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