About MEAJO | Editorial board | Search | Ahead of print | Current Issue | Archives | Instructions to authors | Online submission | Subscribe | Advertise | Contact | Login 
Middle East African Journal of Ophthalmology Middle East African Journal of Ophthalmology
Users Online: 740   Home Print this page Email this page Small font sizeDefault font sizeIncrease font size

  Table of Contents 
Year : 2018  |  Volume : 25  |  Issue : 2  |  Page : 111-114  

Botryoid rhabdomyosarcoma of the conjunctiva in a young boy

Department of Pathology, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA 19107, USA

Date of Web Publication18-Jul-2018

Correspondence Address:
Dr. Carol L Shields
Department of Pathology, Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, 840 Walnut Street, 14th Floor, Philadelphia, PA 19107
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/meajo.MEAJO_8_18

Rights and Permissions

Primary conjunctival rhabdomyosarcoma (RMS) is a rare entity that can present with or without papillomatous features. A 5-year-old Asian boy was referred for a rapidly growing conjunctival tumor in the superior fornix of the left eye. Surgical excision yielded a 28 mm multilobulated papillomatous specimen that exhibited histopathologic and immunohistochemical features consistent with embryonal (botryoid) RMS. Molecular analysis revealed the absence of the PAX3/FOXO1 fusion gene, indicating favorable prognosis. After surgery, he was promptly treated with systemic chemotherapy and proton beam radiotherapy.

Keywords: Botryoid, conjunctiva, papilloma, rhabdomyosarcoma, tumor

How to cite this article:
Pennington JD, Welch R J, Lally SE, Shields JA, Eagle RC, Shields CL. Botryoid rhabdomyosarcoma of the conjunctiva in a young boy. Middle East Afr J Ophthalmol 2018;25:111-4

How to cite this URL:
Pennington JD, Welch R J, Lally SE, Shields JA, Eagle RC, Shields CL. Botryoid rhabdomyosarcoma of the conjunctiva in a young boy. Middle East Afr J Ophthalmol [serial online] 2018 [cited 2021 Oct 23];25:111-4. Available from: http://www.meajo.org/text.asp?2018/25/2/111/237040

   Introduction Top

Malignant tumors of the conjunctiva in children are rare, accounting for only 3% of conjunctival tumors.[1],[2] Rhabdomyosarcoma (RMS), while more commonly a primary orbital tumor, can present as a primary conjunctival lesion.[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17] In a series of 33 patients with ophthalmic RMS, conjunctival involvement was evident in only 12%.[3] Conjunctival RMS can have papillomatous or smooth features, depending on whether the tumor originates in the conjunctiva or represents extension from orbital disease.[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17]

A review of the 264 ophthalmic RMS cases from the Intergroup RMS Studies (IRS I, II, III, and IV), revealed histopathologic classification as embryonal (n = 221, 84%), alveolar (n = 24, 9%), undifferentiated (n = 11, 4%), and other (n = 12, 4%) subtypes.[18],[19],[20],[21],[22] The 10-year prognosis for survival was more favorable with embryonal (94%) compared to alveolar (62%), undifferentiated (91%), and other (52%) subtypes of RMS.[18] In that review, botryoid variant of RMS was included in the classic embryonal RMS subtype with favorable prognosis.[18]

While clinical and histologic characteristics of RMS have historically guided prognostication, molecular data have recently proven highly effective in RMS risk stratification.[23],[24],[25],[26],[27] Specifically, the presence of the PAX3/FOXO1 fusion gene has been associated with alveolar RMS, thus implying poorer prognosis.[23],[24],[25],[26],[27]

RMS is a life-threatening disease, and early recognition with prompt treatment leads to best outcomes.[18],[19],[20],[21],[22] Ophthalmic RMS generally has a favorable prognosis with an overall survival rate of 93%.[3],[18] Herein, we describe a case of embryonal (botryoid), fusion gene-negative, conjunctival RMS, initially suspected to represent benign papilloma, in a young boy.

   Case Report Top

A 5-year-old Asian boy was referred for a conjunctival mass of the left eye (OS). On examination, uncorrected visual acuity was 20/30 in the right eye (OD) and 20/80 OS. Pupillary examination, motility assessment, and intraocular pressure were normal in both eyes. The OD and orbit were normal. The OS revealed fullness of the upper eyelid with 2 mm blepharoptosis [Figure 1]a. There was no eyelid erythema or tenderness. On eyelid eversion, there was a large 22 mm × 12 mm × 8 mm multilobulated, vascularized papillomatous mass arising within the superior conjunctival fornix [Figure 1]b. The remainder of the anterior and posterior segment was unremarkable. The initial diagnostic considerations included conjunctival giant papilloma versus RMS.
Figure 1: A 5-year-old boy with conjunctival rhabdomyosarcoma of the left eye. (a) External photograph demonstrating left upper eyelid fullness and slight blepharoptosis. (b) Eversion of the left upper eyelid revealing a large multilobulated forniceal mass. (c) At the time of surgery, the conjunctival mass had enlarged. (d) Lateral view of the large pedunculated conjunctival mass. (e) Surgical specimen measuring 28 mm × 20 mm × 8 mm

Click here to view

A few days later, at the time of surgery, there was 6 mm rapid enlargement of the mass [Figure 1]c and [Figure 1]d, suspicious for RMS. Following complete surgical resection and surrounding cryotherapy, the tumor measured 28 × 20 in basal diameter [Figure 1]e. Histopathology revealed an infiltrate of malignant cells [Figure 2]a that were intensely immunoreactive for striated muscle markers, desmin, and myogenin, consistent with RMS [Figure 2]b and [Figure 2]c. Molecular analysis revealed the absence of the PAX3/FOXO1 fusion gene, suggestive of the embryonal variant. These findings were consistent with conjunctival embryonal RMS, botryoid growth pattern. Systemic staging revealed no metastatic disease (Stage I, favorable site head and neck), Group 2 (microscopic residua), and the patient was treated with vincristine, actinomycin, cyclophosphamide (VAC) plus VA for 4 cycles (protocol ARST0331) and proton beam therapy (36 Gy).
Figure 2: Histopathology and immunohistochemistry of conjunctival rhabdomyosarcoma. (a) The conjunctival substantia propria contained scattered strap cells and rhabdomyoblasts. (b) Intense cytoplasmic immunoreactivity for desmin was seen. (c) Intense nuclear immunoreactivity for myogenin was noted in at least 70% of the tumor cells

Click here to view

   Discussion Top

RMS is the most common soft-tissue sarcoma in children, comprising approximately 3% of all childhood cancers.[28] There have been relatively few reported cases of primary conjunctival RMS or conjunctival extension of orbital RMS.[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17] In 1,258 patients from the Intergroup RMS Study III (IRS-III) and IRS-IV, the primary site for RMS was the head and neck region (42%), trunk (41%), and extremities (15%).[29],[30] Of those that arose in the head and neck region, 31% occurred in the orbit.[29] In a series of 33 consecutive cases of RMS of the ocular region, Shields et al. noted that all cases were primary orbital malignancies, but 4 (12%) demonstrated secondary conjunctival invasion.[3]

The most common ophthalmic RMS subtype is embryonal, which typically manifests with elongated spindle or strap-like cells and scattered rhabdomyoblasts with eosinophilic cytoplasm. Although cross striations are a characteristic feature, they are absent in many cases.[18] The botryoid variant of embryonal RMS is named for its grape-like appearance and is usually found in the mucous membrane of the urogenital tract or conjunctiva.[31] Botryoid RMS of the conjunctiva with papillomatous features, as seen in our case, has been recognized previously by Polito et al.,[4] Taylor et al.,[5] and Adamopoulou et al.[6] Similar to those cases, our patient displayed a large forniceal papillomatous lesion with rapid growth.

The prognosis for the botryoid variant of ophthalmic RMS is typically favorable. In a 1997 comprehensive review from the Intergroup RMS studies of 264 patients with RMS of the orbit, conjunctiva, and eyelids, the 5-year survival was 94% for embryonal (including botryoid) and 74% for alveolar types.[18] By contrast, embryonal RMS at extraocular locations demonstrated 66% survival estimate.[18]

The prognosis for ophthalmic RMS has drastically improved during the past 40 years to a >90% survival rate based on a combination of surgery, radiotherapy, and chemotherapy.[18],[19],[20],[21],[22] Currently, most therapeutic protocols are based on clinical tumor grouping, combined with histopathology stage and molecular features. The pretreatment staging paradigm from the Intergroup RMS studies includes Stage I (disease involving the orbit, head or neck without parameningeal involvement, biliary tract, or genitourinary without bladder or prostate involvement), Stage II (disease involving the bladder, prostate, extremity, or cranial parameningeal involvement without nodal spread), Stage III (disease involving the bladder, prostate, extremity, or cranial parameningeal involvement with nodal spread), and Stage IV (metastasis).[29] The surgical-pathologic grouping is performed postsurgically and after histopathologic confirmation and includes Group I (no residua), Group II (microscopic residua), Group III (macroscopic residua), and Group IV (metastasis).[29] Our patient exhibited Stage I, Group II RMS. An important molecular feature regarding the presence of PAX3/FOXO1 fusion gene was negative in our patient.[23],[24],[25],[26],[27] Considering these features, the estimated 5-year overall survival rate is 97%.[29],[32]

Cytogenetic analysis of alveolar RMS in 1993 by Galili et al. revealed a characteristic translocation involving the PAX3 gene on chromosome 2 and a member of the forkhead domain family on chromosome 13 (initially termed PAX3-FKHR and later identified as PAX/FOXO1 fusion gene).[23] When assessing 210 patients with RMS by clinical, histopathologic, and molecular features, Williamson et al. found that PAX3/FOXO1 fusion gene status was a critical factor in risk stratification, irrespective of histopathologic grading.[24] RMSs that were PAX3/FOXO1 gene-negative were clinically and molecularly indistinguishable from embryonal RMS while those that harbored the PAX3/FOXO1 fusion gene were consistent with alveolar RMS and had a poorer prognosis.[24] The status of PAX3/FOXO1 fusion gene is now a key factor in RMS prognostication.[23],[24],[25],[26],[27]

   Conclusion Top

Primary conjunctival RMS is rare and can present as a rapidly evolving papillomatous (botryoid) mass. While the prognosis is usually favorable for ophthalmic RMS, information regarding molecular changes in the PAX3/FOXO1 fusion gene strongly correlate with patient prognosis. In all cases of RMS, prompt diagnosis and management are important.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Support provided by Eye Tumor Research Foundation, Philadelphia, PA (CLS, JAS).

Conflicts of interest

There are no conflicts of interest.

   References Top

Shields CL, Chien JL, Surakiatchanukul T, Sioufi K, Lally SE, Shields JA, et al. Conjunctival tumors: Review of clinical features, risks, biomarkers, and outcomes – The 2017 J. Donald M. Gass lecture. Asia Pac J Ophthalmol (Phila) 2017;6:109-20.  Back to cited text no. 1
Shields CL, Sioufi K, Alset AE, Boal NS, Casey MG, Knapp AN, et al. Clinical features differentiating benign from malignant conjunctival tumors in children. JAMA Ophthalmol 2017;135:215-24.  Back to cited text no. 2
Shields CL, Shields JA, Honavar SG, Demirci H. Clinical spectrum of primary ophthalmic rhabdomyosarcoma. Ophthalmology 2001;108:2284-92.  Back to cited text no. 3
Polito E, Pichierri P, Loffredo A, Lasorella G. A case of primary botryoid conjunctival rhabdomyosarcoma. Graefes Arch Clin Exp Ophthalmol 2006;244:517-9.  Back to cited text no. 4
Taylor SF, Yen KG, Zhou H, Patel BC. Primary conjunctival rhabdomyosarcoma. Arch Ophthalmol 2002;120:668-9.  Back to cited text no. 5
Adamopoulou C, Rotberg L, Baker JD. Conjunctival papillomatous lesion. JAMA Ophthalmol 2014;132:1481-2.  Back to cited text no. 6
Smith A, Gupta A, Bonshek R, Leatherbarrow B. Conjunctival rhabdomyosarcoma presenting as a squamous papilloma. Eye (Lond) 2007;21:281-3.  Back to cited text no. 7
Kuchar A, Steinkogler FJ. Rhabdomyosarcoma presenting as subconjunctival tumour. Acta Ophthalmol Scand 2000;78:717-8.  Back to cited text no. 8
Sekundo W, Roggenkämper P, Fischer HP, Fleischhack G, Flühs D, Sauerwein W, et al. Primary conjunctival rhabdomyosarcoma: 2.5 years' follow-up after combined chemotherapy and brachytherapy. Graefes Arch Clin Exp Ophthalmol 1998;236:873-5.  Back to cited text no. 9
Mendez Mdel C, Muiños Y, Blanco G, Saornil MA, García-Alvarez C, Sarasa JL, et al. Embryonal rhabdomyosarcoma of the caruncle in a 4 year-old boy: Case report. Arq Bras Oftalmol 2012;75:207-9.  Back to cited text no. 10
Sarigül Sezenöz A, Karalezli A, Özkan Arat Y, Çoban G, Kiratli H, Terzi A, et al. Metastatic embryonal conjunctival rhabdomyosarcoma in a 4-year-old boy. Ophthalmic Plast Reconstr Surg 2017;33:S125-7.  Back to cited text no. 11
Levy MR. Subconjunctival rhabdomyosarcoma. Am J Ophthalmol 1968;65:452-4.  Back to cited text no. 12
Elsas FJ, Green WR. Epibulbar tumors in childhood. Am J Ophthalmol 1975;79:1001-7.  Back to cited text no. 13
Joffe L, Shields JA, Pearah JD. Epibulbar rhabdomyosarcoma without proptosis. J Pediatr Ophthalmol 1977;14:364-7.  Back to cited text no. 14
Cameron JD, Wick MR. Embryonal rhabdomyosarcoma of the conjunctiva. A clinicopathologic and immunohistochemical study. Arch Ophthalmol 1986;104:1203-4.  Back to cited text no. 15
Brichard B, De Potter P, Godfraind C, Vermylen C. Embryonal rhabdomyosarcoma presenting as conjunctival tumor. J Pediatr Hematol Oncol 2003;25:651-2.  Back to cited text no. 16
Shields JA, Shields CL. Orbital rhabdomyosarcoma: Presentation as a conjunctival mass. In: Eyelid, Conjunctival, and Orbital Tumors. 3rd ed. Philadelphia: Wolters Kluwer; 2016. p. 602.  Back to cited text no. 17
Kodet R, Newton WA Jr. Hamoudi AB, Asmar L, Wharam MD, Maurer HM, 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.  Back to cited text no. 18
Maurer HM, Beltangady M, Gehan EA, Crist W, Hammond D, Hays DM, et al. The intergroup rhabdomyosarcoma study-I. A final report. Cancer 1988;61:209-20.  Back to cited text no. 19
Maurer HM, Gehan EA, Beltangady M, Crist W, Dickman PS, Donaldson SS, et al. The intergroup rhabdomyosarcoma study-II. Cancer 1993;71:1904-22.  Back to cited text no. 20
Crist W, Gehan EA, Ragab AH, Dickman PS, Donaldson SS, Fryer C, et al. The third intergroup rhabdomyosarcoma study. J Clin Oncol 1995;13:610-30.  Back to cited text no. 21
Crist WM, Anderson JR, Meza JL, Fryer C, Raney RB, Ruymann FB, et al. Intergroup rhabdomyosarcoma study-IV: Results for patients with nonmetastatic disease. J Clin Oncol 2001;19:3091-102.  Back to cited text no. 22
Galili N, Davis RJ, Fredericks WJ, Mukhopadhyay S, Rauscher FJ 3rd, Emanuel BS, et al. Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma. Nat Genet 1993;5:230-5.  Back to cited text no. 23
Williamson D, Missiaglia E, de Reyniès A, Pierron G, Thuille B, Palenzuela G, et al. Fusion gene-negative alveolar rhabdomyosarcoma is clinically and molecularly indistinguishable from embryonal rhabdomyosarcoma. J Clin Oncol 2010;28:2151-8.  Back to cited text no. 24
Missiaglia E, Williamson D, Chisholm J, Wirapati P, Pierron G, Petel F, et al. PAX3/FOXO1 fusion gene status is the key prognostic molecular marker in rhabdomyosarcoma and significantly improves current risk stratification. J Clin Oncol 2012;30:1670-7.  Back to cited text no. 25
Jurdy L, Merks JH, Pieters BR, Mourits MP, Kloos RJ, Strackee SD, et al. Orbital rhabdomyosarcomas: A review. Saudi J Ophthalmol 2013;27:167-75.  Back to cited text no. 26
Sorensen PH, Lynch JC, Qualman SJ, Tirabosco R, Lim JF, Maurer HM, et al. PAX3-FKHR and PAX7-FKHR gene fusions are prognostic indicators in alveolar rhabdomyosarcoma: A report from the Children's Oncology Group. J Clin Oncol 2002;20:2672-9.  Back to cited text no. 27
American Cancer Society. Cancer Facts & Figures 2014. Atlanta, GA: American Cancer Society; 2014.  Back to cited text no. 28
Meza JL, Anderson J, Pappo AS, Meyer WH; Children's Oncology Group. Analysis of prognostic factors in patients with nonmetastatic rhabdomyosarcoma treated on intergroup rhabdomyosarcoma studies III and IV: The Children's Oncology Group. J Clin Oncol 2006;24:3844-51.  Back to cited text no. 29
Shields JA, Shields CL. Rhabdomyosarcoma: Review for the ophthalmologist. Surv Ophthalmol 2003;48:39-57.  Back to cited text no. 30
Knowles DM, Jakobiec FA, Potter GD, Jones IS. Ophthalmic striated muscle neoplasms. Surv Ophthalmol 1976;21:219-61.  Back to cited text no. 31
Walterhouse DO, Pappo AS, Meza JL, Breneman JC, Hayes-Jordan AA, Parham DM, et al. Shorter-duration therapy using vincristine, dactinomycin, and lower-dose cyclophosphamide with or without radiotherapy for patients with newly diagnosed low-risk rhabdomyosarcoma: A report from the soft tissue sarcoma committee of the Children's Oncology Group. J Clin Oncol 2014;32:3547-52.  Back to cited text no. 32


  [Figure 1], [Figure 2]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
   Case Report
    Article Figures

 Article Access Statistics
    PDF Downloaded103    
    Comments [Add]    

Recommend this journal