From

the

Archives This article criteriafor

meets the 1.0 credit

hour In Category theAMA Physician’s Recognition To obtain

1 of

of the

Langerhans Margaret

Cell

A. Stull,

Kenneth

0.

MD

Histiocytosis

#{149} Markj

Devaney,

AFIP

Kransdorf

of Bone’

LTC,

MC,

USAR

MD

Award. credit, see

the questionnaire the end oftbe

at article.

Langerhans

cell

histiocytosis

(LCH),

previously

called

histiocytosis

X, refers

to a spectrum of disease characterized by idiopathic proliferation of histiocytes producing focal or systemic manifestations. Causes and pathogenesis remain unclear. However, recent studies suggest abnormal immune regulation

as an

important

factor.

The

three

classic

syndromes

may

have

consider-

able clinical overlap: eosinophilic granuloma, in which the disease is limited to bone in patients usually 5-15 years old; Hand-SchUller-Christian disease, characterized by multifocal bone lesions and extraskeletal involvement of the reticuloendothelial system (RES) usually seen in children 1-5 years old; and Letterer-Siwe disease, in which there is disseminated involvement of the RES with a fulminant clinical course in children less than 2 years old. Osseous involvement is typically in the flat bones, with lesions of the skull, pelvis, and ribs accounting for more than halfofall lesions. About 30% of lesions are in long bones. Radiographic appearance of osseous LCH depends on site of involvement and phase of the disease. Early lesions appear aggressive

with

poorly

lesions

remodeled U

defined

appear

well

margins

defined

and

and

periosteal

sclerotic

reaction.

margins

and

Late expanded

INTRODUCTION

strates

cell

AP

Langerhans

cell

terms:

I From

=

Bones, 1992;

the

Departments

most

of clinical

as benign

and

anteroposterior,

histiocytosis,

RadloGraphlcs

(LCH),

spectrum

as well

Abbreviations:

Index

histiocytosis

a broad

infection

MDP

diseases,

=

methylene

40.60

sas City Address

(K.O.D.). reprint

Armed

opinions

or assertions

or as reflecting Health

C RSNA,

the

views

occurring

in children,

demon-

may

those

features

that

tumors.

Osseous

involvement

of Pathology,

H-E

Forces

Institute

=

mimic

is the

of most

hematoxylin-cosin,

LCH

=

diphosphonate

#{149} Children,

skeletal

system,

40.60

#{149} Histiocytosis,

40.60

12:801-823 of Radiology,

Received requests

commonly

radiologic

malignant

AFIP =

and

Georgetown

University

thology (M.J.K.) and Orthopedic Pathology (K.O.D.), 54, Rm M121, Washington, DC 20306-6000; Radiology Health Sciences, Bethesda, Md (M.J.K.); and Pathology,

the

show

appearance.

Langerhans

The

lamellated

may

February to MJ.K. contained of the

19,

1992;

herein

Department

revision

are

the

of the

Medical

Armed Forces and Nuclear University requested

private Army,

views Department

Center,

Washington,

DC

(M.A.S.);

Radiologic

Pa-

Instiwte ofPathology, Alaska Ave and Fern St, Bldg Medicine, Uniformed Services University of the ofMissouri-Kansas City, Truman Medical Center, )C. March

of the

19 and

authors

of Defense,

received

and

are

April

not

or Uniformed

10; accepted

to be construed Services

April

13.

as official University

of

Sciences. 1992

801

common

manifestation.

skeletal

alterations

disease

is considered

Recognition so

in the

condition.

of the

is important

that

differential

diag-

nosis.

The purpose osseous

of this article

radiologic

Armed

Forces

experience

is to present

features

Institute with

based

480

cases

the

of LCH

of bone

with

clinical

on the (AFIP)

of Pathology

Vital organ dysfunction is associpoor prognosis (8,15,16). LettererSiwe disease generally occurs in children less than 2 years of age and is characterized by disseminated multisystem involvement. The

ated

the

course

morbidity and

to review

is usually

and

(8,14,15).

Recently,

the literature. The disease is discussed as a single entity subdivided into the three overlapping clinical variants. The historical background, pathologic features, clinical

posed

abandoning

egories extent

in favor ofdisease

manifestations

indicator,

of the

various

disorders,

differ-

described. The discussion of radiologic features includes those from radiography, hone scintigraphy, computed tomography (CT), magnetic resonance (MR) imaging, and angiography, augmented where appropriate by accompanying pathologic material. ential

diagnosis,

LCH,

formerly

currently

known

and

The Langerhans

cell,

distinctive disease (2,4-9).

at 0.05-0.5 in the

United

in blacks though

the reticuloendothelial

bones,

skin,

is involved

lymph

affect

is estiper

and three

therapy

clinical major

(ie,

morbidity

Hand-Scb#{252}ller-Cbristian

ized etal

involvement

abdominal

are typically

bone oflymph

viscera.

Children

afflicted

by this

1-5 chronic

is characterextraskelskin, and

years

prognostic

Children (hedysfuncsignifi-

of age with isoLCH have a favor-

OVERVIEW

(1893),

of a manifestation

credited

who

boy with

reported

diabetes

the

petechiae course.

thought

case

of age recurring

(1865),

3-year-old

and

spleen,

and

nodular

renal

tuberculosis

pelves,

(10,16,22first de-

the physician,

Tho-

at the Transactions

Pathological Society ofLondon Smith’s patient, a 41/ryear-old

fluctuant sweffing with well-defined

ofa

exophthalmos,

infiltrates;

liver,

to represent

Smith

Hand

bronzed dry skin, and (22). The child died after Necropsy revealed calvarial

pulmonary

in the

of LCH

Alfred

insipidus,

hepatosplenomegaly,

cutaneous

to Dr

mas

and

nodes,

by the

(3,4,10,13,15,17,19-21).

expres-

(2,8, 10, 13, 14).

lesions

subcat-

with vital organ or pulmonary) prognosis and

24). Some, however, attribute scription of LCH to a British

syndromes,

disease

by multifocal

pro-

and LCH

important

spleen)

Eoslnopbillcgranuloma

has low

high

have

at presentation.

description

is commonly

masses

to a single

and

first

any and

is an

HISTORICAL

The

lesions;

male is rare organ, al-

or few bones and typically occurs in children and young adults. This localized form of LCH responds to minimal is

U

a 2-month

liver,

pathologic

mortality

authors

Patients older than 2 years lated or multifocal osseous able prognosis (4,13,17,20).

disease

system

extent

as is age

2 years of age matopoietic, hepatic, tion have the poorest

a slight

cases.

of LCH include may overlap.

limited

children

The

nodes,

in most

The varied sions which

incidence with

may

histio-

component

100,000

States,

LCH

a unique

The

(8,10-12). (12).

formation

pathologic

per

predominance

prolifera-

granuloma

some

with outcome

these eponyms of characterizing (2,6,13,14,17-19).

under

cant

fatal

X, is

of immune

by abnormal

is the

ofthe mated year

as histiocytosis

manifested

(1-3).

are

a disorder

of histiocytes

cyte,

therapy

considered

regulation,

tion

and

Disease

fulminant,

frequently

over bone

sated yellow material abscess” (23-25). In 1905, Dr Thomas

of the

(23,25). child, had

a

the occiput associated defects and inspisdescribed

as “dried

Kay reported

the

up case

of a 7-year-old boy with exophthalmos, polyuria, and lytic skull lesions (10,24). Subsequently, descriptions of Dr Artur Sch#{252}ller’s two cases in 1916 and Dr Henry Christian’s case

in 1920

(10,15,16,23,24,26)

gave

rise

to

the designation Hand-Sch#{252}ller-Christian disease. More recently, others have suggested adding

802

U

RadioGrapbks

U

Stuli

et al

Kay’s

name

to the

designation

Volume

(10).

12

Number

4

In 1936, Drs Arthur F. Abt and EdwardJ. Denenholz concluded that a childhood disease, manifested by hepatosplenomegaly, petechiae, anemia, multiple osseous lesions, and lymphadenopathy, reported in one case by Dr Erich Letterer (1924) and in seven cases by Dr Sture A. Siwe (1933), represented a single entity, which they called Letterer-Siwe disease (15,16,24,26). By 1940, DrArvid Wallgren and others independently concluded that Hand-SchUller-Christian disease and Letterer-Siwe disease were related entities (16,26-28). During this same period, Drs Louis Lichtenstein and Henry L. Jaffe (1940) applied the name “eosinophiic granuloma of

bone”

to a new

osseous

lesion

that

had

patho-

logic characteristics similar to those described in prior case reports dating to 1929 (4,9, 16,26,27,29,30). Concurrently, Drs Sadao Otani andJoseph C. Ehrlich reported

on the same

disease,

which

they

“solitary granuloma of bone” In 1941, Drs Sidney Farber,

Green,

and

colleagues

that eosinophilic Christian disease,

were

variations

referred

to as

granuloma, Hand-SchUllerand Letterer-Siwe disease

disease

by subsequent

(5, 10, 16,24-26,28,30,35-37), authorities still argue

pro-

unrelated

investigators

that

although disorders

these

was introduced

bistiocytosis

X

in 1953

as a unifying

clinical This

ciety’

1

were as separate

conditions

(2,4,9,27,30,41). to indicate the unknown

was used

terminology

was

by

designation

under which all three conditions grouped yet still distinguished

when

some are

(8,9,16,24,38-40).

The term Lichtenstein

The X causes.

accepted

until

enhance

studies

U

commonality

CAUSES

The

that

clearly

of nomenclature.

PATHOGENESIS pathogenesis of LCH

AND

causes

and

known (1-3,5,8,10,37). tious agent has been

the self-limiting

nature

are insufficient genetic factors

of the disease

in some

data to support metabolic and or immunodeficiency as causes

and there is no conclusive is a malignant neoplastic However, the substantial in infants,

sponse agents, plasia

are unor other infecbecause of

A viral considered

and their response to antibiotics and (35). However, no organism has been from lesions ofLCH (8,10,36). There

especially

cess; this idea was initially rejected by Lichtenstein and Jaffe (4,28,30-32). Soon after, Drs Tracy B. Mallory (1942), Jaffe and Lichtenstein (1944), and others also suggested that the three conditions were interrelated manifestations of the same disease (4,8-10,15,2634). This common-disease theory has been supported

pathologic

identify the Langerhans cell as the distinctive histiocyte in active lesions (6, 18,4 1). The authors agree with the revised classification and recommend its adoption by radiologists to

(3, 16,35), that LCH (1,2,6,36).

(4,9,28,30,31).

basic

contemporary

patients steroids isolated

William T. presented the concept

of the same

sified as Langerhans cell histiocytosis (LCH) and that the aforementioned eponyms be replaced with specific and inclusive diagnostic terms. The revised classification is based on

evidence process mortality,

with

coupled

of patients to some had suggested the

the re-

chemotherapeutic possibility of neo-

(1,6,8,10).

The disease patients radiation lesions

recently, discovered

reactive,

nonneoplastic

nature

of the

is supported by the response of many to steroid therapy or to low doses of and the spontaneous resolution of in some untreated patients (36). More

immunologic in patients

aberrations with LCH

have

18,42), leading to the current concept LCH represents a disorder of immune sponse (1,3,6,8,21,41). The relationship LCH to the immune system is supported

the observation is directly immune

patient,

that

influenced system.

the

more

the severity by the

In general,

severe

that reof by

of the disease of the

immaturity the

the

been

(1,2,8,10,

younger

disease

the

(15).

1987

the Writing Group of the Histiocyte Soproposed that histiocytosis X be reclas-

Founded

national

in 1985, and

the Histiocyte

interdisciplinary

Society

scientific

is an inter-

organization

directed

toward understanding the etiology, pathoand management of the childhood histiocytoses (a group ofdisorders that includes LCH). Members of the Writing Group ofthe Histiocyte Society recommended standardized nomenclature and revised the classification of the histiocytic disorders, physiology,

which

July

1992

was

subsequently

published

in 1987

(6).

Stuil

et al

U

RadioGrapbks

U

803

1.

Figure

Histologic

tion,

X 150; matory cells

graph

characteristics

hematoxylin-eosin and hemorrhage,

(original

magnification,

of LCH. (a) Scanning

low-power

[H-E] giving

stain) shows nodule a classic ‘ ‘granulomatous’

x 480;

H-E stain)

shows

photomicrograph

of Langerhans ‘ appearance.

nuclear

grooves

cells

(original

surrounded (b) High-power

(arrows)

magnifica-

by chronic inflamphotomicro-

characteristic

of the

Langerhans histiocyte. Nuclear margins are sharply delineated and are in sharp contrast to the indistinct cytoplasmic borders. (C) Eosinophils (small arrows) may predominate, in contrast to the previous field (b). Their presence in not required for the diagnosis of LCH. Note few scattered Langerhans cell histiocytes

(large arrows). (Original x 28,000) of Langerhans dark and light bands. (c) brown areas in both the of the nucleus as a result

:

#{149}-

‘‘

“

‘

‘#{149}‘“ 1’.

b

:

-

magnification, X 480; H-E stain.) (d) Electron micrograph (original magnification, histiocyte shows the typical pentalaminar Birbeck granule (arrow) with alternating Positive immunohistochemical staining for antibody to S-100 protein is seen as dark nucleus and cytoplasm of the Langerhans cells. Note ‘ ‘pac-man’ ‘ appearance (arrow) of a prominent nuclear groove. (Original magnification, x 480.)

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804

U

RadioGraphics

U

Stuil

et al

Volume

12

Number

4

U HISTOPATHOLOGIC CHARACTERISTICS LCH represents less than 1% of all biopsyproved primary bone lesions (12,15). The histopathologic features of LCH vary with the site

AND

CLINICAL

. Localized Form of LCH (Eosinophilic Granuloma) The localized form of LCH is commonly referred to as eosinophilic granuloma, a term reserved for those cases in which the disease

of tissue involvement and the stage of the disease (4,7,15). All expressions of LCH are characterized by the proliferation of atypical Langerhans cells, which are mononuclear cells of the dendritic cell line, normally found in the epidermis and normally derived from bone marrow stem cells (1-4,7,9,15,37,42). In LCH, these unique histiocytes form granulomas in conjunction with lymphocytes, polymorphonuclear cells, and eosinophils (2,4,7,8,10,11,43). During the early phase of LCH, specimens are

proximately 70% of cases of LCH, the localized form is the least aggressive and most favorable expression of the disease (15,16,35). About 90% of patients with localized skeletal disease present between 5 and 15 years of age, with an average age at onset of 10-14 years. Solitary or multiple osseous lesions have been identified in younger children,

cellular

adults,

and

are

marked

by aggregates

or

sheets of Langerhans cells. Eosinophils are often identified, although they need not be present for a histologic diagnosis of LCH. Langerhans cells usually have abundant eosinophilic cytoplasm and lobulated nuclei with distinctive longitudinal nuclear grooves (Fig 1) (8,15). Older LCH lesions, which may

be mistaken

for chronic

osteomyelitis,

my-

elofibrosis, or “non-specific benign/fibrous lesions,” are marked by a paucity of Langerhans cells and a fibrous background, with or without eosinophils (7,15). Electron microscopy oflesional tissue reveals the Langerhans cells with characteristic racquet-shaped Birbeck granules (also referred to as Langerhans cell granules, X bodies,

or X granules)

(2-5,8-1

1, 15,37),

which

are necessary for definitive diagnosis in accordance with the Histiocyte Society criterion (6). Birbeck granules are located in the cytoplasm of Langerhans cells and have five layers (3, 15). Langerhans cells also express a variety of surface antigens that may play a role in immune response (2,4,6,7,18). The T6 surface antigen is a specific finding described in recent reports (2,4,6,7). These cells demonstrate positive histochemical staining for adenosine triphosphatase and a-D-mannosidase, characteristic binding of peanut lectin, and positive immunohistochemical staining for 5-100 is differentiated

protein

(Fig 1) (2,3,6,9,15,18). from

other

histiocytic

ders and xanthogranulomatous diseases the presence of Birbeck granules within pathologic Langerhans cells (6).

July

ClASSIFICATION FEATURES U

1992

LCH

is limited

to bone

and

or lung.

rarely

Accounting

ap-

(9,15,21, commonly affected than female patients, with most large series reporting a ratio of male-to-female patients of approximately 2: 1 (9,35,46). Mirra (15) noted a ratio of 2.2: 1 on review of 240 cases. As with all forms of LCH, localized Osseous involvement is uncommon in the nonwhite population. 35,44,45).

Male

Clinical

bone,

in older

for

patients

are more

patients

manifestations

with

local

commonly

relate

pain,

observed

tenderness,

to the

affected

and

masses

(2,8,9,15,34,35,46,47).

A

draining, infected ear frequently accompanies mastoid involvement, which may result in hearing loss (10,43). Spinal involvement may cause severe back pain, stiffness, or scoliosis and may lead to neurologic complications (2, 10,43,44). Most patients present with symptoms ofless than 2 months duration, although lesions may also be clinically silent (2,8,34,45). Localized osseous LCH is often confused clinically with tients may have low-grade erythrocyte sedimentation tosis,

seen

and

normochromic

in cases

Approximately

infection, fever, rate, anemia,

ofosteomyelitis 10%

since paelevated mild leukocyfindings

(15,34,35,47).

of patients

presenting

with solitary LCH of bone will eventually develop multifocal and extraosseous disease (15). In general, patients with the localized form of LCH respond to minimal treatment and have minimal morbidity (2,13).

disor-

by the

Stuil

et al

U

RadioGraphics

U

805

Solitary LCH may occur in any bone, although there is a predilection for the flat bones, with more than half of skeletal lesions occurring in the skull, mandible, ribs, and pelvis

(15,21,31,46,47).

The

skull

is most

the most common mately two-thirds

more and

common

fre-

in solitary

volvement (45) most frequently iliac

bone

pelvic other (8,45).

to the

rami

are other

LCH (8). flat bones

in the

long

joints,

sis

arise

(28%),

in the or

Epiphyseal

most

diaphysis

are

Infrequently,

metaphy-

(2%)

(15,45).

(12,15,38,

simultaneous

and metaphyseal destruction ofthe

In general,

humerus involve(9). Most

(12%)

rare

le-

com-

(58%),

metadiaphysis

lesions

45,48).

is

and

of monostotic bones,

monly the femur, followed by the and tibia (8,9,15,31,45). Long-bone ment is more frequent in children lesions

in-

region iliac wings,

common sites of and clavicle are affected by LCH

25%-35%

occur

tur-

bone

sacroiliac

The scapula occasionally

Approximately sions

or multifocal

The supraacetabular involved (8). The

.

adjacent

ischiopubic

sella

Symptoms

and rib involvement is (8,9,21). Deciduous teeth may be involved during Any portion of the ilium may

(45).

be affected

in the

epiphyseal

involvement results from growth plate (12,15,35,48).

the growth

plate

acts

as a barrier

to lesion extension (12). Solitary lesions of the short tubular bones of the hands and feet are distinctly uncommon (9,15,21,35). When LCH occurs in the spine, the most commonly affected area is the vertebral body. Lesions limited to the neural arch are exceedingly unusual (8,12,15,45). Lesions arise most frequently in the thoracic spine, followed by those in the lumbar and cervical regions, respectively

bone

proximately

Lesions

are

multisystem

erage,

5-10

Chronic

vary in size

from ap1 to 15 cm (average, 4-6 cm). usually larger in patients with disease,

represent .

lesions

measuring

1-25

cm). Larger lesions coalescence of smaller Recurring

Form

(Hand-Schuller-Christian

806

U

cm

(av-

most likely defects (15). of

LCH

exophthalmos,

on

the

extent

of bone

and

destructive

bone

lesion(s)

(usually calvarial) is found in about 10%-15% of patients (8, 15,35,43). Loosening of teeth and bleeding, ulcerated gums are commonly associated with mandibular and maxillary involvement (15,35). Neurologic

complaints

may

develop

from

pathologic fractures of involved vertebrae or, rarely, direct dissemination in the central nervous system. Hepatosplenomegaly and lymphadenopathy result from infiltration of the reticuloendothelial system. Cutaneous manifestations include eczema, xanthomatosis, and soft-tissue nodules (15,35). Petechial or seborrhealike rashes lungs, kidneys, and (15,35). Involvement trointestinal Low-grade

mentation Anemia

The

worsens

to death

include

interstitial

and

biliary

over

involvement

being fatal (15, 16).

fibrosis

a 1-25-year

with

cor

disease

period.

Fulminant

Form

thrommyelitis,

The

remission has been reported, bidity is usually high (15,35).

(Letterer-Siwe

with

transverse

cirrhosis.

of

in approxiComplications

anemia

pneumonia,

chronic

extend

described (2). erythrocyte sedimay develop. indicator (15,35).

with

organ sites, 15% of patients

bocytopenia, nale,

may also occur (2). The brain may be involved ofthe thymus and gas-

tract has been fever, elevated rate, and anemia is a poor prognostic

outcome

multiple mately

I

Disease)

depend

and extraosseous involvement. Cranial involvement occurs in over 90% of patients (15). Otitis media is the most common initial manifestation. Diabetes insipidus due to softtissue involvement at the base of the skull, either secondarily compressing the posterior pituitary gland or related to direct involvement of the neurohypophysis, occurs in less than 50% ofpatients. Exophthalmos or proptosis produced by mass effect from osseous involvement of the orbit is seen in approximately 25% of patients. The classic HandSchUller-Christian triad of diabetes insipidus,

leading

(8,12,44,45).

Solitary

Approxithan 5

of age when they present, although adolescents and older individuals have been reported to have the disease (15,35). There is a slight male predominance with a male-to-female ratio of 1 .3: 1 (15).

in adults

permanent

childhood

occur

(2). less

are

years

quently involved, with the calvaria affected more often than the base, especially in the parietal region. The temporal bone, particularly the petrous ridges and mastoids, is the most commonly involved site at the base of the skull. Lesions also cica and orbits (8). Isolated mandibular

manifestation of patients

pulmo-

may

Spontaneous although

mor-

of LCH

Disease)

The chronic, recurring, disseminated form of LCH, also known as Hand-SchUller-Christian disease, affects bone and extraskeletal sites in about 20% ofcases ofLCH (15,35). As in the

The acute disseminated fulminant form of LCH, also referred to as Letterer-Siwe disease,

localized

the

RadioGrapbics

category

of LCH,

U

StuB

bone

et al

lesions

are

constitutes

(35).

approximately

10%

Most patients develop the first 2 years oflife (15,16,35),

of all cases

disease within although

Volume

12

Number

4

U

AFIP

EXPERIENCE

The

radiologic

480

cases

archives

of the

of histologically

AFIP

proved

contain and

radio-

logically correlated LCH, collected in consultation over 40 years. Of these 480 cases, 383 patients presented with solitary lesions. The average age of presentation of patients with monostotic disease in our series was 19.5 years (range, 3 months to 69 years), which is older than that reported in the literature. These results must be viewed with caution

due to the unique referral Twelve percent of patients years

old,

The

and

8% were

male-to-female

bias in our series. were less than 5 over

ratio

40 years

of age.

was 2 5 : 1 Race .

was

.

identified in 287 of the patients with isolated bone lesions, most ofwhom were white (n = 259), except for 15 black, 10 Hispanic, and three Asian patients. Clinical history was available for 2 1 1 patients with solitary skeletal LCH. All these patients

presented

affected

The next The 2. the anatomic 383

bone

Diagram shows distribution of

cases of solitary LCH of from the archives of the

Numbers centages.

represent

AFIP.

distribution

based

on our

sions,

is indicated

have

and young

been

reported

adults

(35).

Most

studies

children

the course

sive,

resulting

tends

to be rapidly

in multiorgan 1 or 2 years

disease, osteopenia.

July

progres-

dysfunction and (13,15,35). There-

death within fore, the need for early intervention cepted by most clinicians (10,13,14). Most patients have disseminated

of 383

in Figure

is acosseous

similar

solitary

2. Review

to findings

U

The

RADIOLOGIC radiologic

leof the

previously

FEATURES appearance of osseous

LCH depends on the site of involvement and the phase of the disease (1 5,35). Lesions typically appear lytic but may have either poorly defined borders or well-demarcated margins, with or without reactive sclerosis. In general, during the early phase, there is a more aggressive pattern of osteolysis (ie, moth-eaten or permeative), reflecting the biologic activity. Lamellated

periosteal

reaction

fracture may be associated tion (15,34,45). Continuous tion and cortical thickening with less aggressive lesions.

with features form of LCH.

due

of the chronic

or

or swelling. the skeleton,

reported.

by generalized become more apparent as they increase in size (15). Patients commonly develop bacterial infections such as otitis media, mastoiditis, and lymphadenitis during the preterminal stage. Terminally ill patients may have ascites, anasarca, pleural effusion, and hemorrhage. These patients most often succumb to systemic infection (13, 16,35). Occasionally, the clinical course becomes more protracted,

1992

usually manifested Lesions may

typical

pain.

do not

cite any sex predilection. As in the chronic form of LCH, fever, hepatosplenomegaly, lymphadenopathy, progressive anemia, thrombocytopenia, and skin rash occur in patients with the fulminant form of LCH. How-

ever,

throughout

to the

localized was pain

98 solitary long-bone lesions in the AFIP archives revealed that the majority of lesions were in the diaphysis (79%), followed by LCH arising in the metaphysis or metadiaphysis (18%). Only three lesions (3%) occurred in

per-

in older

related

all had

complaint with a mass

collection

the epiphysis, cases

symptoms

VirtUally

most common associated

tenderness Figure

with

structure.

recurring

ostitis

resolves,

and

the

and

pathologic

with the destrucperiosteal reacare associated Later, the peri-

lesion

becomes

sharply circumscribed. Remodeling of bone may impart an ‘ ‘expanded’ ‘ appearance, especially if there was preexistent soft-tissue extension or extensive lamellated periostitis. Chronic lesions may resolve completely without treatment or have a sclerotic appearance

to periosteal

new

bone

formation

(8,15,45).

Stull

et al

U

RadioGraphics

U

807

;

.

a.

b.

3. Skull of a 5-6-year-old child (c. 1800) with radiologic evidence of LCH in multiple bones. (Courtesy of Robert Mann, Smithsonian Institution, Washington, DC.) (a) Gross photograph shows greater involvement of the outer table of the skull resulting in a beveled-edge lesion when viewed en face. (b) En face radiograph demonstrates a typical beveled-edge lesion. Figure

a.

b.

4. LCH ofthe skull in a 20-year-old man who complained of progressive right-sided headaches and tenderness over the parietal region during a 3-month period. (a) Lateral skull radiograph shows a rounded radiolucent area in the right parietal region (arrows) with central mineralization consistent with button sequestrum. (b) Axial CT scan displayed at narrow window setting shows button sequestrum within the diploic space. (c) Axial CT scan displayed at softtissue window setting shows enhancing ring lesions in the right parietal lobe, associated with vasogenic edema. At surgery, this finding represented transdural extension with intraaxial invasion, which is a rare complication of LCH. Figure

C-

808

U

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U

Stull

et al

Volume

12

Number

4

-

‘#{149}

____ a.

b. LCH in a 19-year-old man. (a) Lateral skull radiograph shows a well-defined temporal-occipital region crossing the lambdoid suture. (b) Posterior skull scinitigram increased uptake in the left mastoid region. Remainder of the bone scan was normal,

Figure

lytic lesion in the shows moderately despite radiographic

5.

evidence

of multifocal

involvement.

Figure

6.

22-year-old sions,

LCH

man.

with

localized

to bone

Radiograph

a maplike

in the

shows

skull

coalescing

of a

le-

configuration.

or “bull’s-eye” (Fig 4), simulating infectious or neoplastic diseases (8,9,12,15, 21,30,35,45). Infrequently, lesions may extend across suture lines (Fig 5) (12). Lesions may enlarge, increase in number, and coalesce to form a maplike appearance, referred to as the geographic skull (Fig 6), a feature commonly described in association with the chronic form of LCH. Confluent defects may resemble a “hole-within-a-hole” (9,15, 35), a finding that is also observed in other sequestrum”

Less only

more nant

frequently, diffuse osteopenia skeletal change, an appearance

often form

associated of LCH

with

(8, 15).

is the that is

the acute This

fulmi-

widespread

osseous involvement may progress to fine lytic lesions that increase in size or have associated periostitis (15). Specific radiographic characteristics

are

discussed

by site

of involve-

ment. .

Skull

and

Mandible

In the skull, lesions are typically round or ovoid, with well-defined nonsclerotic margins, and appear “punched out. “ The uneven destruction of the outer and inner cranial tables results in a beveled-edge or double-contour appearance (Fig 3) (4,8,9,12,15,2 1, 30,35,43,47). sidual

July

1992

bone

Lytic fragment,

lesions referred

may

contain

flat bones and in the long bones (45). Penosteal reaction is absent in the skull (9). Osseous perforation may result in an epidural or epicranial soft-tissue mass (Fig 7) (8,21). Transdural extension and intraaxial invasion (Fig 4) are rare complications that may occur in association

with

35).

Caresio

Recently,

disseminated

LCH

et a! (49)

(15,2

described

1, a

case with both intraand extracranial extension of LCH. Mandibular lesions tend to destroy alveolar bone, which produces the radiologic appearance of”floating teeth” (8,12,30,35,45). A similar finding may be seen in the maxilla (Fig 8).

a re-

to as a “button

Stull

et al

U

RadioGrapbics

U

809

a.

b

Figure 7. LCH of the skull in a 1 #{189}-year-old boy who presented with a 2-month history of supraorbital swelling, which was believed to be related to prior trauma. (a) Lateral skull radiograph shows geographic destruction of the frontal bone with beveled edges, best seen anteriorly. Unenhanced (b) and enhanced (c) axial CT scans show osseous destruction with epidural and extracranial soft-tissue extension. Note

marked

contrast

material

Figure 8. Multifocal skull in a 3-year-old

enhancement

intraosseous boy. Lateral

shows numerous lytic calvarial edge of the dominant posterior readily

appreciated.

lIla and mandible appearance (*).

.

Other

Bone

skull

LCH of the radiograph

lesions. parietal

destruction

has resulted

of the soft-tissue

‘.-‘9_

The beveled lesion is of the

max-

in a floating-teeth

Bones may produce geographic, moth-eaten, or permeative osteolysis (Figs 9, 10). Periostitis is often associated with pathologic fracture (Fig 11) (9,45). Not infrequently, an extrapleural mass results from soft-tissue extension (Figs 1 1, 12) (45).

810

U

RadioGrapbics

woman complaining of a painful nodule over the posterior left 10th rib. Collimated radiograph of the inferior left ribs shows a lytic lesion with sharp sclerotic superior margin of the posterior 10th rib. Destruction soft-tissue

Flat

Rib involvement

U

Stull

et al

the

component.

Pelvic

defined become

of inferior extension.

lesions

may

cortex

of the

initially

rib suggests

appear

foci of osteolysis. With time, well defined, with or without

rounding

sclerosis.

destruction

and

The coalescence

nonuniform

as poorly

lesions suncortical

of lesions

create

an appearance similar to that in the skull (Fig 13) (8,9,35,45,47). Lyric pelvic lesions may be

Volume

12

Number

4

lOb.

lOa.

lic. Figures

lid. 10,

11.

(10)

LCH

ofthe

rib in a 26-year-old

man

presenting

with

localized

chest

wall

pain.

Colli-

mated radiograph (a) and corresponding tomogram (b) of the posteromedial right seventh rib demonstrate a well-defined lytic lesion with a central sequestered bone fragment. Subtle periosteal reaction along the superior cortex of the rib is associated with a nondisplaced pathologic fracture (seen on other tomograms). (11) LCH ofthe rib in a 19-year-old woman who complained ofsudden onset ofsevere left shoulder pain. (a) Anteroposterior (AP) view of the left shoulder shows pathologic fracture (arrow) through an aggressive lytic process in the lateral aspect of the second rib, with soft-tissue extension creating an extrapleural mass. (b) Axial proton-density weighted (2,000/20 [repetition time msec/echo time msecj) MR image reveals heterogeneous mass (arrow) arising from the posterolateral aspect of the rib with both intra- and extrathoracic soft-tissue extension. (c) Macroscopic section (original magnification, x 1 ; H-E stain) from a similar case shows the aggressive biologic behavior of the lesion, which infiltrates between existing trabeculae. Note osteal reaction with cartilage formation, likely due to pathologic fracture. (d) Higher-power view (original magnification, x 1 ; H-E stain) shows the cartilage (*) to better advantage, as well as peniosteal new bone

pen-

(an-

row).

July

1992

Stull

et al

U

RadioGraphics

U

811

e

f t

‘

:.

a. Figure

12.

lowing

minor

lesion

of the

(b) Posterior radiotracer

CT scan

LCH

b. rib in a 3-year-old boy who presented (a) Collimated oblique view of the right

of the

trauma. lateral

aspect

of the

bone scan accumulation

reveals

obtained in the

an extrapleunal

.

eighth

rib associated

with technetium-99m night eighth rib and

soft-tissue

mass

with subtle

with 2’/2 weeks ofchest wall tenderness ribs demonstrates an aggressive osteolytic a soft-tissue mass and ill-defined peniostitis.

methylene increased

diphosphonate (MDP) activity in a soft-tissue

associated

with

(arrow)

fol-

shows abnormal mass. (c) Axial

the rib lesion.

‘

r;.

-

I

L

Figure 13. LCH radiograph of the

ence

ofgeographic

ating

a maplike

in a 19-year-old left ilium shows

lytic lesions and

man. AP a conflu-

(arrows),

hole-within-a-hole

pearance.

-

creap-

LCH

1

in a 4-year-oL

,‘l

with

a

2-month history ofleft shoulder pain and swelling. Endocrinologic investigations revealed evidence of diabetes insipidus. Head CT scan (not shown) showed an enhancing suprasellar mass. AP view of the left shoulder shows a large well-defined lytic lesion of the upper half of the scapula. Note scalloped, sclerotic margin along inferior portion of the lesion.

multilocular with scalloped borders. Penosteal new bone formation occurs less commonly in association with pelvic lesions (8). In general, surrounding zones of bone sclerosis and a well-defined sclerotic margin are featunes associated with iliac lesions and are not usually seen at other sites (45).

812

U

RadioGraphics

U

Stulletal

Scapular

lesions

may

appear

defects with a circumferential or may show an indistinct no surrounding sclerosis nous configuration is not

The appearance

of clavicular

able. Abundant peniosteal frequently associated with ment (Fig 15), particularly destroyed (45).

as lyric

ovoid

sclerotic border margin with little or (Fig 14). A serpigiuncommon (45).

lesions

is vari-

bone formation is clavicular involvewhen the cortex is

Volume

12

Number

4

d. Figure

LCH in a 13-year-old boy who blunt trauma to his shoulder.

15.

ten sustaining

e. a left supraclavicular mass approximately 1 month afdiagnosis was Ewing sarcoma. Initial radiograph as normal. (a) Xeroradiograph obtained 4 weeks after injury

developed Preoperative

obtained on the day of injury was interpreted shows a moth-eaten pattern ofosteolysis destroying the medial two-thirds ofthe left clavicle. Ill-defined penostitis and new bone formation have caused an ‘ ‘expansion’ ‘ of the clavicle. A hole-within-a-hole appearance is seen in the distal portion of the lesion. Soft-tissue extension is also suggested. (b) Axial CT scan displayed at bone window settings shows destruction of the anterior cortex of the left clavicle. Extraosseous soft-tissue extension is not well seen at these window settings. (c) Whole-body scintigram shows intense nadiotracer

uptake formation.

within

the left clavicle.

The

tures.

relatively

(d) AP image thynocenvical trunk nonspecific

July

1992

mild

Enlargement

symmetric

uptake

of the left clavicle in the

shoulders

is likely suggests

due little

to extensive

from arterial phase of a left subclavian arteriogram reveals a somewhat (arrow), which supplies the medial left clavicle mass. (e) Late arterial

hypervascularity

peniosteal

to no hyperemia

new

in adjacent

bone struc-

hypentrophied phase image shows

(arrow).

Stull

et al

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RadioGraphics

U

813

g. 17. LCH in a 13’/2-year-old boy with a history ofmandibular and right mastoid involvement 3 years prior who subsequently developed intermittent left elbow pain of 2 months duration. The distal left arm was diffusely swollen and tender at physical examination. Biopsy was performed to rule out Ewing sarcoma or osteomyelitis. AP (a) and lateral (b) radiographs show a large geographic lesion in the distal humeral diaphyFigure

sis associated

with

lamellated

periostitis.

The

superior

margin

is well-defined

and

scalloped,

while

the

bor-

den is less distinct inferiorly and medially. Destruction of the medial cortex and Codman angle are noted on the AP view. Periosteal reaction appears less aggressive on the lateral view, since the lamellations are moderately thick and blend into the native cortex. Elbow joint effusion is also present. (c) Anterior Tc-99m MDP bone scan shows marked radiotracer uptake in the distal humerus and adjacent soft tissues. (d, e) Sagittal Ti-weighted (600/25) (d) and T2-weighted (2,000/70) (e) MR images demonstrate the marrow-replacing process within the distal humeral diaphysis. Signal-intensity alterations within surrounding marrow and musculature suggest either reactive edema or inflammation. Periosteal reaction and effusion are also seen. (f, g) Axial proton-density-weighted (2,000/25) (f) and T2-weighted (2,000/70) (g) MR images show cortical destruction and soft-tissue extension along the ulnar aspect of the distal humerus. Circumferential periosteal reaction and signal-intensity changes in adjacent muscles are again identified.

. Long Bones LCH arising in a long bone initially produces an area of poorly defined medullary destruction. Defects may enlarge and erode endosteal cortex, causing endosteal scalloping

(Figs 16, 17). Occasionally, an expanded cortical shell develops as the lesion enlarges and destroys native bone (30,35,43). Invasion of overlying soft tissue may result if the lesion penetrates through cortical bone (Fig 17) (43).

Variable

amounts

of periosteal

reaction

may occur with or without pathologic (Figs 17-20). Confluent lesions impart

814

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et al

Volume

fracture a hole-

12

Number

4

16. LCH of the pelvis in a 6-year-old girl who presented with a 2-week history of left leg pain and limp. Radiograph shows a geographic lytic lesion in the left femoral neck with poorly defined margins and loss of lateral contex. Subtle solid periosteal reaction (arrowhead) along the femoral neck is in sharp contrast to the otherwise aggressive biologic activity demonstrated by the lesion. Figure

within-a-hole encountered

appearance in flat bones

(Figs 18, 19), also (12,45). Later, wellare seen. A sharply de-

defined lyric defects fined, sclerotic margin ture lesion (Figs 21-23). may pear

July

1992

indicates

a more

ma-

Epiphyseal lesions are relatively rare (Fig 22). Lesions in the short tubular bones of the hands and feet have findings similar to those found in the long bones (Fig 24).

With healing, lesions appear sclerotic or may completely disapwith little or no deformity (Fig 19) (45).

Stull

et al

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RadioGraphics

U

815

i

S

l9a. Figures

19,

20.

of a 2-year-old tamed before (a) Prebiopsy sion

in the

lated

(19)

LCH

arising

in the

left

boy. Serial radiographs were and after biopsy of a diaphyseal left

femur

oblesion.

AP radiograph shows a geographic femoral diaphysis with marked

peniosteal

within-a-hole shows defect

reaction.

The lesion

lelamel-

has a hole-

(b) Postbiopsy AP view lateral cortex corresponding biopsy site. (C) Follow-up radiograph ob6 weeks after biopsy reveals more solid-appeniosteal reaction. (d) Follow-up radioobtained 6 months later, shows progressive of the lesion and assimilation of peniosteal

to the tamed pearing

graph, healing

appearance. along the

new bone. (20) LCH of the left femur old boy with a 3-month history ofleft

in a 6%-yearknee pain and

leg weakness. (a) AP radiograph shows a well-defined area oflysis

of the left femur in the middle of

the femoral diaphysis associated lated peniosteal reaction bridging

with thickly lamelthe margins of un-

involved

marked femoral

bone.

(b)

radiotracer diaphysis.

subtnochantenic

with

mild

Whole-body

scintigram

.‘

portion

hyperemic

of the

left

femur,

U

RadioGraphics

-

shows

uptake in the middle of the left There is minimal uptake in the

,:-

consistent

response.

20a.

816

A

ii,,).

U

Stull

et al

20b.

Volume

12

Number

4

Figure

21.

a 3-month hip.

LCH

history

AP radiograph

geographic

23. 22-24.

(22)

Multicentric

LCH

with

hip

in the left shows

involving

a

the

region of the femur. margin is suggestive

‘Fading’ ‘ sclerotic a Brodie abscess. ance also suggest ‘

Figures

adult

pain

of the

lytic process

intertrochanteric

22.

in a male

of night

Location fibrous

of

and appeardysplasia.

24.

in a 5-year-old

girl.

Radiograph

of the

left hemipelvis

shows

well-

defined lytic lesions with sclerotic margins in the ilium, femoral head, and subtrochantenic region of the femur. Ileal lesion is difficult to distinguish from adjacent bowel gas. Epiphyseal lesion abuts but does not cross the physis. (23) LCH in a 13-year-old boy who presented with a 1-year history of intermittent sharp and dull pain of the left thigh. Preoperative diagnosis was osteomyelitis. AP radiograph shows a large well-defined geographic lesion in the proximal femoral diaphysis with extensive solid peniosteal new bone formation that has been assimilated into the original cortex, a finding that indicates a relatively mature lesion. (24)

graph

July

LCH

arising

of the right

in a phalanx

middle

physis

of the

middle

noted

along

the distal

1992

ofa

finger

phalanx.

aspect

14-year-old

shows Lesion

boy

with

a geographic extends

of the lesion.

proximally

Localized

a 2-month

lytic lesion into

soft-tissue

history

with the

oflocalized

its epicenter

epiphysis.

swelling

tenderness.

AP radio-

in the proximal

An incomplete

sclerotic

metadiamargin

is

is also seen.

Stull

et al

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U

817

b.

a. 25. Multiorgan LCH in a 19-year-old man who initially presented with a 4-month history ofcervical and lumbar pain. (a) Lateral collimated tomogi-am of the lumbar spine reveals a poorly delineated lytic process of the anteroinferior aspect of the L-2 vertebral body, as well as a well-defined lytic lesion of the superior central portion of the L-4 vertebral body. (b) L-4 lesion is barely perceptible on the plain radiograph. (c) Posteroanterior chest radiograph obtained 1 /2 years after initial diagFigure

nosis

shows

extensive

and mediastinal graphic findings normal.

interstitial

lung

adenopathy. Chest at initial presentation

disease

radiowere

. Spine In the spine, early lesions appear lytic (Fig 25), followed by uniform collapse ofthe vertebral body. Extreme vertebral collapse produces the wafer or “coin-on-edge” appearance of the vertebral body, known as vertebra plana (Fig 26). The intervertebral disk spaces

are preserved

on appear

slightly

(8,12,31,35,43-45,50).

wedging

or uneven

lateral

defect

(Figs

27,

28)

during

may

tissue

anterior

vertebral

sion (Fig 27) is encountered stage. An associated paraspinal

dural

widened

Less often,

mass represent

compresthe

early

or extrasoft-

edema

vertebral

mity

U

RadioGraphics

U

StuB

et al

hemorrhage

related

on soft-tissue

to the

extension

of

LCH (8,35). Destruction of the posterior elements (Fig 28) is an atypical finding (8,45). With healing, there is reconstitution of the involved vertebrae toward the oniginal height,

although

818

and

collapse

usually

some

residual

persists

compression (8,34,45,5

defor-

1).

Volume

12

Number

4

r 26.

.;Wb!’.

27....

27b.

U

OTHER

shows increased uptake presumably when lesions reactive bone formation

MODALITIES lesions typically of radiotracer activity, are accompanied by (Figs 12, 15, 17, 20)

(8,43)

activity

Bone

Figures

5-year-old

26, 27. (26) Multifocal osseous LCH in a girl who presented with a 3-month his-

tory ofworsening neck and left shoulder survey was obtained after lesions in the thoracic radiograph

spine were diagnosed. of thoracolumbar

vertebra

plana

deformities.

pain.

Bone

cervical

and

Lateral collimated spine shows multiple

associated

(arrows).

(27)

Lysis

with a paraspinal of the right pedicle

(b)

LCH in a 7-year-old

soft-tissue mass is also present.

Lateral view from a metnizamide study reveals an extradural ventral

myelographic defect at the

level

(c) Axial CT scan

of a T-10

pathologic

fracture.

shows aggressive osteolysis of the T-10 vertebral body with extension into the right pedicle and paraspinal soft-tissue mass. Epidunal extension

not well

1992

or by osteoblastic

abnormal

without

ra-

uptake

on

bone

scans

may

have

no

corresponding radiographic abnormality (8). “Cold” areas of abnormally decreased uptake may show radiographic evidence of pure osteolysis

girl who had a 1-week history oflower thoracic pain, scoliosis, and inability to bear weight on her right foot. (a) AP radiograph of the lower thoracic spine shows incomplete compression deformity of

July

of LCH

diographic evidence of sclerosis (Fig 5). Falsenegative bone scintigraphic findings may be encountered in up to 35% ofcases (8,21,43, 52). These lesions may be clearly identifiable on plain radiographs. Furthermore, areas of

27C

T-10

IMAGING

scintigraphy

(8,43,52).

and radiographic mentary studies LCH

Therefore,

bone

scintigraphy

skeletal surveys are for examining patients

complewith

(8,52). Angiography

uate (Fig

is usually

osseous 15) may

LCH lesions. be associated

(43). CT is useful seous disruption

destruction and

for defining by LCH soft-tissue

not

required

to eval-

Hypenvascularity with the lesions the extent of oslesions. Cortical involvement

may

be

is

seen.

Stuil

et al

U

RadioGrapbics

U

819

b Figure

28.

Solitary

(a) Collimated

LCH

lateral

of bone

radiograph

in a 4-year-old

of the upper

boy

cervical

who

presented

spine

with

torticollis

was interpreted

and

as normal.

neck

tenderness.

On close

inspection,

subtle osteolysis of the body and neural arch is seen. (b) Axial unenhanced CT scans show an area of bone destruction in the left lamina ofC-2, extending into the body ofC-2. Even at bone window settings, a leftsided extradural mass can be identified, as can asymmetric fullness of the left paraspinal muscles. (C) Sagittal Ti-weighted (300/20) gadolinium-enhanced images show marked enhancement ofC-2 as well as enhance-

ment

ofthe

surrounding

demonstrated

soft tissue

by CT (Figs

(arrows).

4, 7, 12, 27,

28)

(8,12,43,47).

To our knowledge, there are limited reports describing MR imaging characteristics of skeletal LCH. Lesions appear as areas of marrow replacement, giving decreased signal intensity on Ti-weighted images and increased signal

intensity

on

T2-weighted

images

(Fig

17) (8). In our limited experience, gadolinium-enhanced MR images show lesional enhancement (Fig 28). MR imaging may demonstrate early bone marrow involvement in the absence of radiographic or scintigraphic abnormalities (8).

U THERAPY Treatment regimens consist of conservative management (ie, observation), surgical intervention (such as incisional biopsy, curettage, or total excision), radiation therapy, chemotherapy, administration of intraosseous steroids,

on some

niques

combination

of these

Treatment varies with the extent of disease. Chemotherapy is rarely used in patients with isolated bone lesions, since these patients generally have an excellent prognosis and spontaneous healing may occur (2,4,8, 10, 13,17,46,51).

Most

series

report

80% ment

response rate, independent of isolated osseous disease gle method has proved superior skeletal

820

U

RadioGrapbics

U

Stull

et al

tech-

(2-4,8,10,16,17,19,45,46,53,54).

LCH

(10,11,30,31,51,53).

Volume

at least

an

of manage(46). No sinfor treating A recent

12

Number

4

multi-institution strated an 87% sions to excision

Treatment

prospective response rate or curettage

of systemic

controversial.

Single

study demonof localized (46).

involvement

le-

is more

or combinations

agents

of chemotherapeutic drugs produce similar results (2, 10, 1 1). Recent reports suggest that

when

chemotherapy

initially peutic served

is employed,

one

should

administer the least toxic chemotheraagents. More toxic medication is nefor patients who fail to respond

seen ation cysts, (9,45). gestive ing a

beveled mia, myelitis,

dependent volvement on therapy

agreed

that

prognosis

better

than

better

(10,

of LCH,

and

to re-

this

appearance

nor

bonder

and

may be seen

under

investigation

The

DIFFERENTIAL DIAGNOSIS differential diagnosis of osseous

LCH depends on the site and extent of involvement, the phase of the disease, and the age of the patient. The differential diagnosis of a solitary lyric skull lesion in a child on young adult includes LCH as well as osteomyelitis, hemangi-

oma,

fibrous

moid

cyst,

and

beveled-edge

dysplasia, epidermoid or denmetastatic neuroblastoma. The or double-contour appearance

of calvarial LCH is characteristic and suggestive of the diagnosis in young patients. Myeloma, osteolytic metastasis, and osteoporosis circumscripta (ie, the early lyric phase of Paget disease) could have a similar appearance and

are more (45). show

Unlike linear

often

considered

osseous striations

in adult

patients

LCH, a hemangioma or a sun-ray appear-

ance, while fibrous dysplasia more typically expands and remodels the diplo#{235}and outer table of the skull. A bone sequestrum (button sequestrum) was teristic of skeletal

July

1992

once thought LCH. However,

to be characit may be

may

should

as

metastatic

teeth also

especially

infectious,

a substantial disseminated LCH

tend

(10,13,14,41). U

structive,

affects

and

osteodis-

in the

suggest

when

the

seen

in

conjunction with multiple skull lesions in a pediatric patient. The floating-teeth appearance can also occur in patients with metastatic neuroblastoma, malignant lymphoma, and familial dysgammaglobulinemia (45). Any dethat

infants

sugcreata

in a child,

and

of floating

diagnosis

Complete remissions in the chronic and acute fulminant forms of LCH are difficult to achieve (i4). The treatment of these patients controversial

appearance

nadi-

leuke-

multifocal angiomatosis

inthan

1 1). Although

also consider

myeloma (45).

or maxilla

on age and extent of systemic at the time of diagnosis rather

must

cystic

mandible

number of patients with respond to therapy, there is no definitive evidence that therapeutic intervention prevents long-term sequelae or shortens the clinical course ofLCH (3,14,41). One researcher found that patients’ responses to any therapeutic regimen were highly idiosyncratic and did not correlate with initial severity of disease (41).

is still

or

is more

(2,3,8,10,15,54). Younger patients tend to have more severe disease (10,15,54). Many children less than 1 year of age, particularly those with vital organ dysfunction, fail to respond to any treatment (10, 1 1,20,4 1). Children older than 1 year of age tolerate chemo-

therapy

One

as multiple in an adult

The

It is generally

edge.

hypenparathyroidism,

well ease

(11,41).

spond

in osteomyelitis, metastatic disease, necrosis, denmoid and epidermoid fibrous dysplasia, and meningioma Multiple lyric skull lesions may be of LCH when they are confluent, maplike or geographic margin with

the

or

neoplastic

alveolar

bone

(45).

Destruction

of the

mandible

with

processes LCH

(45). anising in the

appearance

that

produce of the

is unusual

malignant

be

infe-

in LCH

neoplastic

has a nonspecific

ribs

must

process

may

distinguished

from

that of numerous conditions (30) Less aggressive-appearing lesions may resemble fibrous dysplasia, enchondroma, chondnomyxoid fibroma, on aneurysmal bone cyst (45). A permeative osteolytic process must be differentiated from Ewing sarcoma, myeloma, metastatic cancer, and lymphoma (45). A lytic “expansile” pelvic lesion may mimic fibrous dysplasia, unicameral or aneunysmal bone cyst, chondnomyxoid fibnoma, enchondroma, brown tumor of hyperparathyroidism, hemophiliac pseudotumon, chondnosancoma, or metastatic disease (especially thyroid or renal cell carcinoma) (45). LCH should always .

be considered

in the differential

an iliac lesion In the long

in an infant bones, LCH

intramedullary

and

diagnosis

or child is most

diaphyseal

of

(45). frequently

and

may

have

an aggressive appearance, mimicking that of a Ewing sarcoma (i5,i6,30,35). When metaphyseal, LCH may simulate osteolytic osteosarcoma, leukemia, or acute osteomyelitis. For a less active lesion, one may consider unicam-

eral bone

cyst,

fibrous

dysplasia,

or chronic

osteomyelitis. The rarely occurring epiphyseal lesions may simulate chondroblastoma or Brodie abscess. Disseminated osseous lesions must be distinguished from multifocal osteomyelitis,

leukemia,

lymphoma,

cystic

matosis, fibrous dysplasia, brown hypenparathynoidism, myofibromatosis genital generalized fibnomatosis), disease, and myeloma (15).

Stull

Ct al

U

angio-

tumors

of (conmetastatic

RadioGraphics

U

821

In children, vertebra plana is most often caused by LCH. Vertebra plana was originally attributed to idiopathic osteonecrosis of the vertebral body (Calve disease) (8,34,50) but may also be seen static neuroblastoma

with

leukemia in children.

6.

Myeloma, must

which

that arch

7.

and metaPosterior

tends

be considered

collapse. tis are

ence

Pyogenic

and

8.

followed

body

findings

from

and

those

SUMMARY LCH is a disorder

spondyli-

by sclerosis

more

of other

10.

vertebral

by the

and

destruction in spinal LCH are

with

LCH

narrowing

9. (44).

the pedicles,

nonpyogenic

from

of disk space

vertebral involvement

to spare in an adult

distinguished

struction

more frequently in young adults

pres-

bone

(44,45).

1 1.

deEarly

12.

to differentiate

13.

of unknown

by an abnormal

cause, proliferation

characof histio-

14.

dren,

The disease has a predilection for chilalthough LCH may occur in adults. The

basic

histopathologic

cytes.

findings

are

clinical

identical

the three

well-established

(eosinophilic Christian Prognosis

granuloma, Hand-SchUllerdisease, Letterer-Siwe disease). depends on age of presentation

15.

16.

17.

18.

Langerhans’ cell histiocytosis and pathogenesis. Semin Oncol

1991; Nesbit

Current

18:3-7. ME.

19.

of histiocytosis sis).

concepts

X (Langerhans’

In: Vo#{252}tePA, Barrett

and

treatment

cell histiocyto-

A, Bloom

HJG,

Le-

20.

merle J, Neidhardt MK, eds. Cancer in children: clinical management. 2nd ed. Heidelbeng: Springer-Verlag 1986; 176-184. 3.

Favara cytosis

4.

MakleyJT, CarterJR. Eosinophilic granuloma ofbone. Clin Orthop 1986; 204:37-44. NezelofC, Basset F, Rousseau MF. Histiocy-

5.

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2 1.

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David R, Oria RA, Kumar R, et al. features ofeosinophiic granuloma

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823