CERVICAL LYMPHADENOPATHY OF UNKNOWN PRIMARY (C L U P)

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CERVICAL LYMPHADENOPATHY OF UNKNOWN PRIMARY (C L
U P)

• Dr. MOHAMMED ZAKARIA
• CLINICAL ONCOLOGIST
• MD, DMRT (LONDON)
• JORDANIAN BOARD
• MEMBER OF THE ROYAL COLLEGE OF RADIOLOGISTS
  (LONDON)

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CERVICAL LYMPHADENOPATHY OF UNKNOWN PRIMARY (C L
U P)

• Lymphadenopathy enlargement of a single or a
  group of regional lymph nodes of various etiology
• Lymphatic spread is characteristic of EPITHELIAL
  TUMOURS, its frequency is proportional to the
  histological grading.

M. ZAKARIA PRSENTATIONS
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THE LYMPHOID SYSTEM Comprises

• Lymph capillaries (minute vessels) which commence
  blindly in tissue space and empty their lymph
  into certain veins.
• The lymph nodes are small solid masses of
  lymphoid tissue into which the lymph vessel pour
  the lymph.
• They are small, oval, or bean shaped bodies
  situated in the course of lymph vessels so that
  the lymph passes on its way to the blood through
  the L.N
• 3 Main parts A - HILUS, B CORTEX,
• C - MEDULLA

M. ZAKARIA PRSENTATIONS
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THE LYMPHOID SYSTEM

• (NATURAL DRAINING MECHANISM)
• Provides the most common way for spread of
  carcinomas.
• The extent of L.N involvement is of great
  prognostic significance following surgical
  removal of tumour
• The process of TUMOUR SPREAD via lymphatic
  channels may be RETROGRADE or ORTHOGRADE

M. ZAKARIA PRSENTATIONS
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• Involvement of lymph nodes causes obstructive
  lymphadenopathy with alternative collateral
  pathways
• Fixed nodes are associated with an advanced
  primary lesion.
• Fixed nodes on one side of the neck have BETTER
  PROGNOSIS than mobile bilateral neck nodes
• 
  
  DOBBIEHENK1985

M. ZAKARIA PRSENTATIONS
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The process of tumour spread to L.N

• Stretching of the walls of lymphatic vessels
  creates gaps between the lining endothelial cells
  which leads to negative pressure in the lumen.
• while the interstitial pressure is positive

M. ZAKARIA PRSENTATIONS
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LYMPHATIC SPREAD

• The natural history of lymphatic metastasis is of
  progressive proximal spread with involvement of
  successive groups of regional lymph nodes.
• DOBBIE HENK 1985
  
  
  
  

M. ZAKARIA PRSENTATIONS
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Nodal Regions of the Neck

• CERVICAL
• JUGULAR
• PREAURICULAR
• SUBDIGASTRIC
• JUGULODIGASTIC
• SUPRA CLAVICULAR

M. ZAKARIA PRSENTATIONS
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(No Transcript)
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CAUSES OF L. Ns ENLARGEMENT IN THE NECK

• INFLAMMATORY AND REACTIVE
• A-None SPECIFIC REACTIVE HYPERPLASIA
• B-SPECIFIC DUE TO INFLAMMATION
• -MALIGNANT CAUSES

M. ZAKARIA PRSENTATIONS
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NONE MALIGNANT CAUSES OF L.N ENLARGEMENT IN THE
NECK ..1

• None SPECIFIC REACTIVE HYPERPLASIA
• A- Acute infection tonsillitis
• B-Chronic infection fibrosis of the node
• C-Reactive hyperplasia which can also be
  recognized in L.N draining malignant tumours
  (sinus histocytosis)
• D-collagen disease
• E-Drugs (antiepileptic)
• A D THOMSON R E COTTON

M. ZAKARIA PRSENTATIONS
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NONE MALIGNANT CAUSES OF L.N ENLARGEMENT IN THE
NECK ..2

• INFLAMMATORY REACTIVE.1
• SPECIFIC DUE TO INFLAMMATIONS
• A-Bacterial T B, BRUCELLOSIS
• B-Viral infectious mononucleosis ,measles
• C-clamidial cat scratch disease.
• D-fungal Histoplasmosis, Plastomycosis
• A.D THOMSON COTTON

M. ZAKARIA PRSENTATIONS
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NONE MALIGNANT CAUSES OF L.N ENLARGEMENT IN THE
NECK ..3

• INFLAMMATORY REACTIVE.2
• PARASITIC TOXOPLASMOSIS, FILARIASIS,
• TRYPANOSOMIASIS, LEISHMANIASIS.
• OTHER SARCOIDOSIS, DERMATOPATHIC
  LYMPHADENOPATHY.
• A D THOMSON, R E COTTON

M. ZAKARIA PRSENTATIONS
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MALIGNANT CAUSES OF L.N ENLARGEMENT.1

• LEUKEMIA'S (CLL)
• LYMPHOMAS
• A- HODGKINS DISEASE
• B-NON HODGKINS LYMPHOMAS
• C-BURKITT'S LYMPHOMA
• OTHER N H L
• 1- SEZARY SYNDROME
• ERYTHRODERMA GENERALISED L. N ENLARGEMENT (T
  CELL)
• 2-IMMUNOBLASTIC SARCOMA (RAPIDLY Fatal)
• 3-MALIGNANT HISTIOCYTOSIS (RAPIDLY FATAL)

She did not let me have photograph of her normal
looking neck post RT
M. ZAKARIA PRSENTATIONS
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SECONDARY TUMOURS METASTASIZING TO NECK NODES

• THE MOST COMMON HISTOLOGIC DIAGNOSES OF THE
  INVOLVED NODES WERE
• Squamous cell carcinomas 62
• Undifferentiated ca 28
• Glandular of salivary gland origin 10
• Halnan ,Fletcher, Moss text books

M. ZAKARIA PRSENTATIONS
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METASTATIC NECK NODES..1

• COMMON PRIMARY SITES
• 1 -NASOPHARYNX
• 2 -OROPHARYNX
• 3-VALLECULA
• 4-BASE OF TONGUE ORAL TONGUE
• 5-TONSIL FAUCIAL ARCH
• 6-ORAL CAVITY,
• 7-FLOOR OF THE MOUTH
• 8-SOFT PALATE

M. ZAKARIA PRSENTATIONS
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METASTATIC NECK NODES..2

• LARYNX
• ARYEPIGLOTTIC FOLD
• EPIGLOTTIS
• HYPOPHARYNX
• PYRIFORM FOSSA.
• LIP
• ORBIT
• CHEEK
• SKIN OF THE FACE

M. ZAKARIA PRSENTATIONS
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METASTATIC NECK NODES

• MAXILLARY ANTRUM
• SALIVARY GL .(PAROTID)
• CERVICAL ESOPHAGUS
• THYROID
• LUNG
• PEDIATRIC SOFT TISSUE SARCOMAS OF HN

M. ZAKARIA PRSENTATIONS
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CLINICALLY VE L.N ON ADMISSION TO M .D. ANDERSON
HOSPITAL
643 patients
NASOPHARYNX
TONSIL
BASE OF TONGUE
HYPOPHARYNX
OROPHARYNX
OROPHARYNX
SUPRA GLOTTIC LARYNX
SOFT PALATE
RETROMOLAR TRIANGLE
ORAL TONGUE
FLOOR OF MOUTH
M. ZAKARIA PRSENTATIONS
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L.N. GROUPS INVOLVED ON ADMISSION TO M. D
.ANDERSON HOSPITAL
M. ZAKARIA PRSENTATIONS
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Other Epithelial tumours of GLANDULAR STRUCTURE
WHICH CAUSE NECK NODE ENLARGEMENT

• TUMOURS OF SALIVARY GLANDS
• THYROID
• CERVICAL OESOPHAGUS SUPR .CLAV
• STOMACH SUPRA CLAV .L.N
• PROSTATE CERVICAL L.N

M. ZAKARIA PRSENTATIONS
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CONTRALATERAL L.N. INVOLVEMENT OF SELECTED HEAD
NECK SQUAMOUS .C. CA
M. ZAKARIA PRSENTATIONS
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METASTATIC ADENOCARCINOMA TO CERVICAL L.N FROM
OCCULT PRIMARY SITE

• RETROSPECTIVE ANALYSIS AT THE MIDDLESEX HOSPITAL
  (LONDON) 1987
• THE COMMONEST SINGLE SITE WAS THE
• JUGULODIGASTRIC NODE
• ARISING FROM ONE OF THE FOLLOWING
• BREAST
• THYROID
• OVARY
• STOMACH
• PROSTATE

M. ZAKARIA PRSENTATIONS
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THE PRIMARY SITE MAY REMAIN UNDISCOVERED IN UP TO
10 OF CASES (1)

• IN SOME PATIENTS WITH SECONDARY ADENOCARCINOMA,
  OR SQUAMOUS CELL CARCINOMA
• THE PROGNOSIS FOR THESE PATIENTS IS HOPELESS (2)
• IF CLINICAL EXAM INVESTIGATIONS HAVE FAILED TO
  IDENTIFY THE PRIMARY SITE THEN EXTENSIVE
  INVESTIGATIONS
• ARE RARELY JUSTIFIABLE (3)
• 1JOSSE ET al 1979, (2)NORDBOTRUM et al (3)
  STEWART, TATERS, WOODS AND FOX 1989

M. ZAKARIA PRSENTATIONS
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DISCUSSION1

• A VERY CAREFUL EXAMINATION OF ALL SITES OF
  POSSIBLE PRIMARY IS MANDATORY
• 10 OF CASES WITH CERVICAL LYMPHADENOPATHY, THE
  PRIMARY SITE MAY REMAIN UNDISCOVERED
• THERE IS ALSO THE POSSIBILITY OF GETTING
  HISTOLOGICALLY NEGATIVE RESULTS IN ALL EXAMINED
  PRIMARIES.

M. ZAKARIA PRSENTATIONS
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DISCUSSION.2

• OCCASIONALLY A NODE IN THE NECK MAY BE THE ONLY
  CLINICAL EVIDENCE OF Ca THYROID OR OTHER PRIMARY.
• HISTOLOGICAL EXAMINATION OF THE CERVICAL L.N
  SHOULD INDICATE THE PRIMARY SITE.
• POINTON CLEAVE 1990

M. ZAKARIA PRSENTATIONS
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DIAGNOSIS.1

• HISTORY
• CLINICAL EXAMINATION
• MULTIPLE BIOPSIES BEARING IN MINED THAT THE
  FALSE NEGATIVE RATE IS 14 to 2 0.8
• EXAMPLE SQUAMOUS CELL CARCINOMA OF THE FLOOR OF
  THE MOUTH.
• POINTON CLEAVE 1990

M. ZAKARIA PRSENTATIONS
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DIAGNOSIS2

• AT M. D. ANDERSON HOSPITAL 114 PATIENTS HAD
  DIRECT EXAMINATION UNDER G. A , PALPATION OF
  MUCOSAL SURFACES OF THE UPPER RESPIRATORY AND
  ALIMENTARY TRACTS.
• 62 PTS SQ C CA,28 UNDIF .CA, 10 SAL. GLAND
  ORIGIN, 14 PTS REMAINED WITH UNKNOWN HIS.
• BIOPSIES WERE PERFORMED ON ANY ABNORMAL MUCOSAL
  SURFACE
• RANDOM BIOPSIES ARE USUALLY TAKEN FROM BASE OF
  TONGUE, TONSILS AND PYRIFORM SINUSES.

M. ZAKARIA PRSENTATIONS
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DIAGNOSIS3

• SIMPLE SOFT TISSUE VIEWS OF THE NECK
• CT SCAN HAS LIMITED VALUE IN THE ASSESSMENT OF
  CLINICALLY ACCESSIBLE NODES.
• US MAY BE OF SOME VALUE IN EXPERIENCED HANDS FOR
  THE DETECTION OF DEEP SEATED ACCESSIBLE NODES ,
  THEN
• CONFIRMATION CAN BE ATTEMPTED BY NEEDLE
  ASPIRATION.

M. ZAKARIA PRSENTATIONS
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DIAGNOSIS4

• F N A (FINE NEEDLE ASPIRATION) IS MANDATORY BUT
  THERE IS A LOT OF CONTROVERSY REGARDING
• WHO SHOULD DO IT
• WHEN SHOULD IT BE DONE
• FALSE POSITIVE
• FALSE NEGATIVE RESULTS

M. ZAKARIA PRSENTATIONS
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DIAGNOSIS..5

• FNA FINE NEEDLE ASPIRATION CYTOLOGY1
• IS A DIAGNOSTIC METHOD OF ENLARGED ACCESSIBLE
  LYMPH NODES.
• IT IS AN OUT PATIENT PROCEDURE
• THE DIAGNOSTIC ACCURACY OF F N A IS INFLUENCED BY
  A VARIETY OF FACTORS
• SITE
• SIZE
• FIBROSIS
• NUMBER OF PUNCTURES MADE
• CYTOLOGICAL PREPARATION

M. ZAKARIA PRSENTATIONS
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DIAGNOSIS6

• F N A .2
• FAILURE TO OBTAIN A REPRESENTATIVE ASPIRATION IS
  CONSIDERED TO BE RESPONSIBLE FOR MOST FALSE
  NEGATIVE DIAGNOSES.
• HALNAN

M. ZAKARIA PRSENTATIONS
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DIAGNOSIS7

• F N A 3
• BETSIL HADJDU IN 1980 REVIEWED 361 PTS WHO HAD
  FNA CYTOLOGY OF ACCESSIBLE L.N
• 62 OF THE TOTAL WERE HARD NODES
• BETSIL HADJDU 1980

OF RESULTS OF FNA
M. ZAKARIA PRSENTATIONS
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DIAGNOSIS8

• F N A4
• A NEGATIVE REPORT FOR MALIGNANCY CAN NOT BE
  REGARDED AS DIAGNOSTIC SO OTHER INVESTIGATIONS
  ARE APPROPRIATE.

M. ZAKARIA PRSENTATIONS
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METASTATIC NODES ON PRESENTATION FOR EACH T STAGE

• THEREFORE
• THE INCIDENCE OF METASTATIC L.N
• INCREASES PROPORTIONALLY AS T INCREASES

M. ZAKARIA PRSENTATIONS
THE INCIDENCE OF METASTATIC NODES ON
PRESENTATION FOR EACH T STAGE
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STAGING 1210 PATIENTS PRESENTED WITH CERVICAL
LYMPHADENOPATHY. THE DISTRIBUTION OF L.N
INVOLVEMENT WAS AS FOLLOWS
M. ZAKARIA PRSENTATIONS
OF PTS WITH CERVICAL LYMPHADENOPATHY
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STAGING ACCORDING TO LYMPH NODE SIZE..2

• N1single ipsilateral L.N 3 cm or less.
• N2A single ipsilateral L.N gt3 cm but less lt than
  6 cm.
• N2Bmultiple ipsilateral L.N not gt 6 cm.
• N2Cbilateral or contralateral L.N gt6 cm.
• N3metastasis in a L.N gt 6 cm.
• ROBERT VP HUTTER 1992 (MANUAL FOR STAGING OF
  CANCER)

M. ZAKARIA PRSENTATIONS
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TREATMENT POLICY1

• IN study of large number of head neck tumors
• VERONICI concluded the following.
• PTS FALL IN 3 MAIN CLINICAL GROUPS
• 1 No clinical evidence of involved L.N.
• HE treated the primary tumors elective
  radical neck dissection Vs RT to whole neck
  Equal survival rate and remission.
• 2 IN MOBILE DISCRETE NODES(N1N2) in block RT
  to primary tumour neck RT
• 3 - FIXED NODES N3 best treated by RT

M. ZAKARIA PRSENTATIONS
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O.K. THAT WAS VERONICI TREATMENT, BUT WHAT IS THE
CURRENT TREATMENT

• 1 -No clinical evidence of involved L.N.
• RT to primary whole neck/- adjuvant
  Cisplatinum containing regime chemotherapy
• 2 -In mobile discrete (N1N2) RT to primary
  whole neck Cisplatinum containing regime
  chemotherapy.
• 3 -FIXED NODES N3 best treated by RT CT
• (primary and whole neck) chemotherapy

M. ZAKARIA PRSENTATIONS
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Treatment options1

• We must understand and accept the TREATMENT of
  caner must be multidisciplinary
• The concept of combined clinics must be accepted
  and practiced i.e.
• Combined ONCOLOGY- ENT Clinic So the patient must
  be seen by these two disciplines before , during
  treatment , and follow up jointly.

M. ZAKARIA PRSENTATIONS
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Treatment options2

• Usually the treatment of choice starts by Surgery
  either to
• 1 removal of the tumour totally or
• 2 - debulk the tumour or
• 3 - at least taking biopsy.

M. ZAKARIA PRSENTATIONS
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Treatment options3

• CURATIVE Radiotherapy 6000 -7000 cGy IN 30 -35
  fractions over 6 -7 weeks to the primary without
  irradiating heavily the surrounding normal
  structures.
• RT to neck nodes 5000 cGy in 25 fractions over 5
  weeks avoiding the spinal cord and boost the
  residual tumour in the nodes by Electron beam
  which treats superficial and less deep lesions.
• or just palliative treatment to comfort the pt
  for short period of time.

M. ZAKARIA PRSENTATIONS
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The role of chemotherapy in head neck cancer
with or without cervical Lymphadenopathy

• Chemotherapy Chemotherapy in head neck cancer
  with or without cervical Lymphadenopathy was
  introduced in late 1990s and gave very promising
  results in term of tumour remission and survival
  and cervical node regression.
• Now Cisplatinum based chemotherapy is considered
  one important treatment option in head neck
  cancer.
• The incidence of recurrence rates are much less
  when adding Chemotherapy to the usual Surgery and
  Radiotherapy.

M. ZAKARIA PRSENTATIONS
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Treatment options4

• Chemotherapy 3- 6 courses either pre or post RT
• B M C
• BLEOMYCIN 10 UNITS IM DAYS 1,8,15
• METHOTREXATE IM 40 mg/m2 days 1 and15
• CISPLATINUM50 mg/m2 50 mg/m2 iv on day 4 repeat
  every 21 days
• C F Cisplatin-FLUOROURACIL
• Cisplatin100 mg/m2 iv day 1
• FLUOROURACIL1000mg by continuous iv infusion for
  96 hours repeat every 3 weeks

M. ZAKARIA PRSENTATIONS
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THE RESULTS OF CHEMOTHERAPY in head neck
cancer with or without cervical Lymphadenopathy

• Survival rates have increased dramatically
• Recurrence rates in the primary tumour and
  Cervical Lymphadenopathy are now much less than
  before.
• Cisplatinum based chemotherapy has changed the
  results of treatment as compared with the trials
  using high dose Methotrexate by Strong et al
  in1998.

M. ZAKARIA PRSENTATIONS
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RADIOTHERAPY RESULTS
M. ZAKARIA PRSENTATIONS
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RADIOTHERAPY RESULTS
M. ZAKARIA PRSENTATIONS
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THANK YOU