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Atypical Leydig Cell Tumor in Children

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Atypical Leydig Cell Tumor in Children Atypical Leydig Cell Tumor in Children: Report of 2 Cases Chiara Mameli, MD, a Giorgio Selvaggio, MD, b Chiara Cerini, MD, c Gaetano Bulfamante, MD, d Cristina Madia, MD,a Giovanna Riccipetitoni, MD, b Gian Vincenzo Zuccotti, MDa Leydig cell tumors (LCTs) are rare cord-stromal tumors that may occur in abstract testis or ovaries and may produce androgens or estrogens. The majority has been found in men between the ages of 20 and 60 years. Adults with androgen-secreting LCTs are usually asymptomatic; feminizing syndromes may result from the production of estradiol or the peripheral aromatization of testosterone. In children, LCTs usually present between 5 and 10 years of age with isosexual precocious pseudopuberty or gynecomastia. We report 2 cases of LCT in prepubertal boys presenting with advanced unilateral pubarche and testicular volume asymmetry. Both subjects had normal penis size for age; no axillary hair or other signs of puberty were present. Height velocity was normal, and bone age was coincident with chronological Departments of aPediatrics, and bPediatric Surgery, age. Androgen levels were normal, as well as estrogen, corticotropin, and Children’s Hospital “V. Buzzi, ” University of Milan, Milan, Italy; cDivision of Infectious Diseases, Children’s Hospital cortisol concentration. Testicular ultrasound demonstrated a testicular Los Angeles, Los Angeles, California; and dHuman Pathology mass. Histology examination revealed a well-differentiated LCT. This is Unit, Department of Health Sciences, San Paolo Hospital, University of Milan, Milan, Italy the first report of 2 pediatric patients with LCT presenting with advanced pubarche in absence of systemic hyperandrogenism. We hypothesize Dr Mameli conceptualized the study, collected that the neoplastic cells may locally produce high levels of androgens or cases, and drafted the initial manuscript; Dr Selvaggio collected cases and reviewed and revised androgen-like bioactivity molecules that are responsible for the clinical the manuscript; Drs Cerini and Madia drafted manifestation. We suggest that a testicular ultrasound should be obtained the manuscript; Dr Bulfamante performed the in all children presenting with unilateral pubarche, with or without histological analysis; Drs Riccipetitoni and Zuccotti critically reviewed the manuscript; and all authors hyperandrogenism. approved the fi nal manuscript as submitted. DOI: 10.1542/peds.2016-0151 Accepted for publication Jul 6, 2016 Leydig cell tumors (LCTs) are rare sex G proteins may excessively stimulate Address correspondence to Chiara Mameli, MD, 3 cord-stromal gonadal tumors. LCTs Leydig cells and induce oncogenesis. Department of Pediatrics, Children’s Hospital are steroid-secreting tumors releasing In pediatric subjects, LCTs are rarely “V. Buzzi, ” Via Castelvetro 32, University of Milan, androgens, classically testosterone, reported.4 – 6 Overall, LCTs account Milan, Italy. E-mail: [email protected] but they can also produce estrogens for 0.4% to 9% of all testis tumors in PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, either by direct production of prepubertal males. 1098-4275). estradiol or peripheral aromatization Copyright © 2016 by the American Academy of of the testosterone. 1 In children, LCTs usually present Pediatrics between 5 and 10 years of age, with FINANCIAL DISCLOSURE: The authors have LCTs typically affect males between isosexual precocious pseudopuberty indicated they have no fi nancial relationships 20 and 60 years of life. Malignant or gynecomastia in boys or virilizing relevant to this article to disclose. transformation is rare, and given the syndromes in girls, due to their FUNDING: No external funding. 7 slow growth, prognosis is generally hormonal activity. Gonadotropin- POTENTIAL CONFLICT OF INTEREST: The authors 2 good. dependent precocious puberty have indicated they have no potential confl icts of associated with accelerated growth interest to disclose. The etiology of LCTs remains and bone maturation, may develop unknown. Some authors hypothesized after surgical therapy. 8 that a disorder of the hypothalamic- To cite: Mameli C, Selvaggio G, Cerini C, et al. pituitary axis or structural changes of Radical inguinal orchiectomy is still Atypical Leydig Cell Tumor in Children: Report of 2 Cases. Pediatrics. 2016;138(5):e20160151 the luteinizing hormone receptors and recommended as standard treatment. Downloaded from www.aappublications.org/news by guest on October 1, 2021 PEDIATRICS Volume 138 , number 5 , November 2016 :e 20160151 CASE REPORT FIGURE 1 1, Patient 1. 2, Patient 2. A, Clinical fi ndings. A1, Patient 1: monolateral curled pubic hair on left testis. A2, Patient 2: monolateral testicular hair adult type. B, Testicular ultrasound. Hypoechoic testicular mass. C, Histology. Hematoxylin and eosin staining, ×4. Neoplastic cells with abundant eosinophilic cytoplasm, distinct cell borders arranged in nests and cords. D, Histology. Hematoxylin and eosin staining, ×40. TABLE 1 Hormonal Assessment Subject LH, IU/L FSH, IU/L Testosterone, ng/mL 17-OH-progesterone, Androstenedione, DHEAS, ng/mL ng/mL ng/mL 1 <0.1 (0.1–6) 0.5 (0.5–3.7) 0.01 (<5) 0.5 (0.59–3.44) 0.2 (0.6–3.10) 0.8 (0.3–2.5) 2 0.3 (0.1–6) 1.6 (0.5–3.7) <0.20 (<5) 0.45 (0.59–3.44) 0.61 (0.6–3.10) 1.8 (0.3–2.5) Data are mean (normal range); testosterone is mean (normal level for prepubertal children). However, to preserve male 2 mL and 3 mL, respectively. negative surgical margins ( Fig 1). fertility, in the past decade a more Neither testis had a palpable mass. One month after surgery, pubic hair conservative testis-sparing approach Height and weight were at 50th in the left scrotum decreased, and has been successfully chosen for percentile for sex and age; height varicocele resolved. young adults and children. 9 velocity was normal. Gynecomastia was absent. The hormonal We report 2 cases of LCTs in Patient 2 is a 11-year-old boy who assessment documented normal prepubertal boys presenting with presented with advanced unilateral androgen, estradiol, corticotropin, unilateral advanced pubarche, right pubarche and testicular and cortisol levels. LH, FSH, without hyperandrogenism. asymmetry for 1 month. Physical testosterone, 17-OH-progesterone, examination revealed testicular androstenedione, and hair adult in type, prepubertal CASE REPORTS dehydroepiandrosterone sulfate penis, and no axillary hair ( Fig 1). (DHEA-S) plasma levels are The right and left testicles were Patient 1 is a 6-year 10-month-old shown in Table 1. Tumor markers of 3.5 mL and 3 mL volume, boy who presented with unilateral α-fetoprotein and β-human chorionic respectively, with normal position premature pubarche and history of gonadotropin were unremarkable. and no palpable masses. Height pubic hair development on the left Bone age was 6 years. and weight were at 75th percentile scrotum since age 6-years 4-months, for sex and age; height velocity associated with unilateral testicular Testicular ultrasound of the was normal. Gynecomastia was swelling. left testicle identified a 0.3 cm absent. The hormonal assessment Physical examination revealed dark, hypoechoic mass located at the documented normal androgen, coarse, and curled pubic hair without inferior pole and grade III varicocele. estradiol, corticotropin, and cortisol axillary hair and normal penis size A left-testis-sparing surgery was levels. In particular, testosterone for age ( Fig 1). Mild asymmetry of performed. The histologic report was undetectable. LH, FSH, testicular volume was noted: the demonstrated the diagnosis of well- testosterone, 17-OH-progesterone, right and left testicles measured differentiated Leydig cell tumor with androstenedione, and DHEA-S plasma Downloaded from www.aappublications.org/news by guest on October 1, 2021 e2 MAMELI et al levels are shown in Table 1. Tumor the neoplastic cells were probably thorough work-up are crucial for markers α-fetoprotein, β-human producing locally high levels of diagnosis and treatment. chorionic gonadotropin, and inhibin androgens or substances with We suggest that every male child B were unremarkable. Bone age was androgen bioactivity. The androgen presenting with unilateral pubarche 11 years. microenvironment of the testis is should be evaluated with testicular supposed to be responsible of the Testicular ultrasound revealed a ultrasound regardless the finding of unilateral pubic hair development. hypoechoic mass measuring 0.6 systemic hyperandrogenism. This is in line with the fact that cm in diameter in the right testis. both patients had no pubic hair in a A right-testis-sparing surgery was site other than testis, normal penis performed, and diagnosis of Leydig ABBREVIATIONS growth, and bone age coincident with cell tumor was made. Surgical DHEA-S: dehydroepiandroste- chronological age. margins were negative ( Fig 1). One rone sulfate month after surgery, pubic hair in the On the basis of our findings, we infer FSH: follicle-stimulating hormone left scrotum decreased. that pediatric age LCTs may present LCT: Leydig cell tumor with different clinical and hormonal LH: luteinizing hormone profiles: (1) LCTs with systemic COMMENTS hyperandrogenism manifesting with LCTs are testicular neoplasms symptoms of precocious puberty, infrequently described in children. including increased penis size, REFERENCES They may occur at any age, but most pubic hair development, accelerated skeletal and muscle growth, 1. Leonhartsberger N, Ramoner R, Aigner often in prepubertal boys between F, et al. Increased incidence of Leydig advanced bone age,
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