This protocol is intended to assist pathologists in providing clinically useful and relevant information as a result of the examination of surgical specimens. Use of this protocol is intended to be entirely voluntary. If equally valid protocols or similar documents are applicable, the pathologist is, of course, free to follow those authorities. Indeed, the ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of the individual circumstances presented by a specific patient or specimen.
It should be understood that adherence to this protocol will not guarantee a successful result. Nevertheless, pathologists are urged to familiarize themselves with the document. Should a physician choose to deviate from the protocol based on the circumstances of a particular patient or specimen, the physician is advised to make a contemporaneous written notation of the reason for the procedure followed.
The College recognizes that this document may be used by hospitals, attorneys, managed care organizations, insurance carriers, and other payers. However, the document was developed solely as a tool to assist pathologists in the diagnostic process by providing information that reflects the state of relevant medical knowledge at the time the protocol was first published. It was not developed for credentialing, litigation, or reimbursement purposes. The College cautions that any uses of the protocol for these purposes involve considerations that are beyond the scope of this document.
PROTOCOL FOR THE EXAMINATION OF SPECIMENS FROM PATIENTS WITH UVEAL MELANOMA
I. Cytologic Material
A. Clinical information
1. Patient identification
a. Name
b. Identification number
c. Age (birth date)
d. Gender
2. Responsible physician(s)
3. Date of procedure
4. Other clinical information
a. Relevant history
(1) Clinical findings
(2) Past ocular history
(3) Previous ocular surgery
(4) Previous treatment
b. Relevant findings (eg, liver function tests, ultrasound)
c. Clinical diagnosis
d. Procedure (eg, fine-needle aspiration, anterior chamber paracentesis)
e. Operative findings
f. Anatomic site (right or left eye; part of eye sampled)
B. Macroscopic examination
1. Specimen
a. Unfixed/fixed (specify fixative)
b. Number of slides received
c. Quantity and appearance of fluid specimen
d. Other (eg, core of tissue in needle shaft)
e. Intraoperative/intraprocedural consultation
2. Material submitted for microscopic evaluation (eg, cytocentrifuge, smear, filter preparation)
3. Material submitted for special studies (specify) (eg, immunocytochemistry)
C. Microscopic evaluation
1. Adequacy of specimen for evaluation (if unsatisfactory for evaluation, specify reason)
2. Tumor, if present
a. Histologic type, if possible (note A)
b. Other characteristics (note B)
(1) Presence of pigment
(2) Cytoplasmic indentation of nucleus
(3) Cytoplasmic vacuolization
3. Additional pathologic findings, if present (eg, presence of retinal tissue, inflammatory cells)
4. Results/status of special studies (specify)
5. Comments
a. Correlation with intraprocedural consultation
b. Correlation with other specimens, as appropriate
c. Correlation with clinical information, as appropriate
II. Biopsy
A. Clinical information
1. Patient identification
a. Name
b. Identification number
c. Age (birth date)
d. Gender
2. Responsible physician(s)
3. Date of procedure
4. Other clinical information
a. Relevant history
(1) Clinical findings
(2) Past ocular history
(3) Previous ocular surgery
(4) Previous treatment
b. Relevant findings (eg, liver function tests, ultrasound)
c. Procedure (eg, peripheral iridectomy, iridocyclectomy, sclerouveectomy)
d. Operative findings
e. Anatomic site of specimen (right or left eye)
B. Macroscopic examination
1. Specimen
a. Unfixed/fixed (specify fixative)
b. Orientation (if indicated by surgeon by written instruction, diagram, or suture); ink margins of excisional biopsy specimens
c. Previously opened
d. Number of pieces
e. Size(s) (3 dimensions, if possible)
f. Tumor
(1) Size (3 dimensions, if possible)
(2) Presence of necrotic tissue
(3) Descriptive features
g. Other tissues, as appropriate
h. Results of intraoperative consultation
2. Tissue submitted for microscopic evaluation (specify)
3. Special studies (specify) (eg, special histochemical stains, immunohistochemical stains)
C. Microscopic evaluation
1. Tumor
a. Histologic type (note A)
b. Histologic grade
c. Extent
(1) Involvement of adjacent structures, such as ciliary body
(2) Extraocular extension
(3) Invasion of normal vessels or tumor vessels
d. Other prognostic features (note B)
2. Additional pathologic findings, if present
a. Drusen
b. Neovascularization
c. Nevus
d. Ectropion uveae
e. Other(s)
3. Results/status of special studies (specify)
4. Comments
a. Correlation with intraoperative consultation
b. Correlation with other specimens, as appropriate
c. Correlation with clinical information, as appropriate
III. Resection Specimen (Globe)
A. Clinical information
1. Patient identification
a. Name
b. Identification number
c. Age (birth date)
d. Gender
2. Responsible physician(s)
3. Date of procedure
4. Other clinical information
a. Relevant history
(1) Clinical findings
(2) Past ocular history
(3) Previous ocular surgery
(4) Previous treatment
b. Relevant findings (eg, liver function tests, ultrasound)
c. Clinical diagnosis
d. Procedure (usually enucleation)
e. Operative findings
f. Anatomic site of specimen (right or left eye)
5. Documentation of areas marked by surgeon for orientation (eg, suture, diagram)
B. Macroscopic examination
1. Specimen
a. Organ(s)/tissue(s) included
b. Unfixed/fixed (specify fixative) (note C)
c. Orientation (note D)
d. Description of other tissues, as appropriate
e. Results of intraoperative consultation
2. Globe
a. Evidence of previous excision or treatment
b. Note if previously opened/sectioned and in what fashion (note E)
c. Size
(1) Anteroposterior, horizontal, vertical dimensions of globe
(2) Length and diameter of attached optic nerve
(3) Corneal horizontal and vertical diameter
(4) Diameter of pupil, if visible
d. Transillumination (helpful to identify location of tumor and measure basal dimension prior to sectioning globe)
(1) Quality of transillumination (eg, poor light transillumination, transilluminates light well)
(2) Transillumination defect
i. Location
ii. Relationship to equator of globe
iii. Relationship to limbus
iv. Clock hour(s) of iris/globe
v. Size (2 dimensions)
e. Mark outline with marking implement
f. Extrascleral extension, if present
g. Sectioning of specimen (globe) (note E)
h. Mass/tumor, if present
(1) Location
(2) Size (notes F and G)
i. Base at cut edge (ie, portion of tumor closest to sclera)
ii. Height at cut edge
(3) Distance of anterior margin of tumor base from limbus at cut edge
(4) Distance of posterior margin of tumor base from edge of optic disc
(5) Other descriptive features (color, consistency, shape)
(6) Structures involved and extent (note G)
i. Retinal involvement
ii. Optic nerve involvement
iii. Macroscopic involvement of vitreous
iv. Involvement of ciliary body
v. Macroscopic involvement of anterior chamber angle
i. Features of other (uninvolved) ocular tissues
(1) Cornea (eg, clear, cloudy, opaque)
(2) Anterior chamber (eg, deep, shallow, flat)
(3) Angle (eg, open, narrow, closed)
(4) Iris (eg, color, any abnormalities)
(5) Ciliary body
(6) Lens (eg, clear, cataractous, presence of lens implant, absence)
(7) Vitreous (eg, color, consistency, hemorrhage)
(8) Retina (eg, detachment, total or partial; hemorrhages)
(9) Choroid
(10) Sclera (eg, thinning, defects)
(11) Optic disc (eg, pallor, increased cup/disc ratio)
3. Tissues submitted for microscopic examination (specify) (note E)
4. Special studies (specify) (eg, immunohistochemistry)
C. Microscopic evaluation
1. Tumor
a. Site (choroid, ciliary body, iris) (note G)
b. Histologic type (note A)
c. Histologic grade
d. Extent of invasion (note G)
e. Size (note F)
f. Anatomic extent (notes B and G)
(1) Anterior margin of tumor
(2) Retinal or scleral involvement
(3) Angle involvement
(4) Vitreal involvement
(5) Optic nerve involvement
2. Margins
a. Extrascleral extension (notes B and G)
b. Surgical margin of optic nerve (note B)
3. Other prognostic features (note B)
4. Additional pathologic findings, if present
a. Cancer-related
(1) Cataract
(2) Vitreous hemorrhage
(3) Glaucomatous optic atrophy
(4) Secondary angle closure
(5) Secondary open-angle glaucoma
(6) Iris neovascularization
(7) Retinal atrophy
b. Other
(1) Corneal disease
(2) Diabetic retinopathy
5. Results/status of special studies (specify)
6. Comments
a. Correlation with intraoperative consultation
b. Correlation with other specimens, as appropriate
c. Correlation with clinical information, as appropriate
EXPLANATORY NOTES
A: Histologic Type.—The modified Callender classification shown below is used for determining cell type, but has prognostic significance only for tumors of the choroid and ciliary body, not those of the iris, which generally have a benign course.1–4
Spindle cell nevus: slender cells with fusiform nuclei, delicate nuclear chromatin, and inapparent nucleoli; no mitoses are found
Spindle cell melanoma*
Spindle A: slender cells with a thin oval nucleus, indistinct nucleoli, and often a longitudinal fold in the nuclear membrane
Spindle B: larger plumper nuclei with sharply defined, round nucleoli
Mixed cell melanoma: both spindle and epithelioid cells present
Epithelioid cell melanoma*: larger, more pleomorphic, polygonal cells with large, sometimes multiple nucleoli
* Spindle cell melanomas have the most favorable prognosis and epithelioid cell melanomas the least favorable in terms of survival.
B: Other Pathologic Features of Prognostic Significance.—Other histologic features with prognostic significance in choroidal and ciliary body melanoma include the number of mitoses in 40 high-power fields, pigmentation, degree of inflammation, growth pattern (diffuse choroidal melanomas and ring melanomas of the ciliary body have a much less favorable prognosis), location of anterior margin of tumor, degree and patterns of vascularity, blood vessel invasion (both tumor vessels and normal vessels), tumor necrosis, extraocular extension, and optic nerve involvement.4–15
C: Fixative.—The minimum recommended fixation time for whole globes with intraocular tumors is 48 hours. The globe should be fixed in an adequate volume of fixative with at least a 10:1 ratio of fixative volume to specimen volume recommended. Incisions or windows in the globe are not necessary for adequate penetration of fixative and are not recommended. Injection of fixative into the globe is also not recommended (due to the possibility of introducing artifact).
D: Orientation.—The orientation of a globe may be determined by identification of extraocular muscle insertions, the optic nerve, and other landmarks, as illustrated in Figure 1. The terms temporal and nasal are generally used in place of lateral and medial with reference to ocular anatomy.
Anatomic landmarks of the posterior aspect of the globe (right eye). The position of the inferior oblique muscle relative to the optic nerve is most helpful in orienting the globe. The inferior oblique muscle insertion is located temporal (lateral) to the optic nerve on the sclera, and its fibers travel inferonasally from its insertion. The long posterior ciliary artery is often seen as a blue-gray line in the sclera on either side of the optic nerve and marks the horizontal meridian of the globe. Reprinted with permission from WB Saunders Company
Anatomic landmarks of the posterior aspect of the globe (right eye). The position of the inferior oblique muscle relative to the optic nerve is most helpful in orienting the globe. The inferior oblique muscle insertion is located temporal (lateral) to the optic nerve on the sclera, and its fibers travel inferonasally from its insertion. The long posterior ciliary artery is often seen as a blue-gray line in the sclera on either side of the optic nerve and marks the horizontal meridian of the globe. Reprinted with permission from WB Saunders Company
E: Sectioning the Globe.—The globe is generally sectioned in the horizontal or vertical plane with care to include the pupil and optic nerve along with tumor/mass in the section to be submitted for microscopic examination. If the mass cannot be included with horizontal or vertical sectioning, the globe is sectioned obliquely to include the tumor, pupil, and optic nerve, as illustrated in Figure 2. Alternative methods of sectioning have been described.16
The most common methods of sectioning a globe. After transillumination, the tumor base is marked, if possible, and included in the pupil-optic (p-o) nerve section and submitted for processing. If tumor is found in either of the calottes, these may also be submitted for sectioning. The meridian in which the globe was sectioned should be included in the gross description of the pathology report. It is not uncommon to induce an artifactitious retinal detachment while sectioning the globe. This can be minimized by gentle handling and by avoiding a sawing motion with the blade. Reprinted with permission from WB Saunders Company
The most common methods of sectioning a globe. After transillumination, the tumor base is marked, if possible, and included in the pupil-optic (p-o) nerve section and submitted for processing. If tumor is found in either of the calottes, these may also be submitted for sectioning. The meridian in which the globe was sectioned should be included in the gross description of the pathology report. It is not uncommon to induce an artifactitious retinal detachment while sectioning the globe. This can be minimized by gentle handling and by avoiding a sawing motion with the blade. Reprinted with permission from WB Saunders Company
F: Tumor Size.—Tumor size has prognostic significance. Many studies of choroidal and ciliary body melanoma have defined small tumors as being less than 10 mm in greatest diameter.4 More recently, an ongoing study started in 1986, the Collaborative Ocular Melanoma Study,17,18 defined the following size classification based on clinical measurements.
Small tumors*: smaller than medium or large tumors defined below
Medium tumors: >2.5 mm and <10 mm in height, and <16 mm in basal diameter
Large tumors: >10 mm in height or
>2 mm in height and >16 mm in basal diameter or
>8 mm in height with optic nerve involvement
* Small tumors have a more favorable prognosis.6,7
G: TNM Stage Groupings.—The American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) TNM staging systems for uveal melanoma of the iris, ciliary body, and choroid are shown below.19
* In clinical practice, the tumor base may be estimated in optic disc diameters (dd) (average: 1 dd = 1.5 mm). The elevation may be estimated in diopters (average 3 diopters = 1 mm). Other techniques used, such as ultrasonography and computerized stereometry, may provide a more accurate measurement.
Note.—When dimension and elevation show a difference in classification, the highest category should be used for classification.
It should be noted that regional lymph node involvement is rare in uveal melanoma. Metastasis to the liver and direct extension into the orbit are more common.19
References
Bibliography
This protocol was developed by the Cancer Committee of the College of American Pathologists and submitted for editorial review and publication. It represents the views of the Cancer Committee and is not the official policy of the College of American Pathologists.