ORTHOPEDIC lAN IFEST:\T[O)[S J~ )[EUROFIBROMATO ' l SI

Report of Six Cases

DOXALD S. MILLER, M.D} ROWU\'" LI CHT E R, '\I.D.:I and

:\LVI:\ .I. HARRIS, ~ r.D .1

T HE ma ny and endl s 'Iy variable ma nifes tations o f von Reckling­

hausen's disea'e have claimed t he atten­tion of medical and surgical spec ia lists 'ince 179:3 when Tilesiu de cribed a case of molluscum fibrosum; indeed, a rev ie\\' of the publication ' wri tten from the obselTation posts of the in tel'lli t, t he neurologist, tbe neurosurgeon, the endo­crinologist, t he dermatologist, the hi­tologist , and the orthopedic 'urgeon i likely to be reminiscent. of the storybook blindmen and the elepha nt. In reality, of course, 'ymptom' and 'ign ' a re never restricted to specialities and never ~ppear separately and alone; they a re always multiple, variable, a nd overlapping. The first recognition of any characteristic finding should impel the search for other characteristics ~nd immediately shollid prompt the realization that neurofibroma­to is may be eausative. Becau e of t he musculoskeletal a lterations with t heir di .-abilities, pain , and co. met.ic hin­(tr'ances, the orthopedic con ul tant may \\'ell ha \'e the first diagno t ic opportuni ty.

By definition , neurofibromatosis is a congenital , hereditofamili a l neuro-ecto­dermal dysplasti c condition which be­comes progressively worse as the child grow.' older. And as the phy 'ical develop­ment is abnormal so is t he mental development substanda rd, The most obviou: a nd mo't frequent early findings a re in t he skin : the typica l "coa't of Californ ia" outline of eafe au lait ma rks and the superficia l skin tumors which vary according to rE'ported measurp.­ment : from a fe\\' millimeter ' to :30 em.

IFrom the ~ervice of Dr. Donald S. ~1i11e r , Department o( Ort,hopedlCs, Cook County H ospital. R ecei"cd (or publicatIOn, i\lay . 23, 1957.

:Attending .i\lan in Orthopedics, Cook County Hospital. . Re .. dent 111 Surgery, Cook County Hospital. Dr.

Llc!ttcr .received his 1\1edical Degree from ort.hwc tern Unlverclty :\ledical School in 1950.

·Re.ident in Orthopedic Surgery. Cook ount~· H ospHo l.

and doubtless largei'. The tumor" have underly in O' os 'eoll . ddeds, rangin)! from ob 'cure, mild morpholoo'ic irrrgularitics to bizan e ma lformatiolls, : uch n" 'co­liosis, pseudo-arthrosi ', especially of tbc t ibia, a nd giganti 'm of the axial skpldoll. J'seudo-arthrosi ' i · often pl'('('c(\t'd by 'inuous howing, eyst formatioll and

spontaneous fractUl'E's. The ('utaneou' Ie ,ion ' a rc not ,.;tati(':

they enlarge; carcinomatou ' alld ,.;ar('o­matous degeneration is not at nil Ull­common. and such callccrous ehang ,.; an' likely to be activated by ' urger~' and, possibly, by trauma. Accor ling to I'a('k and Livingston (L), out -tanding amollg ma ny ob 'er\'er ', it i better to let the lesion: a lone than to ri k meta"tati(' activat ion- unle " a ' " 'e belie\'r. thrn' a re strong eosmeti(' or function al ju ·ti­fi eations for surgical inten ' Iltion. Thesr lesions give rise to t he intere ·tin!! liag­no"'tic finding which u ually ha:; I ' E'II described a ' mushroom-like. but b ('<IUS(­

of it. frequent roentgellographie appear­ance a ' a bu tton-likE' Pl'otubt'l'all(·r. it has been termed by on of us (J) . :-; . ~ r. ) the "button sign." Thi, may be oh"cIT('(1 every where or anywhere whell 1'OC'lltgrll­ogra m ' a rf' takell for any reaSOll . \rhrll the e pedun('u lated fi broid growt h" ()('('U r a long a nerve, :arl'omatou: drlTpnl'ratioll and death may emme.

StructUl'a l abnonnalitieH ~tIId dl'fol'm­ities a re ('olTelatcd \\' ith disol'cl(')',.; of thn l'entral nelTOU 'y ·tem or prriphrral nelTe il1\'oh-ement ·, oftrll appearillg ill symptomatie di gui se a ' lll'ul'Opathi i'i or d isc : yndromr ' 0 1' ot hrl' pre,'sul'('-PJ'O­duced phenomE'n:L.

Laboratory ana lysE'S of tell : how a low 'erum pho 'phol'u ', high E'x(')'rtioll of phosphorus in thc mine, ('al(' ium ill til!' feres, allcl inl'rE'a:e I protei II ill tlw "pillal Auid .

245

245 QUARTERLY BULLETI N, N.U.M.S.

Fir/8. 1 through 3, Case 1. Fig. 1. Sm'comatous degeneration; lumbosacral root in'volvement. Fig. 2. Jleta s!a8is to the lungs. Fig. 3. M etastasis to the brain.

Six ease: of neurofibromatosis are re­ported to point up the orthopedic features of this disease as well as the complex interrelat ionship with t he characteristic involvements of other systems.

REPORT OF CASES

Case 1 (figs. 1 th rough 3). (NeU1'o­.fibromatosis with generalized fatal recurrent

sarcoma at the site of hemipelvectomy. ) A. P ., a Negro youth, aged 18, was admitted to Cook Coun ty Hospital on February 9, 1954, because of an enlarging mass. His grandmother, who raised him, recalled t hat at the age of 9 years she had noticed blotches on the boy's skin and a slight bending of the spine. During the summer of 1953, a swelling, about the size of a golfball , had appeared in

MILLER ET AL.- EU ROFIBROMATOS IS 247

Fig. 4 Case 2. Sciatica-li ke neul'opathy simulating di~c ~Ylldrome proved to be astrocytoma of the S7Jinai c~rd ill association with neuToJibromatosis.

the right thigh. A biopsy of t he lesion was made at that t ime in Mississippi . A summary of the record and the sl ide \\'ere obtai ned from the hosoi tal. The lesion \\'a!; a neurofibrosarcoma.

The patient's limp grew worse and his right thigh was painful. He appeared dull and expression less. Right-sided dor­sal scoliosi.· wa present. There were multiple pigmentations over the torso and ext remi tief.!, pa lpable cystic masses over the back and a large mass in the right thigh.

On the day of admiss ion a right hemipelyectomy was performed. The tumor could not be entirely removed. The patient was discharged 10 weeks postoperatively, free of pain and walki ng wi th crutches. Three mon ths after dis­charge, he was readmi tted because his conditi on had greatly deteriorated. Sar­coma had recurred at the site of the hemipelvectomy. The patient died a month later of generalized neurofibro­sarcomatous metastasis.

(Comment: The sarcoma had ap­parently had its origin in the lumbosacral

plexu!;. Surgery had given the patient a temporary re pite from pain but early death wa ' inevitable with or without intervention.)

Case 2 (fig. -I) (Intramedullary cord tumor- astrocyloma- a s soc i at e d wit h neurofibromatosis.) G. S., a ,,,hite man, aged 37, was adm itted to Cook ollnt): Hospital on July 3, 1956 hetau ' 01 unremitting pain. He had been under medical obsel'vation for several year '; rna es had been removed from hi ' fore­arm repeatedly and one of the'e had been over the ulnar nerve area. Residual paralysi followed the nerve reseetion ; the intrin 'ic mu culature of the hand had atrophied so that there wa loss of t he normal grip. A ' an outpatient, he had rep:wted on April 2 , 1956, that he had pain in the right t high and leg and pain in the right gluteal rna ' which did not respond to loeal heat, diathermy or cOItone injection .

There was present an as ociated neuro­dermatitis; the tubero ity of the ischium was tender ; Lasegue' ign was mildly positive; ankle reAexe' were lightly re-

H8 QUARTERLY BULLETIN, N.U. M.S.

Figs. 5 al/d 6, Ca~e 8. (iigmllislI1. Piy. 5 . .l1[(J.1·ked hcmi phyperlro phy of body. Fig. 6. Hoenl­gel/Gyra phil" (/ /'peamllce of ha'lld~ and feet shollJing hemihyperlmph y.

duced; oscillometri c readings were lIorma l (righ t, p lus 1 ; left, plus 3) . Pain persisted and was severe a nd band-like in t he lower 'ixth a rea of the right leg, causing the patient to li mp. P ain \\'as in tensified by ('oughing, sneezing 0 1' strai ning, Weak­lIe.-s of the peroneal muscle group in­('reased. Rest and ana.lgesics were not helpfu l.

:\ myelogram made on admission re­" ealed :.1n ohstruction. T he d iagnos ti c impres.-ioll \\'as of an intramedulla ry tumor assoc iated wi th neurofi broma. Spina l flu id a na lysis showed a norma l gold cun'e; negative serology; protein 2-1-2, Pandy'.- reaction -1: p lus; whi te blood cell ('ount 12.

Under general endotra(' heal anesthesia, H, lamineetomy \\'as performpd a nd an a:;l,rocytoma of the spinal cord was re­mO\'ed at the second lu mbar lm'e l. The immediate po.-toperat iH' ('ou rse was d iffi­('ult , marked by burn ing pain down t hp lC'ft leg and a drop foot. T wo months of physical therapy enabled t he pat ient to \ralk \\'ith a drop foot bra('e a nd the usC' of a ('ane.

(Comment: The symptoms of the cord tumor in this ('ase simulated a d isc syndrome which had been considered ill different ia l diagnosis.)

Case 3 (fi gs. 5 a nd 6). (From the service of Dr. Sidney Sidema n: M IIltiple osseous manifestations and axial Pll large­ment characteristic of neuTOfibroma t osi.s. ) R. D ., a Xegl'O boy, aged 15, had been born wit h abnormall y la rge arm~ a nd ri~h t leg and mul t iple unra ised pate h~r purplish di scolora t.ions of the skill . T he patient had been und er observation at t he Children's Mem(ll'i a l H ospita l. C hi­('ago, from 19-1::3 to 1950. A biop,;.)' of skin t issue made on .June 13, 19+2 showed moderate \'asf'lda ri ty of fat t issues.

Venou ' di stent ion \\'as pron ounced on the bac k and left side of the a bd omen. Li pomatous nodules could be felt in the subeu taneous t issue of t he a bdomf'n and (' he, t wall. Other observations included: a ll umbili cal herni a; ta lipes calc'aneo­\'algus of the left foot; fi brosi,' of t he right hip join t a nd loss of fun ction ; loose fl abby skin exhibit ing ichthyosis hystrix and multiple ('afe au la it spots; g:vne-

M ILLER ET AL.- NEUROFJBROMATO IS 249

comastia ; unilateral enla rgement of the tonglle, the right larger than the left side; dilatation of the veins of the legs and across the back. ; protruberent ab­domen ; hypoton ia of the musculature; Madelung's deformity ; periostitis of the right tibia; bowing and shortening of the right femUl' ; massive elephan tiasis of the right lower extremity ; megalohyper­t rophy of both hands and right upper extremity ; . enlarged glans penis; and mental dullness.

A diagnosis was made of neurofibro­matosi . A biopsy of the right wrist joint area revealed nonspecific myositis.

Pigs. 7 throltgh 9, Case 4. Pig. 7. UnusualmasN at sltpmc/cwicu/ar area. Fig. 8. Enucleation of mass. Fig . . 9. Photogmph of microscopic section of 111 y:cojibrolila in associated neurojibromatosis.

(Comment: Obviou 'Iy, in a ea 'f' of ueh C'omplex, overlapping and varied

and all-inclusive abnormalitie ', any treat­ment would be unavai ling.

Case -4 (figs. 7 through 9) . (Mltltiple osseous defects of neurofibromatous origin associated with myxofibroma at supraclav­icttlar region.) B. R. , a colored gi rl , ag d 17 years, had a hi tory of C'ulTations of the tibia dating from infaney. At the age of 9 years, under moderate trauma, her left wrist had fractured. At 15 year ', ur<Yical exploration of an extensiv soft

nodular tumor of the right upper ex­t remi ty was made; again , under minimal t rauma, t he right clav icle had fractured . The pathologist', report, obtained from Florida, said that the tumor had been a filiform neurofibroma. At L6, th supraclavicula r rna s showed an inerea'(' in size and had become mildly tender.

On examination, the patient exhibited elephant ia' i of the right upper arm, a mass at the right upraclavicular a rea and a tructural deformi ty of the ehest (pectu excavatum); celluli tis of th right ankle and foot; mul tiple cafe au lait mark hav ing the "coa -t of Cali fornia" type outline; generalized mu 'cular hypo­tonia. Underlying an irregular 'urgical scar on the entire right upper extremi ty

:250 QUA RTERL Y BULLETIN, N.U.M .S.

Figs. 10 thl'ough 12, Case 5. Fig. 10. Note mass in upper lateral aspect oj leJt leg involvillg area oj co;m/Loll 7Jeroneal nerve. !'Vlultiple pedunct.latecl cutaneous jiJJromas oj VQ1'ious sizes, typical oj neurofibromato is which w~clerwel!t sarcomatous degenera!ion. Fig. 11. Microscor:ic sectio~l s l~?w­illg sarcomatous degeneralton oj common 1Jeroneal nerve. Iitg. 12. Roen/genologlc button stgn.

" 'as a nodula r tumor \\"hich roughly follo\\"ed the course of t he radia l nerve.

A diagnosis waR made of multiple osseous defects of neurofibromatosis: 1) ('UI"\'Htures of the t ibia; 2) unusua l mass in the righ t l-lupracl a \'inda r a rea; 1I 0n­union of a fract ure and laxity oJ t he medi al al-lpect of the ela\' icle a nd ste rno­ela\' inda r arra; :3 ) right hype rtrophy of t he breast a"so(' iated with pee tus ex­(·u\·atum.

The surgical proc'edure at Cook Cou nty Il ospital in 1957 was prrformed under general endot racheal a nesthesia. A t raJ1i:i­verse .f-in('h inc·ision \\"as made, 2 inches above t he right clavic le. The brae hia l plexul-l was found to encirc le the mass; the mass was carefully en ucleated (fig .8) a nd elosure aceomplished in layers. A biopsy dist'losed a myxofibroma assoel ­a ted ,,·i th neurofi broma tosis.

(Comment: The congenital aspects of t his complex of systemi c involvements is amply illustrated by thi s ease as " 'e ll as by the preeeding one. )

Case 5 (fi g '. 10 throllgh 12) . (Fib ,-o­sarcoma of lhe common peroneal nerve. N.B. " Button Sign," Fig . 12.) E. P ., a Xegro, aged 28, \\"as admi tted to Cook Coun ty Hospital on Oetober 10, 1956, because of s\\"(:dling of the lateral aspe(·t of thE' left upper leg of :3 months' dura­ti on. The swelling \I'as at first slol\"­growing but became more rapid during the last two or t hree " 'eeks before ad­mI SSIon. T he left Irg had been st rll ck by a heavy " 'right 10 years prm· iously. T he patient remembered hav ing the multiple pedunculated cutaneous lesions of varyi ng sizE'S on his trunk and ext rem­it ies since earli est childhood. M ultiple ('afc all la it marks \\"el'e a lso pre.-ent.

MILLER ET Al..- NEUROFIBROMATOSI 2St

Pigs. 18 1hmugh 16, Case 6. Clinical (wd mentgenogmph-ic apfJearaltce~ in cau oj nettroJibro­matosis manijesting pse ltdo-a1·th7-o.~i,~ and .I1odelullg's dejurilli ty.

252 QUARTERLY BULLETIN, N.U.M.S.

Th re was a firm bluish rna , :3}1 inche' hy -t inches, on the upper lateral aspect of the left leg involving the a rea of the ('ommon prroneal nerve. Th a rea wa ' \\'arm and the mass felt adherent to deeper trueture;;. Th re was extreme hyper­

e ihesia O\'er the lateral aspect of the leg and the lateral and dorsal aspects of the foot. The foot drop \\'as complete, \\'ithou t foot or toe exten ion.

A roentgenogram di closed the in­tere. ti ng hu tton-I i ke protu berance in the filmed area .. \ hiopsy made a week after admil;sion at the time of amputation of the left leg confi rmed the impression of neul'Ofibromatosi . and di closed neuro­fibro .. arC'oma of the common peroneal nerve. The laboratory reported: non­protein nitrogen G2 ; creatin ine 1.:3; nega­tive serology.

(Comml'llt: The "button sign" is a di ·dosure of neurofibromato is even in the ah .. enee of many of the other charac­teri ticl; of the disea..:e, which, however, i .. unlikely inasmuch as t he man ife tation arc multiple. I arcomatou degeneration in the peripheral nerve is a recognized eriouslv complicating and fatal even­

tualitv 'of neurofibromatosi .) Ca~e 6 (figs. 1:3 through 16). (P seudo­

arlhrosi. as ocialed with ]\t[ adelung' s de­fonnily in generalized neurofibromalosis.) L. L. , a ~eCTro boy, aged 10 years, pre ented with bowing of . t he lef t t ibia and fibula. P eudo-arth ro J .. had resulted aft er a douhle osteotomy in J anuary, 195-+. In ;\Ia rch of the ame year, a Ru h pinninO' of the tihia had been done, followed bv a bone graft and removal of the pin iJ; August. The patient wore long-leg plaster casts until February, ] 957. I urgical scar ' we re ob rved on phy. 'ieal examination. Madelung's de­formity of the left wrist was pre ent ; cafe au lait diseoloration. were observed on the left th igh and dorsum of the rig~t hand ; typical nodule' co~ l.d b~ felt IJ1

the skin of these extremltJe. . fhe left leg was an inch horter than t he right. A cousin was aid to have one arm larger than the ot.her and t.he b?y's father wa aid to have a large abdomll1a l brown birthmark.

Report of the biopsy made of two of the skin lesions on t he thigh on February 8, 1957, confirmed the impression of neUl'ofihromatosi .

(Comment: The presence of pseudo­arthrosis immediately should sugge t the po sibility of neurofibromato is in dif­ferential diagnosis. Confirmation is al­ways readily available in this disease in t he numerous as ociated findings.)

SUMMAHY AN D CO 'eL USIONS

Reports of six cases of neurofibro­mate. i · exhi biting mu ltiple musculo­skeletal manife tations in association with characteri stic neurologic, dermatologic and endocrinologic involvements have been prpsented.

Case 1 is an example of a rcomatou ' degeneration of the neurofibroma which apparent ly had t hei r origin in the lum­bosacralroot. Scoli osis was a prominent concomit.ant fin.ding.

A case of 'iatica-like neuropathy (Case 2) proved to be an a trccytoma of the pina l cord. The el inical sympt.oms

simulated tho e of a disc syndrome but different iation was quickly made by the presence of other characteri stic symptoms of neurofibromatosi~.

Two cases of gigantism (Cases 3 and 4) have been deta iled. Case 4 represrnts also t he typical mul tiple osseous de­formities and pre ents, in addi t ion, an in teresting tumefaction, a myxofi broma; t his appeared after a clavicular fracture which was incurred on slight t rauma.

Case 5 is another example of sarco­matous degeneration which disclosed roentgenographically what we like to term the " button sign." This sign, we believe, is immediately pathognomonic.

Case 6 represents pseudo-art.hrosi of the t ibia associated with Madelung's deformity which are not infrequent cor­relatives in generalized neurofibromatosis.

Trauma, probably, and surgery, un­doubtedly, activat.e malignant degenera­t ion in neurofibromatou ' lesions. Unless trong cosmetic or functional indjcatjons

make surgery worth t.he risk, it js best to let t.he Ie ions a lone. Roentgen and radium t.herapy a re complet.ely ineffec­tive.

R EFERENCE

1. Pack G. T . and Livingston, E. M.: Treat­ment of Cancer and Allied Diseases, r\ ell' York. Paul B. Hoeher, p. 2024, 1940.