Indian Journal of Nuclear Medicine

PICTORIAL ESSAY
Year
: 2018  |  Volume : 33  |  Issue : 2  |  Page : 118--124

Role of Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Various Orbital Malignancies


Aravintho Natarajan, Piyush Chandra, Nilendu Purandare, Archi Agrawal, Sneha Shah, Ameya Puranik, Venkatesh Rangarajan 
 Department of Nuclear Medicine, Tata Memorial Hospital, Mumbai, Maharashtra, India

Correspondence Address:
Dr. Venkatesh Rangarajan
Department of Nuclear Medicine, Tata Memorial Hospital, Mumbai, Maharashtra
India

Abstract

Orbital swelling comprises wide spectrum of pseudotumors, benign and malignant tumor. Malignant tumor may be primary or secondary tumor, and they constitute about 36% of orbital tumors in adult. Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) scan is extensively used in hematological malignancies and in solid tumors for staging, treatment response, and restaging. Recently, the use of FDG-PET/CT in orbital malignancies has gained importance. The aim of this pictorial essay is to illustrate few important orbital malignancies detected in F-18 FDG-PET/CT and discuss its role in assessing the primary lesion and associated systemic finding.



How to cite this article:
Natarajan A, Chandra P, Purandare N, Agrawal A, Shah S, Puranik A, Rangarajan V. Role of Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Various Orbital Malignancies.Indian J Nucl Med 2018;33:118-124


How to cite this URL:
Natarajan A, Chandra P, Purandare N, Agrawal A, Shah S, Puranik A, Rangarajan V. Role of Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Various Orbital Malignancies. Indian J Nucl Med [serial online] 2018 [cited 2020 Apr 8 ];33:118-124
Available from: http://www.ijnm.in/text.asp?2018/33/2/118/227494


Full Text



 Introduction



Orbital swelling comprises wide spectrum of pseudotumors, benign and malignant tumor. Malignancy constitutes about 36% of orbital tumors in adult and may be classified as primary orbital tumor or secondary deposit from primary elsewhere. Based on the location, it can be intraocular or extraocular tumor, where the extraocular tumors can be further classified into intraconal and extraconal [Table 1].[1] Computed tomography (CT) is the initial of choice of investigation for evaluating orbital tumors, especially for bony detail and calcifications, whereas magnetic resonance imaging (MRI) is superior for evaluation of the visual pathways, the globe, and soft tissues. Fluorodeoxyglucose-positron emission tomography/CT (FDG-PET/CT) is less often used in characterization of the primary orbital mass and is more useful in staging of the pathological proven primary orbital malignancies, assessing response to treatment and evaluation of disease recurrence.{Table 1}

In this pictorial review, we have illustrated few important orbital malignancies detected in FDG-PET/CT and discussed its role in assessing the primary lesion and the associated systemic findings.

 Anatomy



The orbit is divided into the globe, extraocular muscles and intraconal and extraconal spaces. The muscle cone formed by all the extraocular muscles except the inferior oblique separates the intraconal and extraconal spaces [Figure 1]. The globe is continuous with the central nervous system and consists of three distinct layers, namely, the sclera, uvea, and retina. The bony orbit is a pyramidal structure formed by seven skull bones. Erosion of bony orbit usually suggests aggressive pathology. A dedicated CT of the orbit in the PET/CT protocol can be acquired using 0.6–1 mm thin slices after intravenous injection of iodinated contrast material for precise depiction of the globe, optic nerve, intraconal, and extraconal spaces with standard coronal and sagittal reconstructions. CT scan plays important role especially in evaluating calcification of the orbital tumor, bony erosion, and extension to adjacent sinonasal structure or intracranial extension.{Figure 1}

 Normal Appearance of Orbit on Fluorodeoxyglucose-Positron Emission Tomography/computed Tomography



Intense FDG uptake is noted symmetrically in bilateral extraocular muscles; optic nerve and rarely low-grade FDG uptake may be also noted in both the eyelid muscles [Figure 1]. Rest of the orbit does not show any significant FDG uptake. Any asymmetry in the FDG uptake or abnormal sites of increased FDG uptake in the orbit (such as lacrimal gland, choroid, posterior ocular bulb, and prosthesis) should prompt the reader to explore an underlying pathology. Asymmetry in the normal uptake of FDG-PET/CT in extraocular/eyelid muscles is very sensitive in identifying cranial nerve pathologies [Figure 2] (for example, perineural spread of head/neck malignancies and brain metastasis).[2]{Figure 2}

 Ocular Melanoma



Uveal melanomas are the most common primary intraocular tumors in adults. They rise predominantly from the choroid and less commonly from the iris and ciliary body. On CT, choroidal melanoma appears as hyperdense choroidal mass. Although metastases at initial presentation are rare, almost 50% of patients in the course of the disease develop distant metastases. The incidence of distant metastases increases with increasing tumor thickness >10 mm, increasing patient age, presence of subretinal fluid or hemorrhage, and loss of chromosome 3 on cytogenetic studies. Freton et al. evaluated the role of FDG-PET/CT in staging choroidal melanomas in 330 consecutive patients. PET/CT identified distant metastasis at presentation in about 20% patients with the American Joint Committee on Cancer T4 disease. The most common site of metastases was liver followed by bone [Figure 3] and [Figure 4]. In addition, synchronous nonocular second malignancies were noted in 3.3% of patients.[3] PET/CT appears to be more sensitive than liver enzyme assays for screening and detection of liver metastases.[4]{Figure 3}{Figure 4}

Nonuveal melanomas can arise from the conjunctiva or skin of the eyelids. Conjunctival melanomas comprise 5% of intraocular melanomas, showing a significant increasing incidence rates in the western population past few decades. Locoregional spread is usually seen to preauricular and submandibular nodes. Distant metastases are however rare, compared to the uveal melanomas and seen in up to 16% at 5 years. PET/CT was evaluated in staging 14 patients with T3–T4 conjunctival melanoma and did not reveal metastases in any, suggesting that PET/CT might not have a role in staging these subtypes of ocular melanomas.[5]

 Sebaceous Gland Tumors



Sebaceous gland carcinomas (SGC) of eyelids are second most common tumor to involve the eyelid after basal cell carcinoma. These are rare slow-growing tumors, seen predominantly in elderly females. They arise from Meibomian glands, glands of Zeis, or glands associated with the caruncle. They often masquerade clinically as blepharoconjunctivitis or limbic keratoconjunctivitis and diagnosis of malignancy might be delayed. The common sites of the locoregional spread appear to be in orbit, submandibular, and intraparotid nodes [Figure 5]. Due to inadequate treatment at initial presentation, local recurrence is frequent and seen in up to 16%–30% patients. Distant metastases can be seen in 8%–40%, spreading commonly to lungs, pleura, and liver. Higher incidence of metastases are seen in patients with delay in diagnosis (duration of symptoms >6 months), patients with poorly differentiated tumors, size of eyelid tumors >10 mm, infiltration of blood vessels, multicentric origin, and pagetoid spread on histopathology.[6]{Figure 5}

Role of FDG-PET/CT in diagnostic evaluation of SGC is very limited due to rarity of the disease. Baek et al. studied the role of PET/CT in 15 patients with periorbital malignancies which included 6 patients with sebaceous cell carcinoma. Diagnostic accuracy of PET/CT and CT for identification of nodal disease was 98% and 84% respectively. The tumors showed good FDG uptake.[7] Early and more accurate detection of nodal disease, early detection of recurrence, and identification of distant metastases at staging or restaging are potential indications of PET/CT in SGC that can impact treatment decision-making.

 Lacrimal Sac Carcinoma



Primary carcinomas of lacrimal sac are rare malignancy with transitional carcinoma being the common histological subtype after squamous cell carcinoma. Owing to the hidden location within orbit, these tumors have insidious course and present in late stage with symptoms of dacryocystitis and nasolacrimal duct obstruction. Treatment includes wide local excision with adjuvant radiotherapy; however, transitional cell carcinoma has poor prognosis. Review of literature by Preechawai et al. described that one-third of patients have recurrent disease with a 22% rate of distant metastasis to the lungs. The overall mortality rate was 44%.[8] Thus, complete preoperative staging and early detection of disease recurrence is crucial for appropriate treatment to prolong the survival [Figure 6]. Owing to the rarity of the disease, only few case reports exist in literature demonstrating the utility of PET/CT in staging and surveillance of lacrimal sac carcinoma.[9]{Figure 6}

 Rhabdomyosarcoma of Orbit



It is most common soft-tissue sarcoma in the head neck in pediatric age group and comprises 10% of all malignancies of the orbit. On CT, it appears as ill-defined soft-tissue mass in extraconal space with erosion of the bony orbit in about 40%. Most lesions show aggressive local spread with extraorbital spread to sinonasal region and intracranial region. Of all the rhabdomyosarcoma (RMS), pediatric orbital RMS shows the most favorable outcome [Figure 7] to multimodality treatment with 5-year survival ranging from 80% to 90%. Embryonal RMS is most common histological subtype followed by pleomorphic and alveolar. Nodal metastasis is very uncommon in the orbital RMS due to scarce lymphatics in the posterior orbit. Nodal and distant metastases may be seen more frequently with aggressive histopathological features such as an alveolar subtype having a PAX3-FKHR fusion protein [Figure 8]. Multiple studies have successfully demonstrated the clinical utility of FDG-PET/CT in staging childhood RMS and predicting treatment outcomes. However, these were done in RMS predominantly arising from extremities and being of alveolar subtype. Currently, there is not enough evidence to suggest routine use of PET/CT in orbital RMS at present.[10],[11]{Figure 7}{Figure 8}

 Retinoblastoma



These are the most common malignant ocular tumors in children. Multimodality treatment has led to improved outcomes over last few decades; ultrasonography and CT are initial investigations of choice for tumor characterization. CT demonstrates the calcification in the intraocular mass, which has high sensitivity and specificity for the diagnosis of retinoblastoma [Figure 9]. MRI is the best imaging modality to assess optic nerve involvement and extraocular extension. Delay in diagnosis, extrascleral extension, optic nerve involvement, and bilateral disease are associated with higher incidence of metastatic disease.[12] FDG-PET/CT does not have a role in routine diagnostic evaluation of retinoblastoma, except in cases where distal metastasis is clinically suspected [Figure 9]. PET/CT can be also useful in treatment response evaluation of advanced tumors. Prognostic use of PET/CT in retinoblastoma was explored in a prospective study done by Radhakrishnan et al. where they showed that postneoadjuvant chemotherapy response based on the European Organization for the Research and Treatment of Cancer criteria is a strong predictor of event-free survival and overall survival (OS) in Stage III International Neuroblastoma Staging System retinoblastoma.[13]{Figure 9}

 Lymphoma



Orbital lymphoma is relatively rare condition constituting of about 8%–10% of extranodal Non-Hodgkin's lymphoma (NHL).[14] Based on the site of involvement, it is classified as ocular adnexal (OAL) and intraocular lymphoma. Primary intraocular lymphoma is extremely rare and is a subset of primary central nervous system lymphoma. Although OAL is also uncommon, it is the most common orbital malignancy in adults.[1] OAL is mostly extraconal in location and frequently occurs in superolateral quadrant of orbit and typically molds to the adjacent orbital structures. Bone erosion is uncommon. OAL is invariably NHL and mucosa-associated lymphoid tissue [Figure 10] being the most common subtype followed by diffuse large cell lymphoma (DLBCL). Systemic manifestation is noted in about 20% of the cases at presentation and 30% of cases with only orbital disease relapse with systemic lymphoma during follow-up.[15] Radiotherapy is the mainstay of treatment of disease confined to orbit, and chemotherapy is offered in case of high-grade NHL (DLBCL) [Figure 11] and in patients with systemic disease. Since most orbital lymphoma are low-grade lymphoma and show variable FDG avidity, the role of PET has not been clear in the past. However, evidences are mounting in favor of the routine use of FDG-PET for staging. A literature review by Zanni et al. reported that the sensitivity of FDG-PET/CT for detecting primary lesion in low-grade OAL was 66% and for detecting systemic disease was 80%.[16] FDG-PET may also be helpful in radiotherapy planning. FDG avidity correlates with cellular proliferation; thus, dose escalation can be contemplated in lesion with high uptake.[17] Thus, FDG-PET/CT may be useful for radiation treatment planning, response evaluation, and follow-up of OAL.{Figure 10}{Figure 11}

 Granulocytic Sarcoma



Granulocytic sarcomas (GSs) are rare extramedullary presentation of acute myeloid leukemia (AML) and occur in about 2%–8% of cases. Common sites of presentation include bones, lymph nodes, skin, breast, and rarely in gastrointestinal tract or genitourinary tract or in the head neck region. Orbital GS (OGS), although rare in adults, is relatively common in pediatric patients with AML. M2, M4, and M5 are the common subtype of AML associated with OGS. There is no consensus on optimal treatment of OGS and recently external beam radiotherapy is being tried in addition to the standard chemotherapy with cytosine arabinoside.[18] FDG-PET/CT has been evaluated as a noninvasive diagnostic tool for the identification of extramedullary disease in patients with AML [Figure 12]. Although FDG uptake of OGS is variable, it often shows moderate uptake to be detected in PET/CT. In a study done by Stölzel et al. in ten patients with GS, FDG uptake was present in all, but one patient and PET/CT detected additional extramedullary/multifocal disease in about 60% of patients. Multifocal disease is usually associated with adverse prognosis. Few studies have also demonstrated the potential clinical utility of PET/CT in monitoring response to treatment and in early identification of relapse of extramedullary disease during induction or at the end of chemotherapy.[19]{Figure 12}

 Orbital Metastases



Metastases to the orbit are estimated to account for approximately 20% of all orbital neoplasm.[1] Breast cancer is the most common solid tumor metastasizing to orbit in adults [Figure 13], followed by lung and prostate carcinoma, while in pediatric population, it is neuroblastoma [Figure 14]. Blurring of vision, diplopia, proptosis, and pain are the common clinical features, but paradoxically patients can also have enophthalmos due to desmoplasia and fibrosis associated with the tumors. Although most patients with orbital metastases present with known primary [Figure 15], in about 15%–30%, orbital swelling is the presenting complain, and in half of them, conventional imaging fails to demonstrate the primary tumor.[20] The site of primary tumor is an important prognostic factor influencing the OS. Since most common tumor metastasizing to orbit is routinely FDG avid, PET/CT is an ideal noninvasive modality to localize the primary tumor, estimating disease burden, and assess response to novel treatment.{Figure 13}{Figure 14}{Figure 15}

 Neural Tumors of Orbit



Glioma, meningioma, and peripheral nerve sheath tumors (PNSTs) of the orbit constitute about 10% of the orbital tumors and are associated with neurofibromatosis-1 syndrome.[1] Glioma and meningioma are intraconal tumors which appear as fusiform swelling of optic nerve in a CT/MR scan. Meningioma shows uniform enhancement in contrast-enhanced CT/MR while the central optic nerve appears unenhanced giving “tram-track” appearance [Figure 16]. PNSTs (schwannoma and neurofibroma) of the orbit are generally extraconal tumors since they mostly arise from branches of ophthalmic nerve. Although these tumors are generally non-FDG avid, FDG-PET can be used to assess the grade of the glioma and PNST, especially in patients with neurofibromatosis. In addition to FDG-PET, molecular imaging targeting amino acid metabolism and somatostatin expression has shown promising results for the evaluation of glioma and meningioma, respectively.[21],[22]{Figure 16}

 Conclusion



FDG-PET/CT is a highly sensitive diagnostic imaging tool for most orbital tumors as most of these demonstrate enhanced glucose metabolism. However, readers must be aware of the pitfalls of whole-body FDG-PET for assessing orbital tumors [Table 2]. FDG-PET with a dedicated contrast CT of the orbit (or in future PET/MRI) potentially can be a one stop imaging for characterization of primary malignancy, staging the cancer by assessing locoregional/distant spread of the disease, assessing response to treatment and earlier detection of disease recurrence.{Table 2}

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Conflicts of interest

There are no conflicts of interest.

References

1Shields JA, Shields CL, Scartozzi R. Survey of 1264 patients with orbital tumors and simulating lesions: The 2002 Montgomery lecture, part 1. Ophthalmology 2004;111:997-1008.
2Chandra P, Purandare N, Shah S, Agrawal A, Rangarajan V. Common patterns of perineural spread in head-neck squamous cell carcinoma identified on fluoro-deoxyglucose positron emission tomography/computed tomography. Indian J Nucl Med 2016;31:274-9.
3Freton A, Chin KJ, Raut R, Tena LB, Kivelä T, Finger PT, et al. Initial PET/CT staging for choroidal melanoma: AJCC correlation and second nonocular primaries in 333 patients. Eur J Ophthalmol 2012;22:236-43.
4Finger PT, Kurli M, Reddy S, Tena LB, Pavlick AC. Whole body PET/CT for initial staging of choroidal melanoma. Br J Ophthalmol 2005;89:1270-4.
5Kurli M, Chin K, Finger PT. Whole-body 18 FDG PET/CT imaging for lymph node and metastatic staging of conjunctival melanoma. Br J Ophthalmol 2008;92:479-82.
6Wali UK, Al-Mujaini A. Sebaceous gland carcinoma of the eyelid. Oman J Ophthalmol 2010;3:117-21.
7Shields JA, Demirci H, Marr BP, Eagle RC Jr., Shields CL. Sebaceous carcinoma of the eyelids: Personal experience with 60 cases. Ophthalmology 2004;111:2151-7.
8Preechawai P, Della Roccad RC, Della Rocca D, Schaefer S, McCormack S. Transitional cell carcinoma of the lacrimal sac. J Med Assoc Thai 2005;88:138-42.
9Tafti BA, Shaba W, Li Y, Yevdayev E, Berenji GR. Staging and follow-up of lacrimal gland carcinomas by 18F-FDG PET/CT imaging. Clin Nucl Med 2012;37:e249-52.
10Jurdy L, Merks JH, Pieters BR, Mourits MP, Kloos RJ, Strackee SD, et al. Orbital rhabdomyosarcomas: A review. Saudi J Ophthalmol 2013;27:167-75.
11Viswanathan S, George S, Ramadwar M, Shet T, Arora B, Laskar S, et al. Extraconal orbital tumors in children – A spectrum. Virchows Arch 2009;454:703-13.
12Finger PT, Harbour JW, Karcioglu ZA. Risk factors for metastasis in retinoblastoma. Surv Ophthalmol 2002;47:1-6.
13Radhakrishnan V, Kumar R, Malhotra A, Bakhshi S. Role of PET/CT in staging and evaluation of treatment response after 3 cycles of chemotherapy in locally advanced retinoblastoma: A prospective study. J Nucl Med 2012;53:191-8.
14Freeman C, Berg JW, Cutler SJ. Occurrence and prognosis of extranodal lymphomas. Cancer 1972;29:252-60.
15Demirci H, Shields CL, Karatza EC, Shields JA. Orbital lymphoproliferative tumors: Analysis of clinical features and systemic involvement in 160 cases. Ophthalmology 2008;115:1626-31, 1631.e1-3.
16Zanni M, Moulin-Romsee G, Servois V, Validire P, Bénamor M, Plancher C, et al. Value of 18FDG PET scan in staging of ocular adnexal lymphomas: A large single-center experience. Hematology 2012;17:76-84.
17Katayama E, Isao A, Kazuya I, Chikae K, Yoko M, Takayuki S, et al. FDG-PET may be useful in radiation therapy for indolent MALT lymphoma. Int J Radiat Oncol Biol Phys 2013;87:S555.
18Ohanian M, Borthakur G, Quintas-Cardama A, Mathisen M, Cortés JE, Estrov Z, et al. Ocular granulocytic sarcoma: A case report and literature review of ocular extramedullary acute myeloid leukemia. Clin Lymphoma Myeloma Leuk 2013;13:93-6.
19Stölzel F, Röllig C, Radke J, Mohr B, Platzbecker U, Bornhäuser M, et al.18 F-FDG-PET/CT for detection of extramedullary acute myeloid leukemia. Haematologica 2011;96:1552-6.
20Magliozzi P, Strianese D, Bonavolontà P, Ferrara M, Ruggiero P, Carandente R, et al. Orbital metastases in Italy. Int J Ophthalmol 2015;8:1018-23.
21Moharir M, London K, Howman-Giles R, North K. Utility of positron emission tomography for tumour surveillance in children with neurofibromatosis type 1. Eur J Nucl Med Mol Imaging 2010;37:1309-17.
22Valotassiou V, Leondi A, Angelidis G, Psimadas D, Georgoulias P. SPECT and PET imaging of meningiomas. Scientific World J 2012;2012:412580.