Oman Journal of Ophthalmology

: 2016  |  Volume : 9  |  Issue : 2  |  Page : 116--118

Acute lymphoblastic leukemia as second primary tumor in a patient with retinoblastoma

Anasua Ganguly1, Swathi Kaliki1, Faraz Ali Mohammad1, Dilip K Mishra2, S Vanajakshi3, Vijay Anand Reddy1,  
1 Ocular Oncology Service, The Operation Eyesight Universal Institute for Eye Cancer, L. V. Prasad Eye Institute, Hyderabad, India
2 Ophthalmic Pathology Services, L. V. Prasad Eye Institute, Hyderabad, India
3 Department of Pathology, Apollo Health City, Hyderabad, India

Correspondence Address:
Swathi Kaliki
The Operation Eyesight Universal Institute for Eye Cancer, L. V. Prasad Eye Institute, Hyderabad - 500 034, Telangana


Second primary tumor (SPT) is defined as a second tumor that presents either simultaneously or after the diagnosis of an index tumor. Second primary malignancies are the leading cause of death in patients with heritable retinoblastoma (RB). Acute lymphoblastic leukemia (ALL), as SPT in RB patients, is extremely rare. To the best of our knowledge, only five cases of ALL as SPT in patients with RB has been documented in the literature. Herein, we report a case of a 6-year-old girl with bilateral RB, who developed ALL during the course of treatment of RB. This case highlights the importance of reviewing blood investigations regularly to diagnose leukemia as SPT in RB and also the necessity for proper counseling and lifelong follow-up in these patients.

How to cite this article:
Ganguly A, Kaliki S, Mohammad FA, Mishra DK, Vanajakshi S, Reddy VA. Acute lymphoblastic leukemia as second primary tumor in a patient with retinoblastoma.Oman J Ophthalmol 2016;9:116-118

How to cite this URL:
Ganguly A, Kaliki S, Mohammad FA, Mishra DK, Vanajakshi S, Reddy VA. Acute lymphoblastic leukemia as second primary tumor in a patient with retinoblastoma. Oman J Ophthalmol [serial online] 2016 [cited 2019 Nov 15 ];9:116-118
Available from:

Full Text


The improvement in diagnosis and treatment of retinoblastoma (RB) has increased the survival rates and most RB patients survive the disease and live into adulthood. Consequently, second primary nonocular tumors (SPT) are now the leading cause of death in patients with heritable RB. This high incidence of SPT inheritable RB is due to the presence of germline mutation of the RB1 gene in chromosome 13q14 in all the body cells. Thus, the initial step of oncogenesis is already present in all body cells from which the second cancer can eventually develop.

Leukemias as SPT in RB patients is less frequent. [1] To the best of our knowledge, there are only five cases of acute lymphoblastic leukemia (ALL) reported in the literature. [2],[3],[4] Herein, we report a rare, unusual case of a child with RB presenting with ALL as SPT within a very short span of initiation of treatment.

 Case Report

A 6-year-old girl presented to us with painless diminution of vision in both eyes since 10 days. She was the first child born out of a nonconsanguineous marriage. There was a history of death due to malignancy in maternal aunt and grandmother, further details of which were not available. The best-corrected visual acuity was 20/126 in the right eye and counting finger close to face in left eye. Pupillary reflexes were sluggish in both eyes. On examination under anesthesia, the anterior segment of both eyes was unremarkable. Fundus examination revealed bilateral exophytic and endophytic white mass filling the vitreous cavity with diffuse vitreous and subretinal seeds and total retinal detachment [Figure 1]a and b. B-scan ultrasonography confirmed the presence of bilateral acoustically dense intraocular mass with calcification [Figure 1]c and d. Computed tomography scan of orbit also showed the same [Figure 1]e and f. Peripheral blood smear, bone marrow aspiration [Figure 1]g and h, and cerebrospinal fluid cytology were within normal limits. Based on these clinical and radiological findings, a diagnosis of bilateral RB Group D (International Classification of RB) was made. The patient was started on high-dose chemotherapy (HDC) (vincristine, etoposide, and carboplatin) along with concurrent periocular carboplatin (POC) (20 mg/2 ml) injections. After completion of six cycles of HDC, there was a partial regression of main tumors with persistence of subretinal and vitreous seeds in both eyes [Figure 2]a and b. Owing to suboptimal response, another three cycles of HDC with concurrent bilateral POC injections were continued. Post nine cycles of HDC, persistent of subretinal and vitreous seeds were noted in both eyes [Figure 2]c and d, and three more sessions of bilateral POC injection were planned. Examination under anesthesia after two sessions of POC revealed the recurrence of vitreous and subretinal seeds in both eyes [Figure 2]e and f. In view of worsening, the patient was advised to undergo bilateral orbital external beam radiotherapy (EBRT) 4600 cGy in 23 fractions (200 cGy/fraction). However, after receiving 15 fractions, the child had an episode of epistaxis. A complete blood count revealed a white blood cell count of 400,000 cells/mm 3 and a platelet count of 55,000 cells/mm 3 . Peripheral blood smear showed lymphoblasts with Romanowsky stain which were not showing block positivity for periodic acid-Schiff stain and not staining with myeloperoxidase stain [Figure 3]a and b. Flowcytometry confirmed the diagnosis of pro-B-ALL [Figure 3]c-j. This confirmed the diagnosis of SPT of leukemia in this child. The child received systemic chemotherapy for leukemia. At 1-year follow-up, the child is doing well with complete remission of leukemia with no leukemic cells in peripheral blood smear or bone marrow. The RB in both eyes is regressed, and the child is on close follow-up.{Figure 1}{Figure 2}{Figure 3}


SPT is defined as a second tumor that presents either simultaneously or after the diagnosis of an index tumor. Mutational inactivation of both alleles of the RB1 tumor suppressor gene in the developing retina initiates RB. About 40% of RB patients have a hereditary predisposition caused by heterozygous germline mutation in the RB1 gene. [5] These children who survive heritable RB are at a high risk for developing and dying from subsequent SPTs. EBRT administered before the age of 12 months is known to increase this risk. [6] Our patient had bilateral RB and thus suggestive of heritable RB and at risk for SPTs. The first publication in this regard was by Reese et al. in 1949 where he had attributed the second malignancy to radiation alone. [7] Subsequent studies demonstrated that second tumors developed in 14% of bilateral RB patients who underwent enucleation without irradiation. Although the occurrence of these tumors is well recognized, there is controversy regarding their incidence because all the studies differ substantially. Cohort studies have shown the cumulative incidence of second cancer at 50 years after diagnosis of heritable RB to be 36-51% compared with 5-5.7% after nonheritable RB. [8]

Chemotherapy-induced leukemia in RB patients is well documented in literature. Gombos et al. found 15 cases of secondary acute myeloid leukemia (AML) in patients who received chemotherapy for RB. [9] Turaka et al. reported only one case of AML in 245 patients with RB-treated with chemotherapy. [10] It is interesting to note that there are no documented cases of ALL secondary to chemotherapy in literature. The diagnosis of chemotherapy-induced leukemia was less likely in our case since the interval between completion of chemotherapy and onset of disease was <2.5 months.

Leukemia, as SPT, is very rare with a reported incidence of 2.4%. [1] To the best of our knowledge, only five cases of ALL as SPT to RB has been reported. [2],[3],[4] Hoefnagel et al. reported a case of ALL 8 years after only surgical treatment of a patient with unilateral RB. [2] Abramson reported a case of ALL in a patient with unilateral disease among 711 patients with RB. [3] Woo and Harbour did a literature review of 676 published cases of SPTs in patients with RB and found only five cases of ALL. [4] The reason behind chemotherapy inducing only AML and not ALL is unclear. Interplay of factors such as tumor biology, type of RB1 gene defect, chemotherapy, radiotherapy, and age at presentation could have influenced the development of ALL in our patient. Thus, lifelong follow-up of all heritable RB survivors with regular review of blood investigations with knowledge of the condition helps in establishing the diagnosis.

Financial support and sponsorship

Support provided by Operation Eyesight Institute for Eye Cancer (SK) and Hyderabad Eye Research Foundation (SK), Hyderabad, India.

Conflicts of interest

There are no conflicts of interest.


1Moll AC, Imhof SM, Bouter LM, Tan KE. Second primary tumors in patients with retinoblastoma. A review of the literature. Ophthalmic Genet 1997;18:27-34.
2Hoefnagel D, McIntyre OR, Storrs RC, Sullivan PB, Maurer LH. Retinoblastoma followed by acute lymphoblastic leukemia. Lancet 1973;1:725.
3Abramson DH, Ellsworth RM, Kitchin FD, Tung G. Second nonocular tumors in retinoblastoma survivors. Are they radiation-induced? Ophthalmology 1984;91:1351-5.
4Woo KI, Harbour JW. Review of 676 second primary tumors in patients with retinoblastoma: Association between age at onset and tumor type. Arch Ophthalmol 2010;128:865-70.
5Dommering CJ, Marees T, van der Hout AH, Imhof SM, Meijers-Heijboer H, Ringens PJ, et al. RB1 mutations and second primary malignancies after hereditary retinoblastoma. Fam Cancer 2012;11:225-33.
6Kleinerman RA, Yu CL, Little MP, Li Y, Abramson D, Seddon J, et al. Variation of second cancer risk by family history of retinoblastoma among long-term survivors. J Clin Oncol 2012;30:950-7.
7Reese AB, Merriam GR Jr., Martin HE. Treatment of bilateral retinoblastoma by irradiation and surgery; report on 15-year results. Am J Ophthalmol 1949;32:175-90.
8Chan MP, Hungerford JL, Kingston JE, Plowman PN. Salvage external beam radiotherapy after failed primary chemotherapy for bilateral retinoblastoma: Rate of eye and vision preservation. Br J Ophthalmol 2009;93:891-4.
9Gombos DS, Hungerford J, Abramson DH, Kingston J, Chantada G, Dunkel IJ, et al. Secondary acute myelogenous leukemia in patients with retinoblastoma: Is chemotherapy a factor? Ophthalmology 2007;114:1378-83.
10Turaka K, Shields CL, Meadows AT, Leahey A. Second malignant neoplasms following chemoreduction with carboplatin, etoposide, and vincristine in 245 patients with intraocular retinoblastoma. Pediatr Blood Cancer 2012;59:121-5.