Gonadal non-Germ Cell

Tumors

C. Virgone – G. Cecchetto

TREP project (January 2000-March 2012)

TREP Meeting Trieste

April 12, 2012

Gonadal non-Germ Cell Tumors

Various and different histotypes including:

– Sex Cord-Stromal tumors (Ovary and Testis) 45 (13

t) » Juvenile Granulosa Cell tumors 24 (5

testic.)

» Sertoli-Leydig Cell tumors 14 (8

testic.)

» Others (fibrothecoma, GCT,…) 7

– Epithelial tumors 15 » Mucinous/Serous Cystadenoma (benign) 12

» Mucinous/Serous Cystadenoma (border-line) 3

» Mucinous/Serous Cystadenocarcinoma -

– Gonadoblastomas 2

• 23 girls (5-176 mo; median 110)

• Precocious puberty in 9/23 (8 JGCT)

• Ovarian torsion in 2, spontaneous tumor

rupture in 1

Ovarian SCST: staging and treatment

STAGE FEATURES TREATMENT

Stage I

Disease limited to the ovary (or both) and completely excised;

negative peritoneal washing. No clinic, surgical or histologic

evidence of disease extending beyond the ovary and tumoral

markers' and/or hormons' levels in range after surgery.

Surveillance

Stage II Microscopic residuals, spillage or nodes affected by disease

(pathologist's measurement <2 cm); negative peritoneal

washing. Tumoral markers positive or negative.

PEB x 3 cycles

Stage III

Macroscopic residuals or initial biopsy only; local invasion

(omentum, bowel, bladder); positve peritoneal washing; nodes

affected (pathologist's measurement>2cm).

Tumoral markers positive or negative

PEB x 4 cycles, then surgery

if possible

Stage IV Distant metastasis. Negative or positive markers

PEB x 4 cycles, then surgery

(metastasis included)

if possible

Hidden

disease

Stage I but tumoral markers persistently out of normal range

after a complete surgery.

PEB x 4 cycles, then surgery

(metastasis included)

if possible

Treatment

• 16/25 adnectomy, 8/25 ovarectomy; 1 enucleation

• 2 bilateral tumors

» 1 SST: adnectomy and contralateral enucleation

» 1 SLCT: bilateral adnectomy (metachronous)

• 19 St I, 3 St II and 1 St IV: CT in 4/23 (2 St I, 1 St II

and St IV)

• 21 CR, 1 2° CR and 1 DOD

New cases

• 9 new patients registered from 2010 » 7 JGCT

» 1 GCT cistico, variante adulto

» 1 Fibroma/Thecoma

• 7 St I, 1 St II e 1 St III

• PEB in 2 cases

• CR in 9/9 cases

Series’ update (March 31, 2012)

Pts Age Endocrine

Symptoms Side Surgery CT Stage and Outcome (FU)

JGCT 19 70 mo

(4-172)

14 (prec.

puberty)

11 left

8 right

6 ovariectomy

13 adnectomy 4

16 st. I 19 CR

2 st. II (29 mo; 3-86)

1 st. III

SLCT 6 128 mo

(40-176) 0

4 left

1 bil

5 adnectomy

1 adnectomy 2

1 st. I 2nd CR 3 st. II 1 CR, 1 DOD*

1 st. IV CR*

(14; 3-32)

Thecoma 4 125 mo

(59- 175) 0

2 left

2 right

2 ovariectomy

2 adnectomy

0 4 st. I 4 CR

Sclerosing

Stromal

Tumor

2

172 and

133 mo

0 1 right

1 bil

1 ovariectomy

1 adnectomy +

contralateral

enucleation

0 1 st. I 2 CR

1 st. II (12, unk.)

GCT adult 1 144 mo 1 left adnectomy - St I CR (59 mo)

Ovary: conclusive results (follow-up 24 months – range 3-86)

32 cases:

first CR 30

second CR 1

DOD 1

- JGCT: 19/19 first CR

- SLCT: 4/6 first CR

1 second CR

1 DOD

- Other: 7/7 first CR

Remarks General compliance to guidelines

JGCT was the most frequent histotype: early stage at

diagnosis and excellent prognosis

SLCT affected older patients: major aggressiveness in

tumors with heterologous elements and/or retiform

pattern

Fibroma/Thecoma tumors and sclerosing stromal

tumors are uncommon in children and have a benign

behaviour

Remarks

Ovariectomy with sparing of adnexa when feasible

Minimally invasive procedures only in small tumors

Chemotherapy (as for MGCT) seems useful, but larger series are needed

• 11 patients

• 5/11 < 1 year (median 23 mo; 1-171)

• 1/11 with hormonal signs, 9/11 testicular enlargement

Testis SCST: staging and treatment

STAGE FEATURES TREATMENT

Stage I

Disease limited to the testis and completely excised via

inguinotomy. Tumoral markers' and/or hormons' levels in range

after surgery. Negative histological examination after

hemyscrotectomy (performed because of transscrotal approach

at first surg.)

Surveillance

Stage II

Microscopic residuals, nodes affected by disease (pathologist's

measurement <2 cm) or transcrotal orchiectomy with spillage.

Tumoral markers positive or negative. Positive histological

examination after hemyscrotectomy

PEB x 3 cycles

Stage III Nodes affected (pathologist's measurement>2cm). Tumoral

markers positive or negative

PEB x 4 cycles, then surgery

if possible

Stage IV Distant metastasis. Negative or positive markers

PEB x 4 cycles, then surgery

(metastasis included)

if possible

Hidden

disease

Stage I but tumoral markers persistently out of normal range

after a complete surgery.

PEB x 4 cycles, then surgery

(metastasis included)

if possible

Treatment

4 enucleations

1 scrotal approach (St. II)-> no CT

10/11 St I; 11/11 CR

New cases

2 new cases registered from 2010:

1 JGCT: 20 days, testicular

enlargement, left orchifunicolectomy

1 Sertoli Cell tumor (only registration

form)

Series’ update (March 31, 2012)

Pts Mean age

(range)

Endocrine

Symptoms Side Surgery Stage and Outcome (FU)

JGCT 5 91 mo

(1-139) 1

2 right

3 left

3 orchifunicolectomy

1 enucleation

3 st. I 5 CR

1 st. II (29; 12-52)

LCT 4 8 mo

(2-23) 0

3 right

1 left

1 orchifunicolectomy

3 enucleation

4 st. I 4 CR

(47; 12-77)

SCT 2 3 mo 0 1 left

1 ukn

1 orchifunicolectomy

1 unknown

1 st. I 1 CR

1 unknown (52)

SCST

incompl.

diff.

2 1 mo;

171 mo 0 2 left 2 orchifunicolectomy

2 st. I 2 CR

(92;6)

Testis: conclusive results (follow-up 44 months-range 12-92)

13 cases first CR 12 (1 case missing data)

- JGCT: 6/6 first CR (3 enucl.)

- LCT: 4/4 “ (1 enucl.)

- SCT: 1/2 “

- other: 2/2 “

Remarks

General compliance to guidelines

LCT the most common histotype

Clinical benign behaviour (early diagnosis?)

Remarks

Enucleation accepted (if α-FP negative)

Intraoperative frozen section to allow testis-sparing

surgery

Scrotal access doesn’t need emiscrotectomy (if no

micro residuals)?

Epidemiological remarks

Epidemiological remarks

Epidemiological remarks

No children > 15 years in our testis SCST series

» 2 patients > 10 ys

No girls > 15 years in our ovarian SCST series » 11 patients > 10 ys

Girls > 15 ys affected by epithelial tumors

FOG-2 and GATA-4

15 ovarian SCSTs from TREP files

FOG-2 and GATA-4

FOG-2 and GATA-4:

FOG/GATA expression replicates embryonal gonadal phenotype:

» JGCTs replicates primordial ovarian follicles

» SLCTs embryonal testis

In fibroma/thecoma group GATA-4 and FOG-2 indicate abnormal activation of GATA pathway and might be involved in the onset of these tumors

FOG-2 and GATA-4:

No correlation between GATA-4 and prognosis

and/or clinical behaviour both in JGCT and SLCT

GATA-4 expression in JGCTs may be contrasted

by strong FOG-2 expression (inhibiting role)

FOG-2 expression in SLCTs may have a

prognostic value? (lacking in advanced stage

tumors)