A RE-EVALUATION OF SOLITARY PLASMA-CELL

MYELOMA OF BONE
WILLIAM M. CHRISTOPHERSON, M.D.,* and A. J. MILLER,M.D.

M ULTIPLE myeloma runs its natural within a short interval of time and had not had
course in from a few months to an average of an autopsy performed.
two years after diagnosis, with an occasional
case surviving for a longer period of time.45 CRITERIA
Inevitably, there is a fatal termination regard-
less of treatment. Solitary myelomas, on the Criteria to justify the term solitary
other hand, are apparently quite unpredict- myeloma must, of necessity, be somewhat
able in their behavior. Indeed, from our arbitrary. While some writers, we believe,
present concept of the latter lesion, we might have included questionable cases, others per-
conclude that it is a tumor without a natural haps have been hypercritical in rejecting
history, in which individual lesions may likely ones. I n an attempt to obviate this, we
pursue a benign course for several years with have tabulated the cases as to: ( 1 ) those fol-
apparent cure, or may terminate fatally with lowed for at least three years without dis-
dissemination within a few weeks or months. semination; (2) those in which autopsy was
Because of this variance in behavior, the performed and a solitary lesion found; (3)
limited number of cases authenticated by those followed one to three years. A three-
adequate follow-up studies, and the diversity year period was selected because, almost with-
of opinion among writers as to what consti- out exception, those lesions that became dis-
tutes a solitary myeloma, a not-inconsiderable seminated, or proved to be multiple myeloma,
group of authors has indicated doubt that became manifest clinically within that period.
these lesions can be set aside as a n entity In the first group (Table l ) , there were
separate from the more common multiple twenty-two cases to which we are adding three
myeloma.*, 2, z9, 44 Considerable support is for a total of twenty-five. They compose 25.7
added to this belief by the twenty-nine cases per cent of the recorded cases. Actually, the
recorded in the literature; these were either majority were observed for a period of more
instances of multiple myeloma a t the onsrt, than four years. Among these, three cases
or they disseminated while under observation. are open to some question. I n the case reported
The implications of the problem led us to by Rosselet and Decker, three vertebrae were
review the recorded cases, and to re-evaluate involved, C5 to C7. I n a somewhat similar
our own cases observed over a considerable case observed by us, in which the lesion
period of time, in an attempt to help clarify was localized radiographically to three
the situation. adjacent vertebrae, multiple myeloma was
We were able to find ninety-four cases proved by bone-marrow examination. How-
verified by histological examination, recorded ever, the implication in their case is that the
between 1897 and 1949. Ofthese, several were involvement was by continuity, and no evi-
deficient in convincing evidence that the dence of multiple myeloma was found. Batts
lesions were solitary at the time of examina- unfortunately does not give complete informa-
tion. An even greater number were not tion on his case. The third, Christopherson
adequately followed, had already become dis- and Miller case 3, will be discussed later.
seminated at the time of report, or had expired The second group (Table 2) comprises
From the Department of Pathology, University of cases in which the period of follow-up is too
Louisville School of Medicine, Louisville, Kentucky. short to warrant conclusions, but in which
* At present James Ewing Fellow, Memorial autopsy recorded solitary lesions. There were
Hospital, New York, N. Y.
Received for publication, September 23, 1949. twelve cases in this category. I t should be
 SOLITARY PLASMA-CELL MYELOMA OF BONE Christopherson & Miller [241
1
TABLE
SOLITARY MYELOMAS FOLLOWED FOR T H R E E YEARS O R M O R E W I T H O U T EVIDENCE
OF MULTIPLE MYELOMA
Period of
Trealmmt obSCW. Remarks

Aufses 58 Rt. 3d rib Block excis. 3 yrs.. Marrow exam. normal, x-rays neg.; died of
M 6 mos. coronary thrombosis
Bailey 65 Humerus shaft Biopsy; x-rays 7 yrs. Patient well; lesion recalcified
M
Batts I Ilium Not given 4 yrs.. No other demonstrable lesions
? 4 mos.
Bayrd & 23 Lt. femur Biopsy 3 yrs.. No radiographic changes in skull, thorax,
Heck F 6 mos. or spinal column*
Bayrd & 43 Lt. clavicle Biopsy 5 yrs.. No further information given+
Heck M 6 mos.
Ba r d & 54 Rt. scapula Biopsy 5 prs.. No lesions found in skull+
Zeck M 6 mos.
Bayrd & 68 Presacral Biopsy 9 yrs. No radiographic changes in thorax, spinal
Heck M column, or extremities+
Bayrd & 49 Vertebra D7 Biopsy 3 yrs. No radiogra hic changes in thorax; com-
Heck M pression oP D7 *
Bayrd & 38 Vertebra L5 Biopsy 8 Yrs.. No radiographic changes in skull or thorax*
Hetk M 6 mos.
Chestennan 35 Upper tibia Amputation 1 2 yrs. Living and well; no generalization
M
Christophenon & 29 Mandible Excision 16 yrs. Asymptomatic; x-rays and bone-marrow
Miller (case 1) F exam. nee.
Christophenon & 25 Upper tibia Curettage; 12 y n . Asymptomatic; x-ray of skeleton neg.
Miller (case 2) F x-rays
Christopherson & 63 Vertebra D 4 Curettage 7 yrs.. No evid. of mult. myeloma; x-rays neg.;
Miller (case 3) M 6 mos. died, heart dis.; no autopsy
Coley 52 Upper femur Radiation 3 yrs. Patient in good health
F
Cutler e t al. 52 Vertebra D7 X-rays 10 yrs. Lesion still present in vertebra and adjacent
Bone Reg. 1167 M vertebrae
Gootnick 48 Rt. hip Biopsy; 4 yrs. Asymptomatic; x-rays of skeleton normal
M x-rays
Gootnick 68 Rt. ilium Biopsy; 4 yrs.. Died, ca. prostate
M x-rays 11 mos.
Kaufman 14 Occipital bone Curettage; 4 yrs. Living and well; no generalization
M x-rays
Pasternack & 46 Humerus, I t . X-rays; 8 yrs. No recurrence or generalization
Waugh M upper 3d resection
Rogers 34 Rt. femur Curettage; 4 yrs. Purulent drainage 5 mos. after orig. opera-
M radium; amputa- tion; no generalization
tion
Rosselet 8; 55 Vertebrae C5- Radiation 4 yrs. Living after 4 yrs.; local recurrence re-
Decker M c7 sponded well to x-rays
shaw 29 Rt. humerus Curettage 9 yrs. No generalization
M
Stewart & 34 Prox. humerus Amputation 8 yrs. Good health; no evidence of generalization
Taylor M
Stewart & 43 Maxilla Curettage 8 yrs. Good health; no generalization
Taylor M
Vihvelin 59 Vertebra D7 Curettage; 12 yrs. 7 yrs. later. focal disease still present; no
M rewated generalization
* Method of treatment not indicated by these authors, none of the patients had marrow examinations.

noted that there are two prime objections to
a too-hasty acceptance of all of this group.
First, it is most difficult, and often impossible,
to examine adequately an entire skeleton
grossiy and microscopically, although the
vast majority did have adequate examinations
by presently accepted criteria. Second, there
are those who believe, and with some justifica-
tion, that multiple myeloma, in the earliest
stage of the disease, is manifest by a solitary
lesion that later disseminates, or metas-
tasizes, to other bones. If this theory is
accepted, then these lesions, although solitary
at autopsy, could be interpreted as the early
stage of multiple myeloma and, if given
sufficient time, might disseminate. Although
this must be admitted as a possibility, it
seems highly improbable for reasons to be
given later.
The third group (Table 3) is made up of
fifteen cases that are rather difficult to
evaluate. They were observed over a period
varying from one year to twenty-nine months.
I n some instances, it is not clear how complete
the follow-up examinations were. However,
since even a year is a fair range to allow for
2421 CANCER March 1950
TABLE
2
RECORDED CASES OF SOLITARY MYELOMA IN WHICH SINGLE LESIONS
WERE FOUND AT AUTOPSY
Age Period of
Source Sex Location Treatment obserw. Remarks

Bayrd & 15 Verbetra LS 4 mos. Diagnosed a t autopsy

Heck M
Cappell & 57 Skull Curettage; S mos. Single focus a t autopsy
Mathers F radium
Charbonnier & 62 Femur, upper 3d Curettage 6 mos. Single focus a t autopsy
Mermod F
Cutler e t al. 39 Ilium Biopsy; 23 mos. Single focus a t autopsy
F x-rays
Harding & 60 Femur, upper 3d Disarticulation 2 mos. Single focus a t autopsy
Kimball M
Lumb 72 Sacrum None 5 mos. Died in uremia (myeloma, kidney) single
M focus a t autopsy
Mallory et al. 32 Vertebra D 4 Laminectomy 15 days Single focus a t autopsy
(Case 16482) M
Satanowsky 36 Innominate - Single focus a t autopsy
e t al. F
Scheinker 39 Sternum - 1 yr. Single focus a t autopsy (bone exam. limited
M to TTertebrae)
Walthard 55 Vertebra C7 Laminectomy Died Single focus a t autopsy
M POstDp.
Willis 45 Vertebra C2 None - History of compression.of spinal cord for 20
M yrs,; solitary lesion discovered a t autopsy
Zdansky 64 Femur, upper Few days Single focus a t autopsy
F 3d

evidence of multiple myeloma, it seems highly
probable that a considerable number of these
patients will prove to have solitary lesions.
The case reported by Schwartz and followed
for one year is not included, since it is quite
obviously a giant-cell tumor, or one of its
variants, with which we are not immediately
concerned.
There are, then, a total of' fifty-two cases,
or 53 per cent of' those reported, in which
there is good evidence, although not proof', of
solitarity .
The remaining forty-five cases comprise two
categories: (1) those with follow-up periods of'
less than a year, or in which insufficient data
are available to establish the solitary nature
of the lesion. There were sixteen cases in this
group;17, 19. 2 1 , 2 2 , 2 4 , 36, 37, 4 2 . 43, 47, 4 9 , 52, 53. 5 8 . 62.
73 (2) those that were from the onset, or later
proved to be, multiple myeloma, twenty-nine
cases.1, 2 . 5 , 8 , 10, 17. 18, 2 7 , 31, 36, 38, 4 1 , 50,* 59, 62. 63.
64, 70, 1 6 , 77, 79
Among the last group is the case reported
by Bloodgood in 1906. The patient developed
multiple lesions some two months after resec-
tion of the clavicle for a n apparently solitary
myeloma. Other early cases, Schmorl, 1912,
*Reports subsequent course of the patient re-
ported by Geschickter.
and Morax, 1910, were not definitely solitary
and have been rejected. Ewald's case, re-
ported in 1897, has been rejected because of
indefinite histological criteria and lack of
documentation.
CLINICAL
CONSIDERATIONS
Age and Sex Incidence. The age incidence
varied from nineteen months to seventy-two
years, each decade being represented by at
least one case. There was a predilection for
the sixth decade, although cases were not
unusual in the early thirties. Only one patient
was beyond 70 years of' age (Table 4).
The male-to-female ratio was about three to
one. This is higher than the two-to-one ratio
often cited for multiple myeloma.
Site of Tumor. Table 5 gives the site of the
tumor in the various categories. The vertebrae
were the most common location, thirteen
cases, with the femur and pelvis following in
that order. I n the femur, the upper end was
involved in all cases, and in the pelvis, the
ilium was the common site. T h e maxilla,
mandible, clavicle, and sternum were involved
in only one instance each.
Clinical Complaints. The period between
onset of symptoms and observation varied
 SOLITARY PLASMA-CELL MYELOMA OF BONE Christopherson t
3 Miller [243
TABLE
3
SOLITARY MYELOMAS FOLLOWED FROM ONE T O THREE YEARS WITHOUT
EVIDENCE OF MULTIPLE MYELOMA
A .w Ppriod of
Source Sex Location Treatment obsprz'. R cmark s

Ba d & 40 Vertebra DL Biopsy 21 mos. Compression of D2; no other information

geck M given
Ba d & 55 Lt. hip Biopsy 29 rnos. KO radiographic changes in skull, thorax,
gmk F or It. ilium
Bayrd & 14 R t . femur Biopsy 15 mos. NO radiographic changes in skull or thorax
Heck M
Cutler et al. 58 Ilium Biopsy; 20 mos. General condition good
Bone Reg. M x-rays
1195
Fonts Abreu 50 Sacrum 20 mos. Lesion partly recalcified; patient in good
M health
Holden 60 Rt. 1st rib Biopsy; 2 yrs. X-rays of skeleton neg.; patient well
F x-rays
Leedham-Green 56 Lt. innominate Biopsy; 2 yrs.; Recalcification of lesion; n o spread
e t al. M x-rays 5 mos.
Liebman & 50 Ilium Biopsy; 16 rnos. Condition improved; no spread
Goldman M x-rays
Mancini 19 rnos. Femur, upper Exploration; 20 mos. 2d lesion in skull after 7 mos. disappeared
F 3d x-rays following x-rays
Martin et al. 56 Neck of femur Disarticulation 2 yrs. Living: n o spread
F
Mathias 65 Parietal bone Excision 18 mos. Living a t time of report; no recurrence or
M dissemination
Paul & 60 Vertebra C3 Partial removal; 19 mos. Extended to adjacent vertebrae; other bones
Pohle M x-rays neg. t o x-rays
Tavernier & 36 Scapula Biopsy; 2 yrs.. No evidence of dissemination
Leclerc M x-rays 6 mos.
Tilden 34 Frontal Partial removal; 1 yr. Patient well; no other lesion
M x-rays
Wright 31 Vertebra D8 Curettage: 1 yr. Condition normal when last seen
M radon seeds

from a few weeks to twenty years. The present-
ing symptoms, in order of decreasing fre-
quency, were pain, more marked when associ-
ated with trauma or when the lesion involved
the spine, but almost always present to some
extent; swelling, or palpable mass; and frac-
ture. Generalized symptoms such as character-
ize multiple myeloma were rarely in evidence.
One patient died in uremia secondary to
myeloma of the kidney.48 A large proportion
of patients gave a history of trauma or frac-
ture, some recent, obviously pathological; in
others, the trauma or fracture preceded the
diagnosis of the lesion by a significant period
of time. Infection sometimes accompanied, or,
in a few instances, preceded the tumor; this
will be referred to later.
Laboratory Findings. Clinical laboratory
findings were most helpful when the values
were found to be within the normal range.
Bence Jones protein in the urine was found
in three patients in the first two categories, or
in a total of 9 per cent. This is significantly
lower than the range up to 65 per cent often
cited for multiple myeloma.**.87 However, in a
number of cases, there was no mention of the
examination having been made, and it is
doubtful that a concentrated effort, by
repeated examinations, was made in each
case recorded as negative. Significant anemia
was encountered in a very few instances, and
then only where demonstrable complicating
factors were evident. Appreciable hyper-
globulinemia, rouleaux formation, and ab-
normal blood smears were not encountered.
Calcium and phosphorus determinations were
performed in an insignificant number of cases
and are impossible to evaluate.
Radiographic Findings. Two types of lesions
were characteristically found. The first pre-
sented the appearance of a giant-cell tumor,
or bone cyst, found by Pasternack and Waugh
in 66 per cent of the cases they reviewed. The
second type was a purely destructive lesion
commonly of intramedullary location. The ma-
jority of these suggested metastatic carcinoma.
A detailed description of the radiographic
appearance of solitary myeloma is given by
Paul and Pohle and need not be repeated
here. It might be well to mention that, in the
2441 CANCER M arch 1950
TABLE4 the other hand, surgery, in the form of curet-
AGE AND SEX DISTRIBUTION tage or simple excision, has provided survivals
Decade Malt Female Total ranging between nine and sixteen years.
More radical procedures, such as amputation
1 - 1
2 2 2
or disarticulation, have likewise provided
3 1 4 good results; but we are firmly convinced that
4 9 11 such radical procedures are quite unnecessary,
5 8 8
6 10 14 for reasons that will be made apparent later,
7 7 10 unless, of course, amputation is performed to
8 1 1
- - remove a useless limb and not with curative
TOTAL 38 51 results in mind.
I n summary, the method of treatment
cases involving vertebrae, a demonstrable utilized must be based on the location of the
lesion may not be found. The fact that here lesion, a consideration of future function, and
again we have a picture commonly mis- the skill ofthe surgeon or radiotherapist. Ifthe
diagnosed radiographically as giant-cell tumor lesion is truly a local one, any method of
lends support to the maxim that histological complete destruction is suitable; if it is part
examination must be made in conjunction of a generalized disease, no known method is
with clinical and radiographic data to curative and the problem is obviously one of
establish a correct diagnosis of bone tumors. palliation.

Treatment. The types of treatment used in

the cases reviewed indicate that surgical and GENERALCONSIDERATIONS
radiotherapeutic procedures have been The magnitude of the problem as indicated
utilized, separately or in combination, in the by the varied behavior of solitary plasma-cell
majority of cases. A few have gone untreated, tumors of bone is increased by the uncertainty
and Coleys toxin plus irradiation were used of the origin of the cell in question and its
in one. relation to the predominant cell in multiple
Irradiation in the form of external roentgen myeloma. All the cells of the hematopoietic
rays, or radium, and interstitial radium have tissue have been incriminated as the cells of
gained the greatest popularity, perhaps be- origin;60 however, since Maximow (1922-23)
cause of the favorable response of the solitary demonstrated that plasma cells can be pro-
myeloma in contrast to multiple myeloma.*j duced in culture by explants of lymphoid
The fact that some of the patients so treated tissue, the advocates of the lymphoid origin
have survived from three to seven years has of the plasma cell have in~reased.7~ More
given further support to this treatment. O n recently, the theory of reticulum-cell origin
has gained in popularity.6v20 Much of the
TABLE5
evidence for the latter theory is apparently
LOCATION OF SOLITARY MYELOMAS
_ _ _ _ ~ .
based on morphological criteria that, we have
F o l l o ~ u - ~period
__
p
Single
often been reminded, may be precarious
Location
3 Yrs. or
more
I to 3
yrs.
jo0cu.r at
aulopsy Tolal
ground on which to base judgment.
Wintrobe, Lichtenstein and Jaffe, Wood
Femur 4
Vertebra 6 and Luckt, and others believe the cells of
Pelvis 2
Rib 1 multiple myeloma are distinctive tumor cells
Humerus 4
Tibia 2 best designated noncommittally as myeloma
Scapula 1
Maxilla 1 cells. Diggs and Sirridge, among others,
Mandible 1
Skull 1 believe that the term myeloma cell should
Sacrum 1
Sternum - be abandoned, since the cell in question
Clavicle 1
- - - - represents the early plasma cell and its
TOTAL 25 15 12 52
designation as myeloma cell only leads to
 SOLITARY PLASMA-CELL MYELOMA
confusion. I t seems quite evident that the
cell type, whether true plasma cell or not,
may vaiy considerably from one lesion to
another; but almost always some cells indis-
tinguishable from plasma cells are present.
Of equal importance to the genesis of the
cell involved, is the question of'the nature of
the disease. The majority opinion is that
multiple myeloma is a neoplasm, although
this concept is by no means universally
accepted. Morissette and Watkins believe that
multiple myeloma is probably more closely
related to leukemia than to other neoplasms:
Ewing considered multiple myeloma as a
neoplasm characterized by multiple foci of
origin and rare metastases. Others, including
Cutler et al., have indicated belief that
multiple myeloma may originate as a single
lesion with subsequent metastasis to other
bones.
Stout and Kenney, in their discussion of
plasma-cell tumors of the upper air passages
and oral cavity, point out that the plasma-cell
tumor is in somewhat the same category as
Hodgkin's disease and Kaposi's sarcoma.
Theseauthors commentedthat it is possible that
all of the so-called metastases from plasma-
cell tumors of the air passages represent
examples of multiple primary involvement in
which the nasal or oral lesions precede the
involvement of other sites. The absence of lung
metastases in any reported case makes blood-
borne metastases to bone seem almost in-
credible to them. I n the present review, no
instance of pulmonary metastasis was noted in
the cases in which a single demonstrable lesion
existed before the clinical picture of multi-
ple myeloma was manifest, although a few
cases of lung involvement in multiple myeloma
are recorded in the l i t e r a t ~ r e . ~ ~
The weight of evidence seems to indicate
that multiple myeloma, whether a true neo-
plasm or not, is characterized by multiple foci
of origin rather than solitary origin and subse-
quent metastasis. This is the pivotal point in
our conviction that true solitary plasma-cell
lesions are not likely to disseminate subse-
quently, and that eradication of the lesion by
any method usuaIly will be followed by a
favorable course.
OF BONE Christopherson ti? Miller [245
PROBLEMS
OF DIAGNOSIS
Unqualified diagnosis is most difficult and
often impossible at the onset. I t must be based
on an extremely careful clinical evaluation,
in conjunction with adequate histological
examination, and, indeed, often requires a
considerable period of' observation, as has
already been shown.
I n reviewing our material, an attempt was
made to find histological aids in differentiat-
ing solitary from multiple myeloma. The
limitations of this attempt were attested by the
fact that several capable pathologists reviewed
the lesions and, without exception, made the
diagnosis of plasma-cell myeloma in spite of
the subsequent course of these patients.
Histopathology. Since the tumors observed
varied only in minor details, a composite
picture will be given, and when differences
exist, they will be described.
The tumor is composed of cells for the most
part quite indistinguishable from plasma cells,
except for their larger size and apparent rela-
tive immaturity in some instances. T h e cells
are arranged in sheets, or cords, and supported
by a delicate reticular stroma through which
are interspersed thin-walled vascular channels
usually lined by large prominent endothelial
cells. The stroma is never prominent and quite
often imperceptible in hematoxylin-and-eosin
preparations. The nuclei usually are eccen-
trically placed but occasionally appear to be
near the center of the cell. A blocked chroma-
tin pattern stands out in relief against the
lighter parachromatin material; however, a
moderate number of nuclei are hyperchro-
matic. Mitotic figures are rare to the point of
being practically nonexistent. I n the first
case, none was found after extensive search.
An occasional nucleus is of giant proportions,
and many cells are binucleated. No cell con-
tains more than two nuclei. In sections stained
with hematoxylin and eosin, the cytoplasm
takes a slightly eosinophilic tinctorial hue. A
paranuclear Hof is often found, except in
case 1, where it is rare. Russell bodies are
found in moderate numbers in cases 2 and 3.
Of some interest are cytoplasmic extrusion
bodies occurring in small numbers in all
2461 CANCER
cases; these occasionally contain Russell
bodies.
I n the reported cases, as in our own, in so
far as we could discern from descriptions or
photomicrographs of solitary myelomas with
prolonged survival, the variegated picture
often found in multiple myeloma was never
present in the solitary form. From this, one
is tempted to conclude that, given an appar-
ently solitary lesion that presents other than
the well-differentiated picture, the chances
are good that the tumor will not pursue the
favorable course of solitary myeloma. On the
other hand, there are no apparent histological
criteria by which we are able to distinguish
solitary myelomas from the better-differen-
tiated multiple myelomas.
As late as 1937, statements appeared in the
literature that Russell bodies had not been
demonstrated in myeloma and mention
was rarely made of them. However, Bayrd,
and Diggs and Sirridge have found them in a
significant number of their cases, and we
found them in the better-differentiated
multiple myelomas that we reviewed. Simi-
larly, a paranuclear Hof was often found in
multiple myeloma, as were cytoplasmic extru-
sion bodies. Mitotic figures were never promi-
nent in our cases of multiple myeloma, and in
one instance, a biopsy specimen from a verte-
bra, none was found. The lack of mitoses
and the presence of binucleated cells could
possibly be interpreted as evidence of amitotic
cell division in these tumors.
CASEREPORTS
Case 1. M.B. A 29-year-old white woman
was admitted to the Louisville General
Hospital on April 4, 1933, one week follow-
ing extraction of a lower left molar. The left
side of her face had been painful and swollen
for two days. There was no discharge from
the tooth socket, but her face felt warm and
was tender over the left ramus of the man-
dible. Her temperature was 100F., the white
blood count was 7600, with 83 per cent
polymorphonuclear leukocytes. The pain and
swelling abated with hot packs, and she was
discharged.
One month later, she returned with re-
stricted motion of the jaw and swelling of her
face. Her temperature was 98.4OF. The white
March 1950
blood count at this time was 3650, with 50
per cent polymorphonuclear leukocytes, 45
per cent lymphocytes, and 5 per cent mono-
cytes. Roentgen-ray examination showed a
destructive lesion involving the ramus and
posterior portion of the body of the mandible.
This was interpreted as being more suggestive
of bone tumor than osteomyelitis. No soft-
tissue masses were found in the mouth.
On June 8, 1933, the left half of the man-
dible was excised.
The specimen was described in the labora-
tory as consisting of several pieces of gray
tissue measuring up to 20 x 10 x 5 mm. and a
segment of bone 3 0 ~ 1 5 x 5mm. Sections
revealed a tumor composed of solid masses of
typical and atypical plasma cells, a number of
which were binucleated. It was thought to be
quite malignant. The diagnosis was plasma-
cell myeloma.
Following operation, the patient made an
uneventful recovery. N o other lesions were
demonstrable radiographically.
I n January, 1949, the patient was seen
again. She had remained asymptomatic dur-
ing the sixteen-year interval. At this time, a
radiographic bone survey was entirely nega-
tive. The urine was free of Bence Jones protein.
The red blood count was 4,620,000; hemo-
globin, 13 gm. The white blood count was
7200 with a normal differential. No rouleaux
formation was noted. The total protein was
7.62 gm. per 100 cc.; albumin, 5.15 gm.;
globulin, 2.47 gm.; serum calcium, 8.7 mg.
per 100 cc.; serum phosphorus, 3.4 mg. per
100 cc. Bone-marrow biopsy and smears in
June, 1949, showed no abnormalities; two
plasma cells were found in the 500 cells
counted. Again the urine contained no Bence
Jones protein.
Case 2. N.R. A 25-year-old white woman
was admitted to the hospital on December 1,
1936, with a provisional diagnosis of giant-
cell tumor of the left tibia. At the age of seven,
following typhoid fever, she noticed a
lump on her left leg a t the junction of the
lower and middle thirds. At night, especially
after being in the rain, there was a dull ach-
ing pain in this area. Five weeks before entry,
the painful area began to swell and pain
increased.
At examination, there was a tender, hard
tumor mass 4 x 6 cm. over the anterior aspect
of the left tibia. The upper border of the mass
was 2 inches below the lower border of the
patella. It appeared to involve the bone. The
skin over the area was freely movable, of
normal temperature and texture. The remain-
der of the examination was noncontributory.
 SOLITARY PLASMA-CELL MYELOMA OF BONE Christopherson @ Miller [247

FIG. 1. Case 1. Low-power magn$cation. (H. 6'E.) FIG. 2. Case. 1. (H. 9

E. Approx. x 800.) FIG. 3. Case 2. Low-power magn$cation. (H. 6' E.)
FIG. 4. Case 2. (H. 6'E. Approx. x 800.)
2481 CANCER
FIG. 5. Case 3. Low-power magnijcntion. (H. & E.)
3 E. Approx. x 800.)
Laboratory data: red blood count,
4,350,000; hemoglobin, 13 gm.; white blood
count, 12,800; polymorphonuclear leukocytes,
84 per cent; lymphocytes, 12 per cent; mono-
cytes, 4 per cent. Urinalysis was negative.
Roentgen-ray examination of the left leg re-
vealed a large osteolytic lesion in the me-
taphysis of the tibia, thought probably to
represent neoplasm, the nature of which was
not stated.*
The day after admission, the lesion was
explored, with a preoperative diagnosis of
giant-cell tumor. The cortex of the tibia was
found to be thinned considerably. A cavity
the size of an egg containing gray gelatinous
tissue was curetted and spicules of bone were
placed in the defect. The wound was closed
and an unpadded cast was applied.The wound
healed and the patient made an uneventful
recovery. The pathological diagnosis was
plasma-cell myeloma.
Between December 8 and 30, the patient
received five roentgen-ray treatments of 250 r
units to each of two ports far a total of 2500 r.
A complete bone survey revealed no other
lesions.
There had been few symptoms since dis-
* Roentgenograms were not available for review.
March 1950
FIG. 6. Case 3. (H.
charge until November, 1946, when the leg
became painful again. At this time, a second
operation was performed at another hospital.
Necrotic bone and granulation tissue were
removed. Cultures were made, but no growth
obtained. The wound again healed without
drainage. The diagnosis following the second
operation was chronic osteomyelitis. Since
then she has worn a brace.
I n November, 1948, a radiographic skeletal
survey was negative, except for the defect a t
the operative site. Hemograms, serum cal-
cium, phosphorus, alkaline phosphatase, al-
bumin, and globulin were all within normal
range. No Bence Jones protein was found
in the urine.
Case 3. J.C. A 63-year-old white man was
admitted to the hospital on March 10, 1941,
with partial paralysis of the lower extremities.
He first noticed weakness of his legs in June,
1939, and by October he was forced to cease
work as a carpenter. On occasion there was
incontinence of urine and feces.
The legs were moderately spastic and could
not perform motion against slight resistance.
There was loss of pain sensation to the level of
D4. Light touch and temperature were absent
from D11 down. Vibratory sensation was lost
 SOLITARY PLASMA-CELL MYELOMA OF BONE
in both legs. Superficial reflexes were absent.
A positive Babinski was present bilaterally.
The knee jerks were hyperactive. There was
sustained right-ankle clonus.
The spinal fluid was clear, with an initial
pressure of 170 mm. of water. Compression of
the left jugular increased the pressure to 270
mm. and right jugular compression, to 250
mm. ofwater. The pressure was sustained after
release of compression. The fluid contained
two lymphocytes and no red blood cells. The
spinal-fluid Kahn reaction was negative.
Spinal-fluid protein was 200 mg. per 100 cc.
Red blood count, 4,300,000; hemoglobin,
10.5 gm.; white blood count, 8,400 with a
normal differential. Urinalysis was negative.
Roentgen-ray examination of the spineshowed
considerable arthritic change in the dorsal
area.
The Neurosurgical Department made a
diagnosis of extradural tumor, and, on March
15, performed a dorsal laminectomy remov-
ing the spines and laminae of the 3d, 4th, and
5th dorsal vertebrae. The laminae were
excessively thin, and when the canal was
opened, a mass was seen compressing the
dural sac. The tumor was removed piecemeal
and was thought to arise from the body of the
4th dorsal vertebra.
The pathological diagnosis was plasma-cell
myeloma.
The patient made an uneventful recovery.
Bone surveys were made, and no lesions were
found. Repeated urine examinations for
Bence Jones protein were negative. Serum
calcium, phosphorus, phosphatase, albumin,
and globulin examinations were all within
normal limits. He gradually regained power
in his legs and was able to get about with the
aid of a cane.
The patient was followed in the tumor clinic
until November, 1948, at which time the
hemogram and the blood chemistry were
within normal limits. A radiographic bone
survey showed no evidence of multiple
myeloma. I n the interim, the patient had
developed severe cardiac decompensation.
I n April, he failed to return for a bone-marrow lesions, anemia, hyperglobulinemia, hyper-
examination, and the Social Service Depart-
ment learned that he had died at home.
Apparently, death was due to cardiac de-
compensation. Unfortunately, no autopsy was
performed.
DISCUSSION OF CASES
These cases suggest several interesting possi- ported in which extensive lesions were present
bilities. Could the lesion in case I represent an at autopsy without radiographic changes.38.
exaggerated form of plasma-cell granuloma? I t should be remembered that multiple
The alveolus is a favorite site for small granu- myeloma is basically a disease of the bone
ChrLtophrson 8 Miller [249
lomas that are extremely rich in plasma cells.
Usually, they are easily recognized histo-
logically as vascular pyogenic granulation
tissue with an admixture ofinflammatory cells,
predominantly plasma cells. I n our experi-
ence, none has assumed the proportions of'
this lesion nor have they destroyed so much
bone.
Is this then a myeloma originating in the
soft tissue of the mouth, with secondary inva-
sion of the mandible? Since, at the clinical
onset of the disease, a central bony defect
was demonstrable, and at the same time, no
lesion was present in the soft tissues of the
mouth, this seems unlikely. Furthermore, we
believe it to be quite irrelevant, and agree
with Claiborn and Ferris, and others, that
most of' the oral and nasopharyngeal mye-
lomas are benign, and that the malignant ones
are probably manif'estations of' multiple
myeloma.
The third possibility of its being one of the
lesions of multiple myeloma seems rather
remote, for a period of sixteen years has
elapsed since the first observation, and at
present, there is no evidence of'dissemination.
Case 2 suggests the possibility of inflamma-
tory origin. Symptoms date back eighteen
years before operation and osteomyelitis was
present ten years after operation. Loeper,
Vignalou, and Borreau report myeloma de-
veloping in a 30-year-old man as a result
of osteomyelitis of twenty-five years' duration,
in which the tumor became exteriorized
through a residual fistula. Spitzer reports a
case of myeloma of the mandible associated
with osteomyelitis following extraction of a
tooth.
I n case 3, the absence ofdemonstrable bone
calcemia, and lack of Bence Jones protein in
the urine are all important evidence against a
diagnosis of multiple myeloma. However, the
diagnosis would be more secure had bone-
marrow examinations been made. Similar
cases involving the vertebrae have been re-
 CANCER March 1950
marrow and involves bone only secon- require a prolonged period of observation.
d a r i l ~ .80~ , I t will be recalled that in this case
Frequent bone-marrow studies in addition to
the original lesion could not be demonstrated roentgenograms will prove helpful during
roentgenographically, and the possibility re- this period.
mains that further involvement might have Multiple myeloma in its well-differentiated
existed, even though the subsequent clinical form is quite indistinguishable from the
course failed to reveal it. solitary type. However, the favorable solitary
lesions apparently never present the variegated
SUMMARY picture of some multiple myelomas, and when
this latter type tumor is found, the chances
From present available data, we conceive are overwhelming that it will prove to be
of multiple myeloma as a neoplasm of multi- multiple myeloma. We believe the cells of
centric origin, arising from hematopoietic solitary myeloma to be atypical plasma cells
elements of the bone marrow and, occa- in all instances, and if it is possible to dis-
sionally, in extramedullary foci. I t runs a n tinguish between a plasma cell and a myeloma
inevitably fatal course in spite of any known cell, as has been claimed, then histological
treatment. As a result of the present survey, differentiation should be simplified.
we submit that a histologically similar lesion Treatment should be directed toward
exists in a solitary form, which has a favorable destruction or removal of the solitary focus;
outcome, again, possibly, regardless of type this usually consistsof irradiation, surgery, or a
of treatment. The solitary form behaves as a combination of the two, depending on the
granuloma but is a unicellular growth that location, available facilities, and consideration
histologically is better classified as a neoplasm. of future functional results. It is extremely
Extramedullary plasma-cell tumors not asso- doubtful that the more radical methods of
ciated with multiple myeloma are probably treatment such as amputations or disarticula-
of the same nature. tions are necessary to effect a cure of this
Using an arbitrary period of three years tumor. I t seems equally inconceivable that
for evidence of dissemination, twenty-five even such radical measures could alter the
cases are accepted as the solitary form. Of course of multiple myeloma.
the cases reported here, one is dead after
seven and one-half years, the other two are CONCLUSIONS
alive after thirteen and sixteen years respec-
tively. 1. Solitary plasma-cell myeloma of bone
An additional twelve cases have been appears to be a well-established entity un-
autopsied and solitary tumors found. related to multiple myeloma.
Fifteen cases, followed for a period of from 2. The neoplastic nature of plasma-cell
one to three years, are listed as probable in- myeloma ofbone is suggested by its unicellular
stances. The over41 picture has been composition. The natural history ofthe lesion,
obscured by the large number of cases re- however, lends some doubt to this concept.
ported as solitary myeloma that have eventu- 3. Diagnosis depends on roentgenographic
ally been proved to be instances ofthe more bone surveys, bone-marrow examination,
common multiple myeloma. clinical evaluation, and, of necessity, a pro-
Diagnosis is of extreme importance because longed period of observation.
of the divergent progress of the two tumors. 4. The prognosis of true solitary myelomas
Unfortunately, this is most difficult and may of bone is always favorable.
 SOLITARY PLASMA-CELL MYELOMA OF BONE Christopherxon @ Miller (251
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