Describes about presentation, pathology, clinical evaluation and management of cancer of unknown primary

1. CANCER OF
UNKNOWN
PRIMARY
Dr. Pradeep MS MRCS
MCh Surgical Oncology Postgraduate
Prof. M.P. Viswanathan MS MCh
Prof D. Suresh Kumar MS DNB MCh DNB
Tamil Nadu Govt Multi Superspecialty Hospital,
Chennai.
23 Nov 2018

2. 6-Dec-21 2

3. Overview
 Epidemiology
 Oncopathogenesis
 Pathology
 Workup
 IHC and Molecular profiling
 CUP Subset
 Treatment based on Presentation
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4. Definition
----“Histologically confirmed metastatic tumors whose
primary cannot be identified during standard
pretreatment evaluation”
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5. Epidemiology
 3% to 5% of all tumors
 Male=female; average age at 60 years
 2.8% of occult primary are familial
 Median survival 8 to 12 months
 27% patients, primary not identified even on PM
 Low socioeconomic status and tobacco smoking
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6. OncoPathogenesis
 The tumor can develop without any premalignant lesion or
primary tumor.
 CUP metastases are an early event in the tumor process.
 Chromosomal instability was recently suggested as a
plausible explanation for CUP’s more aggressive
presentations, chemoresistance, as well as their poor
prognosis
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7. Loeffler et al
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8. Natural Course
 Multiple sites of involvement seen in 50%
 Cannot rely on patterns of known metastases to determine
primary site
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9. Pathology
60%
29%
5%
5%
1%
CUP
Adenocarcinoma PDC/PDAC SCC PDMN NEC
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10. Evaluation
 History (past biopsy, malignancies, removed lesions and
any spontaneously regressing lesions)
 Physical examination (breast, abdomen, pelvic and rectal)
 Routine labs with LDH
 Contrast CT Chest, Abdomen and Pelvis
 Breast MRI, Serum AFP, HCG, Serum PSA and Head and
neck CT, Endoscopies – for specific CUP subsets
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11. Imaging
 PET CT not recommended in routine screening
 Tumor detection rate is comparatively higher when
compared to CT and MRI (SS and SP 69% and 77%; 41%
and 48%
 PET/MRI was superior to PET/CT in primary tumor
detection, nodal and distant metastases (Single
comparative study)
Level IA evidence
Tumor detection rate 37%
Pooled SS and SP 84%
11 studies, 433 patients
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12. Workup
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13. Workup
 Core needle biopsy or FNA with cell block specimen
 IHC immunostaining
 Gene Expression Molecular Tumor Profiling – Diagnostic
benefit and no clinical benefit
Tier 1
Determine tissue
lineage
Tier 2
Organ specific
markers
Tier 3
Predictive tumor
biomarkers
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14. IHC
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15. Further IHC
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16. Adenocarcinoma – tumor
site
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17. Downsides
 Technical expertise required to perform test accurately
 Experienced pathologist
 False positive and false negative results can occur
 Classic staining patterns can overlap
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18. Molecular Tumor Profiling
 Cancer cells retain some functional characteristics specific
to their tissue of origin
 Gene assays measure gene expression dynamics in relation
to cell lineage, and not molecular abnormalities
 92 gene RT PCR mRNA assay (Cancer TYPE ID)
 Cancer of Origin test (microarray mRNA assay)
 Predict tissue of origin in about 95% of patients
 Accuracy of 75 to 80%
 Helps in site specific therapy which have a survival benefit
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22. Downsides
 Need for adequate biopsy specimens to derive tumor
tissue mRNA
 Assays are not always 100% accurate
 Tumor types that are not included in MTP assay panel
cannot be diagnosed
 Overlapping gene expression – may lead to misdiagnosis
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23. Additional Studies
 Electron Microscopy – ultrastructural features like
neurosecretory granules, premelanosomes but not for
adenocarcinomas
 Cytogenetic analysis
 Chromosome 12 abnormalities (I 12p, del 12p, multiple
copies of 12p)
 Chromosomal rearrangements t(15;19) in midline
carcinomas and t(2;13) in alveolar RMS, 3p del in SCLC,
11p del in Wilms tumor etc.
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25. CUP Subsets
80% Unfavourable
Male gender
Poor PS
Age > 65 years
Multiple visceral mets
Elevated LDH & ALP
Hypoalbuminemia
Liver metastases
Lymphopenia
Empirical approach
to therapy
20% Favourable
Women with Peritoneal
Carcinomatosis
Women with Axillary lymph node
metastases
Men with Osteoblastic metastases
with Raised PSA Extragonadal GCT
Single site Neoplasm
SCC involving Neck nodes
SCC involving inguinal nodes
Poorly differentiated carcinomas
(midline)
Colorectal cancer profile
Neuroendocrine CUP
Tailored Therapy
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26. CUP
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30. Disseminated or
Unfavourable
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31. New Treatment Paradigm
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32. Future
 Personalized medicine and Precision oncology
 Targeted Therapy
 Next Generation Sequencing
 Biomarkers like overexpressed proteins, activating
mutations, protein loss, gene copy number variations
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33. References
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34. Thank You
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