Table 3 Proposal of histological classification of the various types of gonads and additional lesions encountered in disorders of sex development

Histological subtypes

Normal gonad

Testis: Thick and regular albuginea

Round or oval regular seminiferous tubules

Low-abundance or edematous interstitium

α-inhibin +, AMH+

Ovary: Abundant ovarian stroma

Numerous and regular follicles

 Hypoplastic testis

Scarcity of seminiferous tubules

α-inhibin +, AMH+

Germ cell hypoplasia

Abundant edematous stroma

 Dysplasia

Architectural disorganization

α-inhibin+/−, AMH+/−

Irregular, branched seminiferous tubules

Thin, irregular albuginea

Fibrous interstitium

 Streak gonad

Abundant fibroblastic interstitium

α-inhibin−, AMH−

Absence of tubule

Absence of follicle

 Ovotestis

Coexistence in the same gonad of ovarian and testicular tissues

Additional lesions

 Atrophy

α-inhibin+, AMH+

Thickening of the lamina propria of seminiferous tubules

Seminiferous tubules of small diameter

Seminiferous epithelium disorganization

Incomplete spermatogenesis

 Undifferentiated gonadal tissue

+/− germ cell immaturity biomarkers: CD117, OCT4

Germ cells within immature sex cords or isolated in the interstitium

 Tumor

Gonadoblastoma, germ cell neoplasia in situ, germ cell tumor, hamartoma, …

Histological features of dysplasia

 Mild dysplasia

Abnormal branching of tubules located under the testicular capsule, separated from the normal area of testis by an edematous gap

Progressive loss of expression of α-inhibin and AMH in disorganized tubules; absence of expression in severe dysplasia

+/− abnormal expression of CD117 and OCT4 of germ cells

 Moderate dysplasia

Irregular and thin albuginea, irregular tubules, fibrosis and edema of the interstitial tissue

 Severe dysplasia

Absence of albuginea, loss of the lobular pattern, anastomotic tubules, fibrous or fibroblastic interstitium