Residency - Sex Cord Stromal Tumors

Question 1

Leydig cell tumor

Answer 1

The most common sex cord tumor, accounting for ~2% of testicular tumors

Tumor characteristics: Well-circumscribed, 0.5 - 5 cm, 95% benign. Usually intratesticular, 10% with ETE. Reinke’s crystalloids (cyllindrical to rhomboid crystals) present in 40% of cases - best seen on touch prep. Sheet-like growth pattern of oncocytic cells with large, round nuclei and prominent nucleoli. Cytoplasmic lipofuscin is common.

Bimodal age distribution: 20% between 4 and 10 years, 80% between 20 and 60 years.

Symptoms: The mass itself is painless and indolent, but may secrete androgens leading to gynecomastia, impotence, and low libido. Rarely, tumors may secrete corticosteroids and cause Cushing syndrome.

Labs: testosterone, androstenedione, and dehydroepiandrosterone are frequently elevated.

Genetics: Some cases have mutations in FH, sporadically or arising as part of hereditary leiomyomatosis and renal cell carcinoma syndrome. May also be caused by germline DICER1 mutations.

Question 2

Answer 2

Lipid-rich variant of Leydig cell tumor.

Here the usually pink and granular cytoplasm is replaced by numerous fine vesicles.

These types also have a positive inhibin stain.

Question 3

What are the features that make you think a leydig tumor might be malignant?

Answer 3

Size > 5 cm
>3 mitoses/hpf
Atypical mitoses
Necrosis
Frank invasion/LVI

Question 4

Leydig cell tumor IHC

Answer 4

Pos: Inhibin-A, calretinin, MART1, CD99, SF1, STAR

Question 5

SF1 and inhibin-A in testicular tumors

Answer 5

SF1 (steroidogenic factor 1) is highly sensitive for sex cord stromal tumors as a group.

Inhibin A is a great marker for differentiating sex cord stromal tumors (positive) from germ cell tumors (negative).

Question 6

STAR

Answer 6

STAR, or steroidogenic acute regulatory protein, is a protein with a key role in the acute regulation of steroid hormone synthesis.

It is a highly sensitive and specific marker for Leydig cell tumors

Question 7

Sertoli cell tumor

Answer 7

Tumor characteristics: Well circumscribed, about 1/3 with cystic areas. Composed of sex cord cells and shows at least focal tubular differentiation. Generally an indolent tumor. Firm, tan-white tumors on gross. Can show many different architectural patterns, but usually at least part of the tumor will be tubular. Clear to eosinophilic ctoplasm with uniform round-to-oval nuclei and punctate nucleoli. Some may have a microcystic or signet ring appearance.

Seen over a wide age range, but mostly in adults, with a median age of 39.

Symptoms: Often asymptomatic, but some produce estrogen and can lead to gynecomastia or impotence.

Labs: Estrogen.

Genetics: May be caused by germline DICER1 mutations. CTNNB1 mutation (beta catenin) is sometimes present.

Question 8

Answer 8

Sclerosing variant Sertoli cell tumor

Prominent hyaline fibrosis with the cellular component making up less than 50% of the tumor

Better prognosis than conventional Sertoli cell tumors

Question 9

Answer 9

Large cell calcifying variant Sertoli cell tumor

Variant with large cells with abundant eosinophilic cytoplasm and stromal calcification.

40% occur as part of Carney complex (in which tumors are often bilateral and multifocal) , characterized by skin pigmentation, endocrinopathy, and multiple neoplasia.

Genetics: In the setting of Carney complex, tumors show the classical Carney complex mutation in PRKAR1A, a mediator of cAMP signaling in mammals.

Question 10

Age distribution for sex cord stromal tumors

Answer 10

They are rare, but most of them don’t have a specific age window

You are just as likely to have a Leydig cell tumor in a teen or an 80 year old man.