Approach to a Child with Bilateral Proptosis as a Rare

Presentation of Acute Myeloid Leukemia

Shafiq Tanveer, Maryum Khilji, Rao E. Hassan, Safina Tanveer

& Ayesha Khilji
American Journal of Health, Medicine and Nursing Practice
ISSN 2520-4017 (Online)
Vol.9, Issue 2, pp 42 – 53, 2023 www.ajpojournals.org

Approach to a Child with Bilateral Proptosis as a Rare Presentation

of Acute Myeloid Leukemia
1*
Shafiq Tanveer
Department of Ophthalmology, Khyber Teaching Hospital, Peshawar Pakistan
2
Maryum Khilji
Department of Ophthalmology, Khyber Teaching Hospital, Peshawar Pakistan
3
Rao E. Hassan
Department of Surgery, Ayub Teaching Hospital, Abbottabad Pakistan
4
Safina Tanveer
Department of Surgery, Lady Reading Hospital, Peshawar Pakistan
5
Ayesha Khilji
Department of Medicine, Hayatabad Medical Complex, Peshawar Pakistan

Article history
Submitted 23.09.2023 Revised Version Received 01.10.2023 Accepted 02.10.2023

Abstract report emphasizes on the low threshold for

A 6-year-old girl presented with a 2-month hematological malignancies in the
history of sudden onset, painless, presentation of bilateral proptosis.
progressively increasing bilateral proptosis, Ophthalmologists should be cognizant of the
palpable lymphadenopathy and skin pallor. A unusual ophthalmic manifestations of
full blood count showed bicytopenia and the haematological malignancies, as they are a
erythrocyte sedimentation rate (ESR) was diagnostic challenge but knowledge about the
raised. Computerized tomography (CT) scan rare extramedullary manifestations of AML
showed bilateral lacrimal gland enlargement. facilitates early diagnosis and thereby
The bone marrow biopsy was consistent with improves prognosis.
M2 acute myeloid leukemia (AML). The Categories: Ophthalmology, Pediatrics,
patient received symptomatic treatment and Hematology
was sent to pediatric oncologist for induction Keywords: Haematological Manifestations,
chemotherapy and tumor lysis syndrome Pediatric Rare Diseases, Ocular Metastasis,
(TLS) protocol. Bilateral proptosis is a rare Acute Myeloid Leukemia (Aml), Bilateral
manifestation of several diseases. This case Proptosis

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Vol.9, Issue 2, pp 42 – 53, 2023 www.ajpojournals.org

INTRODUCTION
Acute Myeloid Leukemia (AML) is a hematological malignancy characterized by proliferation of
immature myeloid cells (mainly blasts) which eventually replaces the healthy bone marrow,
circulates in the blood and accumulates in other tissues of the body. The common manifestations
of AML are due to suppression of normal hematopoiesis by the leukemic infiltrates [1].. In this
case report, a diagnostic dilemma has been addressed in the form of extensive workup for sudden
onset, rapidly progressing, bilateral proptosis which was later diagnosed as rare presentation of
AML. Proptosis is a condition where the eye protrudes forward from the orbit. It is of utmost
importance to differentiate proptosis from contralateral enophthalmos, microphthalmos and other
causes of pseudoproptosis. The differential diagnosis of bilateral proptosis in pediatric age group
are thyroid ophthalmopathy, idiopathic orbital inflammatory disease, metastatic tumors like
neuroblastoma and Ewings sarcoma, erythropoietic and lymphoproliferative neoplasms like
leukemia, lymphoma and histiocytic disorders like langerhan’s cell histiocytes [2] Proptosis is a
common symptom in various diseases affecting the structures around the eye socket. Evaluating
proptosis involves detailed ocular and systemic history specific to the age group, performing
extensive ocular exam, confirming the cause through peripheral smear, MRI, and bone marrow
assessment, and conducting histopathological examination if necessary [3,4]. The problem
addressed in this abstract is the uncommon occurrence of bilateral proptosis in a 6-year-old girl,
which ultimately led to the diagnosis of M2 acute myeloid leukemia (AML). This case report
highlights the diagnostic challenge faced by ophthalmologists in recognizing the atypical
ophthalmic manifestations of hematological malignancies. By increasing awareness of these rare
extramedullary manifestations of AML, early detection and subsequent treatment can be
facilitated, ultimately improving the patient's prognosis.
Case Presentation
A 6-year-old girl presented to our hospital in the outpatient department with a 2-month history of
slowly progressing bilateral protrusion of the eyes and masses in the orbits (Figure 1, 2). According
to the mother there was sudden onset, gradually progressive, painless protrusion of the eyes. The
mother did not notice any significant change in vision. She had no reported weight loss or gain, no
flushing, sweating or any heat intolerance. There were no associated tremors or palpitations. She
had no significant past history of any trauma or surgery (facial/ophthalmic). No reported systemic
disease, no history of known cancer or any chemo-radio-therapy. There was no family history of
proptosis. All other siblings were ophthalmologically and systemically normal. She was not taking
any regular medications.

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Figure 1: Bilateral Proptosis In A 6 Year Old Child, Frontal View

Figure 2: Bilateral Proptosis In A 6 Year Old Child, Lateral View

Her visual acuity was 6/12 with LEA symbols in both eyes, with no further improvement. The
pupils were round, regular and reactive to light with no relative afferent pupillary defect (RAPD).
Color vision and contrast sensitivity were normal. Visual fields were grossly normal. The
extraocular movements were restricted in all gazes except in depression. The lacrimal glands were
enlarged and palpable. The intraocular pressures were 30mm Hg in the right eye and 24mm Hg in
the left eye. There was a subconjunctival haemorrhage in the superotemporal aspect of bulbar
conjunctiva of the left eye. There were chorioretinal folds on the maculae of both eyes. Table 1
summarizes the ocular exam findings:

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Table 1: Summary of Ocular Examination Findings

OCULAR EXAMINATION
RIGHT EYE (OD) LEFT EYE (OS)
COMPONENTS
VISUAL ACUITY 6/12 with LEA symbols 6/12 with LEA symbols
BEST CORRECTED VISUAL ACUITY No further improvement
No further improvement
Round, regular, reactive to Round, regular, reactive to
PUPILS
light; no RAPD light; no RAPD
COLOR VISION AND CONTRAST SENSITIVITY Normal
Normal
VISUAL FIELDS BY
Grossly unaffected Grossly unaffected
CONFRONTATION
EXTRAOCULAR MOVEMENTS Restriction in all gazes except in depression
Restriction in all gazes except in depression
IOP 30mm Hg 24mm Hg
ADNEXA AND ORBITS Enlarged, palpable lacrimal glands.
Enlarged,palpable lacrimal glands glands
CORNEA Clear Clear
CONJUNCTIVA Subconjunctival haemorrhage in
superotemporal aspect of bulbar conjunctiva in the left eye
ANTERIOR CHAMBER Deep and quiet Deep and quiet
LENS Clear Clear
Chorioretinal folds on the Chorioretinal folds on the
FUNDI
macula macula

RAPD= relative afferent pupillary defect

Physical examination was notable for mild fever, pallor, cervical and preauricular
lymphadenopathy. No facial asymmetry or scars were noted. Axial proptosis was present with no
dystopia, not associated with lagophthalmos or corneal exposure. The lacrimal glands were
enlarged and palpable. No bruit were heard over the orbit and no pulsations felt. The patient was
not cooperative for examination with an exophthalmometer. Laboratory investigations were
performed, the results of which are summarized in Table 2:

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Table 2: Results of the Investigations

Investigations Results Units Reference Ranges
RBCs 2.04 x106/uL 4-6
WBCs 7.79 x103/uL 4-
11
Platelets 64 x103/uL 150-450
Hemoglobin 6.6 g/dL 11.5-
17.5
LDH 684 U/L 91-180
ESR 120 mm at the end of 1st hour 0-
15
CRP 0.3 mg/L <1
Blood Urea 25.9 mg/dL 10-
50
Total Bilirubin 0.29 mg/dL 0.1-1
ALT 14 U/L 10-
50
ALP 135 U/L <269
Creatinine 0.35 mg/dL 0.3-
0.9
28% atypical cells
Blast cells % <5
(blasts)
Cell Morphology Anisocytosis -
Chest X-ray Normal

LDH= lactate dehydrogenase, ESR= erythrocyte sedimentation rate, CRP= c-reactive protein,
ALT= alanine aminotransferase, ALP= alkaline phosphatase.

Bone marrow aspiration cytology confirmed 65% blast cells and acute myeloid leukemia (AML-
M2).
Ocular investigations were performed which included optical coherence tomography retinal nerve
fiber layer (OCT- RNFL) which showed thickening of the nerve fiber layer inferiorly in the right
eye (Figure 3). Fundus photographs showing chorioretinal folds on the maculae of both eyes
(Figure 4, 5, 6, 7). CT brain showed bilateral lacrimal gland enlargement, likely lymphomatous
masses (Figure 8). In view of the confirmed diagnosis of leukemia, considering the financial
constraints and the unstable clinical condition of the child, other forms of neuroimaging were
deferred.

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Figure 3: OCT-RNFL Showing Thickening of the Retinal Nerve Fiber Layer Infero-Temporally
in the Right Eye
OCT-RNFL= Optical Coherence Tomography- Retinal Nerve Fiber Layer

Figure 4: Fundus Photograph, Right Eye

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Figure 5: Fundus Photograph of Right Eye Showing Chorioretinal Folds

Figure 6: Fundus Photograph, Left Eye

Figure 7: Fundus Photograph of Left Eye Showing Chorioretinal Folds

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Figure 8: CT Brain Showing Enlarged Lacrimal Glands (Red Arrows)

Our patient was referred to the pediatric hematology and oncology department where she was
started on induction chemotherapy and 1 month follow up showed subjective remission of the
proptosis and improvement in visual acuity. As the optic discs of the patient showed no signs of
compression (optic disc swelling/ optic atrophy) we expect good visual prognosis. This highlights
the importance of early workup and timely management of bilateral proptosis. Ophthalmologists
should be aware of the unusual ophthalmic manifestations of haematological malignancies, as they
cause diagnostic dilemmas. Knowledge about the rare extramedullary manifestations of AML
facilitates early diagnosis and thereby improves prognosis.
Discussion
Acute myeloid leukemia (AML) is a type of blood cancer where there is an abnormal and
uncontrolled growth of immature myeloid cells, which are malignant versions of the normal
myeloid cell lineages. These cells replace the normal bone marrow and spread to the other tissues
of the body [5]. It is most common in children and young adults; the mean age being 7 years [5].
AML accounts for about 15% of all leukemias in children [4]. ‘Granulocytic sarcoma’ refers to

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the aggregation of the leukemic cells in the extramedullary sites. It was previously called 'Green
tumor' by Allen Burns due to the myeloperoxidase enzyme present in these cancerous cells and
these represent only about 3% of the AML tumors [6]. They can involve skull, orbits, paranasal
sinuses, sacrum, spine, sternum, and ribs. One rare presentation of these granulocytic tumors is as
an orbital mass in AML [6].
The usual differential diagnoses to consider in the paediatric age group are dermoid cyst,
retrobulbar hemangioma, retrobulbar hematoma, orbital cellulitis, orbital spread of retinoblastoma,
pseudoproptosis due to enlargement of the globe or abnormalities of the craniofacial skeleton etc.
Less common diseases are metastatic neuroblastoma, rhabdomyosarcoma and hematological
malignancies such as leukemia and lymphomas. In our patient there was bilateral proptosis with
enlargement of lacrimal glands bilaterally without any bony destruction.
AML has been reported as unilateral or bilateral proptosis as the presenting complaint [8,9]. The
cause of proptosis in these cases can range from leukemic infiltrates to venous blockage including
retrobulbar hemorrhage and orbital muscle infiltration. Unilateral or bilateral ptosis, involvement
of the lacrimal glands, conjunctival masses, incomplete or complete uveal tract involvement are
some other presentations of this disease [9]. Reduction in the visual acuity and limitation of the
extraocular movements are seen in the vast majority of the cases. Peripheral smear is an important
tool in diagnosing AML and gives a clue to diagnosis by showing immature blast cells and relative
neutropenia. Complete neuroimaging was not done in our case except CT brain as the diagnosis
was confirmed with bone marrow aspiration alone and there were financial constraints.
The treatment options with a good response in AML are chemotherapy or radiotherapy or both
[10,11]. Nonetheless, stem cell transplant is the treatment of choice for providing disease-free
survival for the patients [10]. Prognosis is related to the grade and spread of hematologic
malignancy at the time of diagnosis.
A case like ours has been reported by Gupta et al. [2] in a 2-year-old child with bilateral proptosis
and palpable mass in the superomedial aspect of both orbits, diagnosed as AML on aspiration
cytology. Imaging studies were not performed in their case similar to ours.
In conclusion, a low threshold should be kept for AML in a child presenting with sudden onset,
rapidly enlarging bilateral proptosis. For early diagnosis of AML, peripheral blood smear along
with bone marrow aspiration should be performed, supported by radiological imaging in all the
cases. The research gaps of our report include, late presentation, failure to perform complete
proptosis examination due to which the objective improvement could not be assessed, loss of
follow up after 1 month because of which prognosis of this particular patient could not be
ascertained, incomplete neuroimaging due to poor financial status. These are the potential areas of
research in the future. Further studies are needed to establish the relationship of time of
presentation in bilateral proptosis with the prognosis of a patient in hematological malignancies
needs to be studied.

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CONCLUSIONS
Bilateral proptosis is an alarming symptom in children as it points out to the life threatening
conditions. Therefore, meticulous work-up should be done for the early diagnosis and timely
treatment as it can prove life saving for many children. Low threshold must be kept for
leukemias/lymphomas in children with bilateral proptosis as sometimes it is the only presenting
complaint. Ophthalmologists should be vigilant in diagnosing unusual ophthalmic manifestations
of haemotological malignancies, as they are a diagnostic challenge but knowledge about the rare
extramedullary manifestations of AML facilitates early diagnosis and thereby improves prognosis.
Additional Information
Disclosures
Human Subjects
Consent was obtained or waived by all participants in this study. Dr. Farooq Ahmad issued
approval No.447/DME/KMC. Dr.Shafiq Tanveer, TMO (Department of Ophthalmology) MTI
KTH Peshawar (Principal Investigator) has been, on the 2nd August, 2023given approval by the
IREB of the Khyber Medical College/Khyber Teaching Hospital for the following case report:
'Approach to a child with bilateral proptosis as a rare presentation of Acute Myeloid Leukemia'
During the whole work, all personal information of patients/subjects should be kept confidential.
If you make any substantial change in the case report, you will need to inform the IREB for formal
approval.
Conflicts of Interest
In compliance with the ICMJE uniform disclosure form, all authors declare the following:
Payment/Services Info
All authors have declared that no financial support was received from any organization for the
submitted work.
Financial Relationships
All authors have declared that they have no financial relationships at present or within the previous
three years with any organizations that might have an interest in the submitted work.
Other Relationships
All authors have declared that there are no other relationships or activities that could appear to
have influenced the submitted work.

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