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Clinico-Pathological Conference
September 9, 2008
12 Noon, Mountcastle Auditorium
PreClinical Teaching Building
Questions:
(1) What is the most likely cause of the neck, abdominal, and
lung lesions?
(2) If the lesions are malignant, what is the most likely site of
origin?
(3) What types of malignancies often present with metastatic
disease of clinically unclear origin?
Delirium in the Setting of Metastatic Cancer
(present in 20-86% of cases; reversible in ~50%)
Metabolic Abnormalities
hypercalcemia
hyperglycemia
hyponatremia/hypernatremia
uremia
hepatic failure
others
Hypoxia
Medications
opiates
benzodiazepines
corticosteroids
many others
Infections
Brain/Leptomeningeal Metastases
Bowel/Bladder Obstruction
Others
Delirium in the Setting of Metastatic Cancer
(present in 20-86% of cases; reversible in ~50%)
Metabolic Abnormalities
hypercalcemia
hyperglycemia
hyponatremia/hypernatremia
uremia
hepatic failure
others
Ca2+ = 11.0 mg/dL (8.5-10.5 mg/dL)
Hypoxia
ionized Ca2+ = 1.41 mM (1.12–1.32 mM)
PTH = 13 ng/L (10-65 ng/L)
Medications
opiates
benzodiazepines
corticosteroids
many others
Infections
Brain/Leptomeningeal Metastases
Bowel/Bladder Obstruction
Others
Hypercalcemia of Malignancy
Incidence:
10% of cancer cases
more common with squamous cell carcinoma
of the lung, breast cancer,
and multiple myeloma
usually recognized late and managed poorly
Pathophysiology:
PTHrP
other factors associated with bone metastases
(RANKL, TGFa, TNF, IL-1, others)
osteoclastic bone resorption
often aggravated by renal insufficiency
Presentation:
nausea, anorexia, constipation, dehydration,
polyuria, apathy, fatigue
progression to obtundation and death
Treatment:
extracellular fluid volume expansion
calciuresis
bisphosphonates
calcitonin, gallium nitrate, others
Common Oncologic Conditions Requiring
Urgent Evaluation and Intervention
Spinal epidural cord compression
Brain/leptomeningeal mestastases with intracranial edema
Hypercalcemia
Leukostasis
Vascular obstruction (eg. superior vena cava syndrome)
Intestinal obstruction
Urinary obstruction
Tracheal obstruction
Others
Common Oncologic Conditions Requiring
Urgent Evaluation and Intervention
Spinal epidural cord compression
Brain/leptomeningeal mestastases with intracranial edema
Hypercalcemia
Leukostasis
Vascular obstruction (eg. superior vena cava syndrome)
Intestinal obstruction
Urinary obstruction
Tracheal obstruction
Others
Work-up of a Suspected Metastatic Cancer
Initial evaluation
history and physical examination
Questions for consultant
complete blood count
specialist:
serum electrolytes
(i) Does this woman have a cancer?
serum liver enzymes/bilirubin
(ii) Is it curable?
serum creatinine
(iii) Is it treatable to prolong life or
serum calcium
improve quality-of-life?
urinalysis
(iv) Can she tolerate treatment?
chest radiograph
stool hemoccult evaluation
symptom-directed endoscopy
*PET or PET-CT scan for glucose uptake
serum cancer biomarkers (AFP, b-HCG, PSA, CA125, CEA)
Biopsy
fine needle aspiration (FNA) or core needle biopsy
most accessible site
consult pathologist for adequacy of specimens and
need for immunohistochemisty/molecular biology
assessment
Work-up of a Suspected Metastatic Cancer
Initial evaluation
history and physical examination
complete blood count- anemia, leukocytosis
serum electrolytes-hyponatremia
serum liver enzymes/bilirubin
serum creatinine
serum calcium-hypercalcemia
urinalysis
chest radiograph/CT/MR-right kidney mass; liver, lung, bone,
stool hemoccult evaluation
lymph node, muscle lesions
symptom-directed endoscopy
*PET or PET-CT scan for glucose uptake
serum cancer biomarkers-elevated CEA
Biopsy
fine needle aspiration (FNA) or core needle biopsy
most accessible site
consult pathologist for adequacy of specimens and
need for immunohistochemisty/molecular biology
assessment
Carcinoembryonic Antigen (CEA)
Glycoprotein involved in cell adhesion encoded by member of
the immunoglobulin gene superfamily (the carcinoembryonic
antigen family consists of some 29 genes)
First identified in 1965 by Phil Gold and Samuel O. Freedman in human
colon cancer tissue extracts
Serum from individuals with colorectal, gastric, pancreatic, lung,
hepatocellular, and breast carcinomas, or with medullary thyroid
carcinoma, often have higher levels of CEA than healthy individuals
Serum CEA testing best used for monitoring cancer recurrences
after surgical resection
Serum CEA levels are also elevated in smokers, in preneoplastic conditions
(eg. colonic polyps), and in non-cancerous conditions such as
ulcerative colitis, pancreatitis, and cirrhosis
Cancer of Uncertain Primary Origin
Primary site of origin is never found for some 2-6% of adults
with metastatic cancer (the site of origin is still not
evident in 15-25% even at post-mortem examination)
Clinical clues:
pattern of spread
presence of serum biomarkers
Most are adenocarcinomas (~60%; lung cancer, etc.)
others include: poorly differentiated carcinoma
(20-30%), squamous cell carcinoma (5-10%),
neuroendocrine carcinoma (1-5%), others
Median survival ranges from 11 weeks to 11 months
with an overall 5-year survival rate ~11%
Pathological Findings from Biopsy of
Suspected Metastatic Cancer
Epithelial cancer (carcinoma)
Lymphoma
Thyroid cancer
Melanoma
Sarcoma
Germ cell cancer
Non-malignant diagnosis
Gene Expression Profiling as an Aid to the Diagnosis
of Carcinoma of Uncertain Primary Origin*
classification scheme able to predict site of origin in 90% of cases
*Su AI et al. Cancer Res. 61: 7388-93 (2001)
“Physiological Staging”: Does the patient
have any medical problems/conditions that might
affect the choice of treatment if she has cancer?
Systemic Chemotherapy
heart disease- could be exacerbated by anthracyclenes
lung disease- could be further complicated by bleomycin
kidney diseases- could increase the risk of
renal failure from cisplatin
neuromuscular diseases- could be worsened by
exposure to microtubule-targeted antibiotics
uncontrolled infection- could be worsened by any
chemotherapy drug that lowers white
blood cell counts
Radiation Therapy
anatomic abnormalities- eg. a horseshoe kidney
connective tissue diseases- abnormal scarring/response to
damage from ionizing radiation
previous radiation therapy to nearby tissues- reduces tolerance
to further radiation
“Physiological Staging”: Does the patient
have any medical problems/conditions that might
affect the choice of treatment if he has cancer?
Systemic Chemotherapy
heart disease- could be exacerbated by anthracyclenes
lung disease- could be further complicated by bleomycin
kidney diseases- could increase the risk of
renal failure from cisplatin
neuromuscular diseases- could be worsened by
exposure to microtubule-targeted antibiotics
uncontrolled infection- could be worsened by any
chemotherapy drug that lowers white
blood cell counts
Radiation Therapy
anatomic abnormalities- eg. a horseshoe kidney
connective tissue diseases- abnormal scarring/response to
damage from ionizing radiation
previous radiation therapy to nearby tissues- reduces tolerance
to further radiation
Clinico-Pathological Conference
September 9, 2008
12 Noon, Mountcastle Auditorium
PreClinical Teaching Building
Questions:
(1) What is the most likely cause of the neck, abdominal, and
lung lesions? Cancer, but I would like to have had a pathologist
examine biopsy cells or tissues.
(2) If the lesions are malignant, what is the most likely site of
origin? Imaging studies suggest kidney cancer, but renal
cell carcinoma typically does not produce CEA. My guess
would be renal pelvis cancer (mucinous cancer,
adenocarcinoma, transitional cell carcinoma) or lung cancer.
However, again, I would like to have had a pathologist examine a
biopsy.
(3) What types of malignancies often present with metastatic
disease of clinically unclear origin? Adenocarcinomas; however,
almost any type of cancer can present this way. Clinical goal is
to find treatable cancers.
For Additional Information/Further Reading
Glover KY et al. Carcinoma of Unknown Primary. In
Abeloff’s Clinical Oncology, 4th Edition, Abeloff, M.D., Armitage, J.O.,
Niederhuber, J.E., Kastan, M.B., and McKenna, W.G. (Eds.),
Elsevier Inc., Philadelphia, PA (2008).