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Retinoblastoma Treatment (PDQ®)

Health Professional Version
Last Modified: 10/24/2014

Tumor Pathology of Retinoblastoma

Retinoblastoma arises from the photoreceptor elements of the inner layer of the retina. Microscopically, the appearance of retinoblastoma depends on the degree of differentiation. Undifferentiated retinoblastoma is composed of small, round, densely packed cells with hypochromatic nuclei and scant cytoplasm. Several degrees of photoreceptor differentiation have been described and are characterized by distinctive arrangements of tumor cells. The Flexner-Wintersteiner rosettes are specific for retinoblastoma; these structures consist of a cluster of low, columnar cells arranged around a central lumen that is bounded by an eosinophilic membrane analogous to the external membrane of the normal retina. The lumen contains an acid mucopolysaccharide similar to that found around normal rods and cones. These rosettes are seen in 70% of tumors. Homer-Wright rosettes, on the other hand, are composed of irregular circlets of tumor cells arranged around a tangle of fibrils with no lumen or internal-limiting membrane. Horner-Wright rosettes are infrequently seen in retinoblastoma and are most often seen in other neuroblastic tumors, such as neuroblastoma and medulloblastoma.

Retinoblastomas are characterized by marked cell proliferation, as evidenced by high mitosis counts, extremely high MIB-1 labeling indices, and strong diffuse nuclear immunoreactivity for cone-rod homeobox, also known as CRX, a useful marker to discriminate retinoblastoma from other malignant, small, round cell tumors.[1,2]

Cavitary retinoblastoma, a rare variant of retinoblastoma, has ophthalmoscopically visible lucent cavities within the tumor. The cavitary spaces appear hollow on ultrasonography and hypofluorescent on angiography. Histopathologically, the cavitary spaces have been shown to represent areas of photoreceptor differentiation.[3] These tumors have been associated with minimal visible tumor response to chemotherapy, which is thought to be a sign of tumor differentiation.[4]

References
  1. Terry J, Calicchio ML, Rodriguez-Galindo C, et al.: Immunohistochemical expression of CRX in extracranial malignant small round cell tumors. Am J Surg Pathol 36 (8): 1165-9, 2012.  [PUBMED Abstract]

  2. Schwimer CJ, Prayson RA: Clinicopathologic study of retinoblastoma including MIB-1, p53, and CD99 immunohistochemistry. Ann Diagn Pathol 5 (3): 148-54, 2001.  [PUBMED Abstract]

  3. Palamar M, Pirondini C, Shields CL, et al.: Cavitary retinoblastoma: ultrasonographic and fluorescein angiographic findings in 3 cases. Arch Ophthalmol 126 (11): 1598-600, 2008.  [PUBMED Abstract]

  4. Mashayekhi A, Shields CL, Eagle RC Jr, et al.: Cavitary changes in retinoblastoma: relationship to chemoresistance. Ophthalmology 112 (6): 1145-50, 2005.  [PUBMED Abstract]