Download A 13-Year-Old Girl with Recurrent Inguinal Lymphadenopathy

Case Challenge
A 13-Year-Old Girl with Recurrent
Inguinal Lymphadenopathy
Francesca Del Bufalo, MD; Irene Salfa, MD; Valerio Pardi, MD; Giovanna Stefania Colafati, MD; Maria
Antonietta De Ioris, MD, PhD; Rita De Vito, MD; and Andrea Finocchi, MD, PhD
Francesca Del Bufalo, MD, is a Resident Physician, Department of Pediatric Hematology/Oncology, Bambino Gesù Children’s Hospital, IRCCS,
and Pediatric Department, Tor Vergata University
of Rome. Irene Salfa, MD, is a Resident Physician,
Unit of Immunology and Infectious Disease, University Hospital Pediatric Department, Bambino
Gesù Children’s Hospital, IRCCS, and Pediatric
Department, Tor Vergata University of Rome.
Valerio Pardi, MD, is a Pediatric Surgeon, Department of Surgery and Transplantation, Division of
General Surgery, Bambino Gesù Children’s Hospital, IRCCS. Giovanna Stefania Colafati, MD, is a
Pediatric Radiologist, Department of Neuroradiology, Bambino Gesù Children’s Hospital, IRCCS.
Maria Antonietta De Ioris, MD, PhD, is a Pediatric
Oncologist, Department of Pediatric Hematology/Oncology, Bambino Gesù Children’s Hospital, IRCCS. Rita De Vito, MD, is a Pediatric Pathologist, Department of Pathology, Bambino Gesù
Children’s Hospital, IRCCS. Andrea Finocchi, MD,
PhD, is Assistant Professor of Pediatrics, Unit of
Immunology and Infectious Disease, University
Hospital Pediatric Department, Bambino Gesù
Children’s Hospital, IRCCS, and Pediatric Department, Tor Vergata University of Rome.
Address correspondence to: Andrea Finocchi,
MD, PhD, Unit of Immunology and Infectious Disease, University Hospital Department of Pediatrics, Children’s Hospital Bambino Gesù, and University of Rome Tor Vergata, Piazza Sant’Onofrio,
4 - 00165 Rome, Italy; email: andrea.finocchi@
uniroma2.it.
Disclosure: The authors have no relevant financial relationships to disclose.
doi: 10.3928/00904481-20140325-04
136 | Healio.com/Pediatrics
A
13-year-old girl was referred
to our hospital for diagnostic
evaluation of recurrent inguinal lymphadenopathy. Eleven months
before, she had been admitted to another institution with non-specific right
inguinal lymphadenopathy associated
with bi-monthly intermittent mild fever and hypochromic microcytic anemia, elevation of C-reactive protein
(CRP), and hypergammaglobulinemia
at blood screen. After excluding infectious causes by blood exams, diagnostic
lymph nodal excisional biopsy was performed to exclude malignant etiologies.
Histological examination showed nonspecific lymphoid hyperplasia, and the
girl was discharged with the diagnosis of
non-specific lymphadenopathy and irondeficiency anemia, with prescription of
iron supplements. During the following
months, follow-up blood exams showed
persistence of anemia. At admission to
our institution, the physical examination
was unremarkable except for the presence of a mass in the inner upper aspect
of the right thigh. An accurate history
revealed that the mass had reappeared
soon after the biopsy; the lesion was
below the biopsy area and had enlarged
slowly during the course of 10 months.
It did not show any inflammatory signs
(calor, dolor, rubor, or loss of function);
had a solid, woody consistency; and was
not movable.
During the hospital stay, initial diagnostic workup confirmed persistence of
microcytic anemia — interpreted as anemia of chronic disease — elevation of
CRP and erythrocyte sedimentation rate
(ESR) and hypergammaglobulinemia
(Table 1). Considering the elevated inflammatory markers, antibiotic therapy
was started. Nevertheless, all of the extensive microbiological tests performed
both on blood and on bone marrow were
negative. Indeed, an underlying infectious disease was excluded (Table 1).
Auto-inflammatory causes and autoimmune diseases responsible for recurrent
lymphadenopathy were also excluded
because serum auto-antibodies screening results were negative (Table 1). An
inguinal ultrasound scan revealed the
presence of a 4 × 3 × 4 cm oval lesion in
the internal upper side of the right thigh.
The edges of the mass appeared to be
well-defined, and it was predominantly
For diagnosis, see page 137
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are presented, followed by the diagnosis and an explanation of how the diagnosis was
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PEDIATRIC ANNALS 43:4 | APRIL 2014
Case Challenge
solid, with vascular areas containing
semi-solid material (Figure 1A). An ultrasound scan also showed lymph nodes
with reactive aspect.
A malignant disease or Castleman disease was suspected. A larger biopsy including both the mass and a closer lymph
node was performed, revealing a moderate infiltration of the mass into deep tissues. Both specimens were sent for histopathologic examination,which showed
a polymorphous proliferation of spindlecells with voluminous mononucleated
cells, lympho-histiocytic elements, and
a moderate inflammatory infiltrate; an
abundant myxoid stroma was also described. Immunohistochemistry revealed
mild cytoplasmic staining for anaplastic lymphoma kinase and actin, as well
as mild proliferation index with MIB-1.
Histopathologic examination showed a
reactive lymph adenitis, as well, probably
related to the mass.
Diagnosis:
Inflammatory Myofibroblastic
Tumor
DISCUSSION
The evaluation of the child with inguinal lymphadenopathy (LA) is a common scenario for the pediatrician. Most
cases result from benign and self-limiting diseases and resolve without any
consequences. However, sometimes it
can be a result of the manifestation of a
serious systemic disease; in these cases,
prompt identification and diagnosis is
mandatory.1
The patient was admitted for a recurrent inguinal LA diagnosis with a 1-year
history. The clinical history suggested an
indolent but progressive disease. A careful history and physical examination indicated that the mass appeared shortly after
a lymph node biopsy, just below the area
of the biospy. Physical examination led
us to the suspicion that the mass did not
represent a relapse of the inguinal LA,
PEDIATRIC ANNALS 43:4 | APRIL 2014
TABLE 1.
Summary of Diagnostic Work-Up
Admission
1st Follow-Up
After Resection
Normal Reference
Range
4.34 106/mm3
5.59 > 106/mm3
3.90 - 4.90 106/mm3
Hemoglobin (HB)
7.9 g/dL
13.1 g/dL
12-16 g/dL
Hematocrit (HT)
27.9%
42.5%
36%-49%
Test
Red blood cell (RBC)
Mean corpuscular volume (MCV)
64.3 fL
76.1 fL
75-98 fL
Platlet (PLT)
562 103/mm3
326 103/mm3
150-450 103/mm3
C-reactive protein (CRP)
12.19 mg/dL
0.09 mg/dL
0-0.50 mg/dL
68 mm
N.A
0-15 mm
Serum iron
7 mcg/dL
N.A.
50-170 mcg/dL
Ferritin
99 ng/mL
N.A.
9-290 ng/mL
Erythrocyte sedimentation rate (ESR)
Transferrin
164 mg/dL
N.A.
200-360 mg/dL
Immunoglobulin G (IgG)
2,910 mg/dL
N.A.
700-1,600 mg/dL
Immunoglobulin A (IgA)
356 mg/dL
N.A.
70-400 mg/dL
Immunoglobulin M (IgM)
215 mg/dL
N.A.
40-230 mg/dL
Cytomegalovirus (CMV) serology
Negative
N.A.
Epstein-Barr virus (EBV) PCR
Negative
N.A.
Leishmania PCR and serology
Negative
N.A.
Toxoplasma gondii serology
Negative
N.A.
HIV serology
Negative
N.A.
Parvovirus B19 PCR
Negative
N.A.
Mycobacterium tubercolosis
interferon-gamma release assay
Negative
(3 samples)
N.A.
Bartonella serology
Negative
N.A.
Antinuclear antibody (ANA)
Negative
N.A.
Anti-neutrophil cytoplasmatic
antibody (ANCA)
Negative
N.A.
N.A. = not applicable; PCR = polymerase chain reaction.
but rather a neoformation ex novo, which
was subsequently confirmed by histological examination. Inflammatory myofibroblastic tumor (IMT) is an uncommon,
mesenchymal, low-malignancy potential
neoplasm characterized by proliferating
myofibroblasts that typically present as a
mass in children and young adults. The
most commonly involved visceral site is
the lung, although many extrapulmonary
sites are also recognized; soft tissue localization is exceptionally rare.2 IMT
clinical manifestation and symptoms
range from abdominal pain, intestinal obstruction, urinary symptoms, and a pal-
pable mass for abdominal IMT, to mild
to severe respiratory symptoms for intrapulmonary lesions.3,4 Soft-tissue lesions
usually manifest with a mass with locally
aggressive features that make differential diagnosis with malignant neoplasms
difficult; little attention has been paid
in literature to IMTs of the extremities.5
The important inflammatory component
leads to confounding systemic symptoms
such as unexplained fever, weight loss,
weakness, pallor, as well as to laboratory findings including microcytic anaemia refractory to iron therapy, thrombocytosis, hypergammaglobulinemia, and
Healio.com/Pediatrics | 137
Case Challenge
Image courtesy of Andrea Finocchi, MD, PhD.
Distant metastases have been reported
to occur occasionally, mostly in patients
with abdominal tumors. Histological predictors of aggressive behavior in IMTs
have been largely investigated without
much success.10
Figure 1. The sonographic scan (a) shows a mass at the level of internal upper side of the right thigh
with inhomogeneous structure, solid and fluid. Magnetic resonance axial (MRA) T2-weighted turbo
spin echo (TSE) image (b) shows inhomogeneous mass in the soft tissues (black arrow) with close
relationship with blood vessels. MRA TSE T1-weighted images (d) on the same plane show an intermediate-high signal intensity of the mass, consistent with hemorrhagic infarction. Moreover, coronal
T1-weighted image with fat-suppression after gadolinium administration (c) depicts longitudinal
extension and shows enhancement of the solid component of the lesion (white arrow); notice the
presence of enlarged ipsilateral inguinal lymph nodes.
increased inflammatory markers, mimicking other systemic or neoplastic processes.6 The clinical presentation of our
patient was made more confusing by the
previous lymphadenopathy and lymph
node excisional biopsy, which revealed
a non-specific lymphoid hyperplasia.
We believe that this finding represented
a reactive process to the relevant inflammatory component of the tumor that was
developing but not macroscopically visible yet. To our knowledge, recurrent and
preceding lymphadenopathy has never
been described as presenting sign of IMT.
Although the etiology of IMTs is unknown, association with minor trauma,
surgery, infections, and/or other diseases
of the immune system, as reported from
Alaggio and colleagues,4 suggests an inflammatory origin of the disease.
The treatment of choice for IMTs is
surgical excision. In the present case,
after estimating the extension and infiltration of the mass by MRI (Figures 1B138 | Healio.com/Pediatrics
1D), in accordance with the surgeons
and the oncologists, radical surgical
resection was successfully carried out.
Treatment with chemotherapy or radiotherapy is controversial because of the
variable response reported.7 Occasionally, treatment with steroids or non-steroidal anti-inflammatory therapy have
been reported.8
The prognosis of IMTs remains unpredictable, and as such, these tumors
have been categorized as tumors of intermediate biological potential by the
most recent World Health Organization
classification.9 Most IMTs follow a nonrecurring clinical course after complete
surgical excision, but clinical behavior
of IMTs can be locally aggressive with
local recurrence in case of partial resection. Currently, the girl is in good clinical
condition. The anemia rapidly resolved
after surgical resection without further
iron supplements, and CRP and gammaglobulin count also normalized (Table 1).
CONCLUSIONS
In consideration of the intermediate malignant potential and of the multiform clinical presentation of IMTs, we believe that
pediatricians should be aware of this entity
and should consider it in the differential
diagnosis of a soft-tissue lesion associated
with recurrent local lymphadenopathy and/
or inflammatory symptoms.
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