Oral involvement in neuroblastoma

Oral involvement in neuroblastoma

Michael H. Stern, DDS James E. Turner, DDS Thomas P. Coburn, MD, Memphis

Eighty-three patients with

neuroblastoma were

examined retrospectively to determ ine the fre­ quency with which this malignancy affects the os­ seous structures of the oral cavity. These struc­ tures were involved in 21 (25%) of all patients and in 21 (49%) of the 43 with bone métastasés as judged from clinical, radiologic, and pathologic findings. Evidence of oral involvement led to diag­ nosis in two instances and was discovered during the initial evaluation in ten of the 21 patients with facial manifestations. The most common clinical signs were facial or intraoral, swellings or both, loose or displaced teeth, and paresthesia. The most important radiologic findings were lytic le­ sions, expansion of the dental follicle, and poorly defined borders around the crypts of developing teeth. This study indicates that oral involvement in neuroblastoma is much more common than was previously thought, and that clinical and radio­ logic evidence of jaw metastasis may be of value in early diagnosis.

Neuroblastoma, a highly malignant tumor of sympathetic nervous tissue origin,1 is the sec­ ond most common malignancy of children, pre­ ceded only by leukemia.2 It may occur as a lo­ calized lesion but is usually widespread at the time of diagnosis.1-4 Common sites of metas­ tasis are the lymph nodes, bone, liver, and lungs.5,6 The bones most frequently affected are the femur, humerus, skull, and pelvis.7 3 46 ■ JA D A , V o l. 88, F e b ru a ry 1974

Although the skull is a frequent site of meta­ static neuroblastoma, only 12 isolated cases of oral metastasis have been reported to date.2,710 Our experience with this tumor suggested that involvement of the oral cavity was much more frequent than indicated by published findings. A retrospective study was therefore conducted to test this impression and to determine the char­ acteristics that mark the spread of this disease to the jaws.

Patients

The radiographs and records of 83 patients with neuroblastoma treated at St. Jude Children’s Research Hospital between March 1962 and Oc­ tober 1972 were reviewed. In each instance the diagnosis was established from a histologic ex­ amination of biopsy tissue. Clinical, radiograph­ ic, and pathologic reports were used to deter­ mine the frequency and extent of oral involve­ ment. The race, age, and sex of each patient with evidence of jaw metastasis are given in the Ta­ ble. The median age at diagnosis for this group was 3 years (range: 10 months to 8 years, 1 month).

Results

The adrenal gland was the site of tumor origin in most patients in this series. Other areas com­ monly involved were the lymph nodes, bones, and bone marrow. Symptoms were variable and nonspecific, consisting largely of anorexia, fe­ ver, pain, and irritability. The main initial phys­ ical findings were palpable abdominal masses,

Table ■ Summary of patients with oral m anifestations of neuroblastoma. Race/ sex

Age (yr)

1

W/F

8 8/12

2

W/M

3

3

W/F

4

Case*

Primary site & clinical staget

Site of oral involvement

Other sites involved concurrently

Left adrenal gland III B

Mandible

Adrenals, mesentery, liver, scalp, skull, bones

Unknown III B

Mandible

1 6/12

Retroperitoneal tissue III A

B/M

3

5

W/F

6

Survival (y r)i

Major clinical (A) and radiographic (B) features

3

A Pain and numbness related to tumor mass in mandible B None

Bone marrow, bones

0 6/12

A Mass in right side of mandible resulting in hospitalization B Destruction of crypts, lytic lesions, expand­ ed follicle with tooth displacement

Mandible

Supraorbit, liver, omentum

AliveS

A Large mandibular asymmetry B Lytic lesions

Retroperitoneal tissue III B

Maxilla, zygoma

Orbit, maxillary sinus

1 7/12

A Intraoral mass displacing tooth B Lytic lesions

4

Left adrenal gland II B

Mandible

Lymph nodes, adrenal glands

0 3/12

A Intraoral mass elevating molar, toothache; bone metastasis first observed in mandible B Lytic lesion, expanded crypt of mandibular first molar

W/F

1

Left adrenal gland Ml B

Mandible

Bone marrow, abdomen

0 10/12

A Soft tissue mass displacing molar B Lytic areas, poorly defined crypts

7

W/M

5

Left adrenal gland III A

Maxilla, zygoma

Skull, bones

8

W/F

4 5/12

Unknown III B

Mandible

Bone marrow, bones, lungs, skull

0 10/12

A None B Lytic lesions after widespread dissemination of disease

9

W/M

1 7/12

Left adrenal gland III B

Mandible

Bone marrow, bones, lymph nodes, mediastinum

0 5/12

A Mass in mandible B Lytic lesions, displacement of tooth germ, destruction of crypts

10

B/M

3 7/12

Right adrenal gland III B

Mandible, maxilla (palate)

Lymph nodes, bone marrow, liver, bones

0 4/12

A Mass in left side of palate, mobility of maxillary first deciduous molar, mass in left side of mandible B Loss of bone density in region of tumor in maxilla, bilateral lytic lesions in mandible, displacement of tooth germ

11

B/F

3 5/12

Left adrenal gland III B

Mandible

Lymph nodes, bones, bone marrow, liver

0 4/12

A Facial swelling due to tumor mass B Lytic lesions

12

W/M

0 10/12

Left adrenal gland III B

Mandible

Bone, bone marrow

mass

producing

facial

Lost to A Long-standing intraoral mass causing de­ formity of anterior border of mandible, facial follow-up swelling B Displacement of tooth germ

1

A None B Lytic lesions; first admission

floating

teeth

seen

before

13

W/M

6 1/12

Right adrenal gland III B

Mandible

Bone marrow, adrenal glands, orbit, bones

1 1/12

A None B Lytic lesions in ramus, destruction of crypts

14

W/M

4 1/12

Unknown III B

Mandible

Bones, bone marrow

1 5/12

A None B Destruction of crypt, displacement of tooth germ

15

B/M

3

Left sympathetic chain ganglions III B

Mandible

Bone marrow, bones, lymph nodes, abdomen

0 4/12

A None B Lytic lesions, destruction pansion of follicles

of

crypts,

ex­

16

W/F

1 5/12

Left adrenal gland III B

Maxilla

Bone marrow, bones, lymph nodes, liver

0 3/12

A Large intraoral tumor mass B None

17

B/F

1

Left adrenal gland ill B

Mandible, maxilla

Lymph nodes, bones, liver, lungs

0 8/12

A Swelling of left cheekbone leading to ad­ mission; diagnosis established by biopsy of soft tissue intraoral mass, displaced tooth B Lytic lesions

18

W/F

3 5/12

Right adrenal gland ill B

Mandible

Bone, lymph nodes, bone marrow, viscera

0 1/12

A Toothache, palpable mass in right side of mandible, intraoral mass distal to last molar B Lytic lesions

19

B/M

1 9/12

Right adrenal gland III B

Mandible

Bone, bone marrow, lungs, liver

0 6/12

A Intraoral mass at admission, loose tooth B Lytic lesions

20

W/M

2 6/12

Left adrenal gland III B

Zygoma

Adrenal glands, left orbit

1 6/12

A None B Lytic lesions in zygoma and orbit

21

W/M

6 11/12

Left adrenal gland III B

Mandible

Bones, bone marrow

0 4/12

A Enlarged right side of mandible, intraoral mass B Poorly defined crypts, displacement of tooth germ

'Treatment of these patients consisted of chemotherapy, surgery, irradiation, or a combination of these, according to neuroblastoma protocol of St. Jude Hospital (un­ published). tDefinition of tumor stages, according to Pinkel, D., and others. Survival of children with neuroblastoma treated with combination chemotherapy (J Pediatr 73:928 Dec 1968). Stage I: Local, completely resectable. Stage II: regional; A, partially resectable; B, not resectable. Stage III: systemic; A, without bone marrow involve­ ment; B, with bone marrow involvement. iSurvival of patients from time of initial diagnosis. §With evidence of disease. S te rn — T u rn e r— C o b u rn : N E U R O B L A S T O M A ■ 347

r Fig 1 ■ U n ila te ra l fa c ia l s w e llin g in tw o c h ild re n w ith m e ta s ta tic n e u ro b la s to m a . S w e llin g o f rig h t s id e o f ja w o f p a tie n t on le ft led to h is h o s p ita liz a tio n b e fo re d ia g n o s is . S u b s e q u e n t fin d in g s e s ta b lis h e d th a t th is w a s a m e ta s ta tic m ass s e c o n d a ry to n e u ro b la s to m a o f a d re n a l g la n d . A p p e a ra n c e o f c h ild is ty p ic a l o f th a t o f c h ild re n w ith fa c ia l s ig n s o f m e ta s ta tic n e u ro b la s to m a . N ote also p e rio rb ita l a n d in fra la b ia l e cch ym o se s. In p a tie n t on rig h t, s w e llin g w as n o t p re s e n t e a rly b u t d e v e lo p e d as d isease m e ta sta sized fro m p rim a ry a d re n a l tu m o r to in vo lve m any b o n e s. N o te s im ila rity o f th is s w e llin g to th a t ca u se d by a b ­ sce ssed to o th . In th is s tu d y u n ila te ra l fa c ia l s w e llin g a p p e a re d in e ig h t o f 21 p a tie n ts w ith ja w m e ta sta ses.

palpable gross m etastases, elevated blood pres­ sure, hepatom egaly, and subcutaneous nodules. O f the 83 patients review ed, 21 (25%) had evi­ dence o f jaw m etastasis. The mandible was af­ fected in 15 o f these patients, the maxilla in one, the zygom a in one, and a com bination o f sites in the remaining four (Table). Oral evidence o f neuroblastom a w as the presenting complaint in tw o patients and was found on physical exam ­ ination during diagnostic procedures in another ten. In the remaining patients, the mean time from diagnosis until the appearance o f jaw le­ sions was 8.1 months. The oral clinical signs o f neuroblastom a were facial sw elling, intraoral m asses, loose or dis­ placed teeth, and alterations in nerve function (Table). Facial sw elling was unilateral and quite prominent in eight patients (Fig 1). Although the sw elling closely resem bled that caused by ab­ scessed teeth, it w as usually not accom panied by pain. Intraoral m asses o f various sizes were found in 12 patients, mainly in association with lo o se or displaced teeth (F ig 2). Four patients experienced sudden neurological changes as in348 ■ JADA, V o l. 88, F e b ru a ry 1974

Fig 2 ■ In tra o ra l m ass in p a tie n t w ith m e ta s ta tic n e u ro b la s to m a to m a x illa . S im ila r m asses w e re fo u n d in 11 o th e r p a tie n ts and w ere u s u a lly a s s o c ia te d w ith lo o s e o r d is p la c e d te e th . M asses va rie d in size and had in ta c t m u c o s a . N e u ro b la s to m a w as fo u n d o n b io p s y o f th e s o ft tis s u e m ass. N ote h o w m ass has d is p la c e d in c is o r a nd d e c id u o u s m olar.

dicated by pain or num bness. T hese alterations were apparently related to tumor invasion in the area o f the inferior alveolar nerve. Radiographic evidence o f oral m etastasis was

Fig 3 ■ R a d io g ra p h s h o w in g ty p ic a l o ral c h an g e s a s s o c ia te d

w ith

m e ta s ta tic

n e u ro b la s to m a

s ix

w e e k s a fte r d ia g n o s is . N ote e x p a n d e d fo llic le s o f m a n d ib u la r fir s t m o la rs a nd b ila te ra l loss o f d e fin ­ itio n o f w h ite s c le ro tic b o rd e rs a ro u n d d e v e lo p in g p re m o la rs . L y tic le s io n s a re a ls o a p p a re n t in p o s ­ te r io r b o d y and ra m u s o f m a n d ib le .

the only indication o f neuroblastom a in six pa­ tients but was found in conjunction with clinical signs in the others. Radiographic changes con­ sisted o f ill-defined borders around the crypts o f developing teeth, expansion o f the dental fol­ licle, displaced or floating teeth or both, and lytic lesions (Table). L oss o f definition o f the white borders around dental crypts was seen in seven patients. This change was confined to the premolar and molar areas and ranged in appear­

ance from a decreased w hiteness to a com plete, loss o f crypt definition (F ig 3). Unilateral (F ig 4) or bilateral (Fig 3) expansion o f the dental fol­ licle with displacem ent o f the tooth bud w as seen in nine patients. T ooth displacem ent was appar­ ent in five patients. T he absence o f supporting bone around these teeth som etim es suggested the appearance o f floating teeth (Fig 5, 6). Lytic lesions, the most com m on pathologic change, were seen in 16 of the patients. T he lesions were confined to the posterior body and ramus area o f the mandible, and their appearances ranged from

Fig 4 ■ R a d io g ra p h s s h o w in g p ro g re s s io n o f fo llic le e x p a n s io n in p a tie n t w ith o ra l in v o lv e m e n t. T o p , e x p a n d e d fo llic le o f d e ­

Fig 5 ■ R a d io g ra p h s o f p ro g re s s iv e o ra l c h a n g e s in c h ild sh o w n

v e lo p in g se co n d m o la r, rig h t side, o n e m o n th a fte r d ia g n o s is .

in Fig 1, le ft. T o p , p ro m in e n t a lte ra tio n s fo u r days a fte r d ia g n o s is

S econd

m o la r on co n tra la te ra l side a p p e a rs n o rm a l. B o tto m ,

in c lu d e d p o o rly d e fin e d b o rd e rs o f c ry p ts o f d e v e lo p in g te e th ,

d e ta ile d v ie w o f le sio n tw o m o n th s later. N ote fu rth e r e x p a n sio n

r ig h t side, and d is p la c e m e n t o f d e v e lo p in g m o la r. B o tto m , one

o f fo llic le , d e s tru c tio n o f bone, and d is p la c e m e n t o f d e v e lo p in g

m o n th la te r, d e s tru c tio n o f b o n e had a d v a n c e d ra p id ly and d e v e l­

to o th u p w a rd .

o p in g m o la r w a s fu rth e r d is p la c e d and a p p e a re d to be flo a tin g .

S te rn — T u rn e r— C o b u rn : N E U R O B LA S T O M A ■ 349

Fig 6 ■ R a d io g ra p h o f a d v a n c e d ly tic le sio n o f le ft s id e o f m o u th in p a tie n t s h o w n in Fig 1, rig h t. L e s io n has d is p la c e d te e th and d e stro ye d m o st o f p o s te rio r b o d y and ra m u s o f m a n d ib le . Teeth n o w a p p e a r to be flo a tin g b eca u se o f a b s e n c e o f s u p p o rtin g b o n e ; lesio n c o n ta in s area o f d iffu s e w h ite n e s s .

Fig 7 ■ Late ral ja w ra d io g ra p h ta ke n te n d ays a fte r d ia g n o s is o f n e u ro b la s to m a . P ro m in e n t ly tic le sio n s are a p p a re n t in p o s ­ te rio r b o d y and ra m u s o f m a n d ib le . L y tic le sio n s w e re m o st c o m ­ m on p a th o lo g ic ch a n g e e n c o u n te re d in o u r p a tie n ts ; th e y w ere fo u n d in 16 o f 21 c h ild re n w ith ja w m étastasés.

a decreased area o f density to irregular lucent areas with com plete dissolution o f the osseous architecture (Fig 6, 7). Although the lesion s de­ stroyed bone and moved teeth, they did not resorb the roots o f teeth. Sclerotic borders, re­ active bone, and periosteal reactions w ere not seen.

D is c u s s io n Oral involvem ent by neuroblastoma, formerly thought to be rare,2-7'10 was seen in 25% (21 o f 83) o f the patients treated for this malignancy at St. Jude Children’s Research H ospital dur­ ing the past ten years. Improved diagnostic tech­ niques such as dental panoramic radiography, as w ell as a growing aw areness o f the oral com ­ plications o f this disease, have been important 350 ■ JADA, V o l. 88, F e b ru a ry 1974

factors in the recognition o f mandibular and maxillary m etastases. T he actual incidence o f or­ al m etastasis may be greater than that found in this limited series because the natural history o f neuroblastoma is one o f widespread involvem ent with an affinity for bone. Since the skull is one o f the areas m ost frequently affected by this malig­ nancy (57% in this series), w e would expect to find a higher frequency o f oral involvem ent as larger numbers o f patients are exam ined for this com plication. Orofacial signs can be prominent early in the course o f neuroblastoma, and a patient may have oral sym ptom s before any other m anifestations o f the disease. In this study prominent oral sw ell­ ings led to a diagnosis o f neuroblastom a in tw o patients, and oral findings were present at the time o f diagnosis in half the number o f patients with jaw lesions. T he m ost com m on early find­ ings w ere facial or intraoral swellings due to tu­ mor infiltration, loose or displaced teeth, and neurological disturbances with no history o f as­ sociated trauma or infection. W hereas bone pain was often an early physical finding, intraoral or facial pain was noted only late in the course o f the disease. Although oral radiographic findings in neuro­ blastom a are not diagnostic, panoramic radiog­ raphy o f osseou s structures o f the oral region has been included at this hospital as a routine screening procedure for all our patients. T he present findings indicate that certain radiograph­ ic changes in the jaw s o f young children should com pel one to include neuroblastom a in the dif­ ferential diagnosis o f jaw lesions. Such altera­ tions are destruction o f the white sclerotic bor­ der o f the dental crypts, expansion o f the den­ tal follicle, displacem ent o f teeth, floating teeth, and destructive lucent lesions with irregular out­

lines. As shown by this study, oral involvement in neuroblastoma is not rare. M oreover, recogni­ tion of the clinical and radiologic features pecu­ liar to neuroblastoma that has spread to the oral structures may be of prime importance in the establishment of an early diagnosis. By recog­ nizing one or more of these signs and by referring the patient to a physician for immediate eval­ uation, the dentist can provide an essential step in the detection of this malignancy.

This study was supported by Am erican Lebanese Syrian As­ sociated C harities.

lege of D entistry, 847 M onroe Ave, M em phis, 38103. He also is con­ sultant in oral pathology, St. Jude C h ild ren ’s Research Hospital. Dr. C oburn Is an assistant m em ber in radiology at the St. Jude C h ild re n ’s Research Hospital. Address requests for reprints to Dr. Turner. 1. Pratt, C.B . M anagem en t of m alignant solid tum ors in chil­ dren. P ediatr C lin North Am 19:1141 Nov 1972. 2. D eLeon, E.L., and others. N euroblastom a w ith metastasis to m axilla and m andible: review of literature and report of case. J Oral Surg 2 8:7 7 3 Oct 1970. 3. D argeon, H.M . N euroblastom a. J P ediatr 6 1:456 S ept 1962. 4. B ond, J.V. Unusual presenting sym ptom s in neuroblastom a. B r M ed J 2:327 M ay 6, 1972. 5. W illis, R.A. T h e pathology of th e tum ors of children. Lon­ don, O liver & Boyd, 1952, p 7. 6. C urran, R.C., and H arnden, D.G. T h e pathological basis of m edicine. Philadelphia, W . B. Saunders Co., 1972, p 644. 7. A ngelopoulos, A.P.; Tilson, H.B.; and S tew art, F.W. M e ta ­ static neuroblastom a of th e m andible: review of literature and re­

Dr. Stern was acting chief of dentistry, St. Jude C h ild ren ’s Research Hospital, 332 N Lauderdale, Mem phis, 38101, and an

port of case. J Oral Surg 30:9 3 Feb 1972. 8. Bradley, P.F., and Rowe, N.L. M a ndibular m etastasis of a

instructor in th e oral pathology departm ent, University of Ten­ nessee C ollege of Dentistry, M em phis. His present address is

n euroblastom a: report of case. J Oral Surg 28:781 O ct 1970. 9. A rm brecht, E.C., and W aterm an, W.A. N eu ro blastom a of the

University o f Texas Dental S cience Institute, PO B ox 20068, H ouston, 77025. Dr. T u rn er is associate professor and chairm an

m axilla: report of a case. Oral Surg 6:937 Aug 1953. 10. H offm an, S., and G reen, G.H. N euroblastom a with m etas­ tasis to th e m andible: rep ort o f case. J Oral Surg 2 4:7 5 Jan 1966.

of th e oral pathology departm ent, University of Tennessee C ol­

^

Foley’s Footnotes ------------------R epeatedly in th e lay literature nom inations have been presented fo r "th e m eanest m an .” Several of them have a relation to dentistry, usually to dentures. An episode in a short story published in th e A tla n tic M o n th ­ ly of June 1876 gives a good exam ple of this type of relationship. ‘Lisha M anchester had been frettin ’ at th e girls because they w ould hev their m other buried with her false teeth in. T h e teeth w a ’n’t none of his g e ttin ’, but he said they could be m ade over fo r him, or they’d fetch som eth in’ to sell, and it was a dretful w aste to bury ‘em , and he kept on so about 'em that they had to watch him pretty close fo r fear h e ’d take 'em out, say w h at they would! A nother “ m eanest m an” nom ination appeared in H a rp e r's N e w M o n th ly M a g a z in e of N ovem ber 1883. T h e edito r com m ents on “ a rivalry In various parts of th e country as to w h at place can produce th e m eanest m an .” T h e prize is claim ed by a man in th e W est w ho unfortunately lost his w ife just after he had procured her a new set of teeth . Th e husband fe lt th e loss deeply, because she was a good w om an, and pon­ dered how he could lessen his cost. B efore th e funeral he rem oved th e set of te eth and took them back to the dentist, with the request th a t he should have his m oney back, as they had been very little used. A noth er recom m endation for dishonorable m ention in this category of m eanness was an old curm udgeon of C oncord, NH. He m ade his w ife keep a com plete cash account. During one of his weekly exam inations of her financial report he exploded: “ Look here, Sarah, m ustard plasters, 50 cents; three teeth extracted, tw o dollars! T h e re ’s tw o dollars and a half in one w e e k fo r your ow n private pleasure. Do you think I’m m ade o f m oney?” G a rd n e r P. H. Foley

S te rn — T u rn e r— C o b u rn : N E U R O B L A S T O M A ■ 351