Keywords
blindness - leukemia - marrow - neuroblastoma - proptosis
neuroophthalmic symptoms Introduction
neuroophthalmic symptoms Introduction
Childhood malignancies may present with nonspecific and overlapping clinical features,
making it difficult to differentiate them from each other clinically. They often puzzle
clinicians and pose interesting diagnostic challenges.[1]
[2]
[3]
[4]
[5]
[6]
[7] We describe two unique neuroophthalmological presentations of common childhood malignancies
in this report.
Case 1
A 6-year-old boy presented with a 2-week history of headache and painless, progressive
binocular vision loss. There was a preceding history of intermittent fever for 2 months,
nocturnal bone pains, and recent-onset anemia, requiring a transfusion. He had severe
bilateral visual impairment at presentation, with only the perception of light present.
There was no obvious proptosis or raccoon eye. Fundoscopy revealed bilateral blurring
of disk margins without optic atrophy. Severe pallor, generalized bony tenderness,
and hepatomegaly were present on examination. Sutural diastasis was noted at sagittal
and coronal sutures. The constellation of clinical presentation and the examination
findings raised suspicion of acute leukemia or metastatic neuroblastoma.
Skull radiograph revealed remarkable sutural diastasis ([Fig. 1A]). A contrast-enhanced magnetic resonance imaging (CE-MRI) of the brain and orbit
unveiled multiple intracranial, extradural collections over bilateral frontoparietal
and occipital areas ([Fig. 1B]). Soft-tissue depositions over the orbital apices causing bilateral optic nerve
compression were also evident, explaining the binocular blindness. A bone marrow (BM)
aspiration and bilateral trephine demonstrated clusters of small, round, blue tumor
cells ([Fig. 1C]), with immunohistochemistry indicating a positivity for neuron-specific enolase,
CD 56, and CD 81 ([Fig. 1D]), confirming the presence of metastatic neuroblastoma in the BM. Computed tomography
and a DOTATATE positron emission tomography scan were done for staging, showing a
left suprarenal mass (size: 15 × 12 mm), with extensive metastasis to bones, BM, and
cranial meninges over fronto–parieto–occipital regions. Treatment for high-risk neuroblastoma
was initiated with the rapid COJEC protocol.[8]
[9] There was an improvement in the systemic symptoms. However, the vision loss did
not recover. A reassessment was performed after eight cycles of induction chemotherapy,
demonstrating extensive BM disease. After a detailed discussion with the family, a
decision to proceed with palliative care was taken.
Fig. 1 (A) Antero-posterior view of the skull radiograph showing remarkable sutural diastasis
(white arrow), (B) axial section of T1-weighted MRI of the brain illustrating extradural soft tissue
deposits along bilateral parieto-occipital regions (white dotted arrows), (C) bone marrow aspirate smear showing infiltration by blastoid atypical cells, and
(D) immunohistochemistry demonstrating positivity for neuronspecific enolase
Case 2
A 3-year-old boy presented with proptosis involving the left eye for 1 month without
pain, visual impairment, or systemic symptoms. Physical examination was unremarkable,
except for nonaxial proptosis with esotropia and periocular fullness in the left eye
([Fig. 2A]). A CE-MRI of the brain and orbit was performed and demonstrated a homogeneously
enhancing soft tissue mass involving the basisphenoid with extension into the left
orbit ([Fig. 2B]). Dura-based, multifocal, nodular, enhancing soft-tissue deposits along the left
frontoparietal convexity were also apparent. Clinicoradiological possibilities of
metastatic neuroblastoma and parameningeal rhabdomyosarcoma were considered. Abdominal
ultrasonography and chest radiograph were normal. The tumor was at a difficult site
to access for a biopsy. While a complete blood count was normal at the baseline, a
repeat evaluation after 7 days revealed evolving cytopenias with a hemoglobin of 95 g/L,
total leukocyte count of 4.17 × 109 /L, differential leukocyte count of polymorphs: 23%, lymphocytes: 60%, monocytes:
16%, and a platelet count of 165 × 109 /L. Subsequent BM aspiration revealed findings consistent with acute leukemia ([Fig. 2C]). Flow cytometry confirmed the presence of T cell acute lymphoblastic leukemia (ALL).
Cerebrospinal fluid was paucicellular (three cells/µL), and cytospin did not detect
leukemic infiltration. However, the child was considered “central nervous system (CNS)-positive”
due to the MRI findings suggestive of leptomeningeal carcinomatosis. Induction chemotherapy
was initiated for high-risk T cell ALL as per the Indian Childhood Collaborative Leukaemia
Group protocol.[10] The proptosis resolved 2 weeks into treatment. Reassessment by BM, MRI brain, and
18-fluorodeoxyglucose-positron emission tomography confirmed remission at the end
of consolidation. The child will subsequently receive CNS radiotherapy as a part of
the treatment protocol.
Fig. 2 (A) Proptosis of the left eye, (B) sagittal section of T1-weighted CE-MRI of brain illustrating enhancing sheet of
soft tissue at the basisphenoid with extension to the orbit (black arrow), (C) bone marrow aspirate smear showing blasts (May–Grunwald–Giemsa stain; 1,000x), (D) the blast cells were MPO negative (myeloperoxidase stain; 1,000x). CE-MRI, contrast-enhanced
magnetic resonance imaging.
Discussion
Childhood cancers can have protean presentations. Extracranial malignancies may infiltrate
the brain or the orbit and may be the initial manifestation of the disease.[11]
[12]
[13]
[14]
[15]
[16] The unique presenting features of the cases in the current report are binocular
painless visual loss in the absence of proptosis or raccoon's eye in a child with
metastatic neuroblastoma, unilateral proptosis being the sole manifestation of T cell
ALL in a young boy.
While malignancy was correctly suspected in both cases, the initial possibilities
that were considered were different from the final diagnosis. Tissue diagnosis was
rendered difficult due to the CNS location of the mass lesions, with BM aspiration
and trephine clinching the diagnosis.
Orbital involvement is frequent in patients with metastatic neuroblastoma; raccoon's
eye and proptosis are well-recognized manifestations. However, a presentation with
visual loss without proptosis, as seen in case 2, is a rarity. [Table 1] summarizes the limited reports of orbital metastasis of neuroblastoma presenting
with blindness without proptosis.[11]
[12]
[13]
[17]
[18] Treatment modalities to salvage vision have included steroids, decompressive surgery,
and initiation of chemotherapy to treat the primary disease. The vision remained compromised
in the majority of the reported cases, and the role of either steroids or surgery
in salvaging the vision is not clear. Orbital metastasis of neuroblastoma confers
a poor outcome, partially explained by a higher association with MYCN amplification.[19]
[20]
[21]
Table 1
Selected reports of patients with neuroblastoma presenting with blindness without
proptosis
|
S No.
|
Author, year of publication, country
|
Number of patients
|
Age
|
Duration of blindness; visual acuity at diagnosis
|
Site of optic nerve compression by metastatic tumor
|
Treatment
|
Visual outcome; final acuity
|
Oncologic outcome
|
|
1.
|
Roy et al[17], 2021, India
|
1
|
3 y and 9 mo
|
2 wk; perception of light only
|
Optic canal; bilateral
|
High-dose dexamethasone, rapid COJEC chemotherapy
|
No improvement
|
On therapy
|
|
2.
|
Sivakumar et al [18], 2006, USA
|
1
|
4 y
|
2 wk; 20/200
|
Optic canal; bilateral
|
Not included
|
Not included
|
Not included
|
|
3.
|
McGirt et al[11], 2005, USA
|
1
|
33 mo
|
4 d; no perception of light
|
Optic foramen; bilateral
|
High-dose methylprednisolone, decompressive surgery
|
Partial improvement; finger counting, recognizing faces and printed book characters
|
Not included
|
|
4.
|
Lau et al[12], 2004, USA
|
1
|
2 y
|
Several days; no perception of light
|
Intracranial course; bilateral
|
High-dose steroid
|
Partial improvement; right eye-20/400 , left eye-hand movements
|
In clinical remission
|
|
5.
|
Varma et al[13], 2003, United Kingdom
|
1
|
2.5 y
|
3 wk; hand movement perceived
|
Orbital apices; bilateral
|
Pulse methylprednisolone
|
Right eye-partial improvement; 6/60, left eye-no improvement
|
Not included
|
|
6.
|
Current report
|
1
|
6 y
|
2 wk; no perception of light
|
Orbital apices; bilateral
|
Rapid COJEC chemotherapy
|
No improvement
|
Refractory disease
|
Proptosis due to orbital involvement by ALL is not considered a CNS-positive disease.
A summary of selected reports of childhood ALL with proptosis is presented in [Table 2].[22]
[23]
[24]
[25]
[26] Notably, three of six cases, including the current one, had associated intracranial
or optic nerve involvement, translating to CNS positivity. Proptosis may be the presenting
manifestation of precursor B- or T-lineage ALL affecting infants, children, or adolescents.
Orbital infiltration is more frequently unilateral, with bilateral involvement being
quite uncommon. Visual impairment has been reported infrequently with proptosis. The
oncological outcome of these patients does not differ from the patients who do not
have orbital involvement.[22]
[23]
[24]
[25]
[26]
Table 2
Selected reports of childhood acute lymphoblastic leukemia presenting with proptosis
|
S No.
|
Author, year of publication, Country
|
Number of the patient(s)
|
Age
|
Ophthalmic features
|
Radiology
|
Oncologic diagnosis
|
Mode of diagnosis
|
Outcome
|
|
1.
|
Wang et al[22], 2020, China
|
1
|
4 y
|
Unilateral proptosis
|
Orbital extraconal mass
|
Hypodiploid B-cell ALL
|
Bone marrow study
|
Well on therapy
|
|
2.
|
Sathitsamitphong et al[23], 2019, Thailand
|
1
|
3 y
|
Unilateral proptosis
|
Orbital mass with intracranial extension
|
B-cell ALL
|
Bone marrow study
|
In remission; on therapy
|
|
3.
|
Sivaperumal et al[24], 2018, India
|
1
|
5 y
|
Bilateral proptosis
|
Not included
|
B-cell ALL
|
Bone marrow study
|
In remission; on therapy
|
|
4.
|
Ramamoorthy et al[25], 2016, India
|
1
|
4 y
|
Unilateral proptosis
|
Retrobulbar mass with intracranial extension
|
B-cell ALL
|
Biopsy from the orbital mass and bone marrow study
|
Well on therapy
|
|
5.
|
Thakker et al[26], 2006, India
|
1
|
8 mo
|
Right eye tearing, lid swelling, proptosis
|
Large, homogeneous orbital mass causing axial displacement of the globe and expansion
of the orbit
|
B-cell ALL
|
Bone marrow study
|
Alive and well 14 mo posttreatment
|
|
6.
|
Current report
|
1
|
3 y
|
Unilateral proptosis
|
Mass over basisphenoid with extension into the left orbit
|
T-cell ALL
|
Bone marrow study
|
Doing well on therapy
|
Conclusion
Common childhood malignancies may manifest with myriad neuroophthalmic manifestations,
and a high index of suspicion is required to reach the correct diagnosis.
