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Year : 2018  |  Volume : 61  |  Issue : 2  |  Page : 201-203
Is a diagnostic lumbar puncture indicated in intraocular retinoblastoma?

1 Department of Pediatrics, Advanced Pediatrics Center, Pediatric Hematology-Oncology Unit, Postgraduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Ophthalmology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
3 Department of Cytology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
4 Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
5 Department of Radiodiagnosis, Postgraduate Institute of Medical Education and Research, Chandigarh, India

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Date of Web Publication20-Apr-2018


Background: Lumbar puncture (LP) is frequently performed in patients with advanced intraocular retinoblastoma. However, this may not be necessary in a significant proportion of patients. Materials and Methods: A file review of patients who were diagnosed with retinoblastoma over a 13-year-period was performed. Patients who underwent LP as part of staging were included in the study. Results: The study included 223 patients. One-third had bilateral retinoblastoma. The grouping was C, D, and E in 4 (2.9%), 41 (29.9%), and 92 (67.2%) patients, respectively. The stage was 0, I, II, III, and IV in 14 (6.3), 123 (55.2%), 13 (5.8%), 70 (31.4%), and 3 (1.3%) patients, respectively. Eight (3.6%) patients had a positive cerebrospinal fluid (CSF) cytology. None of the patients with intraocular disease and 7 (10%) patients with extraocular disease had a positive CSF. Conclusions: A diagnostic CSF is not indicated in patients with intraocular retinoblastoma.

Keywords: Central nervous system dissemination, cerebrospinal fluid malignant cytology, international retinoblastoma staging system, metastatic retinoblastoma, optic nerve thickening

How to cite this article:
Totadri S, Munikoty V, Singh U, Srinivasan R, Trehan A, Jain R, Kakkar N, Saxena AK, Rajwanshi A, Bansal D. Is a diagnostic lumbar puncture indicated in intraocular retinoblastoma?. Indian J Pathol Microbiol 2018;61:201-3

How to cite this URL:
Totadri S, Munikoty V, Singh U, Srinivasan R, Trehan A, Jain R, Kakkar N, Saxena AK, Rajwanshi A, Bansal D. Is a diagnostic lumbar puncture indicated in intraocular retinoblastoma?. Indian J Pathol Microbiol [serial online] 2018 [cited 2021 Apr 23];61:201-3. Available from: https://www.ijpmonline.org/text.asp?2018/61/2/201/230554

   Introduction Top

Retinoblastoma typically presents as intraocular disease in developed countries.[1] In contrast, extraocular involvement and metastatic disease are not uncommon in lower/middle-income countries (LMIC).[2] The central nervous system (CNS) is the most common site of metastasis and is consequent to direct extension through the optic nerve.[3] Outcome is dismal with CNS metastasis.[3] Cerebrospinal fluid (CSF) cytology enables differentiation of potentially curable Stage III from the largely incurable Stage IVb disease.[2] The indications for performing a lumbar puncture (LP) vary in protocols. Previous studies have demonstrated <10% of patients to test positive for malignant cells in the CSF.[4],[5],[6],[7] The aim of this retrospective study was to address the utility and indication of performing a diagnostic LP in patients with retinoblastoma.

   Materials and Methods Top

A file review of patients diagnosed with retinoblastoma at our center from January 2003 to December 2015 was performed. Patients with intraocular retinoblastoma were grouped according to the International Classification of Retinoblastoma (ICRB).[8] Staging was performed as per the International Retinoblastoma Staging System (IRSS); Stage 0: Patients treated conservatively, Stage I: Eye enucleated with histological evidence of complete resection, Stage II: Eye enucleated with microscopic residual tumor, Stage III: Overt orbital extension or preauricular/cervical lymph nodal involvement, and Stage IV: Hematogenous metastasis or central nervous system extension.[9] The following were considered high-risk features on histopathological examination of enucleated eyes: scleral involvement, massive choroidal invasion, optic nerve involvement posterior to the lamina cribrosa, or an involvement of the anterior chamber, iris, or ciliary body. The unit's policy was to perform a diagnostic LP in patients with intraocular Group D or E disease as well as in patients with extraocular extension evident clinically or on imaging. Informed consent from parents/guardians was obtained before the procedure. A radiological imaging of the brain to identify CNS dissemination was obtained for patients with Group D/E or clinically evident extraocular disease. A contrast-enhanced computerized tomography of the head or a contrast-enhanced magnetic resonance imaging of the brain was obtained depending on finances, availability of dates, and the discretion of the treating physician. A bone marrow aspiration and trephine biopsy were performed in selected patients with overt extraocular disease or unexplained cytopenia at the time of diagnosis. A LP was often not performed in patients with overt evidence of CNS metastasis as they were typically offered palliative care. The CSF cytology for malignant cells was performed on Giemsa and Papanicolaou-stained cytospin preparations. In patients with bilateral retinoblastoma, the group/stage of the eye with the more advanced disease was considered for analysis. Patients with relapsed disease were excluded from the study. The study was approved by the institution's ethics committee.

   Results Top

Three hundred and thirty-four patients were diagnosed with retinoblastoma over the 13-year period. A LP was performed in 223 (67%) patients, who were included for analysis. The median age was 30 months (range: 2–108). One-third (77/223: 34%) had bilateral retinoblastoma. The ICRB grouping was C, D, and E in 4 (2.9%), 41 (29.9%), and 92 (67.2%) patients with intraocular disease, respectively. The IRSS stage was 0, I, II, III, and IV in 14 (6.3%), 123 (55.2%), 13 (5.8%), 70 (31.4%), and 3 (1.3%) patients, respectively. Details of histopathology were available in 107 patients. Of the 107 patients, 33 (30.8%) had evidence of high-risk features. The most common high-risk feature was postlamina cribrosa optic nerve involvement, that was evident in 14 patients. Of these 14, 12 patients had a stage I disease. Scleral involvement and massive choroidal invasion were observed in four and two patients, respectively. The cut end of the optic nerve demonstrated tumor infiltration in 15 (14%) patients.

Eight (3.6%) of the 223 patients had a positive CSF cytology for malignant cells. Of the eight patients, two had bilateral retinoblastoma. None of the patients with intraocular disease had a positive CSF cytology. Seven (10%) of the seventy patients with extraocular disease had a positive CSF cytology. None of the patients with high-risk histopathological features or infiltration of the cut end of optic nerve had a positive CSF cytology. One (33%) patient with overt Stage IV disease, i.e., with radiological evidence of CNS metastasis had a positive CSF. The IRSS staging, high-risk histopathological features, and CSF positivity in the study cohort are summarized in [Table 1]. Thirty-six (16%) patients underwent a bone marrow examination for staging. One (2.8%) among the 36 patients had an evidence of marrow infiltration by retinoblastoma. This patient had extraocular disease infiltrating into the maxillary sinus; however, there was no evidence of dissemination to the CNS on radiology or CSF cytology.
Table 1: Staging, high-risk histopathological features, and cytology of cerebrospinal fluid in the study cohort

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   Discussion Top

The Pediatric Oncology in Developing Countries Committee of the International Society for Pediatric Oncology clinical practice guidelines for retinoblastoma recommend a CSF examination in Stage II and above.[2] The indications for LP vary in protocols from the developed world. The Children's Cancer and Leukemia Group guidelines for advanced unilateral retinoblastoma managed with primary enucleation advocate a LP in patients with Groups D and E disease.[10] A CSF study is not essential in the Children's Oncology Group (COG) ARET0332 trial of unilateral intraocular retinoblastoma with/without high-risk features undergoing primary enucleation.[1] A CSF examination is indicated in enrolled patients with Stage II and beyond in the COG ARET0321 trial of intensive multimodality therapy for extraocular retinoblastoma.[1]

The crux of staging in LMIC is to differentiate Stage III (extraocular disease, which is typically evident clinicoradiologically) from Stage IV.[2],[9] While the former has a realistic likelihood of survival, the latter, particularly CNS dissemination, has <10% survival with conventional therapy.[2],[5] In our study, none of the patients with intraocular disease had a positive CSF. It is noteworthy that the majority of patients with intraocular disease had advanced disease (Group E: 67.2%; D: 29.9%). All the patients with a positive CSF cytology had extraocular disease, which was apparent on imaging. In an earlier study of 259 patients with retinoblastoma from India, patients who had a positive CSF cytology were either Stage III or IV.[5] The staging was based on neuroimaging and histopathology of enucleated eyes.[5] The authors concluded that a LP was not warranted in Stage 0 or I.[5] Pratt et al. reported a study of 115 CSF assessments in patients with retinoblastoma.[7] They concluded that a LP must be part of the evaluation only in patients with high-risk features, such as choroidal/anterior chamber involvement and extraocular spread or with symptoms suggestive of CNS dissemination.[7] Azar et al. and Mohney et al. did not observe any patient with a positive CSF and advised limited usage of LP as a staging investigation in retinoblastoma.[4],[6] Moscinski et al. recommended restriction of LP to patients with clinical, histological, or radiological evidence of local or systemic extension based on a study of 164 CSF examinations.[11] These studies reinforce our findings that a positive CSF for malignant cells at diagnosis is infrequent and is restricted to patients with evidence of extraocular disease on imaging or histopathology. Estimation of minimal disseminated disease (MDD) in CSF is emerging as a potential tool to predict relapse in patients with retinoblastoma with high-risk features.[12] Laurent et al. evaluated MDD in patients with retinoblastoma, employing reverse transcriptase-polymerase chain reaction to detect synthase of ganglioside GD2 messenger ribonucleic acid in CSF.[13] The presence of MDD in CSF-negative (by cytology) patients was significantly associated with massive optic nerve involvement and CNS relapse.[13]

The study is limited by its retrospective design. In addition, the number of patients in Stage II was merely 13. From the evidence generated in this study, we have changed our policy and are now no longer performing a LP in patients with intraocular disease, including Groups D and E. We are now restricting a LP to patients with Stage II or higher disease. This approach has resulted in avoiding the invasive procedure of LP in a significant majority of patients with retinoblastoma.

   Conclusions Top

A diagnostic LP is indicated in IRSS stage II and above. It is not necessary in intraocular retinoblastoma.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Rodriguez-Galindo C, Krailo M, Frazier L, Chintagumpala M, Amatruda J, Katzenstein H, et al. Children's oncology group's 2013 blueprint for research: Rare tumors. Pediatr Blood Cancer 2013;60:1016-21.  Back to cited text no. 1
Chantada G, Luna-Fineman S, Sitorus RS, Kruger M, Israels T, Leal-Leal C, et al. SIOP-PODC recommendations for graduated-intensity treatment of retinoblastoma in developing countries. Pediatr Blood Cancer 2013;60:719-27.  Back to cited text no. 2
PDQ Pediatric Treatment Editorial Board. Retinoblastoma Treatment (PDQ®): Health Professional Version. In: PDQ Cancer Information Summaries. Bethesda (MD): National Cancer Institute (US); 2002. Available from: http://www.ncbi.nlm.nih.gov/books/NBK66006. [Last accessed on 2017 Jan 29].  Back to cited text no. 3
Mohney BG, Robertson DM. Ancillary testing for metastasis in patients with newly diagnosed retinoblastoma. Am J Ophthalmol 1994;118:707-11.  Back to cited text no. 4
Bakhshi S, Meel R, Kashyap S, Sharma S. Bone marrow aspirations and lumbar punctures in retinoblastoma at diagnosis: Correlation with IRSS staging. J Pediatr Hematol Oncol 2011;33:e182-5.  Back to cited text no. 5
Azar D, Donaldson C, Dalla-Pozza L. Questioning the need for routine bone marrow aspiration and lumbar puncture in patients with retinoblastoma. Clin Exp Ophthalmol 2003;31:57-60.  Back to cited text no. 6
Pratt CB, Meyer D, Chenaille P, Crom DB. The use of bone marrow aspirations and lumbar punctures at the time of diagnosis of retinoblastoma. J Clin Oncol 1989;7:140-3.  Back to cited text no. 7
Linn Murphree A. Intraocular retinoblastoma: The case for a new group classification. Ophthalmol Clin North Am 2005;18:41-53, viii.  Back to cited text no. 8
Chantada G, Doz F, Antoneli CB, Grundy R, Clare Stannard FF, Dunkel IJ, et al. A proposal for an international retinoblastoma staging system. Pediatr Blood Cancer 2006;47:801-5.  Back to cited text no. 9
Guidelines for the Management of Children with Advanced Unilateral Retinoblastoma Following Primary Enucleation V2.0. Children's Cancer and Leukaemia Group (CCLG). Retinoblastoma Special Interest Group; May, 2015. Available from: http://www.cclg.org.uk/clinical-information/treatment-guidelines. [Last accessed on 2017 Jan 29].  Back to cited text no. 10
Moscinski LC, Pendergrass TW, Weiss A, Hvizdala E, Buckley KS, Kalina RE, et al. Recommendations for the use of routine bone marrow aspiration and lumbar punctures in the follow-up of patients with retinoblastoma. J Pediatr Hematol Oncol 1996;18:130-4.  Back to cited text no. 11
Laurent VE, Torbidoni AV, Sampor C, Ottaviani D, Vazquez V, Gabri MR, et al. Minimal disseminated disease in nonmetastatic retinoblastoma with high-risk pathologic features and association with disease-free survival. JAMA Ophthalmol 2016;134:1374-9.  Back to cited text no. 12
Laurent VE, Sampor C, Solernou V, Rossi J, Gabri M, Eandi-Eberle S, et al. Detection of minimally disseminated disease in the cerebrospinal fluid of children with high-risk retinoblastoma by reverse transcriptase-polymerase chain reaction for GD2 synthase mRNA. Eur J Cancer 2013;49:2892-9.  Back to cited text no. 13

Correspondence Address:
Deepak Bansal
Department of Pediatrics, Advanced Pediatrics Center, Pediatric Hematology-Oncology Unit, Postgraduate Institute of Medical Education and Research, Chandigarh - 160 012
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPM.IJPM_475_17

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