|Year : 2018 | Volume
| Issue : 4 | Page : 252-255
Mistaken oophorectomy in an adolescent with mccune–Albright syndrome: A case report and literature review
Jun Guan1, Hai-Yun Guan2, Lu Wang2, Wei Zhang3
1 Department of Gynecology, Campus Virchow Clinic, Charite Medical University of Berlin, Corporate Member of Free University of Berlin, Humboldt University of Berlin, and Berlin Institute of Health; Tumor Bank Ovarian Cancer Network, Berlin, Germany
2 Department of Gynecological Endocrinology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China
3 Department of Gynecological Endocrinology, Obstetrics and Gynecology Hospital of Fudan University; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China
|Date of Submission||28-Jul-2018|
|Date of Web Publication||11-Jan-2019|
Department of Gynecological Endocrinology, Obstetrics and Gynecology Hospital of Fudan University, 419 Fangxie Road, Shanghai 200011
Source of Support: None, Conflict of Interest: None
McCune–Albright syndrome (MAS) is a rare disease characterized by café au lait spots, bone fibrous dysplasia, and precocious puberty. Most MAS cases are diagnosed before adolescence. Here, we reported an adolescent girl underwent mistaken oophorectomy for suspected ovarian tumor, and later, she was diagnosed with MAS. An 11-year-old girl was found to have an irregular pelvic mass measuring 9.74 cm × 9.01 cm × 7.30 cm with a cyst–solid component and a clear boundary by magnetic resonance imaging. She underwent right oophorectomy for the suspected ovarian tumor. However, histopathological examination showed ovarian tissue with many antral follicles. One week after the surgery, ultrasonography revealed a left pelvic irregular echo-free mass measuring 60 mm × 53 mm × 48 mm. The patient was then examined by endocrine specialists, and café au lait spots were found predominantly located on the right side of her waist, hip, and thigh. She had her first period before the surgery, and her serum concentrations of sex hormones were normal. Thus, MAS was diagnosed. The patient has been taking dydrogesterone 20 mg/d for 10 days from the 14th day of her period for 2 years. Ultrasonography performed every 3–6 months revealed no enlargement of her left ovary. Awareness of MAS and careful physical and imaging examination should be emphasized, even in the absence of full classic triad of syndromes. Hence, unnecessary oophorectomy and irreversible loss of fertility potential can be avoided in these patients.
Keywords: Adolescent with McCune–Albright Syndrome; Café au lait Spots; Diagnosis; Mistaken Oophorectomy
|How to cite this article:|
Guan J, Guan HY, Wang L, Zhang W. Mistaken oophorectomy in an adolescent with mccune–Albright syndrome: A case report and literature review. Reprod Dev Med 2018;2:252-5
|How to cite this URL:|
Guan J, Guan HY, Wang L, Zhang W. Mistaken oophorectomy in an adolescent with mccune–Albright syndrome: A case report and literature review. Reprod Dev Med [serial online] 2018 [cited 2019 Jan 17];2:252-5. Available from: http://www.repdevmed.org/text.asp?2018/2/4/252/249887
| Introduction|| |
McCune–Albright syndrome (MAS) is a rare disease, classically defined as the triad of precocious puberty (PP), fibrous dysplasia (FD) of bone, and café au lait lesions., The estimated prevalence ranges from 1/100,000 to 1/1,000,000. It is caused by activating mutations of GNAS1, the gene encoding for the alpha subunit of the stimulatory G-protein involved in intracellular signaling in endocrine cells and other tissues. This mutation results in loss of intrinsic GTPase activity, leading to abnormal accumulation of intracellular cyclic adenosine monophosphate and unregulated cell proliferation with overproduction of cellular product. The GNAS1-activating mutation occurring sporadically in a postzygotic cell line can be broadspectrum in both presentation and severity of symptoms. Thus, the mosaic distribution of affected cells can be widespread or limited, depending on the timing of the mutational event., Partial or atypical presentations of MAS, with only one or two of the classic symptoms, have been described in the literature and remain particularly challenging due to the lack of diagnostic phenotype. Autonomous ovarian cysts may be confused with an ovarian tumor, resulting in unnecessary surgery. Successful diagnosis using GNAS mutation analysis has been reported to be associated with disease severity, yet <50% yield positive results in patients with the classic triad. The utility of GNAS mutation analysis in these patients is limited, and the diagnosis is often based on clinical judgment. Here, we report a case of mistaken oophorectomy on a girl later suspected as having MAS and review the challenge in diagnosis and management of such a rare disease.
| Case Report|| |
An 11-year-old Chinese girl visited our hospital in December 2015 because of constant uterine bleeding for 1 month. She had her menarche 5 months ago with an abnormal cycle length 3 times. During her fourth period, she had a sudden right abdominal pain that was relieved substantially 2 days after, when pelvic ultrasonography revealed a low-echo pelvic mass measuring 133 mm × 101 mm × 99 mm, with an unsmooth lining and many small echo-free cysts inside. Magnetic resonance imaging confirmed the presence of an irregular pelvic mass measuring 9.74 cm × 9.01 cm × 7.30 cm with a cyst–solid component and a clear boundary [Figure 1]. Ovarian tumor was suspected, and laparoscopic right oophorectomy was performed. However, histopathological examination showed ovarian tissue with many antral follicles scattered irregularly in clusters [Figure 2]. She was then diagnosed as “right polycystic ovary.” One week after surgery, pelvic ultrasonography revealed a left pelvic irregular echo-free mass measuring 60 mm × 53 mm × 48 mm. Her fifth period started from 3 days after the surgery. One month later, her sixth irregular bleeding came and bled constantly for 1 month, bringing her to our hospital for further investigation.
|Figure 1: Magnetic resonance imaging for detecting ovarian mass. Magnetic resonance imaging confirmed the presence of an irregular pelvic mass measuring 9.74 cm × 9.01 cm × 7.30 cm with cyst–solid component and a clear boundary, before right oophorectomy.|
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|Figure 2: Representative histopathological images of right ovarian mass. Ovarian tissues with numerous antral follicles were found scattered irregularly in clusters, and interstitial edema with bleeding (H and E: [a] ×40; [b] ×100).|
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On physical examination, her breasts were in Tanner Stage 4 with normal axillary and pubic hair. Her external genitalia and clitoris were normal for her puberty stage. Her height and weight measured as 161 cm and 48 kg, respectively. Remarkably, café au lait spots were found predominantly located on the right side of her body, including waist, hip, and thigh [Figure 3]. Ultrasonography revealed an enlarged left ovary, measuring 61 mm × 36 mm × 22 mm, in which >30 antral follicles measured 2–9 mm in diameter per se ction. The serum hormonal analysis revealed testosterone (0.87 ng/mL), estradiol (62.00 pg/mL), follicle-stimulating hormone (FSH, 3.99 mIU/mL), and luteinizing hormone (LH, 6.25 mIU/mL). The results of the other endocrinal analyses were also normal.
|Figure 3: Café au lait skin pigmentation. Café au lait spots were predominantly located on the right side of the patient's body, including the waist, hip, and thigh.|
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When we questioned further, the patient's mother explained that café au lait spots were found since 10 days after her daughter was born. At the age of 9 years, the patient was taken to a local hospital because of the noticed enlarged breasts. However, the exactly onset of the enlargement of her beasts was not clear. A pelvic ultrasonography revealed bilateral enlarged ovaries (right side: 45 mm × 22 mm × 16 mm and left side: 37 mm × 16 mm × 13 mm). She was 155 cm in height, while her bone was 1 year advanced in age at that time. The local hospital did not provide any intervention. Two years later, the patient's menarche came, when she was 11 years old.
Based on the signs, symptoms, and medical history of this girl, MAS was suspected. Molecular analysis of genomic DNA obtained from peripheral lymphocytes was subsequently performed. No presence of GNAS1 gene mutation was revealed, neither was FD found by bone scan. The patient was treated with dydrogesterone 20 mg/d for 10 days to stop the bleeding. After hemostasis, dydrogesterone was taken from the 14th day of the period at 20 mg/d for 10 days. We followed her up for 2 years and performed ultrasonography every 3–6 months, which revealed no enlargement of her left ovary (1 year after dydrogesterone: 55 mm × 45 mm × 35 mm and 2 years after dydrogesterone: 40 mm × 40 mm × 35 mm).
| Discussion|| |
In girls with MAS, café au lait spot is the most common but neglected sign that usually presents at birth or shortly thereafter. Consistent with this, café au lait spots were observed since 10 days after birth in our patient. However, this “skin sign” was neglected by previous surgeons before removing her enlarged right ovary for suspected ovarian tumor. Histopathological examination further confirmed ovarian tissue with numerous antral follicles, rather than malignancy. Her left ovary enlarged quickly after right oophorectomy. Hence, a diagnosis of MAS was strongly considered, although her medical history was insufficient to diagnose PP and the results of the bone scan and GNAS mutation test were both normal. As her FSH and LH levels were of the central puberty level, GnRHa or contraceptive pills in combination with aromatase inhibitors should have been used for excluding MAS before the surgery. Although suspected ovary torsion would require surgery, ovary repositioning should have been considered in priority for preserving fertility potential instead of oophorectomy. Inadequate awareness of MAS led to the suspicion of ovarian malignancy, and subsequently, aggressive oophorectomy was performed.
Diagnosis of MAS based on the classic triad of syndromes remains challenging, owing to its various or atypical clinical manifestations and low specificity of genetic tests. Some MAS patients only presented one or two classic syndromes in the beginning and more syndromes later. This may due to the postzygotic GNAS-activating mutation, resulting in somatic mosaicism with varied distribution of the defect in tissues. A study reported that, of 113 MAS patients, only 24% presented full classic triad of syndromes, as compared with 40% and 33% presenting one and two classic syndromes, respectively. In addition, mutation analysis of serum leukocytes and café au lait spots exhibits positive results in only 8%–46% and 27% of cases, respectively. Although analysis of a sample from the affected tissue (with the exception of the skin) yielded the best specificity of 90%, the invasive procedures to obtain the affected tissue were difficult to perform on all the patients. In the presented patient, only café au lait spots were obvious; the bone scan showed no abnormalities; and the diagnosis of PP was limited by the inexact time for breast development. Atypical MAS, therefore, was considered. However, the previous surgeon did not arrange GNAS mutation test on the affected ovary, reducing the chance to confirm the diagnosis of MAS.
In addition, the patient had an irregular period and enlarged ovaries with many antral follicles, contributing to the potential diagnosis of polycystic ovary syndrome (PCOS). However, before the diagnosis of PCOS, other diseases that could cause similar syndromes must first be disregard. Thus, MAS was still considered the primarily diagnosis.
Ovarian tumors, considering their poor prognosis, should be differentiated from autonomous ovarian cysts or ovarian mass caused by MAS., Sex cord–stromal cell tumors, such as Juvenile granulosa cell tumors (JGCTs), are difficult to distinguish from MAS because of similar elevated estradiol levels, presence of PP, and radiographic evidence of an apparent cystic ovarian mass on pelvic ultrasonography or computed tomography. However, tumor markers, such as alpha-fetoprotein, β human chorionic gonadotropin, and carcinoembryonic antigen, which are mostly elevated in patients with JGCTs, are negative in girls with MAS, and the presence of café au lait spots and/or FD in association with PP is a typical syndrome of MAS., Careful physical (café au lait spots) examination, bone scan (polyostotic FD), and molecular biological analysis (GNAS1 mutation analysis) are helpful to exclude the diagnosis of MAS. Alternatively, aromatase inhibitors or in combination with GnRHa or contraceptive pills (when central puberty begins) could be used for a short period of watchful waiting before performing surgical treatment. The resolution of the ovarian mass revealed by ultrasonographic monitoring could support the diagnosis of MAS. In the reported patient, GnRHa or contraceptive pills in combination with the aromatase inhibitors should have been used for differentiating MAS from ovarian tumors.
Surgical intervention of ovarian cysts or mass is usually not recommended for female patients with MAS, as satisfying outcome with conservative treatments, such as the use of aromatase inhibitors or estrogen receptor agonists, can be achieved in most cases. In MAS, premature puberty due to autonomous ovarian cysts cannot be resolved with oophorectomy or ovarian cystectomy, and new follicular cysts may recur in the remaining ovarian tissue. Similarly, our patient had a rapid enlargement of her left ovary after the right oophorectomy. Moreover, once central puberty in MAS begins, the hypothalamic–pituitary–gonadal axis overrides the autonomous ovarian activation, and normal ovulatory cycles ensue. Nabhan et al. reported three of four girls with MAS who underwent oophorectomy by mistaken had obvious café au lait macules at the initial presentation, although the significance of this finding went unrecognized. In the present case, the café au lait spots of the patient were obvious, although subsequent bone scan and GNAS analysis were normal. Awareness of MAS could contribute to more careful physical examination and appropriate clinical decision to prevent unnecessary Oophorectomy.
Patients with MAS need long-term clinical follow-up as classical symptoms may evolve with time. Chronic hyperestrogenemia in women with MAS may increase the risk of infertility or estrogen-dependent cancers, such as breast, endometrium, or ovarian cancer.,,, Long-term gynecological follow-up should be implemented by regular pelvic ultrasonography and radiographic mammography. In our case, we used dydrogesterone for establishing a regular period to decrease the potential risk for endometrial cancer.
In conclusion, awareness of MAS and careful physical and imaging examination should be emphasized even when full classic triad of syndromes is lacking. Hence, unnecessary oophorectomy and irreversible loss of fertility potential in these patients can be avoided.
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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