Tuesday, December 27, 2005



NOTE: For all surgically enucleated eyes, call the attending pathologist to determine the best way to work up the case. Never proceed on your own without consultation.
If a normal eye, or eyes with suspected melanoma or retinoblastoma, are being removed, it is imperative to have tissue frozen, so alert the attending pathologist when you anticipate a specimen being removed. It is very poor form to call the pathologist after the eye has been received or fixed. In certain cases, patients may have legal grounds for a law suit if the appropriate studies are not performed because of mishandling.
If eyes arrive in formalin and have been fixed for 2 days, wash them in water to remove the formalin ( 2 changes about 5 minutes each) and place them in enough 50% ethanol to cover the eye. Let the eye equilibrate overnight. Change the alcohol the next day and equilibrate for a second day. The eye should return to a normal volume and should not be indented or shrunken. For sectioning the eye it is best to wait 2 days with the eye in 50% ethanol .
Surgically-enucleated eyes (as well as eviscerations and exenterations) must be accompanied by a detailed written clinical history before the work-up is undertaken. Eyes that are enucleated in the JSEI O.R. will be accompanied by a complete history. Be sure that you have sufficient clinical history prior to processing the eye.

Gross The gross description should include the following:
a. complete a diagram by filling out a Gross Description Form for the appropriate eye. This will be invaluable for your description. Put appropriate measurements of the eye, tumor or pathologic processes on this form. There is a different form for coronal cuts.
b. completion of a standard Enucleation Form. (Note that there are separate forms for melanoma and retinoblastoma)
c. photography will often be required

The standard format for microscopic description are included in the Enucleation Form. Examples of completed work-ups are provided. The work-up of a surgically enucleated eye is essentially a mini-autopsy and the following few tips may be helpful. Study the sections with a clear understanding of the clinical history (you will virtually always need more information than provided on the Pathology Consultation Request form), the gross features, and how the eye was microsectioned (step levels, etc., see technologist). Your written narrative description should follow this general plan:

(1) Begin with a comment of the condition of the eye as viewed without optical aids (e.g. normal size, shape, large tumor, retinal detachment, etc.).
(2) Next, describe the most important lesion in the eye (e.g. tumor, retinal detachment, wound, etc.) beginning with low power observations, and adding additional details as needed with higher magnification.
(3) Add descriptions of secondary lesions.
(4) Briefly mention other important ocular structures or areas, even if negative.
(5) If the eye has some general condition which is diffusely involved (for example, in phthisis bulbi) one may elect to sequentially discuss ocular structures or areas (e.g. cornea, anterior chamber, chamber angle, etc.).

This should be comprehensive and should begin with a succinct clinical summary. Remember that in old cases only the diagnosis is stored in the computer: Therefore, one must repeat in the diagnosis all the important aspects already discussed in the narrative description. For example:

FINAL DIAGNOSIS: Eye, "OS" (enucleation)
- Atrophy with shrinkage and disorganization (Phthisis bulbi)
- Corneoscleral scar, superotemporal, healed
- Peripheral anterior synechiae, 360, old
- Rubeosis iridis and ectropion uvea, moderately severe
- Retinal detachment, total, with both epiretinal and retroretinal membranes.

Surgically-enucleated eyes suspected of harboring neoplasms are treated in the following manner:

Melanomas --- use “Melanoma Form”.

A careful external examination must be done before any extraocular tissue is disturbed or removed. Remember if eyes come to you in fixative, you must first wash them in water to remove the formalin and place them in 50% ethanol for at least 30 minutes before external examination; 30 minutes is not ideal but can be used to expedite processing if absolutely necessary. However, the eye should have equilibrated to a normal volume and should not be indented or shrunken. For sectioning the eye it is best to wait 2 days with the eye in 50% ethanol . Alcohol will restore natural color and will facilitate distinguishing pigmented tumor tissue from blood clot. You may decide to do a careful dissection of the episcleral tissue outlying the known location of the tumor, but all tissue should be saved. In general, melanomas reach the episclera and the orbit through scleral canals that have a fairly predictable location (anterior ciliary vessels, vortex veins, short and long posterior ciliary arteries and nerves). These regions should receive especially close examination with the stereomicroscope. See below for processing vortex veins.

Transillumination should be done next. This is accomplished in our laboratory using the examination light fitted with a cardboard box to hold the eye. Examination is facilitated by turning off the room lights. When the intraocular tumor has been located, its margins may be marked with a ball-point pen, with delicate dots of India ink, or with dots of marking ink. These marks will assist you in planning an incision to transect the tumor when the room lights are on. In most cases, the incision to open the eye will be made postero-anteriorly in a plane that will pass through the edge of the tumor.

In general when the eye is to be processed rapidly in order to obtain a preliminary diagnosis, the vortex veins are removed from the episclera and the optic is transected 2 mm from the sclera and these pieces are sent separately. Sometimes, a small piece of tumor in the small calotte can be submitted immediately in order that tissue diagnosis may be rendered the following day. The large calotte can be held for photography, teaching, etc. The brief preliminary report from the microscopic examination of the piece of tumor in the small calotte will amount to little more than a tissue diagnosis. The report is written with a very short gross description, a brief microscopic description of the tumor, and a diagnosis, e.g.;

FINAL DIAGNOSIS: Eye, "OS" (enucleation)- choroidal malignant melanoma (spindle-cell type)

Comment- Complete report of the gross and microscopic findings in the large calotte will follow.

Once the preliminary report of the tumor in the small calotte is completed, the work-up of the remainder of the eye may be conducted at a more leisurely pace, and the specimen may be used for individual instruction and the daily gross conference. When the work-up of the large calotte has been completed and reviewed (signed) by the senior pathologist, the eye is submitted for step-level sectioning completely through the tumor.

Microscopic study should include an analysis of all step-levels (which the technologist will number for reference), but the narrative will be written as a synthesis of the information gained by step-level study. During the gross and microscopic study, the pathologist must anticipate the important questions asked by the surgeon and answer these questions with positive or negative statements in the narrative work-up.

The diagnosis for whole surgical eyes is necessarily more comprehensive than for simpler specimens. It is initiated with a succinct clinical history containing relevant information. In the case of eyes with melanomas, one should then elaborate on the preliminary diagnosis to include the predominant cell type, spindle or epithelioid cells in the tumor (if any), relative size of the tumor, presence or absence of extraocular extension, the vascular pattern (or pattern of vasculogenic mimicry), retinal invasion, emissarial invasion, vitreous involvement etc. Incidental diagnoses (retinal detachment, etc.) should be succinctly characterized to complete the diagnosis.

Example of a melanoma work-up:
Gross Description: Specimen, in formalin, labeled "left eye" consists of an intact left eye measuring 24.0 mm (AP) x 23.5 mm (H) x 25 mm (V) with 1.5 mm of attached optic nerve. The cornea measures 13.0 (H) x 12.0 (V), and the pupil is round and measures 7 mm in diameter. No melanin pigmentation is seen on the episcleral surface. Vortex veins are slightly dilated directly over the tumor, but no hyperpigmentation lesions are seen over these vessels. Transillumination reveals a tumor measuring 19 mm in greatest diameter and extending 7 mm from the optic nerve anteriorly to the pars plana. Horizontal section above the optic nerve reveals a pigmented tumor, 19 mm (diameter) x 12 mm (elevation) in the ciliary body and choroid temporal to the optic nerve. A large serous retinal detachment obscures the posterior boundaries of the tumor. The macula is markedly distorted and the optic nerve is obscured. The tumor lies adjacent to and touches the cataractous lens. The anterior chamber is shallow. There is pigment on the posterior lens surface and a Vossius ring on the anterior capsule. The retina adjacent to the tumor shows areas of punctate superficial pigmentation that follow the distribution of retinal vessels. There is a large coronal adenoma in the ciliary process at 6 o'clock. The peripheral retina shows typical cystoid degeneration.

Microscopic: Sections show a large choroidal tumor composed of predominantly spindled cells with small areas of epithelioid cells containing brown pigment. The spindle cells are arranged in fascicles and contain oval nuclei with small nucleoli. There are occasional areas that contain cells with more abundant cytoplasm and round nuclei with prominent nucleoli. There is broad front invasion of the sclera. The vortex vein centered over the tumor contains extensive melanoma attached to its wall and following both its intrascleral and episcleral course. The retina overlying the tumor shows a serous detachment and exhibits extensive degeneration of photoreceptors including inner and outer segments. There are numerous macrophages with foamy cytoplasm in this area. Within the tumor blood vessels form a pattern of back to back loops. Retinal pigment epithelial drusen are present. Incidental findings include corneal epithelial edema, extensive actinic degeneration of collagen at the limbus, a tumor composed of non pigmented epithelial cells and myxoid stroma confined to the ciliary processes, and typical cystoid degeneration.

FINAL DIAGNOSIS: Eye, "OS" (enucleation)- Choroidal malignant melanoma, mixed cell type (spindle predominant).
-Extensive tumor present in vortex vein
-Serous retinal detachment
-Coronal adenoma of pars plicata

Retinoblastomas -- use “Retinoblastoma Form”

The work-up for eyes harboring retinoblastomas is identical to that used for melanomas or any other intraocular tumor except:
1) If the history is suggestive and/or the patient's family and physician wishes, special genetic studies are done to determine the likelihood of a new or inherited defect. These tests are done on specially-prepared samples and they must be fresh. This is done in conjunction with the attending pathologist.
2) Since the retinoblastoma tumor is often friable, one should measure and remove the optic nerve before opening the eye to prevent floating tumor fragments from "contaminating" the nerve.

A piece of the tumor (usually from the small calotte) and the optic nerve should be sent through in paraffin on the day (or the day following) the enucleation. The entire optic nerve should be embedded, and sectioning should assess the nerve 1-2mm behind the eye and at the cranial (surgical) margin, if indicated. If the intraocular tumor involves the optic disc or choroid (extensively), the large calotte should be sent through soon after the gross work-up.

There is a special data sheet for eyes with retinoblastoma that will serve as a check list to be sure that all morphological features important for the prognosis are assessed.

An example:
Gross: The specimen received in formalin, labeled left eye, consists of a left eye that measures 25mm (V) x 25 mm (H) x 25 mm (AP). The cornea measures 10 mm (V) x 9 mm (H). The pupil is not visible and 4 mm of optic nerve is attached. The eye shows poor transillumination. The anterior chamber is not visible externally and the cornea is opaque. The conjunctiva is markedly elevated superiorly with numerous dilated vessels. The cross section of the optic nerve is distorted by crush artifact. The eye is cut vertically temporal to the optic nerve. Descemet's membrane is wrinkled superiorly. The anterior chamber is filled with a fibrous and fibrinous exudate the obscures ocular structures. The iris and ciliary body are covered by a fibrous membrane that extends into the vitreous cavity. No intraocular lens is visible. The vitreous cavity is filled with pus. The retina is detached posteriorly and there is a thick white subretinal exudate. There is a focal area of pigmentation in this area. The retina is not discernible in many areas. The ciliary body is thickened in focal areas.
Micro: Microscopic sections show severe acute and chronic inflammation in the anterior chamber, cornea, conjunctiva and sclera. The cornea shows absence of the corneal epithelium, neutrophils present between stromal lamellae, and focal marked necrosis. Descemet's membrane is detached in areas and there is a large wound gape superiorly in which lies inflammatory tissue composed of neutrophils, lymphocytes, plasma cells, mast cells, histiocytes, and fibrovascular tissue. The conjunctiva covers the separation of the corneal wound edges. The cornea is focally necrotic at the edges of the wound gape. The anterior chamber is distorted and filled with acute and chronic inflammatory cells, and granulation tissue. The iris is disrupted and necrotic. The intraocular lens and haptics are located in the posterior chamber and surrounded by inflammatory tissue. The lens capsule surrounds the synthetic intraocular lens. There are multinucleated giant cells and focal granulomatous inflammation surrounding the capsule. Blue staining amorphous material is present at the cataract wound site and in the vitreous. The ciliary body is markedly inflamed with acute inflammatory cells. The vitreous cavity is filled with fibrinous exudate and inflammatory cells. There are numerous ghost cells and foamy macrophages in the vitreous cavity. The retina shows complete exudative detachment and marked necrosis with complete loss of photoreceptors in most areas. There is a extensive subretinal fibrous membrane. The pigment epithelium and Bruch's membrane are focally disrupted. The choroid shows marked infiltration by lymphocytes, plasma cells and histiocytes. Numerous lymphocytes are present along blood vessels (Virchow Robin spaces) in the optic nerve posterior to the lamina cribrosa. Gram stains show occasional gram positive clusters of coccoid forms and a few clusters of gram negative forms in the inflamed tissue of the anterior segment.
Diagnosis: Eye, "OS" (enucleation)- Clinical history of cataract surgery, one month prior to enucleation--Severe acute and chronic endophthalmitis
-Exudative retinal detachment
-Subretinal fibrous membrane
-Wound gape
-Pseudophakia, Intraocular posterior chamber lens



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