Post on 02-Jun-2018
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DIAGNOSTIC PROBLEMS
IN GLANDULAR LESIONS
OF THE UTERINE CERVIX
Esther Oliva
Massachusetts General Hospital
eoliva@partners.org
Recent Advances in Gynecologic, Urologic, and
Soft Tissue Pathology. Timisoara, June 2-4, 2013
ADENOCARCINOMA IN SITU (AIS)
Typically begins at the squamocolumnar junction
Concomitant high-grade squamous dysplasia in
approximately 50% of cases
High-risk HPVs frequently found
< 20% skip lesions
!10 to 20 % of cervical adenocarcinomas
AIS: Normal architecture preserved
Sharp transition
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Nuclear enlargement, coarse chromatin, small single or multiple
nucleoli, increased mitotic activity, and +/- nuclear stratification
involving part or all of the surface and/or glandular epithelium
Hanging mitoses
APOPTOTIC BODIES
Significant correlationbetween apoptotic bodiesand mitotic figures
Seen in adenocarcinoma insitu and all types of invasiveadenocarcinoma except inadenoma malignum
May be seen in cervicalendometriosis
Differential diagnosis withintraepithelial lymphocytes
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LOBULAR
ARCHITECTURE
Replacement of pre-existing glands
Endocervical glands may have a complex growth pattern
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Less obvious cytologic atypia, mitoses and apoptosis
PANETH CELLS
MIXED AIS
Intestinal-Type Endocervical Adenocarcinoma In
Situ: An Immunophenotypically Distinct Subset of
AIS Affecting Older Women
Howitt BE, et al , Am J Surg Pathol 2013;37:625
TO REMEMBER:
- Occurs in older age group (44.5 vs 32.6 years)
- Rarely pancreatobiliary/gastric epithelium if few
goblet cells in adjacent conventional AIS
- Subset (4/13) show variable p16 and Ki67 staining
- Not as frequently HPV 16 or 33 positive (6/9)
when compared to conventional AIS
- CDX2 + and p53 -
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STRATIFIED MUCINOUS INTRAEPITHELIAL LESION
(SMILE)
ADENOCARCINOMA IN SITU
Differential Diagnosis
Reactive glandular atypia
High-grade squamous dysplasia involving glands Endometriosis
Tubal metaplasia
Mesonephric hyperplasia
Radiation induced atypia
Invasive adenocarcinoma
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GLANDULAR ATYPIA = REACTIVE
HIGH-GRADE SQUAMOUS DYSPLASIA
INVOLVING GLANDS
S
C
C
In situ
M
I
M
I
C
K
I
N
G
A
I
Sp63 may be helpful
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CERVICAL ENDOMETRIOSIS
Two major categories:
- Superficial: Related to previous trauma
No association with endometriosis
elsewhere
- Deep: Associated with pelvic endometriosis
ENDOMETRIOSIS AIS
CERVICAL ENDOMETRIOSIS WITH ATYPIA
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ENDOMETRIOSIS
DIFFERENTIAL FEATURES
EMOS AIS
Abnormal Pap smear + +
Endometrial stroma + -
Stromal hemorrhage + -
Nuclear pseudostratif + +
Mitotic figures -/+ (also stroma) +
Apoptotic bodies -/+ +
Squamous dysplasia - +
p16 positivity Focal Diffuse
TUBAL METAPLASIA
MIMICKING ADENO-
CARCINOMA IN SITU
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TUBAL METAPLASIA
Frequent finding
More common in hysterectomy specimens than
cone biopsies
Typically in upper endocervix and deep glands
Noassociation with other pathologic conditions
Frequent confusion with endocervical gland
neoplasia on biopsy and Pap smears
TUBAL METAPLASIA
Atypia
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ENDOMETRIOID
CILIATED CARCINOMA
UBAL-TYPE AIS
AIS TEM/EMOS MIB 1 > 30% < 10%
ProExC + (>50% cells) + (
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AIS MESONEPHRIC
LESIONS
CD10 + + (L)
AR - +/-
Calretinin - +/-
Vim - +/-
CEA (m) + -
ER -/+ -
PR +/- -
p16 + -/+
PAX2 - +
PAX8 + +
RADIATION INDUCED ATYPIA
EARLY INVASIVE ADENOCARCINOMA
Pathologic definition
Presence of stromal invasionwitheffacement of the normal glandular
architecture with tumor extending beyondthe deepest normal crypt
Diagnosis cannot be made on biopsy alone
stor AG.Int J Gynecol Pathol 2000;19:29-38
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EARLY INVASIVE ADENOCARCINOMA
stor AG Int J Gynecol Pathol 2000;19:29-38
IN 20% OF CASES IT IS NOT
POSSIBLE TO DISTINGUISH
BETWEEN ADENOCARCINOMA IN
SITU AND EARLY INVASIVE
ADENOCARCINOMA
INVASIVE OR IN SITU?
AIS
vs
ADENOCARCINOMA
WITH EXPANSILE GROWTH
LOOK AT AND COMPARE TO THE
ARCHITECTURE OF THE NON-
NEOPLASTIC ENDOCERVICAL GLANDS
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INVASIVE
ADENOCA
INVASIVE
ADENOCA
OVARIAN METASTASES
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Yemelyanova A et al, Am J Surg Pathol 2009;33:914
ENDOCERVIX ENDOMETRIUM
p16 PgR
ENDOCERVICAL ADCA WITH PROMINENT
ENDOMYOMETRIAL INVOLVEMENT
CERVICAL ADENOCARCINOMA (WHO)
Mucinous
- Endocervical
- Intestinal
- Signet-ring cell
- Minimal deviation
- Villoglandular
Endometrioid
Clear cell
Serous
Mesonephric
Adenoid basal/adenoid cystic
Neuroendocrine tumors
ADENOMA MALIGNUM
(Minimal Deviation Adenocarcinoma)
1-10% of cervical adenocarcinomas
Nonspecific presenting symptoms; mucoid vaginaldischarge in a minority of patients
Association with Peutz-Jeghers syndrome and sexcord tumors with annular tubules
Most tumors HPV negative
Loss of heterozygosity at 19p13.3
Poor prognosis; only 50% of patients with
stage I alive at 2 years after initial diagnosis
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ADENOMA
MALIGNUM
(Minimal
deviation
endocervical
adenoca)
ADENOMA MALIGNUM
ADENOMA MALIGNUM WITH DECEPTIVE APPEARANCE
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ADENOMA MALIGNUM
(Minimal Deviation Adenocarcinoma)
Differential Diagnosis
Deep endocervical glands and Nabothian cysts
Lobular endocervical gland hyperplasia or pyloric
gland metaplasia
Endocervical hyperplasia, NOS
Tunnel clusters
Cervical adenomyoma
Endocervicosis
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LOBULATION
NO STROMAL RESPONSE
NO CYTOLOGIC ATYPIA
WELL-DIFFERENTIATED
VILLOGLANDULAR ADENOCARCINOMA
Occurs at a younger age (average 35 yrs)
than cervical adenocarcinomas in general
In the series reported by Kurman and
colleagues 62% of patients had a history
of oral contraceptive use
If pure it has an excellent prognosis
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VILLOGLANDULAR ADENOCARCINOMA:
Diagnosis
It is very important to evaluate thecytologic features and theadvancing front of the tumor inorder to exclude the presence of aconventional adenocarcinoma
WELL-DIFFERENTIATED
VILLOGANDULAR ADENOCARCINOMA
Differential Diagnosis
Papillary endocervicitis
Mullerian papilloma Villous adenoma
Papillary adenofibroma
Conventional endocervical adenoca withprominent exophytic papillary growth
Serous carcinoma
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ADENOCA, USUAL TYPE,with PAPILLAE
METASTATIC SEROUS CA
CLEAR CELL CARCINOMA
Biphasic age distribution
1/3 associated with in utero exposure to
diethylstilbestrol (DES) and non-steroidal
estrogen before the 18thweek of gestation
Frequent coexistence with vaginal adenosis,
and less commonly transverse vaginal or
cervical ridges
2/3 not associated with DES
CLEAR CELL
CARCINOMA
Typical architectural patterns
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CLEAR CELL CARCINOMA
Differential Diagnosis
Arias-Stella reaction
Microglandular hyperplasia
Squamous cell carcinoma with prominent
clear cells
Yolk sac tumor
Alveolar soft part sarcoma
ARIAS STELLA REACTION
DIFFERENTIAL FEATURES
AS
CCC
Pregnancy/OC + -
Incidental finding + -
Preserved architecture + -
Glandular involvement + -
Intranuclear inclusions + -
Prominent nuclei - +
Mitotic activity Absent Present
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MIC
ROGLANDULAR
H
SOLID MICROGLANDULAR HYPERPLASIA
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SIGNET RING CELLS
MGH CCC
Tubular/Solid +/- +
Hyalinized stroma + +
Cytoplasm Mucin GlycogenAtypia Absent Present
Mitoses/10HPFs "1 Frequent
Invasive growth Absent Present
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MICROGLANDULAR HYPERPLASIA vs
MGH-LIKE CARCINOMA
Features favoring adenocarcinoma:
Postmenopausal age
Absence of typical areas of MGH
Cytologic atypia greater than expected in MGH
Increased mitotic activity (> 1 mitoses/10HPFs)
High MIB-1 index
MESONEPHRIC
CARCINOMA
Tubular growth
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MESONEPHRIC CARCINOMA
Spindle growth Papillary growth
MESONEPHRIC CARCINOMADifferential Diagnosis
Mesonephric hyperplasia
Cervical AIS
Cervical endometrioid adenocarcinoma
Uterine tumor resembling ovarian sex-cord tumor
Endometrioid carcinoma from corpusextending to cervix
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Diffuse Mesonephric Hyperplasia
Tips: No complex architecture, minimal cytologic atypia and
mitotic activity and absent stromal response
ENDOMETRIOID CA EXTENDING TO CERVIX
SIMULATING MESONEPHRIC HYPERPLASIA
THANK YOU
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UNUSUAL ENDOCERVICAL CARCINOMAS
p16 p53 CEAm HPV
MD (3) 0 1 3 0
Gastric (9) 1 5 8 1
CCC (11) 5 1 2 0
Serous (4) 2 1 3 0
Mesonephric (3) 0 0 0 0