Lecture 50 - Paraneoplasms and Presentations of Cancer Flashcards
what are the local Effects on Tumors and Host ?
○ Destruction of normal tissue by tumor
○ Space occupying effect of the tumor
Tumor Erosion of mucosa, vessel, skin, nerves (bleeding, secondary infection, perineural invasion)
what are the “general” Effect on Tumors and Host ?
○ Cachexia – Progressive loss of body fat and lean body/muscle mass
Profound weakness, anorexia, anemia
○ Hormonal Effects - -
when should you suspect cachexia?
Involuntary weight loss of > 10 % of premorbid weight
What are the different kinds of hormonal effects a malignancy can induce?
Tumor of Endocrine tissue which normally produces a hormone
vs
paraneoplastic Syndrome – hormones/ being produced by a malignant tissue that does not normally produce those hormones
what are the different categories of Paraneoplastic Syndromes?
Endocrinopathies
Osseous Tissue syndromes
Dermatologic
Neuromyopathies
vascular/coagulopathies
Endocrinopathies
Paraneoplastic Cushing Syndrome-
Hypercalcemia
Syndrome of Inappropriate ADH secretion (SIADH)
Hypoglycemia
Polycythemia
Paraneoplastic Cushing Syndrome-
what is it?
what type of tumor most commonly causes it ?
Symptoms?
tumor producing ACTH, leading to adrenal production of Cortisol
50% produced by Lung tumors
Symptoms: Cushings – truncal obesity, fat pad, easy bruising, fatigue, depression, etc
Paraneoplastic Hypercalcemia
- Significance?
- cause?
- type of tumor?
- Clinical Presentation:
- lab findings:
– most common incidence and most life threatening
- Lung cancer (that has not metastisized to the bone) that produced PTH or PTH RP leading to “leakage” of calcium from the bone
Symptoms: Confusions, weakness, lethargy, constipation
Labs: Hypercalcemia + Low/normal Serum PTH; elevated PTHRP
Paraneoplasm: Syndrome of Inappropriate ADH secretion (SIADH)
- what is it?
- type of tumor
- lab findings;
- clinical effects? potential cause of death?
Secretion of ectopic ADH
Small Cell Carcinoma of the Lung, intracranial tumors
Labs: Hyponatremia
Clinical :cerebral edema (death); seizures
Paraneoplastic Hypoglycemia
- cause
- type of tumor
Paraneoplastic Polycythemia
- cause
Hypoglycemia: ectopic tumor secretes insulin like substance
- soft tissue sarcomas, hepatocellular carcinoma
Polycythemia:
Erythropoietin secreted by tumors; can cause thrombosis
Osteopathic Paraneoplastic ○ Hypertrophic Osteoarthropathy
- type of tumor
- Triad of symptoms
1-10% of patients with lung cancer
– New periosteal bone formation
– Arthritis of adjacent joints
- new onset clubbing of the fingers (in persons without emphysema)
Dermatologic Paraneoplasm:
- Ancanthosis Nigricans
- what is it?
- benign causes?
- malignant causes?
Gray/Black patches of verrucous hyperkeratosis, usually in the skin folds due to production of epitdermal growth factors
Benign causes: Diabetes
Malignant causes: Epidermal growth factors by Lung, gastric tumors
Paraneoplastic Neuromyopathies –
Presenations?
Causes?
Peripheral Neuropathies, cortical cerebellar damage
- Eaton Lambert Syndrome (auto-antibodies produced against tumor antigen which cross react with calcium channels)
Paraneoplastic - Vascular/Coagulopathies
- DIC (cause, and type of cancer)
NBTE (what is it?)
Trousseau Syndrome - (what is it; types/stage of cancer that causes it?)
DIC –
cancers: APL, Prostate cancer
Cause: Mucin with pro-coagulant effect
NBTE
- Non bacterial thrombotic endocarditis (non bacterial vegetations on the cardiac leaflets which can prduce emboli)
caused by advanced cancers
Trousseau Syndrome -- Advanced cancers (pancreas and lung); secrete mucins which activate the coagulation cascade leading to migratory (sequential) thrombophlebitis
Ancillary Tests of Pathology:
IHC as diagnositic test –
Uses – finding the tissue of origin in met, finding micro mets
Finding an unknown primary
Ancillary Tests of Pathology:
IHC as Prognostic/predictive test –
examples of use of IHC for finding targets for treatment
Proliferation rate –
Her2/neu -- if positive --- Herceptin (positive predictor, negative prognosis) Hormone Receptor Status: Estrogen Receptor of Breast Cancer (positive prognosis and predictive --- Tomoxifen, aromatase inhibitor)
What marker is used as metric for “proliferation rate”
Measured by Ki-67 (MIB1)
- how is Flow cytometry use?
- - how is cytogenic used?
Flow Cytometry – mainstay Dx of leukemias, lymphomas — classify tumor cells by surface markers
Cytogenetic: Used to find chromosomal translocations, etc
How are tumor markers utilized?
They can help with diagnosis of disease, but NOT SPECIFIC or SENSITIVE ENOUGH TO BE PRIMARY DIAGNOSTIC
- can be used to correlate tumor burden
- can be used to track remission/recurrence
The tumors Markers to REMEMBER: which of these can also be used for screening? What are they used to track?
PSA
CEA
AFP
□ PSA (prostate specific antigen): prostate cancer - the only one also used for screening (But nonspecific)
□ CEA (carcino-embryonic antigen): colon, pancreas Ca
□ AFP (alpha feto protein): hepatocellular, testicular Ca
tumor markers — what cancers?
CA-125
HCG:
CA19-9:
□ CA-125: ovarian tumors
□ HCG: testicular cancers
□ CA19-9: colon, pancreas Ca
Molecular analyses of tumors:
Positive/negative predictors?
EML4-ALK fusion in lung cancer
V600E mutation of BRAF in melanoma
EML4-ALK fusion in lung cancer – positive predictive (ALK inhibitor Crisotinib)
□ V600E mutation of BRAF in melanoma – positive predictive (BRAF inhibitor PLX4032)
Molecular analyses of tumors:
Positive/negative predictors?
EGFR –
Ras –
□ EGFR – positive predictive (Erlotinib)
□ Ras - negative prognostic and negative predictive marker (cetuximab) in colon cancer
