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

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1 Carcinoma of Unknown Primary site (CUP) in HEAD & NECK SURGERY SEARCHING FOR THE PRIMARY? 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

2 YES! CUP in general has:.. Dismal prognosis! 7 th 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 CUP in Head & Neck has: 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

3 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

4 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

5 The history 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 m a 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

6 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

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9 The physical examination 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

10 DIFFERENTIAL DIAGNOSIS OF NECK MASSES 15% Inflammatory/Congenital Etiology in Adults (Excluding thyroid) 15% Benign 85% Neoplastic 15% Primary Lymphoma/Salivary 85% Malignant 15% From below the clavicles 85% Metastatic 85% Above the clavicles

11 The neck.all zones 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 m b 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 m a 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 m p h nodes affected

12 Regional lymph node groups draining a specific primary site as first echelon lymph nodes 20/03/2004

13 Imaging 1 st C T a n d / o r M R I w i t h c o n t r a s t 2 nd 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

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15 Initial Dx FNA 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

16 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

17 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

18 EUA Histology report Direct inspection Bimanual palpation Fibre optic endoscopy Esophagoscopy Multiple biopsies No evidence of epithelial dysplasia or of invasive malignancy in any of the sections examined of the 12 biopsies submitted. Tongue base L & R Tonsils L& R Adenoids

19 Newer Diagnostic Aids 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 vs 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 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

20 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

21 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

22 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%

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38 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 20/03/2004

39 YES!!! CUP in general has:..dismal prognosis.. 7 th 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

40 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

41 Markers