DIFFUSE NEONATAL HEMANGIOMATOSIS

(Received February 21; accepted for publication April 21, 1970.)

ADDRESS FOR REPRINTS: (K.R.H.) Section on Child Neurology, NINDS, N.I.H., Room 5S, 242 Clinical

Center, Bethesda, Maryland 20014.

PRESENT ADDRESS: (F.A.) The Department of Pathology, Queens University, Belfast, North Ireland.

411

DIFFUSE

NEONATAL

HEMANGIOMATOSIS

Kenton R. Holden, M.D., and Fred Alexander, M.D.

From The Department of Pediatrics, Children’s Medical and Surgical Center, The Johns Hopkins Hospital and The Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland

ABSTRACT. Two infants with diffuse neonatal

he-mangiomatosis are presented. One infant

devel-oped thrombocytopenia and bleeding while the other infant with more widely diffuse lesions suc-cumbed to extensive central nervous system in-volvement.

Steroid therapy caused no obvious alteration in either of the patient’s course. The vascular lesion

in this disease is possibly congenital absence of ves-sel wall pericytes.

Six previous cases of diffuse neonatal heman-giomatosis are briefly reviewed in relation to the sites of the lesions, cause of death and malignant potential. Pediatrics, 46:411, 1970, NEONATE, HE-MANGIOMATOSIS, THROMBOCYTOPENIA, HYDRO-CEPHALUS, PEBICYTES.

LTHOUGH

cutaneous

hemangiomas

are

common in the neonate and are seldom

of clinical

significance,

generalized

visceral

hemangiomas presenting in the neonatal

period

are

extremely

rare.

Cutaneous

he-mangiomas

are

usually

found

concomi-tantly

with

these

visceral

ones.

A review

of

the

literature

has

revealed

only

six

reports

of

this

condition.6 This abnormality has

been

previously

discussed

under

a variety

of

names.

One

recent

report#{176}referred

to

this

disease

as

“miliary

hemangiomata,”

which

appears

to

be

a

misnomer

since

many

of the

lesions

measured

several

cen-timeters

in diameter.

Because

of the

confusion

which

exists

in

the

classification

of

hemangiomas

and

he-mangiomatous

syndromes,

it is necessary

to

delineate

the

criteria

for

terming

certain

cases diffuse neonatal hemangiomatosis

while

excluding

others.

Previously

reported

cases

of

diffuse

neonatal

hemangiomatosis

have

been

included

in this

review

only

if:

(1)

the

patient

was

recognized

in the

neo-natal

period

to have

visceral

hemangiomas,

(2) three or more organ systems were

af-fected

by

the

hemangiomas,

and

(3)

the

hemangiomas

were

not

malignant.

Diffuse

neonatal

hemangiomatosis is thus

differentiated from

the

other

hemangioma-tous

syndromes.

Multiple

malignant

lesions

of the vascular system resembling

hemangi-omas

must

be

considered

a separate

entity,

although

differentiation

of

these

vascular

neoplasms

from

benign

hamartomas

is

diffi-cult.

Telangiectatic

lesions

usually

desig-nate small focal red lesions on the skin or

mucous membranes that are composed

of

capillaries, venules, or arterioles.7 Although

Osler-Weber-Rendu

disease

presents

at

birth

and

involves

multiple

organ

systems,

the

lesions

are

primarily

telangiectatic,

bleeding

tendency

is common

and

increases

with age, and it is a hereditary disease

un-like most other hemangiomatous

syn-dromes.

Encephalotrigeminal

angiomatosis

(

Sturge-Weber disease) is also a separate entity

and

is distinguished

by

a port

wine

nevus

of the

face

with

ipsilateral

venous

an-giomatous

masses

in

the

leptomeninges

over

the

cortex.7

A rare

entity,

von

Hippel-Lindau

disease

is a multiple

hemangioma-tous

syndrome

consisting

of

hemangiomas

occurring

within

the

cerebellum

or

brain

stem and the fundi, along with frequent he-mangiomatous or cystic lesions in the liver

and

pancreas.T

Diffuse

neonatal

hemangiomatosis

is also

distinguished

from

a single

or few,

superfi-cial or deep, capillary, cavernous, or mixed hemangiomas occurring in early or adult life. While their variability of size, position,

Fic. 1. Right pneumothorax associated with hemangiomatosis involving the lungs (Case 1). Chest radiograph in 12-hour-old infant with progressive respiratory distress since birth which was partially relieved by needle aspira-tion. Residual expanded right lung in the presence of tension pneumothorax

suggested a mass in this area as verified at necropsy.

and degree of arteriovenous shunting may make some of these clinically significant,

most are potentially remediable without

therapy.

The two cases of diffuse neonatal heman-giomatosis presented in this report were markedly different in their clinical and

therapeutic problems. One infant had

thrombocytopenia and hemorrhaging at

birth, while the other had progressive neu-rological signs and hydrocephalus. Neither

clinical presentation has previously been

re-ported in this condition. The lesions of this

congenital defect are considered to be

vas-cular hamartomas possibly associated with

a pericyte deficiency in the vessel walls

CASE

I

D. C., a 2.1 kg Caucasian male was born at 32

weeks’ gestation to a 21-year-old mother at Union Memorial Hospital, Baltimore, Maryland, on Feb-ruary 16, 1964. Her first pregnancy had been

nor-mal but this pregnancy was complicated by

monthly bleeding and no fetal movements until

shortly before admission. There was no family his-tory or evidence of any hemangiomatous syndrome.

Radiographs revealed no fetal abnormality. Amni-otomy produced bloody amniotic fluid. Maternal

WBC was 17,400 with a normal differential; the

platelet count was 345,000/mm’. The infant,

de-livered by low forceps following a 4-hour labor,

was blue and gasping. The Apgar score was 6 and

rose with mask oxygen to 8 within 2 minutes.

Physical examination revealed a mildly cyanotic

premature male in mild to moderate respiratory distress with respiratory rate 60/minute and mild intercostal retractions. The liver edge was felt 3 to

4 cm below the costal margin, and there were

bi-lateral multilocular flank masses. The spleen was not palpable. The skin was clear.

The external genitalia were normal. The initial

urine was grossly bloody but cleared to

micro-scopic hematuria after 5 hours. No gross

gastroin-testinal hemorrhage was apparent. There was

steady progression of respiratory difficulty with

in-creased anteroposterior diameter of the chest and

bilateral inspiratory rales; a chest radiograph showed increased radiolucency along the heart bor-der. Within a few hours, the skin of the entire

4 ‘

I

/

Fic. 2. Cross section of liver in diffuse congenital hemangiomatosis ( Case 1). Microscopy of dark areas revealed these lesions to be thin-walled hemangiomas.

continued to increase in number until death.

Erythrocytes and leukocytes had normal

morphol-ogy on smear, but platelets were totally

made-quate. The hematocrit was 41%, and blood urea nitrogen was 12 mg/100 ml. The infant’s condition deteriorated despite antibiotics, fresh whole blood transfusion, and cortisone 2 hours prior to death. The respiratory distress became severe; examina-lion revealed shift of the heart to the left and

tym-pany of the right chest. Radiographs revealed right

pneumothorax with only partially collapsed lung

(

Fig. 1). Needle aspiration relieved this and

re-sulted in a slight stabilization of the child’s

condi-tion. Eighteen hours following birth, he became

cyanotic and flaccid; thoracentesis produced no im-provement and the child died.

AUTOPSY

FINDINGS

The major findings involved the heart, lungs, liver, kidneys, and brain. The heart weighed 16 gm and contained a few brownish subepicardial

hem-orrhages 2 to 3 mm in surface diameter, which

were located over the left ventricle; larger dark ar-eas overlay the right ventricle. These extended up

to 2 mm into the myocardium. Apart from right

ventricular hypertrophy, no lesion was evident in the heart chambers or valves. The lungs

weighed

30 gm. Raised red nodules which occasionally had whitish central discoloration elevated the pleura. The smaller nodules were a homogeneous red color

throughout. A few of the larger nodules had

rup-tured on the pleural surfaces. The majority of these nodules were located in the periphery, but some

were found toward the hilus. Hemorrhage had

oc-curred into the lung. The liver weighed 30 gm and

was greyish in color with numerous raised dark

soft areas, some with a whitish discoloration. These

measured 3 to 20 mm in diameter. On section the

lesions were scattered throughout the lobes and ac-counted for 60 to 75% of the volume of the liver

(

Fig. 2). They were extremely well demarcated, and pearly white or yellowish white foci were noted

in these blood-filled spaces. The spleen weighed 7

gui and had several raised dark red nodules on the

surface. On section these nodules were cystic,

mtil-tiloculated, and full of blood clot and whitish

fibrous tissue. The right kidney weighed 17 gm and

the left kidney weighed 12 gm; the discrepancy in

weight was explained by larger cystic hemorrhagic

areas in the former. On stripping the capsule, the surfaces of some cystic lesions were peeled off. These lesions measured 3 to 5 mm in diameter,

were raised 1 to 2 mm above the surface, and

in-volved approximately 75 to 80% of the kidney

Ftc. 3. Chest radiograph of 2-day-old infant with

diffuse hemangiomatosis (Case 2). Multiple

radio-dense lesions in lung periphery proved to be

hemangiomas at necropsy.

face. On section, the 1)VramidS of the right kidney were replaced b cystic hemorrhagic areas, some of

which compressed the cortex and bulged on the

surface. l’hese areas were well demarcated from

the adjacent parenchyma and distorted the pyra-mids. The left kidney was similarly, but less Se-‘erel’, involved.

Petechial hemorrhages were scattered over the

skin, meninges, pleura, and in the periadrenal and

perirenal tissues.

The only remarkable feature in the brain was

the presence of what appeared to be fresh hemor-rhage on the inferior surface of the left cerebellar

hemisphere. On section the lesion extended into

the underlying cerebellar cortex and grossly one could not be sure whether it was primary hemor-rhage or had occurred into a pre-existing abnor-mality.

Necrotizing esophagitis was evident in the lower esophagus.

Thin-walled hemangiomas, with no obvious

pro-liferation of endothelial cells or arteriovenous

com-munications, were confirmed histologically in the heart, lungs, liver, spleen, kidneys, and lower

esophagus. The hemorrhagic area of uncertain

etiology in the cerebellum proved to be a

hemangi-oma. There was not evidence of malignancy.

Hem-orrhage was evident in the myocardium, lungs,

eso1)hagus, kidneys, and periadrenal tissues.

CASE

2

D. C., a 3.08 kg Negro female, was born at 40

weeks gestation to a 25-year-old mother at Johns Hopkins hospital, Baltimore, Maryland, on

Janu-ary 5, 1969. The mother’s past medical history was

significant because of history of asthma,

glucose-6-phosphate dehvdrogenase deficiency, and one

tinexplained stillborn following three previous

nor-mal pregnancies. There was no family history or

evidence of heniangiomas. Pregnancy, labor, and

delivery were within normal limits. The infant was

in good condition at birth with an Apgar score of 8

but purplish hemangiomas were apparent on the

left cheek, tongue tip, lower lip, and iris of right

eye. In addition, multiple deep bluish or purple

subcutaneous papules and nodules from 1 to 20 mm in diameter were apparent over the scalp, neck,

truck, and extremities. All other physical findings

were normal. Laboratory data revealed a hemato-crit of 61% which remained stable, platelet count

of 290,000/mm’, prothrombin time of 100%,

mi-croscopic hematuria which later cleared, guaiac

positive stools which persisted without gross

bleed-ing until death, normal EKC, and normal

electro-lytes. Radiographs revealed multiple nodules

throughout the chest (Fig. 3), normal bone survey,

and normal intravenous pyelogram. A skin nodule

was shown by biopsy to be a capillary

hemangi-oma. The infant progressed well until 2 weeks of

age when rapidly progressive neurologic changes were noticed including left arm paralysis, strabis-mus with a right sixth nerve palsy, ptosis of left eye, and abnormal enlargement of head size. With

obvious progression of neurologic deficit, oral

pred-nisone 3 mg/kg/day was begun and continued for

3 weeks. The neurologic deficits remained apparent and there was continuing increase of head size ac-companied by an enlarging tense fontanelle,

vomit-ing, and lethargy. Skull radiographs showed

sepa-ration of sutures; a brain scan demonstrated a right

temporoparietal focus. An EEG was normal. A

ce-rebral arteriogram through the right brachial

showed no evidence of arteriovenous fistulae or

he-mangiomas but there was moderate hydrocephalus

present without any obvious cause. The fluid from

a ventricular tap was xanthochromic with increase

pressure; a pneumoencephalogram revealed two

pedunculated lesions in the lateral ventricles with the aqueduct displaced posteriorly and laterally,

suggesting a midbrain mass. The patient, then

4-weeks-old, remained lethargic and experienced

in-termittent apnea. A right foot drop was noted. A

ventriculoperitoneal shunt was performed but leth-argy and marked periods of apnea and tachvcardia continued until death at 35 days of age.

AUTOPSY

FINDINGS

At autopsy this Negro female weighed 3,450 gm

and was 53 cm long. The maximum head

ARTICLES

415

raised superficial hemangioma, 7.5 mm in diameter,

was situated on the left cheek. A small

hemangi-oma was evident on the tongue.

Numerous smooth deep red areas of varying

consistency, but generally soft, elevated the pleura

and also involved the anterior n#{236}ediastinum (Fig.

4). These measured up to 1.0 x 1.5 cm. Numerous

blood-filled hemangiomas up to 6 mm in diameter were scattered over the serosal surface of the intes-tine and throughout the mesentery and mesocolon. There was a hemangioma in the wall of the oblit-erated umbilical vein and another in the urachal remnant.

The heart weighed 18.5 gm. The chambers were

not dilated or hypertrophied. There was a 3 X 4

mm pale area at the tip of the left atrial appen-dage.

The lungs weighed 76 gm. Deep red

hemangio-mas of fairly uniform size, approximately 1.0 x 1.5

cm, were scattered diffusely over the pleura. On

section, similar areas replaced at least 30 to 40%

of the lung volume. The’ were located chiefly in

the septa. No hemangiomas were seen in the bron-chial vall and there was no abnormality in the ma-jor pulmonary vessels.

The liver weighed 110 gm and the spleen

Ftc. 4. Wide involvement of organ systems with hemangiomas is readily

.e .i

-I ‘

b

J?

, -;

I

F’-0 ‘

‘.

c

I.

S.c-c ‘u-u ‘u

o©© p

,,

-0 0

Z

Z

Z

s

S z

++ +

I,

z

-z

+

+

+

+

+ +++

- + + +

R

+

+++

Cl)!

. ++ + +

a.

++

. _{+ ++ + +}

+ ++ + + +

a

++ ++ + + 0

a

+++ ++ + +

-

.u

11+

Fm. 5. Cross sections of cerebellum, mid-brain, medulla, and cervical cord reveal diffuse involvement with hemangiomas (Case 2). This involvement

correlated with the neurologic deficits that were present.

weighed 14 gm. No hemangioma was seen in

ei-ther.

The

esophagus showed only a few small red

ar-eas indicative of serosal hemangiomas. The

stom-ach contained two similar mucosal and several

serosal lesions. There were no obvious ulcers or bleeding points. Deep red plaques approximately 4 mm in diameter were fairly evenly dispersed over the serosa of the small and large bowel at 3 to 5 cm intervals. On opening the bowel there were fewer mucosal

and

submucosal lesions. No definite mu-cosal ulceration was noted. Similar round or oval

heinangiomas were evident in the mesentery and

mesocolon, the largest measuring 1

x

0.5

x

0.5

cm. A few small dark red lesions were seen in the peripancreatic connective tissue, but there was no abnormality in the pancreas or adrenals.

Each kidney weighed 18 gm. The capsules

con-tamed small hemangiomas. The cut surfaces of the

kidneys were pale and no definite hemangiomas

were seen.

The bladder mucosa was pale, apart from a few

small hemangiomas near the trigone. There were

four pedunculated hemangiomas on the ectocervix.

The thyroid weighed 2 gm and contained no

- \_

Fic. 6. Photomicrograph of small bowel

submu-cosal hemangioma (H. and E. ). This representative lesion has dilated thin-walled channels lined by a

single layer of flattened endothelial cells (Case 2).

the larynx. Hemangiomas were scattered

through-out the diaphragm, thymus, and the cervical

re-gion. No abnormality was found in the bones.

Numerous hemangiomas were scattered over the

entire cerebral hemispheres, brain stem, and cere-bellum. The third ventricle bulged inferiorly and a hemangioma indented the left cerebral peduncle.

Uneal grooving and tonsilar herniation were not

marked. On sectioning the brain, both lateral yen-tricles and the third ventricle were dilated. Angio-mas were seen in the ventricles and involving the

choroid plexus. Both cortex and white matter

con-tamed angiomas as did the basal ganglia, floor of the third ventricle, mid-brain, pons, cerebellum, and the medulla ( Fig. 5 ). Small angiomas were present directly adjacent to and compressing the a(1IIedUct at several levels. These hemangiomas in the brain were of variable size, from pinhead to 1.5 cm in greatest diameter, and each appeared well defined from the surrounding brain tissue.

The spinal cord contained hemangiomas in the

cervical and lumbosacral regions. Three angiomas involved the origins of C, C, and T1. They

mea-sured 5 mm in diameter and were completely

within the cord, situated mainly in the left half.

The lesions in the lower cord were smaller and one very small hemangioma was noted in the cervical dura.

The hemangionias were composed of dilated

thin-walled channels without arteriovenous com-munications lined by a single layer of flattened en-dothelial cells ( Fig. 6 ). Rarely the lining cells were plump and slightly heaped up to form promi-nent clumps. No muscle was found in their walls using Masson’s trichrome stain and reticulin stains revealed no proliferation of cells, either inside or outside the capillary basement membrane. Bodian silver stain demonstrated an absence of pericytes and their processes. Occasionally there was a con-siderable quantity of fibrous tissue between the ramifying sinusoidal channels, as was seen in the intestinal serosal lesions. Rarely, unusual features were seen, e.g., in the left atrial appendage there was a peculiar sclerosing capillary hemangioma with extramedullary hematopoiesis and focal

hemo-siderin deposits. The capillaries in the intestinal

wall underlying serosal hemangiomas were dilated and penetrated the inner muscle layer to

communi-cate with submucosal hemangiomas. Platelet and

fibrin thrombi were encountered in a few small

he-mangiomas. Incidental findings were rare glomeru-lar cysts and focal calcification of the renal tubules. Acute purulent meningitis was extensive over the brain.

DISCUSSION

The unique feature of the first patient is evidence of bleeding during fetal life as

cx-emplified by bloody amniotic fluid and

blood in the first urine specimen. In the see-ond case hydrocephalus from aqueductal compression by hemangiomas and general-ized involvement of the brain, spinal cord, thymus, uterine cervix, skeletal muscle, and iris are being reported for the first time

(

Table I).

The association of vascular lesions with alterations in blood factors has aroused in-terest since the initial report of thrombocy-topenia and hemangioma.8 This association

has occurred almost exclusively in children

less than 1 year of age, yet only two reports involved newborn infants.9b0 The

hemangi-omas were large cavernous skin lesions, and

the thrombocytopenia developed concomi-tantly with increase in the size of the lesion. Splenectomy and steroids have been used with equivocal resultsi,h1 but no prior cases of hemangiomatosis with thrombocytopenia

in the neonate have been treated. The

thrombocytopenia in Case 1 was not altered

by

therapy

and

was

considered

to

result

the

hemangiomas.

Death

apparently

re-suited

from

the

thrombocytopenia

with

see-ondary hemorrhaging, as well as the tension

pneumothorax. There was no evidence of

congestive heart failure.

Pneumothorax has been described in the

newborn with cystic hamartoma of the lung’2

as

well

as in

infants with respiratory diffi-culty

at

birth.13

An

enlightening clinical

finding

was

the

chest

radiograph

showing

residual expanded lung in the presence of

increased

intrapleural

pressure,

suggesting

an intrapulmonary

mass.

The

degree

of

clinicopathological

cor-relation

in

the

second

infant

was

striking.

The

biopsy

of

the

skin

showed

the

he-mangiomatous

nature

of

the

subcutaneous

lesions;

the

hemangiomas

in

the

lungs

ac-counted

for

the

chest

radiographic

appear-ance.

The

persistent

guaiac

positive

stools

were

explained

by

finding

numerous

he-mangiomas

in

all

layers

of

bowel

wall.

Single

vascular

tumors

at each

of the

roots

of C7, C8, and

T1 and

also

in the

lumbosa-cral

region

correlated

with

the

brachial

palsy

and

the

foot

drop

terminally;

the

marked

mid-brain

and

pons

involvement

accounted

for the

sixth nerve palsy and pto-sis. Clinical hydrocephalus was confirmed

at

autopsy

by

finding

dilated

third

and

lateral

ventricles,

due

to

aqueductal

com-pression

by several

hemangiomas

in the

mid-brain.

Death

was

probably

the

direct

result

of involvement

of

the cardiorespiratory

cen-ters

by

hemangiomas,

or

secondary

to the

hydrocephalus; an acute purulent

meningi-tis,

perhaps

secondary

to surgical

interven-tion

1 week

prior

to death,

may

also

have

played

a part

in the

infant’s

demise.

Although

there

was

no

evidence

of

con-gestive

heart

failure

or arteriovenous

shunt-ing

in either

patient

presented,

three

of the

six

previously reported patients showed

evi-dence

of heart

failure.

In one

of these

three

patients,

the

first

clear

demonstration

with

angiograms

of

arteriovenous

communica-tions in multiple hemangiomas explained

cardiac

hypertrophy

and

congestive

heart

failure.

Therefore,

angiographic

studies

may be helpful in infants with

cardiac

hy-pertrophy or failure of unknown etiology when cutaneous hemangiomas are present.

There

was

no family

history

of

telangiec-tasia, hemangiomas, or bleeding tendency in either of these two patients. This is in

agreement

with

the

most

recent

review

of

this

defect.6

Three

of the

six

previous reports of dif-fuse neonatal hemangiomatosis were found in association with a large lesion.3’ This led Taylor and Moore14 to suggest the

pos-sibility

of a primary

malignancy

with

multi-pie metastases. The histological features of

the

present

cases

and

those

in the

literature

lend

no

support

to

such

a

theory,

since

there

were

only

a few

focal

areas

of

endo-thelial proliferation, no other cellular

hy-perplasia or pleomorphism, well formed

vascular

channels,

and

little

or no

evidence

of invasion

of adjacent

structures.

The

his-tological

appearance

of

the

bowel,

with

markedly abnormal capillaries coursing in their normal situation

through

the

muscle

coats, strongly suggests that these

hemangi-omas

are hamartomas

rather

than

a

dissemi-nated malignancy. The hemangiomas seen

here

appear

to have

enlarged

mainly

by

di-latation of capillaries which may have been

congenitally

abnormal

with

marked

loss

of

tone, some lesions consisting of a single

di-lated

channel

rather

than

numerous

small

proliferating

channels.

Generally

they

were

well

demarcated

from

the

adjacent

struc-tures.

Bodian

silver

stains

did

not

demon-strate any pericytes. Therefore, if the pen-cyte or modified smooth muscle cell on the precapillary arteniol&’ is absent and cannot

regulate

capillary

bed

blood

flow,

dilatation

of the true capillary seems possible secon-dary

to a continuous

increased

blood

flow

accompanied by increased intravascular pressure.

Rapid cessation of growth and partial

resolution

of hemangiomas

in children

fol-lowing

prednisone

therapy

suggested

a

caus-al relationship to Zarem and Edgerton.16

They proposed that the immature

with

extensive

enlarging

juvenile

hemangi-omas

not

amenable

to

surgery

should

be

treated

with

a course

of steroids.

This

treat-ment

has

been

successful

in

an

additional

group

of patients.17

In the

present

cases

no

beneficial

effect

was

achieved

by

the

use

of

steroids.

Some

sclerosis

was

evident

in the

serosal lesions of the bowel, but it is

impos-sible

to attribute

this

entirely

to the

steroid

therapy.

IMPLICATIONS

The

eight

infants

reported

with

diffuse

neonatal

hemangiomatosis

had

a mean

sun-vival time

of 71 days

with

or without

thera-peutic

regimens.

Therapy

has

been

aimed

primarily

at

symptomatic

relief,

and

ste-roids

have

now

been

used

in an attempt

to

prevent

extension

of

the

hemangiomas.

Each

mode

of

therapy

has

proved

inade-quate.

Thorough

evaluation

of infants

born

with

this

defect

is recommended

to

fore-warn

of

expected

complications

such

as

gastrointestinal

hemorrhage,

anemia,

cen-tral

nervous

system

involvement

and

pos-sibly

hydrocephalus,

thrombocytopenia,

hemorrhage,

and

heart

failure.

At this

time

the

long-term

therapy

and

prognosis

for

such

a patient

is extremely

poor.

Examination

of biopsy

material

by

histo-chemistry

and

electron

microscopy

may

in

the

future

demonstrate

a deficiency

of

pen-cytes involved in the contraction of blood

vessels.

SUMMARY

Two

infants

with

diffuse

neonatal

heman-giomatosis

are presented. In

one

infant

vis-coral

hemangiomas

presented

as

bilateral

flank

masses

with

thrombocytopenia

and

bleeding terminating

in

death

from

pneu-mothorax

at 18 hours

of age.

The

second

in-fant

showed

more

diffuse

involvement

which

included

skin,

mucous

membranes,

gastrointestinal

tract,

lungs

and

pleura,

thy-mus, mesentery, bladder, lymph node,

lar-ynx,

heart,

skeletal

muscle,

uterine

cervix,

iris,

spinal

cord,

brain

and

meninges

with-out

thrombocytopenia,

bleeding,

or

heart

failure.

Death

resulted

from

severe

brain

involvement,

compression

of

the

aqueduct

of Sylvius,

resultant

hydrocephalus

and

ter-minal postoperative meningitis. Steroid

therapy

caused

no obvious

alteration

in the

progression of the hemangiomas in either

patient.

The

vascular

lesion

in

this

disease

is possibly

secondary

to congenital

absence

of vessel

wall

penicytes.

The

six

previous

patients

with

diffuse

neonatal hemangiomatosis are briefly

re-viewed

in relation

to sites

of lesions,

cause

of death,

and

malignant

potential.

REFERENCES

1. Ramdohr, M.: Em fall von angebornem multi-p1cm angiosarcoma. Virchow Arch. Path. Anat., 73:459, 1878.

2. Von Falkowski, A. : Uber eigenartige

chymale

Hamartome In

Leberund

Milz neben

multiplen eruptiven Angiomen der Haut bei einem Sauglinq. Beitr. Path. Anat., 57:385,

1914.

3. Jaffe, B. H. : Multiple hemangiomas of the skin and of the internal organs. Arch. Path., 7:44,

1929.

4.

Snyder, L. H., and Doan, C. A. : Studies in hu-man inheritance. XXV. Is the homozygous form of multiple telangiectasia lethal?

J.

Lab. Clin. Med., 29:1211, 1944.

5. Cooper, A. C., and Bolande, R. P. : Multiple

hemangiomas in an infant with cardiac

hy-pertrophy; post mortem angiographic

dem-onstration of the arteriovenous fistulae. Pxm-ATBICS, 35:27, 1965.

6. Burman, D., Mansell, P. W. A., and Warm, R.

P. : Miliary hemangiomata in the newborn. Arch. Dis. Child., 42:193, 1967.

7.

Robbins, S. L. : Pathology, ed. 3. Philadelphia:

W. B. Saunders Company, pp. 608-612,

1967.

8. Kasabach, H. H., and Merritt, K. K. : Capillary

hemangioma with extensive purpura. Amer.

J. Dis. Child., 59:1063, 1940.

9. Inglefield, J. T., Jr., Tisdale, P. D., and

Fair-child, J. P. : A case of hemangioma with

thrombocytopenia in the newborn infant

treated by total excision. J. Pediat., 59:238,

1961.

10. Robinson, D. W. : Discussion of Paletta, F. X., Walker, J., and King, J.: Hemangioma-thrombocytopenia syndrome. Plast. Reconstr. Surg., 23:615, 1959.

11. Meeks, E. A., Jay,

J.

B., and Heaton, C. D.:

Thrombocytopenia purpura occurring with

large hemangioma. Amer.

J.

Dis. Child., 90: 349, 1955.

E.

R. : Congenital adenomatoid malforma-lion of the lung with pneumothorax. Arch.

Dis.

Child.,

35:475,

1960.

13. Chernick, V., and Avery, M. E.: Spontaneous alveolar rupture at birth. Pxrn&rmcs, 32: 816, 1963.

14. Taylor, A. C., and Moore, E. : Multiple heman-giomas showing certain malignant character-istics in an infant. Amer.

J.

Cancer, 19:31, 1933.

15. Copenhaver, W. M.: Bailey’s Textbook of His-tology, ed. 15. Baltimore: Williams and

Wil-kins Company, pp. 252-281, 1964. 16. Zarem, H. A., and Edgerton, M. T.: Induced

resolution of cavernous hemangiomas

fol-lowing prednisolone therapy. Plast.

Re-constr. Surg., 39:76, 1967.

17. Fost, N. C., and Esterly, N. B.: Successful

treatment of juvenile hemangiomas with prednisone. J. Pediat., 72:351, 1968.

Acknowledgments

The authors are grateful to Peggy A. Hanson, M.D., of the Pediatric Neurology Department of the Philadelphia Children’s Hospital, for supplying

the clinical summary of the first infant reported.

The autopsy on this infant was performed by

Ed-ward F. Wilson, M.D., of the Baltimore Public

Health Administration, who kindly allowed the use of this autopsy information. Appreciation is also

expressed to Mary E. Avery,

M.D.,

who is the

chair-man of the Department of Pediatrics of McGill Uni-versity, and Ella H. Oppenheimer, M.D., of the Department of Pathology of Johns Hopkins Hos-pital, for advice in preparation of this manuscript.

William R. Creen, M.D., of the Department of

Pathology of Johns Hopkins Hospital, assisted with special microscopic studies. Mr. P. Lund, of the

Department of Pathology of Johns Hopkins

1970;46;411

Pediatrics

Kenton R. Holden and Fred Alexander

DIFFUSE NEONATAL HEMANGIOMATOSIS

Services

Updated Information &

http://pediatrics.aappublications.org/content/46/3/411

including high resolution figures, can be found at:

Permissions & Licensing

http://www.aappublications.org/site/misc/Permissions.xhtml

entirety can be found online at:

Information about reproducing this article in parts (figures, tables) or in its

Reprints

1970;46;411

Pediatrics

Kenton R. Holden and Fred Alexander

DIFFUSE NEONATAL HEMANGIOMATOSIS

http://pediatrics.aappublications.org/content/46/3/411

the World Wide Web at:

The online version of this article, along with updated information and services, is located on

American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.