&n= bsp; &nb= sp; =20 EVALUATION = AND MANAGEMENT OF =

&n= bsp; &nb= sp; =20 UNKNOWN-PRIMARY OF =20 THE NECK = . &n= bsp; &nb= sp; &nbs= p; = ; = &= nbsp; &n= bsp; =20

&n= bsp; &nb= sp; =20 BY

&n= bsp; =20

&n= bsp; =20 Dr.SUNIL KAPUR =20

&n= bsp; =20 MBBS, MS, DNB

&n= bsp; =20 HOD.DEPTT. OF ENT AND HEAD & NECK SURGERY

&n= bsp; =20 NORTHERN RAILWAY CENTRAL HOSPITAL

&n= bsp; =20 BASANT LANE

&n= bsp; =20 NEW DELHI -110001 &n= bsp; &nb= sp; &nbs= p; = ; = &= nbsp; &n= bsp; &nb= sp; =20

&n= bsp; =20

HISTORY

In 1940=92s and 1950=92s the literature was richly = endowed with articles on branchiogenic = carcinoma,Hayes Martin put forwaded four postulates to label a lateral = neck=20 swelling as branchiogenic carcinoma namely-

-This swelling is lying on line along the anterior = margin of=20 sternocleidomastoid.

-Carcinoma must be arising in the wall of an = epidermal=20 cyst.

-Histopathology should be consistent with = bronchiogenic=20 vestigial tissue.

-No mucosal primary malignancy from upper = aerodigestive tract=20 should appear in subsequent 5 yrs.

These postulates made it nearly impossible to = diagnose=20 branchiogenic carcinoma ever again(Maran 1950).Since then only fifteen = cases of=20 branchiogenic carcinoma has been documented in the literature(Black and = Maran=20 1978).In 1960=92s and 70=92s branchiogenic carcinoma articles were = replaced by=20 articles on metastatic cervical cancer from occult primaries.

UNKNOWN NECK MASS=20 WORKUP PROTOCOL

Any neck mass in an adult must be considered as a = metastatic=20 lesion until proved otherwise (Mayo & Lee 1950,Lee & Helmes = 1970, Coker=20 PP et al 1977,).In 1952,Martin and Romieu stated that any assymetrical=20 enlargememt lymphnode/nodes in an adult is cancerous and is secondary = from=20 primary mucosal lesion of aerodigestive tract in head and neck = region.Primary=20 cervical malignancy is rare and almost all malignant cervical tumours of = lateral=20 neck are metastatic.

Immediate excision of enlarged lymph node for = diagnostic=20 purpose is a disservice to the patient.

Distant metastasis and local reccurences are more = frequent in=20 patients who had pretreatment biopsies due to disruption of lymphatic=20 drainage.They also have higher incidence of local wound complications = delaying=20 starting of radiotherapy.

INCIDENCE=20

-Despite detailed clinical and radiological = examination,the=20 primary site remains unidentified in upto 5% of patients who are having=20 metastatic secondaries in neck lymph node.

-The most common histological finding is a squamous = cell=20 carcinoma more than 80%. -- --40% of supraclavicular adenopathy reveals=20 adenocarcinoma.

SITE

The most common single lymph node involvement is of = jugulodigastric region with equal frequency from=20 nasopharynx,oropharynx,laryngopharynx and oral cavity.

Posterior triangle involvement is most likely from=20 nasopharyngeal carcinoma.

A single supraclavicular node is more likely to be = associated=20 with a infraclavicular primary carcinoma rather than a head and neck = primary=20 site,mostly from lung carcinoma.

Comess et al (1967) define what is unknown

-One or more cervical mass proved to be = cancerous.

-No H/o prior malignancy or surgical ablation of = histology=20 are indeterminate lesion.

-No H/o symptoms related to a specific organ.

-No clinical/lab evidence of a prmimary tumour.

DIAGNOSTIC=20 EVALUATION

HISTORY

-Often the history doesn=92t help very much in = arriving at a=20 diagnosis.

-Rule of seven states that any neck swelling of = seven days=20 duration is inflammatory or seven years duration is congenital and of = seven=20 weeks to seven months are usually neoplastic.

-Presence of certain symptoms may point toward the = primary=20 like something sticking in throat(oropharynx)sore in=20 mouth(oral)hoarseness(larynx)dysphagia(oesophagus or laryngopharynx) = dysphagia=20 plus referred pain to ear(supraglottic)pulmonary or gastric symptoms = like=20 cough,haemoptysis,indigestion,fluctuating swelling may point towards=20 laryngocoele.Blocked ear may point towards examination of nasopharynx = .

-Cantonese patient with a cervical lymph node have=20 nasopharyngeal carcinoma until proved otherwise.

EXAMINATION=20

-A confirmation that neck swelling is a lymph node = requires=20 differentiation from

1)Submandibular salivary gland as it is bimanually palpable = whereas a=20 lymph node is not

2)Greater horn of hyoid bone (bony hard continous = with body=20 of hyoid)

3)Transverse process of second vertebrae(bony and = deep)

4)Carotid body tumour(located at bifurcation of = carotid=20 artery opposite greater horn of hyoid)mobile from side to side but not=20 vertically,compressible and slow refilling.

5)Tortuous carotid artery with atheroma(bruit)

6)Laryngocoele and pharyngeal pouch (moves with = swallowing=20 and compressible)

7)Direct extralaryngeal extension of growth through = thyrohyoid and cricothyroid membrane(location and movement with = swallowing)

Other lymphatic sites like = axilla,groin,liver,spleen and=20 stomach is palpated specially if lymph nodes are rubbery(?lymphoma).In = men=20 testicular examination is mandatory,In a female breast examination may = be=20 rewarding.

-50-70% of the patients diagnosed by nodal = examination have=20 had their primary tumour site identified by initial head and neck=20 examination.

-In patient with a neck mass in whom prior routine = physical=20 examination is negative,an independent second careful survey of upper=20 aerodigestive tract is most cost effective tool and reveals primary = lesion in=20 30% of cases.Attention should be directed to oral cavity,oropharynx=20 palpation,Nasopharynx,Laryngopharynx,Larynx,Thyroid,Salivary glands and = Skin of=20 head and neck.

If the results of second examination are negative = FNAC is=20 performed,the result may be positive,negative or equivocal.It is the = first=20 investigation to be ordered after a thorough head and neck examination = as it is=20 easy,cost effective and gives instant report .Identification of EB virus = by PCR=20 in the FNAC specimen indicates nasopharyngeal carcinoma.Though open = biopsy is=20 preferred for diagnosis of lymphoma.FNAC can easily differentitae a = lymphoma=20 from a carcinoma.This distinction avoid the need for endoscopic = examination=20 guided biopsy and general anaesthesia.

In high risks patients who are chronic users of = tobacco and=20 alcohol with inconclusive FNAC report endoscopies and open biopsy for=20 confirmation is still required as the index of suspicion is high.

RADIOLOGY

X ray chest and appropriate scans should preceed = the=20 endoscopic examination.X-ray chest may show involvement of mediastinal = lymph=20 nodes,primary in lung,secondaries,general health (pulmonary koch=92s),It = may be of=20 value for pre-anaesthetic check-up.

Scans before endoscopic examination gives exact = extend of the=20 primary tumor unaltered by surgical edema.CECT scans of head and neck = may reveal=20 a primary but T2-weighted.

MRI is pereferred because of better delineation of = submucosal=20 lesion.Moreover use of iodine contrast media in CT scanning may negate = the use=20 of postoperative RAI(radio-active iodine) in case of need uto 6 = months.

PET- Scanning may detect unknown primary site even = beyond the=20 head and neck region and distant metastasis also.PET scanning is not = routinely=20 advocated as it is expensive,high false positive rate due to salivary = activity=20 and poor resolution.

ENDOSCOPY AND=20 GUIDED BIOSPISES

After scans Panendoscopy is recommended under = general=20 ansesthesia.

Panendoscopy includes laryngoscopy examining larynx = and =20 laryngopharynx,oesophagoscopy,bronchoscopy,nasopharyngoscopy = (through=20 nasal endoscope) and palpation of base of tongue and tonsils.

Any obvious lesion should be biopsied,when no = lesion is seen=20 on palpated guided(not blind)biopsies of the most logical sites for = silent=20 primary tumour as directed by lymphatic drainage pattern is done.These = areas are=20 right and left fossa of Rossenmullar,the ipsilateral tonsil(in which = case=20 tonsillectomy replaces incisional biopsy as no further surgery is = required for=20 T1 & T2 lesions of tonsil),the base of tongue and pyriform = sinuses.The=20 rationale for guided biopsy is that submucous tumour may arises deep in = crypts=20 of tonsil,fold of lingual lymphoid tissue or submucosa of = nasopharynx.Endoscpy=20 can reveal primary tumor in around 16% of cases(JonesAS 1993).Order of = frequency=20 are in nasopharynx,tonsil,retromolar trigone,tongue base and pyriform=20 sinuses.

PROBABLE = SITE OF=20 PRIMARY TUMOUR ACCORDING TO THE LOCATION OF THE CERVICAL=20 METASTASIS.

LOCATION OF SITES &n= bsp; &nb= sp; &nbs= p; =20 PRIMARY TUMOUR SITES

SUBMENTAL &n= bsp; &nb= sp; &nbs= p; = ; =20 Lower lip,floor of mouth ,tip of tongue,

&n= bsp; =20 &n= bsp; &nb= sp; &nbs= p; = ; Lower= =20 central gum.

SUBMANDIBULAR &n= bsp; &nb= sp; &nbs= p; =20 Face,nose,paranasal sinuses,oral cavity

&n= bsp; &nb= sp; &nbs= p; = ; = &= nbsp; =20 Submandibular gland.

JUGULODIAGASTRIC &n= bsp; &nb= sp; &nbs= p; =20 Oral cavity,oropharynx,nasopharynx,

&n= bsp; &nb= sp; &nbs= p; = ; = &= nbsp; =20 Hypopharynx,supraglottic larynx.

MID JUGULAR &n= bsp; =20 &n= bsp; &nb= sp; Thyroid,larynx,hypoph= arynx,cervical=20

&n= bsp; &nb= sp; &nbs= p; = ; = &= nbsp; =20 Oesophagous.

LOWER JUGULAR &n= bsp; &nb= sp; &nbs= p; =20 Thyroid,Subglottis,nasopharynx.

SUPRACLAVICULAR &n= bsp; &nb= sp; &nbs= p; =20 Lung (40%),throid(20%),gastrointes-

&n= bsp; &nb= sp; &nbs= p; = ; = &= nbsp; =20 tinal(12%) and genitourinary(8%).

POSTERIOR TRIANGLE &n= bsp; &nb= sp; =20 Nasopharynx,skin=20 of scalp,thyroid.

Open=20 biopsy

-If no primary lesion is found and result of FNAC = are=20 equivocal(5% of cases) ,open biopsy with frozen section diagnosis is = done=20 next.Consent for radical neck dissection is obtained and biopsy is = performed=20 through an incision along a line extendable for a radical neck = dissection=20 .The surgeon should be = prepared and=20 skilled of doing RND where frozen section dictates so.If frozen section = shows=20 squamous cell carcinoma,melanoma or upper neck adenocarcinoma above the = level of=20 cricoid carilage,comprehensive neck dissection preferrably RND is = done,If=20 lymphoma is found neck is closed and the patient is sent for for staging = and=20 subsequent CT,RT or combination treatment.If adenocarcinoma is found in=20 supraclavicular region,the neck is closed as prognosis is not affected = by=20 treatment to neck,a search for infraclavicular primary must be done.

MANAGEMENT AFTER=20 COMPREHENSIVE NEXT DISSECTION

SURGERY=20 ALONE-Patients with N1 single lymph node with no extracapsular = spread may=20 not require any post operative radiotherapy if patient can be followed = up for=20 prolonged period.Routine post operative radiotherapy has many = disadvantages=20 namely-prolonged treatment and cost,prolonged morbidity in the form of=20 xerostomia,dysphagia and dental caries,induction of new caecinoma.It = precludes=20 the use of radiation therapy to late appearing primaries as radiotherapy = is used=20 once only.

COMBINED=20 MODALITIES-The patients with N 2 and N3 disease or N1 disease with = unfavourable=20 histopahology of the neck dissection specimen like,multiple = nodes,extracapsular=20 extension,perineural ,perivascular alongwith, require post operative=20 radiotherapy.

Debate still continues regarding optimal = radiotherapy=20 field,in these pateients with respect to inclusion of potential head and = neck=20 primary tumor sites and contralateral neck.

Most radiotherapist include = nasopharynx,oropharynx,oropharynx=20 and hypopharynx and larynx with contralateral neck because there is 40% chances of = appearing of=20 primary in those area when post operative radiotherapy is not given and = 15% rate=20 of contralateral neck recurrences when it is not included compared with = no such=20 recurrences in irradiated patients.

Proponent of =20 surgey alone argue that this avoids the prolonged radiotherapy = and side=20 effects of the radiotherapy but may be associated with higher rate of = late=20 primary cancer and contralteral node disease.In practice combined = therapy is=20 often recommended

Palpable lymphadenitis is usually associated = withmultiple=20 occult secondaries,hence comprehensive neck dissection followed by = radiotherapy=20 is required.

RADIOTHERAPY=20 ALONE

1)posterior triangle lymph nodes with = lymphepithelioma anaplastic and poor = differentiated=20 carcinoma are treated = like=20 nasopharyngeal carcinoma with thyroid shield.

2)upper/midjugular lymphnode with=20 lymphoepithelioma,anaplastic and poorly diff. carcinoma are treated like = nasopharyngeal carcinoma without thyroid shield.

3)Multiple bilateral lymphadenopathy is treated = like=20 nasopharyngeal carcinoma.

4)Supraclavicular lymphadenitis =96palliative = radiotherapy.

5)Rarely very small N1 lymph node<2cm in upper = or=20 mid-jugular region can be managed with RT alone.

Proponent of radiotherapy alone argue that = inclusion in the=20 volume treated of the most likely primary mucosal cancer sites and = remainder of=20 cervical lymph nodes fields reduces,risk of later emergence of the = primary=20 cancer or of low and contralateral cervical lymph node metastasis.

CHEMOTHERAPY

In N3 disease local management results are very=20 poor.Chemotherapy in the form of cisplatin and FU before local definite=20 treatment leads to longer survival time than those who did not received=20 chemotherapy.

FOLLOW UP-Patient is to be followed up for = atleast 5=20 years.During this primary site may be revealed upto 30% of cases,and if=20 appropriate can be further treated.Most of the primaries appear in the=20 hypopharynx.The prognosis in patients in whom primary lesion never = appear is=20 better than in those in whom it manifests.The primary usually manifests = within=20 one and a half year of the secondaries.Those presenting after third year = are=20 usually regarded as metachronous second primary.

PROGNOSIS

Prognosis worsens with advanced N categories,when = there are=20 multiple nodes,when nodes are large than 3 cm or when there is evidence = of=20 extracapsular extension.They should have post operative = radiotherapy.

Prognosis is poor in patient with metastatic = adenocarcinoma=20 wherever the node is located(Barrie et al 1970,lae NK19991)

Prognosis is grave =20 3% to 20% at 3 years,when the node is in supraclavicular=20 region(Jesse,1973)

Prognosis of patient is better in whom primary site = is never=20 found(58 % of 3 year survival) than in patient in whom it is found = later(31% of=20 3 year survival)

Relapse is more common in neck than later emergence = of a=20 mucosal primary cancer.

NUGGETS = REGARDING=20 UNKNOWN PRIMARY

1)Patient is usually an elderly male(4:1)

2)The peak age is 50-70 years.

3)The commonest node affected is = jugulodiagastric.

4)Squamous cell carcinoma is the most common=20 histopathology.

5)40% of supraclavicular lymph node has = adenocarcinoma.

6)Prognosis of metachronous lymph node involvement = is better=20 than synchronous primary and regional lymph nodes.

7)Prognosis of supraclavicular secondary with = unknown primary=20 is poor.

8)Supraclavicular lymph nodes secondaries are from=20 infraclavicular primaries from lung,entire digestive=20 tract,breast,testis,ovary,urinary system.

9)These usually becomes apparent within first = year.

10)Lung being the most common infraclavicular = primary.

11)Prognosis with no primary appearing late is = better than=20 those in which primary do appear.

12)Prognosis with the involvement of lymph node = limited to=20 upper half is better than with lower nodes metastasis.

13)Prognosis is better with single lymph node=20 involvement.

14)Prognosis with diagnosis of adenocarcinoma is = poorer.

15)No such histologicalimportance is revealed for = lower=20 neck.

16)The site of adenopathy may provide clue to the = location of=20 primary.

17)Immediate open biopsy is disservice to the = patient by way=20 of local and distant spread and delay in starting radiotherapy.Data = presented by=20 Razack,Sako and Marchetta1977 indicated no adverse effect.

18)Discovery of primary decreases with time.Most of = the=20 primaries appear in first 2 years.

19)The seccondary neck with unknown primary is not = a=20 formidable disease as proper treatment can lead to cure(5 year disease = free=20 survival in around 50% of cases.