Myofibroblastic tumors involving bilateral adrenal glands and skin in a patient with common variable immunodeficiency.

Abstract

Common variable immunodeficiency (CVID) is a heterogeneous form of primary immune deficiency characterized by hypogammaglobulinemia, recurrent bacterial infections, and various immunologic abnormalities. In addition to recurrent infections, patients with this syndrome have an increased incidence of autoimmune diseases and malignancy. A patient with CVID in whom myofibroblastic tumors affecting both adrenal glands and skin is presented.

Full text

Page 1

Myofibroblastic
Skin in a Patient With Common Variable Immunodeficiency
Tumors Involving BilateralAdrenal Glands and
By IsikYalçin, Ayper Somer, Ahmet Akçay, Nesimi Büyükbabani, Nuran Salman, and Nermin Güler
Istanbul, Turkey
Common
neous
by hypogammaglobulinemia,
tions, and various
to recurrent
anincreased
malignancy.
variable
form
immunodeficiency
of primary
(CVID) is a heteroge-
deficiencycharacterized
recurrentbacterial
abnormalities.
with this syndrome
of autoimmune
withCVID in whom
immune
infec-
immunologicIn addition
infections,
incidence
A patient
patientshave
anddiseases
myofibro-
blastic
presented.
J Pediatr Surg 37:124-126. Copyright @ 2002 by W.B.
Saunders Company.
tumors affectingboth adrenalglands and skin is
i
INDEX WORDS: Common variable
blastic tumor,infantile myofibromatosis.
immunodeficiency,myo-
C
and recurrent bacterial infections,
rhea, and malabsorption
normal immune function several years after birth.1,2 In
addition, patientswith this syndrome
creased incidence of autoimmune disease s and gastroin-
testinal or lymphoreticular neoplasms.3,4
We report an unusual case of myofibroblastic
involving bilateral adrenal glands, and skin in 14-year-
old Turkish boy with a diagnosis of CVID, which to OUT
knowledge,represents the first reported example.
OMMON VARIABLE
is characterized
immunodeficiency
by low immunoglobulin
bronchiectasis,
in patients with an interval of
(CVID)
levels
diar-
exhibit an in-
tumors
CASE REPORT
A l4-year-old
ciency, was admitted to the hospital for incidentally
eral adrenal masses by ultrasonography.
His past medical. history
sinusitis, recurrent pneumonia,
ment with various antibiotics.
hospitalizationfor purulent
studies led to the diagnosis
The faiiiily historywas negatiye
deficiency. The patient had nodular lesions of purple-violet
dorsum of the hands and feet present since the age of 5 years. When he
was 10 years old, a skin biopsy was performed.
theskin biopsy showed multiple
throughoutthe superficialand deep dermis.
composed of aggregated epithelioid
lymphocytes. Ziehl-Neelsen stain for acid-fast bacilli and Gram stains
for microorganismswere negatiye.
boy, known to have common variable immunodefi-
discoveredbilat-
was remarkab1e
and diarrhea, which responded
When he was 10 years old, during the
meningitis in our department,
of commonvariable
for recurrent infections
for otitis, pharyngitis,
to treat-
laboratory
immunodeficiency.
or immune
color on the
Histology
granulomas
The granulomas
cells admixed
findings of
seatteredepithelioid
were
with histiocytic
A positiveMantoux test result
From tire Division of Clinical Immunology,
ric.s and Pathology,Istanbul Faculty of Medicine, Istanbul
Aiklressreprint requests to Ayper Somer, MD, Istanbul
Isttmbul Medical Faculty, Department of Pediatrics, 34390 Çapa,
Istanbul.Turkey.
Copyright @)2002 by 1v.n. Saunders
0022- 34681OJB701-0028S35.00/0
Departments of Pediat-
University,
University,
Company
doi: lO.1O53/jpsu.2002.29445
124
(15 X 15 mm of enduration)
from a gastric aspirate was positive.
culosis with skin tuberculosis
was instituted. The patient was treated by intravenous immunoglobulin
infusions (400 mg/kg of body weight per month), but continued to have
recurrent sinopulmonaryinfections and 3 to 4 hospitalizations
On physical examinationat the age of 14 years, he was noted to be
smail for his age (weight, 25 kg; height, 125 cm). Height and weight for
chronologicalage were 1ess than the third percentile
Turkish Standards. On inspection, he was pale, and there were lesions
of purple- violet color on the dorsum of the hands and feet and also on
the left alae nasi, and these conveyed
developedand the acid-fast bacilli stain
A diagnosisof pulmonary
was made and antituberrulous
tuber-
therapy
per year.
accordingto the
a sense of dense nodulationon
palpation
over the lower half of both lungs. The edge of the liver was 5 cm below
the right costal margin, and the spleen descended
costal margin.Sexual development
were prepubertalwith testis volume of 3 mL and axillary and pubic hair
at Tanner Stage 2.
Results of laboratory investigations
peripheralsmear, urinalysis,and blood biochemistry
(Fig 1). On auscultation, insp~atorycrackles were present
2 cm below the left
extemalwas retarded;genitalia
including complete blood count,
were within nor-
mal limits. I~unologic
cells (25%), but decreased serum immunoglobulin
371 mg/dL; IgA, Omg/dL; IgM, 40 mg/dL). The percentage
cells was normal (65%).However,
(16%) of T4 (helper) phenotype
T8 (suppressor)phenotype, resulting in an inverted T4 to T8 ratio of
0.5. Anti-Aallohemagglutinin titer was decreased
Cutaneousdelayed hypersensitivity
and to dinitrochlorobenzene(DNCB) were studied. These results were
negatiye except for a positive test to DNCB.
On chest radiographs, bilateral pneumonic
chest computerizedtomography(CT) sean of the thorax showed diffuse
acinary nodularbronchiectasisevident
segment and right middle and lower lobes as well as in the left lower
lobe. Abdomen ultrasonographyand CT sean showed a right adrenal
mass of 3 X 5 cm and a left adrenal
hyperechogeniccenter cansed by probable
(Fig 2).
Selective tumorectomy was performed under general anesthesia. The
tumor removed from the right side was a 5- X 4- X 3-cm mass, fairly
well encapsulatedand containeda L.5-cm nodular protuberance
surface. The cut surface was white, rubbery, and whorled. The adrenal
gland was visible adjacentto the nodular protuberance.
ovoid masses separatedfrom adrenal tissue by a well-defined
evaluationfound normal percentages
concentrations
of B
(IgG,
of total T
percentage
(32%) of
he had a decreased
and an increased percentage
(less than 1:32).
phytohemagglutinin,to candidin,
infiltrationwas noted. A
in the rightupperanterior
mass of 5 X 7.5 cm, with
necrosis and hemorrhage
on its
Two round-
fibrous
Journalaf Pediatric Surgery,
Vol 37, No 1 (January),2002: pp 124-126

Page 2

MYOFIBROBlASTIC TUMORS IN IMMUNE DEFICIENCY
Fig 1.
hands.
Nodular lesions of purple-violet color on the dorsum of the
capsule were removed from the left side. The big one measured
5 X 4.5 cm, the smaii one 4 X 2.5 X 1.5 cm. The cut surface was
similar in appearanceto the opposite
examinationshowed a tumor consisting of fusiform ceiis with uniform,
spindle-shapednuc1ei and cytoplasm
Smaii focal aggregations of inflammatory
Immunohistochemically,tumor ceiis were found to be positive for
antivimentin (Fig4) and anti-a-smooth musc1eactin antibodies (Fig 5).
There was no immunoreaetivityfor anti-S- 100 antibody.
gation for the presenee of Epstein-Barr
(EBV-LMP)also was earried using an anti-EBV-LMP
immunoreaetivity was deteeted either in tumor ceiis or the inflamma-
tory ceiis. Mitotic count in the rnmor tissue was very low (1 to 2
mitoses per 10 high-power fields). Atypieal
Despite this faet, the possibilityof borderline
gested because of high ceiiularity. The skin biopsy specimens
earlier were reexaminedand found to be consistent with myofibroblas-
tic rnmors.
Afterthe operation,the patient
Foiiow-up CT seans of the abdomen showed no residual or reeurrent
tumor. Two years later, the patient
No autopsy was performed beeause of the reluetance
family.
7 X
side rnmor.Histopathologic
with indistinct
ceiis were noticed.
borders(Fig 3).
An investi-
virus-Iatent membrane protein
antibody. No
mitoses
malignaney
were not found.
was sug-
obtained
recoveredwithout eomplieation.
died of disseminatedcandidiasis.
of the patien!' s
Fig 2.
hyperechogenic center due to probable necrosis and hemorrhage.
CT of the abdomen shows bilateral adrenal masses with
125
Fig 3.
bland, cytoplasmic borders are indistinct.
arrangement of the cells (H&E, original magnification
Tumor tissue consists of spindle shaped cells. Nuclei are
Note the vague fascicular
x200).
.Fig 4.
ity (antivimentin,
Diffuse cytoplasmic antivimentin
original magnification
antibody immunoreactiv-
x200).
Fig 5.
tumor tissue (anti-a-smooth
nification x 100).
Cytoplasmic antismoothmuscle actin immunoreactivity
muscle actin antibodies, original mag-
in

Page 3

I'f
126
DISCUSSION
Infantile myofibromatosis is a rare mesenchymal dis-
order of early childhood manifested by the formation of
tumors in skin, muscle, viscera, bone, and subcutaneous
tissue.5Numerous examples of these tumors have been
described in the literatureunder various names, including
congenital generalized myofibromatosis,multiple vascu-
lar leiomyomas, multiple mesenchymal hamartomas, and
diffuse congenital fibromatosis.6
Myofibromatosis most often presents as a solitary
lesion in the skin or soft tissues. The tumors usually are
rubbery in nature and varyfrom 0.5 to 3 cm in diameterJ
The secondform is the multicentric variety consisting of
multiple nodules, usually confined to skin, soft tissues,
and bones. In the multicentric form, palpable tumors
usually are present at birth. in contrast, although infants
with solitary lesions are most frequenHy diagnosed at
birth, they may present later in infancy.7 Visceral in-
volvement complicates about one third of the multicen-
tric cases.5 In contrast to the solitary and multicentric
forms, the visceral form usually is fatal secondary to
cardiopulmonary or gastrointestinal complications.5,8
Solitary and multicentric myofibromatosis lesions
have a similar histologic appearance,6Distinct, circum-
scribed nodules formed by spindle-shaped cells show
staining characteristics intermediate between fibroblasts
and smooth muscle. Electron microscopic evaluation
also may show features of both smooth muscle and
fibroblasts, The central portion of infantile myofibroma-
tosis lesions often is necrotic (with hyalinization or
ca1cification)or harbors areas of hemangiopericytoma-
like pattem. Thenumber of mitotic figuresvaries from O
to 8 per LOhigh-power fields.6 Immunophenotypical
examination is helpful in this differentiation. Alpha-
YALÇiN ET AL
smooth
CD-34 antibodies are usdul
The histopathologic
in our patient suggested that these multifocally
tumors actually were myofibroblastic
into the category of infantile myofibromatosis,
adrenal neoplasms of soft tissue type are quite rare, It is
thought to arise from the smooth muscle of the adrenal
vasculature.9 In our case, myofibroblastic
located in the adrenallocus,but there was no relationship
of the tumor to normal adrenal tissue. The fact that the
adrenals were involved bilaterally
ment became evident during the second decade in our
patient was noteworthy.
Patientswith CVIDare at high risk of not only
infectionsbut also malignancy,
phoid system.l,4 In a prospective study, Kinlen et alLO
reported that they had observed 5-fold increase of cancer
and 30-fold increase of lymphoma
tients, The most common tumors encountered are gasfuc
carcinomas, thymomas, non-Hodgkin's
benign lymphoproliferativehyperplasias of the gastroin-
testinal tract. The coexistence
mesenchymalorigin has been reported only in one case
until now.II However, it was solitary and involved only
bony tissues. Cases of infantile myofibromatosis
not been associated with congenital or acquired immu-
nodeficiencies.
Although some features noted in our patient like age
of presentation, absence of family history, unusual organ
localization, and the high cellularity of the tumors are not
consistent with the classic picture of infantile myofibro-
matosis, it representsthe first reported case in which
CVID and a multifocal myofibroblastic
muscleactin,vimentin, desmin,S-100, and
for this purpose.
and immunophenotypicalfindings
located
tumors that fell
Primary
tumors were
and tumor develop-
especially of the lym-
among CVID pa-
lymphomas, and
of CVID and a tumor of
have
tumors coexist.
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