TALES OF COMMON OVARIAN TUMOURS WITH A TWIST IN THEIR CLINICAL IMPLICATIONS - PowerPoint Presentation

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TALES OF COMMON OVARIAN TUMOURS WITH A TWIST IN THEIR CLINICAL IMPLICATIONS

DR PRITI JOSHI MBBS, MD,

FRCPath

CONSULTANT ANATOMIC PATHOLOGIST

CLEVELAND CLINIC ABU DHABI

&

CLINICAL ASSOCIATE PROFESSOR

CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE OHIO

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CASE 132 year old female – bilateral

oophorectomy

2cm right

dermoid

cyst was seen on USG

Left ovary – normal on USG

Patient critically ill and

semicomatose

requiring

ventilatory

support but

haemodynamically

stable

Initially presented with

behavioural

and mood changes, abnormal facial movements and appearing depressed at times

C-section 6 months back and a left

teratoma

(

dermoid

cyst) was incidentally found, unilateral ovarian

cystectomy

done

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GLIAL FIBRILLARY ACIDIC PROTEIN (GFAP) STAIN

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DIAGNOSIS

NMDAR ENCEPHALITIS

Anti-N-methyl-D-

aspartate

receptor encephalitis

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ANTI-N-METHYL-D-ASPARTATE RECEPTOR ENCEPHALITIS

Very rare

paraneoplastic

manifestation of ovarian

teratoma

(

dermoid

cyst)

Nervous tissue in ovarian

teratomas

may express NMDAR subunits that react with patient’s antibodies, thereby triggering a cascade of symptoms that is recognized as anti-NMDAR encephalitis and that mainly affects the hippocampus/forebrain regions

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Disease was officially categorised

and named by

Josep

Dalmau

and colleagues in 2007

Asian & African-American > Caucasians/Hispanics

Severe, prolonged and potentially fatal pathologic condition of young women

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PRESENTATION

Neuropsychiatric symptoms (

esp

behavioural

changes), often preceded by nonspecific

prodromal

symptoms

Memory impairment, later involuntary movements of face, mouth and tongue and symptoms of

dysautunomia

Diagnosis - Anti-NMDAR antibodies in serum/CSF

Tumour

resection and immunotherapy

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FOLLOW UP

Positive NMDA antibodies in serum and CSF

Both ovaries had

teratoma

, microscopic in 1

Needed

ventilatory

support

Plasmapharesis

Airlifted to Oxford Centre for Neurosciences in UK

No follow up later

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CASE 256/F postmenopausal - worsening hirsutism and deepening of voice

Serum testosterone - 8nmol/L (normal <1.8)

Investigated by endocrinologist and was found to have a unilateral ovarian mass

Suspected hormone producing

tumour

– Sex Cord

Stromal

Tumour

of Ovary

Bilateral

salpingo-oophorectomy

done

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GROSS FINDINGS

80mm intact mass

E/S - Smooth surface

C/S – partly

unilocular

cystic and partly solid

Cyst contents -

mucoid

No necrosis or haemorrhage

No normal peripheral ovarian tissue

Normal fallopian tube

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MICROSCOPIC FINDINGS

Mixed architecture

- Small & large nests with

pallisading

&

rosetting

Cord-like pattern, ribbons and thick

trabeculae

Few glands lined by mucinous epithelium in EC

mucin

Focal single file and

discohesive

goblet cells

Uniform round to oval

tumour

cells and nuclei

Variable amount pale to light eosinophilic cytoplasm

No necrosis

No mitoses

No LVSI

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Cyst - single layer of cuboidal

to low columnar

mucinous

epithelium

Cyst wall of normal ovarian

stroma

Prominent luteinised cells at the compressed tumour periphery and in b/t tumour cell nests

No thyroid tissue or other

teratoma

elements

Other ovary and both fallopian tubes – normal

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IMMUNOHISTOCHEMISTRYStrongly positive with

synaptophysin

(negative with

chromogranin

and CD56)

Goblet cells CK7 and CDX2 positive, but the rest of

tumour

cells negative

Luteinised

cells highlighted by

inhibin

and

calretinin

No staining with TTF-1 and CK20

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DIAGNOSIS

NOT SEX CORD STROMAL TUMOUR

BUT

CARCINOID TUMOUR, MUCINOUS TYPE

PRIMARY MONODERMAL TERATOMA OF OVARY VS

METASTATIC CARCINOID TUMOUR

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Tumour cells are not hormone producing

Stromal

reaction (prominent luteinized cells) caused by

tumour

Hormone production by

luteinised

cells caused

virulising

symptoms

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FOLLOW UPFeatures of

virulisation

drastically reduced post-surgery and serum testosterone level dropped within 2 days after surgery

Appendectomy – no

carcinoid

Octreotide

scan – no other primary seen

No features of

carcinoid

syndrome

Patient made full recovery and remains well 3 years post surgery

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FINAL DIAGNOSIS

TUMOUR WITH FUNCTIONING STROMA

Term coined by Robert Scully in 1957

Associated with primary or metastatic

tumours

Androgenic or

oestrogenic

manifestations

Luteinized

stromal

cells or rarely

Leydig

cells dispersed within the neoplasm

1/3

rd

cases occur in pregnancy

Most cases with peripheral distribution of luteinized cells have been large sized

monodermal

teratoma

Nonneoplastic

rete

cysts

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MUCINOUS CARCINOID OF OVARY

Monodermal

teratoma

1 of 4 subtypes of primary ovarian

carcinoid

Least common subtype of ovarian subtype

Resembles goblet cell

carcinoid

Most reported cases are clinically benign

3 categories of

mucinous

carcinoid

tumours

- Well differentiated(our case) - small glands l/b columnar and goblet cells, +/-

mucin

, mini cytological

atypia

- Atypical - Confluent/

cribriform

glands, mild-mod

atypia

- Carcinoma arising in

mucinous

carcinoid

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CASE 330/F - unilateral ovarian cystectomy for suspected endometriosis

No other abnormality on laparoscopy

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Histology showed regular features of endometriotic

cyst

Cyst lined partly be endometrial epithelium with underlying

stroma

Extensive old

haemorrhage

in the cyst wall

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IMMUNOHISTOCHEMISTRYER negative

Napsin

positive

Wild-type staining with p53

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DIAGNOSIS

ATYPICAL ENDOMETRIOSIS (IN SITU CLEAR CELL CARCINOMA)

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ENDOMETRIOSIS – clinical significance from cancer perspective

Risk of progression to cancer over lifetime

Risk for occult cancer at initial resection of endometriosis

Precise risks not known, but very low

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ENDOMETRIOSIS ASSOCIATED TUMOURS

Endometrioid

borderline

tumour

or carcinoma

Clear cell borderline

tumour

or carcinoma

Seromucinous

borderline

tumour

or

carcinoma

Adenosarcoma

Endometrial

stromal

sarcoma

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RISK OF OCCULT ENDOMETRIOSIS ASSOCIATD TUMOURPractical implications for gross specimen sampling

Awareness of benign alterations in endometriosis that mimic

neoplasia

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Benign Alterations in Endometriosis

Potential

Neoplastic

Mimics

Mucinous

metaplasia

Mucinous

tumour

Tubal/ciliated

metaplasia

Serous

tumour

Arias Stella reaction

Clear cell

tumour

Reactive

atypia

(inflammatory)

Clear cell

tumour

Polypoid

endometriosis

Endometrioid

tumour

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ATYPICAL ENDOMETRIOSIS

Definition

Hyperplasia +/-

cytologic

atypia

in endometriosis without fulfilling criteria for any type of cancer

Endometriosis with complex (atypical) hyperplasia

Endometriosis with atypical hobnail

metaplasia

Incidence

40% of endometriosis adjacent to ovarian cancer

1-2% endometriosis without cancer

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ATYPICAL ENDOMETRIOSIS Notable cytological

atypia

Absence of papillary,

tubulocystic

and solid growth patterns (distinguish from clear cell carcinoma)

Features

favouring

benign reaction (reactive

atypia

/Arias Stella reaction ) in endometriosis:

Abundant cytoplasm

Intraepithelial inflammation

Smudged chromatin

Intranuclear

inclusions

AND LACK OF - Mitoses

- Increased N/C ratio and

hyperchromasia

- Lack of papillary,

cribriform

, branching growth

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ARIAS STELLA REACTION

Clear cells

Hobnail

Nuclear

atypia

Mitoses

IHC - HNF1-b exp

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ARIAS STELLA REACTIONNo mass lesion

Noninvasive and non-infiltrative growth pattern

Background non-

neoplastic

endometriosis

Progestational

effects frequent

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TAKE HOME MESSAGESignificance of Atypical Endometriosis

Likely precursor of endometriosis-associated

tumours

Precise risk of progression not known

Only limited data in the literature; subject to reproducibility problems

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ATYPICAL ENDOMETRIOSIS

Alteration

Significance

Mild cytological

atypia

, no

hypeprlasia

Likely reactive

atypia

Moderate to severe cytological

atypia

, no hyperplasia

Possible precursor, sample more tissue, advise follow up

Hyperplasia

Possible precursor, sample more tissue, advise follow up

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Atypical endometriosis has similar genetic alterations to clear cell carcinoma which suggests that atypical endometriosis is a pre-malignant lesion

A small percentage of ovarian endometriosis has already undergone genetic alterations (including loss of BAF250a

exp

, HNF-1b up-

reg

, and loss of ER and PR

exp

), before showing morphological

atypia

.

These molecules might be potentially useful in screening high-risk endometriosis.

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ReferencesLoss of ARID1A/BAF250a expression in ovarian endometriosis and clear cell carcinoma.

Int

J

Clin

Exp

Pathol

2012

Clear

cell carcinoma of the ovary arising in atypical endometriosis: a report of 8 cases. Arch

Gynaecol

Obstret

2011

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RETROPERITONEAL CLEAR CELL CARCINOMA

51/F Large retroperitoneal mass

8 yr post hysterectomy and bilateral

salpingo-oophorectomy

-

adenomyosis

, ovarian endometriosis and pelvic peritoneal endometriosis

Current retroperitoneal mass histology – Classical features of Clear Cell Carcinoma (in the absence of ovaries and uterus)

PAX8 ,

napsin

, AE1/AE3, EMA - positive

WT1, ER, (germ cell markers – PLAP, Oct4, CD30 and CD117) - negative, p53 wild-type

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DIAGNOSIS

EXTRA-OVARIAN CLEAR CELL CARCINOMA,

possibly arising at an

endometriotic

site

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HYPOTHESIS FOR EXTRA-OVARIAN RETROPERITONEAL CCCRemoval of ovary/

ies

may not have been complete due to adhesions caused by endometriosis at the time of previous surgery

Retroperitoneal deposit of recurrence from an occult or

smouldering

clear cell carcinoma in previously excised ovary/

ies

Malignant transformation of extra-ovarian endometriosis

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THANK YOU