Carcinoma of Unknown Primary - H/O

Question 1

Carcinoma of Unknown Primary

Answer 1

• Relatively common clinical entity
• Accounts for 3-5% of all invasive cancers

Can be defined as:
-A biopsy-proven metastatic cancer in the absence of pathologically or radio graphically detectable primary tumor after an intensive diagnostic evaluation.

• Different from cancers where the primary site is known
• Tx easier if you can identify primary source

Question 2

Natural History

Answer 2

The fundamental characteristics of CUP are:

• Early dissemination
• Clinical absence of primary site at presentation
• Generally quite aggressive
• Unpredictable metastatic pattern

Hypothesis for tumors presenting as CUP:
-Primary tumor regresses after seeding the metastasis or remains so small that it is no longer detected.Adenocarcinoma metastatic to the liver or other organs
Non-papillary malignant ascites (adenocarcinoma)
Multiple cerebral metastases (adeno or squamous Ca)
Multiple lung/pleural metastases(adenocarcinoma)
Multiple metastatic bone disease (adenocarcinoma)

-Primary may have been eliminated or contained by body’s defenses.

Question 3

Clinical manifestations

Answer 3

-Constitutional symptoms : weight loss, fever
Physical exam : pleural effusions/ ascites, adenopathy, hepatomegaly, other abnormalities related to the involved sites.
-Multiple sites of involvement observed in more than 50% of patients with occult primary tumors.
-Common sites of involvement : liver, lungs, bones, and lymph nodes.
-Certain patterns of metastases suggest possible primaries, occult primaries can metastasize to any site.
-Should not rely on patterns of metastases to determine the primary site.

Question 4

DIAGNOSTIC EVALUATION

Answer 4

• Focused on determining the primary site depending upon: histologic category, the site of presentation.
• The initial work-up of patients presenting with a presumed CUP should not be exhaustive, and should instead be focused toward evaluation of likely primary sites.
• A precise diagnosis is desirable since therapy for these tumors is quite different and may be potentially curative

Question 5

Histopathology

Answer 5

• Most are adenocarcinoma under histologic evaluation
• Once tumor is classified as a “Carcinoma” , other histo-pathological features can be used to suggest the site of origin :

Examples:

• Comedo-necrosis ( breast cancer)
• Prominent Nucleoli ( prostate cancer)
• Pseudo-stratification – Good clue in GI cancers
• None of these features are 100% specific for the site of origin

Question 6

Immunohistochemistry

Answer 6

IHC stains:
-These are peroxidase labeled antibodies against specific tumor antigens that are used to define tumor lineage.

• 10 key markers generally being tested for
• 70% of CUP patients will have high serum levels of more than one tumor marker.
• IHC stains should be used in conjunction with the patient’s clinical presentation and imaging studies to select the best therapy.
• Monoclonal antibodies to specific CK subtypes have been used to help classify tumors according to their site of origin
• There are > 20 subtypes of cytokeratin(CK) intermediate filaments
• Commonly used CK stains in CUP are CK7 and CK 20

Question 7

FAVOURABLE SUBSETS

Answer 7

1. Poorly differentiated Ca with midline distribution (extragonadal germ cell syndrome)
2. Women with papillary adenocarcinoma of peritoneal cavity
3. Women with adenocarcinoma involving only axillary lymph nodes
4. Squamous cell Ca involving cervical lymph nodes
5. Poorly differentiated neuroendocrine Ca
6. Men with blastic bone metastases and elevated PSA(adenocarcinoma)
7. Isolated inguinal adenopathy (squamous Ca)
8. Patients with a single, small, potentially resectable tumor

Question 8

UNFAVORABLE SUBSETS

Answer 8

1. Adenocarcinoma metastatic to the liver or other organs
2. Non-papillary malignant ascites (adenocarcinoma)
3. Multiple cerebral metastases (adeno or squamous Ca)
4. Multiple lung/pleural metastases(adenocarcinoma)
5. Multiple metastatic bone disease (adenocarcinoma)