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Pediatric adenoid cystic carcinoma of the lacrimal gland treated with intra-arterial cytoreductive chemotherapy
Short Reports Pediatric adenoid cystic carcinoma of the lacrimal gland treated with intra-arterial cytoreductive chemotherapy Amaka Eneh, MD,a Kami Parsa, MD,b Kenneth W. Wright, MD,c and Yi Ning J. Strube, MD, FRCSCa Adenoid cystic carcinoma (ACC) of the lacrimal gland is the most common primary malignant tumor of the lacrimal gland. It typically affects patients in the fifth decade of life and presents with rapid progression of pain, ptosis, motility disturbances, and sensory deficits of less than 1 year’s duration. ACC is rare in children. Due to early, aggressive perineural and bony spread, there is a high risk of intracranial extension. Additionally, due to frequent hematogenous and lymphatic spread, there is a high rate of distant metastases even after treatment, which can occur late up to a decade or more. The currently accepted treatment for ACC is radical exenteration with orbitotomy and adjuvant chemotherapy and/or radiation therapy. Recently, intra-arterial cytoreductive chemotherapy (IACC) has been investigated as a neoadjuvant treatment modality. It has the advantage of increasing local concentration at the target tissue and decreasing systemic distribution. We report the first known pediatric case of ACC treated with IACC, followed by exenteration, radiation, and adjuvant intravenous chemotherapy. The patient was followed for 4 years, with no recurrence and no known complications.
FIG 1. Left-sided, soft, nontender superotemporal orbital mass on initial presentation. Note the globe infradisplacement as well as s-shaped lid ptosis.
FIG 2. Initial magnetic resonance imaging demonstrating a 3.7 cm lobulated T2 hyperintense enhancing, well-circumscribed extraconal mass in the left superotemporal orbit in the area of the lacrimal gland fossa.
Case Report
A
14.5-year-old boy presented at the private practice of one of the authors (KWW) for routine refraction with a chief complaint of difficulty with distance vision. At this visit, left upper eyelid ptosis and globe infradisplacement was noted (Figure 1). He reported gradual onset of symptoms 2 months prior and a progressive course without pain or diplopia. He recalled being poked in that eye during a basketball game 6 months prior but the ensuing periorbital swelling had resolved uneventfully after 2 weeks. Past ocular history included right
Author affiliations: aDepartment of Ophthalmology, Hotel Dieu Hospital, Queen’s University, Kingston, Ontario, Canada; bCedars-Sinai Medical Center, Los Angeles, California; cWright Foundation for Pediatric Ophthalmology, Los Angeles, California, United States of America Presented at the International Pediatric Ophthalmology and Strabismus (IPOS IV) meeting, Chicago, Illinois, October 15, 2010. Submitted July 29, 2014. Revision accepted January 18, 2015. Correspondence: Yi Ning J. Strube, MD, MS, FRCSC, DABO, 166 Brock Street, Department of Ophthalmology, Hotel Dieu Hospital, Kingston, Ontario, Canada (email: [email protected]). J AAPOS 2015;-:1-3. Copyright Ó 2015 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/$36.00 http://dx.doi.org/10.1016/j.jaapos.2015.01.016
Journal of AAPOS
anisometropic amblyopia diagnosed at 5 years of age and treated with part-time occlusion for 2 years. His amblyopia resolved, and he had been followed yearly until age 12. Final visual acuity after treatment was 20/20 in each eye. On examination, vision was 20/30 in each eye. Extraocular motility, ductions, versions, stereoacuity, pupils, and color plate scores were normal. There was a soft, nontender, superotemporal orbital mass on the left side. Magnetic resonance imaging (MRI) of the orbits revealed a 3.7 cm lobulated T2 hyperintense enhancing, wellcircumscribed mass situated in the left lacrimal gland fossa (Figure 2); a normal lacrimal gland was not found. The cranial compartment and cavernous sinuses were normal. Computed tomography (CT) of the orbits showed deformation of the orbital roof, with possible pitting erosion of the boney lining. The patient was referred to an oculoplastics surgeon (KP), and an incisional biopsy of the orbital lesion through a transcutaneous lid crease approach was performed, revealing adenoid cystic carcinoma (ACC) of the lacrimal gland. Treatment was started according to the protocol detailed by Tse and colleagues1: 2 cycles of intra-arterial cis-platinum followed by systemic chemotherapy with doxorubicin were administered. Two months later a lidsparing exenteration of the left orbital content, including
1
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Volume - Number - / - 2015
FIG 3. Computed tomography (CT) findings of the orbital mass (arrow) before (A) and after (B) intra-arterial cytoreductive chemotherapy (IACC), demonstrating significant interval reduction in size of the left superior orbital mass. Before IACC the mass measured 23 16 32; after, 19 12 25 mm, a reported decrease in tumor size by 5–15 mm in all dimensions when compared to the before IACC CT scan.
the tumor was performed. To reconstruct and close, a myocutaneous advancement on the left was performed. Figure 3 shows the change in tumor size after intraarterial cytoreductive chemotherapy (IACC) but before surgery. The exenteration specimen confirmed ACC limited to the lacrimal gland, with no ocular involvement and no involvement of margins. Perineural invasion was identified, but no angiolymphatic invasion was identified, and no tumor necrosis was reported. The histological grade of the tumor was G2, moderately differentiated, 3% basaloid (solid) pattern. Tumor size was smaller postintra-arterial chemotherapy. Biopsies of the periosteum, deep orbit, and eyelid were all negative for carcinoma. Postoperative radiation therapy involved 6000 cGy in 30 fractions over 39 days. Postoperative chemotherapy included 6 cycles of intravenous cis-platinum and doxorubicin. Systemic evaluation before and after treatments confirmed no metastatic disease, with normal CT of the brain, chest, pelvis, and abdomen, normal whole body nuclear scan, and normal echocardiogram and audiogram. The patient recovered well from treatment, other than mild eyelid erythema due to radiation therapy and hair loss due to chemotherapy. Four years after treatment, there have been no recurrences or metastases.
Discussion ACC is rare in children and adolescents, with the youngest reported case of ACC in a 6-year-old child.2 However, ACC should be considered in the differential diagnosis of a superotemporal orbital mass in a child. The prognosis for ACC is poor. With conventional therapy, 10-year survival rates are 20% to 30% because of high rates of intracranial extension and distant metastases, especially to lung and bone.3,4 Several studies have documented recurrence rates of 55% to 88% over 5-6 years.1 The risk of distant metastases is as high as 50% in 5 years.1 Prognosis is partially dependent on the histological subtype; basaloid has the poorest prognosis, with 5-year survival only 20% and a higher
recurrence rate.5 Although ACC of the lacrimal gland is rare in children, it has a better prognosis because the histological features tend to be less aggressive. In a case series of 11 patients aged 6.5-18 years, median survival was .10 years, compared to \5 years for all age groups combined.6 The current IACC treatment protocol is as follows: intra-arterial cis-platinum and intravenous doxorubicin followed by orbital exenteration, removal of involved orbital bone, radiotherapy, and repeat intravenous doxorubicin and cis-platinum.1 To date, the limited literature on IACC for treating ACC has been promising. Tse and colleagues7 reported 100% 10-year survival rates for the subset of patients treated with IACC who had an intact lacrimal artery and in whom all elements of the protocol were followed without deviation. By comparison, the 10-year survival rate in patients treated with conventional therapy was 28.6%; no children were involved in the study. Our patient may have a better chance of long-term survival and a lower risk of recurrence, because of his young age, low-grade tumor (\25% basaloid cells), and having undergone IACC treatment. The 4-year disease-free survival without locoregional recurrence in the present case exceeds the recurrence rate of conventional treatment modalities, and our patient tolerated the treatment well. The long-term systemic side effects of chemotherapy or secondary malignancy in a child are unknown. These risks however should not deter the consideration of IACC therapy for lacrimal gland ACC. More studies examining the use of this treatment modality in pediatric patients, including long-term follow-up, is warranted. References 1. Tse DT, Benedetto PW, Dubovy S, Schiffman JC, Feuer WJ. Clinical analysis of the effect of intraarterial cytoreductive chemotherapy in the treatment of lacrimal gland adenoid cystic carcinoma. Am J Ophthalmology 2006;141:44-53. 2. Galliani CA, Faught PR, Ellis FD. Adenoid cystic carcinoma of the lacrimal gland in a six-year-old girl. Pediatr Pathol 1993;13:559-65. 3. Font RL, Croxatto JO, Rao NA. Tumors of the lacrimal gland. In: Silverberg SG, ed. Tumours of the Eye and Ocular Adnexa. 4th ed.
Journal of AAPOS
Volume - Number - / - 2015 Washington, DC: American Registry of Pathology / Armed Forces Institute of Pathology; 2006:223-46. 4. Wright JE, Rose GE, Garner A. Primary malignant neoplasms of the lacrimal gland. Br J Ophthalmol 1992;76:401-7. 5. Gamel JW, Font RL. Adenoid cystic carcinoma of the lacrimal gland: the clinical significance of a basaloid histologic pattern. Human Pathol 1982;13:219-25.
Journal of AAPOS
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6. Tellado MV, McLean IW, Specht CS, Varga J. Adenoid cystic carcinomas of the lacrimal gland in childhood and adolescence. Ophthalmology 1997;104:1622-5. 7. Tse DT, Kossler AL, Benedetto PW. Long-term outcomes of neoadjuvant intra-arterial cytoreductive chemotherapy for lacrimal gland adenoid cystic carcinoma. Ophthalmology 2013;120: 1313-23.
FIG 1. Left-sided, soft, nontender superotemporal orbital mass on initial presentation. Note the globe infradisplacement as well as s-shaped lid ptosis.
FIG 2. Initial magnetic resonance imaging demonstrating a 3.7 cm lobulated T2 hyperintense enhancing, well-circumscribed extraconal mass in the left superotemporal orbit in the area of the lacrimal gland fossa.
Case Report
A
14.5-year-old boy presented at the private practice of one of the authors (KWW) for routine refraction with a chief complaint of difficulty with distance vision. At this visit, left upper eyelid ptosis and globe infradisplacement was noted (Figure 1). He reported gradual onset of symptoms 2 months prior and a progressive course without pain or diplopia. He recalled being poked in that eye during a basketball game 6 months prior but the ensuing periorbital swelling had resolved uneventfully after 2 weeks. Past ocular history included right
Author affiliations: aDepartment of Ophthalmology, Hotel Dieu Hospital, Queen’s University, Kingston, Ontario, Canada; bCedars-Sinai Medical Center, Los Angeles, California; cWright Foundation for Pediatric Ophthalmology, Los Angeles, California, United States of America Presented at the International Pediatric Ophthalmology and Strabismus (IPOS IV) meeting, Chicago, Illinois, October 15, 2010. Submitted July 29, 2014. Revision accepted January 18, 2015. Correspondence: Yi Ning J. Strube, MD, MS, FRCSC, DABO, 166 Brock Street, Department of Ophthalmology, Hotel Dieu Hospital, Kingston, Ontario, Canada (email: [email protected]). J AAPOS 2015;-:1-3. Copyright Ó 2015 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/$36.00 http://dx.doi.org/10.1016/j.jaapos.2015.01.016
Journal of AAPOS
anisometropic amblyopia diagnosed at 5 years of age and treated with part-time occlusion for 2 years. His amblyopia resolved, and he had been followed yearly until age 12. Final visual acuity after treatment was 20/20 in each eye. On examination, vision was 20/30 in each eye. Extraocular motility, ductions, versions, stereoacuity, pupils, and color plate scores were normal. There was a soft, nontender, superotemporal orbital mass on the left side. Magnetic resonance imaging (MRI) of the orbits revealed a 3.7 cm lobulated T2 hyperintense enhancing, wellcircumscribed mass situated in the left lacrimal gland fossa (Figure 2); a normal lacrimal gland was not found. The cranial compartment and cavernous sinuses were normal. Computed tomography (CT) of the orbits showed deformation of the orbital roof, with possible pitting erosion of the boney lining. The patient was referred to an oculoplastics surgeon (KP), and an incisional biopsy of the orbital lesion through a transcutaneous lid crease approach was performed, revealing adenoid cystic carcinoma (ACC) of the lacrimal gland. Treatment was started according to the protocol detailed by Tse and colleagues1: 2 cycles of intra-arterial cis-platinum followed by systemic chemotherapy with doxorubicin were administered. Two months later a lidsparing exenteration of the left orbital content, including
1
2
Eneh et al
Volume - Number - / - 2015
FIG 3. Computed tomography (CT) findings of the orbital mass (arrow) before (A) and after (B) intra-arterial cytoreductive chemotherapy (IACC), demonstrating significant interval reduction in size of the left superior orbital mass. Before IACC the mass measured 23 16 32; after, 19 12 25 mm, a reported decrease in tumor size by 5–15 mm in all dimensions when compared to the before IACC CT scan.
the tumor was performed. To reconstruct and close, a myocutaneous advancement on the left was performed. Figure 3 shows the change in tumor size after intraarterial cytoreductive chemotherapy (IACC) but before surgery. The exenteration specimen confirmed ACC limited to the lacrimal gland, with no ocular involvement and no involvement of margins. Perineural invasion was identified, but no angiolymphatic invasion was identified, and no tumor necrosis was reported. The histological grade of the tumor was G2, moderately differentiated, 3% basaloid (solid) pattern. Tumor size was smaller postintra-arterial chemotherapy. Biopsies of the periosteum, deep orbit, and eyelid were all negative for carcinoma. Postoperative radiation therapy involved 6000 cGy in 30 fractions over 39 days. Postoperative chemotherapy included 6 cycles of intravenous cis-platinum and doxorubicin. Systemic evaluation before and after treatments confirmed no metastatic disease, with normal CT of the brain, chest, pelvis, and abdomen, normal whole body nuclear scan, and normal echocardiogram and audiogram. The patient recovered well from treatment, other than mild eyelid erythema due to radiation therapy and hair loss due to chemotherapy. Four years after treatment, there have been no recurrences or metastases.
Discussion ACC is rare in children and adolescents, with the youngest reported case of ACC in a 6-year-old child.2 However, ACC should be considered in the differential diagnosis of a superotemporal orbital mass in a child. The prognosis for ACC is poor. With conventional therapy, 10-year survival rates are 20% to 30% because of high rates of intracranial extension and distant metastases, especially to lung and bone.3,4 Several studies have documented recurrence rates of 55% to 88% over 5-6 years.1 The risk of distant metastases is as high as 50% in 5 years.1 Prognosis is partially dependent on the histological subtype; basaloid has the poorest prognosis, with 5-year survival only 20% and a higher
recurrence rate.5 Although ACC of the lacrimal gland is rare in children, it has a better prognosis because the histological features tend to be less aggressive. In a case series of 11 patients aged 6.5-18 years, median survival was .10 years, compared to \5 years for all age groups combined.6 The current IACC treatment protocol is as follows: intra-arterial cis-platinum and intravenous doxorubicin followed by orbital exenteration, removal of involved orbital bone, radiotherapy, and repeat intravenous doxorubicin and cis-platinum.1 To date, the limited literature on IACC for treating ACC has been promising. Tse and colleagues7 reported 100% 10-year survival rates for the subset of patients treated with IACC who had an intact lacrimal artery and in whom all elements of the protocol were followed without deviation. By comparison, the 10-year survival rate in patients treated with conventional therapy was 28.6%; no children were involved in the study. Our patient may have a better chance of long-term survival and a lower risk of recurrence, because of his young age, low-grade tumor (\25% basaloid cells), and having undergone IACC treatment. The 4-year disease-free survival without locoregional recurrence in the present case exceeds the recurrence rate of conventional treatment modalities, and our patient tolerated the treatment well. The long-term systemic side effects of chemotherapy or secondary malignancy in a child are unknown. These risks however should not deter the consideration of IACC therapy for lacrimal gland ACC. More studies examining the use of this treatment modality in pediatric patients, including long-term follow-up, is warranted. References 1. Tse DT, Benedetto PW, Dubovy S, Schiffman JC, Feuer WJ. Clinical analysis of the effect of intraarterial cytoreductive chemotherapy in the treatment of lacrimal gland adenoid cystic carcinoma. Am J Ophthalmology 2006;141:44-53. 2. Galliani CA, Faught PR, Ellis FD. Adenoid cystic carcinoma of the lacrimal gland in a six-year-old girl. Pediatr Pathol 1993;13:559-65. 3. Font RL, Croxatto JO, Rao NA. Tumors of the lacrimal gland. In: Silverberg SG, ed. Tumours of the Eye and Ocular Adnexa. 4th ed.
Journal of AAPOS
Volume - Number - / - 2015 Washington, DC: American Registry of Pathology / Armed Forces Institute of Pathology; 2006:223-46. 4. Wright JE, Rose GE, Garner A. Primary malignant neoplasms of the lacrimal gland. Br J Ophthalmol 1992;76:401-7. 5. Gamel JW, Font RL. Adenoid cystic carcinoma of the lacrimal gland: the clinical significance of a basaloid histologic pattern. Human Pathol 1982;13:219-25.
Journal of AAPOS
Eneh et al
3
6. Tellado MV, McLean IW, Specht CS, Varga J. Adenoid cystic carcinomas of the lacrimal gland in childhood and adolescence. Ophthalmology 1997;104:1622-5. 7. Tse DT, Kossler AL, Benedetto PW. Long-term outcomes of neoadjuvant intra-arterial cytoreductive chemotherapy for lacrimal gland adenoid cystic carcinoma. Ophthalmology 2013;120: 1313-23.