s u r v e y o f o p h t h a l m o l o g y 6 2 ( 2 0 1 7 ) 2 3 7 e2 4 0

Available online at www.sciencedirect.com

ScienceDirect

journal homepage: www.elsevier.com/locate/survophthal

Clinical challenges

Ptosis Shmosis

Michael Kinori, MDa,b,c,*, Guy J. Ben Simon, MDb,c,

Tzukit Zehavi-Dorin, MDc, Shira L. Robbins, MDa,
R. Michael Siatkowski, MDd
a
Ratner Children’s Eye Center at the Shiley Eye Institute, Department of Ophthalmology, University of California San
Diego, La Jolla, California, USA
b
The Dr. Pinchas Borenstein Talpiot Medical Leadership Program, Ramat Gan, Israel
c
Department of Ophthalmology, Goldschleger Eye Institute, Sheba Medical Center, Tel Aviv University, Ramat Gan, Israel
d
Dean McGhee Eye Institute, Department of Ophthalmology, University of Oklahoma, Oklahoma City, Oklahoma, USA

article info (In keeping with the format of a clinical pathologic conference, the abstract and key words appear at
the end of the article.)
Article history:
Received 18 February 2016
Accepted 19 February 2016
Available online 26 February 2016
Peter Savino and Helen Danesh-
Meyer, Editors

1. Case report proptosis, or pseudoptosis from ipsilateral hypotropia or

enophthalmos. If these are ruled out, I would consider the
A friend noted that the left eyelid of a 10-year-old girl was following categories of acquired ptosis in children: diseases
droopy. Her pediatrician suspected Horner syndrome and affecting the muscle/neuromuscular junction, dysfunction of
referred her to neurology and ophthalmology. A chest X ray nerves supplying the eyelid, and mechanical disruption of
was normal. The pediatric neurologist’s examination was normal lid function (which could occur in the lid, on the globe, or
normal except for an isolated eyelid ptosis. The comprehen- in the orbit). Overall, in the first 2 decades of life, trauma
sive ophthalmologist also suspected Horner syndrome and (including postsurgical) would be the most common cause of
referred her to a tertiary care center. She arrived 5 weeks after acquired ptosis. In the absence of such a history, one would
her initial encounter with the pediatrician. place the following in a topical diagnosis: chronic eye drop use,
What is the main differential diagnosis of acquired ptosis in children? contact lens-related inflammation, aponeurotic disinsertion,
myasthenia gravis, chronic progressive external oph-
thalmoplegia or other mitochondrial myopathy, congenital
2. Comments cranial dysinnervation disorders (CCDD), Horner syndrome,
third cranial nerve palsy, and periocular or orbital mass.
2.1. Comments by R. Michael Siatkowski, MD On her examination, she appeared pale. Visual acuity was
20/20 in each eye, and confrontation visual fields were full.
An initial caution is to be sure that the clinical impression of She had 3-mm left upper lid ptosis. The marginal reflex dis-
unilateral ptosis is not actually contralateral lid retraction or tance in the left eye was 1 mm compared to 4 mm on the right

* Corresponding author: Dr. Michael Kinori, MD, Ratner Children’s Eye Center, Shiley Eye Institute, University of California San Diego.
E-mail address: [email protected] (M. Kinori).
0039-6257/$ e see front matter ª 2016 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.survophthal.2016.02.004
238 s u r v e y o f o p h t h a l m o l o g y 6 2 ( 2 0 1 7 ) 2 3 7 e2 4 0

mitochondrial process. There is no history of trauma, surgery,

eye drop, or contact lens use. The presence of a palpable firm
mass posterior to the ptotic lid creates high suspicion for
mechanical ptosis caused by a solid neoplasm or potentially a
thrombosed vascular mass. Myasthenia gravis must always
remain a consideration. If the patient had no evidence of fa-
tigue, curtaining, or Cogan lid twitch, and no history of diurnal
variability, I would be much less concerned about myasthenia
and would not perform an edrophonium test or obtain anti-
Ach receptor antibody testing at this time. Rather, I would
recommend orbital and cranial imaging to assess the extent
and characteristics of the mass. To assess soft tissue and
extraocular muscle anatomy as well as minimize radiation
exposure, I would perform an MRI with and without gadolin-
Fig. 1 e Initial presentation. Notice paleness, left upper lid ium infusion.
“fullness,” and ptosis.

eye. The upper lid crease was present with normal levator 4. Case report (Continued)
function. A nontender hard mass was palpated in the left
upper lid (Fig. 1). Eyelid eversion was unremarkable. There An MRI of brain and orbits revealed a mass in the superior
was no proptosis. The pupils were reactive and equal in both portion of the left orbit measuring 10 by 23 mm (Fig. 2).
light and dark conditions with no relative afferent pupillary Complete blood count revealed pancytopenia (hemoglobin
defect. Eye movements were full. The anterior segment was 9.7 g/dL, platelets 50,000 per microliter, white blood cells 3,600
normal with an unremarkable dilated fundus examination. per microliter). Blood smear showed 13% blast cells, compat-
Has the differential diagnosis been narrowed given the physical ible with leukemia. A bone marrow aspiration confirmed the
examination? What further workup would you recommend? diagnosis of acute myelogenous leukemia (AML). Biopsy of the
orbital lesion, now thought to be a myeloid sarcoma, was
deferred. After appropriate systemic chemotherapy, the mass
3. Comments (Continued) disappeared, and the lid returned to its normal portion (Fig. 3).
At the age of 14.5 years, 4.5 years after the initial diagnosis, she
3.1. Comments by Dr. Siatkowski remains disease free.
Should a biopsy from the orbital lesion in this clinical situation
Using the same thought processes as stated previously, the have been performed?
presence of normal ocular alignment and symmetric position
of globes in the orbits confirms that this is true ptosis on the 4.1. Comments (Continued)
left. Because the amount of ptosis is at the upper end for an
oculosympathetic paresis, and the pupils are normal, Horner 4.1.1. Comments by Dr. Siatkowski
syndrome is ruled out. Similarly, full ocular motility removes Without a diagnosis of AML, biopsy would clearly be indicated;
third nerve palsy, chronic progressive external oph- however, with the information obtained from complete blood
thalmoplegia, and a CCDD from the differential. In addition, count and bone marrow biopsy, as well as consistent imaging
such notable asymmetry would be atypical for any characteristics, it is reasonable to assume that the lesion is a

Fig. 2 e T1 (left) and T2 (middle) coronal sections and a sagittal section (right) of magnetic resonance imaging showing a mass
in the left superior orbit.
 s u r v e y o f o p h t h a l m o l o g y 6 2 ( 2 0 1 7 ) 2 3 7 e2 4 0 239

preferred terminology in the 2001 World Health Organization

classification.1
About 2%e13% of pediatric patients with AML have a focal
myeloid sarcoma tumor at some point in their disease.2,12 Up to
25% of myeloid sarcomas are in the orbit, and this is the most
common site in children with AML.2,12 Orbital sarcomas can be
the presenting sign of systemic disease. If not initially consid-
ered, it can precede a diagnosis of AML by months or years.10 In
patients with previously diagnosed AML, it can be the first sign
of a relapse.6,13,16 The common manifestations of orbital
involvement of myeloid sarcoma are proptosis, eyelid ptosis, or
a visible mass on the surface of the eye (which can be consid-
ered as a “conjunctival mass” or an anterior extent of an orbital
lesion, i.e., visualized within the interpalpebral fissure).6,15
Bilateral13,14 and congenital3 myeloid sarcomas are rare.
In case reports of orbital myeloid sarcoma, it is common to
Fig. 3 e Resolution of ophthalmic findings after induction
find an initial incorrect diagnosis that delayed critical treat-
chemotherapy including resolution of pallor.
ment, For example, a 19-year-old man who presented with
upper eyelid ptosis was initially treated with systemic steroids
myeloid sarcoma (formerly called a chloroma) and treat with for idiopathic orbital inflammation, but later, the diagnosis
systemic chemotherapy. One might argue that this is a suffi- was made by the finding of critically low hemoglobin levels
ciently rare lesion that biopsy should have been performed, (4.6 g/dL).11 In this particular case, the diagnosis of AML was
but on the other hand, when present, a myeloid sarcoma is the reached 1 year after the initial presentation with the misdi-
presenting sign of AML in up to 20% of cases, and the orbit is agnosis of the cause of ptosis thus delaying treatment. This
the site of the mass in almost a third of patients. Another might have led to the poor outcome in this patient who
potential argument to biopsy is the fact that this patient is eventually died. In another case report, a 10-year-old girl with
relatively immunosuppressed and could have an abscess or a history of AML in remission presented with a conjunctival
infection with an unusual organism; however, the clinical mass and was initially treated as conjunctivitis with tobra-
presentation did not yield a high index of suspicion for this. In mycin eye drops.6 In our patient, the initial diagnosis was
summary, I agree with the management, but if the lesion had Horner syndrome that resulted in a 5-week delay in the
not responded to chemotherapy, then histologic examination diagnosis of AML.
of the tissue would be mandatory. The key to decreasing mortality in this disease is early
diagnosis and prompt treatment. If treatment is initiated early,
patients presenting with myeloid sarcoma and no signs of AML
5. Discussion may never develop acute leukemia.8 Although myeloid sarcoma
is a rare ophthalmic manifestation of leukemia, it should be high
The most common cause of ptosis in the pediatric population is on the differential diagnosis list in children with acquired eyelid
a myogenic developmental abnormality, typical congenital ptosis or proptosis because of its severe consequences. This is
ptosis.4,7 Congenital ptosis is usually benign, and a systemic especially true in patients with a history of leukemia who pre-
workup is generally not required. Therefore, the main concerns sent with cutaneous or eyelid masses. It is reasonable to
for the clinician in cases of congenital ptosis are development consider obtaining a complete blood count in every case of ac-
of amblyopia as a result of induced astigmatism or a blocked quired ptosis or proptosis in a child. This simple test could be the
visual axis5 and/or the development of a compensatory chin- difference between quick diagnosis with prompt treatment and
up posture. These factors taken together are the main driving missed diagnosis with delayed treatment.
force toward surgical correction of eyelid position.
When a child presents with an acquired ptosis, although
amblyopia and abnormal head posture may be sequelae, the
references
main concern is to find an underlying cause that can include
serious, sometimes life-threatening conditions. Main causes
for acquired ptosis in childhood are neurogenic (third nerve
1. Brunning RD, Matutes E, Flandrin G. Acute myeloid leukaemia
palsy, Horner syndrome, myasthenia gravis), mechanical not otherwise categorized, in Jaffe ES, Harris NL, Stein H,
(orbital or eyelid mass, inflammation), myogenic (orbital Vardiman JW (eds) World Health Organization Classification
fibrosis syndrome, Kearns-Sayre syndrome), or aponeurotic of Tumours. Pathology and Genetics of Tumours of
(post-traumatic). Haematopoietic and Lymphoid Tissues. Lyon, France, IARC
Myeloid sarcoma (also known as chloroma, granulocytic Press; 2001, pp 91e5
2. Byrd JC, Edenfield WJ, Shields DJ, Dawson NA. Extramedullary
sarcoma, and myeloblastoma9) is a rare tumor that may occur
myeloid cell tumors in acute nonlymphocytic leukemia: a
in isolation or concurrently with a myelodysplastic syndrome,
clinical review. J Clin Oncol. 1995;13:1800e16
myeloproliferative disease, or AML.11 When associated with 3. Ford JG, Yeatts RP, Hartz JW, Chauvenet A. Granulocytic
AML, it is composed of myeloid blast cells that infiltrate soft sarcoma of the eyelid as a presenting sign of leukemia.
tissue in an extramedullary site.17 Myeloid sarcoma is the J Pediatr Ophthalmol Strabismus. 1993;30:386e7
240 s u r v e y o f o p h t h a l m o l o g y 6 2 ( 2 0 1 7 ) 2 3 7 e2 4 0

4. Griepentrog GJ, Diehl NN, Mohney BG. Incidence and 12. Pui MH, Fletcher BD, Langston JW. Granulocytic sarcoma in
demographics of childhood ptosis. Ophthalmology. childhood leukemia: imaging features. Radiology.
2011;118:1180e3 1994;190:698e702
5. Harrad RA, Graham CM, Collin JR. Amblyopia and strabismus 13. Rosenberg C, Finger PT, Furlan L, Iacob CE. Bilateral epibulbar
in congenital ptosis. Eye (Lond). 1988;2(Pt 6):625e7 granulocytic sarcomas: a case of an 8-year-old girl with acute
6. Hong ES, Longmuir SQ, Goins KM. Ocular myeloid sarcoma in myeloid leukaemia. Graefes Arch Clin Exp Ophthalmol.
a 10-year-old child. J AAPOS. 2011;15:504e5 2007;245:170e2
7. Lee V, Konrad H, Bunce C, et al. Aetiology and surgical 14. Shields JA, Stopyra GA, Marr BP, et al. Bilateral orbital myeloid
treatment of childhood blepharoptosis. Br J Ophthalmol. sarcoma as initial sign of acute myeloid leukemia: case report
2002;86:1282e6 and review of the literature. Arch Ophthalmol.
8. Meis JM, Butler JJ, Osborne BM, Manning JT. Granulocytic 2003;121:138e42
sarcoma in nonleukemic patients. Cancer. 15. Shinder R. Ocular myeloid sarcoma in a 10-year-old child.
1986;58:2697e709 J AAPOS. 2012;16:213
9. Menasce LP, Banerjee SS, Beckett E, Harris M. Extra-medullary 16. Yaghouti F, Nouri M, Mannor GE. Ocular adnexal granulocytic
myeloid tumour (granulocytic sarcoma) is often misdiagnosed: sarcoma as the first sign of acute myelogenous leukemia
a study of 26 cases. Histopathology. 1999;34:391e8 relapse. Am J Ophthalmol. 1999;127:361e3
10. Montoro J, Tormo M. Images in clinical medicine. Myeloid 17. Zimmerman LE, Font RL. Ophthalmologic manifestations of
sarcoma. N Engl J Med. 2013;369:2332 granulocytic sarcoma (myeloid sarcoma or chloroma). The
11. Phelps PO, Marcet MM, Hong AR, Nichols JW. Eyelid myeloid third Pan American Association of Ophthalmology and
sarcoma: ominous presentation of acute myelogenous American Journal of Ophthalmology Lecture. Am J
leukemia. Orbit. 2015;34:30e2 Ophthalmol. 1975;80:975e90

abstract

Keywords: A 10-year-old girl presented with painless unilateral left upper lid ptosis. A nontender hard
childhood ptosis mass was palpated in the left upper lid. Blood smear was compatible with the diagnosis of
acute myelogenous leukemia leukemia. The cause of ptosis was now thought to be a mass composed of myeloid blast
chloroma cells (myeloid sarcoma).
myeloid sarcoma ª 2016 Elsevier Inc. All rights reserved.
granulocytic sarcoma
myeloblastoma
orbital mass