Cap Ovary Fallopian 2018protocol 1100
Cap Ovary Fallopian 2018protocol 1100
Cap Ovary Fallopian 2018protocol 1100
For accreditation purposes, this protocol should be used for the following procedures AND tumor types:
Procedure Description
Resection Includes oophorectomy, salpingo-oophorectomy, salpingectomy,
subtotal resection, or removal of tumor in fragments
Tumor Type Description
Primary malignant tumors of Includes all primary epithelial borderline tumors and carcinomas,
ovary, fallopian tube or carcinosarcoma, malignant germ cell tumors, and malignant sex
peritoneum cord-stromal tumors.
This protocol is NOT required for accreditation purposes for the following:
Procedure
Biopsy
Primary resection specimen with no residual cancer (eg, following neoadjuvant therapy)
Cytologic specimens
The following tumor types should NOT be reported using this protocol:
Tumor Type
Peritoneal mesothelioma
Lymphoma (consider the Hodgkin or non-Hodgkin Lymphoma protocols)
Sarcoma (consider the Soft Tissue protocol)
Authors
Saeid Movahedi-Lankarani, MD*; Uma Krishnamurti, MD, PhD*; Debra A. Bell, MD; George G. Birdsong, MD;
Charles V. Biscotti, MD; Christopher N. Chapman Jr, MD; Veronica Klepeis, MD, PhD; Christopher N. Otis, MD
With guidance from the CAP Cancer and CAP Pathology Electronic Reporting Committees.
* Denotes primary authors. All other contributing authors are listed alphabetically.
Accreditation Requirements
This protocol can be utilized for a variety of procedures and tumor types for clinical care purposes. For
accreditation purposes, only the definitive primary cancer resection specimen is required to have the core and
conditional data elements reported in a synoptic format.
• Core data elements are required in reports to adequately describe appropriate malignancies. For
accreditation purposes, essential data elements must be reported in all instances, even if the response is
“not applicable” or “cannot be determined.”
• Conditional data elements are only required to be reported if applicable as delineated in the protocol. For
instance, the total number of lymph nodes examined must be reported, but only if nodes are present in the
specimen.
• Optional data elements are identified with “+” and although not required for CAP accreditation purposes,
may be considered for reporting as determined by local practice standards.
The use of this protocol is not required for recurrent tumors or for metastatic tumors that are resected at a
different time than the primary tumor. Use of this protocol is also not required for pathology reviews performed at
a second institution (ie, secondary consultation, second opinion, or review of outside case at second institution).
Synoptic Reporting
All core and conditionally required data elements outlined on the surgical case summary from this cancer protocol
must be displayed in synoptic report format. Synoptic format is defined as:
• Data element: followed by its answer (response), outline format without the paired "Data element:
Response" format is NOT considered synoptic.
• The data element should be represented in the report as it is listed in the case summary. The response for
any data element may be modified from those listed in the case summary, including “Cannot be
determined” if appropriate.
• Each diagnostic parameter pair (Data element: Response) is listed on a separate line or in a tabular format
to achieve visual separation. The following exceptions are allowed to be listed on one line:
o Anatomic site or specimen, laterality, and procedure
o Pathologic Stage Classification (pTNM) elements
o Negative margins, as long as all negative margins are specifically enumerated where applicable
• The synoptic portion of the report can appear in the diagnosis section of the pathology report, at the end of
the report or in a separate section, but all Data element: Responses must be listed together in one location
Organizations and pathologists may choose to list the required elements in any order, use additional methods in
order to enhance or achieve visual separation, or add optional items within the synoptic report. The report may
have required elements in a summary format elsewhere in the report IN ADDITION TO but not as replacement for
the synoptic report ie, all required elements must be in the synoptic portion of the report in the format defined
above.
CAP Laboratory Accreditation Program Protocol Required Use Date: April 2019
2
CAP Approved Female Reproductive • Ovary, Fallopian Tube, Peritoneum 1.1.0.0
+ Hysterectomy Type
+ ___ Abdominal
+ ___ Vaginal
+ ___ Vaginal, laparoscopic-assisted
+ ___ Laparoscopic
+ ___ Laparoscopic, robotic-assisted
+ ___ Other (specify): __________________
+ ___ Not specified
+ Data elements preceded by this symbol are not required for accreditation purposes. These optional elements may be 3
clinically important but are not yet validated or regularly used in patient management.
CAP Approved Female Reproductive • Ovary, Fallopian Tube, Peritoneum 1.1.0.0
Tumor Size
Note: For bilateral tumors, please report maximum dimension for each primary tumor, specifying by laterality.
Greatest dimension (centimeters): ___ cm
+ Additional dimensions (centimeters): ___ x ___ cm
___ Cannot be determined (explain): _______________________
+ Data elements preceded by this symbol are not required for accreditation purposes. These optional elements may be 4
clinically important but are not yet validated or regularly used in patient management.
CAP Approved Female Reproductive • Ovary, Fallopian Tube, Peritoneum 1.1.0.0
Histologic Grade (required for serous, endometrioid, mucinous, and seromucinous carcinomas, immature
teratomas, and Sertoli-Leydig cell tumors) (Note H)
Note: Serous carcinomas are graded via a 2-tier system. Immature teratomas can be graded using a 2-tier or 3-tier system.
Endometrioid and mucinous carcinomas are graded via a 3-tier system. Sertoli-Leydig cell tumors are graded via a modified 3-
tier grading system with grade 2 tumors being termed “intermediate differentiated.” Clear cell carcinomas, borderline epithelial
neoplasms, carcinosarcomas, all other malignant sex-cord stromal and germ cell tumors are not graded.
Two-Tier Grading System (required for immature teratomas and serous carcinomas only)
___ Low grade
+ Data elements preceded by this symbol are not required for accreditation purposes. These optional elements may be 5
clinically important but are not yet validated or regularly used in patient management.
CAP Approved Female Reproductive • Ovary, Fallopian Tube, Peritoneum 1.1.0.0
Implants (required for advanced stage serous/seromucinous borderline tumors only) (Note I)
Note: Serous tumor implants that were formerly classified as “invasive implants” are now classified as low-grade serous
carcinoma of the peritoneum.
___ Not sampled
___ Not identified
___ Present (specify sites): _______________________
Peritoneal/Ascitic Fluid
___ Not submitted/unknown
___ Negative for malignancy (normal/benign)
___ Atypical and/or suspicious (explain): ____________________
___ Malignant (positive for malignancy)
___ Unsatisfactory/nondiagnostic (explain): ______________________
___ Other (specify): _______________________
___ Results pending
+ Pleural Fluid
+___ Not submitted / unknown
+___ Negative for malignancy (normal/benign)
+___ Atypical and/or suspicious (explain): ____________________
+___ Malignant (positive for malignancy)
+___ Unsatisfactory/nondiagnostic (explain): ______________________
+___ Results pending
+ Data elements preceded by this symbol are not required for accreditation purposes. These optional elements may be 6
clinically important but are not yet validated or regularly used in patient management.
CAP Approved Female Reproductive • Ovary, Fallopian Tube, Peritoneum 1.1.0.0
Lymph Node Examination (required only if lymph nodes are present in the specimen)
___ pT1b: Tumor limited to both ovaries (capsules intact) or fallopian tubes; no tumor on ovarian or fallopian
tube surface; no malignant cells in ascites or peritoneal washings
___ pT1c: Tumor limited to one or both ovaries or fallopian tubes with any of the following:
___ pT1c1: Surgical spill
___ pT1c2: Capsule ruptured before surgery or tumor on ovarian or fallopian tube surface
___ pT1c3: Malignant cells in ascites or peritoneal washings
___ pT2: Tumor involves one or both ovaries or fallopian tubes with pelvic extension below pelvic brim or
primary peritoneal cancer
___ pT2a: Extension and/or implants on uterus and/or fallopian tube(s) and/or ovaries.
___ pT2b: Extension to and/or implants on other pelvic tissues.
___ pT3: Tumor involves one or both ovaries or fallopian tubes, or primary peritoneal cancer with
microscopically confirmed peritoneal metastasis outside the pelvis and/or metastasis to
retroperitoneal (pelvic and/or para-aortic) lymph nodes
___ pT3a: Microscopic extra-pelvic (above the pelvic brim) peritoneal involvement with or without positive
retroperitoneal lymph nodes
___ pT3b: Macroscopic peritoneal metastasis beyond pelvis 2 cm or less in greatest dimension with or without
metastasis to retroperitoneal lymph nodes
___ pT3c: Macroscopic peritoneal metastasis beyond pelvis more than 2 cm in greatest dimension with or
without metastasis to the retroperitoneal lymph nodes (includes extension of tumor to capsule of
liver and spleen without parenchymal involvement of either organ)
# Note: Serous tubal intraepithelial carcinoma (STIC) should be staged as pT1a if it involves one tube only, as pT1b if it
involves both tubes, and as pT1c3 if it is accompanied by positive peritoneal washing washings or ascites. Nonmalignant
ascites is not classified. The presence of ascites does not affect staging unless malignant cells are present.
+ Data elements preceded by this symbol are not required for accreditation purposes. These optional elements may be 8
clinically important but are not yet validated or regularly used in patient management.
CAP Approved Female Reproductive • Ovary, Fallopian Tube, Peritoneum 1.1.0.0
+ Data elements preceded by this symbol are not required for accreditation purposes. These optional elements may be 9
clinically important but are not yet validated or regularly used in patient management.
CAP Approved Female Reproductive • Ovary, Fallopian Tube, Peritoneum 1.1.0.0
+ Comment(s)
+ Data elements preceded by this symbol are not required for accreditation purposes. These optional elements may be 10
clinically important but are not yet validated or regularly used in patient management.
Background Documentation Female Reproductive • Ovary, Fallopian Tube, Peritoneum 1.1.0.0
Explanatory Notes
Ovarian Surface
Involvement of the ovarian surface is an important element in staging tumors limited to the ovary, and the
presence of surface involvement may influence treatment. Therefore, careful examination of the ovarian surface is
crucial. Furthermore, in patients who undergo prophylactic (salpingo-) oophorectomy because of a family history
of ovarian and/or breast cancer, very small foci of involvement of the ovarian surface may be present that may be
1-6
potentially lethal and may be missed if the macroscopic inspection is not optimal.
Ovarian/Adnexal Tumor
One section for each centimeter of the tumor’s largest dimension is generally recommended, with modification
based on the degree of heterogeneity of the tumor and the difficulty of diagnosis. Borderline (atypical proliferative)
serous tumor, borderline serous tumors with micropapillary features/noninvasive low-grade serous carcinoma,
and borderline (atypical proliferative) mucinous tumors require more sections (2 sections for each centimeter of
the tumor’s largest dimension is recommended in such cases).Some sections should include the ovarian surface
where it is most closely approached by tumor on gross examination, with the number of sections depending on
the degree of suspicion of surface involvement. Tumor adhesions and sites of rupture should be sampled and
labeled specifically for microscopic identification.
Figure 1. Protocol for Sectioning and Extensively Examining the Fimbriated End (SEE-FIM) of the Fallopian Tube.
This protocol entails amputation and longitudinal sectioning of the infundibulum and fimbrial segment (distal 2 cm) to allow
10
maximal exposure of the tubal plicae. The isthmus and ampulla are cut transversely at 2- to 3-mm intervals. From Crum et al.
Copyright © 2007 Lippincott Williams & Wilkins. Reproduced with permission.
Sampling Issues
The recommendation for the number of sections to be taken of an ovarian/adnexal tumor is a general guideline,
with the pathologist determining how many sections are necessary. If a tumor is obviously malignant and
11
Background Documentation Female Reproductive • Ovary, Fallopian Tube, Peritoneum 1.1.0.0
homogeneous throughout on gross examination, fewer sections may be needed. In contrast, if there is great
variability in the gross appearance of the sectioned surfaces or opened cysts, it may be necessary to take more
sections to sample the tumor adequately. In addition, as a general recommendation, borderline serous tumors
with micropapillary foci or with microinvasion should be extensively sampled to ensure adequate assessment of
the extent of invasion, when present. Mucinous tumors (particularly those with solid areas), solid teratomas, and
malignant germ cell tumors often require careful gross examination and judicious sampling. Of note, additional
sampling of a tumor that poses problems in differential diagnosis may be more informative than special studies.
Fallopian Tube(s)
For patients with high-grade serous carcinoma, if no gross lesion is present in the fimbrial end of each fallopian
tube, complete microscopic examination is recommended. If a gross fimbrial lesion is present, representative
sections of tumor to determine its distribution and relationship to tubal epithelium are recommended.
For patients with high-grade serous carcinoma, in contrast to other tumor histologic types covered by this
protocol, a small, sometimes microscopic focus of tumor may be present in the mucosa of the fallopian tube that
is the probable primary site (see Note C). The identification of tubal involvement can usually be accomplished by
careful macroscopic examination and, if nothing is identified grossly, by submitting the fimbrial end of the fallopian
10
tubes in toto for microscopic examination using the SEE-FIM protocol.
Uterus
If tumor is grossly present, sections should be taken to determine its extent, including depth of invasion of
myometrium if tumor possibly originated in endometrium, and to determine its relation to ovarian tumor
(metastatic to, metastatic from, independent primary). If uterine serosa is grossly involved, sections to show this
should be taken.
Omentum
If tumor is grossly identifiable, representative sections are enough. It is recommended to take multiple sections
when no tumor is detected grossly. Although there is no general consensus regarding the number of sections that
should be taken on a grossly normal omentum of a patient with an ovarian serous borderline tumor, serous
carcinoma, or immature teratoma, a general recommendation would be to take 5 to 10 sections. Implants in
serous borderline tumors and immature teratomas may vary from noninvasive to invasive low-grade serous
11 12
carcinoma and from mature to immature, respectively. Identification of invasive carcinoma or an immature
implant may considerably alter the prognosis and therapy. For borderline tumors or immature teratoma with
grossly apparent implants, multiple sections of the implants should be taken.
For patients who have received neoadjuvant chemotherapy for advanced stage tubo-ovarian carcinoma (typically
of high-grade serous type), 4 to 6 sections of omentum, to sample the most abnormal areas, are recommended to
allow assessment of response to chemotherapy (see Note J).
Lymph Nodes
If the lymph nodes are grossly involved by tumor, representative sections are enough. However, if the lymph
nodes appear grossly free of tumor, they should be entirely submitted. In either case, the dimension of the largest
metastatic deposit should be documented.
12
Background Documentation Female Reproductive • Ovary, Fallopian Tube, Peritoneum 1.1.0.0
B. Rupture of Tumor
It is important to know if the tumor is intact or ruptured, because in the latter situation, malignant cells may have
spilled into the abdominal cavity. In tumors that have an admixture of benign, borderline, and/or malignant areas,
13,14
it may also be important to know which area ruptured.
C. Site of Origin
Although determination of primary site for most histologic types of tumor is relatively straightforward, as they
present with tumor confined to the ovary, when a tumor involves ovary, fallopian tube, uterus, and multiple
intraperitoneal sites, it may be difficult or impossible to determine the primary site of the tumor.
Although historically primary site was assigned based on the dominant mass, this resulted in ovarian metastases
from a number of extra-ovarian primary sites (eg, stomach, vermiform appendix, colon, endocervix, endometrium)
being mistaken for primary ovarian neoplasms. Increased awareness of the ability of small extra-ovarian primary
tumors to metastasize to the ovary and their characteristic morphological features, and the introduction of
immunostains that aid in primary site determination, have led to improved recognition of ovarian metastases in
practice.
There remain challenges in assignment of primary site in cases of advanced stage high-grade serous carcinoma.
Table 1 reflects current recommendations for site assignment in such cases.
1,3,5
Table 1. Criteria for Assignment of Primary Site in Tubo-Ovarian High-Grade Serous Carcinoma (HGSC)
Criteria Primary Site Comment
Serous tubal intraepithelial carcinoma Fallopian tube Regardless of presence and size of ovarian and peritoneal
(STIC) present disease.
Invasive mucosal carcinoma in tube, Fallopian tube Regardless of presence and size of ovarian and peritoneal
with or without STIC disease.
Fallopian tube partially or entirely Fallopian tube Regardless of presence and size of ovarian and peritoneal
incorporated into tubo-ovarian mass disease.
No STIC or invasive mucosal Ovary Both tubes should be clearly visible and fully examined by a
carcinoma in either tube in presence of standardized SEE-FIM protocol.
ovarian mass or microscopic ovarian Regardless of presence and size of peritoneal disease.
involvement
Both tubes and both ovaries grossly Primary As recommended in World Health Organization (WHO) 2014
and microscopically normal (when peritoneal HGSC classification.
examined entirely) or involved by This diagnosis should only be made in specimens removed at
benign process in presence of primary surgery prior to any chemotherapy; see below for
peritoneal HGSC samples following chemotherapy.
HGSC diagnosed on small sample, Tubo-ovarian Note: this should be supported by clinicopathological findings
peritoneal/omental biopsy or cytology including immunohistochemistry to exclude mimics,
principally uterine serous carcinoma
Post-chemotherapy with residual Same criteria as
disease described above
Post-chemotherapy with no residual Tubo-ovarian
disease
Site assignment as “undesignated” should be avoided as far as possible and used only in the rare event that a case does not
fit into any of the above categories and/or there remains doubt over whether it is of tubo-ovarian or endometrial origin.
An adenocarcinoma is primary in the peritoneum when the ovaries and fallopian tubes are not involved or are
involved only with minimal surface/serosal implants.
It is important to note that serous carcinomas of endometrium may present with adnexal mass(es). In such cases
there is often not the extensive omental involvement characteristic of primary tubo-ovarian high-grade serous
carcinoma. Within the endometrium, there may be a co-existent precursor lesion (in situ serous carcinoma,
serous endometrial intraepithelial carcinoma), supporting primary endometrial origin of the tumor. WT-1 staining is
typically strong and diffuse in tubo-ovarian high-grade serous carcinoma and weak/focal or negative in
endometrial serous carcinoma. However, WT-1 is not completely sensitive or specific in determining primary
1,3
site. Further study is needed to improve the ability to distinguish between high-grade serous carcinoma of
13
Background Documentation Female Reproductive • Ovary, Fallopian Tube, Peritoneum 1.1.0.0
endometrial and tubo-ovarian origin; however, it is likely that most instances where high-grade serous carcinoma
involves the endometrium, the tumor is primary endometrial serous carcinoma.
D. Tumor Location
Distribution of tumor in the ovary may be a clue to its origin. If the tumor is mainly present on the surface of the
ovary without forming a discrete lesion, the tumor is more likely to be secondary ovarian involvement. If a tumor is
centered or mainly involves the ovarian hilus, it is most likely to be a metastasis. In the case of mucinous
neoplasms, if they are bilateral or associated with mucinous ascites or peritoneal/ovarian surface involvement,
15,16
they are more likely to be metastatic.
E. Contralateral Ovary
Contralateral ovary refers to the ovary that is non-dominant because it is either (1) involved by a tumor that is
similar to but smaller than the dominant ovarian tumor, (2) contains only what appears to be metastatic tumor on
gross examination, or (3) is negative for tumor. If the contralateral ovary contains only focal tumor, the gross and
microscopic examination should concentrate on determining whether the tumor is an independent primary or it is
metastatic from the dominant ovary. Metastatic involvement is supported by the same criteria that are used to
distinguish primary and metastatic cancers to the ovary (multiple nodules, surface implants, and hilar vascular
space invasion favor metastasis).
F. Histologic Type
It is recommended that the World Health Organization (WHO) classification and nomenclature of ovarian tumors
17
be used because of its wide acceptance. An abbreviated form of this classification is shown below.
Serous Tumors
Serous tubal intraepithelial carcinoma (STIC)
Serous borderline tumor/atypical proliferative serous tumor
Serous borderline tumor, micropapillary variant/noninvasive low-grade serous carcinoma
Low-grade serous carcinoma
High grade serous carcinoma
Mucinous Tumors
Mucinous borderline tumor/atypical proliferative serous tumor
Mucinous carcinoma
Seromucinous Tumors
Seromucinous borderline tumor/atypical proliferative seromucinous tumor
Seromucinous carcinoma
Endometrioid Tumors
Endometrioid borderline tumor
Endometrioid carcinoma
Clear Cell Tumors
Clear cell borderline tumor
Clear cell carcinoma
Brenner Tumors
Borderline Brenner tumor/atypical proliferative Brenner tumor
Malignant Brenner tumor
Mixed Epithelial Borderline Tumor
Mixed Epithelial Carcinoma
Carcinoma, Subtype Cannot Be Determined
Undifferentiated Carcinoma
Carcinosarcoma (malignant mixed Müllerian tumor)
Malignant Sex Cord-Stromal Tumors
Granulosa cell tumor, adult type
Granulosa cell tumor, juvenile type
Sertoli-Leydig cell tumor
Other sex cord-stromal tumor
Malignant Germ Cell Tumors
Dysgerminoma
14
Background Documentation Female Reproductive • Ovary, Fallopian Tube, Peritoneum 1.1.0.0
Histologic type of ovarian carcinoma can be diagnosed with a high degree of reproducibility in routine practice and
17
does have clinical implications. For example, hereditary breast and ovarian cancer syndrome is associated with
high-grade serous carcinoma, while Lynch syndrome is associated with endometrioid and clear cell tumors (both
tumors that can be seen in association with endometriosis), so accurate diagnosis is important.
The distinction between high-grade serous carcinoma and low-grade serous carcinoma is not an assignment of
grade based on a continuum. They differ with respect to risk factors, precursor lesions, response to
chemotherapy, and genetic events during oncogenesis, and merit consideration as distinct histologic types. The
criteria for distinguishing between high-grade serous carcinoma and low-grade serous carcinoma are primarily
based on nuclear variability (>3-fold nuclear size variation). In cases where the distinction is difficult, p16 and p53
immunostaining and assessment of mitotic activity (>12 mitoses/10 high-power fields) can be used. Such a
17
system has molecular and prognostic validity and excellent inter-observer agreement.
High-grade tumors with ambiguous features, such that 1 of the specific histologic types listed cannot be
diagnosed, should be classified as “carcinoma, subtype cannot be determined”; however, this is a very infrequent
situation, and every effort should be made to subclassify such tumors.
Serous tubal intraepithelial carcinoma (STIC) is an unusual entity. Although an “in situ” neoplasm, it has malignant
18
potential to spread throughout the peritoneal cavity. Therefore, with cases of only a STIC as a primary site and
negative staging and negative peritoneal washing, it is recommended to stage such cases as an AJCC
pT1a/FIGO IA tumor.
The diagnosis of mixed carcinoma was relatively common in the past, but with application of current
histopathologic criteria, fewer than 1% of tubo-ovarian carcinomas are mixed, and the most common admixture is
17
of endometrioid and clear cell carcinoma. It is now appreciated that high-grade serous carcinomas show a wide
range of histopathologic features, and glandular (pseudoendometroid) differentiation, solid architecture,
transitional growth pattern, or clear cell change are now accepted as being within the spectrum of high-grade
17,19
serous carcinoma, and the presence of these variants does not warrant diagnosis as mixed carcinoma.
Therefore, a mixed carcinoma should only be used when there are 2 or more distinct and separate histologic
types in the tumor.
Quantitation of various epithelial cell types within a carcinoma, as well as quantitation of tumor types within
20
primitive germ cell tumors, may be prognostically important.
H. Histologic Grade
Epithelial Carcinomas
Clear cell carcinoma and carcinosarcomas are not graded; at present there is no grading system that has
consistently been shown to prognosticate for these histologic types. Serous carcinomas are stratified into low
grade and high grade. Endometrioid carcinomas may be graded according to the FIGO system used for
endometrioid carcinomas of the endometrium, as shown below.
15
Background Documentation Female Reproductive • Ovary, Fallopian Tube, Peritoneum 1.1.0.0
Notable nuclear atypia, inappropriate for the architectural grade, raises the grade of a grade 1 or grade 2 tumor by
1 grade.
There are no defined grading systems in widespread use for the remaining histologic types of ovarian carcinoma
(eg, mucinous), and a gestalt 3-tier grading system can be used, acknowledging that it is not well validated.
Seromucinous tumors are tumors with more than one Müllerian epithelial cell type. Although most commonly seen
cell types are serous and mucinous, on occasion clear cell, transitional, or squamous epithelium can be seen.
Such tumors can be classified as by the 2-tier (almost always low grade) or the 3-tier grading systems listed
above.
Note that implants with invasive carcinoma (formerly designated as “invasive implants,” as per Bell and Scully
criteria) result in a diagnosis of low-grade serous carcinoma or seromucinous carcinoma, based on the WHO
17
2014 classification, as they are associated with a poor prognosis (identical to that of low-grade serous
carcinomas).
16
Background Documentation Female Reproductive • Ovary, Fallopian Tube, Peritoneum 1.1.0.0
CRS 2: Appreciable tumor response amidst viable tumor, both readily identifiable and tumor
regularly distributed
#
Ranging from multifocal or diffuse regression associated fibro-inflammatory changes, with viable
tumor in sheets, streaks, or nodules, to extensive regression associated fibro-inflammatory
#
changes with multifocal residual tumor which is easily identifiable
According to 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.
Pathologic staging is usually performed after surgical resection of the primary tumor. Biopsies of all frequently
involved sites, such as the omentum, mesentery, diaphragm, peritoneal surfaces, pelvic nodes, and para-aortic
nodes, are required for ideal staging of early disease. For example, a patient can be confidently coded as stage
IA (T1 N0 M0), if negative biopsies of all of the aforementioned sites are obtained to exclude microscopic
metastases. Pathologic staging depends on pathologic documentation of the anatomic extent of disease, whether
or not the primary tumor has been completely removed. If a biopsied tumor is not resected for any reason (eg,
when technically infeasible), and if the highest T and N categories or the M1 category of the tumor can be
confirmed microscopically, the criteria for pathologic classification and staging have been satisfied without total
removal of the primary cancer.
TNM Descriptors
For identification of special cases of TNM or pTNM classifications, the “m” suffix and “y,” “r,” and “a” prefixes are
used. Although they do not affect the stage grouping, they indicate cases needing separate analysis.
17
Background Documentation Female Reproductive • Ovary, Fallopian Tube, Peritoneum 1.1.0.0
The “m” suffix indicates the presence of multiple primary tumors in a single site and is recorded in parentheses:
pT(m)NM.
The “y” prefix indicates those cases in which classification is performed during or after initial multimodality therapy
(ie, neoadjuvant chemotherapy, radiation therapy, or both chemotherapy and radiation therapy). The cTNM or
pTNM category is identified by a “y” prefix. The ycTNM or ypTNM categorizes the extent of tumor actually
present at the time of that examination. The “y” categorization is not an estimate of tumor before multimodality
therapy (ie, before initiation of neoadjuvant therapy).
The “r” prefix indicates a recurrent tumor when staged after a documented disease-free interval and is identified
by the “r” prefix: rTNM.
N Category Considerations
Isolated tumor cells (ITCs) are single cells or small clusters of cells not more than 0.2 mm in greatest dimension.
Lymph nodes or distant sites with ITCs found by either histologic examination (eg, immunohistochemical
evaluation for cytokeratin) or nonmorphological techniques (eg, flow cytometry, DNA analysis, polymerase chain
reaction [PCR] amplification of a specific tumor marker) should be so identified. There is currently no guidance in
the literature as to how these patients should be coded; until more data are available, they should be coded as
“N0(i+)” with a comment noting how the cells were identified.
L. Other Lesions
The presence of endometriosis, particularly if it is in continuity with either an endometrioid or clear cell carcinoma,
is an important clue as to the primary nature of the ovarian tumor.
M. Special Studies
Special studies including histochemical, immunohistochemical, and molecular genetic studies may be used in
some cases. Evaluation for BRCA1/BRCA2 testing on patients with high-grade serous carcinoma of
tubal/ovarian/peritoneal origin should be performed at the discretion of genetic counselors with assessment of
other risk factors. Immunohistochemical stains for DNA mismatch repair enzymes MLH1, MS2, MSH6, and PMS2
28-29
for Lynch syndrome screening is recommended on all endometrioid and clear cell carcinomas of the ovary.
References
1. Singh N, Gilks CB, Wilkinson N, et al. Assessment of a new system for primary site assignment in high-grade
serous carcinoma of the fallopian tube, ovary, and peritoneum. Histopathology. 2015;67(3):331-337.
2. Gilks CB, Irving J, Kobel M, et al. Incidental nonuterine high-grade serous carcinomas arise in the fallopian
tube in most cases: further evidence for the tubal origin of high-grade serous carcinomas. Am J Surg Pathol.
2015;39:357-364.
3. McCluggage WG, Judge MJ, Clarke BA, et al. Data set for reporting of ovary, fallopian tube and primary
peritoneal carcinoma: recommendations from the International Collaboration on Cancer Reporting (ICCR).
Mod Pathol. 2015;28(8):1101-1122.
4. Morrison JC, Blanco LZ Jr, Vang R, Ronnett BM. Incidental serous tubal intraepithelial carcinoma and early
invasive serous carcinoma in the nonprophylactic setting: analysis of a case series. Am J Surg Pathol.
2015;39(4):442-53.
5. Singh N, Gilks CB, Hirschowitz L, et al. Adopting a uniform approach to site assignment in tubo-ovarian high
grade serous carcinoma – the time has come. Int J Gynecol Pathol. In press.
6. Bell DA, Scully RE. Early de novo ovarian carcinoma: a study of fourteen cases. Cancer. 1994;73(7):1859-
1864.
7. Lamb JD, Garcia RL, Goff BA, Paley PJ, Swisher EM. Predictors of occult neoplasia in women undergoing
risk-reducing salpingo-oophorectomy. Am J Obstet Gynecol. 2006;194(6):1702-1709.
8. Kindelberger DW, Lee Y, Miron A, et al. Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma:
evidence for a causal relationship. Am J Surg Pathol. 2007;31(2):161-169.
9. Medeiros F, Muto MG, Lee Y, et al. The tubal fimbria is a preferred site for early adenocarcinoma in women
with familial ovarian cancer syndrome. Am J Surg Pathol. 2006;30(2):230-236.
18
Background Documentation Female Reproductive • Ovary, Fallopian Tube, Peritoneum 1.1.0.0
10. Crum CP, Drapkin R, Miron A, et al. The distal fallopian tube: a new model for pelvic serous carcinogenesis.
Curr Opin Obstet Gynecol. 2007;19(1):3-9.
11. Bell DA, Weinstock MA, Scully RE. Peritoneal implants of ovarian serous borderline tumors: histologic
features and prognosis. Cancer. 1988;62(10):2212-2222.
12. Robboy SJ, Scully RE. Ovarian teratoma with glial implants on peritoneum: an analysis of 12 cases. Hum
Pathol. 1970;1(4):643-653.
13. Vergote I, De Brabanter J, Fyles A, et al. Prognostic importance of degree of differentiation and cyst rupture in
stage I invasive epithelial ovarian carcinoma. Lancet. 2001;357(9251):176-182.
14. Trimble EL. Prospects for improving staging of ovarian cancers. Lancet. 2001;357(9251):159-160.
15. Lee KR, Young RH. The distinction between primary and metastatic mucinous carcinomas of the ovary: gross
and histologic findings in 50 cases. Am J Surg Pathol. 2003;27(3):281-292.
16. Yemelyanova AV, Vang R, Judson K, et al. Distinction of primary and metastatic mucinous tumors involving
the ovary: analysis of size and laterality data by primary site with reevaluation of an algorithm for tumor
classification. Am J Surg Pathol. 2008;32(1):128-38.
17. Kurman RJ, Carcangiu ML, Harrington CS, Young RH, eds. WHO Classification of Tumors of the Female
Reproductive Organs. Geneva, Switzerland: WHO Press; 2014. World Health Organization Classification of
th
Tumors. 4 edition.
18. Schneider S, Heikaus S, Harter P, et al. Serous tubal intraepithelial carcinoma associated with extraovarian
metastases. Int J Gynecol Cancer. 2017;27(3):444-451.
19. MacKenzie R, Talhouk A, Eshragh S, et al. Morphologic and molecular characteristics of ovarian mixed
epithelial cancers. Am J Surg Pathol. 2015;39:1548-1557.
20. Kurman RJ, Norris HJ. Malignant mixed germ-cell tumors of the ovary: a clinical and pathologic analysis of 30
cases. Obstet Gynecol. 1976;48(5):579-589.
21. Norris HJ, Zirkin HJ, Benson WL. Immature (malignant) teratoma of the ovary: a clinical and pathologic study
of 58 cases. Cancer. 1976;37(5):2359-2372.
22. O'Connor DM, Norris HJ. The influence of grade on the outcome of stage I ovarian immature (malignant)
teratomas and the reproducibility of grading. Int J Gynecol Pathol. 1994;13(4):283-289.
23. Bohm S, Faruqi A, Said I, et al. Chemotherapy response score: development and validation of a system to
quantify histopathologic response to neoadjuvant chemotherapy in tubo-ovarian high-grade serous
carcinoma. J Clin Oncol. 2015;33(22):2457-2463.
24. Amin MB, Edge SB, Greene FL, et al, eds.. AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer;
2017.
25. Brierley JD, Gospodarowicz M, Wittekind Ch, eds. TNM Classification of Malignant Tumors. 8th ed. Oxford,
UK: Wiley; 2016.
nd
26. Wittekind CH, Henson DE, Hutter RVP, Sobin LH. TNM Supplement: A Commentary on Uniform Use. 2 ed.
New York, NY: Wiley-Liss; 2001.
27. FIGO Cancer Report Update on the diagnosis and management of gestational trophoblastic disease. Int J
Gynecol Obstet. 2015;131(Suppl 2):S123-S126.
28. Lu FI, Gilks CB, Mulligan AM, et al. Prevalence of loss of expression of DNA mismatch repair proteins in
primary epithelial ovarian tumors. Int J Gynecol Pathol. 2012;31(6):524-31.
29. Bennett JA, Morales-Oyarvide V, Campbell S, et al. Mismatch repair protein expression in clear cell
carcinoma of the ovary: incidence and morphologic associations in 109 cases. Am J Surg Pathol.
2016;40(5):656-663.
19