Childhood proptosis: Relevance of aspiration cytology in the era of newer molecular diagnostic and imaging techniques.

Introduction

Proptosis in a child can often present a diagnostic dilemma. Several types of lesions may cause proptosis in a child [Table 1]. It is important to keep in mind a categorized differential diagnosis so that relevant investigations may be ordered to facilitate early diagnosis and treatment. One investigation that is most often overlooked in the rush to get a computerized tomography (CT) scan or biopsy is a peripheral blood smear examination. This examination can establish the diagnosis of acute myeloid leukemia (AML) in most cases of granulocytic sarcoma, even in the absence of systemic features.[1]

Table 1

Common causes of childhood proptosis

Parents of a 2-year-old gave history of a sudden onset of bilateral proptosis, more of the right eye, of 15 days’ duration. There was difficulty in closure of right eye (i.e., lagophthalmos) along with swelling of cheeks. The child had delayed milestones. There were no symptoms of raised intracranial tension.

Ocular examination revealed bilateral proptosis, more in the right eye than in the left [Figure 1]. There was a firm, nontender mass palpable in the superomedial aspect of both orbits. The right lid was showing lagophthalmos with inadequate closure; the rest of the adnexa were normal. Visual acuity was 6/9 in both eyes. Ocular movements were bilaterally restricted in all the directions of gaze. The anterior segment and fundus examination was unremarkable.

Figure 1

Bilateral proptosis with a palpable mass (arrow) in the superomedial aspect of both orbits

Blood examination revealed Hb 7.9 gm/dl and TLC 66,800/mm3. Peripheral smear showed 52% blasts along with other immature cells of myeloid series. The blasts cells had a high nuclear/cytoplasmic ratio, a round to indented nucleus with fine nuclear chromatin and three to five nucleoli. Few blast cells showed Auer rods [Figure 2]. Platelet count was 40,000/mm3. The bone marrow aspirate confirmed the findings of peripheral smear. These findings were suggestive of AML.

Figure 2

Peripheral smear: Numerous blast cells (myeloblast) 400× [inset: promyelocyte showing Auer rod (arrow)] Giemsa stain

Fine needle aspiration cytology (FNAC) performed from the mass palpable in the superomedial aspect of both orbits showed clusters of atypical cells with a high nuclear-cytoplasmic ratio against a hemorrhagic background. The cells contained irregularly shaped nuclei, with prominent nucleoli and scanty cytoplasm [Figure 3]. This cytology was suggestive of a leukemic infiltrate.

Figure 3

FNAC from swelling at superomedial aspect of orbit with a hemorrhagic background showing blast cells Giemsa stain, 400×

Following this diagnosis, the child underwent two cycles of intensive chemotherapy, including cytosine arabinoside (100 mg/m2) and doxorubicin (30 mg/m2) in a 7-day cycle, with consequent remission of the disease. He did not report for a subsequent follow up at our center.

The pediatric orbit can be involved in many diseases, with varying and often puzzling clinical features. Some of the commoner conditions are orbital cellulitis, dermoid cyst, and hemangioma. However, primary malignancies like rhabdomyosarcoma and those secondary to AML and neuroblastoma are not uncommon [Table 1]. Diagnosis of such cases can be made by a combination of a good clinical examination and relevant investigations.

Investigations that can be done include imaging studies (CT scan, magnetic resonance imaging, and ultrasonography), pathology (aspiration cytology and biopsy), and hematological studies. Though imaging studies are of utmost importance in orbital mass lesions, it may not be the investigation of choice in conditions such as leukemias. Most of these cases can be diagnosed on peripheral smear examination, which is widely available and inexpensive.

AML accounts for nearly 15% of all leukemias in children. Extramedullary leukemic deposits is an unusual manifestation of AML, accounting for approximately 3% of cases of AML, and is commonly called as granulocytic sarcoma.[23] The incidence of granulocytic sarcoma seems to be slightly higher in Asia.[4] In a study of 86 Indian patients with AML, 8 (9.3%) were found to have orbital deposits in one or both eyes.[5] Further study is needed to determine the reason for this predisposition.

In a study of 32 children with extramedullary myeloid cell tumor done at an Indian center, 8 had been referred with the wrong diagnosis.[6] None had undergone a peripheral smear examination.

The prognosis for patients with extramedullary deposits/granulocytic sarcoma depends on the course of the underlying systemic malignancy.[7] Chemotherapy is the mainstay of treatment. The rate of remission following chemotherapy also does not seem to be significantly affected due to the presence of granulocytic sarcoma. Growth factor helps in stimulating marrow following the intensive phase of chemotherapy. At the end of 4 weeks, bone marrow aspirate and biopsy should be repeated to assess for remission. If remission has not been achieved, the same cycle of chemotherapy is repeated. In case remission has been achieved, the consolidation phase starts in the form of cytosine arabinoside (over a period of 4-8 months).[8] Despite the advances in chemotherapeutic schedules, an allogenic bone marrow transplantation from a matched family donor still remains the best long-term option that provides remission-free survival for most patients.[8]

AML should be kept in the differential diagnosis of a child presenting with proptosis or orbital mass with or without skull lesions. A peripheral blood smear should be performed in all cases along with bone marrow aspirate and FNAC for an early detection of AML.