|Year : 2019 | Volume
| Issue : 1 | Page : 68-71
Hepatoblastoma with precocious puberty
Enono Yhoshu, Yasir A Lone, Jai K Mahajan, Umesh Bahadur Singh
Department of Pediatric Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India
|Date of Web Publication||19-Dec-2018|
Dr. Jai K Mahajan
Department of Pediatric Surgery, Advanced Pediatric Centre, Postgraduate Institute of Medical Education and Research, Chandigarh - 160 012
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Hepatoblastoma (HB), a primary liver tumor of childhood, is often accompanied by raised levels of alpha-fetoprotein (α-FP). Rarely, the beta-human chorionic gonadotropin (β-hCG) levels may also be elevated, which can cause peripheral precocious puberty (PPP). We report a case of HB with precocious puberty wherein hormonal assays showed an increase in α-FP, β-hCG, and testosterone levels, and suppression of follicle-stimulating and luteinizing hormone levels. After chemotherapy and surgery, α-FP, β-hCG, and testosterone levels normalized, and the signs of virilization did not progress further. New therapeutic approaches have made a previously reported grim prognosis of virilizing HB, more favorable now. In the assessment of PPP, the possibility of a tumoral source for the hormones should also be considered.
Keywords: Hepatoblastoma, precocious, puberty, virilization
|How to cite this article:|
Yhoshu E, Lone YA, Mahajan JK, Singh UB. Hepatoblastoma with precocious puberty. J Indian Assoc Pediatr Surg 2019;24:68-71
| Introduction|| |
Hepatoblastoma (HB) is the most common liver malignancy in children and accounts for approximately 1% of childhood cancers. Precocious puberty (PP) associated with HB is a recognized but rare and poorly documented entity. The first case was described by Behrle et al. in 1963 in a 3-year-old child. About 40 other cases have been reported since then.,, Interestingly, all the reported cases of HB with PP were associated with elevated beta-human chorionic gonadotropin (β-hCG) levels except two. HBs typically present with an elevated alpha-fetoprotein (α-FP), and only 18% have a raised β-hCG level. Virilization is due to β-hCG-induced testosterone production as a paraneoplastic phenomenon because both serum level of β-hCG and testosterone are elevated in these cases. Virilizing HBs are rare and reported to have a poor outcome. We report one such case with good result in the short term.
| Case Report|| |
A 3-year-old male child presented to our department with a history of gradually progressive abdominal distention and excessive growth of pubic hair growth for 4 months. There was no history of pain abdomen, fever, or vomiting, and the child was feeding well. Bowel and urinary habits were normal. On general physical examination, the height and weight were less than the 3rd centile for his age, and there was no jaundice or lymphadenopathy. The abdomen had a visible mass in the right upper quadrant, which was palpable up to 8 cm below the right costal margin, firm in consistency, and nontender. The testes as well as penis looked large for his age with a stretched phallus length of 5 cm. There was some growth of pubic hair which is usually not seen at this age [Figure 1] (Tanner Stage-3 genitalia).
Serum levels of α-FP, β-hCG, and testosterone were raised (40,500 ng/ml, 58.58 mIU/ml, and 467.39 ng/ml, respectively). The values of both follicle-stimulating hormone and luteinizing hormone (LH) were suppressed (<0.5 mIU/ml and <0.07 mIU/ml, respectively) suggesting peripheral production of virilizing hormones. However, dehydroepiandrosterone, cortisol, and adrenocorticotrophic hormone were within normal range. Ultrasonography of the abdomen showed a solid mass arising from the inferior surface of the liver. Magnetic resonance imaging revealed a large, well-circumscribed, and lobulated mass approximately 7.5 cm × 7.1 cm × 7 cm, arising from the inferior surface of the right lobe of the liver [Figure 2]. It had a variegated appearance with foci of hemorrhage, necrosis, and curvilinear calcification with contrast enhancement of peripheral capsule and a few internal septae. The lesion was seen to be abutting the anterior surface of the right kidney which was otherwise normal in contour and corticomedullary differentiation. A fine-needle aspiration cytology of the hepatic mass confirmed the diagnosis of HB.
|Figure 2: Magnetic resonance images showing tumor in the right lobe of the liver|
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As per the institutional protocol, the patient received four preoperative cycles of cisplatin-based chemotherapy before being subjected to surgical excision. At surgery, resection of hepatic segments V and VI was performed along with cholecystectomy. Hepatic and common bile ducts were uninvolved and away from the tumor. Histopathological examination confirmed the diagnosis and showed resection margins to be free of tumor. The patient is doing well and has received two more cycles of postoperative chemotherapy with no evidence of recurrence at 6 months after surgery. After chemotherapy and surgery, α-FP, β-hCG, and testosterone levels normalized, and the signs of virilization did not progress further.
| Discussion|| |
The precocious puberty associated with HB is a gonadotropin-releasing hormone-independent peripheral PP, secondary to high serum level of β-hCG and testosterone. There are two potential explanations for this phenomenon as follows: (i) majority of the reports suggest that testosterone is produced from the Leydig cells stimulated by the high levels of β-hCG, which shares LH properties; and (ii) a direct testosterone secretion by the tumor cells. We believe that virilization was a paraneoplastic manifestation due to β-hCG-induced testosterone production and in our patient both β-hCG and the testosterone levels were elevated. Paraneoplastic syndromes are rare disorders that are triggered by an altered immune system response to a neoplasm and occur remotely from the tumor itself. The symptoms may be endocrine, neuromuscular or musculoskeletal, cardiovascular, cutaneous, hematologic, gastrointestinal, renal, or miscellaneous. The endocrine syndromes result from the aberrant production of protein hormones, hormone precursors, or hormone-like substances by the tumor.
First described by Behrle et al. in 1963 in a 3-year-old child, the precocious puberty associated with HB is a recognized but rare entity and about 40 other cases having been reported till now,,, [Table 1]. All the previous cases have been exclusively found in male children and more commonly in the right lobe. In the majority of the patients, age ranged from 7 months to 3 years except the two, who were 8 years old. In a review of all these cases, a trend is toward improvement; survival is noticeable which may be attributable to complete excision of the tumor and the efficacious use of chemotherapeutic regimens particularly cisplatin.
Both PPP and HB are rare disorders. However, PPP can be the presenting clinical feature of a tumor, and investigations should include a search not only for the tumors originating from the gonads and adrenals but also in other organs such as liver, mediastinum, and central nervous system. Early diagnosis can further improve the outcome in HB with newer modalities of treatment.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]