南區GYN討論會
WHO Classification of Tumors of
Female Reproductive Organs –
Uterine cervix, Vagina, Vulva
2014/09/13
台大醫院 林明杰
Uterine Cervix - Squamous Precursors
2014
 Squamous
intraepithelial lesions

Low-grade squamous
intraepithelial lesion
(8077/0)

High-grade squamous
intraepithelial lesion
(8077/2)
2003
 Squamous
intraepithelial neoplasia

Cervical intraepithelial
neoplasia (CIN3) (8077/2)
/ squamous cell
carcinoma in situ (8070/2)
Uterine Cervix - Squamous Precursors

LSIL:







CIN1
Mild squamous dysplasia
Flat condyloma
Koilocytosis, koilocytotic atypia
Condyloma acuminatum (p172)
Papillary immature metaplasia (p182)
HSIL:



CIN2, CIN3
Moderate/severe squamous dysplasia
Squamous carcinoma in situ
40X
100X
Papillary immature metaplasia
(immature condyloma)
200X
Uterine Cervix – Squamous Cell Carcinoma
2014

Squamous cell carcinoma,
NOS (8070/3)








2003

Keratinizing
Non-keratinizing
Papillary
Basaloid
Warty
Verrucous
Squamotransitional
Lymphoepithelioma-like
Squamous cell carcinoma,
NOS (8070/3)









Keratinizing
Non-keratinizing
Basaloid
Verrucous
Warty
Papillary
Lymphoepithelioma-like
Squamotransitonal
Early invasive (microinvasive)
squamous cell carcinoma
(8076/3)
Microinvasive Squamous Cell Carcinoma (MICA)

FIGO


IA1
Society of Gynecological Oncologists
(SGO)




< 3 mm stromal invasion
No vascular invasion
Low recurrence rate and the risk of lymph node
metastasis
The diagnosis of MICA is always based on
histologic examination of a cone biopsy specimen
that includes the entire lesion
The Role of p16 in LSIL




Immunostaining for p16 in LSIL may be
negative, patchy positivity or be truly
positive (“block-type”)
Approximately 1/3 of histological LSIL:
diffuse (so-called “block-positive”) p16
immunostaining involving the basal and
parabasal cell layers
The diffuse pattern should not be
interpreted as absolutely indicative of HSIL.
The diagnosis rests on the appearance of
the lesion on H&E stains
Uterine Cervix – Benign squamous lesions
2014
 Squamous metaplasia
(No code)


Condyloma
acuminatum (No code)
Squamous papilloma
(8052/0)

Transitonal metaplasia
(No code)
2003
 Condyloma
acuminatum (No code)
 Squamous papilloma
(8052/0)

Fibroepithelial polyp
(No code)
Squamous Papilloma

2003



A single papillary frond in which mature
squamous epithelium without atypia or
koilocytosis lines a fibrovascular stalk
There is no evidence that squamous papilloma is
or is not related to HPV
2014


A papillary frond(s) with an internal fibrovascular
core covered by mature squamous epithelium
without atypia
The lesion is specifically not an HPV-associated
process
Uterine Cervix – Glandular precursors
2014
 Adenocarcinoma in
situ (8140/2)
2003
 Adenocarcinoma in
situ (8140/2)
 Glandular dysplasia
code)
(No
Uterine Cervix – Adenocarcinoma
2014

Adenocarcinoma








(8140/3)
Endocervical adenocarcinoma,
usual type (8140/3)
Mucinous carcinoma, NOS (8480/3)
 Gastric type (8482/3)
 Intestinal type (8144/3)
 Signet-ring cell type (8490/3)
Villoglandular carcinoma (8263/3)
Endometrioid carcinoma (8080/3)
Clear cell carcinoma (8310/3)
Serous carcinoma (8441/3)
Mesonephric carcinoma (9110/3)
Adenocarcinoma admixed with
neuroendocrine carcinoma (8574/3)
2003

Adenocarcinoma






(8140/3)
Mucinous adenocarcinoma (8480/3)
 Endocervical (8482/3)
 Intestinal (8144/3)
 Signet-ring cell (8490/3)
 Minimal deviation (8480/3)
 Villoglandular (8262/3)
Endometrioid adenocarcinoma (8380/3)
Clear cell adenocarcinoma (8310/3)
Serous adenocarcinoma (8441/3)
Mesonephric adenocarcinoma (9110/3)
Early invasive adenocarcinoma
(8140/3)
Mucinous Carcinoma, Gastric type

Minimal deviation adenocarcinoma
(adenoma malignum)



Extremely well-differentiated form of
gastric type mucinous carcinoma
Not associated with HPV
IHC markers



MUC 6
HIK1083
Annexin A10
100X
Mucinouos ca, gastric type
400x
Mucinouos ca, gastric type
Annexin A10
HIK1083
Adnoma malignum
Annexin A10
HIK1083
Early Invasive Adenocarcinoma


Recognizing microinvasive adenocarcinoma
is often problematic and less is known
about behavior of microinvasive
adenocarcinoma compared to microinvasive
SCC
The irregular distribution and architecture
of the normal endocervical crypts marke
actual depth of the invasion very difficult to
measure
Uterine Cervix – Benign glandular tumors
and tumor-like lesions
2014













Endocervical polyp
Mullerian papilloma
Nabothian cyst
Tunnel clusters
Microglandular hyperplasia
Lobular endocervical glandular
hyperplasia
Diffuse laminar endocervical
hyperplasia
Mesonephric remnants and
hyperplasia
Arias Stella reaction
Endocervicosis
Endometriosis
Tuboendometrioid metaplasia
Ectopic prostate tissue
2003
 Mullerian papilloma
 Endocervical polyp
Uterine Cervix – Other Epithelial Tumors
2014
 Adenosquamous
carcinoma




2003
 Adenosquamous
carcinoma
Glassy cell carcinoma
Adenoid basal
carcinoma
Adenoid cystic
carcinoma
Undifferentiated
carcinoma




Glassy cell carcinoma
Adenoid basal
carcinoma
Adenoid cystic
carcinoma
Undifferentiated
carcinoma
Uterine Cervix – Neuroendocrine Tumors
2014
 Low-grade
neuroendocrine tumor



Carcinoid tumor
Atypical carcinoid tumor
High-grade
neuroendocrine tumor


Small cell
neuroendocrine
carcinoma
Large cell
neuroendcrine
carcinoma
2003
 Carcinoid
 Atypical carcinoid
 Small cell carcinoma
 Large cell
neuroendocrine
carcinoma
Uterine Cervix – Mesencymal Tumors
and Tumor-like Lesions
2014
 Benign



Leiomyoma
Rhabdomyoma
others
2003
 Leiomyoma
 Genital rhabdomyoma
Uterine Cervix – Mesencymal Tumors
and Tumor-like Lesions
2014
 Malignant






Leiomyosarcoma
Rhabdomyosarcoma
Alveolar soft-part
sarcoma
Angiosarcoma
MPNST
Others



Liposarcoma
Undifferentiated
endocervical sarcoma
Ewing sarcoma
2003
 Leiomyosarcoma
 Endometrioid stromal
sarcoma, low grade
 Undifferentiated
endocervical sarcoma
 Sarcoma botryoides
 Alveolar soft part
sarcoma
 Angiosarcoma
 MPNST
Uterine Cervix – Mesencymal Tumors
and Tumor-like Lesions
2014
 Tumor-like lesions


Postoperative spindlecell nodule
Lymphoma-like lesion
2003

Postoperative spindle-cell
nodule
Uterine Cervix – Mixed Epithelial and
Mesenchymal Tumors
2014
 Adenomyoma
 Adenosarcoma
 carcinosarcoma
2003
 Carcinoma (malignant
mullerian mixed
tumor; metaplastic
carcinoma)
 Adenosarcoma
 Wilms tumor
 Adenofibroma
 adenomyoma
Uterine Cervix – Melanocytic Tumors
2014
 Blue nevus
 Malignant melanoma
2003
 Malignant melanoma
 Blue nevus
Uterine Cervix – Miscellaneous Tumors
2014
 Germ cell tumors


Yolk sac tumor

Lymphoid and myeloid
tumors



2003
 Germ cell tumors
Lymphomas
Myeloid neoplasm



Secondary tumors
Lymphoid and
hematopoetic tumors



Yolk sac tumor
Dermoid cyst
Mature cystic teratoma
Malignant lymphoma
Leukemia
Secondary tumors
Uterine Cervix – Staging
2014


2003
FIGO no longer includes Stage 0
(Tis)
FIGO II (T2) Tumor invades beyond
uterus but not to pelvic wall or to
lower third of vagina


Invasion of bladder or rectal mucosa
should be biopsy proven
FIGO Stage 0: carcinoma in situ
(preinvasive carcinoma)
FIGO II Tumor invades beyond
uterus but not to pelvic wall

IIA1 Clinically visible lesion 4 cm or
less in greatest dimension
IIA2 Clinically visible lesion more than
4 cm in greatest dimension
FIGO IVA (T4) Tumor invades
mucosa of the bladder or rectum, or
extends beyond true pelvis


IIA Tumor without parametrial
invasion




IIA Tumor without parametrial
invasion
FIGO IVA Tumor invades mucosa
of the bladder or rectum, or
extends beyond true pelvis
Vagina – Squamous precursors
2014
 Squamous
intraepithelial lesions

Low-grade squamous
intraepithelial lesion
(8077/0)

High-grade squamous
intraepithelial lesion
(8077/2)
2003
 Squamous
intraepithelial
neoplasia

Vaginal intraepithelial
neoplasia 3 (8077/2)/
squamous cell
carcinoma in situ(8070/2)
Vagina – Squamous Cell Carcinoma
2014
 Squamous cell
carcinoma, NOS






Keratinizing
Non-keratinizing
Papillary
Basaloid
Warty
Verrucous
2003
 Squamous cell
carcinoma, NOS





Keratinizing
Non-keratinizing
Basaloid
Verrucous
Warty
Vagina – Benign Squamous Lesions
2014
 Condyloma
acuminatum (no code)
 Squamous papilloma
(8052/0)

Fibroepithelial polyp
(no code)


Tubulosquamous
polyp (8560/0)
Transitional cell
metaplasia (no code)
2003
 Condyloma
acuminatum (no code)
 Squamous papilloma
(vaginal micropapillomatosis)
(8052/0)

Fibroepithelial polyp
(no code)
Vagina - Adenocarcinoma
2014

Adenocarcinomas




Endometrioid carcinoma
Clear cell carcinoma
Mucinous carcinoma
Mesonephric carcinoma
2003
 Adenocarcinomas




Clear cell adenocarcinoma
Endometrioid
adenocarcinoma
Mucinous adenocarcinoma
Mesonephric
adenocarcinoma
Vagina – Benign glandular lesions
2014
 Tubovillous adenoma
 Villous adenoma
 Mullerian papilloma
 Adenosis
 Endometriosis
 Endocervicosis
 cysts
2003
 Mullerian papilloma
 Adenoma, NOS



Tubular
Tubulovillous
Villous
Vagina – Other Epithelial Tumors
2014




Mixed tumor (2003 put in
category of mixed epi and
mesen tumors)
Adenosquamous carcinoma
Adenoid basal carcinoma
High-grade neuroendocrine
carcinoma


Small cell neuroendocrine
carcinoma
Large cell neuroendocrine
carcinoma
2003






Adenosquamous carcinoma
Adenoid cystic carcinoma
Adenoid basal carcinoma
Carcinoid
Small cell carcinoma
Undifferentiated carcinoma
Vagina – Mesenchymal Tumor and
Tumor-like lesions
2014

2003
Mesenchymal tumor




Leiomyoma
Rhabdomyoma
Leiomyosarcoma
Rhabdomyosarcoma, NOS




Undifferentiated sarcoma
Angiomyofibroblastoma
Aggressive angiomyxoma

Myofibroblastoma
Tumor-like lesions

Postoperative spindle cell
nodule
Mesenchymal tumor



Embryonal
rhabdomyosarcoma
(8841/0)







Sarcoma botryoides
Leiomyosarcoma
Endometrioid stromal
sarcoma, low grade
Undifferentiated sarcoma
Leiomyoma
Genital rhabdomyoma
Deep angiomyxoma (8841/1)
Tumor-like lesions

Postoperative spindle cell
nodule
Vagina – Mixed Epithelial and
Mesenchymal Tumors
2014
 Adenosarcoma
 Carcinosarcoma
2003
 Carcinosarcoma
(malignant mullerian
mixed tumor;
metaplastic
carcinoma)
 Adenosarcoma
 Malignant mixed
tumor resembling
synovial sarcoma
 Benign mixed tumor
Vagina – Melanocytic Tumors
2014
 Nevi



Melanocytic nevus
Blue nevus
Malignant melanoma
2003
 Malignant melanoma
 Blue nevus
 Melanocytic nevus
Vagina – Lymphoid and Myeloid Tumors
2014
 Lymphoma
 Myeloid neoplasms
2003
 Malignant lymphoma
 leukemia
Vagina – Miscellaneous Tumors
2014
 Germ cell tumors





Mature teratoma
Yolk sac tumor
Others

2003
 Germ cell tumors



Ewing sarcoma
Paraganglioma
Secondary tumor
Others



Yolk sac tumor
Dermoid cyst
PNET/Ewing tumor
Adenomatoid tumor
Secondary tumor
Vagina – Staging
2014

FIGO no longer includes
Stage 0 (Tis)
2003

FIGO Stage 0: carcinoma
in situ (preinvasive
carcinoma)
Vulva – Squamous Precusors
2014
 Squamous
intraepithelial lesion

Low-grade squamous
intraepithelial lesion
(8077/0)

High-grade squamous
intraepithelial lesion
(8077/2)

Differentiated-type
vulvar intraepithelial
neoplasia (8071/2)*
* New code was approved by the IARC/WHO
Committee for ICD-O in 2013
2003

Squamous
intraepithelial neoplasia

Vulvar intraepithelial
neoplasia (VIN3) (8077/2)
/ squamous cell
carcinoma in situ (8070/2)
Differentiated-type VIN






Carcinoma in situ of simplex type
HPV-negative
Abnormal keratinocyte differentiation and
basal cell atypia
Elderly women
 Lichen sclerosus
 Lichen simplex chronicus
p53 mutation
Keratinizing SCC
Vulva – Squamous Cell Carcinoma
2014

Squamous cell
carcinomas






2003
 Squamous cell
carcinoma, NOS
Keratinizing
Non-keratinizing
Basaloid
Warty
Verrucous





Basal cell carcinoma




Keratinizing
Non-keratinizing
Basaloid
Warty
Verrucous
Keratoacanthoma-like
Variant with tumor
giant cells
Others
Basal cell carcinoma
Vulva – Benign squamous lesions
2014
 Condyloma
acuminatum
 Vestibular papilloma
(8052/0)
 Seborrheic keratosis
 keratoacanthoma
2003
 Condyloma
acuminatum
 Vestibular papilloma
(micropapillomatosis)
(8052/0)
 Fibroepithelial polyp
 Seborrheic and
inverted follicular
keratosis
 keratoacanthoma
Vulva – Glandular Tumors
2014


2003
Paget disease
Tumors arising from
Bartholin and other
specialized anogenital
glands

Bartholin gland carcinoma





Adenocarcinoma
Squamous cell carcinoma
Adenosquamous
carcinoma
Adenoid cystic carcinoma
Transitional cell
carcinoma


Paget disease
Bartholin gland tumors









Adenocarcinoma
Squamous cell carcinoma
Adenoid cystic carcinoma
Adenosquamous
carcinoma
Transitional cell carcinoma
Small cell carcioma
Adenoma
Adenomyoma
others
Vulva – Glandular Tumors
2014




Adenocarcinoma of
mammary gland type
Adenocarcinoma of Skene
gland origin
Phyllodes tumor, malignant
2013


Adenocarcinoma of other
types


Adenocarcinoma of sweat
gland type
Adenocarcinoma of
intestinal type
Tumors arising from
specialized anogenital
mammary-like glands






Adenocacinoma of
mammary gland-type
Papillary hidradenoma
Others
Adenocarcinoma of Skene
gland origin
Adenocarcinoma of other
types
Adenoma of minor
vestibular glands
Mixed tumor of the vulva
Vulva – Glandular Tumors
2014

Benign tumors and cysts









Papillary hidradenoma
Mixed tumor
Fibroadenoma
Adenoma
Adenomyoma
Bartholin gland cyst
Nodular Bartholin gland
hyperplasia
Other vestibular gland
cysts
Other cysts
2003

Tumors of skin appendage
origin







Malignant sweat gland
tumors
Sebaceous carcinoma
Syringoma
Nodular hidradenoma
Trichoepithelioma
Trichilemmoma
others
Vulva – Neuroendocrine and
Neuroectodermal Tumors
2014

Neuroendocrine tumors

High-grade
neuroendocrine
carcinoma




Small cell
neuroendocrine
carcinoma
Large cell
neuroendocrine
carcinoma
Merkel cell tumor
Neuroectodermal tumors

Ewing sarcoma
2003
 Small cell carcinoma
 Merkel cell tumor
 pPNET/Ewing tumor
Vulva – Soft Tissue Tumors
2014

Benign tumors



Lipoma
Fibroepithelial stromal polyp
Superficial angiomyxoma
(8841/0)




Superficial myofibroblastoma
Cellular angiofibroma
Angiomyofibroblastoma
Aggressive angiomyxoma
(8841/0)



Leiomyoma
Granular cell tumor
Other benign tumors
2003

Benign


Deep angiomyxoma (8841/1)
Superficial angiomyxoma
(8841/0)





Angiomyofibroblastoma
Cellular angiofibroma
Leiomyoma
Granular cell tumor
others
Vulva – Soft Tissue Tumors
2014

2003
Malignant tumors

Rhabdomyosarcoma






Embryonal
Alveolar
Leiomyosarcoma
Epithelioid sarcoma
Alveolar soft part sarcoma
Other sarcomas





Liposarcoma
MPNST
Kaposi sarcoma
Fibrosarcoma
Dermatofibrosarcoma
protuberans (8832/1)






Sarcoma botryoides
Leiomyosarcoma
Proximal epithelioid
sarcoma
Alveolar soft part sarcoma
Liposarcoma
Dermatofibrosarcoma
protuberans (8832/3)
Vulva – Melanocytic Tumors
2014
 Melanocytic nevi






Congenital melanocytic
nevus
Acquired melanocytic
nevus
Blue nevus
Atypical melanocytic
nevus of genital type
Dysplastic melanocytic
nevus
Malignant melanoma
2003






Malignant melanoma
Congential melanocytic
nevus
Acquired melanocytic
nevus
Blue nevus
Atypical melanocytic nevus
of the genital type
Dysplastic melanocytic
nevus
Vulva – Miscellaneous Tumors
2014
 Germ cell tumors


Yolk sac tumor

Lymphoid and myeloid
tumors



2003
 Miscellaneous tumors
Lymphomas
Myeloid neoplasms



Secondary tumors
Hematopoetic and
lymphoid tumorsd



Yolk sac tumor
Merkel cell tumor
pPNET/Ewing tumor
Malignant lymphoma
Leukemia
Secondary tumors
Vulva – Staging
2014


FIGO no longer includes Stage 0 (Tis)
FIGO I (T1) Tumor confined to vulva or
vulva and perineum


2003


IA Tumor 2 cm or less in greatest
dimension and with stromal invasion no
greater than 1 mm
IB Tumor greater than 2 cm or any size
with stromal invasion greater than 1 mm
FIGO Stage 0 (Tis): carcinoma in situ
(preinvasive carcinoma)
FIGO I (T1)Tumor confined to vulva or
vulva and perineum, 2 cm or less in
greatest dimension




FIGO II (T2) Tumor of any size with
extension to adjacent perineal structures:
lower third urethra, lower third vagina,
anus
FIGO IVA (T3) Tumor of any size with
extension to the following structures:
upper 2/3 urethra, upper 2/3 vagina,
bladder mucosa, rectal mucosa, or fixed
to the pelvic bone



IA Tumor 2 cm or less in greatest
dimension and with stromal invasion no
greater than 1 mm
IB Tumor 2 cm or less in greatest
dimension and with stromal invasion
greater than 1 mm
FIGO II (T2) Tumor confined to vulva
or vulva and perineum, more than 2
cm in greatest dimension
FIGO III (T3)Tumor invades any of the
following: lower urethra, vagina, anus
FIGO IV (T4) Tumor invades any of the
following: bladder mucosa, rectal
mucosa, upper urethra, or is fixed to
pubic bone
Active hypophosphorylated
Inactive hyperphosphorylated
Ki-67