9.10  Histopathology Analysis SOP

9.10.1  Objectives

Confirmation of the clinical diagnosis of retinoblastoma; determination of risk for tumor extension beyond the eye.

9.10.2  Applicability

Pathologist, ophthalmologist, oncologist.

9.10.3  Scope

Accurate description of the extent of retinoblastoma in the eye.

9.10.4  Clinical Significance

Histopathological examination determines the diagnosis and evaluates the risk of extraocular tumor spread:

•The most common and dangerous route of metastasis is direct extension into the optic nerve [37, 38], with tumor cells growing toward the optic chiasm and beyond, or into the subarachnoid space into the leptomeninges.

•Systemic metastases occur via choroid invasion or aqueous drainage, particularly if glaucoma is present­ [39].

•Direct extension through the sclera or along the ciliary vessels and nerves may occur.

disease involving anterior chamber, iris, ciliary body, and lens, and extension beyond ora serrata).

•A central papillary-optic nerve calotte is submitted for sectioning and H&E staining. Serial sections through the optic nerve head, if the tumor is near the optic nerve, are examined, to determine if the tumor invades past the cribriform plate, and the distance of the tumor extension into the optic nerve (Fig. 9.12b). The separated optic nerve specimen is sectioned to evaluate the nerve fibers and evidence of tumor in the nerve or meninges.

9.10.6  Consequences

Inaccurate pathological evaluation may lead to inadequate treatment and death. Overestimation of the disease extent may lead to unnecessary invasive treatment.

9.10.7  Related SOPs

PATH gross; PATH microscopic; OPTHO extraocular retinoblastoma.

9.11  Cryotherapy SOP

9.11.1  Objectives

Physical ablation of small retinoblastoma; increased intraocular penetration of chemotherapy.

9.11.2  Applicability

Ophthalmologist, oncologist

•Gross examination of the specimen evaluates the risk or actual evidence of extraocular disease (choroid­ and sclera involvement, anterior segment

•Treatment of small peripheral retinoblastoma primarily, or after other therapy.

Fig. 9.12  Asymmetric presentation in a 4 year-old-girl with bilateral retinoblastoma. (a) The right side showing IIRC Group A with seven small tumors located close to the ora serrata, which appeared like white-with-pressure until they were actually depressed, making the tumor elevation evident. (b) Histopathology slide of the enucleated left eye shows massive choroidal invasion and tumor

extension 3 mm beyond the lamina cribrosa (pT2b). Although prophylactic­ chemotherapy and bone marrow aspiration and cerebrospinal fluid examination every 2 months were recommended, the child was lost to follow-up until she returned with metastatic disease that was fatal (images by Carmelina Trimboli and Dr. William Halliday)

•Cutting-cryotherapy for posterior retinoblastoma refractory to laser focal therapy.

•Prechemotherapy cryotherapy 24–48 h before chemotherapy to increase drug penetration [40].

9.11.4  Clinical Significance

•Traditional therapeutic transcleral cryotherapy can eradicate small tumors up to 4 mm dimension, which are located at or anterior to the equator (IIRC Groups A and some B).

•For residual tumor masses after systemic chemotherapy (IIRC Groups B, C, and D).

•For small recurrences, and sometimes treatment of vitreous seeding close to tumor masses that can be included in the freeze application.

9.11.5  Procedure

•Transcleral cryotherapy:

−−Requires adequate visualization of the tumor mass with indirect ophthalmoscopy or RetCam® imaging while indenting the area to be treated with the cryo-probe (Fig. 9.13).

−−Triple freeze–thaw cycles are applied in each session to physically destroy the tumor. The tumor should be completely encased by the ice ball (Fig. 9.13b–d). Complete thawing for at least a full minute between successive freezes is important for the destruction of the tumor cells during the thaw phase.

−−No more than four different sites should be frozen in each session, in no more than two quadrants. Repeat treatment in consecutive EUAs every 4–6 weeks until no residual active tumor is found.