Case Reports Congenital Eyelid Rhabdomyosarcoma Yi-Ching Lee, M.D.*, Yung-Hsiang Hsu, M.D.†, Shan-Hsien Yang, M.D.‡, and Tzu-Lun Huang, M.D.*§¶ Abstract: Rhabdomyosarcoma is the most common type of soft tissue sarcoma in children. The authors present a rare case of eyelid rhabdomyosarcoma in a newborn, who was found to have a reddish eyelid tumor in his OD. A mass with a clear margin, confined to the upper eyelid, was revealed using orbital MRI. Intralesional steroids were injected under the impression of a capillary hemangioma and the tumor shrank initially, but grew rapidly later. Therefore, a debulking surgery was performed and the final diagnosis was embryonal rhabdomyosarcoma. After the operation, metastases still occurred despite the treatment with chemotherapy and concurrent radiation. The patient expired at 6 months of age. In an autopsy, a neuroblastoma was incidentally found in his left adrenal gland. Early biopsy may help lead to an early correct diagnosis and avoid metastases in similar cases.
R
habdomyosarcoma (RMS) is uncommon in infants,1–4 and to the authors’ knowledge, there are no reports of eyelid RMS in newborns. The authors report a rare case with a congenital RMS confined to the eyelid. The tumor was initially mistaken for a capillary hemangioma because of its red hue.
CASE REPORT A 1-day-old newborn, delivered by an elective cesarean section with no complications, at 38 weeks of gestation, with a birth body weight of 3,200 g, was found to have a tumor having a red hue in his right upper eyelid (Fig. 1A). The patient had 3 healthy siblings and no family history of cancer. On examination, the tumor was indurated, firm, and blocking the patient’s visual axis. The other findings of the ocular structures were normal. Orbital MRI showed a heterogeneously enhanced, hypervascular lesion confined to the eyelid. The orbital area was not involved (Fig. 1B). A diagnosis of an eyelid capillary hemangioma was made, and an intralesional corticosteroids injection was given (20 mg methylprednisolone and 4 mg dexamethasone) with a 30-gauge needle, at 4 days of age of the patient. The tumor shrank in the following several days, and the patient was lost to follow up shortly thereafter. At 5 weeks of age, the patient was brought back to the outpatient clinic because of the rapid growth and active oozing of the tumor. Severe necrotic changes were noted on the tumor surface (Fig. 2A). Orbital MRI also showed the enlargement of the tumor, which invaded the orbit and compressed the OD (Fig. 2B). The tumor was excised, and histopathologic examinations revealed many small blue round cells with positive stains for myogenin and desmin (Fig. 3A,B). After the diagnosis of embryonal RMS was confirmed, systemic investigation, including whole-body bone scan, chest CT, bone Departments of *Ophthalmology, †Pathology, and ‡Pediatrics, Buddhist Tzu Chi General Hospital; §Department of Ophthalmology and Visual Science, Tzu Chi University, Hualien; and ¶Department of Ophthalmology, Far Eastern Memorial Hospital, Taipei, Taiwan Accepted for publication July 1, 2014. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Tzu-Lun Huang, m.d., Department of Ophthalmology, Far Eastern Memorial Hospital, No. 21, Section 2, Nanya S. Road, Banciao District, New Taipei City 220, Taiwan. E-mail: [email protected] DOI: 10.1097/IOP.0000000000000290
Ophthal Plast Reconstr Surg, Vol. XX, No. XX, 2014
marrow biopsy, and cerebrospinal fluid cytology, was arranged. All tests showed negative results. The patient was treated with a debulking surgery of the tumor (Fig. 3C,D), followed by chemotherapy, consisting of vincristine and actinomycin D, and concurrent radiation therapy. However, CT scans performed 2 weeks after systemic treatment, due to the progressive enlargement of the right upper abdomen, revealed a metastatic growth in the liver. Due to persistent neutropenic fever and sepsis, the patient’s parents elected palliative therapy at 13 weeks of age of the patient. The patient expired at 24 weeks of age. The autopsy found that there were no tumor cells in the eyelid. Metastatic areas included the right neck, right flank area, lungs, and liver. Histopathologic and immunohistochemical studies incidentally revealed that there was a neuroblastoma in the patient’s left adrenal gland (Fig. 3E,F).
DISCUSSION Clinicians should carefully differentiate between congenital eyelid RMSs and capillary hemangiomas. The latter is one of the most common benign orbital tumors in children, and approximately one third of capillary hemangiomas are apparent at birth. Clinically, a capillary hemangioma may present as a cutaneous, subcutaneous, or deep orbital lesion, or a combination of the 3. The superficial cutaneous lesion, or “strawberry nevus,” is initially evident as a confluence of telangiectasias, and later progresses to a red, raised, nodular lesion. The diagnosis of superficial cutaneous capillary hemangioma is usually clinical.5 It is difficult to distinguish between a congenital eyelid RMS and a superficial cutaneous capillary hemangioma at the onset of the 2 diseases. Therefore, an early biopsy may be useful in equivocal cases. To the best of the authors’ knowledge, their case is the youngest patient with a congenital eyelid RMS combined with an adrenal neuroblastoma. Previous studies have demonstrated that age is a prognostic factor in RMS, and a poorer outcome is reported for infants than for older children.6 In infants with nonmetastatic RMSs treated using the IRS protocols, the 5-year failure-free survival and overall infant survival rates were 57% and 76%, respectively, compared with 81% and 87%, respectively, for children between the ages of 1 and 9 years.7 In this case, the fulminant clinical course and poor response to standard protocol may also have contributed to a genetic predisposition.8 Pediatric RMS includes 2 major histological subtypes, namely alveolar and embryonal RMS. Patients with embryonal RMS generally show a better 5-year survival rate than those with alveolar RMS.9 The pathogenesis of embryonal RMS showed a common genomic program. Inactivation of the tumor suppressor genes p53 and CDKN2A/B, and activation of fibroblast growth factor receptor(FGFR), Rat sarcoma (RAS), and Hedgehog signaling have been suggested.10 One recent study investigated the oncogene mutations of pediatric solid tumors, and mutations were found to be more common in embryonal RMS (28.3%) than in alveolar RMS (3.5%). Oncogene mutations in embryonal RMS included previously identified RAS, FGFR4, and BRAF, and recently found PIK3CA and CTNNB1; mutations in neuroblastomas included Anaplastic lymphoma kinase (ALK) and Mitogen-activated protein kinase kinase (MAP2K1), as well as a novel finding of rare presentations of BRAF and RAS, which have been found in embryonal RMS.8 There is an increased incidence of RMS and other childhood cancers in genetic syndromes, with germline RAS/MAPK pathway and BRAF mutations, including cardiofacio-cutaneous syndrome, Costello syndrome, and Noonan syndrome.11,12 Patients with these syndromes have unique appearance and frequent cardiac problems, which are not found in this patient. The authors hypothesize that both RMS and the
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Copyright © 2014 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc. Unauthorized reproduction of this article is prohibited.
Ophthal Plast Reconstr Surg, Vol. XX, No. XX, 2014
Case Reports
FIG. 1. Initial presentation of the tumor and MRI.
FIG. 2. Rapid growth of the eyelid rhabdomyosarcoma and MRI.
FIG. 3. Histopathologic and immunohistochemical findings. Small blue and round cells (A, hematoxylin-eosin, ×400). Desmin was stained diffusely (B). The specimen from the debulking surgery showed many mitotic cells (C, hematoxylin-eosin, ×400); the presentation of desmin was low compared with B (D). The neuroblastoma (E, hematoxylin-eosin, ×50) was stained with synaptophysin, indicating its neuroendocrine origin (F).
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© 2014 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.
Copyright © 2014 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc. Unauthorized reproduction of this article is prohibited.
Ophthal Plast Reconstr Surg, Vol. XX, No. XX, 2014
neuroblastoma in their case were associated with the oncogene mutations, whether 1 common mutation or multiple pathways. Further chromosomal and genetic studies in similar cases of double or multiple pediatric solid tumors may be necessary to elucidate the relationship between them. In conclusion, the authors report a newborn with congenital RMS in the right upper eyelid. An early biopsy would have been beneficial for differentiating it from a superficial cutaneous hemangioma, and it may also have helped avoid delaying the diagnosis and further metastases. Clinicians should also survey other possible coincident solid tumors and perform oncogene analysis in similar cases.
REFERENCES 1. Shields JA, Shields CL. Rhabdomyosarcoma: review for the ophthalmologist. Surv Ophthalmol 2003;48:39–57. 2. Garay M, Chernicoff M, Moreno S, et al. Congenital alveolar rhabdomyosarcoma in a newborn. Eur J Pediat Dermatol 2004;14:9–12. 3. Jung JH, Lee JE, Shin JH, et al. Lower eyelid rhabdomyosarcoma in a 3-month-old infant. J AAPOS 2010;14:285–7. 4. Castillo BV Jr, Kaufman L. Pediatric tumors of the eye and orbit. Pediatr Clin North Am 2003;50:149–72. 5. Peralta RJ, Glavas IP. Ophthalmic Pearls: Pediatrics. Review of Capillary Hemangioma. EyeNetMagzine [serial online]. 2009.
Case Reports
Available at: http://www.aao.org/ publications/eyenet/200902/ pearls.cfm. Accessed September 2, 2014. 6. Orbach D, Rey A, Oberlin O, et al. Soft tissue sarcoma or malignant mesenchymal tumors in the first year of life: experience of the International Society of Pediatric Oncology (SIOP) Malignant Mesenchymal Tumor Committee. J Clin Oncol 2005;23:4363–71. 7. Malempati S, Rodeberg DA, Donaldson SS, et al. Rhabdomyosarcoma in infants younger than 1 year: a report from the Children’s Oncology Group. Cancer 2011;117:3493–501. 8. Shukla N, Ameur N, Yilmaz I, et al. Oncogene mutation profiling of pediatric solid tumors reveals significant subsets of embryonal rhabdomyosarcoma and neuroblastoma with mutated genes in growth signaling pathways. Clin Cancer Res 2012;18:748–57. 9. Kodet R, Newton WA Jr, Hamoudi AB, et al. Orbital rhabdomyosarcomas and related tumors in childhood: relationship of morphology to prognosis–an Intergroup Rhabdomyosarcoma study. Med Pediatr Oncol 1997;29:51–60. 10. Paulson V, Chandler G, Rakheja D, et al. High-resolution array CGH identifies common mechanisms that drive embryonal rhabdomyosarcoma pathogenesis. Genes Chromosomes Cancer 2011;50:397–408. 11. Nava C, Hanna N, Michot C, et al. Cardio-facio-cutaneous and Noonan syndromes due to mutations in the RAS/MAPK signalling pathway: genotype-phenotype relationships and overlap with Costello syndrome. J Med Genet 2007;44:763–71. 12. Rodriguez-Viciana P, Tetsu O, Tidyman WE, et al. Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome. Science 2006;311:1287–90.
© 2014 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.
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Copyright © 2014 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc. Unauthorized reproduction of this article is prohibited.
R
habdomyosarcoma (RMS) is uncommon in infants,1–4 and to the authors’ knowledge, there are no reports of eyelid RMS in newborns. The authors report a rare case with a congenital RMS confined to the eyelid. The tumor was initially mistaken for a capillary hemangioma because of its red hue.
CASE REPORT A 1-day-old newborn, delivered by an elective cesarean section with no complications, at 38 weeks of gestation, with a birth body weight of 3,200 g, was found to have a tumor having a red hue in his right upper eyelid (Fig. 1A). The patient had 3 healthy siblings and no family history of cancer. On examination, the tumor was indurated, firm, and blocking the patient’s visual axis. The other findings of the ocular structures were normal. Orbital MRI showed a heterogeneously enhanced, hypervascular lesion confined to the eyelid. The orbital area was not involved (Fig. 1B). A diagnosis of an eyelid capillary hemangioma was made, and an intralesional corticosteroids injection was given (20 mg methylprednisolone and 4 mg dexamethasone) with a 30-gauge needle, at 4 days of age of the patient. The tumor shrank in the following several days, and the patient was lost to follow up shortly thereafter. At 5 weeks of age, the patient was brought back to the outpatient clinic because of the rapid growth and active oozing of the tumor. Severe necrotic changes were noted on the tumor surface (Fig. 2A). Orbital MRI also showed the enlargement of the tumor, which invaded the orbit and compressed the OD (Fig. 2B). The tumor was excised, and histopathologic examinations revealed many small blue round cells with positive stains for myogenin and desmin (Fig. 3A,B). After the diagnosis of embryonal RMS was confirmed, systemic investigation, including whole-body bone scan, chest CT, bone Departments of *Ophthalmology, †Pathology, and ‡Pediatrics, Buddhist Tzu Chi General Hospital; §Department of Ophthalmology and Visual Science, Tzu Chi University, Hualien; and ¶Department of Ophthalmology, Far Eastern Memorial Hospital, Taipei, Taiwan Accepted for publication July 1, 2014. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Tzu-Lun Huang, m.d., Department of Ophthalmology, Far Eastern Memorial Hospital, No. 21, Section 2, Nanya S. Road, Banciao District, New Taipei City 220, Taiwan. E-mail: [email protected] DOI: 10.1097/IOP.0000000000000290
Ophthal Plast Reconstr Surg, Vol. XX, No. XX, 2014
marrow biopsy, and cerebrospinal fluid cytology, was arranged. All tests showed negative results. The patient was treated with a debulking surgery of the tumor (Fig. 3C,D), followed by chemotherapy, consisting of vincristine and actinomycin D, and concurrent radiation therapy. However, CT scans performed 2 weeks after systemic treatment, due to the progressive enlargement of the right upper abdomen, revealed a metastatic growth in the liver. Due to persistent neutropenic fever and sepsis, the patient’s parents elected palliative therapy at 13 weeks of age of the patient. The patient expired at 24 weeks of age. The autopsy found that there were no tumor cells in the eyelid. Metastatic areas included the right neck, right flank area, lungs, and liver. Histopathologic and immunohistochemical studies incidentally revealed that there was a neuroblastoma in the patient’s left adrenal gland (Fig. 3E,F).
DISCUSSION Clinicians should carefully differentiate between congenital eyelid RMSs and capillary hemangiomas. The latter is one of the most common benign orbital tumors in children, and approximately one third of capillary hemangiomas are apparent at birth. Clinically, a capillary hemangioma may present as a cutaneous, subcutaneous, or deep orbital lesion, or a combination of the 3. The superficial cutaneous lesion, or “strawberry nevus,” is initially evident as a confluence of telangiectasias, and later progresses to a red, raised, nodular lesion. The diagnosis of superficial cutaneous capillary hemangioma is usually clinical.5 It is difficult to distinguish between a congenital eyelid RMS and a superficial cutaneous capillary hemangioma at the onset of the 2 diseases. Therefore, an early biopsy may be useful in equivocal cases. To the best of the authors’ knowledge, their case is the youngest patient with a congenital eyelid RMS combined with an adrenal neuroblastoma. Previous studies have demonstrated that age is a prognostic factor in RMS, and a poorer outcome is reported for infants than for older children.6 In infants with nonmetastatic RMSs treated using the IRS protocols, the 5-year failure-free survival and overall infant survival rates were 57% and 76%, respectively, compared with 81% and 87%, respectively, for children between the ages of 1 and 9 years.7 In this case, the fulminant clinical course and poor response to standard protocol may also have contributed to a genetic predisposition.8 Pediatric RMS includes 2 major histological subtypes, namely alveolar and embryonal RMS. Patients with embryonal RMS generally show a better 5-year survival rate than those with alveolar RMS.9 The pathogenesis of embryonal RMS showed a common genomic program. Inactivation of the tumor suppressor genes p53 and CDKN2A/B, and activation of fibroblast growth factor receptor(FGFR), Rat sarcoma (RAS), and Hedgehog signaling have been suggested.10 One recent study investigated the oncogene mutations of pediatric solid tumors, and mutations were found to be more common in embryonal RMS (28.3%) than in alveolar RMS (3.5%). Oncogene mutations in embryonal RMS included previously identified RAS, FGFR4, and BRAF, and recently found PIK3CA and CTNNB1; mutations in neuroblastomas included Anaplastic lymphoma kinase (ALK) and Mitogen-activated protein kinase kinase (MAP2K1), as well as a novel finding of rare presentations of BRAF and RAS, which have been found in embryonal RMS.8 There is an increased incidence of RMS and other childhood cancers in genetic syndromes, with germline RAS/MAPK pathway and BRAF mutations, including cardiofacio-cutaneous syndrome, Costello syndrome, and Noonan syndrome.11,12 Patients with these syndromes have unique appearance and frequent cardiac problems, which are not found in this patient. The authors hypothesize that both RMS and the
e1
Copyright © 2014 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc. Unauthorized reproduction of this article is prohibited.
Ophthal Plast Reconstr Surg, Vol. XX, No. XX, 2014
Case Reports
FIG. 1. Initial presentation of the tumor and MRI.
FIG. 2. Rapid growth of the eyelid rhabdomyosarcoma and MRI.
FIG. 3. Histopathologic and immunohistochemical findings. Small blue and round cells (A, hematoxylin-eosin, ×400). Desmin was stained diffusely (B). The specimen from the debulking surgery showed many mitotic cells (C, hematoxylin-eosin, ×400); the presentation of desmin was low compared with B (D). The neuroblastoma (E, hematoxylin-eosin, ×50) was stained with synaptophysin, indicating its neuroendocrine origin (F).
e2
© 2014 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.
Copyright © 2014 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc. Unauthorized reproduction of this article is prohibited.
Ophthal Plast Reconstr Surg, Vol. XX, No. XX, 2014
neuroblastoma in their case were associated with the oncogene mutations, whether 1 common mutation or multiple pathways. Further chromosomal and genetic studies in similar cases of double or multiple pediatric solid tumors may be necessary to elucidate the relationship between them. In conclusion, the authors report a newborn with congenital RMS in the right upper eyelid. An early biopsy would have been beneficial for differentiating it from a superficial cutaneous hemangioma, and it may also have helped avoid delaying the diagnosis and further metastases. Clinicians should also survey other possible coincident solid tumors and perform oncogene analysis in similar cases.
REFERENCES 1. Shields JA, Shields CL. Rhabdomyosarcoma: review for the ophthalmologist. Surv Ophthalmol 2003;48:39–57. 2. Garay M, Chernicoff M, Moreno S, et al. Congenital alveolar rhabdomyosarcoma in a newborn. Eur J Pediat Dermatol 2004;14:9–12. 3. Jung JH, Lee JE, Shin JH, et al. Lower eyelid rhabdomyosarcoma in a 3-month-old infant. J AAPOS 2010;14:285–7. 4. Castillo BV Jr, Kaufman L. Pediatric tumors of the eye and orbit. Pediatr Clin North Am 2003;50:149–72. 5. Peralta RJ, Glavas IP. Ophthalmic Pearls: Pediatrics. Review of Capillary Hemangioma. EyeNetMagzine [serial online]. 2009.
Case Reports
Available at: http://www.aao.org/ publications/eyenet/200902/ pearls.cfm. Accessed September 2, 2014. 6. Orbach D, Rey A, Oberlin O, et al. Soft tissue sarcoma or malignant mesenchymal tumors in the first year of life: experience of the International Society of Pediatric Oncology (SIOP) Malignant Mesenchymal Tumor Committee. J Clin Oncol 2005;23:4363–71. 7. Malempati S, Rodeberg DA, Donaldson SS, et al. Rhabdomyosarcoma in infants younger than 1 year: a report from the Children’s Oncology Group. Cancer 2011;117:3493–501. 8. Shukla N, Ameur N, Yilmaz I, et al. Oncogene mutation profiling of pediatric solid tumors reveals significant subsets of embryonal rhabdomyosarcoma and neuroblastoma with mutated genes in growth signaling pathways. Clin Cancer Res 2012;18:748–57. 9. Kodet R, Newton WA Jr, Hamoudi AB, et al. Orbital rhabdomyosarcomas and related tumors in childhood: relationship of morphology to prognosis–an Intergroup Rhabdomyosarcoma study. Med Pediatr Oncol 1997;29:51–60. 10. Paulson V, Chandler G, Rakheja D, et al. High-resolution array CGH identifies common mechanisms that drive embryonal rhabdomyosarcoma pathogenesis. Genes Chromosomes Cancer 2011;50:397–408. 11. Nava C, Hanna N, Michot C, et al. Cardio-facio-cutaneous and Noonan syndromes due to mutations in the RAS/MAPK signalling pathway: genotype-phenotype relationships and overlap with Costello syndrome. J Med Genet 2007;44:763–71. 12. Rodriguez-Viciana P, Tetsu O, Tidyman WE, et al. Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome. Science 2006;311:1287–90.
© 2014 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.
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