Biopsy proven cancer of the neck, which even after a complete clinical & radiological workup (that includes physical examination, CT scan, esophgeoscopy, laryngoscopy, bronchoscopy & multiple survillence biopsies) reveals or yields no primary demonstrable lesion.
2. Introduction
• Biopsy proven cancer of the neck, which even after a
complete clinical & radiological workup (that includes
physical examination, CT scan, esophgeoscopy,
laryngoscopy, bronchoscopy & multiple survillence
biopsies) reveals or yields no primary demonstrable
lesion.
3. Epidemology
Exact incidence is unknown.
Head-and-neck carcinoma of unknown primary
(HNCUP) is the final diagnosis in 3–7% of patients
with head-and-neck cancer initially presenting with
metastatic squamous cell carcinoma (SCC) to the
cervical lymph nodes
4. risk of lymph node metastases depends
upon:-
1) Density of capillary lymphatics
2) Location of the primary tumor
3) Histologic differentiation,
4) Size of the lesion
5) Recurrent v/s untreated lesions
5. Density of capillary lymphatics
Profuse capillary lymphatic network present in
Nasopharynx & Pyriform sinus
Paranasal sinuses, middle ear and true vocal
cords have sparse capillary lymphatics
6. Risk Groups based on location of primary tumor
Group
Estimated Risk of
Subclinical Neck
Disease % Stage Site
Low risk <20 T1 FOM, RMT, gingiva, hard palate,
buccal mucosa
Intermediate
risk
20-30 T1 Oral tongue, soft palate,
pharyngeal wall, supraglottic
larynx, tonsil
T2 FOM, oral tongue, RMT, gingiva,
hard palate, BM
High risk >30 T1-4 Nasopharynx, Pyriform sinus,
BOT
T2-4 Soft palate, pharyngeal wall,
supraglottic larynx, tonsil
T3-4 FOM, oral tongue, RMT, gingiva,
hard palate, BM
7. Histological differentiation
The majority of patients have either
squamous cell or poorly differentiated carcinoma.
Adenocarcinoma
High chances of primary lesion below the clavicles
If nodes are located in the upper neck
Salivary gland
Thyroid
Parathyroid primary tumor.
8. Diagnostic workup
History
Physical examination
Careful examination of the neck and supraclavicular
regions with attention to skin
Examination of oral cavity, pharynx, and larynx
Mirror & fiberoptic examination to visualise
nasopharynx, oropharynx, hypopharynx, larynx
11. Radiological Studies
Chest imaging
CT with contrast or MRI with Gd (skull base through thoracic inlet)
PET CT scan (If other tests do not reveal a primary)
Laboratory studies
Complete blood cell count
Blood chemistry profile
HPV testing (Suggestive of occult primary in BOT or Tonsil, helps in
customize radiation targets)
EBV testing
12. Evidence on role of PET CT
In a meta-analysis of 16 studies looking at the role of
PET in 302 patients with cervical node metastases where
a primary has yet to be discovered through the work up,
25% of primaries are identified through PET. Previously
unrecognized regional or distant metastases were
identified in 27% of patients
Rusthoven, KE, Koshy, M, Paulino, AC, The role of fluorodeoxyglucose PET in
cervical lymph node metastases from an unknown primary tumor. Cancer 2004;
101:2461
13. FNACFNAC
SCC
H & N exam ,radiological studies
Primary
found Primary not
found
14. Examination under anasthesia
Direct laryngoscopy
Level I,II,III &
upper V
Nasopharyngeal survey
1)Directed biopsies of
areas of clinical concern
2) Tonsillectomy
Level IV &
lower V
Esophageoscopy
Chest/Abdominal or
Pelvic CT or PET CT
Biopsy to be taken from
(Nasopharynx, tonsils, BOT, Pyriform sinuses & any suspicious mucosal areas)
In a study of 87 patients with unknown primaries, 26% were
discovered to have a tonsillar primary after tonsillectomy
Lapeyre, M, Malissard, L, Peiffert, D et al. Cervical lymph node metastasis from an
unknown primary: Is a tonsillectomy necessary? Int J Radiat Oncol Biol Phys; 39: 291
15. Least investigated of all head-and-neck cancers
Few prospective studies or clinical trials reported
No definitive evidence proving the superiority of one
approach over others.
Management of
HNCUP
16.
17.
18.
19.
20.
21.
22.
23.
24. RT treatment: Unilateral neck or Comprehensive
(Nieder C et al: (2001) Cervical lymph node metastases from
occult squamous cell carcinoma: cut down a tree to get an apple?
Int J Radiat Oncol Biol Phys 50:727-733
25. Considerations for the node positive or postoperative
neck
Situation Proposed action
Level I node positive Consider inclusion of oral cavity if
comprehensive RT offered
Level II node positive Include retrostyloid space cranially
Level IV or Vb node positive Include supraclavicular fossa caudally
Postoperative setting Include entire surgical bed
Extra-capsular spread Include adjacent muscles
26. Neck dissections
Radical
Gold standard operation
Modified radical
Preservation of non lymphatic structures
Selective
Preservation of lymph node groups
Extended
Removal of additional lymph node groups or non
lymphatic structures
27. Standard radical neck
dissection
Involves removal of :-
Lymph nodes in levels I to V
sternocleidomastoid muscle,
Omohyoid muscle,
Internal and external jugular
veins,
Spinal accessory nerve,
Submandibular gland.
Tail of parotid
29. Modified Radical Neck Dissection
Removes
Nodal groups I-V
Preserves one or more of
the nonlymphatic
structures
XI (I)
IJV(II)
SCM(III)
30. Selective Neck Dissection
Remove high risk lymph node groups based on
tumor site.
Supraomohyoid
Levels I-III
Lateral
Levels II-IV
Posterolateral
Levels II-V
small oral cavity cancers and a
clinically negative neck.
laryngeal, oropharyngeal, and
hypopharyngeal
31. Post surgery management depends upon:-
1)Stage
N1/N2-N3
2) Level of LN
I/II-III-upper V/IV/lower level V
3)Presence of extracapsular extension
If present chemotherapy to be added
32. Removal of
Additional lymph node groups
Nonlymphatic structures
Extended radical neck dissection
33.
34. PART I: THE BASICS
Introduction
IHC methods
Procedure
35. IHC involves localization of antigen in tissues and
cells and is based on the principle of antigen-
antibody reaction which is detected by a tagged
visible label
Antibodies raised specifically against the substance
of interest, and they are detected by
immunochemical methods
Once antigen antibody reaction has occurred, an
enzyme capable of reacting with chromogen is
brought into close proximity of the antigen.
36.
37. Albert Coons used fluorescence technique in 1945
1966 Nakane and Pierce developed enzyme labeling
method
1977 Taylor - IHC on paraffin sections.
38. Uses
Diagnose and classify undifferentiated tumors.
Differentiate benign from malignant lesions
Detection of small group of cancer cells
Prognostic information on cancers
Infections in the sections can also be detected
51. The procedure…
Formalin-fixed, paraffin-embeded blocks
Sections are picked on slides coated with
3-aminopropyltriethoxysilane
Deparaffinise in xylene and alcohol
Wash in tris buffer, peroxidase block 30 minutes
Wash, Microwave(antigen retrieval)
Wash, Power block 30 minutes
52.
53. Primary antibody for 45-60 minutes
Wash, super enhancer 30 minutes
Wash, S S label (secondary antibody with poly HRP)
Wash, DAB (diaminobenzidine) for 5 minutes
Wash, haematoxylin 20 seconds
Wash, mount (DPX)
54. Precautions
Do not allow the slides to dry, incubate in moist
chamber
Handle the reagents carefully
Do not stop the procedure midway
Cover whole sections
55. Quality control
Consistency of performance and reproducibility
Reagent control
Tissue controls
Positive control
Negative control
Internal or “built in” control