|Ahead of print publication
Complete androgen insensitivity syndrome with intra-abdominal seminoma in a phenotypic female: A rare presentation
Savita Arora, Neha Sharma, Arun Kumar Rathi, Kishore Singh, Kavita Sehrawat
Department of Radiotherapy, Maulana Azad Medical College and Associated Lok Nayak Hospital, New Delhi, India
|Date of Submission||07-May-2018|
|Date of Decision||26-Nov-2018|
|Date of Acceptance||16-Jan-2019|
|Date of Web Publication||20-Jan-2020|
Department of Radiotherapy, Maulana Azad Medical College and Associated Lok Nayak Hospital, New Delhi
Source of Support: None, Conflict of Interest: None
Androgen insensitivity syndrome (AIS) is a rare, X-linked recessive disorder which causes alterations in androgen receptor gene leading to hormone resistance, which may present clinically under three phenotypes: complete AIS (CAIS), partial AIS, or mild AIS. The symptoms range from phenotypically normal males with impaired spermatogenesis to phenotypically normal women with primary amenorrhea. We report a case of a 35-year-old woman who was diagnosed with CAIS and presented with malignant transformation of the undescended testis. The histopathology confirmed the presence of seminoma. In this case report, we reviewed the literature which describes the biochemical and endocrinological abnormalities leading to the syndrome. It also highlights the potential for malignant changes of the undescended testes, diagnosis, and therapeutic management.
Keywords: Malignancy in androgen insensitivity syndrome, malignant transformation of undescended testes, seminoma in androgen insensitivity syndrome
|How to cite this URL:|
Arora S, Sharma N, Rathi AK, Singh K, Sehrawat K. Complete androgen insensitivity syndrome with intra-abdominal seminoma in a phenotypic female: A rare presentation. J Can Res Ther [Epub ahead of print] [cited 2020 May 25]. Available from: http://www.cancerjournal.net/preprintarticle.asp?id=276132
| > Introduction|| |
Androgen insensitivity syndrome (AIS) is a rare X-linked recessive disease. It is the most common cause of disorders of sex development in 46 XY individuals.
The clinical phenotypes of AIS can vary in presentation. AIS can be classified into three categories, i.e., complete AIS (CAIS), partial AIS (PAIS), and mild AIS (MAIS) according to the severity of androgen resistance. CAIS usually presents as primary amenorrhea in adolescent females while PAIS presents with varying degrees of masculinization of the external genitalia due to partial androgen responsiveness. MAIS is associated with androgen receptor mutations but without external genitalia abnormalities.
Typically, laboratory diagnosis is made through elevated levels of luteinizing hormone and testosterone, with little or no virilization. The AIS with malignant testicular disorder is very rare. Here, we present a case of 35-year-old female who presented with symptoms of abdominal distension. The case was subsequently investigated and diagnosed as a case androgen insensitivity.
| > Case Report|| |
A 35-year-old married female, resident of New Delhi, presented in the department of obstetrics and gynecology with complaints of distension of abdomen since 4 months, which was insidious in onset, gradually progressive over a period of 4 months. The patient also complained of loss of appetite and constipation. She also gave a history of never having any menstrual cycle and obstetric history of not being able to conceive in the past 8 years of her married life. She never visited infertility clinic for the above complaints. Her family history revealed that she had one maternal aunt and one sister with primary amenorrhea. Her sister had consulted a gynecologist and was diagnosed as a case of testicular feminization syndrome. On general and physical examination, the patient was phenotypically female with no facial, axillary, and pubic hair. The breast was well developed (tanner Grade Intravenous [IV]). On per abdomen examination, a large ill-defined mass measuring about 20 cm was palpable in hypogastrium which was firm, nontender with restricted mobility. Genitourinary examination revealed a normal female external genitalia with the absence of uterus and cervix. The blind vagina was 4 cm long. Routine blood investigations were normal.
Findings of magnetic resonance imaging Pelvis (07.09.17) were evidence of a heterogeneously, enhancing solid mass measuring 18 cm × 16 cm × 11 cm in abdominopelvic region, appearing hypointense on T1-weighted images [Figure 1]. Bilateral ovaries were not seen separately. The lower part of vagina was seen and appeared normal in signal intensity. The mass was separate from vagina, displacing the bowel loops peripherally. The mass was closely abutting bladder with no signs of obvious invasion. Mild ascites was present. The enlarged pelvic lymph node was noted along right common and external iliac arteries. The patient was provisionally diagnosed as a case of germ cell tumor. The patient was provisionally diagnosed as a case of germ cell tumor.
|Figure 1: Magnetic resonance imaging abdomen and pelvis showing a solid mass 18 cm × 16 cm × 11 cm in abdominopelvic region. The mass is separate from vagina. Also showing lower part of vagina which ends blindly|
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The patient underwent exploratory laparotomy with debulking of tumor and pelvic lymphadenectomy. Her intraoperative findings revealed a mass of approximately 20 cm × 20 cm in pelvis extending till umbilicus. Fat planes with bladder and rectum were ill-defined. Left gonad was not separately palpable. The uterus was absent. The right gonad was present in the right iliac fossa. Debulking was done along with removal of the right gonad. Right external iliac nodes were dissected.
The postoperative histopathology report revealed tumor cells arranged in sheets and clusters, surrounded by the fibrous septa. Cells had clear cytoplasm with vesicular nuclei and prominent nucleoli. The fibrous septa showed the presence of lymphocytes. Focal areas of necrosis identified. Features were suggestive of seminoma [Figure 2].
|Figure 2: Histopathology consists of tumor cells with central round to polygonal nuclei and distinct cell border with eosinophilic to clear cytoplasm. The fibrous septa showed the presence of lymphocytes|
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Sections from right gonad showed seminiferous tubules. Interstitium showed the presence of Leydig cell hyperplasia. No spermatogenesis was seen within seminiferous tubules. Resected end of cord was unremarkable.
Single right iliac lymph node isolated showed focus of epithelioid cell granuloma.
Peritoneal washing for cytology showed no atypical cells.
As shown in [Table 1], tumor markers were as follows:
The preoperative elevated serum testosterone levels are characteristic of CAIS.
Postoperative whole-body positron emission tomography-computed tomography (WB PET-CT) scan (31.10.17) showed hypermetabolic irregular peritoneal nodular lesion involving left lateral pelvic peritoneal reflection near postsurgical clips suggestive of residual disease.
Mild ascites was noted. Peritoneal nodules were present along with left supraclavicular, left cervical level IV (1.5 cm × 0.9 cm SUVmax 2.9), abdominopelvic (2.5 cm × 1.8 cm, SUVmax 12.2), and right inguinal lymph node (1.1 cm × 0.9 cm, SUVmax 5.0) [Figure 3] and [Figure 4].
|Figure 3: Whole-body positron emission tomography-computed tomography scan showing right external iliac lymph node 2.5 cm × 1.8 cm, SUVmax 12|
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|Figure 4: Whole-body positron emission tomography computed tomography scan showing increased fluorodeoxyglucose uptake in bilateral common iliac lymph nodes|
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The patient was planned for bleomycin (30 IU/week IV on days 1, 8, and 15), etoposide (100 mg/m2/day IV on day 1–5), cisplatin (20 mg/m2/day IV on days 1–5)-based chemotherapy, given every 21 days. A total of four such cycles were given to the patient till 24.01.18. As shown in [Table 2], tumor marker levels after each cycle were as follows:
WB PET-CT Scan, 6 weeks after last chemotherapy (29.02.18) revealed hyper-metabolic abdominopelvic (2.1 cm × 1.6 cm, SUVmax 10.1) and right inguinal lymphadenopathy (1.1 cm × 0.9 cm, SUVmax 3.2) – likely residual metastatic [Figure 5].
|Figure 5: Whole-body positron emission tomography computed tomography scan showing right external iliac lymph node 2.1 cm × 1.6 cm, SUVmax 10.1|
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As compared to the previous PET scan, there was metabolic resolution of left supraclavicular, abdominal, and some of pelvic lymph nodes evident. Overall findings were suggestive of partial response to therapy. A repeat biopsy from right inguinal lymph node confirmed the residual disease.
The patient was planned for salvage chemotherapy (paclitaxel, cisplatin, and ifosfamide). The patient received 2 cycles of chemotherapy, last cycle given on 03.04.18. The patient received 2 cycles of chemotherapy, last cycle given on 03.04.18. WB PET-CT Scan (22.05.18) revealed nonfluorodeoxyglucose avid abdominopelvic lymph nodes and right inguinal lymph node (1 cm × 0.9 cm, SUVmax 1.1). The patient was then kept on regular monthly follow-up. Tumor marker levels monitored on 13.07.18 were within normal limits.
| > Discussion|| |
The prevalence of AIS has been estimated to be one case in every 20,000–64,000 newborn males for the CAIS. The prevalence is unknown for the partial syndrome (PAIS). CAIS is characterized by primary amenorrhea, a 46XY chromosomal, female phenotype with adequate breast development, normal external genitalia, a vagina of variable depth, absent uterus, and sparse or absent pubic hair and axillary hair. Testes are bilaterally retained either in the abdominal 50%–70%, in inguinal region 20% or located both in the abdomen on one side and in the inguinal region on the other side 10%–30%. Occasionally, the testes may be seen even in the retroperitoneum.
New studies have suggested a somewhat lower risk malignant transformation of testes. Around 5% of AIS transform into malignancy, with a particularly low prevalence of <1% in CAIS.
Literature suggests that AIS female phenotype patients retaining their testes through puberty have a 5% chance for developing malignant tumors. The risk of malignancy in patients with AIS is considerably low before puberty; malignancy in patients with AIS occurs at a later age compared with patients with other types of DSD. Risk of the development of malignancy is lower in CAIS as compared to PAIS. Tumor prevalence prominently increases after adolescence and reaches 33% at the age of 50 years.
The diagnosis of CAIS is usually based on clinical findings and hormonal evaluation. Other diagnostic modalities include karyotyping, visualization methods, and genetic analysis. The diagnosis of CAIS, as in our case, was based on clinical picture, hormonal analysis [Table 1], imaging, and postoperative histopathology. Prophylactic orchidectomy is recommended after puberty to avoid development of an invasive germ cell tumor within the intra-abdominal testis. After orchidectomy, estrogen replacement therapy should be started to maintain feminization and avoid osteoporosis. Surgery is deferred before puberty because such malignancy is quite uncommon before puberty. Postponing surgery until after puberty allows the development of secondary sex characteristics in the patient and bone mass accrual during puberty through peripheral conversion of androgens to estrogen. However, such an approach warrants the use of adequate screening program to detect any malignant changes at an early stage.
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.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2]