This report describes a case of an otherwise fit 43-year-old male, with a background of childhood mumps orchitis and subsequent infertility, presenting with left hemi-scrotal pain. Histology demonstrated Leydig cell hyperplasia. To the best of our knowledge, we describe the first case of Leydig cell hyperplasia following mumps orchitis.
Case Report
A 43 year old male, with a past medical history of hypertension, presented to primary care with a one-year history of left hemi-scrotal pain. He was a non-smoker and otherwise fit and well, with a history of mumps orchitis in childhood, and subsequently found to be azoospermic in early adulthood. At this time, the patient was offered testicular sperm extraction (TESE), however, declined. There was no history of cryptorchidism.
A referral to the local urology service was sought. On examination, he had normal testes bilaterally, with no lymphadenopathy. An ultrasound was undertaken, which showed a 4mm lesion in the upper pole of the left testis, and a small left epididymal cyst. There were no varicosities and a follow-up scan was advised by the ultrasonographer.
The case was discussed in the urology department X-ray meeting, and a follow-up scan was arranged for 6 weeks after the initial scan. This revealed a ‘3mm rounded hypoechoic avascular lesion with slightly ill-defined borders sited within the parenchyma of the upper pole of the left testis. (See appendix 1). The nature was unclear, therefore tumour markers were checked and the case was re-discussed at the urology department X-ray meeting.
Upfront ultrasound scan
Interval ultrasound scan at 1 month
Tumour markers were normal (AFP 7, beta-hCG <1, LDH 286). The outcome of the X-ray meeting was that the gentleman should be offered either surveillance of the lesion or a radical inguinal orchidectomy, given the diagnostic uncertainty. The patient opted for an orchidectomy due to known infertility and for reassurance.
He underwent a left radical orchidectomy. The histology report was as follows: ‘The pale lesion comprises a fairly well-circumscribed non-encapsulated nodular lesion composed of uniform polygonal cells with abundant eosinophilic cytoplasm dispersed in the form of nodules and diffuse sheets. The cell infiltrate between the seminiferous tubules. The nuclei are round with prominent nucleoli. There is minimal cytological atypia. There are no mitoses. Necrosis is not seen. The background testicular parenchyma shows atrophic tubules. The epididymis and spermatic cord are within normal limits. Conclusion: The appearances favour Leydig Cell hyperplasia. There is no evidence of malignancy.’
He went on to make a full recovery post-operatively and was advised regarding regular self-examination in the future. To our knowledge, there are no case reports of Leydig cell hyperplasia in adults following childhood mumps, with no other congenital abnormalities.
Discussion
Leydig Cell Hyperplasia: The peak age of presentation of adult Leydig Cell Hyperplasia (LCH) is 30-601 and the presenting feature is usually a painless lump.1,2 A palpable mass is present in >90% of patients.3 LCH is rare, but the most common benign testicular tumour.2 They are usually unilateral and benign3 as is described in this case report. Patients most commonly notice a painless mass, however in this case the patient presented with tenderness unilaterally but no palpable lump in his testicle.
The factors determining malignant potential include size (>5cm),1-3 presence of necrosis,1-3 nuclear atypia,2,3 lymphovascular invasion,1-3 infiltrating margins,1-3 areas of haemorrhage,1 and the number of mitotic features.2,3 In the histology report for this case, none of these features were present.
LCH has been linked to genetic disorders, including Kleinfelter’s4 and Congenital Adrenal Hyperplasia.3 This is explained by the abnormalities in the hypothalamic- pituitary- testis axis. Abnormally high Luteinising Hormone (LH) levels have been shown to play an important role in Leydig cell development and LH plays a trophic role in adult Leydig cells.5 LH is raised due to decreased testosterone levels in these conditions.5 Physiological Leydig cell development is related to the fluctuations of testosterone during a male lifetime.3 The patient described in this case had his LH and testosterone checked at another hospital as part of investigations for infertility a few years previously, due to his previous mumps orchitis, and these levels were reported to be normal.
In addition, there is a link with inflammation of the testes6,7 and LCH. Orchitis results in fibrosis and aspermatogenesis, leading to hyperplasia of Leydig cells.7 A link between interstitial macrophages and Leydig cell development has been established, in regulating steroidogenesis, and as such, positive correlation between the two cell lines has been found in histological specimens.
Mumps orchitis is not specifically described in the literature; however extrapolating the research, it could be suggested that there is a link between reduced testosterone production and high LH levels in mumps orchitis, and subsequent development of LCH.
In this particular case, ultrasound was used to evaluate the lesion, and was accurate at diagnosing LCH. However, because 10% of Leydig cell tumours are malignant,1 and difficult to assess on USS,8 the option was given to the patient of surveillance or radical orchidectomy. The patient chose to undergo radical orchidectomy, confirming the USS findings with the histopathology analysis.
Mumps Orchitis: A study of 27 men9 has demonstrated that LH and FSH are significantly increased in patients with acute mumps orchitis. This can be persistent, and also seen in those with other viral infections including mumps without orchitis.9 The study concludes that mumps orchitis does impair Leydig cell function, although LCH is not described. A more historical study describes how mumps orchitis affects testicular volume, pain scores, testicular consistency, and atrophy, and disrupted spermatogenesis with abnormal ejaculates.10 It did not discuss the effect on Leydig Cells specifically, we can infer from the other studies that theoretically, due to the effect on spermatogenesis, Leydig cell function was disrupted.
Conclusion
Elevated LH levels have been proven sequelae of mumps orchitis and also proven as aetiology for LCH.
To the best of our knowledge, this is the first case report of a patient who had childhood mumps orchitis subsequently developing Leydig cell hyperplasia.
Declarations
- Conflicting interests: The Authors declare that there is no conflict of interest.
- Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
- Informed consent: Written informed consent was obtained from the patient(s) for their anonymized information to be published in this article.
- Ethical approval: Mid Cheshire Hospital Trust does not require ethical approval for reporting individual cases or case series.
- Guarantor: GB
- Contributorship: ST identified the case and made the proposal for a case report and gained consent from the patient. GB researched the literature and wrote the first draft. All authors reviewed and edited the manuscript, and approved the final version.
Authors: Grace Bennett & Margaret Lyttle, Mid Cheshire Hospital Trust
References:
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Published November, 2021