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CARCINOMA OF UNKNOWN PRIMARY Target Audience: Oncologists, Oncology Fellows Archer Board Reviews www.CcsWorkshop.com
Carcinoma of Unknown Primary ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Definition ,[object Object],[object Object]
Epidemiology ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
CUP - Biology   ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Clinical manifestations ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
DIAGNOSTIC EVALUATION ,[object Object],[object Object],[object Object],[object Object],[object Object]
Clinico-Pathological Entities of CUP Site of presentation Histology Liver (mainly) and/or other organs Adenocarcinoma,  Moderately/ poorly differentiated ,[object Object],[object Object],[object Object],[object Object],[object Object],-Un or poorly differentiated CA - Adenocarcinoma, Well to poorly differentiated  - Squamous Cell Carcinoma - Undifferentiated Ca, SCC, Mixed SCC/ Adeno Ca ,[object Object],[object Object],[object Object],-  Serous/ papillary adenocarcinoma (+/- Psammoma bodies) -  Mucinous adenoca – moderately/ poorly differentiated ( +/- signet ring cells) ,[object Object],[object Object],[object Object],[object Object],[object Object],Bones – solitary / multiple -  Adeno Ca, various diff Brain – solitary/ multiple -  Adeno Ca, various diff Neuroendocrine Tumors - Pdiff cancer with neuroendocrine features (mainly), low grade neuroendocrine ca, small cell anaplastic ca
“ Adequate” Evaluation ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
 
Pathology ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Pathology ,[object Object],Histology  Proportion %  Adenocarcinoma,  well to moderately differentiated 60% Squamous Cell Carcinoma 5% Poorly differentiated carcinoma/ poorly differentiated Adeno ca 30% Neuroendocrine 2% Undifferentiated Malignancy 3%
Adenocarcinoma ,[object Object],[object Object],[object Object]
 
Pathology ,[object Object],[object Object],[object Object]
Pathology ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Pathology ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Pathology
 
CUP - IHC ,[object Object],[object Object]
Immunohistochemistry ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Immunohistochemistry -  Cytokeratins (CKs)
Immunohistochemistry ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Immunohistochemistry Other Markers Tissue Marker Diagnosis TTF-1 Lung, Thyroid CDX-2  GI tract Gross Cystic Disease Fibrous Protein 15 (GCDFP) Breast  ER, PR Breast BRST1 Breast Thyroglobulin Thyroid cancer PSA Prostate cancer Calretinin, Mesothelin Mesothelioma Chromogranin, Synaptophysin, Neuron specific enolase Neuroendocrine cancer URO III, thrombomodulin Urothelial Ca/ Bladder Ca Beta-HCG Germ cell tumor Alpha-Feto-protein HCC, germ cell tumor S-100, HMB 45 Melanoma Leucocyte common antigen Lymphoma
CUP Imaging
Imaging Studies in CUP Imaging  Diagnostic Value Chest X-Ray Pre-Requisite test CT chest/ abdomen/ pelvis 40% accuracy/ guidance to biopsy Mammogram Low sensitivity MRI ( breast) 60% accuracy  Barium Studies Not Useful PET/CT scan  Useful in certain situations
Role of PET-CT in CUP ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
CUP Endoscopy
Endoscopy in CUP ,[object Object],Procedure Indication in CUP ENT – Pan-endoscopy Cervical Node involvement Bronchoscopy Symptoms or radiographic indications Colonoscopy Relevant symptoms and signs Proctoscopy Inguinal node involvement
Serum Tumor Markers ,[object Object],[object Object],[object Object],Tumor Marker Indication PSA In men with bone metastatic  adenocarcinoma B-HCG & AFP In men with undifferentiated tumor AFP Patients with hepatic tumors CA 125 Women with papillary adenocarcinoma of peritoneal cavity
How often can the Primary be Identified?
Molecular Analysis ,[object Object],[object Object],[object Object],[object Object],[object Object]
 
CUP - Treatment ,[object Object],[object Object],[object Object]
 
 
Favorable prognostic factors
 
Poorly differentiated carcinoma with midline distribution ( Extra-gonadal germ cell syndrome) Favorable subset
 
Women with  papillary  adenocarcinoma of peritoneal cavity (Peritoneal adeno-carcinomatosis/ papillary) Favorable subset
 
.    Women with papillary serous adenocarcinoma of the peritoneal cavity   ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
 
Isolated Axillary Nodal  Adeno-carcinoma in women  Favorable subset
Women with isolated axillary adenopathy ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Women with isolated axillary adenopathy ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Chemotherapy  followed by hormone therapy where indicated
Squamous cell  carcinoma involving cervical lymph nodes Favorable Subset
Squamous cell carcinoma of the cervical lymph nodes ,[object Object],[object Object],[object Object],[object Object]
Squamous cell carcinoma of the cervical lymph nodes ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Squamous cell carcinoma of the cervical lymph nodes ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
 
Squamous cell carcinoma of the cervical lymph nodes ,[object Object],[object Object],[object Object],[object Object],[object Object]
Neuroendocrine Carcinoma of Unknown Primary Favorable Subset
Poorly Differentiated Neuroendocrine Carcinoma ,[object Object],[object Object],[object Object],[object Object],[object Object]
 
Other Favorable Subsets
 
Unfavorable features ,[object Object],[object Object],[object Object],[object Object],[object Object]
Adenocarcinoma of unknown origin (AUP) ,[object Object],[object Object],[object Object],[object Object],[object Object]
AUP with a colon cancer profile  ,[object Object],[object Object],[object Object],[object Object]
Patients with AUP do not fit into any of the clinical subgroups  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
 
[object Object],[object Object],[object Object],[object Object],[object Object]
 
[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object]
Predictors of Response to empiric Chemotherapy - AUP ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Poorly differentiated  neoplasm ,[object Object],[object Object],[object Object],[object Object]
Follow-Up – CUP after Treatment ,[object Object],[object Object]
Conclusion ,[object Object],[object Object],[object Object]
 
 
CASE  1 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object]
Extra slides for use
 
 
ELECRON MICROSCOPY ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
CYTOGENETIC ANALYSIS

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Carcinoma of unknown primary

Notes de l'éditeur

  1. "carcinoma" is tumor tissue derived from putative epithelial cells
  2. "carcinoma" is tumor tissue derived from putative epithelial cells
  3. "carcinoma" is tumor tissue derived from putative epithelial cells
  4. Caveat 1. Especially, in poorly or undifferentiated tumors – staining patterns can be very abnormal… ….some poorly differentiated carcinomas lose all specific markers and are negative for keratin markers as well.
  5. Antibodies to intermediate filament proteins (vimentin, keratin, and desmin) are also useful to distinguish between lymphoma and other neoplasms. LYMPHOMAS can be positive for vimentin but are negative for keratin and desmin. keratin – CHARECTERESTIC FOR for benign and malignant epithelial tissue ( CARCINOMA) respectively . Desmin is charecterestic for muscular tissues ( sarcoma) However, none of these staining patterns are completely specific for antbroad type of cancer….… some sarcomas can stain for keratin and some carcinomas may stain for vimentin. Conversely, some poorly differentiated carcinomas lose all specific markers and are negative for keratin markers also!!!
  6. Caveat 1. Especially, in poorly or undifferentiated tumors – staining patterns can be very abnormal…
  7. Caveat 1. Especially, in poorly or undifferentiated tumors – staining patterns can be very abnormal…
  8. Caveat 1. Especially, in poorly or undifferentiated tumors – staining patterns can be very abnormal…
  9. Caveat 1. Especially, in poorly or undifferentiated tumors – staining patterns can be very abnormal…
  10. Persistent cough/ hemoptyisis, cxr showing mass etc – bronchoscopy Colonoscopy when altered bowel movements, constipation, rectal bleeding, iron deficiency anemia
  11. This slide is for Poorly differentiated CUP with midline distribution Men with poorly differentiated carcinoma of midline distribution : Extragonadal germ cell tumors Patients typically have some of the following characteristics Young age Male gender Predominant tumor location in the mediastinum or retroperitoneum Marked elevation of the serum tumor markers hCG or AFP Presence of 12p chromosomal gain (isochromosome 12p) on molecular genetic analysis Tumor immunohistochemical staining for octamer binding transcription factor 4 (also called POU domain class 5 transcription factor). Responsive to Cisplatin-based chemotherapy (BEP) .
  12. Outcomes are similar to ovarian cancer at equivalent stage. Respond well to chemotherapy regimens that are effective in the treatment of advanced epithelial ovarian cancer. Taxane/platinum regimens have proven superior for advanced ovarian cancer and should be the treatment of choice for these patients. For bulky disease surgical debulking followed by chemotherapy .
  13. MAMMO / MRI if +ve for lump – go with standard treatment. If negative for lump , go with complete ALND + ipsilateral mastectomy or complete ALND/ Whole breast radiation . This followed by chemotherapy. Chemotherapy followed by hormone therapy where indicated. Post-mastectomy radiation is indicated if more than 5 axillary nodes test positive.
  14. Regional lymph nodes (N)NX: Regional lymph nodes cannot be assessed. N0: No regional lymph node involvement. N1: Unilateral metastasis in lymph node(s), ≤ 6 cm in greatest dimension, above the supraclavicular fossa N2: Bilateral metastasis in lymph node(s), ≤ 6 cm in greatest dimension, above the supraclavicular fossa N3: Metastasis in lymph node(s) > 6 cm and/or to supraclavicular fossa N3a: >6 cm N3b: Extension to the supraclavicular fossa
  15. Regional lymph nodes (N)NX: Regional lymph nodes cannot be assessed. N0: No regional lymph node involvement. N1: Unilateral metastasis in lymph node(s), ≤ 6 cm in greatest dimension, above the supraclavicular fossa N2: Bilateral metastasis in lymph node(s), ≤ 6 cm in greatest dimension, above the supraclavicular fossa N3: Metastasis in lymph node(s) > 6 cm and/or to supraclavicular fossa N3a: >6 cm N3b: Extension to the supraclavicular fossa