Myofibroblastic Tumors Involving Bilateral Adrenal Glands and Skin

Myofibroblastic Tumors Involving Bilateral Adrenal Glands and
Skin in a Patient With Common Variable Immunodeficiency
By Isik Yalçin, Ayper Somer, Ahmet Akçay, Nesimi Büyükbabani, Nuran Salman, and Nermin Güler
Istanbul, Turkey
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 myofibro-
C
OMMON VARIABLE immunodeficiency (CVID)
is characterized by low immunoglobulin levels
and recurrent bacterial infections, bronchiectasis, diarrhea, and malabsorption in patients with an interval of
normal immune function several years after birth.1,2 In
addition, patients with this syndrome exhibit an increased incidence of autoimmune disease s and gastrointestinal or lymphoreticular neoplasms.3,4
We report an unusual cas e of myofibroblastic tumors
involving bilateral adrenal glands, and skin in 14-yearold Turkish boy with a diagnosis of CVID, which to OUT
knowledge, represents the first reported example.
CASE REPORT
A l4-year-old boy, known to have common variable immunodeficiency, was admitted to the hospital for incidentally discovered bilateral adrenal masses by ultrasonography.
His past medical. history was remarkab1e for otitis, pharyngitis,
sinusitis, recurrent pneumonia, and diarrhea, which responded to treatment with various antibiotics. When he was 10 years old, during the
hospitalization for purulent meningitis in our department, laboratory
studies led to the diagnosis of common variable immunodeficiency.
The faiiiily history was negatiye for recurrent infections or immune
deficiency. The patient had nodular lesions of purple-violet color on the
dorsum of the hands and feet present since the age of 5 years. When he
was 10 years old, a skin biopsy was performed. Histology findings of
the skin biopsy showed multiple epithelioid granulomas seattered
throughout the superficial and deep dermis. The granulomas were
composed of aggregated epithelioid histiocytic cells admixed with
lymphocytes. Ziehl-Neelsen stain for acid-fast bacilli and Gram stains
for microorganisms
were negatiye. A positive Mantoux test result
From tire Division of Clinical Immunology, Departments of Pediatric.s and Pathology, Istanbul Faculty of Medicine, Istanbul University,
Aiklress reprint requests to Ayper Somer, MD, Istanbul University,
Isttmbul Medical Faculty, Department of Pediatrics, 34390 Çapa,
Istanbul. Turkey.
Copyright @)2002 by 1v.n. Saunders Company
0022- 34681OJB701-0028S35.00/0
doi: lO.1O53/jpsu.2002.29445
124
blastic tumors
presented.
affecting
both adrenal
glands
and skin is
i
J Pediatr Surg 37:124-126. Copyright @ 2002 by W.B.
Saunders Company.
INDEX WORDS: Common variable immunodeficiency,
blastic tumor, infantile myofibromatosis.
(15 X 15 mm of enduration)
myo-
developed and the acid-fast bacilli stain
from a gastric aspirate was positive. A diagnosis of pulmonary tuberculosis with skin tuberculosis was made and antituberrulous therapy
was instituted. The patient was treated by intravenous immunoglobulin
infusions (400 mg/kg of body weight per month), but continued to have
recurrent sinopulmonary infections and 3 to 4 hospitalizations per year.
On physical examination at the age of 14 years, he was noted to be
smail for his age (weight, 25 kg; height, 125 cm). Height and weight for
chronological age were 1ess than the third percentile according to the
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 a sense of dense nodulation on
palpation (Fig 1). On auscultation, insp~atory crackles were present
over the lower half of both lungs. The edge of the liver was 5 cm below
the right costal margin, and the spleen descended 2 cm below the left
costal margin. Sexual development was retarded; extemal genitalia
were prepubertal with testis volume of 3 mL and axillary and pubic hair
at Tanner Stage 2.
Results of laboratory investigations including complete blood count,
peripheral
smear, urinalysis,
and blood biochemistry
were within nor-
mal limits. I~unologic
evaluation found normal percentages of B
cells (25%), but decreased serum immunoglobulin concentrations (IgG,
371 mg/dL; IgA, O mg/dL; IgM, 40 mg/dL). The percentage of total T
cells was normal (65%). However, he had a decreased percentage
(16%) of T4 (helper) phenotype and
T8 (suppressor) phenotype, resulting
0.5. Anti-A allohemagglutinin
titer
Cutaneous delayed hypersensitivity
and to dinitrochlorobenzene
(DNCB)
an increased percentage (32%) of
in an inverted T4 to T8 ratio of
was decreased (less than 1:32).
to candidin, phytohemagglutinin,
were studied. These results were
negatiye except for a positive test to DNCB.
On chest radiographs, bilateral pneumonic infiltration was noted. A
chest computerized tomography (CT) sean of the thorax showed diffuse
acinary nodular bronchiectasis evident in the right upper anterior
segment and right middle and lower lobes as well as in the left lower
lobe. Abdomen ultrasonography and CT sean showed a right adrenal
mass of 3 X 5 cm and a left adrenal mass of 5 X 7.5 cm, with
hyperechogenic
center cansed by probable necrosis and hemorrhage
(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 encapsulated and contained a L.5-cm nodular protuberance on its
surface. The cut surface was white, rubbery, and whorled. The adrenal
gland was visible adjacent to the nodular protuberance. Two roundovoid masses separated from adrenal tissue by a well-defined fibrous
Journalaf
Pediatric Surgery, Vol 37, No 1 (January),
2002: pp 124-126
MYOFIBROBlASTIC TUMORS IN IMMUNE DEFICIENCY
Fig 1.
hands.
Nodular lesions of purple-violet color on the dorsum of the
125
Fig 3. Tumor tissue consists of spindle shaped cells. Nuclei are
bland, cytoplasmic borders are indistinct. Note the vague fascicular
arrangement of the cells (H&E, original magnification x200).
capsule were removed from the left side. The big one measured 7 X
5 X 4.5 cm, the smaii one 4 X 2.5 X 1.5 cm. The cut surface was
similar in appearance to the opposite side rnmor. Histopathologic
examination showed a tumor consisting of fusiform ceiis with uniform,
spindle-shaped nuc1ei and cytoplasm with indistinct borders (Fig 3).
Smaii focal aggregations of inflammatory ceiis were noticed.
Immunohistochemically,
tumor ceiis were found to be positive for
antivimentin (Fig 4) and anti-a-smooth musc1eactin antibodies (Fig 5).
There was no immunoreaetivity for anti-S- 100 antibody. An investigation for the presenee of Epstein-Barr virus-Iatent membrane protein
(EBV-LMP) also was earried using an anti-EBV-LMP
antibody. No
immunoreaetivity was deteeted either in tumor ceiis or the inflammatory ceiis. Mitotic count in the rnmor tissue was very low (1 to 2
mitoses per 10 high-power fields). Atypieal mitoses were not found.
Despite this faet, the possibility of borderline malignaney was suggested because of high ceiiularity. The skin biopsy specimens obtained
earlier were reexamined and found to be consistent with myofibroblastic rnmors.
After the operation, the patient recovered without eomplieation.
Foiiow-up CT seans of the abdomen showed no residual or reeurrent
tumor. Two years later, the patient died of disseminated candidiasis.
No autopsy was performed beeause of the reluetance of the patien!' s
family.
Fig 2. CT of the abdomen shows bilateral adrenal masses with
hyperechogenic center due to probable necrosis and hemorrhage.
.Fig 4. Diffuse cytoplasmic antivimentin antibody immunoreactivity (antivimentin, original magnification x200).
Fig 5. Cytoplasmic antismooth muscle actin immunoreactivity in
tumor tissue (anti-a-smooth muscle actin antibodies, original magnification x 100).
I'
f
126
YALÇiN ET AL
DISCUSSION
Infantile myofibromatosis is a rare mesenchymal disorder of early childhood manifested by the formation of
tumors in skin, muscle, viscera, bone, and subcutaneous
tissue.5 Numerous examples of these tumors have been
described in the literature under various names, including
congenital generalized myofibromatosis, multiple vascular 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 vary from 0.5 to 3 cm in diameterJ
The second form 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 involvement complicates about one third of the multicentric 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,6 Distinct, circumscribed 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 myofibromatosis lesions often is necrotic (with hyalinization or
ca1cification) or harbors areas of hemangiopericytomalike pattem. Thenumber of mitotic figures varies from O
to 8 per LO high-power fields.6 Immunophenotypical
examination is helpful in this differentiation. Alpha-
smooth muscle actin, vimentin, desmin, S-100, and
CD-34 antibodies are usdul for this purpose.
The histopathologic and immunophenotypical findings
in our patient suggested that these multifocally located
tumors actually were myofibroblastic tumors that fell
into the category of infantile myofibromatosis, Primary
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 tumors were
located in the adrenallocus, but there was no relationship
of the tumor to normal adrenal tissue. The fact that the
adrenals were involved bilaterally and tumor development became evident during the second decade in our
patient was noteworthy.
Patients with CVID are at high risk of not only
infections but also malignancy, especially of the lym-
phoid system.l,4 In a prospective study, Kinlen et al LO
reported that they had observed 5-fold increase of cancer
and 30-fold increase of lymphoma among CVID patients, The most common tumors encountered are gasfuc
carcinomas, thymomas, non-Hodgkin's lymphomas, and
benign lymphoproliferative hyperplasias of the gastrointestinal tract. The coexistence of CVID and a tumor of
mesenchymal origin has been reported only in one case
until now. II However, it was solitary and involved only
bony tissues. Cases of infantile myofibromatosis have
not been associated with congenital or acquired immunodeficiencies.
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 myofibromatosis, it represents the first reported case in which
CVID and a multifocal myofibroblastic tumors coexist.
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