Pathology-Neoplasia Flashcards by Shane Hagen

What is P-glycoprotein?

Aka multidrug resistance protein 1 (MDR1).

Classically seen in adrenal cell carcinoma but also expressed by other cancer cells (e.g. colon, liver). Used to pump out toxins, including chemo agents

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What are some reversible types of cell changes?

Hyperplasia, metaplasia, and dysplasia

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What are some irreversible types of cell changes?

anaplasia, neoplasia, and desmoplasia

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What is anaplasia?

Loss of structural differentiation and function of cells, resembling primitive cells of same tissue; often equated with undifferentiated malignant neoplasma

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What is neoplasia?

An uncontrolled and excessive clonal proliferation of cells that may be benign or malignant

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What is desmoplasia?

fibrous tissues formation in response to neoplasm (e.g.linitis plastica in diffuse stomach cancer)

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What is tumor grade?

Degree of cellular differentiation and mitotic activity on histology. Usually graded 1-4

Stage almost always has more prognostic value than grade

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What is tumor stage?

Degree of localization/spread based on site and size of the primary lesion, spread to regional lymph nodes, and presence of MET

TNM staging most common

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What is the difference between carcinoma and sarcoma?

Carcinoma implies epithelial origin, whereas sarcoma denotes mesenchymal origin.

Both terms imply malignancy.

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Most carcinomas spread via _______

lymph (while most sarcomas spread via blood)

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What is a choristoma?

Normal tissue in a foreign location (e.g. gastric tissue located in the small bowel in Meckel diverticulum)

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What are some benign epithelium derived tumors?

adenoma and papilloma

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What are some malignant epithelium derived tumors?

adenocarcinoma or papillary carcinoma

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What are the benign and malignant tumors of blood cells?

Benign: None

Malignant: Leukemia, lymphoma

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What are the benign and malignant tumors of blood vessels?

Benign: hemangioma

Malig: Angiosarcoma

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What are the benign and malignant tumors of smooth muscle?

Benign: Leiomyoma

Malignant: Leiomyosarcoma

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What are the benign and malignant tumors of striated muscle?

Benign: Rhadbomyoma

Malignant: Rhabdomyosarcoma

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What are the benign and malignant tumors of CT?

Benign: Fibroma

Malignant: Fibrosarcoma

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What are the benign and malignant tumors of bone?

Benign: Osteoma

Malig: Osteosarcoma

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What is cachexia?

Syndrome of weight loss, muscle atrophy, and fatigue that occur in chronic disease (e.g. cancer, AIDS, heart failure, etc.) mediated by TNF-a (aka cachectin), IFN-y, IL-1, and IL-6

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What malignant might this indicate?

Rare paraneoplastic indicator of visceral malignancy (more commonly associated with insulin resistance)

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What malignant might Barrett esophagus lead to?

Esophageal adenocarcinoma

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What malignant might chronic atrophic gastritis lead to?

Gastric adenocarcinoma

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What malignant might cirrhosis lead to?

HCC

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What malignant might Ulcerative colitis lead to?

Colon adenocarcinoma

What malignancy might this lead to?

Squamous cell carcinoma of skin (pic: actinic keratosis)

What malignancy might multiple seborrheic keratoses lead to?

GI, breast, lung, and lymphoid malignancies

What malignancy might Paget disease of bone lead to?

secondary osteosarcoma and fibrosarcoma

What malignancy might Plummer-Vinson Syndrome lead to?

Squamous cell carcinoma of the esophagus

What malignancy might tuberous sclerosis lead to?

Often manifests with multiple hamartomas (benign) tumors including giant cell astrocytomas, renal angiomyolipomas, cardiac rhabdomyomas NOTE: These tumors MAY become malignant

Down syndrome classically predisposes to what blood cancer?

acute lymphocytic leukemia

Autoimmune disorders like Hashimoto and SLE classically predispose to what cancers?

Lymphoma

Radiation exposure mostly increases risk of developing which cancers?

leukemia, sarcoma, papillary thyroid cancer, breast cancer

Note that for oncogenes to cause cancer, only 1 mutation has to be present, while both alleles of tumor suppressors must be absent to cause disease

What is BCR-ABL (oncogene) and what cancer is it associated with?

Tyrosine kinase with CML and ALL

What is Bcl-2 (oncogene) and what cancer is it associated with?

Antiapoptotic molecule with follicular and undifferentiated lymphoma

What is BRAF (oncogene) and what cancer is it associated with?

Serine/tyrosine kinase with melanoma and non-Hodgkin lymphoma

What is c-kit (oncogene) and what cancer is it associated with?

Cytokine receptor with GIST tumor

What is c-myc (oncogene) and what cancer is it associated with?

Transcription factor with Burkitt lymphoma

What is HER2/neu (c-erbB2) (oncogene) and what cancer is it associated with?

Tyrosine kinase in breast, ovarian, and gastric carcinoma

What is L-myc (oncogene) and what cancer is it associated with?

Transcription factor with **l**ung tumors

What is N-myc (oncogene) and what cancer is it associated with?

Transcription factor with neuroblastoma

What is RAS (oncogene) and what cancer is it associated with?

GTPase with colon cancer, lung cancer, and pancreatic cancer

What is RET (oncogene) and what cancer is it associated with?

Tyrosine kinase with MEN2A/2B and medullary thyroid cancer

What is APC (tumor suppressor gene) and what cancer is it associated with?

Colorectal cancer (associated with FAP)

What is BRCA1/2 (tumor suppressor gene) and what cancer is it associated with?

DNA repair protein with Breast and ovarian cancer

What is DCC (tumor suppressor gene) and what cancer is it associated with?

Deleted in colon cancer (DCC)

What is DPC4/SMAD4 (tumor suppressor gene) and what cancer is it associated with?

Deleted in pancreatic cancer (DPC)

What is MEN1 (tumor suppressor gene) and what cancer is it associated with?

Menin with MEN1

What is NF1 (tumor suppressor gene) and what cancer is it associated with?

Ras GTPase activating protein (neurofibromin) with NF1

What is NF2 (tumor suppressor gene) and what cancer is it associated with?

Merlin (schawannomin) protein with NF2

What is p16 (tumor suppressor gene) and what cancer is it associated with?

Cyclin-dependent kinase inhibitor 2A with melanoma

What is p53 (tumor suppressor gene) and what cancer is it associated with?

transcription factor for p21, blocks G1 to S transition (seen in many cancers)

What is PTEN (tumor suppressor gene) and what cancer is it associated with?

Breast cancer, prostate cancer, and endometrial cancer

What is Rb (tumor suppressor gene) and what cancer is it associated with?

Inhibits E2F to block G1 to S transition with **Retinoblastoma, osteosarcoma**

What is TSC1 (tumor suppressor gene) and what cancer is it associated with?

Hamartin protein with tuberous sclerosis

What is TSC2 (tumor suppressor gene) and what cancer is it associated with?

Tuberin protein with tuberous sclerosis

What is VHL (tumor suppressor gene) and what cancer is it associated with?

Inhibits hypoxia inducible factor 1a with von Hippel-Lindau disease and renal cell carcinoma (3p)

What is WT1/2 (tumor suppressor gene) and what cancer is it associated with?

Wilms Tumor

Note about tumor markers: They should NOT be used as the primary tool for cancer diagnosis OR screening, but only to monitor tumor recurrence and response to therapy.

What is alk phos a good tumor marker for?

METS to bone or liver, Paget disease of bone, and seminomas (Placental ALP\_

What is a-fetoprotein a good tumor marker for?

HCC, hepatoblastoma, yolk sac (endodermal sinus) tumors, and mixed germ cell tumors NOTE: Normally made by fetus and transiently elevated in pregnancy but very high levels are assoicated with neural tube and abdominal wall defects, and low levels are associated with Down syndrome

What is B-hCG a good tumor marker for?

Hydatidiform moles and choriocarconomas (gestattiional trophoblastic disease), testicular cancer, and mixed germ cell tumors Produced by syncytiotrophoblasts of the placenta

What is CA15-3/CA27-29 a good tumor marker for?

Breast cancer

What is CA19-9 a good tumor marker for?

Pancreatic adenocarcinoma

What is CA125 a good tumor marker for?

Ovarian cancer

What is calcitonin a good tumor marker for?

Medullary thyroid carcinoma

What is CEA a good tumor marker for?

**C**arcino-**E**mbryonic **A**ntigen that is very nonspecific but produced by ~70% of colorectal and pancreatic cancers and also by gastric, breast, and medullary thyroid carcinomas

What is Chromogranin a good tumor marker for?

Neuroendocrine tumors/carcinoid tumors

What is PSA a good tumor marker for?

Prostate cancer and may be elevated in BPH and prostatitis (not that good)

EBV is associated with which cancers?

Burkitt lymphoma Hodgkin lymphoma nasopharygneal carcinoma Primary CNS lymphoma in immunocompromised

HBV/HCV is associated with which cancers?

HCC

HHV-8 is associated with which cancers?

kaposi sarcoma

HPV is associated with which cancers?

Cervical and penile/anal carcinoma (16/19), and head and neck cancer

H. pylori is associated with which cancers?

Gastric adenocarcinoma and MALT lymphoma

HTLV-1 is associated with which cancers?

Adult T-cell leukemia/lymphoma

Liver flukes (clonorchis sinensis) is associated with which cancers?

Cholangiocarcinomas

Schistosoma haematobium is associated with which cancers?

Bladder cancer (squamous cell)

Alfatoxins (aspergillus) is associated with which cancers?

HCC

Alkylating agents is associated with which cancers?

Leukemia and lymphoma

Aromatic amines (eg. benzidine, 2-naphthylamine) is associated with which cancers?

Transitional cell carcinoma

Arsenic is associated with which cancers?

Angiosarcoma Lung cancer Squamous cell carcinoma

Asbestos is associated with which cancers?

Bronchogenic carcinoma over mesothelioma

Carbon tetrachloride is associated with which cancers?

centrilobular necrosis and fatty change

Cigarettes are associated with which cancers?

Transitional cell carcinoma of the bladder Cervical carcinoma Squamous cell carcinoma/adenocarcinoma of the esophagus Renal cell carcinoma Squamous cell carcinoma of the larynx Squamous cell and small cell carcinoma of the lung Pancreatic adenocarcinoma

Nitrosamines (smoked foods) is associated with which cancers?

gastric cancer

Ethanol is associated with which cancers?

HCC and squamous cell of the esophagus

Ionizing radiation is associated with which cancers?

Papillary thyroid carcinoma

Radon is associated with which cancers?

Lung cancer

Vinyl chloride is associated with which cancers?

Angiosarcoma

Hypercalcemia as a result of calcitriol overproduction is a paraneoplastic symptom of what cancer(s)?

Hodgkin and non-Hodgkin lymphoma

ACTH (Cushing syndrome) is a paraneoplastic symptom of what cancer(s)?

Small cell lung carcinoma and renal cell carcinoma

ADH (SIADH) is a paraneoplastic symptom of what cancer(s)?

Small cell lung carcinoma and intracranial neoplasms

Abs against presynaptic Ca2+ channels at the NMJ (Lambert Eaton syndrome) is a paraneoplastic symptom of what cancer(s)?

Small cell lung carcinoma

EPO production is a paraneoplastic symptom of what cancer(s)?

Renal cell carcinoma, hemangioblastoma, HCC, leiomyoma, and pheochromocytoma

PTHrP (hypercalcemia) is a paraneoplastic symptom of what cancer(s)?

Squamous cell lung carcinoma, renal cell carcinoma, and breast cancer

What are Psamomma bodies?

Laminated, concentric spherules with dystrophic calcifications

**PS**a**MM**oma bodies are seen in what diseases?

**P**apillary carcinoma of the thyroid **S**erous papillary cystadenocarcinoma of the ovary **M**eningioma **M**alignant mesothelioma

What are the most common cancers in men?

1. Prostate 2. Lung 3. CRC

What are the most common cancers in women?

1. Breast 2. Lung 3. CRC

What are the most common cancer **killers** in men?

1. Lung 2. Prostate 3. CRC

What are the most common cancer **killers** in women?

1. Lung 2. Breast 3. CRC

What are the most common sources of METS to the **brain**?

Lung \> breast \> prostate \> melanoma \> GI NOTE: 50+% of brain tumors are METS

What are the most common sources of METS to the **liver**?

Colon \>\> stomach \> pancreas

What are the most common sources of METS to the **Bone**?

Prostate, breast \> lung, thyroid, and kidney NOTE: Bone METS are much more common than primaries (e.g. MM or lytic bone disease)

More on the typical presentation of METS to bone:

Breast and lung (mixed) Thyroid and kidney (lytic) Prostate (blastic)