)
  2. Veneral warts (condyloma acuminatum)
  3. Cervical neoplasia
  4. Anal carcinoma
  5. Laryngeal carcinoma
  6. Recurrent juvenile laryngeal papillomatosis
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21
Q

Cytopathic effect of HPV

A

Seen with Pap smear

Characterized by cells with cytoplasmic clearing around the nucleus, dense cytoplasm at the periphery, resulting in perinuclear halo, along with a large, dark nucleus with irregular contours (raisinoid appearance), which is called koilocytosis

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22
Q

Cachexia

A

Results froma action of cytokines produced by tumors

Tumor necrosis factor-alpha, IL-6, IL-1, and gamma-interferon, which can suppress appetite and increase the basal metabolic rate

Characterized by atrophy of skeletal muscle due to degradation of proteins via the ubiquitin-proteasome pathway

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23
Q

Tumor grading

A

Based on histologic degree of differentiation and degree of mitotis activity = indicators of aggresiveness of malignant neoplasm

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24
Q

Tumor staging

A

Based on the size of the primary lesions, presence of lymph node metastases, and presence of blood-borne metastases

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25
Q

Tumor markers and proteins

A

Alpha fetoprotein (AFP) - tumor marker for ataxia talangectasia. Can also be elevated with liver cancer and some germ cell tumors (and pregnancy w/ nueral tube defects)

Cytokeratin - suggests tumor has epithelial origin

Vimentin - marker for a mesenchymal (i.e. fibroblast) origin of tumor cells

Desmin - expressed in tumors composed of muscle cells such as malgnant rhabdomyosarcomas (striated muscle) or benign leiomyomas (smooth muscle)

Chromogranin and synaptophysin - markers for neuroendocrine cells, which give rise to many malignancies, such as small cell carcinomas of the lung, carcinoid tumors, and adrenal medullary tumors

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26
Q

Staging vs. grading

A

Staging is a measure of tumor spread and is generally more significant in determining the prognosis than tumor grading

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27
Q

Hamartoma

A

Tumor composed of elements that are in the right place but form the wrong structure - i.e. hamartoma of the lungs is a tumor composed of cartilage

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28
Q

Choristoma

A

Tissue in the wrong place but in the right structure - ectopic tissue

ectopic gastric epithelium in Meckle’s diverticulum of the distal ileum (wrong place - gastric epithelium should be in the stomach, but histologically the tissue looks normal)

29
Q

Malignant neoplasm general classifications

A

Carcinomas - of epithelial origin

Sarcomas - mesenchymal origin

30
Q

Organs associated with development of adenocarcinoma

A

Lung, colon, stomach, prostate, and endometrium

31
Q

Where do squamous cell carcinomas arise

A

Organs that are normally lined by stratified squamous epithelium

Skin, oral cavity, lung, esophagus, and cervix

Squamous carcinomas consist of disorganized mass of malignant cells that produce keratin (ESM shows tonofilaments and desmosomes)

32
Q

What tumors usually have a papillary appearance

A

A tumor that originates from transitional epithelium (uroepithelium) of the urinary bladder or renal pelvis - transitional cell carcinoma (urothelial carcinoma)

33
Q

Examples of malignant mesenchymal tumors

A

Rhabdomyosarcomas

Leiomyosarcomas

Fibrosarcomas

Liposarcomas

34
Q

Leiomyosarcomas

A

Malignant mesenchymal tumor

Arise from smooth muscle

The differentiation between a benign leiomyoma and a malignant leiomyosarcoma is based on the number of mitoses that are present and the degree of atypia displayed by the neoplastic cells.

35
Q

Rhabdomyosarcomas

A

Malignant mesenchymal tumors

Arise from skeletal muscle (contain cross-striations) - contain desmin or actin

36
Q

Tumors that have the suffix -blastoma

A

Usually childhood malignancies

i.e - retinoblastoma, neuroblastoma, nephrobalstoma, hepatoblastoma…etc.

37
Q

Clear cell carcinomas

A

Tumors that have clear cytoplasm due to their high lipid content - renal cortex and vagina

The clear cell type of renal cell carcinoma is the most common type of malignant kidney neoplasm in the adult.

38
Q

Signet cell carcinomas

A

Intracellular mucin that pushes the nucleus to the periphery (like a signet ring) - usually originate in the stomach or the ovaries

Associated with previous diethystilbestrol (DES) exposure

39
Q

What protease is essential for invasion of tumor cells into connective tissue

A

Type IV collagenase

40
Q

Spread of sarcomas vs carcinomas (medium in which they spread)

A

Sarcomas - hematologic spread

Carcinomas - lymphatic spread

41
Q

Where are the highest rates of gastric carcinoma

A

Japan

might be related to dietary factors, such as eating smoked and salted foods, but is more likely due to the high incidence of infection with Helicobacter pylori.

42
Q

Where are the highest rates of nasopharyngeal carcinoma

A

Parts of India and China

Associated with EBV

43
Q

Where are the highest rates of liver cancer

A

Parts of Africa and Asia

associated with both hepatitis B infection and high levels of aflatoxin B1 (which is secreted by the mold Aspergillus flavus, found on moldy grain or peanuts)

44
Q

Where are the highest rates of trophoblastic diseases (i.e. choriocarcinoma and hydatidiform mole)

A

High rates of occurrence in parts of China

45
Q

Bloom syndrome

A

Due to defect invlovling BLM helicase

Characterized by severe immunodeficiency, growth retardation, and increased sensitivity to radiation

Sings of bloom syndrome - short stature, parrot-beak nose, and facial rash in butterfly-distribution

Cell cultures reveal quadriradial configurations (four-armed chromatid interachange) and increased sister chromatid exchange (involves homologous recombination)

46
Q

Tumors associated with the production of PTHrP

A

Squamous cell carcinoma of the lungs, clear cell carcinomas of the kidney, endometrial adenocarcinomas, and transitional carcinomas or the urinary bladder

47
Q

Acanthosis nigricans

A

Paraneoplastic syndrome - abnormal pigmentation of the axilla (or groin)

Benign type - associated w/ insulin resistance

Malignant type - associated with visceral malignancies (especially gastric cancer)

48
Q

Ectopic ACTH secretion

A

Paraneoplastic syndrome

Seen with small cell carcinoma of the lung - may produce Cushing syndrome

Paraneoplastic

49
Q

Ectopic secretion of ADH

A

Syndrome of inappropriate ADH secretion (SIADH)

May produce hyponatremia

Also seen with small cell carcinoma of the lung

Paraneoplastic

50
Q

Troussea sign

A

Migratory thrombophlebitis associated with lung cancers and more classically with carcinoma of the pancreas

The carcinoid syndrome can result from excess secretion of serotonin as seen with a large carcinoid tumor of the small intestines

51
Q

Polycythemia

As paraneoplastic syndrome

A

Associated with increased erythropoietin levels and some tumors (particularly renal cell carcinomas, hepatocellular carcinomas, and cerebellar hemangioblastomas)

52
Q

What tumor is associated with myasthenia gravis

A

Tumor of the thymus

53
Q

Chromagranin and synaptophysin

A

Markers for neuroendocrine cells - give rise to many malignancies (i.e. small cell carcinomas of the lung, carcinoid tumor, adrenal medullary tumors (neuroblastoma in children)

54
Q

S-100 (stain)

A

Nonspecific stain for neural crest cells - give rise to many different malignancies - malignant melanoma, neural tumors, and astrocytomas

55
Q

Specific special stain for malignant melanoma

A

MART-1 and HMB-45

56
Q

CA 15-3

A

Tumor marker for breast cancer

57
Q

CA 125

A

Tumor marker for epithelial ovarian cancer

58
Q

CA19-9

A

Tumor marker for pancreatic cancer

59
Q

CEA

A

Carcinoembryonic antigen - glycoprotein associated with many cancers - adenocarcinomas of the colon, pancreas, lung, stomach, and breast

60
Q

Cervical biopoys from a 25-y/o female shows koilocytes (dyplastic cells characterized by cytoplasmic clearing aorund the nucleus, dense cytoplasm at the periphery, resulting in a perinuclear halo, along with a large, dark nucleus with irregular contours (rasinoid appearance). The virus that most likely caused this abnormality produces two oncoproteins: E6 and E7. What gene is inactivated by E6?

A

TP53

The cytopathic effect of human papillomavirus (HPV) seen with a Pap smear is characterized by cells with cytoplasmic clearing around the nucleus, dense cytoplasm at the periphery, resulting in a perinuclear halo, along with a large, dark nucleus with irregular contours (raisinoid appearance), which is called koilocytosis. HPV E6 protein is responsible for the inactivation of the TP53 gene by degradation in proteosomes.

61
Q

Germline mutations in DNA mismatch repair genes, such as MLH1, MSH2, and MSH6, result in ________

A

Microsatellite instability and are the underlying cause of hereditary nonpolyposis cancer syndrome (Lynch syndrome), which is the most common hereditary form of colorectal cancer (especially right-sided colon mucinous adenocarcinomas)

Lynch syndrome is also associated w/ gastric, endometrial, and ovarian cancers

62
Q

What class of enzymes degrade the extracellular matrix and also participates in both normal tissue remodeling and tumor invasion through the basement membrane and connective tissue?

A

Metalloproteinases

63
Q

What stain is used to ID neuroendocrine cells?

A

Chromogranin and synaptophysin are markers for neuroendocrine cells, which give rise to many malignancies, such as small cell carcinomas of the lung, carcinoid tumors, and adrenal medullary tumors.

64
Q

Normal sequence of events for cervical cancer development

A
  1. Normal
  2. Squamous metaplasia
  3. Dysplastic (HPV infection)
  4. Carcinoma in situ
  5. Invasive malignancy
65
Q

A 70-year-old man comes to the physician because of a 4-month history of epigastric pain, nausea, and weakness. He has smoked one pack of cigarettes daily for 50 years and drinks one alcoholic beverage daily. He appears emaciated. He is 175 cm (5 ft 9 in) tall and weighs 47 kg (103 lb); BMI is 15 kg/m2. He is diagnosed with gastric cancer. Which cytokines are the most likely direct cause of this patient’s examination findings?

AMBOSS

A

Interleukin 1, interleukin 6, interferon-gamma, and tumor necrosis factor-alpha play an important role in the development of cancer anorexia-cachexia syndrome. These cytokines, which are secreted as a chronic inflammatory response to malignancy, increase the basal metabolic rate in cancer patients. The combination of decreased caloric intake and a hypermetabolic state results in significant weight loss from muscle atrophy.

AMBOSS

66
Q

A 59-year-old woman with stage IV lung cancer comes to the physician because of progressively worsening weakness over the past 3 months. She has had a 10.5-kg (23-lb) weight loss during this period. Her BMI is 16 kg/m2. She appears thin and has bilateral temporal wasting. What is the likely primary mechanism underlying this woman’s temporal muscle atrophy?

A

Proteasomal degradation of ubiquitinated proteins

Muscle wasting in the setting of cancer cachexia is associated with the increased release of proinflammatory cytokines such as IL-1, IL-6, and TNF-α from cancer cells. These cytokines activate NF-κB, which stimulates the ubiquitin-proteasome pathway. Ubiquitinated proteins (e.g., myosin chains in skeletal muscle cells) undergo proteasomal degradation, leading to increased muscle catabolism. TNF-α in particular is known to stimulate muscle catabolism via the alteration of hormone levels that regulate muscle growth (i.e., IGF-1, GH). Furthermore, TNF-α-mediated suppression of appetite in the hypothalamus, as well as peripheral activation of lipases, leads to the reduction of body fat. Cachexia occurs not only in the setting of cancer but also in conditions such as AIDS, COPD, heart failure, or end-stage renal disease.

67
Q

Koilocytes

A

Finding correlated with HPV infection

68
Q

What histological finding is always correlated with the worst clinic outcome of metastasis?

A

Anaplasia

Very poorly differentiated cells

69
Q

TP53 tumor suppressor gene mutation

A

Li-Fraumeni syndrome

Common malignancies:

Osteosarcomas
Breast cancer
Brain tumors
Adrenocortical carcinomas

M1 FMK (55 decks)

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