SciELO - Scientific Electronic Library Online

vol.89 número3Síndrome de Cushing iatrogénico en un lactante por uso prolongado de corticoides tópicos. Reporte de casoOnicomadesis secundaria a enfermedad pie-mano-boca: una manifestación frecuente y motivo de preocupación de los padres índice de autoresíndice de materiabúsqueda de artículos
Home Pagelista alfabética de revistas  

Servicios Personalizados




Links relacionados

  • En proceso de indezaciónCitado por Google
  • No hay articulos similaresSimilares en SciELO
  • En proceso de indezaciónSimilares en Google


Revista chilena de pediatría

versión impresa ISSN 0370-4106

Rev. chil. pediatr. vol.89 no.3 Santiago jun. 2018 


Beta-hCG-producing thymic teratoma: an uncommon cause of peripheral precocious puberty

Claudia Lozano C.A 

Marcela Molina P.B 

A Pediatrician. Faculty of Medicine, University of La Frontera, Temuco, Chile.

B Pediatric Endocrinologist, Pediatric Service, Dr. Hernán Henríquez Aravena Hospital. Faculty of Medicine, University of La Frontera, Temuco, Chile.



Among the causes of peripheral precocious puberty in men are the beta- human cho rionic gonadotropin (Β-HCG)-secreting tumors, such as hepatoblastomas, dysgerminomas, chorio carcinomas, and immature teratomas. In pediatrics, the mediastinal teratomas are rare, representing the 7-10% of extragonadal teratomas.


To describe the case of a patient with peripheral precocious puberty due to a Β-HCG -secreting thymic teratoma.

Clinical case:

A seven-years-old schoolboy presents a three-months history of voice changes, gynecomastia, pubic hair appearance, and increased genital volume. In the exams, bone age of nine years, total testosterone 9.33ng/ml (< 0.4ng/ml), dehydroepiandrosterone sulfate (DHEAS), 17-hydroxyprogesterone (17-OHP), and normal adrenocorticotropic hormone (ACTH) test stand out; luteinizing hormone (LH) and follicle stimulating hormone (FSH) with low basal levels, P-HCG 39.5mU/ml (< 2.5 mUI/ml), alpha feto protein (Α-FP) 11,2ng/ml (0.6-2.0 ng/ml). Imaging study to determine the origin of P-HCG secretion shows normal testicular ultrasound and thoracic, abdominal, and pelvic computerized axial tomo graphy (CAT); brain and sellar resonance without significant findings. The positron emission tomography/computed scan (PET SCAN) shows a tumor image in the anterosuperior mediastinum. The tumor is resected, and the biopsy shows an immature cystic teratoma in the thymus. Post-operatory evolution was satisfactory, with normalization of hormonal levels.


The appearance of a teratoma in a pediatric patient is rare, even more if it is immature, with thymic location and Β-HCG- secretor. It is important to consider it within the differential diagnosis facing precocious puberty, as a better way to handle appropriately.

Keywords: Teratoma; precocious puberty; beta-human chorionic gonadotropin


Teratoma is a germ cell tumor that develops as a result of embryonic differentiation1. It contains tissues from the three germinal layers: ectoderm, mesoderm, and endoderm1. Teratomas composed of mature ce llular elements show a higher degree of differentiation, are classified as benign and do not produce tumor markers1,4. Elevated levels of these are indicative of the discovery of an immature or potentially malignant component1,4. A small portion of germ cell tumors can produce Β-HCG2. 5-10% of germ cell tumors are ex tragonadal, including those of mediastinal location9. Immature mediastinal teratomas (TM) account for 1% of all these4,7. Clinical manifestations will depend on the location and effect of the markers secreted by the tumour1. Most patients with TM have no symptoms. In case of manifestations, they are generally respira tory. The small proportion of patients with a teratoma producing P-HCG has unique clinical features, such as the development of precocious puberty and other endocrine dysfunctions depending on their location2. The development of precocious puberty is explained by the fact that the molecules of Β-HCG and LH have identical alpha subunits (a) and similar beta subunits (P), thus the Β-HCG stimulates the production of tes tosterone by the cells of Leydig10,11,12. Within the TM we can find those located in thymus8. To date, there are no reports of cases of early puberty caused by teratoma producing Β-HCG in Chilean pediatric patients.

The objective of this study is to describe a clinical case of a male school-child patient who underwent pe ripheral precocious puberty due to thymic teratoma secreting Β-HCG.

Clinical case

A 7-year-old schoolboy, he consulted an endo crinology polyclinic for a 3-month evolution characterized by pubertal development that included voice changes, facial acne, pubic hair appearance and in creased genital volume. Previously healthy. Pregnancy and childbirth without pathology. Physical examina tion: Eutrophic, size 131.5 cm, 0.68 standard deviation (SD), on target size (172 cm, -0.68 DE), (Figure 1), normotensive, thick voice, presence of gynecomastia, axillary hair, Tanner pubic hair 4, thickened penis with glans formation and increased length, 3 ml testes, nor mal segmental in the rest of the examination; compa tible with diagnosis of peripheral precocious puberty. Some of the most important results from the reques ted examinations were: bone age 9 years according to Greulich and Pyle atlas (2 x 18.2 months), total testos terone 9.33 ng/ml (< 0.4 ng/ml), androstenedione 1.2 ng/ml (0.1-0.9 ng/ml), DHEAS 47.3 ug/dl (80-560 ug/ dl), estradiol 68.4 pg/ml (< 10 pg/ml prepubescent man), FSH < 0.1 mUI/ml (0.26-3.0 mUI/ml), LH < 0.1 mUI/ml (0.02-0.3 mUI/ml), 17-OH-P 0.62 ng/ml (0.3 2.2 ng/ml), ACTH test for 17-OH-P basal 1.3 ng/ml - 60 min 2.1 ng/ml (normal) and Β-HCG 39.5 mUI/ ml (< 2.5 mUI/ml), Α-FP 11.2 ng/dl (0.6-2.0 ng/ml). In joint evaluations with the pediatric hemato-oncologist, imaging was requested to look for the origin of Β-HCG tumor secretion: testicular ultrasound, normal thoracic, abdominal and pelvic CT scans, brain and selar resonance reports small pineal cyst that is considered as a finding (Figure 2); in parallel, periodic clini cal and hormonal controls were performed, including measurement of Β-HCG in cerebrospinal fluid (CSF), (Table 1). Due to a negative tumor localization study, a positron emission tomography scan (PET/CT F18- FDG) was ordered, revealing soft tissue in an upper- anterior mediastinum, which may suggest a germinal tumor (Figure 3). At 8 years and 4 months of age, an exploratory thoracotomy was performed and the thy mus was dissected. Between the lobes of this gland, a more consistent mass of 2 cm in diameter, spherical, was found and removed, including the left lobe. Contemporary biopsy reported cystic teratoma of the thy mus (Figure 4). A decrease of Β-HCG was observed in the postoperative period to < 1.5 mUI/ml (< 2.5 mUI/ ml), (Table 1). In endocrinological evaluations after surgery, regression of pubertal development was ob served: disappearance of gynecomastia, partial regres sion of Tanner 3 pubic hair, no progression of penile development and normalization of hormonal values (Table 1).

Figure 1 Growth curve. 

Figure 2 Brain magnetic resonance imaging (MRI). Brain and sellar resonance reports a small pi neal cyst that is con sidered a finding. 

Table 1 Laboratory tests. 

Figure 3 Positron emission tomography/computed scan (PET SCAN) reveals tissue of soft parts in antero-superior mediastinum, which can corres pond to a germinal tumor. 

Figure 4 Thymic tissue with cystic formation coated by epidermoid ephitelium in keratinized parts, ciliated pseudostratified columnar ephitelium, glandular tissue and neuroectodermal tissue, with neuroepithelial cells driving rosette formation. The lesion contains approximately a 20% immature neuroectodermal tissue, therefore, teratoma under study is in G2 of González Crussi grading system (10-50% of immature tissue)13. Courtesy of Dr. Lilia Antonio. Anatomic Pathology Unit, Dr. Hernán Henríquez Aravena Hospital, Temuco. 


Germ cell tumors are a heterogeneous group of neoplasms, with a diverse clinical and biological behavior1. During the embryonic development in the third gestation week, the primordial germ cells dorsally mi grate from their origin towards the wall of the yolk sac, following a route through the posterior mesentery towards the gonadal anlage1. In this process, it can be ectopically nest along the midline, in the central ner vous system, mediastinum, sacrococcygeal zone, retro- peritoneum, and gonads. They can then proliferate and experience a neoplastic transformation. If this occurs without differentiation, a dysgerminoma1 will occur. On the other hand, in the case of differentiation, if it is an embryonic type, it can lead to embryonic carcinoma or teratoma; if it is extra-embryonic, choriocarcinoma or endodermal breast tumor will form1. Germ cell tu mors represent 3% of all malignant tumors in children under 15 years of age2.

Teratoma contains tissues derived from the three germinal layers: ectoderm, mesoderm, and endoderm1. It is found in different stages of maturity, with solid and cystic areas. Histologically, they can be classified according to the World Health Organization (WHO) as: mature, immature, mixed, monodermal and with somatic malignant phenomena3. Teratomas composed of differentiated or mature cellular elements are classified as benign and do not produce tumor markers such as alpha-fetoprotein (Α-FP) or Β-HCG14. Eleva ted levels of these markers indicate the discovery of an immature or potentially malignant component1,4. A small proportion of teratomas can produce Β-HCG2. TM contains undifferentiated tissue that may resem ble embryonic structures, such as areas containing immature neuroectoderm and mesenchymal tissue3,4. Germ cell tumors are commonly found in gonads, but 5-10% are extragonadal, in locations such as the pineal gland, retroperitoneum, mediastinum, and sacral area; being the mediastinum, the most common extrago nadal location in adults, however in children the sa crococcygeal corresponds to 40%-80% of cases4,5,6. Of mediastinal tumors, 6-18% are caused by germ cell tumors and 86% of these are benign9. Immature MTs are very rare and constitute 1% of all these,7. TM may originate from primitive germ cells lost in the mediastinum during caudal migration in early embryogenesis or from native pluripotent mediastinal cells6. Most of these teratomas are located in the anterior mediasti num, only 3-8% are located in posterior mediastinum6,7. Studies show that in patients under 15 years of age, immature TMs often behave in a similar way to mature teratomas, following a benign course, as oppo sed to those over 15 years of age4,7. Clinical manifesta tions will depend on the location and effect of markers secreted by the tumour1. Most patients with TM are asymptomatic, usually not diagnosed until they have an imaging study that shows them6. The patient signs are usually respiratory, such as respiratory distress, coughing, wheezing, chest pain6. The mass may cause deformation of the chest wall or signs of spinal cord compression6.

The small proportion of patients with a teratoma that produces Β-HCG is related to a delay in diagnosis in 60% of cases and presents unique clinical characte ristics, such as the development of early puberty, as our patient, and other endocrine dysfunctions depending on their location which includes growth alterations, diabetes insipidus and hypopituitarism2. The develo pment of precocious puberty is due to the fact that the molecules of Β-HCG and LH have identical subunits a and similar subunits Β, thus the Β-HCG stimulates the production of testosterone by the cells of Leydig10,11,12. Precocious puberty occurs independently of gonado trophin levels and occurs more frequently in males2. It is less frequent in females because both FSH and LH activity is necessary for follicular maturation2,14. About ten cases of pediatric patients with immature teratoma have been reported, of which five10,11,12,14 evolved with early puberty because the tumor was secreting Β-HCG. Regarding the latter cases, they all refer to immature teratomas located in the central nervous system; one in pellucidum septum11, three in the pineal gland10,12, and one described as a suprasellar mass14; in two of the cases the teratoma was associated with choriocarcinoma10. Four of the patients were male, the age range was between 6 and 7 years, all of the patients had early pu berty, one of them also had headache12, and another had diabetes insipidus and increased intracranial pressure14. In all cases, an elevation of Β-HCG in plasma and cerebrospinal fluid was observed, and the tumor was observed in cerebral magnetic resonance imaging. All had surgical resection and chemotherapy, while three received radiotherapy10,11,12. One of the patients died10, his tumor was an immature pineal teratoma as sociated with choriocarcinoma. The rest of the cases showed a favorable evolution. The case reported in this article differs from those previously mentioned in the location of the teratoma, which was thymic, did not require treatment with radiotherapy or chemotherapy, since the current evidence indicates that it is not neces sary to indicate it in pure teratoma without elements of other tumor tissue. Surgical resection was performed with a satisfactory clinical response.

Among the TM we can find those located in the thymus, which are described as of epithelial origin, classified as mature or immature8.

Teratoma treatment typically consists of complete surgical resection without the need for chemotherapy6. The prognosis of patients with immature teratomas is determined by factors such as the age of the patient, anatomical site of the tumor, number of immature elements of the teratoma, and integrity of surgical resection4.

This particular case involved a patient who presen ted a thymic teratoma containing approximately 20% immature neuroectodermal tissue, and who secreted Β-HCG, triggering peripheral precocious puberty.

When the tumor was resected, the manifestations of puberty involuted.


Male early puberty should alert about possible tu moral causes, especially if the clinical course is rapid and progressive, performing a diagnostic evaluation intended to discard these aetiologies. If there is puber tal development with tests in the pre-pubertal range it is an indicator of independent cause of gonadotrophin secretion, and within these, in addition to congenital adrenal hyperplasia, there are tumoral pathologies and therefore the study should be directed to discard an etiology of this type, and if so, look for its origin, as this determines treatment and prognosis.

The presentation of a teratoma, in pediatric pa tients, is infrequent, even more so, if it is immature, if its location is mediastinal, specifically thymic and is a secretor of P-HCG generating a picture of peripheral precocious puberty, being not always easy to find tu moral source of secretion of Β-HCG, as in our patient. Therefore, despite its low prevalence, it is important to consider this pathology within the spectrum of diffe rential diagnoses compared to a similar clinical situation, so that timely management can be carried out, in this case, a tumor resection that meant its definitive resolution.

Ethical Responsibilities

Human Beings and animals protection: Disclosure the authors state that the procedures were followed according to the Declaration of Helsinki and the World Medical Association regarding human experimenta tion developed for the medical community.

Data confidentiality: The authors state that they have followed the protocols of their Center and Local regulations on the publication of patient data.

Rights to privacy and informed consent: The authors have obtained the informed consent of the patients and/or subjects referred to in the article. This docu ment is in the possession of the correspondence author.

Financial Disclosure: Authors state that no economic support has been asso ciated with the present study.

Conflicts of Interest: Authors declare no conflict of interest regarding the present study.


1. Pardo N, Muñoz A, Maldonado M. Tumores de células germinales. Clin Transí Oncol. 2005;7(8):361-9. [ Links ]

2. Chien-Ming Lin, Cheng-Ting Lee, Yi-Ching Tung, et al. Endocrine dysfunction in Taiwanese children with human chorionic gonadotropin- secreting germ cell tumors. Journal of the Formosan Medical Association 2014;113:102-5. [ Links ]

3. Portelli C, Lépore M, Rojas-Bilbao E, Amante M. Oligoastrocitoma originado en teratoma quístico inmaduro de ovario. Descripción de un caso. Revista Española de Patología 2012;45(2): 234-7. [ Links ]

4. McLeod N, Vallely M, Mathur M. Massive Immature Mediastinal Teratoma Extending into the Left Pleural Cavity. Heart Lung and Circulation 2005;14:45-7. [ Links ]

5. Roy N, Blurton D, Azakie A, Karl T. Immature Intrapericardial Teratoma in a Newborn With Elevated Alpha- Fetoprotein. Ann Thorac Surg 2004; 78:e6-8. [ Links ]

6. Mosk C, Van de Ven C, Bessems J, Van Noesel M, Looijenga L, Wijnen R. Unusual presentation of a posterior mediastinal teratoma. J Ped Surg Case Reports 2013;1:164-6. [ Links ]

7. Peterson C, Buckley C, Holley S, Menias C. Teratomas: A Multimodality Review. Curr Probl Diagn Radiol. 2012;41(6):210-9. [ Links ]

8. Marx A, Chan J, Coindre J, et al. The 2015 World Health Organization Classification of Tumors of the Thymus. J Thorac Oncol. 2015;10(10):1383-95. [ Links ]

9. Coran A, Caldamone A, Adzick S, Krummel T, Laberge J, Shamberger R. Pediatric Surgery. Seventh Edition, 2012. Chapter 37. [ Links ]

10. Nogueira K, Liberman B, Rodrigues F, et al. hCG-Secreting Pineal Teratoma Causing Precocious Puberty: Report of Two Patients and Review of the Literature. Journal of Pediatric Endocrinology & Metabolism 2002;15:1195-201. [ Links ]

11. Inamo Y, Hiyoshi K, Hanawa Y, Okuni M. Precocious puberty caused by an hCG-producing tumor of the septum pellucidum. Acta Paediatr Jpn. 1991;33(5):681-4. [ Links ]

12. Cohen A, Wilson J, Sadeghi-Nejad A. Gonadotropin-secreting pineal teratoma causing precocious puberty. Neurosurgery. 1991;28(4):597-602; discussion 602-3. [ Links ]

13. Harms D, Zahn S, Gobel U, Schneider D. Pathology and Molecular Biology of Teratomas in Childhood and Adolescence. Klin Padiatr. 2006;218(6):296-302. [ Links ]

14. Kitanaka C, Matsutani M, Sora S, Kitanaka S, Tanae A, Hibi I. Precocious puberty in a girl with an hCG-secreting suprasellar immature teratoma. Case report. J Neurosurg. 1994;81(4):601-4. [ Links ]

Received: September 28, 2017; Accepted: February 15, 2018

**Correspondence: Claudia Lozano

Creative Commons License Este es un artículo publicado en acceso abierto bajo una licencia Creative Commons