CK NAUGHTON*, RB NADLER†, JW BASLER* and PA HUMPHREY‡* Department of Surgery, Division of Urologic Surgery, Washington University School of Medicine,† Department of Urology, Northwestern University Medical School and‡ Lauren V. Ackerman Surgical Pathology Laboratory, Department of Pathology, Washington University School of Medicine, St Louis, Missouri, USA arrest of spermatogenesis. In their survey of the litera-Introduction ture, they proposed that Leydig cells in the testes may undergo a graded series of changes from hyperplasia to As early as 1937, Jemerin [1] attempted to diCerentiate Leydig cell hyperplasia (LCH) from neoplasia. He found formation of benign and malignant tumours. Valensi et al.[12] describe a case of LCT in a 32-year-old man only isolated cases of hyperplastic interstitial cells, which in retrospect may have been misinterpreted as neoplasia. presenting with gynaecomasia who 4 years previously had orchiectomy for contralateral gynaecomastia. LCH is frequently associated with cachexia and chronic diseases including tuberculosis, syphilis, carcinoma, per- Juxtatumoral LCH was noted in areas where the tumour was well encapsulated, suggesting the existence of a nicious anaemia, alcoholism and in the elderly. LCH has also been observed in local conditions, such as chronic factor stimulating Leydig cell multiplication. They believed that the resulting imbalance between Sertoli compression of the spermatic cord, stricture of the vas deferens and chronic diseases of the bladder and prostate. and Leydig cells could induce changes in Leydig cell function and multiplication. Thus far, we have discussed There have been several experimental studies in animals resulting in LCH [1] similar to the Leydig cell proliferation secondary LCH from numerous disease entities and LCH associated with LCT. In contrast, Schedewie et al.[13] found in humans. Conditions causing cessation of spermatogenic activity and tubular atrophy appear to lead to described LCH as a cause of familial sexual precocity in two brothers (primary LCH). Congenital LCH, seen in 21 LCH. Experiments in dogs with testicular atrophy after exposure to irradiation, ligation of the vas deferens in of 2518 newborn consecutive autopsies [14] may be another presentation of primary LCH; placental secretion rabbits, and chronic alcohol consumption or tuberculous infection in rats all resulted in LCH [1]. Similarly, LCH of hCG was proposed as the aetiology. LCH can therefore be viewed broadly as primary or secondary (Table1); is seen in pseudohermaphrodites in whom testicular function is diminished or absent. only sexual precocity and congenital LCH appear to be represented in the literature as forms of primary LCH. It There have been numerous reports of secondary LCH as a result of several diCerent aetiologies, including is still unclear if LCH in the presence of LCT represents a precursor proliferation or an epiphenomenon. cryptorchism [2], adrenal hyperplasia [3, 4], embryonal carcinoma [5], exogenous hCG [5], seminoma [6], Unfortunatelythereisnodefinitivecommonmechanism described for LCH. There are hypotheses applicable Klinefelter’s syndrome [7], pineal choriocarcinoma [8], choriocarcinoma in the testis, and exogenous oestrogen to certain clinical situations, but no one theory exists to account for all cases of LCH. One theory proposes in mice [9]. There have also been reported cases of LCH associated with Leydig cell tumour (LCT), which has a faulty negative-feedback loop of the hypothalamicpituitary-testis axis, resulting in elevated serum levels of prompted speculation that LCH harbours the potential for transformation into tumour …