Keywords
Blueberry muffin - children - metastasis - neuroblastoma - skin
Introduction
Neuroblastoma is the most common extracranial solid tumor in childhood, accounting
for more than 7% of malignancies in children younger than 15 years of age and 15%
of all pediatric oncology deaths.[1] The most common presentation is as an abdominal mass, with 35% of cases arising
from the adrenergic cells in the adrenal medulla. Other sites of origin are paraspinal
ganglia (35%), posterior mediastinum (20%), and pelvis and neck (5%).[2] Distant metastatic disease at presentation is encountered in 60%–70% of children
with the most commonly affected sites being the bone marrow, followed by the lymph
nodes, liver, and skin.[3] Skin metastasis in the form of bluish, nontender subcutaneous nodules resembling
blueberry muffins are seen almost exclusively in infants.[4]
Case Report
A 2-month-old male infant presented with 1 month history of multiple bluish skin nodules
over trunk and extremities along with significant abdominal distension for 15 days.
At admission, the child was lethargic, irritable, moderately pale, and undernourished.
He had a pulse rate of 110/min, respiratory rate of 48/min, blood pressure of 84/52
mmHg, and SpO2 of 99% on room air. Multiple light bluish subcutaneous nodules [Figure 1] of 1–4 cm diameter were present all over the body. These mobile and nontender nodules
were asymmetrically spread over trunk, extremities, and face. The abdomen was significantly
distended and two large masses were palpable below the right and left costal margin.
Rest of the systemic examination was unremarkable. Hematological evaluation revealed
a hemoglobin of 7.7 g/dl, total leukocytes count of 6280/mm 3 (polymorph 22%, lymphocyte
66%), platelet count of 1.89 lakh/mm 3 and general blood picture suggestive of normocytic
normochromic anemia. Ultrasonography abdomen revealed an enlarged liver with multiple
hyperechoic well-defined rounded nodules. A large ill-defined heteroechoic lesion
was seen in the right subhepatic region measuring 3.6 cm × 1.5 cm displacing the kidney
anteromedially. Another similar lesion was seen in left lienorenal fossa measuring
3.9 cm × 2.8 cm displacing the left kidney. Contrast enhanced computed tomography
(CECT) abdomen confirmed the presence of large heterogeneously enhancing bilateral
paravertebral lesions merging in midline measuring approximately 7.7 cm × 7.3 cm ×
6.4 cm [Figure 2]. Anteriorly, the lesion was causing displacement of pancreas, stomach, and bowel
loops while laterally displacing bilateral kidneys with encasement of renal vessels.
There was evidence of heterogeneous calcification within the lesion along with encasement
of the aorta, celiac artery, superior mesenteric artery, and inferior vena cava. The
liver was grossly enlarged with multiple heterogeneously enhancing nodular lesions
of varying sizes in both lobes. Multiple heterogeneously enhancing calcified lesions
were also seen in bilateral lung bases, superficial soft tissue of posterior abdominal
wall, pelvic, and perineal soft tissues. Overall findings were suggestive of bilateral
neuroblastoma with metastatic lesions involving liver, lungs, and superficial soft
tissues. 24 h urinary vanillylmandelic acid (VMA) level was found to be elevated.
A provisional diagnosis of bilateral neuroblastoma stage 4-S was made. For further
confirmation and staging of the tumor, immunohistochemistry, exploratory laparotomy,
and tumor biopsy were required. As our center was not having a specialized oncology
department, we preferred to refer the child to a tertiary care oncology center for
further management.
Figure 2: Sagittal (a) and Coronal (b) sections of contrast enhanced computer tomography
abdomen showing presence of large heterogeneously enhancing ill marginated lesions
(arrows) in bilateral paravertebral location and merging in midline
Figure 1: Blueberry muffin baby with multiple light bluish subcutaneous nodules over
trunk and extremities
Discussion
Neuroblastoma is the most common solid tumor of infancy with a median age at presentation
being 23 months.[2] Clinically, it may present with abdominal distension, proptosis, bone pain, pancytopenia,
hypertension, watery diarrhea, and rarely subcutaneous skin nodules.[5] Young infants can present with bluish skin metastases in the form of subcutaneous
nodules. These non-tender, bluish, and mobile nodules popularly known as “blueberry
muffin sign” are almost exclusively seen in infants with stage 4-S neuroblastoma.[2],[4] Stage 4-S neuroblastoma is characterized by metastases confined to skin, liver,
and bone marrow in infants younger than 1 year but no distant osseous metastasis.[6] Blueberry muffin baby is the morphologic term used to describe the appearance of
nonblanching, bluish nodules in young babies. These eruptions are often generalized
but favors the trunk, head, and neck. It had been reported to be a manifestation of
either dermal erythropoiesis or neoplastic infiltrations. Among the neoplastic diseases
with blueberry muffin babies, neuroblastoma is most commonly associated, whereas rhabdomyosarcoma,
Langerhans cell histiocytosis, and leukemia are less frequently reported.[7] Abdominal ultrasonography is the preferred initial investigation if the abdominal
mass is the presentation. CECT scan clearly delineate an abdominal mass with evidence
of regional invasion, vascular encasement, lymphadenopathy, and calcification. Final
diagnosis rests on pathological confirmation after examination of tumor tissue obtained
by tru-cut biopsy in metastatic or nonresectable cases or during definitive surgery
in localized resectable cases. Elevated urinary catecholamines support the diagnosis
in over 90% of cases.[2] Patients with Stage IV-S disease have an excellent prognosis (>90%) without the
use of adjuvant chemotherapy and radiotherapy.[8]
Conclusion
Neuroblastoma is one of the most common reported childhood malignancy, but sometimes,
it can present in an extremely unpredictable manner. Infantile neuroblastoma, especially
stage 4-S can present exclusively as multiple skin metastasis in the form of bluish
subcutaneous nodules resembling blueberry muffins. Although blueberry muffin baby
has conventionally been reported as a manifestation of dermal erythropoiesis in many
congenital viral infections, the possibility of neoplastic infiltration and most commonly
neuroblastoma should be taken into account. Although blueberry muffin as a presentation
of stage 4-S neuroblastoma has been correlated well with excellent prognosis in most
of the available literatures, its early detection will definitely help in timely management
and overall prognosis.
Declaration of patient consent
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In the form the patient(s) has/have given his/her/their consent for his/her/their
images and other clinical information to be reported in the journal. The patients
understand that their names and initials will not be published and due efforts will
be made to conceal their identity, but anonymity cannot be guaranteed.
