carcinoma of unknown primary site (cup) in head & neck … · mucoepidermoid ca – high...
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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
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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 !
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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 !
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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
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• 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
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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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• 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
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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)
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• 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
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Regional lymph node groups draining a specific primary site as first echelon lymph nodes
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• 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
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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
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• 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
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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
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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.
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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
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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
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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
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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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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
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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
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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
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Markers