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Boy notices left eye sinking over 1 month
Left hypoglobus and 2.5 mm of relative left proptosis were seen on examination.
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A 12-year-old boy presented to our hospital complaining of his left eye “moving gradually downward.”
He was accompanied by his aunt, his primary caretaker, who reported that approximately 1 month prior he had complained of left eye achiness and pain that had since resolved. Since that time, his aunt had noticed that his eye had gradually been moving outward and downward. He noticed no change in vision and had no pain. He had no significant medical history and was on no medications. There was no history of orbital trauma. His aunt reported he had been slightly more tired than usual over the past month, but he otherwise felt well and there was no history of fever, chills or weight loss. There was no history of diplopia and no history of upper respiratory infection or nasal congestion. He had been seen on the day of presentation at an outside hospital and transferred to our hospital urgently for further management.
Examination
At the time of presentation, uncorrected visual acuity was 20/25+ in each eye. External exam was significant for left hypoglobus and 2.5 mm of relative left proptosis. The lids were soft without significant erythema or edema. Motility was full in both eyes, and the patient was orthotropic on cover testing. IOPs were within normal limits. Pupils were round and reactive to light in both eyes without afferent defect. Ishihara color plate testing was full in each eye. Slit lamp exam was unremarkable, and dilated funduscopic exam demonstrated normal posterior segments of both eyes. Optic nerves were both found to have 0.2 cup-to-disc ratio with no edema or pallor. Confrontational visual field testing was full in each eye.
What is your diagnosis?
Eye moving downward
Although the patient was referred for management of orbital cellulitis, the duration of symptoms and lack of pain or other typical signs of infection meant that a neoplastic process was high on our differential. Antibiotics were initially deferred, and an MRI of the orbits demonstrated severe left frontal sinus opacification and destruction of the orbital roof adjacent to the frontal sinus and possibly some of the posterior table of the frontal sinus with an associated 2-cm rim-enhancing fluid collection, which extended into the left frontal intracranial fossa (Figure 1). This study was read as severe frontal sinusitis with left intraorbital subperiosteal abscess. Blood work obtained on presentation, including a complete blood count and chemistry panel, was within normal limits.
Figure 1. T1 MRI post-contrast axial (a to c) and coronal (d to f) images demonstrate opacification of the left frontal sinus with bone destruction involving the inferior and the posterior wall as well as a mass growing into the superior aspect of the orbit and minimally into the intracranial epidural space. This was read as most likely in keeping with left frontal sinusitis and secondary osteomyelitis with bone destruction with abscess to the superior aspect of the orbit and very tiny early epidural abscess.
Images: Tawse KL, Joshi A
The differential diagnosis for an orbital mass in a 12-year-old is broad and includes inflammatory, infectious, traumatic, neoplastic and congenital causes. However, the presence of bony erosion on imaging helped to narrow the differential significantly and is generally only seen in infectious and neoplastic processes. Although the MRI was read as sinusitis with orbital abscess and this remained a consideration, the duration of symptoms, the slowly progressive nature of the lesion and the lack of pain were concerning for a neoplastic process such as rhabdomyosarcoma. Moreover, the lack of sinus disease elsewhere and the presence of a rim-enhancing lesion, as opposed to a homogenously enhancing lesion, on imaging was atypical for orbital cellulitis. Ultimately, tissue was needed for definitive diagnosis, and the patient was promptly taken to the operating room for biopsy.
An anterior orbitotomy through an upper lid crease incision was performed and revealed a gelatinous mass in the superior orbit and frontal sinus with significant bony erosion of the superior orbital rim and roof. Debridement and debulking were performed, and a specimen was sent fresh for culture, pathology and cytology. No organisms were identified on Gram stain, and culture demonstrated no growth. The biopsy section showed inflammation with small areas of necrosis (Figure 2). Careful inspection demonstrated sheet-like proliferation of intermediate-sized histiocytoid cells that were uniform and did not show increased mitoses or severe atypia. These cells were present on a variably vascular and mucinous background with numerous eosinophils (Figure 3). Flow cytometry demonstrated CD1a positivity, and immunostain for BRAF V600E was also positive, which in combination with the morphologic findings, confirmed the diagnosis of Langerhans cell histiocytosis.
Discussion
Langerhans cell histiocytosis, previously known as histiocytosis X, is a rare disease involving a clonal proliferation of abnormal histiocytoid cells that has a range of clinical manifestations from isolated bone lesions to multisystem disease. The exact pathophysiology of the disease remains unclear, and there is evidence for both an atypical immunoreactive and neoplastic process underlying its development. Although it is characterized by a clonal proliferation of cells with mutations in the BRAF proto-oncogene, the cell cycle remains reasonably intact, unlike in other neoplasms. Unifocal disease, previously known as eosinophilic granuloma, is characterized by lytic bone lesions in a single area of histiocytic proliferation. This represents the most common presentation of the disease and has a predilection for the superior and superolateral orbit. Hand-Schuller-Christian disease refers to a multifocal unisystem variant of the disease characterized by the triad of diabetes insipidus (due to pituitary involvement), exophthalmos and lytic bone lesions (classically of the skull). Finally, Abt-Letterer-Siwe disease refers to the acute multifocal multisystem form of disease often seen in young children that carries a poor prognosis.
Figure 2. Biopsy of orbital roof lesion demonstrating inflammation with small areas of necrosis.
Figure 3. Higher magnification of the biopsy section shows a sheet-like proliferation of intermediate-sized histiocytoid cells. Characteristic reniform (white arrow) and peripheral coffee bean shaped nuclei (black arrow) are seen. The cells are uniform and do not show increased mitoses or severe atypia. There are numerous scattered eosinophils (pink cells), in a variably mucinous and vascular background.
Langerhans cell histiocytosis represents less than 1% of orbital tumors in children, although 23% of patients have orbital involvement and can present with proptosis, ptosis, erythematous swelling or impaired extraocular movements. The appearance can mimic orbital cellulitis, and the diagnosis should be considered when the clinical picture is atypical for an infectious etiology. Imaging demonstrates well-defined bony lesions with a classic “punched out” lytic appearance usually with soft tissue involvement. Diagnosis is confirmed histologically with tissue biopsy demonstrating pathologic Langerhans cells, which resemble macrophages rather than the typical dendritic Langerhans cells in the skin, over a background of inflammation that may contain giant cells and eosinophils. A combination of at least two immunohistochemical markers, including S100 (neuronal), CD1a, langerin (both specific for Langerhans cells) or BRAF V600E (mutant protein in Langerhans cell histiocytosis), is sufficient for diagnosis. Additionally, Birbeck granules, small rod or tennis racket-shaped granules found in the cytoplasm of Langerhans cells seen by electron microscopy, when present, are regarded as pathognomonic for Langerhans cell histiocytosis.
Treatment is based on the extent of the disease and generally consists of excision for unisystem or unifocal disease and chemotherapy for multifocal or multisystem disease and “CNS risk” disease (lesions in contact with dura mater). Radiation can be considered in recurrent disease, and the use of bone marrow transplant has been described in cases of uncontrolled disease.
Overall, Langerhans cell histiocytosis, particularly when unifocal, generally portends a favorable prognosis, with greater than 90% disease-free survival in some studies, but urgent biopsy is needed to guide prompt initiation of treatment and exclude other neoplastic diagnoses.
Follow-up
After diagnostic biopsy, a skeletal survey was performed in our patient and demonstrated no other lesions. Additionally, a CT of the chest, abdomen and pelvis was read as normal. Given the intracranial extension, our patient was classified as having single-system disease with CNS risk disease and thus underwent port placement for initiation of chemotherapy. When last seen, the patient had completed 9 weeks of IV vinblastine and oral prednisone and was doing well, with improvement in the external appearance of the orbital mass.
References:
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Howarth DM, et al. Cancer. 1999;doi:10.1002/(SICI)1097-0142(19990515)85:10<2278::AID-CNCR25>3.0.CO;2-U.
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For more information:
Kirstin L. Tawse, MD, and Amar Joshi, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.Edited by Gregory D. Lee, MD, and Nora W. Muakkassa, MD. They can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.