SEARCHING FOR THE PRIMARY ?

Carcinoma of Unknown Primary site (CUP) in HEAD & NECK

SURGERY

P r o f J P P r e t o r i u s

H e a d : C l i n i c a l U n i t

C r i t i c a l C a r e

U n i v e r s i t y O f P r e t o r i a &

S t e v e B i k o A c a d e m i c H o s p i t a l

CUP in general has:…..

Dismal prognosis !

CUP in Head & Neck has:

7th most common malignancy No primary site in 3 – 5% of

patients with metastatic cancer

3 – 4 months mean survival <25% alive at 1 year <10% alive at 5 years Make up 15% of metastatic

cervical lymph nodes Usually affect supraclavicular

or lower jugular nodes Are usually adenocarcinoma

SCC is most common – 90%

10% of cases with metastatic SCC has no primary

1 – 3% of new cases of SCC annually present as CUP

AdenoCA in upper neck Thyroid

Salivary glands

Parathyroid

Metastases in upper & mid neck – good prognosis on Rx

YES !

CUP below the clavicles:

CUP in Head & Neck:

Generally incurable due to late presentation

Represents distant metastases

Brief longevity

?Chemotherapy

Mx is directed at cure

Locoregional disease

Treat aggressively to prevent local recurrence

To prevent primary emergence

Imperative to find the primary

YES !

How to find the primary……

….comprehensive evaluation essential….to treat H & N CUP lesions optimally….

Comprehensive history

Extensive physical examination

Appropriate imaging

Full panendoscopy plus biopsies

• E x p o s u r e t o

• etiological factors • to carcinogens • Occupational hazards

• C o u n t r y o f o r i g i n • P r e v i o u s ma l i g n a n c i e s • D e r m a t o l o g i c a l h i s t o r y • A n y H & N s y m p t o m s

pain, trismus, odynophagia, dysphagia, haemoptysis, hoarseness, epistaxis, nasal congestion, aspiration

• P a i n l e s s n e c k m a s s … . w e e k s … . m o n t h s

The history

Case History

43 year old male Smokes 20 pack years, uses alcohol, good general condition HIV non-reactive 9/12 “rapidly” enlarging submental tumour Submental but slightly to the left, firm 15x15 cm mass. 3 Round, umbilicated areas of ulceration with central

necrosis. Mass mobile. Floor of mouth clear. Rest of neck clinically non-significant nodes. CT-scan: ring enhancing mass in multiple cervical lymph

nodes FNA: SCC Biopsy: poorly differentiated, infiltrating,

keratinizing SCC TxN3Mo …… ?CUP

• T h o r o u g h

• T o t a l H & N r e g i o n

• N e w s k i n l e s i o n s o r s c a r s

• C r a n i a l n e r v e s

• A L L a n a t o m i c a l s t r u c t u r e s

• Scalp, skin, ears, nose, nasal vestibules, salivary glands, oral cavity, oropharynx, nasopharynx, hypopharynx, larynx

• S u b m u c o s a l l e s i o n s … . p a l p a t i o n

• E U A

• H i g h - y i e l d a n a t o m i c a l s i t e s

• B i o p s y s a m p l e s

The physical examination

DIFFERENTIAL DIAGNOSIS OF NECK MASSES

15% Inflammatory/Congenital

15% Benign

15% Primary Lymphoma/Salivary

15% From below the clavicles

85% Above the clavicles

85% Metastatic

85% Malignant

85% Neoplastic

Etiology in Adults

(Excluding thyroid)

• S y s t e m a t i c e x a m i n a t i o n

• S i z e a n d n u mb e r

• F i x a t i o n

• V i t a l s t r u c t u r e s

• U n i l a t e r a l … . i p s i l a t e r a l p r i ma r y

• B i l a t e r a l … . m i d l i n e p r i m a r y

• L y m p h a t i c d r a i n a g e p a t t e r n s

• A r e a o f p r i m a r y i n d i c a t e d b y l e v e l o f l y mp h n o d e s a f f e c t e d

The neck….all zones

20/03/2004

Regional lymph node groups draining a specific primary site as first echelon lymph nodes

• 1 s t … C T a n d / o r M R I w i t h c o n t r a s t

• 2 n d … F D G - P E T o r i n t e g r a t e d P E T / C T

• Before panendoscopy

• Guide biopsies

• Avoid false positive FDG avidity after biopsies

Imaging

Initial Dx

1. 1. FNA

2. 2. Tru-cut

Histology report 1. FNA – SCC 2. Tru-cut: poorly differentiated

infiltrating keratinizing squamous cell carcinoma…..

3. After personal communication with pathologist…..consider….

?Salivary gland primary Epidermoid Adenoid cystic Low grade polymorphous adenoCA Plan: fresh tissue fore more

immunohistochemical evaluations eg PAS, PAS-d, SMA

4. Perform panendoscopy

• D i r e c t i n s p e c t i o n a n d p a l p a t i o n

• F l e x i b l e f i b e r o p t i c e n d o s c o p y

• Sinuses, nasal cavity, nasopharynx, base of tongue, hypopharynx, larynx

• Directed biopsies of high-yield sites, suspicious areas, contact bleeding

• B i l a t e r a l t o n s i l l e c t o m y

• E s o p h a g o s c o p y

Panendoscopy

EUA

Procedure: Panendoscopy Adenotonsillectomy Multiple biopsies

Findings: Left base of tongue smooth, non-ulcerating “mass” extending to palatoglossal fold. Left tonsil superficial ulceration Adenoid tissue(minimal) in Nasopharynx Normal Right base of tongue Normal hypopharynx, pyriform fossae, post cricoid area, posterior

pharyngeal wall Bimanual palpation of floor of mouth – no clear submucous pathology Normal larynx and trachea up to the carina Normal oesophagus in its entirety

EUA Direct inspection

Bimanual palpation

Fibre optic endoscopy

Esophagoscopy

Multiple biopsies

Tongue base L & R

Tonsils L& R

Adenoids

Histology report

No evidence of epithelial dysplasia or of invasive malignancy in any of the sections examined of the 12 biopsies submitted.

1 . H P V – h u m a n p a p i l l o m a v i r u s : p o s i t i v e i n > 5 0 % o f o r o f a r y n g e a l S C C t u m o u r s v s n o n - o r o f a r y n g e a l t u m o u r s .

2 . P 1 6 – v a l u a b l e i m m u n o h i s t o c h e m i c a l a n a l y s i s t o i d e n t i f y H P V a s s o c i a t e d t u m o u r s .

3 . E p s t e i n B a r r v i r u s – s e n s i t i v e P C R m a r k e r f o r n a s o p h a r y n g e a l C A .

4 . T i m e - r e s o l v e d l a s e r - i n d u c e d f l u o r e s c e n c e s p e c t r o s c o p y – n o n i n v a s i v e , c a n d i s c r i m i n a t e b e t w e e n m a l i g n a n t a n d n o n -m a l i g n a n t t i s s u e .

5 . I m m u n o h i s t o c h e m i c a l s t a i n i n g f o r k e r a t i n s , l e u k o c y t e c o m m o n a n t i g e n a n d S 1 0 0 e x p r e s s e d i n m e l a n o m a

6 . G e n e e x p r e s s i o n p r o f i l i n g t o i d e n t i f y s i t e o f o r i g i n o f a d e n o C A C U P l e s i o n s

7 . E l e c t r o n m i c r o s c o p y – H & N C U P : d e s m o s o m e s a n d t o n o f i l a m e n t s a r e c h a r a c t e r i s t i c o f S C C

Newer Diagnostic Aids

Final Pathological Information

Personal communication with your pathologist !

After more staining and re-evaluation, found: Intermediate cells

Squamous or epidermoid cells

Mucus-producing cells

Final diagnosis: NOT A CUP LESION Mucoepidermoid CA – high grade…. From sublingual glands ?

Auclair and Brandwein classification assessing for:

Nerve and blood vessel infiltration

Cellular atypia

>4 mitoses / 10x magnification

Mucous cyst content

Bone infiltration

Necrosis

Treatment Options for H&N SCC CUP

1. N1 and N2a disease

2. Stage 2b or higher

3. Primary emergence from high yield sites

1. a)Single modality RTx with IMRT technique to spare the mucosa

b)Formal neck dissection in selected cases

2. a)Concurrent CTX-RTx with IMRT technique b)Surgery reserved for persistent / recurrent disease after RTx c)Formal Neck dissection and post op RTx with or without CTx is a second option

3. Radiation with/without CTx to minimize primary recurrence

Conclusion – YES, search for the primary and treat aggressively.

Locoregional control in H&N SCC CUP lesions:

Two components:

Controlling neck disease

Preventing primary recurrence

Prognosis determined by clinical stage at Dx

Combination therapy best to contain neck recurrence + emergence of primary tumours

SCC CUP overall survival comparable to that of patients with known primary

5 Year survival as high as 30-50%

20/03/2004

20/03/2004

20/03/2004

CUP / CARCINOMA OF UNKNOWN PRIMARY ORIGIN

Plan of Examination - patient presenting with a neck mass

Skin – scalp, face, ears, neck Nose – inside Oral cavity - ?EUA Salivary glands and Thyroid Arms, chest wall, breasts Abdomen and genitalia Transilluminate sinuses Panendoscopy - nasopharynx, larynx, oesophagus - biopsy primary / blind Lymph nodes - FNA or needle biopsy - Do not excise lymphnode primarily TB Lymphoma

YES !!!

CUP in general has:…..Dismal prognosis…..

7th most common malignancy

No primary site in 3 – 5% of patients with metastatic cancer

3 – 4 months mean survival

<25% alive at 1 year

<10% alive at 5 years

Make up 15% of metastatic cervical lymph nodes

Usually affect supraclavicular or lower jugular nodes

Are usually adenocarcinoma

YES !!!

CUP in Head & Neck has:

10% of cases with metastatic SCC has no primary

1 – 3% of new cases of SCC annually present as CUP

Squamous cell cancer is the most likely histological finding (90%) in patients with:

Cervical metastatic lymphadenopathy

Adenocarcinoma

Melanoma or even

Anaplastic tumours may also be found

Markers