Leydig cell tumour, also Leydig cell tumor (US spelling), (testicular) interstitial cell tumour and (testicular) interstitial cell tumor (US spelling), is a member of the

sex cord-stromal tumour Sex is the biological trait that determines whether a sexually reproducing organism produces male or female gametes. During sexual reproduction, a male and a female gamete fuse to form a zygote, which develops into an offspring that inherit ...

group of

ovarian The ovary () is a gonad in the female reproductive system that produces ova; when released, an ovum travels through the fallopian tube/oviduct into the uterus. There is an ovary on the left and the right side of the body. The ovaries are endoc ...

and

testicular cancer Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system. Symptoms may include a lump in the testicle or swelling or pain in the scrotum. Treatment may result in infertility. Risk factors include an c ...

s. It arises from

Leydig cell Leydig cells, also known as interstitial cells of the testes and interstitial cells of Leydig, are found adjacent to the seminiferous tubules in the testicle and produce testosterone in the presence of luteinizing hormone (LH). They are polyhedral ...

s. While the tumour can occur at any age, it occurs most often in young adults. However, in women it tends to happen after menopapuse. A Sertoli–Leydig cell tumour is a combination of a Leydig cell tumour and a Sertoli cell tumour from

Sertoli cell Sertoli cells are a type of sustentacular "nurse" cell found in human testes which contribute to the process of spermatogenesis (the production of sperm) as a structural component of the seminiferous tubules. They are activated by follicle-sti ...

Presentation

The majority of Leydig cell tumors are found in males, usually at 5–10 years of age or in middle adulthood (30–60 years). Children typically present with

precocious puberty In medicine, precocious puberty is puberty occurring at an unusually early age. In most cases, the process is normal in every aspect except the unusually early age and simply represents a variation of normal development. There is early developm ...

. In men, testicular swelling is the most common presenting feature. Other symptoms depend on age and the type of tumour. If it is secreting

androgen An androgen (from Greek ''andr-'', the stem of the word meaning ) is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This includes ...

s the tumour is usually asymptomatic, but can cause

in pre-pubertal boys. If the tumour secretes oestrogens it can cause feminisation in young boys. In adults, this causes a number of problems including

gynaecomastia Gynecomastia (also spelled gynaecomastia) is the non-cancerous enlargement of one or both breasts in men due to the growth of breast tissue as a result of a hormone imbalance between estrogens and androgens. Updated by Brent Wisse (10 Novemb ...

, erectile dysfunction, infertility, feminine hair distribution, gonadogenital atrophy, and a loss of libido. In women it tends to happen after menopause, but premenopausal cases have been reported. Sertoli–Leydig cell tumours of women tend to happen earlier, in the second or the third decade of a woman's life. Due to excess

testosterone Testosterone is the primary male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...

secreted by the tumour, one-third of female patients present with a recent history of progressive

masculinization Virilization or masculinization is the biological development of adult male characteristics in young males or females. Most of the changes of virilization are produced by androgens. Virilization is a medical term commonly used in three medical a ...

. Masculinization is preceded by

anovulation Anovulation is when the ovaries do not release an oocyte during a menstrual cycle. Therefore, ovulation does not take place. However, a woman who does not ovulate at each menstrual cycle is not necessarily going through menopause. Chronic anovulat ...

oligomenorrhea Oligomenorrhea is characterised by infrequent menstrual periods. Generally, the menstrual periods occur at intervals of greater than 35 days, with fewer than 9 periods in a year, where previously there had been a regularly established pattern. Th ...

amenorrhea Amenorrhea or amenorrhoea is the absence of a menstrual period in a female organism who has reached reproductive age. Physiological states of amenorrhoea are most commonly seen during pregnancy and lactation (breastfeeding). In humans, it is wher ...

and ''

defeminization In developmental biology and zoology Zoology ( , ) is the scientific study of animals. Its studies include the anatomy, structure, embryology, Biological classification, classification, Ethology, habits, and distribution of all animals, both ...

''. Additional signs include

acne Acne ( ), also known as ''acne vulgaris'', is a long-term Cutaneous condition, skin condition that occurs when Keratinocyte, dead skin cells and Sebum, oil from the skin clog hair follicles. Typical features of the condition include comedo, ...

and

hirsutism Hirsutism is excessive body hair on parts of the body where hair is normally absent or minimal. The word is from early 17th century: from Latin ''hirsutus'' meaning "hairy". It usually refers to a male pattern of hair growth in a female that ma ...

, voice deepening,

clitoromegaly Clitoromegaly (or macroclitoris) is an abnormal enlargement of the clitoris that is mostly congenital; it is otherwise acquired through deliberately induced clitoral enlargement, a form of body modification, by use of anabolic steroids, in parti ...

, temporal hair recession, and an increase in musculature. Serum testosterone level is high.

Cause

Animal studies a suggest possible link with C8 (C₈HF₁₅O₂,

perfluorooctanoic acid Perfluorooctanoic acid (PFOA; conjugate acid, conjugate base perfluorooctanoate; also known colloquially as C8, from its chemical formula C8HF15O2) is a perfluorinated carboxylic acid produced and used worldwide as an industrial surfactant in ch ...

Diagnosis

Presence of an ovarian tumour plus hormonal disturbances suggests a Leydig cell tumour,

granulosa cell tumour Granulosa cell tumours are tumours that arise from granulosa cells. They are estrogen-secreting tumours and present as large, complex, ovarian masses. These tumours are part of the sex cord–gonadal stromal tumour or non-epithelial group of tumou ...

thecoma Thecomas or theca cell tumors are benign Ovarian cancer, ovarian neoplasms composed only of theca cells. Histogenetically they are classified as sex cord-stromal tumours. They are typically estrogen-producing and they occur in older women (mean a ...

. However, hormonal disturbances, in Leydig tumours, is present in only 2/3 of cases. Testicular Leydig cell tumours can be detected sonographically, ultrasound examinations may be ordered in the event of a palpable scrotal lump, however incidental identification of these lesions is also possible. Leydig cell tumour1

A conclusive diagnosis is made via

histology Histology, also known as microscopic anatomy or microanatomy, is the branch of biology that studies the microscopic anatomy of biological tissue (biology), tissues. Histology is the microscopic counterpart to gross anatomy, which looks at large ...

, as part of a pathology report made during or after surgery.

Reinke crystals Reinke crystals are rod-like cytoplasmic inclusions which can be found in Leydig cells of the testes. Occurring only in adult humans and wild bush rats, their function is unknown. Ovarian stromal tumors having a predominant pattern of fibroma or t ...

are classically found in these tumours and help confirm the diagnosis, although they are seen in less than half of all Leydig cell tumours. Immunohistochemical markers of Leydig cell tumours include inhibin-alpha,

calretinin Calretinin, also known as calbindin 2 (formerly 29 kDa calbindin), is a calcium-binding protein involved in calcium signaling. In humans, the calretinin protein is encoded by the ''CALB2'' gene. Function This gene encodes an intracellular ...

, and melan-A.

Treatment

The usual chemotherapy regimen has limited efficacy in tumours of this type, although

imatinib Imatinib, sold under the brand names Gleevec and Glivec (both marketed worldwide by Novartis) among others, is an oral targeted therapy medication used to treat cancer. Imatinib is a small molecule inhibitor targeting multiple tyrosine kinases ...

has shown some promise. There is no current role for radiotherapy. The usual treatment is surgery. The surgery for females usually is a fertility-sparing unilateral salpingo-oophorectomy. For malignant tumours, the surgery may be radical and usually is followed by adjuvant chemotherapy, sometimes by radiation therapy. In all cases, initial treatment is followed by surveillance. Because in many cases Leydig cell tumour does not produce elevated

tumour marker A tumor marker is a biomarker that can be used to indicate the presence of cancer or the behavior of cancers (measure progression or response to therapy). They can be found in bodily fluids or tissue. Markers can help with assessing prognosis, su ...

s, the focus of surveillance is on repeated physical examination and imaging. In males, a radical inguinal orchiectomy is typically performed. However, testes-sparing surgery can be used to maintain fertility in children and young adults. This approach involves an inguinal or scrotal incision and ultrasound guidance if the tumour is non-palpable. This can be done because the tumour is typically unifocal, not associated with precancerous lesions, and is unlikely to recur. The

prognosis Prognosis ( Greek: πρόγνωσις "fore-knowing, foreseeing"; : prognoses) is a medical term for predicting the likelihood or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) ...

is generally good as the tumour tends to grow slowly and usually is

benign Malignancy () is the tendency of a medical condition to become progressively worse; the term is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous benign tumor, ''benign'' tumor in that a malig ...

: 10% are

malignant Malignancy () is the tendency of a medical condition to become progressively worse; the term is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous benign tumor, ''benign'' tumor in that a malig ...

. For malignant tumours with undifferentiated histology, prognosis is poor.

Additional images

Image:Leydig cell tumour2.jpg, Intermediate magnification

micrograph A micrograph is an image, captured photographically or digitally, taken through a microscope or similar device to show a magnify, magnified image of an object. This is opposed to a macrograph or photomacrograph, an image which is also taken ...

of a Leydig cell tumour.

H&E stain Hematoxylin and eosin stain ( or haematoxylin and eosin stain or hematoxylin–eosin stain; often abbreviated as H&E stain or HE stain) is one of the principal tissue stains used in histology. It is the most widely used stain in medical diag ...

. Image:Leydig cell tumour3.jpg, High magnification

of a Leydig cell tumour.

. File:Gross pathology of a Leydig cell tumor of ovary.jpg, Typical gross pathology of a Leydig cell tumor (in this case of the ovary): A well circumscribed, solid homogeneous mass with golden brown to brownish green cut surface. Topic Completed: 4 March 2021. Minor changes: 12 April 2021.

References

External links

{{DEFAULTSORT:Leydig Cell Tumour Ovarian cancer Male genital neoplasia Rare cancers Endocrine neoplasia Endocrine-related cutaneous conditions