Introduction
Aggressive angiomyxoma is a rare mesenchymal tumour typically occurring in the female pelvis and peritoneumReference Steeper and Rosai1 and the male genital tract.Reference Idrees, Hoch, Wang and Unger2 It has only once been described in the larynx.Reference Teixeira de Maghalhaes and Pardal de Oliveira3
We present the case of 47-year-old, dysphonic man diagnosed as the second known laryngeal case of aggressive angiomyxoma.
Case report
A 47-year-old man presented with a one-month history of dysphonia. Although this had been preceded by subtle changes over the previous year, he had remained systemically well, with no other features of malignancy apparent.
Flexible fibre-optic laryngoscopy showed a left-sided, mucosa-covered, smooth, supraglottic mass.
The patient was subsequently admitted for microlaryngoscopy and biopsy. Endoscopic examination of the larynx proved difficult due to prominent incisors and limited cervical spine extension. Laryngoscopy confirmed the above findings; inferior to the known mass, the larynx was normal. Biopsies were taken, which unfortunately proved inadequate.
Computed tomography of the larynx confirmed a well defined tumour confined to the supraglottis (Figure 1).
Fig. 1 Axial computed tomography scan showing left-sided, supraglottic mass.
Due to the above anatomical considerations, an open approach to the larynx was deemed most appropriate. The patient subsequently underwent a laryngofissure approach excision biopsy and covering tracheostomy. Intra-operatively, the left-sided supraglottic mass was completely excised.
The patient was successfully decannulated one week post-operatively and later discharged home.
Macroscopically, the mass measured 4.0×2.5×1.0 cm and was well circumscribed, oval, rubbery and white. Microscopically, a bland, hypocellular, myxoid stroma was seen, with a proliferation of abnormal blood vessels. Spindle cells were seen scattered throughout the entire specimen. The nuclei were small and hyperchromatic, but there was no nuclear atypia or mitoses. Neutrophil polymorphic cells were also scattered throughout (Figure 2). Immunostaining for S-100 protein, desmin, cluster of differentiation 34 glycoprotein and smooth muscle actin was negative.
Fig. 2 Photomicrograph showing bland, hypocellular, myxoid stroma with a proliferation of abnormal blood vessels (H&E; ×100).
After four years of follow up the patient remained well, with no evidence of loco-regional recurrence or distant metastasis.
Discussion
Although little is currently known about laryngeal aggressive angiomyxoma, research into the immunohistochemical, cytogenic and clinical course of its female pelvic counterpart may aid our understanding. The term ‘aggressive’ was introduced by Steeper and Rosai in 19831 in their case report of this distinctive neoplasm of the female pelvis and perineum. The term refers to the tumour's locally aggressive behaviour and propensity for local recurrence, rather than its metastatic potential. To date, only two cases of metastatic aggressive angiomyxoma have been published, both arising in the female pelvis.Reference Siassi, Papadopoulos and Matzel4, Reference Blandamura, Cruz, Faure Vergara, Machado Puerto and Ninfo5
Histologically, this neoplasm is characterised by a proliferation of spindle-shaped or stellate cells widely separated by loose, myxoid stroma, in which is dispersed a prominent vascular component. Immunohistochemically, female pelvic aggressive angiomyxomas have been found to be invariably positive for vimentin, desmin, cluster of differentiation 44, 34 and K4 glycoprotein, oestrogen receptors, progesterone receptors, smooth muscle actin,Reference Amezcua, Begley, Mata, Felix and Ballard6 and cytokeratin AE1/AE3.Reference van Roggen, van Unnik, Briaire de Bruijn and Hogendoorn7 Negativity for S-100 protein is consistent,Reference Amezcua, Begley, Mata, Felix and Ballard6, Reference van Roggen, van Unnik, Briaire de Bruijn and Hogendoorn7 and negativity for muscle-specific antigen variable.Reference Amezcua, Begley, Mata, Felix and Ballard6, Reference Fetsch, Laskin, Lefkovitz, Kindblom and Meis-Kindblom8 In our case, the only similarity with the pelvic form was negativity for S-100 protein, as positivity for desmin, cluster of differentiation 34 glycoprotein and smooth muscle actin was not found, suggesting either little immunohistochemical similarity or greater variability in the laryngeal form.
Chromosomal aberrations have been documented in numerous pelvic cases, identifying a non-random involvement of chromosomal band 12q15.Reference Kazmierczak, Wanschura, Meyer-Bolte, Caselitz, Meister and Bartnitzke9–Reference Micci, Panagopoulos, Bjerkehagen and Heim11 An additional case with 12q15 rearrangement has been described using fluorescence in situ hybridisation.Reference Rabban, Dal Cin and Oliva12 Such rearrangements lead to alterations of the high mobility group gene HMGA2.
Aggressive angiomyxoma has been classified by the World Health Organization under ‘tumours of uncertain differentiation’.Reference Fletcher, Unni and Mertens13 Its tendency for local recurrence has meant that, in the female pelvic form, complete excision is favoured when possible, preferably with a wide margin. Furthermore, the first case report of a laryngeal aggressive angiomyxoma suggested that this approach should be used for the laryngeal form, given that the tumour recurred after incomplete excision.Reference Teixeira de Maghalhaes and Pardal de Oliveira3
The use of chemotherapy and radiotherapy for aggressive angiomyxomas of the pelvis is not particularly effective, presumably because of the low mitotic activity demonstrated. However, due to the expression of oestrogen and progesterone receptors in the female genital tract forms, therapy with gonadotrophin-releasing hormone agonists has been applied. It has been suggested that this is useful in patients with recurrence or in whom surgical excision is not possible.Reference McCluggage, Jamieson, Dobbs and Grey14
• Aggressive angiomyxoma is a rare mesenchymal tumour now known to be found in the larynx
• Its more common pelvic counterpart demonstrates a propensity for local recurrence, and has metastatic potential
• Treatment is surgical; a wide excision margin is favourable
• It is currently unclear whether the immunohistochemical and genetic characteristics of the laryngeal form are similar to those of its pelvic counterpart
Given that the presented patient is only the second reported case of laryngeal aggressive angiomyxoma, the long-term prognosis remains undetermined. Although the female pelvic form was not previously thought to have metastatic potential, two case reports have now been published describing pulmonary,Reference Siassi, Papadopoulos and Matzel4 and pulmonary and mediastinal,Reference Blandamura, Cruz, Faure Vergara, Machado Puerto and Ninfo5 metastases. Long-term follow up and reporting of further cases will help to determine whether the laryngeal disease bears the same metastatic traits.
Conclusion
Angiomyxoma of the larynx is an uncommon, malignant tumour of unknown aetiology and prognosis. Comparison with the female pelvic form would suggest that complete surgical excision with a wide margin is the treatment of choice. Research into the pelvic form may aid our understanding; however, it is currently unclear to what extent the laryngeal form shares the immunohistological, cytogenetic and clinical traits of its pelvic counterpart.
