Musculoskeletal Salutarmo

Martinez,

MD

#{149} James

B. Vogler

Imaging of Tumoral New Observations’ Five

patients

with

tumoral

calcino-

sis were evaluated with radiography, bone scintigraphy, computed tomography (CT), and magnetic resonance (MR) imaging. The arthropathy of calcium pyrophosphate dihydrate deposition disease was seen in two of the patients and pseudoxanthoma elasticum-like syndrome in three. Identification of calcific paraarticular masses on radiographs is characteristic of tumoral calcinosis. Marrow lesions could be identified as patchy areas of calcification (calcific myelitis) in long bones and the calvarium. Bone scmtigraphy appears to be the best modality for detection of the masses

dural

and

vascular

MR imaging

also showed increased signal on T2-weighted images.

overlooked,

however,

myelitis Index

is the terms:

malities,

only

#{149} Soft

affected

cluded

that

has this

variable kindred,

with

the

1990;

(1),

our

un-

remains group

incomstudied

(2) and

disease

mode

masses.

study

in

the

evaluation. The is to (a) reassess

boy

and

his

two

woman and All subjects

to the

clinical

studies

that

proved

by the Institutional

The

patients

unit,

and

Whole-body

images

sessed

From

the

Departments

grant

of Radiology

M01-RR-30

from

National

Institutes

Program, K.W.L.

(c RSNA,

is recipient 1990

with

(SM.,

J.B.V.),

Surgery

(J.M.H.),

and

been

with

the

Division

of Health,

of NIA

Academic

of Research

and

the Award

Resources,

Veterans AG-00367.

General Address

reprint

requests

in four

5) were

(9800;

paas-

GE Mcdi-

as were

bone

with

an intramedullary 1. MR imaging

a Signa

system

operating

tibial per-

was

(GE Medical

at 1.5 T. Spin-echo

and coronal (500/ marrow lesion

tibial

(patient

1) were

diologic tients

examination 1 and 3; the

also

acquired. was

other

Dental

done patients

in

ra-

pawere

edentulous.

All mic

subjects and had

were elevated

hydroxy-vitamin

hypenphosphateserum 1,25-di-

D levels

(3).

a

Calcified

Soft-Tissue

Masses

Radiography.-Early

ap-

sions

Board.

were

gions

(5).

(K.W.L.),

October

4,

small

Ic-

located in reto be occupied by bun-

known (Fig

and

distinctively

1). Some

A total

masses

bunsae, (4) and of 15 masses

ed in our five were distributed

involved

such as the calcaneal bursae were

evaluat-

patients. Most masses in a paraanticular

Supported

Research

Medical

hips

Milwaukee),

(500/25, 2,000/40-80) 25) images of the

differ-

Received

Clinical

Administration

of the

sequences with various repetition (TRs) and echo times (TEs) were The shoulder was evaluated with axial (500/25 [TR msec/TE msecJ, 2,000/ 40-80) and coronal (500/25) images. Axial

Administration 26.

a

all

had

July

with

RESULTS

Review

Medicine

obtained

a CT scanner

extraarticulan ischiogluteal Center, Box 3169, Durham, NC 27710; and Veterans NC (K.W.L.). From the 1987 RSNA annual meeting. November 2; revision received July 24, 1989; accepted

were

pulse times used.

reported subjects,

imaged

delay.

1, 2, 4, and

Systems,

Systems)

ages

where

methylene

a 2-hour

in the area (patients,

formed

re-

uncles,

performed were

MBq)

the shoulder and lesion in patient

a 77-year-old were admitted

research were

of technetium-99m

of a 10-year-

maternal

scans

Radionu-

(740

diphosphonate

METHODS

consisted

bone

patient.

marrow lesions involving the femoral shaft and skull in three patients (patients 1, 3, and 5). MR imaging was used to evaluate a calcific paraarticular mass of

purpose

53, all from a previously (2), and two unrelated

33-year-old man (Table).

calcification,

AND group

in each

scans were obtained after the administration of 20 mCi

cal

three

comprises

Conventional

radionuclide

clide bone intravenous

tients

In subjects

These

modalities.

and

obtained

masses

and

clinical expressivity. we found three

calcific

a

con-

is inherited

dominant

study

58 and kindred

abnor-

MD

large-field-of-view gamma camera and all-purpose collimator. Calcific soft-tissue

174:215-222

Duke University Medical Medical Center, Durham, 1988; revision requested

vice.

were

sac

Radiology

by

1899

our

the

present

old

40.818

I

in

kindred

PATIENTS

manifestation.

tissues,

Duret

calcinosis Recently,

The

calcific

W. Lyles,

diagnostic

radiographs

the radiobogic features of the best-known components of turnoral calcinosis, (b) describe new observations on computed tomographic (CT) and magnetic resonance (MR) imaging of tumonal calcinosis, and (c) discuss new components of this unique disease.

be

#{149} Extremities,

Calcium

40.818

when

by

large

Marrow

may

#{149} Kenneth

ent

as seen on radiographs. the disease was first de-

subts of this of this article

When calcified paraarticular masses are present the diagnosis is rarely in diagnosis

is an uncorn-

patients, in addition to two unrelated patients, were evaluated clinically, biochemically, and radiognaphicalby.

calcifications.

calcific

calcinosis

an autosomab

attenuthat in with

lesions intensity

The

the

mon disorder characterized by presence of cabcified, paraarticu-

tumoral plete.

masses was remarkable in that the masses displayed high signal intensity on T2-weighted images despite

question.

UMORAL

The

a large

MD

derstanding of the clinical, biochemical, and radiobogic manifestations of

of the paraarticular

component.

T

scribed

a varied appearance, and solid to large and marrow abnormality ap-

pears as an area of increased ation and spotty calcification the skull may be associated

M. Harrelson,

Calcinosis:

bar masses, Although

and marrow lesions and for monitoring therapy. At CT the masses demonstrated from small cystic. The

#{149} John

III, MD

Radiology

Centers

Research to SM.

SerAbbreviations: tion

TE

=

echo

time,

TR

=

repeti-

time.

215

Clinical

Findings

in Patients

Age Patient

1*

10/M/black

2* 3*

58/M/black 53/M/black 33/F/black 77/M/white

5

large

along

the

site

in the

region

chantenic distribution sites

left

the

Lesion

+

+ t + t t

left

+ -

+ CPPD

surface

of

by a buncommon four masses greaten

bursa and three on the right

included

Myelitis

tro-

in the same side. Other

ischiogluteal

bursa in two instances and night ischiogluteal bursa in one, and one mass was seen in each of the following bursae: left and right olecranon, right

shoulder,

left

toes.

masses in the

right

calcaneus,

No soft-tissue

were knees.

found These

and

paraarticular

masses in the Four asyrnppatients were this modal-

CT.-Five paraarticular hip and three ischiogluteal masses in four patients were evaluated in the axial plane with this modality. All masses occupied a posterior position in the buttock at approximately the level of the lesser trochanten and deep to the regional muscles. At this level, the

of the

characteristically

located

grow into the into the 1 and masses, sciatic

216

femonis

and

to the inferior gluteal neurobundle and the sciatic nerve. involving the ischiogluteal

#{149} Radiology

+ -

-

-

+

+ +

present,

medial

tuberosity

femoris

to the

sciat-

surface

of

and

the

origin

and

semiten-

(6). As the masses to extend superiorly

gluteab region or infeniorly back of the thigh. In patients

was noted. Where the fasciab planes are not well defined, the masses with the adjacent the false impression tramuscular.

The

CT appearance

rnuscbes and of being in-

of the

b. Figure

paraarti-

1. Radiographs of evolving soft-tissue calcific masses of tumoral calcinosis in 10-year-old boy (patient 1). (a) Frog-leg projection of the left hip. The beginning of a calcific deposit (open arrow) in the ischiogluteal bums can be seen. This could be misdiagnosed as common calcific bursitis. A larger concretion (solid arrows) is seen in the region of the greater trochanteric bursa. (b) Twenty-one months later both calcific masses have become much larger and both

cuban masses varied. In three patients, the masses consisted mainly of large cystic components and some high-attenuation septations. Discrete thin layers of calcium outlined the wall of these cysts, and most of the centers

had low attenuation. aspect of the cysts

The showed

dependent calcium

layering, resulting in what has been termed the “sedimentation sign” (Fig 3a). In one patient, the mass consist-

ed of multiple of attenuation than sion mur in all MR used mass

small, globular areas with a solid rather

pect of the right shoulder in patient (Fig 4). The most informative images were the axial views obtained with T2-weighted

ages

the

sequences.

signal

Two

eas

patterns were

very

pattern

signal

weighted appeared

im-

(Fig

in which

4c).

images the inhomogeneous

an-

alternat-

void and

(Fig less

the same

pattern

of calcification.

that and

Typi-

and amorand often

low signal dominantly

intensity nodular

was preprobably

lated

to the

posits

(Fig

long Ti of the calcific 4a). The bone marrow

re-

deand

cortical bone appeared normal. No additional information was obtained from the coronal Ti-weighted image.

Bone

Marrow

mass

mostly high, component.

intensity

areas of signal (b) a more diffuse pattern

1

of increased signal inobserved: (a) a nodular

ed with signal

these

of the

but calcific

bright

of high

On

intensity

was inhomogeneous despite the large

and

have

cally this pattern is multinodular phous, with a cystic appearance with fluid-fluid levels (arrow).

cystic appearance (Fig 3b). Eroon destruction of the adjacent feor ischial tuberosity was absent eight masses. imaging.-MR imaging was to assess a large paraarticular located in the postenolaterab as-

and

quadratus

-

+ +

5, both with ischiogbuteal extension medially into the notch and ischionectal fossa

lay

the

-

posterior

muscles they tend

tensity

above

found

biceps

dinosus

under the gluteus maximus in the intermuscular fibrofatty tissue. Masses that arose at the site of the trochantenic bursa of the gluteus maximus lateral vascular Masses

pathy

dihydrate,

on the

ischial

give

ity.

were

the

blend

in a characteristic

were

ic nerve

paraarticular

distribution. Two small feet were not detected. tomatic masses in three discovered by means of

masses

CPPD Arthro-

Syndrome

pyrophosphate

bursa

in the fingers or soft-tissue lesions

have a distinctive radiographic appeanance, comprising multiple globular, amorphous calcific components separated by radiolucent bands. The cystic nature of these globular calcifications is demonstrated by a fluidfluid level on an upright radiograph in one patient. Bone scintigraphy.-All five patients were screened with this modality to define the location and possible cxtent of the masses (Fig 2). All 15 calcific lesions were evaluated. Thirteen showed marked increased tracer activity

calcium

PXElike

a.

extensor

of the

Dental

-

elasticum,

joints (often protected The hip was the most of involvement, with

sa).

Calcinosis

Calcific

+ + + + +

Note.-PXE - pseudoxanthoma = absent. * Same kindred. t Edentulous.

fashion

Tumoral

Calcific Masses

Sex/Race

4

-

(y)/

with

4b) bright

On Timasses again and had

Radiography.-Three patients had abnormalities of the bone marrow that accounted for a total of five besions.

Long

bones

patient 1 and the and 5. In a period

developed separate

narrow sites (right

were

involved

in

skull in patients of 3 years, patient

lesions tibia,

3 1

at three left femur,

and left tibia). The middle third of the shaft was affected in most of these long bones. The night tibial beJanuary

1990

a. 4 Figure 2. Bone scintigrams of calcific paraarticular masses and calcific myelitis (same patient as in Figure 1, obtained at the same time as radiograph in Figure la). (a) Right anterior oblique projection shows

abnormal

increased

paraarticular

soft

shoulder relates nosis

in the of

the

that radiographically with a typical tumoral soft-tissue

mass

ed). (b) Anterior

b.

uptake tissues

(not

right

corcalciillustrat-

projection

demon-

strates focal areas of increased uptake in the left elbow and hemipelvis that correspond to calcified soft-tissue masses of these sites seen on radiographs. The left elbow mass (curved arrow) had been surgically

C.

excised

14 months

earlier.

Thus,

tracer uptake on the present study indicates recurrence of the mass. Focal areas of increased uptake in the region of the left ischiogluteal bursa (open arrow) and the left greater trochanter

spond Figure time).

(solid

less and

a. 3. CT images CT scan of the

of calcific soft-tissue left hip obtained just

some

of which

patient as in Figure 1. demonstrates two large masses compressing adjacent muscles. The intermuscular fibrofatty plane with the sciatic nerve (arrow) separates the ischiogluteal mass (most medial) from the mass located in the region of the trochanteric bursa of the gluteus maximus. The cystic appearance of the masses reflects multiple low-attenuation septations separating nodular calcific components,

thin

have

walls

outlined

masses. (a) Image distal to the lesser

by calcium

and

of same trochanter

some

of which

have

fluid-fluid

demonas the

only

radiographic abnormality. The left femorab lesion demonstrated mild concentric peniosteab reaction incorporated into the cortex, and ill-dcfined patchy areas of calcification within

the

medullary

cavity

without

cortical destruction. A more discrete active periosteal response occurred with the left tibiab lesion. Clinically, Volume

174

#{149} Number

1

the patient ness, and

area,

experienced pain, tenderswelling of the affected

associated

with

bow-grade fever. lesion, there was and the medublary

pied bone three

malaise

As with periosteal cavity

and

the

femorab reaction was occu-

by a calcifying process without bysis (Fig 5a). In this patient, all marrow

lesions,

including

and

intense

(c) Anterior tibia

area

shows

a

of activity

1ev-

els (arrowheads). (b) Image of 58-year-old man (patient 2). Two masses are again seen on the left side: one in the ischiogluteal bursa (small arrow) and the other in the trochanteric bursa of the gluteus maximus (large arrow). These two lesions are much smaller than those in a and contain solid, not cystic, concretions. This solid pattern is considered to indicate metabolic inactivity, with less potential for growth.

sion was symptomatic and strated peniosteab reaction

corre-

corresponding to a marrow process in the midshaft. Radiographs (Fig 5) and MR images (Fig 7) at this site illustrate the calcific and inflammatory nature of the marrow process (calcific myelitis).

b.

Figure Axial

not palpable. of right

projection

large

arrows)

to the masses illustrated in la (obtained at the same These two masses were pain-

the

calcifications, resolved completely, as seen on follow-up radiographs. The

lesion (patient 3) was initially suspected on a radionuclide bone scan. On lateral radiographs, distinct dural calcifications were seen, in addition to patchy, focal calcifications within the dipboic bone. Skull radioskull

graphs in patient 5 failed to demonstrate the marrow lesion. Bone scintigraphy.-On scintigrams, three of the four intramedullany ab-

associated

normabities

were

moderately

to intensely

dionucbide uptake cavity of the bones

with increased

ra-

in the medulbary affected (skull

in

patient patient silent

3 and left femur and tibia in 1). In patient 1, the clinically lesion in the left femur was de-

tected

with

the

initiab

radionucbide Radiology

S

217

b.

a.

Figure

4. Axial (a) Ti-weighted

MR images of right shoulder image (500/25) shows a deep

flect the calcific nature of this dominantly high-signal-intensity in the

soft

tissues.

Small

soft-tissue posterolateral

process and associated nodular component

nodular

areas

of low

At this level the inflammatory reaction to the calcific components are again seen. 80).

study. That same study did any evidence of the earlier the right tibia. Similarly, a bone scan 1 1 months later

not show lesion in second demon-

signal

mass

edema forms

are

5.

Radiographic

cific myelitis. the right tibia

Anteroposterior of patient

fined,

mineralized

faintly

shaft

of the

left

femoral

later-

heads).

An active,

al skull projections demonstrated a peculiar patchy increased uptake involving the entire calvarium. In patient 5, however, the uptake in the

process

is stimulating

Figure

7, all obtained

skull

scans

in patients

(Fig

was

2c).

In patient

3, both

normal.

CT.-Only the two skull lesions (patients 3 and 5) and the left femonal bone marrow lesion (patient 1 ) were evaluated with CT. The fernoral Icsion appeared as increased attenuation and spotty calcification of the marrow. The cortex, peniosteum, and peniosseous soft tissues were normal (Fig 6a). In patient 3, CT dernonstrated patchy intradipboic calcifications in the occipital and panietal regions. Patient 5 had marrow calcifications in the facial bones and cabvanium (Fig 6b). Radiographs and bone scans were normal in this patient. MR imaging.-MR images of the clinically symptomatic right tibial diaphyseal lesion in patient 1 were abnormal. Focally increased signal intensity in marrow was demonstrated on T2-weighted images. Multiple small foci of decreased T2 signal intensity in the marrow correlated with small cabcific deposits. A thick penitibial ring of increased signal intensity was present in addition to increased signal intensity in the anterolateral subcutaneous fat (Fig 7b). On Tiweighted images, the marrow abnonmabity demonstrated decreased signab intensity (Fig 7a).

Other

218

#{149} Radiology

diffuse systemic calcifications on nadiognaphs

and cenwere and CT

2a. re-

calcifying

Foci

of signal

void

related

lesion

intramedullary

the periosteal with Figure at the same

(Compare

(arrowheads).

medullary cavity bone. Thick bone formation cortices (arrow-

2, 3, and

bone 2c and time.)

5. Pnomi-

nent dural calcification was evident on CT scans in patients 3 and 5. Of interest was a hand and wrist anthropathy

had

in patients

the

3 and

radiographic

5 that

appearance

of

calcium pynophosphate dihydrate crystal deposition disease. Calcification of articular cartilage

(metacarpophabangeal joints) and anticubar capsules (distal interphabangeal joints), in association with anticulan abnormalities of the left shoulden and right hip were all present in patient 3. Punctate cutaneous calcifications

were

graphs

of the

noticed

only

hand

on

radio-

in patient

5

(Fig 8).

Dental

Lesions

The dental abnormalities in 3 were previously reported (2). comparable lesion was seen in tient i Calcific deposits of the .

ben

pulp

tion

(pulp

of the

cavity

turnonal calcinosis. roots are bulbous

stones)

with

patient A pacham-

oblitena-

are characteristic

of

In addition, the and short (Fig 9).

been this

an abundance disease,

DISCUSSION

unusual

named beginning

calcifying

tumonal of the

masses,

calcinosis century,

(8).

of case

biochemical

of the deby

which

they

(7). Since there

has

the

which

other

More

(with familial

important

histories)

with

(2,9-12). features

not received

con-

incomplete in are

de-

the biochemical

recently, studied

on cases

literature

masses

associated

were

den have

of the

paraanticular

abnormalities masses

Most

reports and

the

scnibed.

of publications more than 2,000

with

reported sists

In 1943, Inclan et al, unaware previous publication by Duret, scnibed a condition characterized

Calcifications

Extensive ebral vascular demonstrated

formation.

a reflection of the a more diffuse pattern

marrow

marrow lesion and characteristic uptake in the symptomatic left tibial

resolution

in Figure that mainly

appearance of calradiograph of 1. Note the ill-dc-

(arrows) and the narrowed with well-preserved cortical uniform layers of peniosteal cover the medial and lateral

strated

scintigrams (arrows)

image (2,000/80) illustrates that a prerepresenting an inflammatory reaction calcific deposits. (c) T2-weighted image (2,000/

also seen, may have

soft tissues

Figure

C.

1) obtained at the same time as the bone nodular areas of decreased signal intensity

caused by inflammation. (b) T2-weighted the bulk of the mass (arrow), probably

intensity

involving

(patient mass with

the

However,

of the

dison-

attention. January

The 1990

a.

b.

a.

Figure 6. CT appearance of calcific myelitis. (a) Axial image of the middle thighs of patient 1 shows diffuse increased attenuation and foci of calcification within the left medullary cayity. This asymptomatic lesion (discovered by means of bone scintigraphy) is probably in a regressing state and does not induce any reaction in the adjacent tissues. (b) Axial image (bone windows) of the facial bones of 77-year-old man (patient 5). The medullary cavity is abnormal, with multiple foci of calcific attenuation in the distribution of the lateral wall of both orbits and nasal bones (arrowheads). These marrow lesions, quiescent at bone scintigraphy,

are probably

metabolically

inactive. b. Figure 9. abnormalities.

teeth

Panoramic radiographs of dental (a) Image of nonerupted

in patient

deposits bers,

(arrows)

1 shows within

typical several

so-called

“pulp

stones.”

the

calcareous pulp cham(b)

Image

of teeth in 53-year-old man (patient 3) shows multiple deformed roots (arrows)

have become with a.

bulbous

permission,

and

from

short

that

(reprinted,

reference

2).

b.

Figure

7.

Axial

MR

imaging

of calcific

myelitis.

(a) Ti-weighted

image

(500/25)

of both

legs of patient

1 illustrates decreased signal intensity in the right tibial marrow due to calcific myelitis. (b) With a longer TRITE sequence (2,000/80), increased signal intensity is seen in the marrow, concentrically about the tibial shaft, and in the peniosseous tissues. This reflects the active inflammatory nature of the medullary process and a similar reaction in the

periosseous

tissues.

2nd decade the earliest

was noted at 3 years of age, in patient Although tumoral calcinosis is a lifelong disorder, it seems to be metabolically

I Figure 8. Radiograph (magnified soft-tissue technique) demonstrates calcium pyrophosphate dihydrate anthropathy and other calcifications in the hand of a 77-year-old man (patient 5). Note vascular calcifications and small punctate calcifications of the skin (solid arrow). Triangular cartilage, articular calcifications (chondrocalcinosis) (open arrows), and articular abnormalities of the 5ccond and third metacarpophalangeal joints can be seen.

of life (8). In our patients, manifestation of the disease

active

in the

plains

the

from

Africa

number of cases reported and the southern United States. Tumonal calcinosis among whites is less common (i6). About onethird of the reported cases are familial (1,2,15,17). Almost all of them occur in siblings,

with

an inborn

error

metabolism is accepted cause (2,8-12). The predefect is unknown but

as the primary cisc biochemical

probably relates to abnormal phosphate reabsorption and i,25-dihydroxy-vitamm

D formation

tubule.

The

in the

resulting

proximal

renal

hyperphosphate-

mia and hypervitarninosis D may ulate the formation of extracellular

stimma-

trix vesicbes in the synoviab bunsae, marrow, dental pulp, vessels, skin, perhaps

the

ization full nadiobogic cinosis

is not

spectrum well

of tumonab

known.

CT and

features of the paraanticular marrow lesions have, to our edge, not been described. Multiple

posed Volume

theories

to explain 174

have

1

MR

and

knowl-

been

the cause

#{149} Number

masses

cal-

of this

in the form

dis-

inducing

of hydnoxyapatite

masses may range to 79 years, although

typically

occur

within

from they the

When patient slowly

age 3 will 1st

or

af-

disorder,

tumoral

several

members

calcinosis of various

present

in the hip,

escape

physical

4. The masses over a period

quite

large.

they

may

detection,

as

miin

tend to grow of years and may

Generally

they

are

painless and do not limit range of motion of adjacent joints unless they be-

come of the

in

as such, have been well described in the literature (1,7,13,14). Characteristicabby, these tumorous masses occur in the panaarticular tissues, most often in the hips, shoulders, elbows, and feet.

become may reac-

tion of tumonal cabcinosis. In tumonal calcinosis the onset

most

and

affect

prevalence

(8). Although this favors an autosomal

generations in one kindred, suggesting a dominant pattern (2). Soft-tissue masses are the bestknown component of the disease and,

tiably

mineral-

crystals. This calcium deposition elicit the typical gnanubomatous

soft-tissue months

pro-

retina,

a 50%

fected generations hereditary pattern may

At present,

population.

There is apparently no sex predorninance (8,15). Most of the reported cases have been in blacks (7,8), which cx-

recessive ease (i3,i4). of phosphorus

younger

i.

large.

When

symptoms

occur,

from compression of adjacent neural structures such as the sciatic nerve (14). When large, the besions tend to ulcerate the skin and form they

may

result

Radiology

#{149} 219

a sinus

track that drains chalky, milklike fluid. This fluid may look like pus but is usually sterile and contains calciurn phosphate and calcium carbonate. The masses can, however, become a site of secondary infection. Recently, association of a diaphyseal

paraanticular masses, may be absent (20,27,28). Awareness of the different clinical components of tumoral calcinosis, as well as the variability in expression, are vital for the diagnosis of this condition. Specific biochemical abnormalities

bone marrow panaanticular

distinguish

sis

was

lesion masses

suggested

pearance

with the classical of tumoral calcino(18).

The

typical

unique

ap-

is that

of an inflammatory process involving the shaft of long bones (diaphysitis). Clinically, these patients have an elevated sedimentation rate. Because of reactive changes

adjacent

soft tissues,

these

in

marrow

be-

sions may be misdiagnosed as osteomyelitis on neoplasm. Dental abnormalities, consisting mainly of root enlargement and intrapulp calcifications, were initially observed in tumoral calcinosis by Hunter

et al (19). Other tab lesions

described

in association

paraanticulan rnia,

reports

with

masses,

deneither

hyperphosphate-

or diaphyseal

lesions

(20).

In a

more recent report (2) of a kindred affected by tumoral calcinosis, it was found that three of the patients had the same dental lesions described by Huntpoorly

recognized

compo-

nent of tumonal calcinosis is a group features that resemble pseudoxanthoma elasticurn, including skin calcifications,

and

vascular

angioid

association

streaks

of the retina. calcinosis

ported

elasticum

simultaneously

Engel

(21)

groups

which

may

be active

Cystic

spaces

containing

cific

granules

and

was

by

Barton

described

The first

McPhaul

et al (22).

the same

neand

brothers,

(1,7,35);

with

stroys

lesion

are scant

(18,28). We hydnoxyapatite

and

the

results

in

deposition of in the marrow

calcification,

eliciting

bone marrow inflammatory with peniosteal new bone in bone marrow infarction. myelitis usually involves

aphysis

of

long

bones,

(eg, the skull

but

term

reformaThis the di-

other

in our patients)

bones

may

be

diaphysitis

our patients 2 and 3. Kaplan et al reviewed this association in five patients, in addition to one of their own (23). Re-

The radiographic hallmark of tumoral calcinosis is the demonstration of large multigbobulan calcific deposits in

cently three other cases have been reported (18,24), making a total of nine cases. All nine (including three children) have vascular calcification, six have angioid streaks, and three have demonstrated skin calcifications. Skin

a panaarticular distribution, along the extensor surface

calcifications without other

oma

elasticum

other

cases

scnibed

in tumoral features

were (17,25).

described with

in two et al (26)

calcific

skin

de-

tu-

mons. One of our patients (patient 5) had skin and vascular calcification. Patients 2 and 3 had the retinal lesions and vascular calcification. We believe that this pseudoxanthoma elasticum-

like complex is another of tumoral calcinosis. All

moral logic

the

clinical

of tu-

calcinosis

are related

to patho-

calcification

of various

(paraarticular teeth,

manifestation

components

skin,

tissue, and

vessels).

bone

tissues

marrow, These

compo-

nents may be variably expressed in affected individuals (2). Furthermore, the most characteristic component, the 220

#{149} Radiology

features

of

these

Ra-

masses

have received the most attention in the literature (7,13-15,22). The multinodulan appearance is due to the radiolucent fibrous septa that separate the spaces containing the calcaneous material. This calcified material may be pastelike

calcinosis of pseudoxanth-

McKee

16 patients

diognaphic

and

have

a homogeneously

diognaphic semifluid,

appearance, like “milk

demonstrate

sedimentation

radiognaphs

(32,33).

sedimentation

sign

bolically

active

dense

na-

or it may of calcium,”

be and

on

We

lesion

the a meta-

with

potential

grow in size on diminish in response phosphate depletion therapy. We observed nadiognaphically the initial

development

masses

in

located

in the

berosity,

and

of

three

1 . These

patient

left left

elbow, greater

calcific

bursitis.

recent

literature,

the

synovial

because of in histologAs an explaviews, it is

calcific

process

tissue

of

the

debunsae

growth. It is important to realize that these paraarticulan masses may not develop in all patients with tumonal calcinosis. In the present study, as in other senies, the hips were the most common site of involvement. In the largest sungical series, the paraarticuban masses were located, in order of decreasing frequency, in the hips, elbows, shouldens, and feet (i5). Often the masses were multiple and bilateral. masses

are

not

exclusive

to tumoral calcinosis, however. Masses that are radiologically indistinguishable from those described in tumonal calcinosis may be seen in patients with chronic renal failure who are undergoing hemodialysis (36). Although these patients also have hypenphosphatemia, vascular calcifications, and various types of anthropathies, they do not manifest the calcific myelitis on dental lesions. Furthermore, a history of renal

failure

and

the

features

of renal osteodystrophy are clues to the connect diagnosis. Other conditions with similar soft-tissue calcifications have been reported (i4), but in our cxpenience these are exceptionally rare. It is important to recognize that there is a spectrum of soft-tissue calcification in tumoral calcinosis that ranges from none to the large panaarticulan tumonal masses. Rather than tumonal, however, the soft-tissue calcifications may manifest as an unusual diffuse subcutaneous pattern

(37)

more

characteristic

of

colla-

gen vascular often referred

upright

believe

indicates

that the

chronic

usually of joints.

most

Panaarticulan

nonspecific

suspect that crystals

of

with

cal-

identify

the

conceivable

(29).

fluid,

at the edges,

affected. Thus, the may be misleading.

Both

on inactive

appearance

however, rejects this concept the absence of bunsal tissue ic specimens of the masses. nation for these conflicting

active phase, and collagen sclerosis without fluid suggests inactivity. Recent electron microscopic and crystalbographic investigations (30,3i) defined the ultrastructune of tumoral calcinosis and identified the crystal as hydnoxyapatite. Histologic data from the mar-

tissues

and

as a

bone disease, including renal phosphate reabsorption threshold (9,10), (b) hyperphosphatemia (2,8,14), and (c) elevated serum i,25-dihydroxy-vitamin D level. However, serum calcium, panathyroid hormone, renal function, and alkaline phosphatase are normal (2,9-12). Pathologic features of the soft-tissue masses (15,29,30) are reflected in radiologic findings. The mass is a granubomatous reaction to a foreign body,

a local action tion as calcific

calcifications,

of tumonal

pseudoxanthoma

of

calcinosis

metabolic (a) elevated

row

en et al. Another

tumoral

typical

We believe these calcifications initially take place in the bunsae and, with growth, extend to the adjacent fascial tissues but rarely cause bone erosion (24). This concept of the calcification originating in the bunsae is not new. Early investigators considered tumoral calcinosis a primary process of bursae

to

to

soft-tissue

diseases. This pattern is to as calcinosis univensalis. Cutaneous calcification (calcinosis cutis) of the flexunal surfaces, described clinically in tumonal calcinosis (17,25), had not, to our knowledge, been radiographically documented but was demonstrated in our oldest patient (Fig 8). Vascular

calcification,

scnibed dnen

in young (18),

was

previously

adults present

(38) in

de-

and

our

chil-

three

masses were left ischial tu-

est

trochanter.

was observed in our patients 3 and These two patients also demonstrated

All these early calcific deposits were bocalized to anatomic sites known to be occupied by bunsae (6,34) and had the

patients.

cation

was

calcification (chondrocalcinosis)

disk

Intervertebral reported

previously

of anticular

old-

calcifi(38)

and

5.

cartilage and

anticulan

January

cap-

1990

sules, in addition to articular abnormalities radiographically consistent with calcium pyrophosphate dihydrate crystab deposition disease. To date, the association of tumoral calcinosis and calciurn pyrophosphate dihydnate has not, to our knowledge, been reported. Whether this is a true association or a coincidental association cannot be determined from this small series. Extensive intracranial dural calcifications were also encountered in patients 3 and 5. A similar distribution was previously

described

(25).

Radionuclide imaging has been used in diagnosing the paraarticular soft-tissue masses of tumoral calcinosis (39-. 43). These reports demonstrated similar massive soft-tissue localization of the nadionuclides. Uptake of Tc-99m-labeled phosphate compounds by the calcific masses is probably related to surface adsorption (44) of the hydnoxyapatite crystals. Radionuclide imaging is the most reliable and simplest method for detection, localization, and assessment of extension of the calcific masses. Scmntignaphy may demonstrate

abnormalities

even

when

physical

cx-

(42). Bone scintignaphy is useful in the assessment of the effects of phosphate depletion therapy. In the present series of 15 masses, only two small masses in the feet were not detected with nuclear amination

results

imaging,

are

whereas

masses

were

negative

four

depicted

unsuspected with

this

modal-

ity. Response to surgery was assessed by means of bone scan in one patient (patient 1). In this case, scintigraphy demonstrated recurrence of an elbow lesion, ablation of a large hip lesion, and growth of the unnesected shoulder mass. CT

imaging

has been

quently to evaluate (24,36). We studied five patients. The

these calcific of calcification

used

The

mally

on distally

masses

in of

and CT patterns analyzed. Axial CT

may in

extend

proxi-

fascial

planes

the

anteriorly and medially of the sciatic notch. The

these

masses

often

into the margins

blend

with

of the

may

mass,

inflammatory

be

seen

perhaps

in

the

or

adjacent

periphery

to a reactive in adjacent tis-

sues.

The patterns

Volume

masses demonstrated of calcification.

174

#{149} Number

varied CT In three pa1

of

tions)

many

sac.

They

then

often

grow,

with

pro-

gressive destruction of the synovial sues making histologic proof difficult. MR imaging of the paraanticular masses

and

marrow

lesions

of

tis-

tumoral

calcinosis has, to our knowledge, not been previously described. Despite the known limitations of MR for imaging calcific processes (45), an inflammatory

component not ing

in the panaarticubar

demonstrated modality,

weighted

by any is conspicuous

images.

This

masses,

other

imagon T2-

can be best

cx-

plained by the long T2 values associated with the granubomatous foreignbody reaction characteristic of tumoral calcinosis (30). It is possible that in metabolically stable lesions this reaction is less evident. Peripheral scattered areas of increased signal intensity on Ti- and T2-weighted images may indicate displaced regional fatty tissue. Calcific deas expected,

display

long

had

masses of tumoral calcinosis, lesion (interpreted as Engelmann disease), a dental lesion, or hypenphosphatemia (20). We believe that the bone marrow lesions, usually seen in children, are a definite component of tumoral calcinosis, most often affect-

a cortical

low-attenuation

Ti

and

T2 relaxation characteristics. Although other conditions may have similar MR features, in the setting of hyperphosphatemia without renal failure the presence of panaarticular masses with this MR pattern is most consistent with tumoral cabcinosis. The association of calcific panaarticu-

ing

long

bones

to pathologic

and

probably

relating

calcification

of

row tissue, which elicits tony peniosteal reaction.

mar-

an inflamma-

This be misdiagnosed graphically as bone marrow osteomyelitis, or neoplasm. of this process may obviate antibiotics. In patient 1, all sodes of diaphysitis resolved could

myelitis

the

calcific radioinfarction, Awareness biopsy or three epiwithout

antibiotics.

Scintigraphic marrow lesion not

been

features of the bone have, to our knowledge,

previously

reported.

Four

bone marrow lesions in our series were studied with this modality. Two involved long bones, femur and tibia (patient 1), and two affected the calvarial dipbo#{235}(patients 3 and 5). Moderately to intensely increased tracer uptake was observed in all instances, except in patient

5. In

cabby

involved

long

bones,

shaft

in a homogeneous,

the

the

uptake

middle

typi-

third

of the

diffuse

pat-

tern indicative of bone marrow lesions. In the skull the pattern was diffuse and patchy. The increased uptake probably results from a combination of factors that include bone marrow calcification and inflammation in addition to peniosteal and endosteal reaction. Once this

pathologic

process

the scans return two lesions had normal

on

becomes

a follow-up

bone

tient 5 had gross marrow of the skull on CT scans take on bone scans. The pattern in long bones in with soft-tissue paraanticulan in our opinion, characteristic al calcinosis. CT features of calcific to our

quiescent,

to normal. In patient become completely

knowledge,

scan.

1, Pa-

cabcifications but normal upscintigraphic combination uptake is, of tumormyelitis

not been

have,

reported.

lesion. A similar condition was reported in hyperphosphatemic patients (six children and one adult), but these patients did not display soft-tissue masses

When this condition involves long bones, there is focal increase in the attenuation of the bone marrow due to an inflammatory reaction. In addition, discrete spotty calcific areas of attenuation are seen. Peniosteal new bone formation may be seen depending on the activity of the marrow lesion but without lysis of the cortical bone. These CT features could be confused for those of a neoplastic process on bone marrow infanction. The intradipboic calcifications, readily depicted by CT, are more patchy in appearance and more diffuse in distribution and involve most of the

(27,28,46).

skull

masses

and

diaphyseal

bone

lesions was recently described diognaphicably, this marrow the appearance of peniostitis

region of

due

process

composed with

centers and calcific walls. These masses also demonstrated the layering phenomenon believed to represent calcium salt in suspension (36), a pattern indicative of a metabolically active lesion undergoing ion exchange with the extracellular fluid. These cysts may become confluent and form large cavities, as in patient 5. Another pattern consisted of multiple globular components that uniformly calcify. In this instance, the masses are more metabolically stable and have little potential for growth. The CT location of the paraanticular masses, together with their pattern of early calcification, which resembles bursitis, leads us to conclude that the calcific panaarticulan deposits of tumoral calcinosis anise in the synovial bun-

lan

muscles and give the appearance of intnamusculan location or extension. In other instances, a thin layer of fatty tissue separates the masses from adjacent muscles. Occasionally, a capsulelike structure

were

structures

short

images best showed the location of the masses deep in the buttock. All of them occupied the fibrofatty plane deep to the gluteus maximus. This may make the mass appear poorly defined at

times.

they

cystic

posits,

infre-

tumoral calcinosis 10 pelvic masses origin and location

deposits were

tients,

calcification. 1 had three

ullary

tient tis

in

long

bones

diploic marrow radiologically is confusing

The

(18). Ralesion has with mcd-

In our series, paepisodes of diaphysi-

and, of the abnormal.

with

in patient 3, the cabvanium was The literature

regard

to this

disorder

was

(all

report, children

six members of three

marrow

diagnosed

as a new syndrome of hyperostosis ticalis and hyperphosphatemia.

other

marrow

conIn an-

of a kindred

different

genera-

Osseous

and

even

the

destruction

flammatory changes at these sites. These deposits

in

association

facial

bone

marrow.

on peniosseous

in-

were not observed calvanial marrow with

the

Radiology

previ-

#{149} 221

ously

described

cifications

dural and vascular cala distinct triad of CT may be specific for tumor-

form

findings

that

ab calcinosis. The marrow

lesions

produced

MR

signal

probably

because involving

of an mar-

changes

Acknowledgment: We give special acknowledgment to Juanita Cates for her patient assistance in the preparation of this manuscript.

References 1.

inflammatory reaction row, peniosteum, peniosseous soft tissues, and subcutaneous fat. The process is identified increased

on signal

T2-weighted intensity

images occurring

2.

by fo-

cabby in the marrow and appearing as a peniosseous ring and as strands in the subcutaneous fat. Small scattered foci of bow signal intensity within the marrow on Ti- and T2-weighted images are consistent with calcific deposits. The

3.

Duret MH. Tumours multiples et singulieres des bourses sereuses (endotheliomes, peutetre d’origine parasitaire). Bull Mem Soc Anat Paris 1899; 74:725-733. Lyles KW, transmission dominant

Burkes EJ, Ellis GJ, et al. Genetic of tumoral calcinosis: autosomal variable clinical expressivity.

J Clin Endocrinol Lyles KW, Halsey

Metab 1985; 60:1093-1096. DL, Friedman NE, Lobaugh

Swartout sitis:

R, Compere

the

pain

EL.

in the

Ischiogluteal

arse.

JAMA

6.

appropriate

7.

Inclan

8.

nosis. Viegas

specific.

clinical

Similar

setting,

awareness

of this lesion may obviate surgery. thenmore, it is important to realize this marrow process may be present without the panaarticular masses.

Furthat

A syndrome

pseudoxanthoma a component

elasticum of this disorder.

abnormalities, phosphate thy, may

calcinosis. to confirm observations.

similar

similar dihydnate be another the

research

true

of

the

opinion,

the para-

and

marrow

soft

tissues,

11.

bone

12.

2. Philadelphia:

A, Leon

P. Gomez

surface 32.

anato-

33.

Tumoral

34.

J, et a!. Tumoral calcinosis: a case report and review of the literature. J Hand Surg [Am] 1985; 10:744-

35.

Zerwekh JE, Sanders LA, Townsend J, et al. Tumoral calcinosis: evidence for concurrent defects in renal tubular phosphorus transport and in la, 25-dihydroxycholecalciferol syn-

36.

thesis.

37.

Calcif

Tissue

Int

1980;

32:1-6.

R, Chesney

RW,

Eisenstein

14.

Baldursson calcinosis Joint Surg

H, Evans EB, Warren with hyperphosphatemia. [Am] 1969; 51:913-925.

F.

38.

D’Aboville M, Gaussin G, Regouby Y. et al. Calcinose tumorale chez une femme blanche. J Radiol 1983; 64:429-432.

17.

Pursley TV. Chausmer AB. Cutaneous festations of tumoral calcinosis. Arch tol 1979; 115:1100-1102. Clarke E, Swischuk LE, Hayden CK.

18.

tine and pulp nosis. Br Dent Thurmon TF,

20.

.

23.

with

tumoral

calci-

J 1973; 135:446-448.

Jackson J. Tumoral calcinosis and Engelmann disease. Birth Defects 1976; 12:321-325. McPhaul JJ, Engel F. Heterotopic calcification,

22.

associated

hyperphosphatemia

and

angioid

light

and

electron

microscopic

study with electron diffraction and x-ray microanalysis of the mineral deposit. J Submicrosc Cytol 1984; 16:577-583. Boskey AL, Vigorita VJ, Sencer 0. Chemical, microscopic, and ultrastructural characterization of the mineral deposits in tumoral calcinosis. Clin Orthop 1983; 178:258-269. Oosthuizen SF, Roux P, Wet AS. Calcino-un-

type lipo-calcino-granulomatosis. 1950; 23:598-600. J. Tumoral calcinosis sedimentation sign. Br J Radiol 1974; Hug

Br with 47:734-

I, Cuncaga

736. Bywaters EGL. The bursae of the body. Ann Rheum Dis 1965; 24:215-218. Ghormley RK, Manning CF. Power MH. Multiple calcified bursae and calcified cysts in the soft tissues. Funct West Surg Assoc 1942; 51:292-309. Cordon LF, Arger PH, Dalinka MK, et al.

tomography

in soft tissue

calcifica-

tion layering. J Comput Assist Tomogr 1984; 8:71-73. Feldman ES. Dalinka MK, Schumacher HR. et al. Diffuse soft tissue calcification in tumoral calcinosis. Skeletal Radiol 1981; 7:33-35. Hacihanefioglu U. Tumoral calcinosis: a clinical and pathological study of eleven un-

reported cases in Turkey. J Bone [Am] 1978; 60:1131-1 135.

Joint

Surg

Lafferty FW, Reynolds ES, Pearson OH. Tumoral calcinosis: a metabolic disease of obscure etiology. Am J Med 1965; 38:105-1 17.

40.

Abbud

41.

Scintiscans of two siblings with tumoral calcinosis. Clin Nucl Med 1979; 4:117-119. Leicht E, Berberich R, Lauffenburger T, et al.

Tumoral seeking

Y, Balachandran

5, Prince

calcinosis: accumulation tracers in the calcium

MJ, et al.

of bonedeposits. Eur

42.

Nucl Med 1979; 4:419-421. Balachandran W, Abbud Y, Prince Tumoral calcinosis: scintigraphic

43.

an affected family. Br J Radiol 1980; 53:960964. Manaster BJ, Anderson TM. Tumoral calcinosis: serial images to monitor successful dietary therapy. Skeletal Radiol 1982; 8:123-

44.

Epstein

MJ, et al. studies of

125.

DA, Solar

M, Levin

tion of long-standing calcification by 99m 1977; 128:145-147.

Tumoral

calcinosis, diaphysitis, and hyperphosphatemia. Radiology 1984; 151:643-646. Hunter IP, MacDonald, DC, Ferguson MM, et al. Developmental abnormalities of the den-

19.

21

maniDerma-

of hy-

J Pediatr

39.

Tumoral J Bone

16.

hyperphosphatemia.

hy-

a new

1981; 99:900-904. Thomson JC. Calcifying collagenolysis (tumoural calcinosis). Br J Radiol 1966; 39:526532. Dryll A, Bardin T, Lansaman J, et al. Tumor-

Computed

B, et al.

Yaghmai I, Mirbod P. Tumoral calcinosis. AJR 1971; 111:573-578. Bishop AF, Destouet JM, Murphy WA. Tumoral calcinosis: case report and review. Skeletal Radiol 1982; 8:269-274.

Cortical

iversalis: J Radiol

calci-

Elevated serum calcitriol concentrations do not fall in response to hyperphosphatemia in familial tumoral calcinosis. Am J Dis Child

45.

Boyko imaging

46.

OB, Cory

EJ.

DA, Cohen

of osteogenic

Demonstra-

metastatic soft Tc diphosphonate.

and

MD, Ewing

tissue AJR

et al.

MR

sarcoma.

AJR 1987; 148:317-322. Le Lost x, Ducastelle C, Hemet J, et al. Hyperostose corticale et r#{233}tr#{233}cissement du canal m#{233}dullaire

des

Os avec

hyperphosphatas#{233}mie is 1976; 52:2149-2154.

hyperphosphor#{233}mie

alcaline.

Scm

Hop

et

Par-

streaks

of the retina. Am J Med 1961; 31:488-492. Barton DE, Captain MC, Reeves RJ. Tumoral calcinosis: report of 3 cases and review. AJR 1961; 86:351-358. Kaplan

C, Vinceneux

P, Grossin

L’associatiori d’une calcinose pseudo-xanthome elastique. Osteoartic 1980; 47:657-660. 24.

Bard

H, Kuntz

D, Molle

m#{233}tabolisme du phosphore calcinose tic 1984;

#{149} Radiology

31.

Lippincott,

CM.

and

al calcinosis:

exostosis Am

JAMA 1943; 121:490-495. SF, Evans EB, Calhoun

Steinherz

marrow,

and dental region strongly suggest tumoral cabcinosis. CT and MR imaging are excellent in assessing the calcific masses and myelitis. Although the diagnosis of tumoral cabcinosis is appanent when the calcified soft-tissue masses are present, it may be elusive when the only manifestation is the calcific myelitis. U

222

plantar

Prince MJ, Schaefer PC, Goldsmith RS, et al. Hyperphosphatemic tumoral calcinosis. Ann Intern Med 1982; 96:586-591.

le-

sions and to help monitor therapy. Findings of increased uptake in the paraarticular

30.

487.

is needed of these

masses

of the

Mitnick PD, Goldfarb S. Slatopolsky E, et al. Calcium and phosphate metabolism in tumoral calcinosis. Ann Intern Med 1980; 92:482-

15.

articular masses originate from bursal calcifications. Bone scintigraphy is the best modality to depict and enable bocalization

10.

13.

pyno-

prevalence

In our

29.

1985; 139:816-819.

is probably Anticubar

crystal arthropasign of tumonal

Further

perostosis

748.

to

to calcium

Bursitides

my. 6th ed. Vol 1932; 436-437.

9.

In summary, tumorab calcinosis is a hereditary metabolic disease characterized by a calcific process that affects different osseous and extnaosseous soft tissues and is best known nadiognaphicabby for panaanticulan calcified masses. Less well known manifestations indude (a) hyperphosphatemia, (b) dcvated 1,25-dihydroxy-vitamin D levels, (c) cabcific myelitis, and (d) dental ab-

nonmalities.

A.

JC, et al.

28.

227:551-552.

findings can be seen in neoplastic processes, infarction, infection, and some traumatic insults. Nevertheless, in the

not

1W, Kallmeyer

perostosis with hyperphosphatemia: syndrome. J Pediatr 1970; 77:986-990. Mikati A, Melhem RE. The syndrome

1974;

of the foot, painful heel. gonorrheal of the os calcis, metatarsal neuralgia. Surg 1926; 1:117-126. Spalteholz W. Hand atlas of human

are

bur-

DA, Simson

Unusual cutaneous lesions in tumoral calcinosis. Arch Dermatol 1970; 102:465-473. McKee PH, Liomba NC, Hutt MSR. Tumoral calcinosis: a pathological study of 56 cases. Br

J Dermatol 1982; 107:669-674. Melhem RE, Khachadurian AK.

Correlations of serum concentrations of 1,25-dihydroxyvitamin D, phosphorus, and parathyroid hormone in tumoral calcinosis. Clin Endocrinol Metab 1988; 67:88-92.

4.

Whiting

27.

C.

Hertzler

features

26.

with

5.

MR

25.

tumorale. 51:63-68.

Rev

M, et al.

tumorale et d’un Rev Rheum Mal

D, et al.

dans Rheum

Etude

du

un cas de Mal

Osteoar-

January

1990