Pathology 1 - Block 2 - Part 4

davidwurbel7's version from 2016-02-29 20:02

Neoplasia 4

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Exposure to sufficient dose of carcinogenic agent. Causes permanent change (DNA), and it is irreversible. But cannot give rise to a tumorInitiation
These induce tumors in initiated cells, but by themselves, promoters are non-tumorigenicPromoters
Compounds which do not require no metabolic conversion to become carcinogenic. Said to be weak carcinogens. The “second” malignancy comes decades laterDirect Acting Compounds
Cyclophosphamide, chlorambucil, busulfan, melphalan are examples of these type of carcinogensDirect Acting Compounds
Cyclophosphamide, chlorambucil, busulfan, melphalan are used to do thisAnti-Cancer Drugs
The most common second malignancy is thisAcute Myeloid Leukemia (AML)
Compounds which require metabolic conversion to produce ultimate carcinogenIndirect Acting Compounds
A product of P- 450 which can metabolize polycyclic aromatic hydrocarbons to its active form (carcinogen)- benzopyreneCYP1A1
This CYP1A1 polymorphism is seen in 10% of this populationCaucasian
Benzopyrene, most potent carcinogen require metabolic activation ingredients of tobacco smoke, broiling of animal fat/fish cause lung and bladder malignanciesPolycyclic Aromatic Hydrocarbons
An example of this indirect acting agent is β- napthylamine (aniline dye, rubber industry). This can lead to transitional cell carcinoma (TCC). Bladder mucosa secrete an enzyme β-glucuronidase which splits the detoxified compound to produce ultimate carcinogenAromatic Amines
An example of this indirect acting agent is Aflatoxin B1. It is the mycotoxin from some strains of Aspergillus flavus. Exposure to this can lead to hepatocellular carcinoma (HCC)Naturally Occurring Carcinogens
Aflatoxin B1 is a naturally occurring carcinogen produced by this organismAspergillus flavus
Contain alkaloid arecoline, which is a carcinogen mutagenic, cytotoxic, and genotoxic effect. These compound in “paan” and “gutka” are addictiveBetel Nuts
Chewing of betel nuts can lead this seen in the oral cavityOral Leukoplakia
Malignant mesotheliomas is due to exposure to thisAsbestos
Long latent period of 25 to 45 years after exposure. Presents with chest pain, dyspnea, and recurrent pleural effusionsMalignant Mesothelioma
NITRITES  carcinoma of the stomach
Used as food preservatives
DIETHYLSTILLBESTROL (DES)  Clear cell adenocarcinoma of vagina and cervix in the babies, breast cancer in moms
Drug to help prevent abortions
UV RAYS  skin cancer
IONIZING RADIATION  myeloid leukemias, thyroid malignancies
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A retrovirus, high risk for T cell leukemia/lymphoma seen in the Caribbean and Japan. The virus contains TAX gene which activates NFkappaB which activates the PI3K activates AKT pathway. This interferes with DNA repair mechanism (genomic instability)Human T-Cell Leukemia Virus Type 1
HUMAN T-CELL LEUKEMIA VIRUS contains this geneTAX Gene
Angiosarcoma of liver is caused due to exposure to thisPoly Vinyl Chloride (PVC)
Exposure to poly vinyl chloride, arsenic, or Thorotrast (an old contrast agent no longer used) can lead to this conditionAngiosarcoma of Liver
Used as food preservatives nitrosamines formed, act as carcinogens and can lead to carcinoma stomachNitrates
Used earlier for threatened abortion. Women who took this during pregnancy have an increased risk of breast cancer. A female neonate had increased risks of clear cell adenocarcinoma of the vagina and cervixDiethylstilbestrol (DES)
This type of radiation is associated with squamous cell carcinoma, basal cell carcinoma, and melanoma of the skinUltraviolet Radiation
The mechanism for formation of cancer due to UV rays is the formation of thisPyrimidine Dimers
Exposure to this can lead to risk of leukemia in children, myeloid leukemias, thyroid malignancies (papillary carcinoma thyroid) in adults. There is an intermediate risk of breast, lung, salivary glandIonizing Radiation
Papillary carcinoma of the thyroid has concentrically calcified structures termedPsammoma Bodies


Question Answer
Retrovirus. High risk for T-cell leukemia/lymphoma. Seen in Caribbean & Japan. Transmission by sexual, blood products, breast feeding, long latency 40 to 60 years. The virus has tropism for CD4+ cells (like HIV). Virus contain ‘TAX’ gene, activates transcription of host genes. TAX interacts with PI3K which then activates AKT pathway. TAX gene also activates NF-κB,Human T-cell Leukemia Virus type 1 (HTLV-1)
Produces anogenital warts (condyloma acuminatum, benign). Exists as an episome in infected cellsHPV type 6 & 11
Produces cervical dysplasia/cancer. Exists as an integrated endosome into the host DNAHPV types 16 & 18
Viral protein binds to p53 and promotes its degradationE6
Viral protein binds to hypophosphorylated (active) form of RB and promotes its degradationE7
HPV can only infect these type of cellsImmature Squamous Epithelial Cells
Burkitt lymphoma (African), B- cell lymphomas (immunosuppressed), Hodgkin lymphoma, Nasopharyngeal carcinoma are associated with infection of this virusEpstein Barr Virus (EBV)
Infects the B cells by binding CD21 and in majority of cases, EBV establishes a latent infectionEpstein Barr Virus (EBV)
Epstein Barr Virus (EBV) infects B cells by binding to this proteinCD21
This EBV protein binds the EBV genome to host cell chromosomes during mitosisEBNA1
This EBV protein drives B-cell activation and proliferation also, trigger downstream events that activate NF-κB and the JAK/STAT signaling pathwayLatent membrane protein 1 (LMP1)
This EBV protein also promotes B-cell activation and replicationEBNA2
Lymphoma may arise if these cells acquire mutations , t(8;14) translocation. This gene is located in ch. 8 gets translocated leading to Burkitt lymphomaC-MYC
Cancer caused by HBV or HCV in 70% to 85% casesHepatocellular Carcinoma
HBV contains this which activates transcription factorsHBx
Infection of this organism is linked to gastric carcinomas and lymphomasHelicobacter pylori
Lymphomas arising from ‘mucosa- associated lymphoid tissue’MALTomas
Vascular neoplasm caused by human herpesvirus 8 (HHV8). Patches are red-purple macules typically confined to the distal lower extremities. Raised plaques composed of dermal accumulations of dilated, jagged vascular channels lined and surrounded by plump spindle cellsKaposi Sarcoma (KS)
1) Classic KS: uncommon in the United States
most associated with malignancy or altered immunity,
but is not associated with HIV infection
2) Endemic African KS: typically occurs in HIV-seronegative individuals younger than age 40
3) Transplant-associated KS: occurs in solid organ transplant recipients
in the setting of T-cell immunosuppression
4) AIDS-associated (epidemic) KS: is an AIDS-defining illness


Question Answer
Equal loss of both fat and lean muscle. Elevated basal metabolic rate. Evidence of systemic inflammation (e.g., an increase in acute phase reactants)Cancer Cachexia
Some cancer patients develop signs and symptoms that cannot readily be explained by the anatomic distribution of the tumor or by the elaboration of hormones indigenous to the tissue from which the tumor arose; these are known asParaneoplastic Syndromes
Cushing syndrome - Small cell Carcinoma of the lung - ACTH or ACTH analog
SIADH - Small cell Carcinoma of the lung - ADH or ADH analog - patient will also present with hyponatremia
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Small-cell carcinoma cells positive for thisChromogranin
The production of calcemic humoral substances parathyroid hormone-related protein (PTHRP) by extraosseous neoplasmsParaneoplastic Syndrome
Most common lung neoplasm associated with hypercalcemia isSquamous Cell Carcinoma
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Ectopic ADH production by tumors commonly seen in patients with small cell carcinoma of lung (SCLC) cause this syndromeSyndrome of inappropriate antidiuretic hormone (SIADH)
Most patients are asymptomatic and are identified because of the presence of hyponatremia on routine chemistry testing. Symptoms may include weakness, lethargy, nausea, confusion, depressed mental status, and seizuresSyndrome of inappropriate antidiuretic hormone (SIADH)
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Are substances that can be detected in higher than normal amounts in the serum, urine, or tissues of patients with certain types of cancer. They are biochemical indicators of presence of tumorTumor Makers
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Metastasis manifesting as a periumbilical nodule secondary to abdominal or pelvic cancers spread to the umbilicus is colloquially known asSister Mary Joseph Node
Tumor deposits (pelvic malignancies, gastric, and pancreas) may be found in this spacePouch of Douglas