Mutation of an X chromosome in aggressive angiomyxoma: Report of a case and review of the literature

Highlights

► Cytogenetic analysis performed on peripheral blood showed a similar abnormal chromosomal complement in tumor tissue. ► Thus, mutation of an X chromosome appears to be confined to the neoplasm. ► This anomaly has not been previously described in aggressive angiomyxoma.

Introduction

Aggressive angiomyxoma, first described by Steeper and Rosai in 1983 (Steeper and Rosai, 1983) and now called “deep angiomyxoma” according to the World Health Organization classification, is a rare benign slow-growing hypocellular soft tissue neoplasm composed of cytologically bland stellate and spindle-shaped cells in a myxoid background, with a conspicuous vascular component.

Clinical misdiagnosis, most commonly as a Bartholin cyst, is a common problem, reported in as many as 82% of cases (Smith et al., 1991). Although aggressive angiomyxoma is benign, it is locally infiltrative with a high rate of recurrence (71% at 3 years, in one study), with intervals from 9 to 180 months. The high rate of recurrence is thought to be secondary to inadequate primary excision (Peihai et al., 2011).

Cytogenetic studies of myxomas are few. To date, abnormal cytogenetic findings have been reported for only twelve cases of aggressive angiomyxoma. Here, we report both the neoplasm and peripheral blood cytogenetic abnormality for an aggressive angiomyxoma arising in the vulval wall of a 32-year-old woman.

Case report

An otherwise healthy 32-year-old female was seen at the Women's hospital, School of Medicine, ZheJiang University, complaining of a mass on the right vulva. The mass had gradually increased in size in a year period. Gynecologic history was unremarkable, with menarche at age 15 and regular cyclic menses. Physical examination was normal with the exception of an exophytic polypoid mass measuring 7 × 6 × 5 cm in the right vulva region (Fig. 1). Computerized tomography and magnetic resonance imaging of the abdomen and pelvis were performed. A soft tissue mass extending from the right labium majus was identified. Differential diagnostic considerations included a complicated Bartholin gland cyst, or a soft tissue sarcoma. A fine-needle biopsy of the mass was obtained. Histopathologic examination of the biopsy specimen demonstrated a hypocellular lesion consisting of cytologically bland spindle-shaped cells in a myxoid background. No significant nuclear pleomorphism or mitotic activity was present. The spindle cells were immunoreactive for desmin, SMA, CD10, CD34, VIM, ER and PR.

Fig. 1.

Anatomy of vulvar aggressive angiomyxioma.

Excision of the mass was accomplished without difficulty; the base of the lesion was well demarcated, and a deep dissection was not necessary. The specimen was examined in the operating room and consisted of a soft tissue mass with overlying skin that measured 10 × 6 × 3 cm in total. A portion of this specimen was submitted for cytogenetic analysis. The procedure was well tolerated. One year later the patient was well without evidence of recurrence.

Histologically, the lesion was a hypocellular myxoid neoplasm composed of a monotonous population of stellate and spindle cells with occasional admixed mast cells. Extracellular ground substance associated with focal microcystic degeneration was present. There was a prominent vascular component, composed predominantly of capillaries and venules, which were focally dilated and congested, with lumenal fibrin thrombi. Necrosis, cellular atypia, and mitotic figures were not present.

Immunohistochemistry revealed strong positivity for vimentin, SM actin, desmin and CD34 were positive. Progesterone was positive and estrogen weakly positive, and CD10 were negative.

Analysis of one hundred metaphase cells from representative tumor tissue revealed mutation in X chromosome in thirteen cells (45,X(Kenny-Moynihan et al., 1996)/47,XX + 21(Peihai et al., 2011)/47,XXX(Smith et al., 1991)/48,XXXX(Peihai et al., 2011)) and a normal complement in the remaining eighty seven. A representative karyotype is presented in Fig. 2. Analysis of one hundred metaphase cells from the peripheral blood sample revealed similar mutation in X chromosome complement.

Fig. 2.

Mutation karyotype in X chromosome in thirteen cells(45,X[5]/47,XX+21[3]/47,XXX[2]/48,XXXX[3]).

Discussion

The immunohistochemical study of our case revealed positive progesterone receptors and weakly positive estrogen indicating a high rate of relapse. Fishman et al. (Sun and Li, 2010) described a case of a 37-year-old woman with a diagnosis of aggressive angiomyxoma who was weakly estrogen-positive and progesterone-negative, and relapsed during pregnancy. On the other hand, Htwe et al. (Kenny-Moynihan et al., 1996) found that a 41-year-old woman diagnosed as having aggressive angiomyxoma during pregnancy was with positive progesterone receptors and negative estrogen receptors. Recent reports suggest a role for hormone manipulation in the management of these tumors. Sun (Nilsson et al., 2006) reported a 31-year-old woman, postsurgery, a GnRH agonist (3.75 mg triptorelin) was injected intramuscularly every month for 3 months to prevent tumor recurrence and no relapse has been observed. Whether treatment is with surgery, hormone therapy or both, it is clear that aggressive angiomyxoma requires close, long-term follow-up to monitor for disease recurrence and that the individualization of each case is essential for adequate management. Because of weakly estrogen-positive, this patient rejected GnRH agonist injection, we have followed-up this patient for two years but no relapse was found, and longer monitoring was recommended (Fig. 3).

Fig. 3.

Vascular Component were immunoreactive for ACT, CD10, CD34, Desmin, ER and PR.

Aggressive angiomyxoma is rare and benign in vulvar soft connective tissue. Cytogenetic abnormalities have been identified in twelve cases of aggressive angiomyxoma to date (Rawlinson et al., 2008). Abnormalities of chromosome X were detected in two of these cases. In this case of aggressive angiomyxoma of the vulva region of an otherwise healthy 32-year-old female, mutation of an X chromosome was seen (45,X/47,XX+21/47,XXX/48,XXXX). The woman bore a 6-year-old son, whose peripheral blood sample was normal. This finding is of interest with respect to the observation of the loss of X chromosome in another clonally aberrant myxomas cytogenetically described. The latter was normal in peripheral blood chromosome.

Cytogenetic abnormalities involving chromosome 12 are reported in eight cases of aggressive angiomyxoma. Chromosome 12 is reported to be rearranged with chromosome (Tsuji et al., 2007). Another article reported chromosome 15 rearranged with chromosome 25 (Kazmierczak et al., 1995). Chromosomal aberrations involving the breakpoint region 12q14-15 are frequently seen in aggressive angiomyxoma (McCluggage et al., 2006). In this case, chromosome 21 rearranging with chromosome X was seen.

In summary, the present case of aggressive angiomyxoma demonstrated a 45,X/47,XX+21/47,XXX/48,XXXX. Further studies are needed to determine if sex chromosome mutation or translocation of chromosome 21 is characteristic of aggressive angiomyxoma in general. Recent reports suggest a role for hormone manipulation in the management of these tumors. It has been reported that a recurrent aggressive angiomyxoma can be treated using GnRH agonists, which makes it possible to avoid further destructive surgery. Given the positive progesterone and weakly positive estrogen receptor status of the tumor described here, we don't consider hormonal treatments in the case of a future relapse. One year later the patient was well without evidence of recurrence.

Conflict of interest statement

The authors have no conflicts of interest to disclose.