Leydig cell tumours of the testis and variants

Epidemiology

Leydig cell tumours constitute 1-3% of all testicular tumours.

Clinical features

In children, they may present with isosexual pseudoprecocity. In adults, they present with a mass and/or gynaecomastia.

Histopathology

The usual appearance is of sheets of polygonal cells with abundant eosinophilic cytoplasm. they may be divided by hyalinised fibrous septa into lobules. Crystals of Reinke may be seen in 30-70% of cases. The presence of lipid may cause vacuolation.

Variants include:

• pseudoglandular or pseudofollicular
  

• microcystic
  

• myxoid
  

• small cells with scanty cytoplasm
  

• lipid-rich adrenocortical-like
  

• calcification, which may be psammomatous and ossification
  

• adipose metaplasia¹; the adjacent Leydig cells may contain lipid droplets.
  

• spindle cell differentiation¹; the spindle cell component may be bland or sarcomatoid

Immunohistochemistry²

a-inhibin	15/163, 33/334, 28/285
Cytokeratins	Usually negative or weakly positive, some may show moderate / dot-like positivty2
Cam5.2	7/163
AE1/AE3	14/334
CK7	~50% of cases focally positive4
CK20	~50% of cases focally positive4
vimentin	14/163
S-100	10/163, 2/26 benign tumours4, 0/7 malignant tumours4
chromogranin	24/26 benign tumours4, 3/7 malignant tumours4
synaptophysin	23/334
desmin	2/163
EMA	4/163
ER	some4
PR	some4
CD99	10/155
Melan-A	4/?46, 4/47
PLAP	4/155
CEA	0/163

Immunohistochemistry of variants¹

	Leydig cell tumour with adipose cells		Leydig cell tumour with spindle cells
	usual component	fat component	usual component	spindle component
a-inhibin	6/7	5/7	4/5	3/5 : the one sarcomatoid example was negative
Melan-A (A-103)	5/7	4/7	6/7	5/7 : the one sarcomatoid example was negative
Calretinin	6/7	6/7	5/6	5/7 : the one sarcomatoid example was negative
S-100	1/7 : focal in one case	5/7	1/5	1/5 : the one sarcomatoid example was negative
SMA	ND	ND	0/5	0/5
HHF-35	ND	ND	0/5	0/5

Differential diagnosis

• Leydig cell hyperplasia

• sex-cord-stromal tumour (unclassified) with incomplete Leydig cell differentiation.

• Testicular "tumour" of the adrenocortical syndrome (TTAGS); may show fatty metaplasia, sometimes with haemopoiesis. There is prominent lipofuscin and an absence of Reinke crystals.

• Large cell calcifying Sertoli cell tumour: frequently bilateral / multifocal, lacks Reinke crystals

• If lipid droplets present, seminoma, but Leydig cell tumours lack abundant glycogen and lack lymphocytic / granulomatous infiltrate.

• Coalesced lipid droplets may resemble microcystic spaces of yolk sac tumour.

• Malakoplakia

• Plasmacytoma

Prognosis

• All childhood Leydig cell tumours are benign.

• About 10-17% of adult cases are malignant. Features associated with malignancy are²:

  • increasing age

  • large size (>5 cm)

  • infiltrative margins / invasion beyond the testis

  • lymphovascular invasion

  • marked nuclear pleomorphism

  • tumour necrosis

  • mitotic index >3/10HPF / atypical mitotic figures

• A spindle cell component is only associated with malignant behavior if it is sarcomatoid¹.

References

¹Ulbright, T. M., J. R. Srigley, et al. (2002). "Leydig cell tumors of the testis with unusual features: adipose differentiation, calcification with ossification, and spindle-shaped tumor cells." Am J Surg Pathol 26(11): 1424-33.

²Shanks JH, Iczkowski KA. Non-germ cell tumours of the testis. Current Diagnostic Pathology 2002;8:83-93.

³McCluggage, W. G., Shanks, J. H., Whiteside, C., Maxwell, P., Banerjee, S. S., Biggart, J. D. Immunohistochemical study of testicular sex cord-stromal tumors, including staining with anti-inhibin antibody. Am J Surg Pathol 1998;22:615.

⁴Iczkowski, K. A., Bostwick, D. G., Roche, P. C., Cheville, J. C. Inhibin A is a sensitive and specific marker for testicular sex cord- stromal tumors. Mod Pathol 1998;11:774.

⁵Kommoss, F., Oliva, E., Bittinger, F., Kirkpatrick, C. J., Amin, M. B., Bhan, A. K., Young, R. H., Scully, R. E. Inhibin-alpha CD99, HEA125, PLAP, and chromogranin immunoreactivity in testicular neoplasms and the androgen insensitivity syndrome. Hum Pathol 2000;31:1055-61.

⁶Busam, K. J., Iversen, K., Coplan, K. A., Old, L. J., Stockert, E., Chen, Y. T., McGregor, D., Jungbluth, A. Immunoreactivity for A103, an antibody to melan-A (Mart-1), in adrenocortical and other steroid tumors. Am J Surg Pathol 1998;22:57-63.

⁷Kaufmann, O., Koch, S., Burghardt, J., Audring, H., Dietel, M. Tyrosinase, melan-A, and KBA62 as markers for the immunohistochemical identification of metastatic amelanotic melanomas on paraffin sections Mod Pathol 1998;11:740-6.

This page last revised 30.11.2002.

©SMUHT/PW Bishop