Introduction

Malignancies that exhibit peaks in incidence, in children younger than age 10 years, ALL, neuroblastoma, Wilms tumor, hepatoblastoma, retinoblastoma, rhabdomyosarcoma, Ewing sarcoma etc Histologically, many of the malignant non-hematopoietic pediatric neoplasms are unique.

In general, they tend to have a more primitive (embryonal) undifferentiated appearance and are often characterized by sheets of cells with small, round nuclei, childhood tumours have been collectively referred to as their malignant small round blue cell tumors, due to their primitive histologic appearance.[ 1],[2]

The most common paediatric intraocular malignant neoplasm is retinoblastoma[3]. Assessing the bone marrow status of newly diagnosed patients is essential for management and prognosis. Here we discuss 6 such cases of Retinoblastoma involving bone marrow and their clinical presentation, management and prognosis.

This study aimed to give an overview of the disease along with the utility of bone marrow examination in cases of retinoblastoma. Early diagnosis, advancements in management and follow-up of the cases have resulted in improved eye and vision salvage. Retinoblastoma(RB) is an intraocular malignant neoplasm which is most commonly seen in children.[3]

cell of origin neuronal progenitor. Around 40% of retinoblastomas have an inherited germline mutated RB gene allele. It is usually diagnosed by 5 years of age[3].

The overall survival rate in patients diagnosed early and with localized intraocular disease exceeds 95% however, in developing countries delayed diagnoses and treatment are common and may lead to extra-ocular and distant metastases.

The sites of distant metastases in Retinoblastoma include the central nervous system, bone marrow, bone, lymph nodes, and other organs [4 ] Older age at diagnosis and advanced tumor stage are independent risk factors which are associated with the worst prognosis [4,5 ] Here we present 16 such cases of Retinoblastoma. 6 cases came to our institute at an advanced stage of disease with bone marrow involvement at presentation.

Table 2: bone marrow involvement of RB among pediatric patients

Male preponderance was noted. The most common manifestation of Retinoblastoma is Leukocoria (fig1,2,3,4 ),

Figure: 1,2,3,4 showing Leukocoria. , a reflection of light by the white mass in the fundus

Tumor growth can be Endophytic,tumor grows into the vitreous cavity, exophytic in which tumor grows towards sub retinal space, or it could be a diffuse infiltrating tumor.[ 3],[4 ] In 1971 Knudson proposed the two-hit hypothesis. In hereditary RB the initial hit is a germinal mutation, found in all cells, and the second hit in somatic retinal cells leading to RB In unilateral retinoblastomas 15% are caused by germinal mutations, while rest, the majority are sporadic Pathology of retinoblastoma both hereditary sporadic are identical. Tumor may contain both differentiated and undifferentiated elements, on H& E.undifferentiated appear as small round cells with hyperchromatic nuclei. Well-differentiated tumors have Flener-Wintersteiner rosettes, arrangements of a single layer of tumor cells around a lumen .dystrophic calcification might be seen. The diagnosis of Retinoblastoma is done by examination of the eye under anesthesia. Imaging of the brain and orbits is also done to evaluate the extent of the spread of tumour. Bone marrow examination and cerebrospinal fluid (CSF) analysis are done to rule out the systemic spread in cases of extraocular Retinoblastoma. The most common metastatic site of RB is the intracranial area, accounting for approximately half of cases. Bone is the second most common site. [ 4],[5],[6],[7 ]

.Anaemia was the common abnormality due to bone marrow involvement, the leucopenia/neutropenia and thrombocytopenia followed respectively. Pancytopenia was found in 2 children. Normal blood picture, in the majority of patients, confirmed hematological abnormality may not be always present in bone marrow metastasisRetinoblastoma has to be differentiated from, endophthalmitis retinal dysplasia retinal detachment, vitreous haemorrhage, Coats' disease, and toxocariasis [8],[9] The incidence of retinoblastoma is constant worldwide at 1 in every 16,000 live births. Retinoblastoma is the most common eye cancer in children. It arises in the developing retina, part of the central nervous system (CNS). Thus, retinoblastoma is a CNS cancer viewable from the outside. Medical diagnosis of retinoblastoma is based on the clinical features of the tumors visible in the eye upon dilation of the pupil. This differs from the diagnosis of other cancers, where histological confirmation via biopsy is usually required. Biopsy of retinoblastoma is not recommended, as it can induce seeding and extraocular spread along the needle tract.[3],[8]

Differential diagnosis includes other small round blue cell tumours like Ewing’s sarcoma. The probability of a second primary tumour is higher in cases of hereditary Retinoblastoma if radiotherapy is used for treatment.[14] ⁾ None of the cases in the current study, had prior radiotherapy history.

A thorough clinical evaluation, along with B scan ultrasonography aids in diagnosis.[ 14],[18] CT/MRI gives the detail of intra/extracranial spread. Intraocular RB is treated by cryotherapy trans scleral thermos therapy, external beam radiotherapy, enucleation etc. Treatment of metastatic Retinoblastoma is challenging as it has poor prognosis, low survival and high recurrence.

Systemic Chemotherapy along with surgery, intrathecal chemotherapy, radiotherapy, and hematopoietic stem cell transplantation is considered effective in the management of such cases[16.17,18]. Early detection of retinoblastoma, standardized treatment protocols and long-term follow-up are essential to improve the prognosis.

Conclusion

The risk of death in patients with Retinoblastoma is increased in those who present with metastatic disease.A diligent and exhaustive search for metastatic cells in Bonemarrow helps in treatment and prognosis.

Retinoblastoma though not frequent, are not so rare. A diligent search of metastatic cells and the Use of immunohistochemistry markers on bone marrow biopsies may result in a higher detection rate primary goal of RB treatment is to save the patient's life, salvage of the eye and vision are secondary goals, need a multidisciplinary team approach.

reduction in the rate of systemic metastasis by identification of high-risk factors and appropriate adjuvant therapy improves survival.

Abbreviations: SRCT: small round cell tumours, RB: Retinoblastoma

Permission from Institutional Research Board (IRB): Yes

Funding: Nil

Conflicts of interest:none