AJR 2003; 180:501-503
© American Roentgen Ray Society
Testicular Leydig's Cell Hyperplasia: MR Imaging and Sonographic Findings
Laura R. Carucci1,
A. Temel Tirkes1,
E. Scott Pretorius1,
Elizabeth M. Genega2 and
Susan P. Weinstein1
1 Department of Radiology, University of Pennsylvania Medical Center, 1 Founders
Pavilion, 3400 Spruce St., Philadelphia, PA 19104.
2 Department of Pathology, University of Pennsylvania Medical Center,
Philadelphia, PA 19104.
Received May 24, 2002;
accepted after revision July 16, 2002.
Address correspondence to E. S. Pretorius.
Introduction
Testicular Leydig's cell hyperplasia is a rare benign condition that is
characterized by small, multifocal, and frequently bilateral, testicular
nodules
[1,2,3,4].
In the primary form, male children may present with precocious puberty
[1,
3,4,5,6].
However, in the secondary form, which more often occurs in adults, the nodules
of Leydig's cell hyperplasia are typically not palpable, and the diagnosis of
Leydig's cell hyperplasia is often made with imaging studies or pathologically
[2,
3,
7,
8]. One previous report has
described the sonographic findings of this entity
[1]. To our knowledge, the MR
imaging findings in Leydig's cell hyperplasia have not been previously
described.
Case Report
A 44-year-old man with no remarkable medical history presented with a
1-year history of intermittent right scrotal pain that had increased in
frequency and intensity over the past 3 months. Physical examination revealed
bilaterally descended testicles of normal size with no palpable masses.
Gynecomastia was not present. Serum tumor markers were within normal limits:
the human chorionic gonadotropin (hCG) level was less than 5 mIU/mL, and the
-fetoprotein level was 3 IU/mL (normal range, 0-5 IU/mL).
An initial sonogram showed a 3 x 5 mm hypoechoic lesion in the
superior right testicle. MR imaging at that time showed two lesions in the
right testicle, one measuring 3 mm and the other, 4 mm. The patient was
treated with antibiotics, and the scrotal pain resolved. However, pain
recurred after 6 months. No changes were seen on physical examination. A
follow-up sonogram showed a stable lesion in the superior right testicle and a
new lesion in the superior medial right testicle. Both lesions were hypoechoic
with increased color flow, indicative of vascularity (Figs.
1A and
1B). A follow-up MR image
(Fig. 1C) revealed the two
previously seen lesions as well as several new lesions ranging in size from 1
to 4 mm and a new lesion of 4 mm in the superior aspect of the contralateral
testicle. The lesions showed intermediate signal intensity on T1-weighted
images and decreased signal intensity on T2-weighted images, relative to the
testicular parenchyma. Mild enhancement was seen after gadolinium enhancement
(Fig. 1D).
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Fig. 1A. —44-year-old man with 1-year history of intermittent scrotal
pain. Sonogram of right testicle reveals subcentimeter-size hypoechoic lesion
(double arrows) in upper pole and smaller hypoechoic lesion
(single arrow) in mid pole.
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Fig. 1B. —44-year-old man with 1-year history of intermittent scrotal
pain. Black and white image from color-flow Doppler sonography shows color
flow within lesion in upper pole of right testicle, indicative of
vascularity.
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Fig. 1C. —44-year-old man with 1-year history of intermittent scrotal
pain. Sagittal fat-suppressed fast spin-echo T2-weighted MR image (TR/TE,
4467/143) of right testicle shows two well-defined subcentimeter-size lesions
(arrows) that are hypointense relative to testicular parenchyma.
Small hydrocele may also be seen.
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Fig. 1D. —44-year-old man with 1-year history of intermittent scrotal
pain. Coronal gadolinium-enhanced gradient-echo MR image (68/2.9) shows
multiple subcentimeter-size lesions in right testicle (arrows).
Lesions show mild enhancement.
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Concern about multifocal germ cell tumor prompted right radical
orchiectomy. At gross pathology, a poorly demarcated white nodule of 4 mm was
identified in the superior right testicle. Microscopic examination revealed
multifocal Leydig's cell hyperplasia with diffuse sheets and nodules of
Leydig's cells (Fig. 1E). The
largest nodule was 6 mm in diameter. Associated focal fibrosis and atrophy
were present. No neoplasia was identified.
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Fig. 1E. —44-year-old man with 1-year history of intermittent scrotal
pain. Photomicrograph of section of right testicle reveals increased Leydig's
cells in interstitium (black arrows) between normal seminiferous
tubules (white arrow). A nodular aggregate of hyperplastic Leydig's
cells is identified in lower half of image.
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Discussion
Leydig's cell hyperplasia is a rare benign condition that must be
distinguished from testicular neoplasia
[2,
3].
Histologically, Leydig's cell hyperplasia is characterized by an increased
number of testicular Leydig's cells with increased nucleoli, decreased
lipofuscin, and decreased smooth endoplasmic reticulum
[3]. The hyperplastic cells
infiltrate between seminiferous tubules, rather than displacing and
compressing them as occurs with Leydig's cell tumors
[3,
6,
7]. In Leydig's cell
hyperplasia, cells are arranged in multifocal nodules. The nodules of Leydig's
cell hyperplasia often occur bilaterally and range in size from 1 to 6 mm
[1,2,3,4].
No necrosis, vascular invasion, or frequent mitoses occurs in Leydig's cell
hyperplasia [3], and Leydig's
cell hyperplasia is not known to be a preneoplastic lesion
[3,
8].
Adult patients with Leydig's cell hyperplasia are usually asymptomatic
[2]. However, some patients may
present with testicular pain, swelling, or infertility
[3]. No changes in libido
occur, and gynecomastia does not develop
[2]. Lesions typically are not
palpable, and serum tumor markers are usually normal
[2,
4]. Therefore, Leydig's cell
hyperplasia is often an incidental finding. In contrast, patients with
Leydig's cell tumor present with endocrine abnormalities, such as adult
feminization, gynecomastia, and, in 30% of patients, decreased libido due to
production of estrogen or androgen by tumor cells
[7].
Although no one cause can account for all cases, Leydig's cell hyperplasia
is thought to be due to a faulty hypothalamic—pituitary—testicular
axis with resultant chronic Leydig's cell stimulation
[2,3,4].
Because normal Leydig's cells produce androgens as a result of luteinizing
hormone stimulation, increased serum luteinizing hormone can result in
Leydig's cell hyperplasia. Human chorionic gonadotropin is structurally
similar to luteinizing hormone and can also cause Leydig's cell hyperplasia
[2,
3].
Primary Leydig's cell hyperplasia is caused by either a familial activating
mutation of the luteinizing hormone receptor that causes elevated serum
testosterone and results in male-limited precocious puberty or a congenital
placental hCG stimulation of the testes
[1,
3,4,5,6].
Secondary Leydig's cell hyperplasia is usually idiopathic and results from
supraphysiologic hormonal stimulation of the testes
[1]. This hormonal stimulation
may be due to transient or sustained elevation of serum luteinizing hormone,
elevated serum hCG, decreased testosterone production, or unknown testicular
paracrine growth factors [3,
8]. Identifiable causes of
Leydig's cell hyperplasia include cryptorchidism, congenital adrenal
hyperplasia, hCG production by germ cell tumors or choriocarcinoma, pituitary
abnormalities, Klinefelter's syndrome, exogenous hCG therapy, and antiandrogen
therapy for prostate cancer
[1,2,3,
6,
8]. Leydig's cell hyperplasia
has also been associated with cachexia and chronic diseases such as
tuberculosis, syphilis, and alcoholism
[3]. In mice,
5--reductase inhibitor therapy and prolonged estrogen exposure have
been associated with Leydig's cell hyperplasia
[1,2,3,
7,
8].
Radiologic descriptions of Leydig's cell hyperplasia in the literature are
brief and not comprehensive. Sonographic findings of Leydig's cell hyperplasia
are variable. A previous case report described small echogenic testicular
masses in Leydig's cell hyperplasia caused by congenital adrenal hyperplasia
[1]. However, two other
examples of Leydig's cell hyperplasia in the pediatric and urologic literature
describe small hypoechoic solid masses—as can be seen in our patient
[2,
4]. To our knowledge, the
vascularity seen within the lesions on color-flow Doppler sonography in our
patient has not been previously reported.
Because increasing numbers of patients are examined with MR imaging of the
scrotum, it is important to be aware of the MR imaging findings characteristic
of Leydig's cell hyperplasia. On the basis of the MR imaging in this case,
Leydig's cell hyperplasia may be depicted as multiple, bilateral solid lesions
that are hypointense on T2-weighted images relative to normal testicular
parenchyma, display mild contrast enhancement, and range in size from 1 to 6
mm. In our patient, MR imaging definitively identified many more lesions than
were revealed on sonography and correctly depicted the presence of bilateral
lesions. Sonography may miss such lesions because they are very small and
because the technique is operator-dependent.
In conclusion, Leydig's cell hyperplasia should be considered in the
differential diagnosis of small (<6 mm) multifocal testicular lesions.
Other differential possibilities would include lymphoma, leukemia, metastatic
disease, and bilateral primary testicular neoplasm. Leydig's cell hyperplasia
may be detected on sonography, and the condition may be characterized more
completely with MR imaging. MR imaging is also useful in the assessment of
lymphadenopathy and osseous metastases in the setting of testicular neoplasm.
When diagnostic imaging reveals multiple small bilateral testicular lesions
that are clinically nonpalpable, a diagnosis of Leydig's cell hyperplasia
should be strongly considered. If clinical history and laboratory workup
reveal a cause for Leydig's cell hyperplasia, medical treatment may be
feasible, thereby sparing the patient from operative exploration and possible
radical orchiectomy.
References
- Cooper SG, Richman AH, Carpenter TO, Rosenfield AT. Scrotal
ultrasonography in Leydig cell hyperplasia. J Ultrasound
Med 1989;8:689
-692[Medline]
- Olumi AF, Garnick MB, Renshaw AA, Benson CA, Richie JP. Leydig cell
hyperplasia mimicking testicular neoplasm. Urology
1996;48:647
-649[Medline]
- Naughton CK, Nadler RB, Basler JW, Humphrey PA. Leydig cell
hyperplasia. Br J Urol
1998;81:282
-289[Medline]
- Leschek EW, Chan W-Y, Diamond DA, et al. Nodular Leydig cell
hyperplasia in a boy with familial male-limited precocious puberty.
J Pediatr
2001;138:949
-951[Medline]
- Schedewie HK, Reiter EO, Beitins IZ, et al. Testicular Leydig cell
hyperplasia as a cause of familial sexual precocity. J Clin
Endocrinol Metab
1981;52:271
-278[Abstract]
- Leung AC, Kogan SJ. Focal lobular spermatogenesis and pubertal
acceleration associated with ipsilateral Leydig cell hyperplasia.
Urology
2000;56:508
-509
- Castle WN, Richardson JR Jr. Leydig cell tumor and metachronous
Leydig cell hyperplasia: a case associated with gynecomastia and elevated
urinary estrogens. J Urol
1986;136:1307
-1308[Medline]
- Clegg ED, Cook JC, Chapin RE, Foster PMD, Daston GP. Leydig cell
hyperplasia and adenoma formation: mechanisms and relevance to humans.
Reprod Toxicol
1997;11:107
-121[Medline]
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Introduction
Case Report
