Protocol for the
Examination of Specimens from Patients with UVEAL MELANOMA:
A Basis for Checklists
Procedures:
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/intraprocedure
consultation
2.
Material submitted for microscopic evaluation (eg, cytocentrifuge, smear,
filter preparation)
3.
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, inflammatory cells)
4.
Retinal tissue
5.
Results/status of special studies (specify)
6.
Comments
a. Correlation with intraprocedural
consultation
b. Correlation with other specimens,
as appropriate
c. Correlation with clinical
information, as appropriate
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 type)
b. Orientation(if indicated by
surgeon)
c. Previously opened
d. Number of pieces
e. Size(s) (3 dimensions, if
possible)
f.
Orientation (if designated by surgeon by suture/diagram) – ink posterior
margins of iridocyclectomy specimens (excisioned biospy)
g. Tumor
(1) size (3 dimensions,
if possible)
(2) descriptive features
h. Other tissues(as appropriate)
i. Results or 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) sclera
(3) 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) back Top Main Page
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.
Sectioning of specimen (globe) (Note E)
3.
Globe
a. Evidence of previous excision or
treatment
b. Previously opened
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.
quadrant/relationship to equator of globe
iii.
relationship to limbus
iv.
clock-hour of iris
v. size (2
dimensions)
e. Mark outline with marking
implement
f. Extrascleral extension, if
present
g. Mass/tumor, if present
(1) location
(2) size (Note 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
h.
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)
(7) vitreous (eg, color,
consistency, hemorrhage)
(8) retina (eg,
detachment--total, partial; hemorrhages)
(9) choroid
(10) sclera (eg,
thinning, defects)
(11) optic nerve (eg,
pallor, increased cup/disc ratio)
4.
Tissues submitted for microscopic examination (specify)
5.
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 (Note s 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
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 back Top Main Page
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.
Other
histologic features with prognostic significance in choroidal and ciliary body
melanoma include: mitotic activity, 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)
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 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.
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.
The
globe is generally sectioned in the horizontal or vertical plane with care to
include the pupil and optic nerve 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)
Tumor
size has prognostic significance. Many
studies of choroidal and ciliary body melanoma have defined small tumors as
being less than 10mm 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, <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)
The
AJCC/UICC TNM staging systems for uveal melanoma of the iris, ciliary body and
choroid are shown below.(19)
Iris
Tumor (T)
TX Primary tumor cannot be assessed
TO No evidence of primary tumor
T1 Tumor limited to the iris
T2 Tumor involves one quadrant or less,
with invasion into the anterior chamber angle
T3 Tumor
involves more than one quadrant, with invasion into the anterior chamber angle,
ciliary body, and/or choroid
T4 Tumor with extraocular invasion
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed
NO No regional lymph node metastasis
N1 Regional lymph node metastasis
Distant Metastasis (M)
MX Presence of distant metastasis cannot be
assessed
M0 No distant metastasis
M1 Distant metastasis
Tumor (T)
TX Primary tumor cannot be assessed
TO No evidence of primary tumor
T1 Tumor limited to the ciliary body
T2 Tumor invades into the anterior chamber
and/or iris
T3 Tumor invades choroid
T4 Tumor with extraocular invasion
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed
NO No regional lymph node metastasis
N1 Regional lymph node metastasis
Distant Metastasis (M)
MX Presence of distant metastasis cannot be
assessed
M0 No distant metastasis
M1 Distant metastasis
Choroid
Tumor (T)
TX Primary tumor cannot be assessed
TO No
evidence of primary tumor
T1* Tumor 10 mm or less in greatest dimension
with an elevation of 3 mm or less
T1a Tumor
7 mm or less in greatest dimension with an elevation of 2 mm or less
T1b Tumor
more than 7 mm but not more than 10 mm
in greatest dimension with an elevation of more than 2 mm but not more than 3
mm
T2* Tumor more than 10 mm but not more than 15
mm in greatest dimension with an elevation more than 3 mm but not more than 5
mm
T3* Tumor more than 15 mm in greatest
dimension or with an elevation more than 5 mm
T4 Tumor with extraocular invasion
*
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.
Regional Lymph Nodes (N)
NX Regional lymph nodes cannot be assessed
NO No regional lymph node metastasis
N1 Regional lymph node metastasis
Distant Metastasis (M)
MX Presence of distant metastasis cannot be
assessed
M0 No distant metastasis
M1 Distant metastasis
Stage I T1 N0 M0
Stage II T2 N0 M0
Stage III T3 N0 M0
Stage IVA T4 N0 M0
Stage IVB Any
T N1 M0
Any
T Any N M1
Stage IA T1a N0 M0
Stage IB T1b N0 M0
Stage II T2 N0 M0
Stage III T3 N0 M0
Stage IVA T4 N0 M0
Stage IVB Any
T N1 M0
Any
T Any N M1
It
should be noted that regional lymph node involvement is rare in uveal melanoma,
but metastasis to the liver and direct extension into the orbit are more
common.(19)
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•
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Authors: Daniel Albert, M.D. and Nasreen Syed, M.D.
For
members of the Cancer Committee, College of American Pathologists
Originally
published in the Archives of Pathology
& Laboratory Medicine, September 2001.