Disclosures l My co-authors and I have no relevant financial or - - PDF document

4/3/2015 1

Veronica I. Alaniz, MD, MPH Pediatric & Adolescent Gynecology Fellow University of Michigan

Utility of Ultrasound and MRI in Patients with Disorders of Sex Development Undergoing Prophylactic Gonadectomy

Veronica I. Alaniz, MD, MPH, Melina Dendrinos, MD, Noam Smorgick- Rosenbaum, MD, Elisabeth H. Quint, MD

Disclosures

l My co-authors and I have no relevant

financial or non-financial relationships to disclose.

Disorders of Sex Development (DSD)

l Defined as atypical development of

chromosomal, gonadal, or anatomic sex

l 46 XX DSD l 46 XY DSD l Sex Chromosome DSD

l Estimated incidence is 1 in 4,500 births [1]

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Prophylactic Gonadectomy

l Indicated for patients with Y chromosome material at

risk for developing Germ Cell Tumors (GCTs) [5-7]

l Premalignant: Gonadoblastoma (GB), intratubular germ cell

neoplasia (ITGCN)

l Malignant: Dysgerminoma, seminoma, and non-seminoma

l Risk of GCT varies by degree of virilization, location of

gonads, and DSD diagnosis

Germ Cell Tumor Risk

DSD Diagnosis Estimated Tumor Risk [7,9] Denys Drash Syndrome 40% 46 XY Gonadal Dysgenesis 30% 45 X/46 XY DSD 15-40% 17 β hydroxysteroid dehydrogenase deficiency 17% Partial androgen insensitivity syndrome 15% Ovotesticular DSD 2.6% Complete androgen insensitivity syndrome 0.8% High Risk Intermediate Risk Low Risk

Pre Operative Evaluation

l No standard diagnostic guidelines for

patients undergoing prophylactic gonadectomy

l Unless gonads are easily palpated, imaging

is performed to:

l Evaluate for the presence and type of

Mullerian structures

l Locate gonads l Identify any features concerning for malignant

transformation

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Study Objectives

• 1. To evaluate ultrasonography (US) and

magnetic resonance imaging (MRI) in identifying gonads in patients with Disorders of Sex Development (DSD) undergoing prophylactic gonadectomy

• 2. To assess the capacity of pre-operative

imaging to detect pre-malignant and malignant transformation

Methods

l Retrospective case series at tertiary care academic

center

l Chart review of patients with relevant ICD-9 codes seen

between January 1998 and August 2014

l Inclusion criteria:

l Karyotype showing 46 XY or 45 X/46 XY l Unilateral or bilateral prophylactic gonadectomy l Pre operative MRI and/or ultrasound

l Exclusion criteria:

l Incomplete records

Methods

l Data was abstracted from demographic

facesheets, outpatient clinic visits, radiology reports, operative reports, and pathology reports

l Proportions were compared with a chi-square

test with a statistical significance set at 0.05

l Institutional IRB approval was obtained

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Results

l 39 patients met inclusion and exclusion criteria l Most were non-Hispanic white (77%), English

speaking (97%), and had a female gender of rearing (82%)

l Average age at the time of surgery was 8.1 years

l Bimodal distribution

l 48% had surgery before age 5 l 44% had surgery after age 11

l 7 patients (18%) had a family history significant

for a first degree relative with a DSD

Results

DSD Diagnosis, N=39 ¡ n (%) ¡ Complete Gonadal Dysgenesis ¡ 9 (23) ¡ Partial Gonadal Dysgenesis ¡ 4 (10) ¡ Complete Androgen Insensitivity ¡ 5 (13) ¡ Mosaic Turner/Mixed Gonadal Dysgenesis ¡ 10 (26) ¡ 5 Alpha Reductase Deficiency ¡ 4 (10) ¡ 17 β hydroxysteroid dehydrogenase Deficiency ¡ 2 (5) ¡ Denys-Drash Syndrome ¡ 1 (3) ¡ 46 XY DSD, Unknown Diagnosis ¡ 4 (10) ¡

Results

Germ Cell Tumors, N=39 ¡ n (%) ¡ Gonadoblastoma/ITGCN ¡ 11 (28) ¡ Dysgerminoma ¡ 1 (3) ¡

Germ Cell Tumor by DSD Diagnosis ¡ n/N (%) ¡ Complete Gonadal Dysgenesis ¡ 3/9 (33)* ¡ Partial Gonadal Dysgenesis ¡ 3/4 (75) ¡ Complete Androgen Insensitivity ¡ 1/5 (20) ¡ Mosaic Turner/Mixed Gonadal Dysgenesis ¡ 4/10 (40) ¡ 5 Alpha Reductase Deficiency ¡ 0/4 (0) ¡ 17 Beta Hydroxysteroid Dehydrogenase Deficiency ¡ 0/2 (0) ¡ Denys-Drash ¡ 0/2 (0) ¡ 46 XY DSD, Unknown Diagnosis

¡ ¡ ¡* ¡Includes ¡pa-ent ¡with ¡Dysgerminoma ¡

1 /4 (25) ¡

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Study Objective #1

l Evaluate ultrasonography and magnetic

resonance imaging (MRI) in identifying gonads in patients with Disorders of Sex Development (DSD) undergoing prophylactic gonadectomy

Results

l 33 patients had pre operative ultrasound

l 35 out of 65 gonads (54%) were identified

l 14 patients had pre operative MRI

l 11 out of 27 gonads (41%) were identified l *No significant difference between imaging

modalities in identification of gonads (p=0.25)

Results

US US MRI MRI 0% 10% 20% 30% 40% 50% 60% 70% 80% Dysgenetic Testes

Gonads Identified by Imaging Modality and Gonad Type

*

* indicates statistical significance

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Study Objective #2

l Assess the capacity of pre-operative

imaging to detect pre-malignant and malignant transformation.

Results

l Pre-malignant lesions (gonadoblastoma

and ITGCN) were diagnosed in 28% of patients

l There were no distinguishing characteristics

documented on pre-operative imaging

l Dysgerminoma was diagnosed in one

patient (2.5%)

l Described as an ovary with “normal size and

echotexture” on both ultrasound and MRI

Streak Gonad vs Dysgerminoma

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Results

l No significant difference in pre-malignant

gonadal tumors among those gonads that were visualized versus non-visualized on both ultrasound (17 % vs 23 %, p=0.57) and MRI (9% vs 25%, p=0.62)

Conclusions

l Both ultrasound and MRI were limited in

identifying gonads

l Ultrasound better at identifying dysgenetic gonads

l Pre-malignant lesions were not identified on

either imaging modality

l The dysgerminoma was mistaken for a normal

• vary in a patient expected to have streak

gonads

Clinical Implications

l Ultrasound should be considered as the

first line imaging modality in DSD patients undergoing prophylactic gonadectomy

l Because pre malignant lesions cannot be

identified on imaging, surveillance of gonads in patients with DSD at low risk for GCT (such as CAIS) is controversial

4/3/2015 8 STRENGTHS AND LIMITATIONS

l Strengths

l Thorough chart review l Adds to limited available data

l Weaknesses

l Small heterogeneous patient group l Retrospective study

Special thanks to: Elisabeth Quint Emily Kobernik Previous PAG fellows

Questions?

References

l

1. Hughes, I.A., et al., Consensus statement on management of intersex disorders. J Pediatr Urol, 2006. 2(3): p. 148-62.

l

2. Gomez-Lobo, V., Multidisciplinary care for individuals with disorders of sex development. Curr Opin Obstet Gynecol, 2014. 26(5): p. 366-71.

l

3. Moran, M.E. and K. Karkazis, Developing a multidisciplinary team for disorders of sex development: planning, implementation, and operation tools for care providers. Adv Urol, 2012. 2012: p. 604135.

l

4. Lee, P.A., A perspective on the approach to the intersex child born with genital ambiguity. J Pediatr Endocrinol Metab, 2004. 17(2): p. 133-40.

l

5. Ulbright, T.M. and R.H. Young, Gonadoblastoma and selected other aspects of gonadal pathology in young patients with disorders of sex development. Semin Diagn Pathol, 2014. 31(5): p. 427-40.

l

6. Pleskacova, J., et al., Tumor risk in disorders of sex development. Sex Dev, 2010. 4(4-5): p. 259-69.

l

7. Cools, M., et al., Germ cell tumors in the intersex gonad: old paths, new directions, moving frontiers. Endocr Rev,

• 2006. 27(5): p. 468-84.

l

8. Cools, M. and L.H. Looijenga, Tumor risk and clinical follow-up in patients with disorders of sex development. Pediatr Endocrinol Rev, 2011. 9 Suppl 1: p. 519-24.

l

9. Pleskacova, J., et al., Tumor risk in disorders of sex development. Sex Dev, 2010. 4(4-5): p. 259-69.