Neoplasia Flashcards
Lipomas
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
Liposarcomas
Malignant tumors that originate from adipose tissue
Adenocarcinomas
Originate from glandular epithelium and consist of a disorganized mass of malignant cells that form glandular structures that may stain positive for mucin
Where is keratin production seen in metastatic disease?
Squamous cell carcinomas - arise in organs that are normally lined by stratified squamous epithelium
Anaplasia
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.
Carcinoma in situ is characterized by what?
Irreversible nuclear changes and lack of invasion (aka stage 0)
E-cadherin in metastatic processes
Plays an important role in cellular adhesion
Acts to oppose metastatic processes
Metalloproteinase
Zinc-containing enzyme that degrades the extracellular matrix, participates in normal tissue remodeling and in tumor invasion through the basement membrane and connective tissue
Key GF that promotes angiogenesis in neoplastic and granulation tissue
Vascular endothelial growth factor (VEGF) and fibroblast growth factor (lesser extent)
Most common cause of cancer death for men and women in US
Lung cancer
Top three cancers in men and women
Men - prostate>lung>colon
Women - breast>lung>colon
After skin cancer in both sexes
Lynch syndrome
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.
Li-Fraumeni Syndrome
Mutation of the TP53 gene - associated with multiple cancers at early age
Xeroderma pigmentosa
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
Ataxia-telangiectasia
Defective DNA break repair
Decreased IgA/G/E levels lead to recurrent sinopulmonary infections
Also characterized by cerebellar ataxia, conjunctival telangiectasia
Fanconi anemia
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
Epstein-Barr virus
Can lead to what cancers?
- Burkitt lymphoma
- Nasopharyngeal carcinoma
- Pirmary CNS lymphoma
- Some types of Hodgkin lymphoma
HPV E7 protein
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.
HPV E6 protein
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.
HPV infection
- Skin warts (verruca vulgaris)
- Veneral warts (condyloma acuminatum)
- Cervical neoplasia
- Anal carcinoma
- Laryngeal carcinoma
- Recurrent juvenile laryngeal papillomatosis
Cytopathic effect of HPV
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
Cachexia
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
Tumor grading
Based on histologic degree of differentiation and degree of mitotis activity = indicators of aggresiveness of malignant neoplasm
Tumor staging
Based on the size of the primary lesions, presence of lymph node metastases, and presence of blood-borne metastases
Tumor markers and proteins
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
Staging vs. grading
Staging is a measure of tumor spread and is generally more significant in determining the prognosis than tumor grading
Hamartoma
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
Choristoma
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)
Malignant neoplasm general classifications
Carcinomas - of epithelial origin
Sarcomas - mesenchymal origin
Organs associated with development of adenocarcinoma
Lung, colon, stomach, prostate, and endometrium
Where do squamous cell carcinomas arise
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)
What tumors usually have a papillary appearance
A tumor that originates from transitional epithelium (uroepithelium) of the urinary bladder or renal pelvis - transitional cell carcinoma (urothelial carcinoma)
Examples of malignant mesenchymal tumors
Rhabdomyosarcomas
Leiomyosarcomas
Fibrosarcomas
Liposarcomas
Leiomyosarcomas
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.
Rhabdomyosarcomas
Malignant mesenchymal tumors
Arise from skeletal muscle (contain cross-striations) - contain desmin or actin
Tumors that have the suffix -blastoma
Usually childhood malignancies
i.e - retinoblastoma, neuroblastoma, nephrobalstoma, hepatoblastoma…etc.
Clear cell carcinomas
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.
Signet cell carcinomas
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
What protease is essential for invasion of tumor cells into connective tissue
Type IV collagenase
Spread of sarcomas vs carcinomas (medium in which they spread)
Sarcomas - hematologic spread
Carcinomas - lymphatic spread
Where are the highest rates of gastric carcinoma
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.
Where are the highest rates of nasopharyngeal carcinoma
Parts of India and China
Associated with EBV
Where are the highest rates of liver cancer
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)
Where are the highest rates of trophoblastic diseases (i.e. choriocarcinoma and hydatidiform mole)
High rates of occurrence in parts of China
Bloom syndrome
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)
Tumors associated with the production of PTHrP
Squamous cell carcinoma of the lungs, clear cell carcinomas of the kidney, endometrial adenocarcinomas, and transitional carcinomas or the urinary bladder
Acanthosis nigricans
Paraneoplastic syndrome - abnormal pigmentation of the axilla (or groin)
Benign type - associated w/ insulin resistance
Malignant type - associated with visceral malignancies (especially gastric cancer)
Ectopic ACTH secretion
Paraneoplastic syndrome
Seen with small cell carcinoma of the lung - may produce Cushing syndrome
Paraneoplastic
Ectopic secretion of ADH
Syndrome of inappropriate ADH secretion (SIADH)
May produce hyponatremia
Also seen with small cell carcinoma of the lung
Paraneoplastic
Troussea sign
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
Polycythemia
As paraneoplastic syndrome
Associated with increased erythropoietin levels and some tumors (particularly renal cell carcinomas, hepatocellular carcinomas, and cerebellar hemangioblastomas)
What tumor is associated with myasthenia gravis
Tumor of the thymus
Chromagranin and synaptophysin
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)
S-100 (stain)
Nonspecific stain for neural crest cells - give rise to many different malignancies - malignant melanoma, neural tumors, and astrocytomas
Specific special stain for malignant melanoma
MART-1 and HMB-45
CA 15-3
Tumor marker for breast cancer
CA 125
Tumor marker for epithelial ovarian cancer
CA19-9
Tumor marker for pancreatic cancer
CEA
Carcinoembryonic antigen - glycoprotein associated with many cancers - adenocarcinomas of the colon, pancreas, lung, stomach, and breast
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?
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.
Germline mutations in DNA mismatch repair genes, such as MLH1, MSH2, and MSH6, result in ________
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
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?
Metalloproteinases
What stain is used to ID neuroendocrine cells?
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.
Normal sequence of events for cervical cancer development
- Normal
- Squamous metaplasia
- Dysplastic (HPV infection)
- Carcinoma in situ
- Invasive malignancy
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
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
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?
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.
Koilocytes
Finding correlated with HPV infection
What histological finding is always correlated with the worst clinic outcome of metastasis?
Anaplasia
Very poorly differentiated cells
TP53 tumor suppressor gene mutation
Li-Fraumeni syndrome
Common malignancies:
Osteosarcomas
Breast cancer
Brain tumors
Adrenocortical carcinomas
