Table 3 GRADE evaluation of literature for use of gonadal biopsy

Farrugia, et al. 2013 [48]

Observational Retrospective study

Histology of 46 gonads from patients with 45,X/46,XY or 45,X/47,XYY PGD was reviewed.

In patients raised as males, where dysgenetic testes are retained, biopsy at orchidopexy and also post-pubertal with immunohistochemical staining (OCT 3/4 and TSPY) is recommended

Limited sample size, lack of blinding, lack of allocation concealment

Does not specify who had biopsy vs. gonadectomy.

No evidence of malignancy in any patient

Wunsch, et al. 2012 [33]

Observational Cohort study

6 out of 12 patients with mixed or partial GD had biopsy to evaluate for malignancy (no gonadectomy).

Biopsy can be used for early diagnosis of germ cell tumors and follow-up.

Limited sample size, lack of blinding, lack of allocation concealment

1 patient found to have tubular in situ neoplasia.

Cools, et al. 2011 [36]

Observational Study

Histology of 87 gonads from patients with 45,X/46,XY was reviewed.

For mildly undervirilized males, recommend 1 prepubertal biopsy and 1 post-pubertal biopsy.

Limited sample size, lack of blinding, lack of allocation concealment

Biopsy was done in 15 patients.

All of the tumors in this series were in situ germ cell neoplastic lesions, discovered after prophylactic gonadectomy.

In patients with ambiguous genitalia, biopsy can be used to asses tumor risk, but low threshold for gonadectomy

No tumors identifed in the patients who had gonadal biopsy alone.

Gourlay, et al. 1994 [42]

Observational Retrospective Study

Reviewed pathology from 21 patients with DSD who underwent bilateral gonadectomy at time of diagnosis.

Gonadal biopsy is unreliable in excluding the presence of small tumors

Limited sample size, lack of blinding, lack of allocation concealment

Pathology revealed many different combinations of testis, ovary, streak, and tumor within the same individual gonad.

Müller, et al. 1985 [49]

Observational Study

Gonadal tissue from multiple scrotal or labial gonadal biopsies was studied in 4 patients with 45,X/46,XY GD (ages 1 month to 18 years)

Biopsy of scrotal gonads should be done at time of diagnosis of GD to exclude presence of tumor.

Limited sample size, lack of blinding, lack of allocation concealment

All 4 patients had evidence of CIS:

-2 patients had CIS on initial biopsy

In boys without signs of CIS on initial biopsy, repeat biopsy should be performed after puberty because prepubertal CIS lesions may be missed.

-2 patients had CIS only on repeat biopsy (8 months and 16 years)