120e Carcinoma of Unknown Primary

Question 1

Biopsy-proven malignancy for which the anatomic site of origin remains unidentified after an intensive search

Answer 1

Carcinoma of unknown primary (CUP)

Question 2

One hypothesis for CUP

Answer 2

Primary tumor either regresses after seeding the metastasis or remains so small that it is not detected

Question 3

CUP biology

Answer 3

Studies have not been successful.

1. Abnormalities in chromosomes 1 and 12
2. Aneuploidy
3. Overexpression of genes (Ras, bcl-2, her-2 and p53

Question 4

2 goals in the initial CUP evaluation

Answer 4

1. Search for the primary tumor based on pathologic evaluation of metastases
2. Determine the extent of disease

Question 5

T or F: Most tumor markers when elevated are specific and will be helpful in determining the primary tumor site.

CEA, CA-125, CA19-9, CA 15-3

Answer 5

False

Are nonspecific and NOT helpful in determining the primary tumor site

Question 6

Standard of care on imaging for CUP

Answer 6

If no contraindications:

Baseline CT with IV contrast of CHEST, ABDOMEN, PELVIS

Question 7

Test that should be performed in all women who present with metastatic adenocarcinoma and presenting with isolated axillary lymphadenopathy

Answer 7

Mammography

Question 8

If your female patient with CUP tested negative for mammography and ultrasound, what is the next step?

Answer 8

MRI of breast

Negative MRI: predicts low tumor yield at mastectomy

Question 9

Conventional workup for squamous cell carcinoma and cervical CUP (neck lymphadenopathy with no known primary tumor)

Answer 9

1. CT scan or MRI
2. Indirect and direct laryngocscopy
3. Bronchoscopy
4. Upper endoscopy
5. Ipsilateral (or bilateral) staging tonsillectomy has been RECOMMENDED for these pt
6. 18-Fluorodeoxyglucose positron emission tomography scan are useful

Question 10

T or F: PET is not routinely recommended

Answer 10

True

Question 11

T or F: Invasive studies, including upper endoscopy, colonoscopy, and bronchoscopy should be done in all patients to determine the primary cause in CUP.

Answer 11

False

Should be limited to SYMPTOMATIC patients or those with labs, imaging or pathologic abnormalities suggesting high yield in these procedures

Question 12

T or F: Detailed pathologic examination of the most accessible biopsied tissue specimen is mandatory in CUP patients using H&E stains and immunohistochemical tests

Answer 12

True

Question 13

Cancers that rarely present as CUP

Answer 13

1. Prostate Ca

2. Thyroid Ca

Question 14

Cytokeratin markers used in adenocarcinoma of unknown primary

Answer 14

CK7 and CK20

See Figure 120e-1, p.120e-2

Question 15

Cytokeratin marker found in tumors of the lung, ovary, endometrium, breast and upper GI tract including pancreaticobiliary cancers

Answer 15

CK7

Question 16

Cytokeratin marker normally expressed in GI epithelium, urothelium and Merkel cells

Answer 16

CK20

Question 17

Thyroid transcription factor 1 (TTF-1) nuclear staining is typically positive in what type of cancers?

Answer 17

Lung cancer

Thyroid cancer

Question 18

Markers used to diagnose lesions of urothelial origin

Answer 18

UROIII
High molecular weight cytokeratin
Thrombomodulin
CK20

Question 19

Product of homeobox gene necessary for intestinal organogenesis often used to aid in diagnosis of GI adenocarcinomas

Answer 19

CDX-2 transcription factor

Question 20

Phenotypes very suggestive of lung and lower GI cancer profiles

Answer 20

LUNG CA: TTF-1/CK7+

Lower GI CA: CK20+/CDX-2+/CK7-

Question 21

Immunohistochemical stains for diagnosis of CUP

Answer 21

See Table 120e-2

Question 22

Median survival duration of most patients with disseminated CUP

Answer 22

6-10 months

Question 23

Primary treatment modality in most patients with disseminated disease

Answer 23

Systemic chemotherapy

Question 24

Prognostic factors in treatment of CUP

Answer 24

1. Performance status
2. Site and number of metastases
3. Response to chemotherapy
4. Serum LDH

Question 25

Management of women with carcinoma/adenoCA with Isolated Axillary Adenopathy

Answer 25

Treat for Stage II or III breast CA based on pathologic findings

Question 26

Factors to consider on what therapy to use: chemotherapy and/or hormonal therapy

Answer 26

1. Age of patient 2. Nodal disease bulk 3. Hormone receptor status

Question 27

Term used to describe CUP with carcinomatosis with the pathologic and laboratory (elevated CA-125 antigen) characteristics of ovarian cancer but no ovarian primary tumor identified on transvaginal sonography or laparotomy

Answer 27

Primary Peritoneal Papillary Serous Carcinoma (PPSC)

Question 28

Management for patients with PPSC

Answer 28

Candidates for cytoreductive surgery then | Adjuvant taxane- and platinum-based chemo

Question 29

Colon cancer profile in IHC

Answer 29

CDX-2+/CK20+/CK7-

Question 30

If your male patient with CUP presented with metastases only on the bones, and PSA is not elevated, what is the next step?

Answer 30

Chemotherapy or Radiotherapy as indicated

Question 31

In a patient with CUP presenting with solitary site of metastasis, and the tumor is unresectable, what is the next step?

Answer 31

Chemotherapy, Radiotherapy OR chemoradiotherapy depending on location of tumor

Question 32

In a patient with CUP and IHC suggests possible peritoneal carcinoma, probably PRIMARY peritoneal cancer. What is your next step?

Answer 32

Treat as OVARIAN cancer

Question 33

Patient with CUP, presented with disseminated cancer, 2 or more sites involved. What is your next step?

Answer 33

Chemotherapy IF good performance status

Question 34

For a patient suspected with squamous cell CUP, presenting with metastatic cervical adenopathy, what is your next step?

Answer 34

1. Triple endoscopy 2. Consider tonsillectomy 3. CT scan of neck and chest PET is optional See Figure 120e-3 for the algorithm

Question 35

Men with poorly differentiated or undifferentiated carcinoma that presents as midline adenopathy should be evaluated for what malignancy?

Answer 35

Extragonadal germ cell malignancy If older pt and smokers: suspect lung or head-and-neck cancer profile

Question 36

Neuroendocrine carcinoma treatment decisions are based on symptoms and tumor bulk. Often they are treated with this hormone for symptoms such as diarrhea, flushing, and nausea.

Answer 36

Somatostatin analogues

Question 37

Management for patients with early-stage squamous cell CA involving the cervical lymph nodes

Answer 37

Candidates for node dissection and radiation therapy

Question 38

Chemotherapeutic regimens for CUP presenting as metastatic disease

Answer 38

1. Paclitaxel-Carboplatin 2. Gemcitabine-Cisplatin 3. Gemcitabine-Oxaliplatin 4. Irinotecan and fluoropyrimidine-based therapies