Protocol applies to all gestational trophoblastic
malignancies.
Procedures
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. Where a physician chooses 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.
I. Dilatation and
Curettage back
Top Main
Page
A. CLINICAL INFORMATION
1. Patient identification
a. Name
b. Identification number
c. Age (birth date)
2. Responsible physician(s)
3. Date of procedure
4. Other clinical information
a. Relevant history (Note A)
(1) menstrual history
(2) week of pregnancy
(3) passage of tissue
(4) history of hydatidiform mole
b. Relevant findings (e.g. size of uterus, ultrasound, hCG level)
c. Clinical diagnosis
d. Procedure (e.g. endometrial biopsy, D&C, spontaneous passage
of tissue)
e. Anatomic site(s) of specimen(s) (e.g. uterine
corpus, cervix)
B. MACROSCOPIC EXAMINATION
1. Specimen
a. Unfixed/fixed (specify fixative)
b. Size (aggregate dimensions if multiple, after
separating tissue from blood)
c. Lesion/tumor
(1) dimensions
(2) descriptive features
(3) vesicles with size of largest
(4) fetal tissue and anomaly
(5) firmness
(6) necrosis
d. Results of intraprocedural
consultation
2. Tissue submitted for microscopic evaluation
a. Villous tissue
(1) representative samples, if abundant
(2) All, if sparse
b. Fetal tissue
c. Uterine tissue
3. Special studies (specify) (e.g.
immuno-histochemistry, DNA analysis [specify type], oncogene analysis,
karyotype analysis)
C. MICROSCOPIC EVALUATION
1. Adequacy of specimen (if inadequate for
evaluation, specify reason)
2. Lesion/tumor
a. Histologic type (Note B)
b. Presence in sharp curettage specimen
c. Presence in suction curettage specimen
3. Additional tissues or pathologic findings, if
present
a. Implantation site
b. Endometrium
c. Myometrium
d. Cervix
e. Fetal tissues (cord, amnion, chorion, yolk
sac)
f. Fetal anomalies, if present
4. Results/status of special studies
5. Comments
a. Correlation with
intraprocedural consultation, as appropriate
b. Correlation with other specimens, as appropriate
c. Correlation with clinical information, including hCG level, as appropriate
II. Resection back Top Main Page
A. CLINICAL
INFORMATION
1. Patient identification
a. Name
b. Identification number
c. Age (birth date)
2. Responsible physician(s)
3. Date of procedure
4. Other clinical information
a. Relevant history (Note A)
(1) menstrual history
(2) week of pregnancy
(3) passage of tissue
(4) history of hydatidiform mole
b. Relevant findings (e.g. size of uterus,
ultrasound, hCG level)
c. Clinical diagnosis
d. Procedure (e.g. abdominal hysterectomy,
radical hysterectomy with bilateral salpingo-oophorectomy, staging laparotomy,
pelvic exenteration)
e. Anatomic site(s) of specimen(s) (e.g. uterine
corpus, cervix)
B. MACROSCOPIC EXAMINATION
1. Specimen
a. Organ(s)/tissue(s) included
b. Unfixed/fixed (specify fixative)
c. Number of pieces
d. Dimensions
e. Orientation (if indicated by surgeon)
f. Areas indicated by surgeon for specific
microscopic evaluation
g. Results of intraoperative consultation
2. Lesion/tumor
a. Location (e.g.
corpus/fundus/cornu/isthmus/cervix)
b. Size (three dimensions)
c. Descriptive characteristics (e.g. villous
tissue/exophytic/color)
d. Extent of invasion (Note C)
(1) into myometrium/serosa/parametrium/cervix
(2) to other organ(s)/tissue(s)
e. Distance from margins
3. Additional pathologic findings, if present
a. Evidence of prior sampling or treatment at
apparent site of lesion
4. Uterine corpus
b. Dimensions
c. Descriptive features of endometrium,
myometrium and serosa
d. Lesion/tumor
(1) descriptive features including size, location
and extent
(2) relation to main lesion/tumor
e. Resection margins if, appropriate
f. Additional findings, if present
5. Uterine cervix
a. Descriptive features including appearance of
ectocervix and endocervix
b. Lesion/tumor
(1) descriptive features, including
size/location/extent
(2) relation to main lesion/tumor
c. Resection margins, if appropriate
d. Additional findings, if present
6. Vagina
a. Size (length, circumference, thickness)
b. Descriptive features (inner and outer
surfaces; wall)
c. Lesion/tumor
d. Descriptive features (size/location/ relation
to main lesion/tumor)
e. Resection margins, if appropriate
f. Additional findings, if present
7. Fallopian tube(s)
a. Dimensions
b. Descriptive features, including dimensions
c. Lesion/tumor
(1) descriptive features (size/location/extent)
(2) relation to main lesion/tumor
d. Resection margins if appropriate
e. Additional findings
8. Ovary(ies)
a. Descriptive features, including measurements,
outer surface, sectioned surface
b. Lesion/tumor
(1) descriptive features (size/location/extent)
(2) relation to main lesion/tumor
c. Resection margins if appropriate
d. Additional findings (e.g. multiple luteinized
follicle cysts)
9. Organ in which lesion/tumor primary
(uninvolved component)
a. Dimensions
b. Descriptive features
c. Resection margins if appropriate
d. Additional findings, if present
10. Regional lymph nodes
a. Lesion/tumor
(1) size
(2) descriptive features
b. Additional findings, if present
11. Other organ(s) or tissue(s) removed (e.g.
omentum, staging biopsy specimens)
a. Type(s) or site(s)
b. Dimensions and other descriptive features
c. Lesion/tumor
(1) descriptive features (size/location/extent)
(2) relation to main lesion/tumor
d. Resection margins if appropriate
12. Tissues submitted for microscopic evaluation
a. Primary lesion/tumor of uterus or other organ
- adequate number to demonstrate:
(1) deepest myometrial invasion or extent of
involvement
(2) distance from serosa or resection margin
(3) cornual/isthmic/cervical/parametrial
involvement, if present
b. Other lesions
c. Grossly uninvolved tissue, as appropriate
d. Staging and lymph node specimens - at least
one section of each
e. Omentum - multiple sections whether or not
grossly involved
f. Vaginal cuff
g. Frozen section tissue fragment(s) (unless
saved for special studies)
h. Other organs/tissues - as appropriate for
gross/clinical indications
13. Special studies (e.g. DNA flow cytometry,
genetic studies such as karyotype analysis, image analysis, DNA polymorphism analysis, etc).
C. MICROSCOPIC
EVALUATION
1. Organ primarily involved
a. Lesion/tumor
(1) histologic type (Note B)
(2) site
(3) extent of invasion (Note C)
(4) depth of invasion from
endometrial-junction/thickness of myometrium; or extent of primary tumor in other organs
(5) closest distance to serosa
(6) blood/lymphatic vessel invasion
b. Resection margins
c. Status of inked areas or areas designated by
surgeon
2. Additional pathologic findings, if present
a. Implantation site, if present: endometrium,
myometrium, cervix
b. Fetal tissues (chorion/amnion/yolk sac)
c. Fetal anomalies, if present
3. Regional lymph nodes
a. Total number
b. Number involved by tumor
c. Other findings (e.g. decidua)
4. Other organ(s) and tissue(s)
a. Lesion/tumor
(1) Location
(2) Extent
(3) Relation to primary lesion/tumor
b. Resection margins, if appropriate
c. Additional findings (e.g.
decidua/hyperreactio luteinalis of ovaries)
5. Results/status of special studies (specify)
6. Comments
a. Correlation with intraoperative consultation,
as appropriate
b. Correlation with other specimens, as
appropriate
c. Correlation with clinical information, as
appropriate
EXPLANATORY NOTES
A. Previous
History back Top Main Page
Previous slides should be reviewed by the
pathologist if it is deemed necessary by the gynecologist or pathologist for
optimal evaluation of the specimen.
B. Histologic
Type back Top Main Page
Histologic Classification of Gestational
Trophoblastic Lesions (World Health Organization Classification of Gestational
Trophoblastic Lesions).
Hydatidiform
mole
- Complete*
- Partial**
Invasive
hydatidiform mole
Choriocarcinoma
Placental
site trophoblastic tumor***
Trophoblastic
lesions, miscellaneous
- Exaggerated placental site
- Placental site nodule and plaque****
Unclassified
trophoblastic lesions
* Usually diploid, 46 chromosomes; no fetal tissues unless
with a twin gestation; villi markedly enlarged, hydropic, central cistern;
prominent trophoblastic hyperplasia.
** Usually triploid, 69 chromosomes; fetal tissues
present; villi scalloped, have stromal trophoblastic inclusions; focal
trophoblastic hyperplasia, usually of syncytiotrophoblast.
*** Malignant tumor of intermediate trophoblast.
**** Retention of a nodule or plaque of benign
intermediate trophoblast.
The TNM staging system of the American Joint
Committee on Cancer (AJCC) and the International Union Against Cancer (UICC)(2)
and the corresponding staging system of the International Federation of Gynecology
and Obstetrics (FIGO) are recommended and shown below. They are both based not
only on the anatomic extent of the tumor, but on additional factors, including
clinical and laboratory findings.
FIGO
Staging for Gestational Trophoblastic
Tumors
(GTTs) (1991)
Stage I Disease
confined to the uterus
IA Disease
confined to the uterus with no risk factors
IB Disease
confined to the uterus with one risk factor
IC Disease
confined to the uterus with two risk factors
Stage II GTT
extends outside of the uterus but is limited to the genital structures (adnexa,
vagina, broad ligament)
IIA GTT
involving genital structures without risk
factors
IIB GTT
extends outside of the uterus but limited to genital structures with one risk
factor
IIC GTT
extends outside of the uterus but limited to the genital structures with two
risk factors
Stage III GTT
extends to the lungs with or without known genital tract involvement
IIIA GTT
extends to the lungs with or without genital tract involvement and with no risk
factors
IIIB GTT
extends to the lungs with or without genital tract involvement and with one
risk factor
IIIC GTT
extends to the lungs with or without genital tract involvement and has two risk
factors
Stage IV All
other metastatic sites
IVA All
other metastatic sites without risk factors
IVB All
other metastatic sites with one risk factor
IVC All
other metastatic sites with two risk factors
Risk factors affecting staging include the
following:
1. HCG
> 100,000 mIU/ml
2. Duration
of disease > 6 months from termination of the antecedent pregnancy
AJCC/UICC
TNM Staging for Trophoblastic Tumors
Primary
Tumor (T)*
TX Primary
tumor cannot be assessed
T0 No
evidence of primary tumor
T1 Tumor
confined to uterus
T2 Tumor
extends to other genital structures: vagina, ovary, broad ligament, fallopian
tube by metastasis or direct extension
*By AJCC/UICC convention, the designation T
refers to a primary tumor that has not been previously treated. The symbol p
refers to the pathologic classification of the TNM, as opposed to the clinical
classification and is based on gross and microscopic examination. pT entails a resection of the primary tumor
or biopsy adequate to evaluate the highest pT category; pN entails removal of
nodes adequate to validate lymph node metastasis; and pM implies microscopic
examination of distant lesions.
Clinical classification (cTNM) is usually carried out by the referring
physician before treatment during initial evaluation of the patient or when
pathologic classification is not possible.
Tumor
Remaining in the Patient
Tumor remaining in a patient after therapy with
curative intent (e.g., surgical resection for cure) is categorized by a system
known as R classification, shown below.
RX Presence
of residual tumor cannot be assessed
R0 No
residual tumor
R1 Microscopic
residual tumor
R2 Macroscopic
residual tumor.
For the surgeon, the R classification may be
useful to indicate the known or assumed status of the completeness of a
surgical excision. For the pathologist,
the R classification is relevant to the status of the margins of a surgical
resection specimen. That is, tumor
involving the resection margin on pathologic examination may be assumed to
correspond to residual tumor in the patient and may be classified as
macroscopic or microscopic according to the findings at the specimen margin(s).
Tumor
Remaining in a Specimen
In contrast, tumor remaining in a resection
specimen from a patient who has undergone previous (neoadjuvant) treatment of
any type (radiation therapy alone, chemotherapy therapy alone, or any combined
modality treatment) is codified by the TNM using a prescript y (e.g.,
ypT1). Thus, yTNM indicates the
post-treatment status of the tumor. For
many neoadjuvant therapies, the classification of residual disease may be a
strong predictor of postoperative outcome.
In addition, the ypTNM classification provides a standardized framework
for the collection of data needed to accurately evaluate new neoadjuvant therapies.
Locally
Recurrent Tumor
In contrast to residual tumor, classification
of a tumor as recurrent requires a documented disease-free interval after
definitive therapy. Recurrent tumor may
also be classified according to the TNM categories, but the prefix r (e.g.,
rpT1) is used to indicate the recurrent status of the tumor.
Distant
Metastasis (M)
MX Distant
metastasis cannot be assessed
M0 No
distant metastasis
M1 Distant
metastasis
M1a Metastasis to lung(s)*
M1b Other distant metastasis (e.g. brain) with
or without lung metastasis*
* Genital metastasis (vagina, broad ligament,
ovary, fallopian tube) is classified as T2.
TNM
Stage Groupings
Stage T M Risk Factors
IA T1 M0 without
IB T1 M0 one
IC T1 M0 two
IIA T2 M0 without
IIB T2 M0 one
IIC T2 M0 two
IIIA Any
T M1a without
IIIB Any
T M1a one
IIIC Any
T M1a two
IVA Any
T M1b without
IVB Any
T M1b one
IVC Any
T M1b two
The following factors should be considered and
noted in reporting:
1. Prior
chemotherapy for known GTT.
2. Placental
site tumors should be reported separately.
3. Histological verification of disease is not required.
1. Scully
RE, Bonfiglio TA, Kurman RJ, Silverberg SG, Wilkinson EJ. World Health
Organization International Histological Classification of Tumours. Histological
Typing of Female Genital Tract Tumours. New York: Springer-Verlag; 1994.
2. Fleming ID, Cooper JS, Henson DE, et al. eds.
AJCC Manual for Staging of Cancer. 5th ed. Philadelphia, PA: Lippincott Raven;
1997.
BIBLIOGRAPHY
Bagshawe
KD, Lawler SD, Paradinas FJ, Dent J, Brown P, Boxer GM. Gestational
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Collins
RJ, Ngan HYS, Wong LC. Placental site trophoblastic tumor: With features
between an exaggerated placental site reaction and a placental site
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Conran
RM, Hitchcock EI, Popek EJ, et al. Diagnostic considerations in molar
gestations. Hum Pathol. 1993;24:41-48.
Fukunaga
M, Ushigome S, Fukunaga M, Sugishita M. Application of flow cytometry in
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Fukunaga
M, Ushigome S. Malignant trophoblastic tumors: Immunohistochemical and flow
cytometric comparison of choriocarcinoma and placental site trophoblastic
tumors. Hum Pathol. 1993;24:1098-1106.
Howat
AJ, Beck S, Fox H, et al. Can histopathologists reliably diagnose molar
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PC, Gersell DJ. Placental site nodule: A clinicopathologic study of 38 cases.
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Kurman
RJ, Young RH, Main CA, et al. Immunohistochemical localization of placental
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SD, Fisher RA, Dent J. A prospective genetic study of complete and partial
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D, Jackson R, Ehlen T, McMurtie E. Case report: Complete hydatidiform mole
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Author:
Janice M. Lage, MD
©2000. College of American Pathologists
(CAP). All rights reserved. None of the contents of this publication may be reproduced,
stored in a retrieval system or transmitted in any form or by any means
(electronic, mechanical, photocopying, recording, or otherwise) without prior
written permission of the publisher.
Expires
as CAP policy in May 2001. A year prior, the protocol will be reviewed and
updated.
Contributors:
back Top Main Page
CAP
Cancer Committee; Donald E. Henson, MD; Enrique Hernandez, MD; Maureen
Killacky, MD; Beverly B. Kramer, MD; Rachelle Lanciano, MD; Stanley J. Robboy,
MD; Steven G. Ruby, MD; Robert E. Scully, MD; Steven G. Silverberg, MD; Richard
Zaino, MD