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Solitary myeloma of mandible
Report of a Case Ii. I. Il. Whitlock, M.D.S.(Lond.), F.D.S.li.C.S.(E’ng.j, and N. (1. Hu.ghes, F.R.C.S.(Eng.), Belfast, Nortlwrn Ireland
cases of multiple myeloma with jaw lesions are fairly common in A the literature, and a few such cases have been first diagnosed from the jaw lesion,l-’ the solitary myeloma or plasmacytoma in the jaws is an extremely LTHOWFI
rare condition. As far as can be ascertained, only ten cases have been r+ ljorted; 5-13of these ten cases, six occurred in t.he mandible and four in the maxilla. It should be stressed, however, that lesions which show heavy infiltrations of plasma cells are fairly common in the oral region. Although most c:f t.hese are inflammatory lesions which histologically can easily bc differentiatotl from plasma.-ccl1neoplasms, there may be dificulty in diagnosing a given stat’tion. 1)oubt can therefore be placed on the accuracy of t.he diagnosis of some of these reported cases, and it is quite possible that a few were not ncoplastic but. intiammatory in origin. Thrrct are no apparent histologic criteria by which we arc able to distinguish solitary from multiple myeloma. Consequenbly, there has been much argument as to whethtlr or not the single lesion is a forerunner of t.he generalized typca. EwingI considered multiple myeloma a neoplasm characterized by multiple foci of origin and rarely metastasized. Others, including Cutler and associates.“’ believe tha.t multiple myeloma may originate as a single lesion with subsequent metastases to other bones. Most authorities t.oday believe in t.he multicentric* origin of myeloma, but a single survey of the skeletal sysbem is not sufficient to exclnde it since it,s multicent,ric origin may not manifest itself for several years. Boyd,16 however, states that the plasmacytoma is a rare, localized variant. of the generalized type, that it is usually composed of well-differentiated plasma cells rather than highly neoplastic cells, and that it is amenable to treatment. Christopherson and &Iiller,6 in reviewing nin&y-four cases of the solitary tppc occurring in bone, also believe it to be a clinical entity, unrelated to multiple myeloma, with a favorable prognosis. From a study of the reported cases of the solitary type of myeloma Wcurring in the jaws, notably those cases described by Christopherson a.nd Miller,” Lane.’ Davis and Havens,‘O and Hinds and Pleasants,13 there does seem From the Plastic
and Maxilla-Facial
Centre, 23
Throne
Hospital,
Belfast,
Northern
Ireland.
WHZTLOCK
24
OS., O.M. & O.P. January, 1960
AND HUGHES
to be some basis for this belief. Whereas multiple myeloma runs a natural course of from a few months to a.n average of two years after diagnosis, the solitary myeloma may pursue a benign course for several years with apparent cure. The following case of a supposedly solitary myeloma with no recurrence five years after operation gives further support to this view. Although perhaps it is not a dist.inct entity, suueha tumor behaves clinically in quite a different way from the generalized type. In this respect, it bears some resemblance to the reticulum-cell sarcoma.. CASE REPORT
The patient, a 6i-year-old retired farmer, was referred from another hospital in 1953 for diagnosis and treatment of a large, rounded, nontender swelling at the point of the chin. History.-The patient had first noticed a swelling on the right side of his lower jaw some sixteen years earlier. This swelling had gradually increased in size over the years until it had now become most pronounced over the point of the chin. There was a history of an
Fig. L-Preoperative
appearance showing
swelling
on chin.
operation on the jaw twelve years previously and another eight years previously. Both procedures had been performed via an intraoral approach. (An attempt made at the hospital to obtain some case notes regarding the operations was unsuccessful.) Recently the patient had become worried %bout his appearance, and he also had oncountered some difficulty in eating since there was only one area on the right side of the mandible which was not tender when he chewed upon it. There was nothing relevant in the past medical history; the patient had always enjoyed good health. Examinatdm.General : The patient was a chcerfuh olderly-looking man with no cyanosis, anemia, or finger-clubbing. The physical examination revealed no abnormality. Extraoral findings : A large, rounded, fluctuant but painless swelling about the size of a tennis ball was present at the point of the c:hin (Fig. 1). The overlying skin was thinned but of normal color and freely mobile. The lower border of the mandible could be
SOLITARY
Volun1e I? NnmLwr I
MYELOMA
OF K4NDIRl,E
2:;
palpated on both sides from the angle to the premolar region, but the external surface of There wx3 no nerve palsy, aucsthcsi:1, the bone on the right side felt expanded and uneven. or lymphadenopathy. i 3 2 1 / 1 2 3 i 5 ‘t-h! lO\WI Twelve teeth were prrsont : -.- _A Zwtraoral findtigs: 6 i 8’ I left first, second, and third molars were cxtrcmely loose. Tllc! lower alveolus was cxpautlt~~l both buccally and lingually from the q region to the 13 rcgion. The mucous memluauc regioll, had ulcerated, revealing t,he underlying growth, in thrrc areas: the Fi region; the m, where the growth had become pedunculatid; and from the -g, region to the 7 region, wlt~~rc there was a large, oval-shaped, ulcerated arca obliquely wt ( k’ig. 2). Wo provisional vlinic*:tl diagnosis
~\‘Rs made.
Fig.
?.-Ulceration
in mouth.
Roentgenographic findings : There was a polycystic expansion of the mandible from the right ramus to the region of the lower left first molar (Fig. 3). At the symphysis (Fig. 4) there was a spherical shadow corresponding to the fluct,uaut area on the chin, across whic!h traversed radiating spicules of bone in the form of a sunray. A provisional diagnosis of adamantinoma, or endosteal osteoelastoma, was made. Osreogenie sarcoma was also considered but was ruled out bcxcausr of the long history. -4 biopsy was now considered &cause of the disfigurement,, however, it was decilled that a radical operation involving removal of the fluct.nant growt.11 at the point of the chin should be performed. Operation.-Following induction of endotracheal anesthesia, two curved submandibular incisions wero made to enclose the swelling over Dhe chin. From t,heir juncture they nerc This part of the growth was fount1 to extended on either side to the angles of the mandible. be a soft solid, and it shelled out quite easily with the overlying skin attached. The rest af the growth was contained within the expanded body of the mandible; on both sides the outer plate was much thinned and had become deficient in several places. There ww uo After the remainder of t.hc outer expansion at t.hr lower border, which was still inta&. plate had been peeled off with bone nibblers, the inside was found to be riddled with multiple cavities of varying sizes separated by iucomplete bony septa; it cont.ained a brownish fluid and was lined by what appeared to be an epithelial lining. The growth extcndtrl from the ramus on the right side to the premolar region on the left side.
26
WHITLOCK
AND HUGHES
0.5.. O.M. & OP. January, 1960
Volume
SOLITARY
15
Kumber I
MYELOMA
OF MANDIBLE
27
On the basis of this clinical appearance, the lesion was assumed to be an adamantiuoma. Because of its extent, however, a radical resection wit.h an immediate bone-graft replacement was not feasible, and therefore a radical local removal was decided upon. All the cavities were carefully curetted, and the bone was trimmed back with bone nibblers until only the lingual plate remained. The lower left first, second, and third molars were then removed, and great care wss taken in repairing the mucous membrane of the mouth, especially wharc! it had been ulcerated. The external incision was next repaired in layers, and two corrugated. rubber drains were inserted extraorally. Healing was quite uneventful. The drains were removed after forty-eight hours, and in twelve days the patient was discharged From 111( hospital wvit.h the mouth and external incisions completely heah~d. Pathologic
Report
(1. B. E. Kramer).-
Yncroscopk: Two specimens were submitted. The first wss a heart-shaped soft-tissue mass measuring 30 by 24 by 20 mm. The surface was brown and mainly smooth, and tin% cut surface appeared a ‘ ‘ marbled’ ’ brown and white. The second specimen was a roughl: spherical tumor, 6.5 cm. in diameter. The superficial surface was pa.rtly covered by a halfcircle of skin 7 cm. in diameter; the deep surface was rough and r.ont,ainnd embedded spiculc> of bone. When cut, the tumor was mainly firm and chocolate brown; it xppeart~tl to I)(, bounded peripherally by a thin layer of bone. Microwopic : The first tumor specimen was mainly composed of dcnsc!ly packed rouutlotl and polygonal cells, each having a moderately bulky and sometimes “foamy” eosinophilir c.ytoplasm and a single large nucleus showing a very clear ehromatin pattern (Fig. 5, :1 am1 B). There was some variation in nuclear size, and scatt.ered throughout the tissue warm cells with giant nuclei. The mass was moderately vascular and showed numerous awas ol hemorrhage. l+ripherally, in some areas there was a fibrous capsule, but part of the surface was Presumably, t.ltis are>; oovelod with necrotic tissue and fibrin infiltrated with polymorphs. reprcsentod thr site of oral ulceration. S&ions from the larger tumor mass (second specimen) ahowed essentially the sann histologic appearances. Iling9bosis
:
Atypical
myeloma.
1’oetoperatiz;e Obseruat&w.-Two months later (January, 1954) the patieut was readmitted t.o t.he hospital for further investigations in view of the possibility of his having generalized myeloma. A complete skeletal roentgenographic examination, however, failed t4) show any other lesions, and no further cavities had developed in the mandible. There was, unfortunat.ely, a fracture at the symphysis region, but clinically only slight pathologic movement. was elicited, with no displacement or pain. It was not known whet,her this fracturtt had occurred at the time of surgery or whether a pathologic fracture had taken place subs**. quent t,o the operation. There was a slight evening rise in Cemperature, and a slight tr;u*(’ of Rtmcte-Jones proteose was found in the urine. All hematologic t&s were within normal limits. Hemoglobin was 85 per cent = 12.6 Gnl. Granulopoiesis was normal, A Ibone marrow report revealed that the marrow was active. Occasional plasmacytes were seen but in illand crythropoiesis was normoblastic in type. suffieirnt numbers to substantiate a diagnosis of multiple myeloma. A study by I). W. Neil1 of serum samples, including clectrophoretic pattern, rcveahnd t,hat total serum proteins were 9.2 Gm. per cent, and a qualitative assessment of the cleetrophoretie distribution showed a raised gamma globulin with some increase in the beta globulin. This was consistent with the state of affairs found in generalized myeloma. Electrophoresis, the migration of colloidal particles under the influence of an electric current, gives us a method of separating the various blood proteins which cannot be sepThe separation in this case was done by arated chemically or by other physical methods. the horizontal paper &rip technique described by Grassmann and collr%gues~~ with minor modifications.1 e The densities of the dyed protein bands on the dried strips were evaluattrd The protein concentrations corresponding to by graphic plotting with a strip densitometer. the curve so obtained were derived by planimetrie measurement.
WlIlTLOCH
28
Fig.
6.-Photcmnicrogmphs
of lesion.
iiN11
HUGHEB
(IUagniflcation:
O.S., O.M. 110.1’. January, 1960
A.
x150;
B,
X425.1
the patient was again admitted tll In April, 1955, sixteen months after the oporation, He had no complaints, and his general health had remained ~OWI the hospital for a chrckup. A complete skeletal roentgenographic examination was ttgaiu during the intervening period. negative, and this time the x-ray pictures of the mantlilde showed that bony regeuwxtio~~ hack taken place in the cystic areaa which had been ruret.ted (Fig. 6,1. h fracture was ~1ill During present in the symphysis region, howevcar, but this WLS not. t.rouMing the paticlnt. this stay in the hospital the patient was fitted wit,11 a lowcar dtWturt2. Thcb llc~rutdologic eramiuation Joues protcose in the urine.
Pig. Ii.--l&teral
roentgenogrnm
was negative
and this times tllcw
of left body of nmntlible
WlS no trm?! of 1~PllV1~
two years after
operation.
‘l’hc total protein 011 this occasion was 7.4 GM. p(Ar a’(*nt, :MI~ thr ctrntributicms indivitluril protein fractions w\‘tlr(a as follows: 4.5 0.3 il.4 0.7 I.0
Albumin Alpha, globulin Alpha2 globulin Reta globulin Gamma globulin This distribution welt within the limits Thus, after
on1. Gm. Gn1. Gni. Gm.
pc” per prr prr *“‘r
wut ceut Wilt cent (*lout.
was quite normal, the apparent slight rise iu gamuut of experimeutal error of the method usetl.
sixteen
months the serum protein
puttcru
had twn
01’ tills
globulitr
b&l::
wst~orcd to Nrtmd.
In February, 1957, three years and two months after the operetion, the! paticxnl. ww His gt9icral hdth was still g(;ootl, :mtl iw again admitt~f~d to tlw hospital for investigat.ions. was even wrariug his lower denture. RoentgenogrtLphic: and hc~matoloyir: c~xaminaCous ww nc~gativr, ant1 thtlrr was no Hence-Jones proteosr in the, urine. At this tinw
the total
.\lbumin Alpha, globulin -Mph& globulin &+.a. globulin Gamma globulin
protein
was 7.4 Gm. per Ck:nt, with Ib Ilistribut.ion 3.3 0.5 0.9 0.9 1.8
Gm. Gm. Gm. Gm. Gm.
per par per per pw
ilH
PoltowS:
c:cnt cent ccut ccut cent
WHITLOCK
30
OS.. O.M. b O.P. January. 1960
AND HUGHES
While this pattern W&Bnot normal, the abnormality was a result of a fall in the albumin level with a corresponding rise in the globulin fraction. It would not appear to bear any relationship to the specific effect of plasmacytoma. A further check was made in December, 1958. The patient was still well (Fig. 7). The serum study wae reported as follows: “The pattern shows marked reduction in albumin with slight rise in gamma globulin plus marked rise in alpha, globulin. There is no suggestion of myelomatosis, but the pattern resembles that found in rheumatoid arthritis. There is definitely no indication of the rise in gamma-globulin which coincided with his plasmaaytoma just after it was removed.”
Fig.
‘I.-Appearance
flve years after
operation.
DISCUSSION
The multiple myelomas are considered malignant tumors of the bone marrow in which the marrow cavity is expanded by a soft gray or red mass, but since there is no corresponding bone formation the cortex becomesthinned and pathologic fractures are common. The tumor, which varies from the size of a pea to the size of an orange, affects chiefly the sternum, ribs, and vertebrae with the skull, pelvis, and clavicle the next most frequently affected. The long bones are the least likely to be involved. The tumor characteristically consists of plasma cells, but these do not show typical staining reactions and their nuclei are larger and do not have halos. Some pathologists have attempted to classify myeloma as to cell type (plasma, myeloma, etc.). Lichenstein and Jaffe,le however, state that the neoplasm has a single cell type. They say that this should not be subdivided into various subvarieties but that the cells, which may vary in their morphology, should be designated as the myeloma cells. The disease, however, is not merely a bone marrow tumor; it is also characterized by abnormal protein in the blood, presumably produced by the enormous numbers of these “myeloma” tumor cella. This protein may act in different ways : (1) it may be excreted in the urine as Bence-Jones proteose (50 per cent of cases), and in advanced casesit may cause a blockage of the tubules
phm&
1;
SOLITARY
MYELOMA
OF MANDIBLE
31
with subsequent renal failure; (2) it may be retained in the blood, causing A hyperproteinemia with a raised serum globulin, which probably accounts for the fact that in such casesthere usually is only a tract! of Bence-Jones prot.eoxc! in the urine; or (3) it may possibly be deposited in the tissues as atypical amyloid. Due to the destruction of the marrow, anemia is also a symptom ill a high proportion of cases. Hist.ologically, biochemically and electrophoretical.ly, the tumor in t.be ca.sc reported here resembled the lesion seen in multiple myeloma. That. the biochemical changes and the electrophoretic pattern were only mild is presumed 10 be due partly to the fact t.hat the lesion was confined to the mandible and part.l> to t.he fact t,hat tests were not performed until two months after the operation. It is interesting to note that in the case reported by Lane’ a. snvall localizetl plasmacytoma of the mandible caused an increase in t.he serum globulin ratio which began to return to normal two months after operation and was compltrtt~l> normal five months later. The general belief now is that myelomas are multicentric in origin and thal, although there is a possibility of a solitary lesion being first. discovered, lesions in other bones very quickly follow. It might, be argued that, inasmuch as ollr pat.ient remained free from the disease five years after operat.ion, thc?re is ;I possibility that myelomas start as a local disease and early removal will result. in a cure. In our case, however, there was only a thorough curettage instead o(: complete local removal, but this st.ill resulted in complet,c hc4inp. In t.his rtlspecb our case differs from that reported by Lane.7 who performrd a compl(jte excision of the lesion, but in all ot.her respects the rasfhsHW fry similar. As yet there is no means of differentiating plasma-cc11tumors. Thcxr two eases,however, as well as the other nine reported in the literature. lend grounds -for t.he belief that there occurs in the jaws a tumor which, although not a tlistinct clinical mt.it.y, has quite a different clinical course from gencralizt4 myeloma and is amenable to surgery, Such a tumor might be cousidorrd a solitary myeloma. Only time will Ml, however, whether or not such a tumor will develop into one of the generalized variety. SUMMARY
1. A case in which an extensive myeloma of the mandible healed despite the fact that only a curettage was performed is reported. The patient. has rema.incbd well after five years, and so far generalized myeloma has not developed. 2. It is suggested that there is evidence to show that t.hcre occurs in thr jaws a plasma-cell tumor which runs a differrnt course from the generaliz variety and is amenable to surgical t.reatment. This might br ronsidered a ROIL tary myeloma.. We wish to thank Mr. I. R. H. Kramer, M.D.S.(Lond.). Head of the Pathology 1)~. partment, Eastman Dental Hospital, for pathologic reports and advice given in the prepars.. tion of this paper, and Mr. D. W. Neill, M.&z., F.R.I.C., Principd Scientific Oftlcer, Royal Victoria Hospital, Belfast, for the reports on the serum protein electrophoratie studies.
32
WHITLOCK
AND HUGHES
0,s..
O.M. & OP. .lanuary, I%0
1. Wolff, E., and Nolan, L.: Radiology 42: 76, 1944. 2. Meloy, T. M., Jr., Gunter, J. H., and Sampson, D. A.: Am. J. Orthodontics & Oral Surg. 31: 685, 1945. 3. Calman. H.: ORAL SURQ..ORAL MED. & ORAL PATH. 6: 1302. 1932. 4. Bruce, K. W., and Boyer,‘R. Q. : ORAL SURQ.,ORAL MED. & &AL PATH. 6: 729, 1953. 5. Spiteer, R., and Price, L. W.: Brit. M. J. 1: 1027, 1943. 6. Christopherson, W. M., and Miller, A. J.: Cancer 3: 240, 1950. 7. Lane, 8. L.: ORAL Suno., OR& MED. & ORAL PATH. 5: 434, 1952. 8. Navarro-Sanehe, F.: Odontoiatria (ma&.) 9: 105, 1952. 9. Mancusi-Materi, G. : Gior. ital. chir. 10: 274, 1954. 10. Davis, G. D., and Havens, F. Z.: Proc. Staff Meet. Mayo Ciin. 29: 569, 1954. 11. Villa, V. G., and Laico, J. E.: Philippines Med.-Dent. J. 1: 33, 1955. 12. Fink, K.: Medizinische 22: 812, 1955. 13. Hinds, E. C., and Pleasants, J. E.: ORAL SURG., ORAL MED. & ORAL PATH. 9: 193, 1956. 14. Ewing, J.: A Treatise on Tumours, ed. 3, Philadelphia, 1928, W. B. Saunders Company, p. 321. 15. Cutler, M., Busche, F., and Cantril, S. T.: Burg. Gynec. & Obst. 62: 918, 1936. 16. Royd, F-V.: Pathology for the Surgeon, ed. 7, Philadrlphia, 1954, TV. B. Saunders Company, p. 576. 17. Grassmann, W., Hannig, K., and Knedel, M.: Deutschc med. Wchnschr. 76: 333, 1951. 16. Neily, R. A., and Neill, D. W.: Nature, London 176: 33, 1955. 19. Lichenstein, L., and Jaffe, H. L.: A. M. A. Arch. Path. 44: 207, 1947.
cases of multiple myeloma with jaw lesions are fairly common in A the literature, and a few such cases have been first diagnosed from the jaw lesion,l-’ the solitary myeloma or plasmacytoma in the jaws is an extremely LTHOWFI
rare condition. As far as can be ascertained, only ten cases have been r+ ljorted; 5-13of these ten cases, six occurred in t.he mandible and four in the maxilla. It should be stressed, however, that lesions which show heavy infiltrations of plasma cells are fairly common in the oral region. Although most c:f t.hese are inflammatory lesions which histologically can easily bc differentiatotl from plasma.-ccl1neoplasms, there may be dificulty in diagnosing a given stat’tion. 1)oubt can therefore be placed on the accuracy of t.he diagnosis of some of these reported cases, and it is quite possible that a few were not ncoplastic but. intiammatory in origin. Thrrct are no apparent histologic criteria by which we arc able to distinguish solitary from multiple myeloma. Consequenbly, there has been much argument as to whethtlr or not the single lesion is a forerunner of t.he generalized typca. EwingI considered multiple myeloma a neoplasm characterized by multiple foci of origin and rarely metastasized. Others, including Cutler and associates.“’ believe tha.t multiple myeloma may originate as a single lesion with subsequent metastases to other bones. Most authorities t.oday believe in t.he multicentric* origin of myeloma, but a single survey of the skeletal sysbem is not sufficient to exclnde it since it,s multicent,ric origin may not manifest itself for several years. Boyd,16 however, states that the plasmacytoma is a rare, localized variant. of the generalized type, that it is usually composed of well-differentiated plasma cells rather than highly neoplastic cells, and that it is amenable to treatment. Christopherson and &Iiller,6 in reviewing nin&y-four cases of the solitary tppc occurring in bone, also believe it to be a clinical entity, unrelated to multiple myeloma, with a favorable prognosis. From a study of the reported cases of the solitary type of myeloma Wcurring in the jaws, notably those cases described by Christopherson a.nd Miller,” Lane.’ Davis and Havens,‘O and Hinds and Pleasants,13 there does seem From the Plastic
and Maxilla-Facial
Centre, 23
Throne
Hospital,
Belfast,
Northern
Ireland.
WHZTLOCK
24
OS., O.M. & O.P. January, 1960
AND HUGHES
to be some basis for this belief. Whereas multiple myeloma runs a natural course of from a few months to a.n average of two years after diagnosis, the solitary myeloma may pursue a benign course for several years with apparent cure. The following case of a supposedly solitary myeloma with no recurrence five years after operation gives further support to this view. Although perhaps it is not a dist.inct entity, suueha tumor behaves clinically in quite a different way from the generalized type. In this respect, it bears some resemblance to the reticulum-cell sarcoma.. CASE REPORT
The patient, a 6i-year-old retired farmer, was referred from another hospital in 1953 for diagnosis and treatment of a large, rounded, nontender swelling at the point of the chin. History.-The patient had first noticed a swelling on the right side of his lower jaw some sixteen years earlier. This swelling had gradually increased in size over the years until it had now become most pronounced over the point of the chin. There was a history of an
Fig. L-Preoperative
appearance showing
swelling
on chin.
operation on the jaw twelve years previously and another eight years previously. Both procedures had been performed via an intraoral approach. (An attempt made at the hospital to obtain some case notes regarding the operations was unsuccessful.) Recently the patient had become worried %bout his appearance, and he also had oncountered some difficulty in eating since there was only one area on the right side of the mandible which was not tender when he chewed upon it. There was nothing relevant in the past medical history; the patient had always enjoyed good health. Examinatdm.General : The patient was a chcerfuh olderly-looking man with no cyanosis, anemia, or finger-clubbing. The physical examination revealed no abnormality. Extraoral findings : A large, rounded, fluctuant but painless swelling about the size of a tennis ball was present at the point of the c:hin (Fig. 1). The overlying skin was thinned but of normal color and freely mobile. The lower border of the mandible could be
SOLITARY
Volun1e I? NnmLwr I
MYELOMA
OF K4NDIRl,E
2:;
palpated on both sides from the angle to the premolar region, but the external surface of There wx3 no nerve palsy, aucsthcsi:1, the bone on the right side felt expanded and uneven. or lymphadenopathy. i 3 2 1 / 1 2 3 i 5 ‘t-h! lO\WI Twelve teeth were prrsont : -.- _A Zwtraoral findtigs: 6 i 8’ I left first, second, and third molars were cxtrcmely loose. Tllc! lower alveolus was cxpautlt~~l both buccally and lingually from the q region to the 13 rcgion. The mucous memluauc regioll, had ulcerated, revealing t,he underlying growth, in thrrc areas: the Fi region; the m, where the growth had become pedunculatid; and from the -g, region to the 7 region, wlt~~rc there was a large, oval-shaped, ulcerated arca obliquely wt ( k’ig. 2). Wo provisional vlinic*:tl diagnosis
~\‘Rs made.
Fig.
?.-Ulceration
in mouth.
Roentgenographic findings : There was a polycystic expansion of the mandible from the right ramus to the region of the lower left first molar (Fig. 3). At the symphysis (Fig. 4) there was a spherical shadow corresponding to the fluct,uaut area on the chin, across whic!h traversed radiating spicules of bone in the form of a sunray. A provisional diagnosis of adamantinoma, or endosteal osteoelastoma, was made. Osreogenie sarcoma was also considered but was ruled out bcxcausr of the long history. -4 biopsy was now considered &cause of the disfigurement,, however, it was decilled that a radical operation involving removal of the fluct.nant growt.11 at the point of the chin should be performed. Operation.-Following induction of endotracheal anesthesia, two curved submandibular incisions wero made to enclose the swelling over Dhe chin. From t,heir juncture they nerc This part of the growth was fount1 to extended on either side to the angles of the mandible. be a soft solid, and it shelled out quite easily with the overlying skin attached. The rest af the growth was contained within the expanded body of the mandible; on both sides the outer plate was much thinned and had become deficient in several places. There ww uo After the remainder of t.hc outer expansion at t.hr lower border, which was still inta&. plate had been peeled off with bone nibblers, the inside was found to be riddled with multiple cavities of varying sizes separated by iucomplete bony septa; it cont.ained a brownish fluid and was lined by what appeared to be an epithelial lining. The growth extcndtrl from the ramus on the right side to the premolar region on the left side.
26
WHITLOCK
AND HUGHES
0.5.. O.M. & OP. January, 1960
Volume
SOLITARY
15
Kumber I
MYELOMA
OF MANDIBLE
27
On the basis of this clinical appearance, the lesion was assumed to be an adamantiuoma. Because of its extent, however, a radical resection wit.h an immediate bone-graft replacement was not feasible, and therefore a radical local removal was decided upon. All the cavities were carefully curetted, and the bone was trimmed back with bone nibblers until only the lingual plate remained. The lower left first, second, and third molars were then removed, and great care wss taken in repairing the mucous membrane of the mouth, especially wharc! it had been ulcerated. The external incision was next repaired in layers, and two corrugated. rubber drains were inserted extraorally. Healing was quite uneventful. The drains were removed after forty-eight hours, and in twelve days the patient was discharged From 111( hospital wvit.h the mouth and external incisions completely heah~d. Pathologic
Report
(1. B. E. Kramer).-
Yncroscopk: Two specimens were submitted. The first wss a heart-shaped soft-tissue mass measuring 30 by 24 by 20 mm. The surface was brown and mainly smooth, and tin% cut surface appeared a ‘ ‘ marbled’ ’ brown and white. The second specimen was a roughl: spherical tumor, 6.5 cm. in diameter. The superficial surface was pa.rtly covered by a halfcircle of skin 7 cm. in diameter; the deep surface was rough and r.ont,ainnd embedded spiculc> of bone. When cut, the tumor was mainly firm and chocolate brown; it xppeart~tl to I)(, bounded peripherally by a thin layer of bone. Microwopic : The first tumor specimen was mainly composed of dcnsc!ly packed rouutlotl and polygonal cells, each having a moderately bulky and sometimes “foamy” eosinophilir c.ytoplasm and a single large nucleus showing a very clear ehromatin pattern (Fig. 5, :1 am1 B). There was some variation in nuclear size, and scatt.ered throughout the tissue warm cells with giant nuclei. The mass was moderately vascular and showed numerous awas ol hemorrhage. l+ripherally, in some areas there was a fibrous capsule, but part of the surface was Presumably, t.ltis are>; oovelod with necrotic tissue and fibrin infiltrated with polymorphs. reprcsentod thr site of oral ulceration. S&ions from the larger tumor mass (second specimen) ahowed essentially the sann histologic appearances. Iling9bosis
:
Atypical
myeloma.
1’oetoperatiz;e Obseruat&w.-Two months later (January, 1954) the patieut was readmitted t.o t.he hospital for further investigations in view of the possibility of his having generalized myeloma. A complete skeletal roentgenographic examination, however, failed t4) show any other lesions, and no further cavities had developed in the mandible. There was, unfortunat.ely, a fracture at the symphysis region, but clinically only slight pathologic movement. was elicited, with no displacement or pain. It was not known whet,her this fracturtt had occurred at the time of surgery or whether a pathologic fracture had taken place subs**. quent t,o the operation. There was a slight evening rise in Cemperature, and a slight tr;u*(’ of Rtmcte-Jones proteose was found in the urine. All hematologic t&s were within normal limits. Hemoglobin was 85 per cent = 12.6 Gnl. Granulopoiesis was normal, A Ibone marrow report revealed that the marrow was active. Occasional plasmacytes were seen but in illand crythropoiesis was normoblastic in type. suffieirnt numbers to substantiate a diagnosis of multiple myeloma. A study by I). W. Neil1 of serum samples, including clectrophoretic pattern, rcveahnd t,hat total serum proteins were 9.2 Gm. per cent, and a qualitative assessment of the cleetrophoretie distribution showed a raised gamma globulin with some increase in the beta globulin. This was consistent with the state of affairs found in generalized myeloma. Electrophoresis, the migration of colloidal particles under the influence of an electric current, gives us a method of separating the various blood proteins which cannot be sepThe separation in this case was done by arated chemically or by other physical methods. the horizontal paper &rip technique described by Grassmann and collr%gues~~ with minor modifications.1 e The densities of the dyed protein bands on the dried strips were evaluattrd The protein concentrations corresponding to by graphic plotting with a strip densitometer. the curve so obtained were derived by planimetrie measurement.
WlIlTLOCH
28
Fig.
6.-Photcmnicrogmphs
of lesion.
iiN11
HUGHEB
(IUagniflcation:
O.S., O.M. 110.1’. January, 1960
A.
x150;
B,
X425.1
the patient was again admitted tll In April, 1955, sixteen months after the oporation, He had no complaints, and his general health had remained ~OWI the hospital for a chrckup. A complete skeletal roentgenographic examination was ttgaiu during the intervening period. negative, and this time the x-ray pictures of the mantlilde showed that bony regeuwxtio~~ hack taken place in the cystic areaa which had been ruret.ted (Fig. 6,1. h fracture was ~1ill During present in the symphysis region, howevcar, but this WLS not. t.rouMing the paticlnt. this stay in the hospital the patient was fitted wit,11 a lowcar dtWturt2. Thcb llc~rutdologic eramiuation Joues protcose in the urine.
Pig. Ii.--l&teral
roentgenogrnm
was negative
and this times tllcw
of left body of nmntlible
WlS no trm?! of 1~PllV1~
two years after
operation.
‘l’hc total protein 011 this occasion was 7.4 GM. p(Ar a’(*nt, :MI~ thr ctrntributicms indivitluril protein fractions w\‘tlr(a as follows: 4.5 0.3 il.4 0.7 I.0
Albumin Alpha, globulin Alpha2 globulin Reta globulin Gamma globulin This distribution welt within the limits Thus, after
on1. Gm. Gn1. Gni. Gm.
pc” per prr prr *“‘r
wut ceut Wilt cent (*lout.
was quite normal, the apparent slight rise iu gamuut of experimeutal error of the method usetl.
sixteen
months the serum protein
puttcru
had twn
01’ tills
globulitr
b&l::
wst~orcd to Nrtmd.
In February, 1957, three years and two months after the operetion, the! paticxnl. ww His gt9icral hdth was still g(;ootl, :mtl iw again admitt~f~d to tlw hospital for investigat.ions. was even wrariug his lower denture. RoentgenogrtLphic: and hc~matoloyir: c~xaminaCous ww nc~gativr, ant1 thtlrr was no Hence-Jones proteosr in the, urine. At this tinw
the total
.\lbumin Alpha, globulin -Mph& globulin &+.a. globulin Gamma globulin
protein
was 7.4 Gm. per Ck:nt, with Ib Ilistribut.ion 3.3 0.5 0.9 0.9 1.8
Gm. Gm. Gm. Gm. Gm.
per par per per pw
ilH
PoltowS:
c:cnt cent ccut ccut cent
WHITLOCK
30
OS.. O.M. b O.P. January. 1960
AND HUGHES
While this pattern W&Bnot normal, the abnormality was a result of a fall in the albumin level with a corresponding rise in the globulin fraction. It would not appear to bear any relationship to the specific effect of plasmacytoma. A further check was made in December, 1958. The patient was still well (Fig. 7). The serum study wae reported as follows: “The pattern shows marked reduction in albumin with slight rise in gamma globulin plus marked rise in alpha, globulin. There is no suggestion of myelomatosis, but the pattern resembles that found in rheumatoid arthritis. There is definitely no indication of the rise in gamma-globulin which coincided with his plasmaaytoma just after it was removed.”
Fig.
‘I.-Appearance
flve years after
operation.
DISCUSSION
The multiple myelomas are considered malignant tumors of the bone marrow in which the marrow cavity is expanded by a soft gray or red mass, but since there is no corresponding bone formation the cortex becomesthinned and pathologic fractures are common. The tumor, which varies from the size of a pea to the size of an orange, affects chiefly the sternum, ribs, and vertebrae with the skull, pelvis, and clavicle the next most frequently affected. The long bones are the least likely to be involved. The tumor characteristically consists of plasma cells, but these do not show typical staining reactions and their nuclei are larger and do not have halos. Some pathologists have attempted to classify myeloma as to cell type (plasma, myeloma, etc.). Lichenstein and Jaffe,le however, state that the neoplasm has a single cell type. They say that this should not be subdivided into various subvarieties but that the cells, which may vary in their morphology, should be designated as the myeloma cells. The disease, however, is not merely a bone marrow tumor; it is also characterized by abnormal protein in the blood, presumably produced by the enormous numbers of these “myeloma” tumor cella. This protein may act in different ways : (1) it may be excreted in the urine as Bence-Jones proteose (50 per cent of cases), and in advanced casesit may cause a blockage of the tubules
phm&
1;
SOLITARY
MYELOMA
OF MANDIBLE
31
with subsequent renal failure; (2) it may be retained in the blood, causing A hyperproteinemia with a raised serum globulin, which probably accounts for the fact that in such casesthere usually is only a tract! of Bence-Jones prot.eoxc! in the urine; or (3) it may possibly be deposited in the tissues as atypical amyloid. Due to the destruction of the marrow, anemia is also a symptom ill a high proportion of cases. Hist.ologically, biochemically and electrophoretical.ly, the tumor in t.be ca.sc reported here resembled the lesion seen in multiple myeloma. That. the biochemical changes and the electrophoretic pattern were only mild is presumed 10 be due partly to the fact t.hat the lesion was confined to the mandible and part.l> to t.he fact t,hat tests were not performed until two months after the operation. It is interesting to note that in the case reported by Lane’ a. snvall localizetl plasmacytoma of the mandible caused an increase in t.he serum globulin ratio which began to return to normal two months after operation and was compltrtt~l> normal five months later. The general belief now is that myelomas are multicentric in origin and thal, although there is a possibility of a solitary lesion being first. discovered, lesions in other bones very quickly follow. It might, be argued that, inasmuch as ollr pat.ient remained free from the disease five years after operat.ion, thc?re is ;I possibility that myelomas start as a local disease and early removal will result. in a cure. In our case, however, there was only a thorough curettage instead o(: complete local removal, but this st.ill resulted in complet,c hc4inp. In t.his rtlspecb our case differs from that reported by Lane.7 who performrd a compl(jte excision of the lesion, but in all ot.her respects the rasfhsHW fry similar. As yet there is no means of differentiating plasma-cc11tumors. Thcxr two eases,however, as well as the other nine reported in the literature. lend grounds -for t.he belief that there occurs in the jaws a tumor which, although not a tlistinct clinical mt.it.y, has quite a different clinical course from gencralizt4 myeloma and is amenable to surgery, Such a tumor might be cousidorrd a solitary myeloma. Only time will Ml, however, whether or not such a tumor will develop into one of the generalized variety. SUMMARY
1. A case in which an extensive myeloma of the mandible healed despite the fact that only a curettage was performed is reported. The patient. has rema.incbd well after five years, and so far generalized myeloma has not developed. 2. It is suggested that there is evidence to show that t.hcre occurs in thr jaws a plasma-cell tumor which runs a differrnt course from the generaliz variety and is amenable to surgical t.reatment. This might br ronsidered a ROIL tary myeloma.. We wish to thank Mr. I. R. H. Kramer, M.D.S.(Lond.). Head of the Pathology 1)~. partment, Eastman Dental Hospital, for pathologic reports and advice given in the prepars.. tion of this paper, and Mr. D. W. Neill, M.&z., F.R.I.C., Principd Scientific Oftlcer, Royal Victoria Hospital, Belfast, for the reports on the serum protein electrophoratie studies.
32
WHITLOCK
AND HUGHES
0,s..
O.M. & OP. .lanuary, I%0
1. Wolff, E., and Nolan, L.: Radiology 42: 76, 1944. 2. Meloy, T. M., Jr., Gunter, J. H., and Sampson, D. A.: Am. J. Orthodontics & Oral Surg. 31: 685, 1945. 3. Calman. H.: ORAL SURQ..ORAL MED. & ORAL PATH. 6: 1302. 1932. 4. Bruce, K. W., and Boyer,‘R. Q. : ORAL SURQ.,ORAL MED. & &AL PATH. 6: 729, 1953. 5. Spiteer, R., and Price, L. W.: Brit. M. J. 1: 1027, 1943. 6. Christopherson, W. M., and Miller, A. J.: Cancer 3: 240, 1950. 7. Lane, 8. L.: ORAL Suno., OR& MED. & ORAL PATH. 5: 434, 1952. 8. Navarro-Sanehe, F.: Odontoiatria (ma&.) 9: 105, 1952. 9. Mancusi-Materi, G. : Gior. ital. chir. 10: 274, 1954. 10. Davis, G. D., and Havens, F. Z.: Proc. Staff Meet. Mayo Ciin. 29: 569, 1954. 11. Villa, V. G., and Laico, J. E.: Philippines Med.-Dent. J. 1: 33, 1955. 12. Fink, K.: Medizinische 22: 812, 1955. 13. Hinds, E. C., and Pleasants, J. E.: ORAL SURG., ORAL MED. & ORAL PATH. 9: 193, 1956. 14. Ewing, J.: A Treatise on Tumours, ed. 3, Philadelphia, 1928, W. B. Saunders Company, p. 321. 15. Cutler, M., Busche, F., and Cantril, S. T.: Burg. Gynec. & Obst. 62: 918, 1936. 16. Royd, F-V.: Pathology for the Surgeon, ed. 7, Philadrlphia, 1954, TV. B. Saunders Company, p. 576. 17. Grassmann, W., Hannig, K., and Knedel, M.: Deutschc med. Wchnschr. 76: 333, 1951. 16. Neily, R. A., and Neill, D. W.: Nature, London 176: 33, 1955. 19. Lichenstein, L., and Jaffe, H. L.: A. M. A. Arch. Path. 44: 207, 1947.