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Dr Kanishka de Silva
MBBS, MS, FRCS
Consultant Oncological Surgeon
National Cancer Institute, Maharagama
What is CUP ?
Malignant deposits from an unknown primary site
What are possible Presentations ?
- Lymph node enlargement
(Upp. Cx/ Sup scp, Axillary, Mediastinal ,
Paraaortic, Inguinal )
- Lung mets
- Liver mets
- Pleural effusions
- Peritoneal – mets , ascites
- Other – bone, Brain, Skin etc.
MCQ A 60 years old woman presented with an enlarged level IV
neck lymph node. Clinical examination of head and neck was normal. Excision biopsy was reported as adenocarcinoma deposits. Out of the following investigations which one is most relevant in the management of this patient :
a) CT scan of head and neck
b) Immuno histochemistry
c) Fibro - optic naso laryngoscopy
d) tonsiller biopsy
e) Upper gastrointestinal endoscopy
How do you evaluate suspected CUP? Complete History & Examination:
(esp.- oro-pharynx, breast, chest, abdom.
genito urin., PV/PR)
Esp. Review in PH –
- Past Bx, Past CA, Removed lesions,
- Spontaneously regressing lesion
- Previous imaging
Non invasive Investigations
- Blood counts,
- Bio chemistry (LFT/renal/Cal),
- hemoccult test,
- Imaging - relevant region
- Symptom directed endoscopy
Invasive investigations ? Place of FNAC ?
- Quick / freely available - esp as 1st test for L/N
– Deep inaccessible risky sites - guided FNAC safer
- Differentiate
- Benign / Malignant
– Squamous/ Adeno/ Thyroid/ Melanoma
Problems of FNAC ?
- inadequate sample/ blood only/ infection can mask
- Lymphoma / reactive nodes
- Poorly differentiated ca
- Tissue of origin in adeno CA
Histopathology
Tissue Bx techniques ?
- Core Bx - preferable
- Excision Bx - (L/N)
- Incision Bx - large deposits
Value of tissue biopsy ?
- Histology
- IHC
- Gene signature profiling ?
Possible histopathology ? Benign
Malignant Non site specific Epithelial
– Adeno / Squamous / Neuroendocrine
Thyroid CA
Melanomas
Germ cell tumours
Additional workup :- Differences in Ix approaches
Approach for Adeno CA ? Site specific imaging / endoscopy
If possible 1ry found
– non guided Bx / guided BX / endoscopic Bx
IHC of tissue block from deposit
Tumour markers
Approach for Squamous CA ? Site specific imaging / endoscopy
Biopsy :
- If suspicious lesions found - Bx
- Place for blind bX of oropharynx ?
IHC for CUP
To find tissue of origin
Basic pannel 1st ;
Broad spectrum CKs (pancytokeratin)
s100, HMB45
CD45
If epithelial
CK7/CK20 other appropriate IHC markers
To find aggressiveness :
Ki 67
Further management : - based on site & histology
Once possible pathology and site worked out :
Further imaging for staging - Chest Xray/ Us abdomen/ CT / PET CT
Site specific management protocols based on the site / histo - appropriate for the stage
Localized deposits of CUP : If resectable
- Surgery +/- RT for selected sites
If unresectable
- Rx as metastatic disease / Alternative local Mx (RFA etc.)
Place of Chemotherapy ?Decision based on :
- Histo & Performance status
CT …… If primary site found :
Site specific management protocols based on the site / histo - appropriate for the stage
For CUP :Consider Chemotherapy according to histo based on performance status :
- Symptomatic Pts. (PS 1,2)- Asymptomatic Pts. (PS 0) – if aggressive CA
CT regimes :Paclitaxel + Carboplatin – Among different regimes P+C
is interchangeable for adeno & squamous orif poorly differentiated
Neuro endocrine – Mx as carcinoids( poorly diff- Mx as small cell lung ca
Follow up for all occult primaries
Based on clinical needs.
Active / Incurable disease :
Psychological support , Symptom MX. ,
end of life discussions & palliative care etc.
Case Discussion Lateral neck masses
• DD of lateral neck lump ? L/N, Branchial cyst, Carotid body tumour
other soft tissue / bony masses
(cystic hygroma, St mastoid tumour in children)
• Clinical reasons to call lump - lymph node ? site, plane, shape and consistency,
multiplicity,
obvious 1ry reason (for 2ry neck nodes)
• 1ry causes for 2ry nodal enlargement ? Infection
– Regional / Extra regional / Systemic
Malignancy
– Regional / Extra regional / Systemic
2 Cases of Lateral Neck Masses
L/N enlargement – with no obvious 1ry reason
Possible explanations ?
CUP syndrome
Lymphomas (& leukemia)
Occult Infections – eg ?
Lack of authentic information on
possible past 1ry cause
Rare causes
Different Reasons for L/N enlargement
What are the hidden sites in H/N area? Usually pharynx & larynx area
Tongue base
Tonsillar fossae
Nasal caity
Fossae of rossenmuller – Trotter’s syndrome
Pirifom fossae
Vocal cords
Larynx
Looking for 1ry in Cx CUP?
History & Examination ( esp . palpate tongue base & oropharynx) Investigation - US neck & FNAC
FNAC possibilities : Epithelial (squam, adeno,anaplastic), Thyroid, Lymphoma,melanoma
Epithelial CUP :a) Level I, II, III, upper V – above clavicle H/N tumoursb) Level IV , lower V - cup Primary - below the clavicle
GIT, Lungs, Breast, Ovary,Testes, Prostate, Kidny• Bx – IHC of LN
- If CUP (a) - FOL,EUA – Bx from suspisious sites, Tonsilectomy- if CUP (b) - FOL,EUA, UGIE, CT (chest,abd,pelvic) / PETCT
- If adono CA - Women – mammo, (if histo breast MRI /US )- Men - >40 yrs. PSA
Lymph node regions / levels of the neck
Possible 1ry sites for different levels
MCQ A 60 years old woman presented with an enlarged level IV
neck lymph node. Clinical examination of head and neck was normal. Excision biopsy was reported as adenocarcinoma deposits. Out of the following investigations which one is most relevant in the management of this patient :
a) CT scan of head and neck
b) Immuno histochemistry
c) Fibro - optic naso laryngoscopy
d) tonsiller biopsy
e) Upper gastrointestinal endoscopy
Management of Cx CUP
If primary found - treat as site specific guide
Aadeno CUP
a) I-III : CBD ( +/- RT)b) IV,V : CBD – sos
CT - as discussed under general CUP
Squamous / anaplastic CUP
<N2 - CBD (or RT)>N2 - CT/RT & if residual disease surgery
Surgical Treatment of Neck Nodes
Classification of neck dissectionsPreserved
A)Comprehensive Radical I-V -M/R- I I-V SAN
II I-V SAN,IJVIII I-V SAN,IJV,SCMM
B)Selective Lateral II-IV ,, ,, ,,Anterolateral I-IV ,, ,, ,,Supraomohyoid I-III ,, ,, ,,
upper V