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Letters to the Editor and quick to assess, it may reflect ONH blood flow as well as large vessel diameter, calling for additional, future validation of its usefulness. In conclusion, our results suggest that ARBS accurately represents vessel area ratio in the ONH, and promises to help predict the progression of PPG to glaucoma.
ACKNOWLEDGEMENTS The authors thank Tomoki Yasui at Yasui Eye Clinic, Keiichi Kato at Kato Eye Center and Aiko Iwase at Tajimi Iwase Eye Clinic for collecting subjects, and Tim Hilts for reviewing the manuscript.
Naoki Kiyota MD,1 Yukihiro Shiga MD,1 Hidetoshi Takahashi MD PhD1 and Toru Nakazawa MD PhD1,2,3 1 Departments of Ophthalmology, 2Retinal Disease Control and 3Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan Received 5 June 2015; accepted 13 June 2015.
REFERENCES 1. Maekawa S, Shiga Y, Kawasaki R, Nakazawa T. Usefulness of novel laser speckle flowgraphy-derived variables of the large vessel area in the optic nerve head in normal tension glaucoma. Clin Experiment Ophthalmol 2014; 42: 887–9. 2. Aizawa N, Kunikata H, Yokoyama Y, Nakazawa T. Correlation between optic disc microcirculation in glaucoma measured with laser speckle flowgraphy and fluorescein angiography, and the correlation with mean deviation. Clin Experiment Ophthalmol 2014; 42: 293–4. 3. Kawasaki R, Wang JJ, Rochtchina E, Lee AJ, Wong TY, Mitchell P. Retinal vessel caliber is associated with the 10-year incidence of glaucoma: the Blue Mountains Eye Study. Ophthalmology 2013; 120: 84–90.
843 An 80-year-old Indigenous Australian man was hospitalized during the dry season with a 2-week history of arthralgia, fevers, headaches, visual hallucinations and deteriorating left vision. He had a history of non-insulindependent diabetes mellitus, had his own accommodation and denied overseas travel, smoking or other environmental exposures. On ophthalmic examination, visual acuity (VA) was 6/9 and hand movements in the right and left eyes, respectively. Conjunctival injection was absent. The left eye had 2+ anterior chamber cells, 3+ vitritis and a raised, three disc diametre, cream–yellow submacula lesion with overlying haemorrhage (Fig. 1). Ultrasound characterized the 6 × 3 × 5 mm lesion as non-vascular and isoechoic. Microscopy and culture of vitreous tap from the left eye isolated no organisms. Empirically, intravitreal ceftazidime, vancomycin and foscarnet were administered. Extensive investigations for a systemic source were performed. Echocardiography was negative for infective endocarditis and multiple blood cultures were sterile. Abnormal hepatic enzymes included alkaline phosphatase (275 U/L), alanine aminotransferase (200 U/L) and gamma-glutamyl transferase (292 U/L), while liver function was preserved. Ultrasound detected a 5-mm echogenic, shadowing focus within a prominent, diffusely echogenic and attenuating liver. Previous syphilis and hepatitis B infections were confirmed, although active infections with these, as well as other hepatitis viruses, cryptococcus and human immunodeficiency virus were excluded. A whole body bone scan identified prominent abnormal focal rib and vertebral bony reactivity, suggestive of metastases. Computer tomography revealed a 63 × 57 × 50 mm subcarinal para-oesophageal lymphoid necrotic mass, small atelectasis and a porcelain gallbladder. Bronchoscopic fine-needle aspiration of the mediastinal lesion and bronchoalveolar lavage was non-diagnostic. After 1 week, ongoing close ophthalmic monitoring detected a new, small, cream–yellow subretinal lesion with overlying haemorrhage in the temporal periphery of
Bilateral subretinal abscesses: the first case of disseminated Nocardia beijingensis in Australia Nocardia, an obligate aerobic, Gram-positive, filamentous, soil-dwelling bacterium, causes nocardiosis, a rare, lifethreatening infection and frequent diagnostic dilemma.1 We present the first Australian case of disseminated Nocardia beijingensis, causing bilateral subretinal abscesses. The diagnosis was facilitated by vitrectomy and biopsy of a submacula abscess, allowing the timely commencement of appropriate antibiotics and a favourable outcome. Conflict of interest: None.
Figure 1. Colour fundus photograph of the left choroidal lesion in the first week of admission.
Funding sources: None. © 2015 Royal Australian and New Zealand College of Ophthalmologists
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Figure 2. Colour fundus photograph of the right temporal periphery demonstrating a choroidal abscess and retinitis. the right eye. The lesion continued to grow and VA deteriorated to 6/60 from dense vitritis after 2 weeks. Prednisolone per OS 60 mg was trialled for 2 days, improving vitritis and right VA to 6/24. Sudden onset of delirium was associated with multiple widespread cerebral abscesses on brain magnetic resonance imaging. This clinical deterioration, along with concerns about the risks of a mediastinal biopsy, led to a diagnostic left vitrectomy with oil insertion and forceps-assisted subretinal biopsy. Nocardia was confirmed on microscopy and culture of subretinal tissue, but not aspirated vitreous, and Nocardia beijingensis was isolated by sequencing of the 16S region. Resistance to ciprofloxacin and amoxycillin/clavulanate was reported. Appropriate systemic antibiotics were commenced the following day, including meropenem, ceftriaxone and trimethoprim-sulphamethoxazole. Meropenem was changed to amikacin after 1 week, resulting in slow cognitive improvement and resolution of cerebral abscesses. The right subretinal abscess enlarged and formed adjacent retinitis, requiring three intravitreal injections of amikacin (400 mcg/0.1 mL) to successfully stabilize (Fig. 2). Right VA improved to 6/12 on discharge, whereas left hand movements vision was retained. As far as the authors are aware, this is the first clinical case of Nocardia beijingensis in Australia. Isolated in 2001 from a sewage ditch at Xishan mountain in Beijing,2 this rare species was recognized as a human pathogen in 2004.3 Two case reports from patients outside Asia have been confirmed, including in Europe in 20124 and North America in 2014.5 Nocardia, usually transmitted by inhalation, most commonly causes serious pulmonary infections in the immunocompromised.1 Disseminated infection occurs in 20% of cases1 and can involve almost any tissue;5 however, an affinity for the brain (15%) and choroid (3–5%) is recognized.1 Diagnostic delays are often attributed to clinician unfamiliarity with this rare pathogen that causes a highly variable clinical picture.1 This is further exacerbated by the fact that Nocardia is a fastidious and slow-growing organ-
ism, such that it is not uncommon for blood, tissue and fluid cultures to initially be negative. Frequent resistance to standard empiric antibiotics also contributes to poor outcomes. Our case had a positive outcome, despite a 26-day delay from presentation to diagnosis, contributed by the lack of growth from vitreous fluid, multiple blood cultures and mediastinal biopsy. Further masking the diagnosis, our patient was not a typical candidate for disseminated infection, although advanced age and diabetes are known risk factors for reduced immune function. This is not the first case to demonstrate that nocardiosis cannot be excluded in the presence of immunocompetence.1 Mortality increases from 25% to 80% without adequate treatment.1 Cognition sharply deteriorated in our patient after starting prednisolone, an established risk factor with 73% of patients with endogenous ocular nocardiosis presenting on systemic steroids.1 The subretinal biopsy had no possibility of salvaging vision, but was likely lifesaving because it enabled the immediate commencement of appropriate antibiotics in an elderly, delirious patient. It also allowed sight-preserving treatment of the right eye. This case illustrates the difficulty, but importance, of adequate tissue sampling for diagnosis, although the fundus appearance, in combination with brain and lung involvement, should raise suspicion.
ACKNOWLEDGEMENTS The authors would like to thank Professor Peter McCluskey, Associate Professor Ivan Ho and Professor Sue Lightman for their management advice at various stages throughout the clinical course.
Angela DM Richards MBBS(Hons) BSc, Christopher Stewart MBBS(Hons), Hema Karthik FRANZCO and Stewart R Lake FRANZCO Ophthalmology Department, Royal Darwin Hospital, Darwin, Northern Territory, Australia Received 26 February 2015; accepted 22 June 2015.
REFERENCES 1. Eschle-Meniconi ME, Guex-Crosier Y, Wolfensberger TJ. Endogenous ocular nocardiosis: an interventional case report with a review of the literature. Surv Ophthalmol 2011; 56: 383–415. 2. Wang L, Zhang Y, Lu Z et al. Nocardia beijingensis sp. nov., a novel isolate from soil. Int J Syst Evol Microbiol 2001; 51: 1783–8. 3. Kageyama A, Poonwan N, Yazawa K, Mikami Y, Nishimura K. Nocardia beijingensis, is a pathogenic bacterium to humans: the first infectious cases in Thailand and Japan. Mycopathologia 2004; 157: 155–61. 4. Derancourt C, Theodose R, Deschamps L et al. Primary cutaneous nocardiosis caused by Nocardia beijingensis. Br J Dermatol 2012; 167: 216–8.
© 2015 Royal Australian and New Zealand College of Ophthalmologists
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5. Crozier JA, Andhavarapu S, Brumble LM, Sher T. First report of Nocardia beijingensis infection in an immunocompetent host in the United States. J Clin Microbiol 2014; 52: 2730–2.
Congenital orbital primitive neuroectodermal tumour A 14-day-old female presented to the eye department with left proptosis present at birth. She was born in the 39th week of gestation via an uncomplicated vaginal delivery. On examination, she had a palpable mass over her left superior orbital margin. There was left proptosis and her eye was displaced downward and outwards, with no visible pulsation or inflammation (Fig. 1). The pupils were normal and a complete physical examination was unremarkable. Magnetic resonance imaging demonstrated an isolated left extraconal orbital mass (Fig. 2). Her chest X-ray and ultrasound of the abdomen were normal. Full blood count, biochemical studies, coagulation studies and liver function tests were normal except for a slightly raised activated partial thromboplastin time (32 s) and bilirubin (32 μmol/ L), and some normochromic irregular-shaped cells on the blood film. She underwent a biopsy of the extraconal mass with the rest of the mass being extensively debulked by suction aspiration. Histologically, the tumour had a lobulated architecture with sheets of cells divided into lobules by prominent thin-walled vascular network. The cells were small and monotonous with round to oval nuclei, fine chromatin, multiple small nucleoli and ill-defined, vacuolated, pale-staining cytoplasm. There was no necrosis. (Fig. 3a). Immunohistochemistry was strongly positive for CD99 (Fig. 3b), vimentin and S-100, but negative for CD56, NSE, cytokeratin cocktail, leucocyte common antigen, desmin and myogenin. Fluorescent in-situ hybridization (FISH) detected an EWSR1 (22q12) gene rearrangement in all 100 cells examined (Fig. 3c), which confirmed the diagnosis of orbital primitive neuroectodermal tumour (PNET). The parents were offered intensive chemotherapy for their child, followed by local therapy consisting of either complete surgical excision with clear margins of the tumour or adjunct radiotherapy if clear margins were not obtained, followed by additional chemotherapy. Given the extremely poor prognosis and significant treatment sideeffects, the parents opted for palliation therapy only, and the infant passed away 7 weeks later. Primary orbital PNET is a subset of peripheral PNET (pPNET) tumour. It is part of the Ewing sarcoma (ES) family of tumours.1 pPNET and ES are considered mani-
Figure 1. Prominent supraorbital mass on the left with obvious proptosis and incomplete lid closure. The eye appeared noninflammed, and it is displaced inferiorly and temporally. festations of the same disease spectrum, with pPNET having a higher degree of neural differentiation than ES.2 It is extremely rare and believed to affect primarily children and adolescents, with no gender predilection. To the best of our knowledge, there have been 26 reported cases of primary orbital PNET in the literature, of which 17 cases occurred in the paediatric population. There are only two congenital orbital PNET reported in the literature based on histology and immunohistochemistry.3,4 We believed our patient is the first congenital orbital PNET where the diagnosis confirmation has included cytogenetic testing besides histology and immunohistochemistry. The diagnosis of PNET can be made based on the following:
1
2
3
Conflict of interest: None. Funding sources: None. © 2015 Royal Australian and New Zealand College of Ophthalmologists
Histology: These tumours contain a high nuclear to cytoplasmic ratio. The hyperchromatic cell nucleus may contain one or more nucleoli, giving it the characteristic features of a ‘small round cell’ tumour. The cells usually contain glycogen, which can be detected by the periodic acid Schiff stain.1 Occasionally, rosette formation is observed.1 Immunohistochemistry: A profile of the tumour is obtained by recognizing the surface antigens present on the tumour cell surface. CD99, S-100 protein, glial fibrillary acidic protein, cytokeratin, epithelial membrane antigen, neurofilament, neuron-specific enolase, vimentin and synaptophysin have all been associated with PNET.2 CD99 is present in up to 95% of pPNET and ES tumour, making it a highly sensitive marker,5 although with poor specificity, as other tumours such as lymphoblastic lymphoma, rhabdomyosarcoma, synovial sarcoma also express CD99. Absence of certain gene products helps rule out other differential diagnoses.5 Cytogenetic studies: More than 85% of pPNET/ES tumour have a t(11;22) (q24:q12) translocation resulting in the fusion of EWRS1 (also known as EWS) gene on chromosome 22q12 to the FLI1 gene on chromosome 11q24. This translocation gives rise to a chimeric fusion gene known as EWS-FLI1, which expresses CD99 surface antigen.1 Another 10–15% involve a t(21;22) (q22;q12) translocation giving rise to
Letters to the Editor and quick to assess, it may reflect ONH blood flow as well as large vessel diameter, calling for additional, future validation of its usefulness. In conclusion, our results suggest that ARBS accurately represents vessel area ratio in the ONH, and promises to help predict the progression of PPG to glaucoma.
ACKNOWLEDGEMENTS The authors thank Tomoki Yasui at Yasui Eye Clinic, Keiichi Kato at Kato Eye Center and Aiko Iwase at Tajimi Iwase Eye Clinic for collecting subjects, and Tim Hilts for reviewing the manuscript.
Naoki Kiyota MD,1 Yukihiro Shiga MD,1 Hidetoshi Takahashi MD PhD1 and Toru Nakazawa MD PhD1,2,3 1 Departments of Ophthalmology, 2Retinal Disease Control and 3Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan Received 5 June 2015; accepted 13 June 2015.
REFERENCES 1. Maekawa S, Shiga Y, Kawasaki R, Nakazawa T. Usefulness of novel laser speckle flowgraphy-derived variables of the large vessel area in the optic nerve head in normal tension glaucoma. Clin Experiment Ophthalmol 2014; 42: 887–9. 2. Aizawa N, Kunikata H, Yokoyama Y, Nakazawa T. Correlation between optic disc microcirculation in glaucoma measured with laser speckle flowgraphy and fluorescein angiography, and the correlation with mean deviation. Clin Experiment Ophthalmol 2014; 42: 293–4. 3. Kawasaki R, Wang JJ, Rochtchina E, Lee AJ, Wong TY, Mitchell P. Retinal vessel caliber is associated with the 10-year incidence of glaucoma: the Blue Mountains Eye Study. Ophthalmology 2013; 120: 84–90.
843 An 80-year-old Indigenous Australian man was hospitalized during the dry season with a 2-week history of arthralgia, fevers, headaches, visual hallucinations and deteriorating left vision. He had a history of non-insulindependent diabetes mellitus, had his own accommodation and denied overseas travel, smoking or other environmental exposures. On ophthalmic examination, visual acuity (VA) was 6/9 and hand movements in the right and left eyes, respectively. Conjunctival injection was absent. The left eye had 2+ anterior chamber cells, 3+ vitritis and a raised, three disc diametre, cream–yellow submacula lesion with overlying haemorrhage (Fig. 1). Ultrasound characterized the 6 × 3 × 5 mm lesion as non-vascular and isoechoic. Microscopy and culture of vitreous tap from the left eye isolated no organisms. Empirically, intravitreal ceftazidime, vancomycin and foscarnet were administered. Extensive investigations for a systemic source were performed. Echocardiography was negative for infective endocarditis and multiple blood cultures were sterile. Abnormal hepatic enzymes included alkaline phosphatase (275 U/L), alanine aminotransferase (200 U/L) and gamma-glutamyl transferase (292 U/L), while liver function was preserved. Ultrasound detected a 5-mm echogenic, shadowing focus within a prominent, diffusely echogenic and attenuating liver. Previous syphilis and hepatitis B infections were confirmed, although active infections with these, as well as other hepatitis viruses, cryptococcus and human immunodeficiency virus were excluded. A whole body bone scan identified prominent abnormal focal rib and vertebral bony reactivity, suggestive of metastases. Computer tomography revealed a 63 × 57 × 50 mm subcarinal para-oesophageal lymphoid necrotic mass, small atelectasis and a porcelain gallbladder. Bronchoscopic fine-needle aspiration of the mediastinal lesion and bronchoalveolar lavage was non-diagnostic. After 1 week, ongoing close ophthalmic monitoring detected a new, small, cream–yellow subretinal lesion with overlying haemorrhage in the temporal periphery of
Bilateral subretinal abscesses: the first case of disseminated Nocardia beijingensis in Australia Nocardia, an obligate aerobic, Gram-positive, filamentous, soil-dwelling bacterium, causes nocardiosis, a rare, lifethreatening infection and frequent diagnostic dilemma.1 We present the first Australian case of disseminated Nocardia beijingensis, causing bilateral subretinal abscesses. The diagnosis was facilitated by vitrectomy and biopsy of a submacula abscess, allowing the timely commencement of appropriate antibiotics and a favourable outcome. Conflict of interest: None.
Figure 1. Colour fundus photograph of the left choroidal lesion in the first week of admission.
Funding sources: None. © 2015 Royal Australian and New Zealand College of Ophthalmologists
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844
Letters to the Editor
Figure 2. Colour fundus photograph of the right temporal periphery demonstrating a choroidal abscess and retinitis. the right eye. The lesion continued to grow and VA deteriorated to 6/60 from dense vitritis after 2 weeks. Prednisolone per OS 60 mg was trialled for 2 days, improving vitritis and right VA to 6/24. Sudden onset of delirium was associated with multiple widespread cerebral abscesses on brain magnetic resonance imaging. This clinical deterioration, along with concerns about the risks of a mediastinal biopsy, led to a diagnostic left vitrectomy with oil insertion and forceps-assisted subretinal biopsy. Nocardia was confirmed on microscopy and culture of subretinal tissue, but not aspirated vitreous, and Nocardia beijingensis was isolated by sequencing of the 16S region. Resistance to ciprofloxacin and amoxycillin/clavulanate was reported. Appropriate systemic antibiotics were commenced the following day, including meropenem, ceftriaxone and trimethoprim-sulphamethoxazole. Meropenem was changed to amikacin after 1 week, resulting in slow cognitive improvement and resolution of cerebral abscesses. The right subretinal abscess enlarged and formed adjacent retinitis, requiring three intravitreal injections of amikacin (400 mcg/0.1 mL) to successfully stabilize (Fig. 2). Right VA improved to 6/12 on discharge, whereas left hand movements vision was retained. As far as the authors are aware, this is the first clinical case of Nocardia beijingensis in Australia. Isolated in 2001 from a sewage ditch at Xishan mountain in Beijing,2 this rare species was recognized as a human pathogen in 2004.3 Two case reports from patients outside Asia have been confirmed, including in Europe in 20124 and North America in 2014.5 Nocardia, usually transmitted by inhalation, most commonly causes serious pulmonary infections in the immunocompromised.1 Disseminated infection occurs in 20% of cases1 and can involve almost any tissue;5 however, an affinity for the brain (15%) and choroid (3–5%) is recognized.1 Diagnostic delays are often attributed to clinician unfamiliarity with this rare pathogen that causes a highly variable clinical picture.1 This is further exacerbated by the fact that Nocardia is a fastidious and slow-growing organ-
ism, such that it is not uncommon for blood, tissue and fluid cultures to initially be negative. Frequent resistance to standard empiric antibiotics also contributes to poor outcomes. Our case had a positive outcome, despite a 26-day delay from presentation to diagnosis, contributed by the lack of growth from vitreous fluid, multiple blood cultures and mediastinal biopsy. Further masking the diagnosis, our patient was not a typical candidate for disseminated infection, although advanced age and diabetes are known risk factors for reduced immune function. This is not the first case to demonstrate that nocardiosis cannot be excluded in the presence of immunocompetence.1 Mortality increases from 25% to 80% without adequate treatment.1 Cognition sharply deteriorated in our patient after starting prednisolone, an established risk factor with 73% of patients with endogenous ocular nocardiosis presenting on systemic steroids.1 The subretinal biopsy had no possibility of salvaging vision, but was likely lifesaving because it enabled the immediate commencement of appropriate antibiotics in an elderly, delirious patient. It also allowed sight-preserving treatment of the right eye. This case illustrates the difficulty, but importance, of adequate tissue sampling for diagnosis, although the fundus appearance, in combination with brain and lung involvement, should raise suspicion.
ACKNOWLEDGEMENTS The authors would like to thank Professor Peter McCluskey, Associate Professor Ivan Ho and Professor Sue Lightman for their management advice at various stages throughout the clinical course.
Angela DM Richards MBBS(Hons) BSc, Christopher Stewart MBBS(Hons), Hema Karthik FRANZCO and Stewart R Lake FRANZCO Ophthalmology Department, Royal Darwin Hospital, Darwin, Northern Territory, Australia Received 26 February 2015; accepted 22 June 2015.
REFERENCES 1. Eschle-Meniconi ME, Guex-Crosier Y, Wolfensberger TJ. Endogenous ocular nocardiosis: an interventional case report with a review of the literature. Surv Ophthalmol 2011; 56: 383–415. 2. Wang L, Zhang Y, Lu Z et al. Nocardia beijingensis sp. nov., a novel isolate from soil. Int J Syst Evol Microbiol 2001; 51: 1783–8. 3. Kageyama A, Poonwan N, Yazawa K, Mikami Y, Nishimura K. Nocardia beijingensis, is a pathogenic bacterium to humans: the first infectious cases in Thailand and Japan. Mycopathologia 2004; 157: 155–61. 4. Derancourt C, Theodose R, Deschamps L et al. Primary cutaneous nocardiosis caused by Nocardia beijingensis. Br J Dermatol 2012; 167: 216–8.
© 2015 Royal Australian and New Zealand College of Ophthalmologists
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5. Crozier JA, Andhavarapu S, Brumble LM, Sher T. First report of Nocardia beijingensis infection in an immunocompetent host in the United States. J Clin Microbiol 2014; 52: 2730–2.
Congenital orbital primitive neuroectodermal tumour A 14-day-old female presented to the eye department with left proptosis present at birth. She was born in the 39th week of gestation via an uncomplicated vaginal delivery. On examination, she had a palpable mass over her left superior orbital margin. There was left proptosis and her eye was displaced downward and outwards, with no visible pulsation or inflammation (Fig. 1). The pupils were normal and a complete physical examination was unremarkable. Magnetic resonance imaging demonstrated an isolated left extraconal orbital mass (Fig. 2). Her chest X-ray and ultrasound of the abdomen were normal. Full blood count, biochemical studies, coagulation studies and liver function tests were normal except for a slightly raised activated partial thromboplastin time (32 s) and bilirubin (32 μmol/ L), and some normochromic irregular-shaped cells on the blood film. She underwent a biopsy of the extraconal mass with the rest of the mass being extensively debulked by suction aspiration. Histologically, the tumour had a lobulated architecture with sheets of cells divided into lobules by prominent thin-walled vascular network. The cells were small and monotonous with round to oval nuclei, fine chromatin, multiple small nucleoli and ill-defined, vacuolated, pale-staining cytoplasm. There was no necrosis. (Fig. 3a). Immunohistochemistry was strongly positive for CD99 (Fig. 3b), vimentin and S-100, but negative for CD56, NSE, cytokeratin cocktail, leucocyte common antigen, desmin and myogenin. Fluorescent in-situ hybridization (FISH) detected an EWSR1 (22q12) gene rearrangement in all 100 cells examined (Fig. 3c), which confirmed the diagnosis of orbital primitive neuroectodermal tumour (PNET). The parents were offered intensive chemotherapy for their child, followed by local therapy consisting of either complete surgical excision with clear margins of the tumour or adjunct radiotherapy if clear margins were not obtained, followed by additional chemotherapy. Given the extremely poor prognosis and significant treatment sideeffects, the parents opted for palliation therapy only, and the infant passed away 7 weeks later. Primary orbital PNET is a subset of peripheral PNET (pPNET) tumour. It is part of the Ewing sarcoma (ES) family of tumours.1 pPNET and ES are considered mani-
Figure 1. Prominent supraorbital mass on the left with obvious proptosis and incomplete lid closure. The eye appeared noninflammed, and it is displaced inferiorly and temporally. festations of the same disease spectrum, with pPNET having a higher degree of neural differentiation than ES.2 It is extremely rare and believed to affect primarily children and adolescents, with no gender predilection. To the best of our knowledge, there have been 26 reported cases of primary orbital PNET in the literature, of which 17 cases occurred in the paediatric population. There are only two congenital orbital PNET reported in the literature based on histology and immunohistochemistry.3,4 We believed our patient is the first congenital orbital PNET where the diagnosis confirmation has included cytogenetic testing besides histology and immunohistochemistry. The diagnosis of PNET can be made based on the following:
1
2
3
Conflict of interest: None. Funding sources: None. © 2015 Royal Australian and New Zealand College of Ophthalmologists
Histology: These tumours contain a high nuclear to cytoplasmic ratio. The hyperchromatic cell nucleus may contain one or more nucleoli, giving it the characteristic features of a ‘small round cell’ tumour. The cells usually contain glycogen, which can be detected by the periodic acid Schiff stain.1 Occasionally, rosette formation is observed.1 Immunohistochemistry: A profile of the tumour is obtained by recognizing the surface antigens present on the tumour cell surface. CD99, S-100 protein, glial fibrillary acidic protein, cytokeratin, epithelial membrane antigen, neurofilament, neuron-specific enolase, vimentin and synaptophysin have all been associated with PNET.2 CD99 is present in up to 95% of pPNET and ES tumour, making it a highly sensitive marker,5 although with poor specificity, as other tumours such as lymphoblastic lymphoma, rhabdomyosarcoma, synovial sarcoma also express CD99. Absence of certain gene products helps rule out other differential diagnoses.5 Cytogenetic studies: More than 85% of pPNET/ES tumour have a t(11;22) (q24:q12) translocation resulting in the fusion of EWRS1 (also known as EWS) gene on chromosome 22q12 to the FLI1 gene on chromosome 11q24. This translocation gives rise to a chimeric fusion gene known as EWS-FLI1, which expresses CD99 surface antigen.1 Another 10–15% involve a t(21;22) (q22;q12) translocation giving rise to
