Pediatric Head and Neck Malignancies

Pediatric Head and Neck Pediatric Head and Neck MalignanciesMalignancies

Elizabeth J. Rosen, MDElizabeth J. Rosen, MD

Ronald W. Deskin, MDRonald W. Deskin, MD

4/9/034/9/03

Pediatric CancerPediatric Cancer

22ndnd leading cause of death in age range of leading cause of death in age range of 5-14 years5-14 years

1/333 children diagnosed annually1/333 children diagnosed annually

11,000 new cases in children under 20 11,000 new cases in children under 20 years of age each yearyears of age each year

Head and Neck Malignancies make up 5% Head and Neck Malignancies make up 5% of pediatric cancer cases = 500 kids/yearof pediatric cancer cases = 500 kids/year

Pediatric CancerPediatric Cancer

Albright, et al in Archives of Oto-HNS Albright, et al in Archives of Oto-HNS June 2002June 2002– Overall annual incidence of pediatric Overall annual incidence of pediatric

cancercancer1973-1975 = 11.22 cases/100,000 person/years1973-1975 = 11.22 cases/100,000 person/years

1994-1996 = 14.03 cases/100,000 person years1994-1996 = 14.03 cases/100,000 person years

Increase of 25%Increase of 25%

– Annual incidence of pediatric H&N cancerAnnual incidence of pediatric H&N cancer1973-1975 = 1.10 cases/100,000 person/years1973-1975 = 1.10 cases/100,000 person/years

1994-1996 = 1.49 cases/100,000 person/years1994-1996 = 1.49 cases/100,000 person/years

Increase of 35%Increase of 35%

Pediatric Head and Neck Pediatric Head and Neck MalignanciesMalignancies

Lymphoma = 59%Lymphoma = 59%Rhabdomyosarcoma = 13%Rhabdomyosarcoma = 13%Thyroid Malignancies = 10%Thyroid Malignancies = 10%Nasopharyngeal Carcinoma = 5%Nasopharyngeal Carcinoma = 5%Neuroblastoma = 5%Neuroblastoma = 5%Nonrhabdomyosarcoma Soft-tissue Sarcoma Nonrhabdomyosarcoma Soft-tissue Sarcoma = 4.5%= 4.5%Salivary Gland Malignancies = 2.5%Salivary Gland Malignancies = 2.5%Malignant Teratoma = 1%Malignant Teratoma = 1%OthersOthers

Non-Hodgkin’s LymphomaNon-Hodgkin’s Lymphoma

Lymphoma = 11.5% of all pediatric Lymphoma = 11.5% of all pediatric cancerscancers

NHL occurs in 60% of lymphoma casesNHL occurs in 60% of lymphoma cases

M:F = 3:1M:F = 3:1

Peak incidence between 7-11 years of agePeak incidence between 7-11 years of age

Increased risk with T-cell deficiencyIncreased risk with T-cell deficiency– Congenital immunodeficiency syndromesCongenital immunodeficiency syndromes– Acquired immunodeficiency syndromeAcquired immunodeficiency syndrome– Immunosuppressive drug therapyImmunosuppressive drug therapy


Low-, intermediate-, and high-grade Low-, intermediate-, and high-grade lesions lesions

90% of children with NHL have high-grade 90% of children with NHL have high-grade disease at presentationdisease at presentation

High-gradeHigh-grade– Large cell lymphomaLarge cell lymphoma– Lymphoblastic lymphomaLymphoblastic lymphoma– Small cell noncleaved lymphomaSmall cell noncleaved lymphoma


Large cell lymphomaLarge cell lymphoma– 27% pediatric cases27% pediatric cases– t(2;5) anomalyt(2;5) anomaly– Rare presentation inRare presentation in

H&NH&N

From, Diagnostic Surgical Pathology of the Head and Neck, From, Diagnostic Surgical Pathology of the Head and Neck, W.B.Saunders, p 762.W.B.Saunders, p 762.


Lymphoblastic Lymphoblastic lymphomalymphoma– 29% pediatric29% pediatric

casescases– t(7 or 14)t(7 or 14)– Mediastinal massMediastinal mass

From, Diagnostic Surgical Pathology of theFrom, Diagnostic Surgical Pathology of the

Head and Neck, W.B.Saunders, p 759.Head and Neck, W.B.Saunders, p 759.


Small cell noncleavedSmall cell noncleaved– 34% pediatric cases34% pediatric cases– Burkitt’s lymphomaBurkitt’s lymphoma

Epstein-Barr virusEpstein-Barr virus

t(8;2,14,22)t(8;2,14,22)

MandibleMandible

Head and NeckHead and Neck

From, Surgical Pathology of the Head and Neck, From, Surgical Pathology of the Head and Neck,

Lippincott Williams & Wilkins, p 161.Lippincott Williams & Wilkins, p 161.


Presentation in the H&N in 5-10% of casesPresentation in the H&N in 5-10% of cases– Cervical lymphadenopathyCervical lymphadenopathy– Salivary gland, larynx, sinuses, orbit, scalpSalivary gland, larynx, sinuses, orbit, scalp– Waldeyer’s ringWaldeyer’s ring

Asymmetric tonsils-how concerning is it?Asymmetric tonsils-how concerning is it?

– Associated symptomsAssociated symptomsFever, night sweats, weight lossFever, night sweats, weight loss


EvaluationEvaluation– H&PH&P– BiopsyBiopsy

TonsillectomyTonsillectomyLymph nodeLymph node

– Staging w/uStaging w/uBlood studiesBlood studiesLumbar punctureLumbar punctureBone marrow biopsyBone marrow biopsyCT chest/abdomen/pelvisCT chest/abdomen/pelvisBone scanBone scan



Multiagent ChemotherapyMultiagent Chemotherapy– CyclophosphamideCyclophosphamide– DoxorubicinDoxorubicin– VincristineVincristine– PrednisonePrednisone– +/- Methotrexate+/- Methotrexate

– XRT—not routinely usedXRT—not routinely used


SurvivalSurvival– Overall Stage I and II NHL = 85-95%Overall Stage I and II NHL = 85-95%– Overall Stage III and IV NHL = 65-75%Overall Stage III and IV NHL = 65-75%– Stage III and IV BL = 75-85%Stage III and IV BL = 75-85%

Hodgkin’s DiseaseHodgkin’s Disease

Less common than NHLLess common than NHL

More frequently in 15-20 y/o populationMore frequently in 15-20 y/o population

4% under 10 years 4% under 10 years

M:F = 3:1M:F = 3:1

Association with EBVAssociation with EBV


Nodular SclerosingNodular Sclerosing

From, Diagnostic Surgical Pathology of the Head and Neck, From, Diagnostic Surgical Pathology of the Head and Neck, W.B.Saunders, p 750 & 764.W.B.Saunders, p 750 & 764.

Lymphocyte PredominantLymphocyte Predominant


Mixed CellularityMixed Cellularity

From, Diagnostic Surgical Pathology of the Head and Neck, From, Diagnostic Surgical Pathology of the Head and Neck, W.B.Saunders, p 750.W.B.Saunders, p 750.

Lymphocyte DepletedLymphocyte Depleted


PresentationPresentation– Asymmetric lymphadenopathy—90%Asymmetric lymphadenopathy—90%

Firm, rubberyFirm, rubbery

Supraclavicular fossaSupraclavicular fossa

– Spleen, liverSpleen, liver– Constitutional symptoms—1/3 of casesConstitutional symptoms—1/3 of cases

Fever, night sweats, anorexia, weakness, weight Fever, night sweats, anorexia, weakness, weight lossloss


EvaluationEvaluation– H&PH&P– Biopsy = Reed-Biopsy = Reed-

Sternberg cellsSternberg cells– Staging w/uStaging w/u

Similar to NHLSimilar to NHLLaparotomyLaparotomy

– ControversialControversial

From, Principles and Practice of PediatricFrom, Principles and Practice of PediatricOncology, Lippincott Williams & Wilkins,Oncology, Lippincott Williams & Wilkins,P 640.P 640.



Localized diseaseLocalized disease– Extended field XRTExtended field XRT

Disseminated diseaseDisseminated disease– MOPP = nitrogen mustard, vinblastine, MOPP = nitrogen mustard, vinblastine,

procarbazine, prednisoneprocarbazine, prednisone– ABVD = adriamycin bleomycin, vincristine, ABVD = adriamycin bleomycin, vincristine,

dacarbazinedacarbazine


SurvivalSurvival– Stages I, II, and III = 90%Stages I, II, and III = 90%– Stage IV = 75-80%Stage IV = 75-80%

RhabdomyosarcomaRhabdomyosarcoma

Most common soft tissue sarcoma in Most common soft tissue sarcoma in childrenchildren

4.5 cases/1,000,000 children under 14 4.5 cases/1,000,000 children under 14 yearsyears

Majority diagnosed before age 10Majority diagnosed before age 10

M:F = 1.5:1M:F = 1.5:1


EmbryonalEmbryonal– Most common in kids:Most common in kids:

60-70% of cases60-70% of cases

– Chromosome 11p15 Chromosome 11p15 deletiondeletion

– Lack of gene Lack of gene

amplificationamplification– Hyperdiploid DNAHyperdiploid DNA

From, Surgical Pathology of the Head and Neck, LippincottFrom, Surgical Pathology of the Head and Neck, Lippincott

Williams & Wilkins, p 157.Williams & Wilkins, p 157.


AlveolarAlveolar– 20% of pediatric cases20% of pediatric cases– Chromosomal translocation: Chromosomal translocation:

t(2;13) or t(1;13)t(2;13) or t(1;13)

– Gene amplificationGene amplification– Tetraploid DNATetraploid DNA

From, Surgical Pathology of the Head and Neck, Lippincott Williams & Wilkins,From, Surgical Pathology of the Head and Neck, Lippincott Williams & Wilkins,

p 157.p 157.


BotryoidBotryoid– 5-10% of pediatric 5-10% of pediatric

casescases– Grape-like tumor Grape-like tumor

massesmasses

PleomorphicPleomorphic– Rare in childrenRare in children

From, Diagnostic Surgical Pathology of the Head and Neck,From, Diagnostic Surgical Pathology of the Head and Neck,

W.B.Saunders, p 554.W.B.Saunders, p 554.


Most common site of presentation is Most common site of presentation is H&N--40% of casesH&N--40% of cases

1/3 of cases involve the orbit1/3 of cases involve the orbit

Oral cavity & oropharynx, face & neck, Oral cavity & oropharynx, face & neck, middle ear & mastoid, nose & paranasal middle ear & mastoid, nose & paranasal sinusessinuses

Localized swelling, proptosis, nasal Localized swelling, proptosis, nasal obstruction, epistaxis, otorrhea, hearing obstruction, epistaxis, otorrhea, hearing loss, fetor and cranial nerve deficitsloss, fetor and cranial nerve deficits


EvaluationEvaluation– H & PH & P– Biopsy Biopsy – CT/MRI of primaryCT/MRI of primary– Metastatic w/u Metastatic w/u

Chest CTChest CT

Bone scanBone scan

Bone marrow biopsyBone marrow biopsy


Intergroup Rhabdomyosarcoma Study Intergroup Rhabdomyosarcoma Study Clinical Grouping Classification (IRSCGC)Clinical Grouping Classification (IRSCGC)



TreatmentTreatment– SurgerySurgery

Goal = complete excision with marginGoal = complete excision with margin

Consider morbidity of surgeryConsider morbidity of surgery– Cranial nervesCranial nerves– CosmesisCosmesis

DebulkingDebulking

Exception is orbital rhabdomyosarcoma—surgery Exception is orbital rhabdomyosarcoma—surgery offers no advantage over chemo/XRToffers no advantage over chemo/XRT


TreatmentTreatment– ChemotherapyChemotherapy

Low-risk: vincristine, dactinomycin, +/- Low-risk: vincristine, dactinomycin, +/- cyclophosphamidecyclophosphamide

Intermediate- and High-risk: vincristine, Intermediate- and High-risk: vincristine, dactinomycin and cyclophosphamidedactinomycin and cyclophosphamide


TreatmentTreatment– Radiation TherapyRadiation Therapy

Postoperative microscopic diseasePostoperative microscopic disease– 4,000-4,500 cGy4,000-4,500 cGy

Gross diseaseGross disease– 4,500-5,000 cGy4,500-5,000 cGy

Hyperfractionated XRTHyperfractionated XRT

BrachytherapyBrachytherapy


SurvivalSurvival– Before 1970 = 33%Before 1970 = 33%– Currently = 70%Currently = 70%– Intergroup Rhabdomyosarcoma StudyIntergroup Rhabdomyosarcoma Study– Prognostic factorsPrognostic factors

Tumor sizeTumor size

Regional node statusRegional node status

Margins after surgeryMargins after surgery

Genetic factorsGenetic factors

NeuroblastomaNeuroblastoma

Most common extracranial solid tumor in Most common extracranial solid tumor in childrenchildren

8-10% of childhood cancers8-10% of childhood cancers

90-95% of cases diagnosed before age 1090-95% of cases diagnosed before age 10

More common in boys and CaucasiansMore common in boys and Caucasians

? Genetic or environmental factors? Genetic or environmental factors


““Small blue round cell” tumorSmall blue round cell” tumor

Immunohistochemical stains: Immunohistochemical stains: neurofilament proteins, neurofilament proteins, synaptophysin, NSEsynaptophysin, NSE

Electron microscopy: Electron microscopy: neurosecretory granules, neurosecretory granules, microtubules and filamentsmicrotubules and filaments

Chromosome 1 deletions or Chromosome 1 deletions or N-N-mycmyc oncogene amplification oncogene amplification

From, Principles and Practice of Pediatric Oncology, Lippincott Williams & Wilkins,From, Principles and Practice of Pediatric Oncology, Lippincott Williams & Wilkins,

p 903.p 903.


2-5% in the H&N region—most often as 2-5% in the H&N region—most often as lateral neck masslateral neck mass

Airway obstruction, aspiration, dysphagia, Airway obstruction, aspiration, dysphagia, Horner’s syndrome, proptosis, periorbital Horner’s syndrome, proptosis, periorbital ecchymosis, opthalmoplegia, conjunctival ecchymosis, opthalmoplegia, conjunctival or eyelid edema, papilledemaor eyelid edema, papilledema

Heterochromia iridesHeterochromia irides


EvaluationEvaluation– H & PH & P– BiopsyBiopsy– Urine catecholamine studiesUrine catecholamine studies– Metastatic w/uMetastatic w/u

CXRCXR

Bone marrow biopsyBone marrow biopsy

Bone scanBone scan

CT or MRI CT or MRI



TreatmentTreatment– SurgerySurgery– ChemotherapyChemotherapy

Intermediate- or High-riskIntermediate- or High-risk

Low-risk with recurrenceLow-risk with recurrence

Cyclophosphamide, ifosfamide, doxorubicin, Cyclophosphamide, ifosfamide, doxorubicin, teniposide, etoposide, cisplatin or carboplatinteniposide, etoposide, cisplatin or carboplatin

– Radiation TherapyRadiation TherapyLimited useLimited use


Prognostic FactorsPrognostic Factors– Age at diagnosisAge at diagnosis– Stage at diagnosisStage at diagnosis

Overall, Stage I or II = 75-90%Overall, Stage I or II = 75-90%

Infants: Stage III = 80-90%; Stage IV = 60-Infants: Stage III = 80-90%; Stage IV = 60-75%75%

Children: Stage III = 50%; Stage IV = 15%Children: Stage III = 50%; Stage IV = 15%

EsthesioneuroblastomaEsthesioneuroblastoma

100 pediatric cases in the literature100 pediatric cases in the literature

Teenagers, boys > girlsTeenagers, boys > girls

PresentationPresentation

HistologyHistology

StagingStaging

TreatmentTreatment


HistologyHistology

From, Surgical Pathology of the Head and Neck, Lippincott Williams & Wilkins, p 86.From, Surgical Pathology of the Head and Neck, Lippincott Williams & Wilkins, p 86.


100 pediatric cases in the literature100 pediatric cases in the literature

Teenagers, boys > girlsTeenagers, boys > girls


HistologyHistology

StagingStaging

TreatmentTreatment

Nasopharyngeal CarcinomaNasopharyngeal Carcinoma

5% of pediatric H&N malignancies5% of pediatric H&N malignanciesTeenagers, M=F, African AmericansTeenagers, M=F, African AmericansSignificantly higher incidence in ChineseSignificantly higher incidence in Chinese– HLA-A2, HLA-B-Sin 2HLA-A2, HLA-B-Sin 2– Smoke, dust, nitrosamine rich salted fishSmoke, dust, nitrosamine rich salted fish

EBVEBV

From, Diagnostic Surgical Pathology of From, Diagnostic Surgical Pathology of

the the Head and Neck, W.B.Saunders, p 43.Head and Neck, W.B.Saunders, p 43.


WHO ClassificationWHO Classification– Type I – squamous cell Type I – squamous cell

carcinomacarcinoma– Type II – non-keratinizing Type II – non-keratinizing

squamous cell carcinomasquamous cell carcinoma– Type III – undifferentiated Type III – undifferentiated

or lymphoepitheliomaor lymphoepithelioma

From, Diagnostic Surgical Pathology of the Head From, Diagnostic Surgical Pathology of the Head and Neck, and Neck, W.B.Saunders, p 43W.B.Saunders, p 43


PresentationPresentation– Neck mass and hearing lossNeck mass and hearing loss– Nasal obstruction, rhinorrhea, epistaxis, Nasal obstruction, rhinorrhea, epistaxis,

headache, otalgiaheadache, otalgia– Cranial neuropathyCranial neuropathy

Abducens palsyAbducens palsy

CN III, IV, VCN III, IV, V

CN IX, X, XIICN IX, X, XII


EvaluationEvaluation– H & PH & P– EndoscopyEndoscopy– BiopsyBiopsy– CT/MRI for local extentCT/MRI for local extent– Metastatic w/uMetastatic w/u

CT chest/abdomenCT chest/abdomen

Bone scanBone scan



TreatmentTreatment– Radiation TherapyRadiation Therapy

Primary and local lymphaticsPrimary and local lymphatics

6,500-7,000 cGy6,500-7,000 cGy

– ChemotherapyChemotherapyAdvanced diseaseAdvanced disease

Vincristine, doxorubicin, cyclophosphamide, Vincristine, doxorubicin, cyclophosphamide, cisplatin, 5-fluorouracilcisplatin, 5-fluorouracil

– SurgerySurgery


SurvivalSurvival– Overall 5-year = 40%Overall 5-year = 40%

– Prognostic FactorsPrognostic FactorsPositivePositive

– Locally confined diseaseLocally confined disease– Ipsilateral nodesIpsilateral nodes

NegativeNegative– Bilateral nodesBilateral nodes– CNS penetrationCNS penetration

Soft-tissue SarcomasSoft-tissue Sarcomas

4.5% of pediatric H&N malignancies4.5% of pediatric H&N malignanciesDiverse group of tumorsDiverse group of tumors

fibrosarcomafibrosarcoma epitheloid sarcomaepitheloid sarcomasynovial sarcomasynovial sarcoma chondrosarcomachondrosarcomadermatofibrosarcoma protuberansdermatofibrosarcoma protuberansosteosarcomaosteosarcoma leiomyosarcomaleiomyosarcomahemangiopericytomahemangiopericytomaliposarcomaliposarcoma clear-cell clear-cell sarcomasarcoma

Soft-tissue SarcomasSoft-tissue Sarcomas


EvaluationEvaluation

StagingStaging

TreatmentTreatment

SurvivalSurvival

Primitive Neuroectodermal Primitive Neuroectodermal TumorsTumors

RareRare

42% involve the H&N region42% involve the H&N region

““small blue round cell” tumorsmall blue round cell” tumor

From, Diagnostic Surgical Pathology of the Head and Neck, W.B.Saunders, p 527.From, Diagnostic Surgical Pathology of the Head and Neck, W.B.Saunders, p 527.

Primitive Neuroectodermal Primitive Neuroectodermal TumorsTumors


EvaluationEvaluation

StagingStaging

TreatmentTreatment

SurvivalSurvival

ConclusionConclusion

Rare diseasesRare diseases

Broad differential diagnosisBroad differential diagnosis

High index of suspicionHigh index of suspicion

Early diagnosisEarly diagnosis

Accurate stagingAccurate staging

Multimodality therapyMultimodality therapy

Improved prognosisImproved prognosis

Documents

Pediatric Head and Neck Malignancies