Glandular Lesions of the Cervix

8/10/2019 Glandular Lesions of the Cervix

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DIAGNOSTIC PROBLEMS

IN GLANDULAR LESIONS

OF THE UTERINE CERVIX

Esther Oliva

Massachusetts General Hospital

[email protected]

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)


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


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


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

Glandular Lesions of the Cervix

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