120e Carcinoma of Unknown Primary Flashcards
Biopsy-proven malignancy for which the anatomic site of origin remains unidentified after an intensive search
Carcinoma of unknown primary (CUP)
One hypothesis for CUP
Primary tumor either regresses after seeding the metastasis or remains so small that it is not detected
CUP biology
Studies have not been successful.
- Abnormalities in chromosomes 1 and 12
- Aneuploidy
- Overexpression of genes (Ras, bcl-2, her-2 and p53
2 goals in the initial CUP evaluation
- Search for the primary tumor based on pathologic evaluation of metastases
- Determine the extent of disease
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
False
Are nonspecific and NOT helpful in determining the primary tumor site
Standard of care on imaging for CUP
If no contraindications:
Baseline CT with IV contrast of CHEST, ABDOMEN, PELVIS
Test that should be performed in all women who present with metastatic adenocarcinoma and presenting with isolated axillary lymphadenopathy
Mammography
If your female patient with CUP tested negative for mammography and ultrasound, what is the next step?
MRI of breast
Negative MRI: predicts low tumor yield at mastectomy
Conventional workup for squamous cell carcinoma and cervical CUP (neck lymphadenopathy with no known primary tumor)
- CT scan or MRI
- Indirect and direct laryngocscopy
- Bronchoscopy
- Upper endoscopy
- Ipsilateral (or bilateral) staging tonsillectomy has been RECOMMENDED for these pt
- 18-Fluorodeoxyglucose positron emission tomography scan are useful
T or F: PET is not routinely recommended
True
T or F: Invasive studies, including upper endoscopy, colonoscopy, and bronchoscopy should be done in all patients to determine the primary cause in CUP.
False
Should be limited to SYMPTOMATIC patients or those with labs, imaging or pathologic abnormalities suggesting high yield in these procedures
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
True
Cancers that rarely present as CUP
- Prostate Ca
2. Thyroid Ca
Cytokeratin markers used in adenocarcinoma of unknown primary
CK7 and CK20
See Figure 120e-1, p.120e-2
Cytokeratin marker found in tumors of the lung, ovary, endometrium, breast and upper GI tract including pancreaticobiliary cancers
CK7
Cytokeratin marker normally expressed in GI epithelium, urothelium and Merkel cells
CK20
Thyroid transcription factor 1 (TTF-1) nuclear staining is typically positive in what type of cancers?
Lung cancer
Thyroid cancer
Markers used to diagnose lesions of urothelial origin
UROIII
High molecular weight cytokeratin
Thrombomodulin
CK20
Product of homeobox gene necessary for intestinal organogenesis often used to aid in diagnosis of GI adenocarcinomas
CDX-2 transcription factor
Phenotypes very suggestive of lung and lower GI cancer profiles
LUNG CA: TTF-1/CK7+
Lower GI CA: CK20+/CDX-2+/CK7-
Immunohistochemical stains for diagnosis of CUP
See Table 120e-2
Median survival duration of most patients with disseminated CUP
6-10 months
Primary treatment modality in most patients with disseminated disease
Systemic chemotherapy
Prognostic factors in treatment of CUP
- Performance status
- Site and number of metastases
- Response to chemotherapy
- Serum LDH
Management of women with carcinoma/adenoCA with Isolated Axillary Adenopathy
Treat for Stage II or III breast CA based on pathologic findings
Factors to consider on what therapy to use: chemotherapy and/or hormonal therapy
- Age of patient
- Nodal disease bulk
- Hormone receptor status
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
Primary Peritoneal Papillary Serous Carcinoma (PPSC)
Management for patients with PPSC
Candidates for cytoreductive surgery then
Adjuvant taxane- and platinum-based chemo
Colon cancer profile in IHC
CDX-2+/CK20+/CK7-
If your male patient with CUP presented with metastases only on the bones, and PSA is not elevated, what is the next step?
Chemotherapy or Radiotherapy as indicated
In a patient with CUP presenting with solitary site of metastasis, and the tumor is unresectable, what is the next step?
Chemotherapy, Radiotherapy OR chemoradiotherapy depending on location of tumor
In a patient with CUP and IHC suggests possible peritoneal carcinoma, probably PRIMARY peritoneal cancer. What is your next step?
Treat as OVARIAN cancer
Patient with CUP, presented with disseminated cancer, 2 or more sites involved. What is your next step?
Chemotherapy IF good performance status
For a patient suspected with squamous cell CUP, presenting with metastatic cervical adenopathy, what is your next step?
- Triple endoscopy
- Consider tonsillectomy
- CT scan of neck and chest
PET is optional
See Figure 120e-3 for the algorithm
Men with poorly differentiated or undifferentiated carcinoma that presents as midline adenopathy should be evaluated for what malignancy?
Extragonadal germ cell malignancy
If older pt and smokers: suspect lung or head-and-neck cancer profile
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.
Somatostatin analogues
Management for patients with early-stage squamous cell CA involving the cervical lymph nodes
Candidates for node dissection and radiation therapy
Chemotherapeutic regimens for CUP presenting as metastatic disease
- Paclitaxel-Carboplatin
- Gemcitabine-Cisplatin
- Gemcitabine-Oxaliplatin
- Irinotecan and fluoropyrimidine-based therapies
