Case Report Progesterone receptor expression in sinonasal leiomyoma: a case report and review of the literature
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1 Int J Clin Exp Pathol 2014;7(3): /ISSN: /IJCEP Case Report Progesterone receptor expression in sinonasal leiomyoma: a case report and review of the literature Pao-Yu Tseng 1*, Yu-Shih Lai 1*, Mu-Kuan Chen 1,3*, Ko-Hung Shen 2* Departments of 1 Otorhinolaryngology, Head and Neck Surgery, 2 Pathology, Changhua Christian Hospital, Changhua, Taiwan; 3 Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. * Equal contributors. Received January 1, 2014; Accepted January 31, 2014; Epub February 15, 2014; Published March 1, 2014 Abstract: Leiomyomas are benign myogenic tumors that seldom occur in the sinonasal cavity. They were commonly found in middle-aged adults with a female predominance. Clinical symptoms include nasal obstruction with discharge, nasal bleeding and pain. We describe the case of a 48 year-old woman with a leiomyoma arising from right inferior nasal turbinate. Transnasal endoscopic excision was performed with satisfied result. The tumor was found to be progesterone receptor positive on immunohistochemical analysis. The clinical findings are addressed with a review of the literature. To the best of our knowledge, this is the third reported case that supports the growth of the tumor may be hormone-dependent. Keywords: Paranasal sinuses, nasal cavity, angioleiomyoma, sex hormone-binding globulin receptor, progesterone receptor, intranasal surgery Introduction Sinonasal leiomyomas are extremely rare. Barnes reported that less than 1% of all leiomyomas were found in the head and neck area and within these, only 3% occurred in the nasal cavity [1]. The paucity of smooth muscle in the nasal cavity might explain why the tumors were rare. Since the first report of an intranasal leiomyoma by Maesaka et al in 1966, about sixty subsequent cases had been described in the English-language literatures. We present a new case of sinonasal leiomyoma that immunohistochemical results suggest the tumor may be hormone-dependent with focal positivity to progesterone receptor (PR). The clinical characteristics, histopathological findings, the role of sex hormones in tumor growth and treatment options were discussed. Case report Clinical presentation A 48-year-old woman presented with nasal mucopus and occasional blood-tinged discharge for three months. She was otherwise healthy before and denied any nasal trauma or surgical history. Nasopharyngoscopic survey revealed some yellowish mucopus over bilateral middle meatuses and a 1 cm x 1 cm sized mass located near anterior third of right inferior nasal turbinate. No other abnormality was found in the nasopharynx, oral cavity, larynx and neck. Computed tomography (CT) scan of nose and paranasal sinus showed a homogeneous soft tissue mass originating from right inferior nasal turbinate and mucoperiosteal thickenings with fluid level in bilateral maxillary sinuses (Figure 1). The lesion was completely removed endoscopically under general anesthesia. Postoperative recovery was uneventful. There was no evidence of recurrence four years after surgery. Gross and histopathology Grossly, the resected specimen was brownish and elastic. Microscopically, a submucosal tumor consisted of interlacing bundles of blandlooking spindle cells and many thick-walled vessels was seen. The spindled cells had elongated vesicular nuclei with blunt ends, perinuclear vacuoles and eosinophilic cytoplasm (Figure 2). Immunohistochemical analysis showed strong positivity for smooth muscle actin and focal
2 Figure 1. Non-contrast CT image reveal a homogeneous soft tissue mass (white arrow) originating from superior aspects of the right inferior nasal turbinate. Note fluid level over bilateral maxillary sinuses. nuclear positivity for PR (Figure 3A and 3B). Negativity for S-100 protein and estrogen receptor (ER) were also noted (Figure 3C). The feature was consistent with a benign vascular leiomyoma. Discussion Sinonasal leiomyoma, a benign neoplasm, is rarely found in the head and neck region. It can be thought as a middle-aged disease with most patients diagnosed in their fifth and sixth decade [2-5]. A female to male ratio of 2 to 1 was noticed [2]. More tumors were found in the right sinonasal cavity, but the reason remained unknown [5]. Inferior nasal turbinate, nasal septum and nasal vestibule were the most common sites of occurrence [2, 3, 5]. The presenting symptoms were nonspecific and usually characterized by nasal obstruction, epistaxis and nasal discharge. These symptoms resulted from the mass effect related airflow change which caused nasal crusting and nasal desiccation. Local pain wasn t that common in sinonasal leiomyoma. Figure 2. A: A well circumscribed submucosal neoplasm composed of spindled cells arranged in interlacing fascicles (H & E staining; 2 x magnification). B: The neoplasm consisted of thick-walled vessels and spindled tumor cells surrounding around (H & E staining; 100 x magnification). C: The spindled cells had elongated vesicular nuclei, perinuclear vacuoles and fibrillar eosinophilic cytoplasm (H & E staining; 400 x magnification). The etiology of sinonasal leiomyoma remains uncertain. Marioni et al hypothesized the tumor growth might be hormone-dependant due to a female predominance and the increased pain during pregnancy or the menstrual cycle in patients described elsewhere [3]. They published the first case of nasal vascular leiomyoma with immunopositivity for PR and negativity for ER in a 70-year-old woman. He et al reported another case with the same immunoreactivity and suggested the role might also work even in a male patient [6]. However, there were three cases presented totally different results with negativity to both ER and PR [7-9]. The present case had similar result to Marioni et al; the 1225 Int J Clin Exp Pathol 2014;7(3):
3 immunohistochemical study showed positivity for PR and negativity for ER. To our knowledge, this is the third case that supports this hormone hypothesis (Table 1) [3, 6-9]. Furthermore, all three cases showed immunopositivity to PR had symptom of nasal bleeding while the other three didn t. Maybe the expression of PR could influence the clinical performance. The association between the tumor and the sex steroid receptor should be clarified. Most authors accepted three hypotheses to explain the origin of the sinonasal leiomyoma. They could stem from aberrant undifferentiated mesenchymal or smooth muscle elements in the blood vessel wall [10]. In the nasal vestibule, they might arise from erector pilae or sweat gland muscles [11]. The observation of many tumors located in nasal turbinates seemed to support the hypotheses; these areas had relatively abundant blood vessels and smooth muscles. But some authors suggested that vascular leiomyoma could be a vascular malformation or a progressive development of smooth muscle proliferation from hemangioma, to an angioma with much muscle, to a leiomyoma with many vessels, and to a solid leiomyoma [12]. Figure 3. A: The tumor cells showed peripheral tramtracking pattern of smooth muscle actin expression (100 x magnification). B: Focal nuclear immunopositivity to progesterone receptor (400 x magnification). C: Immunonegativity to estrogen receptor (400 x magnification). World Health Organization (WHO) classified leiomyoma into three groups: nonvascular leiomyoma (solid leiomyoma), vascular leiomyoma (angiomyoma), and epithelioid leiomyoma (atypical or bizarre leiomyoma and leiomyoblastoma). Morimoto divided angiomyoma into three histologic subtypes in 1973: solid or capillary, cavernous, and venous. The vascular subtype is the most common one and angiomyoma of head and neck usually present as venous or cavernous type [12]. Microscopically, interlacing bands of spindle-shaped cells with cigarshaped nuclei are usually seen. The differential diagnosis includes hemangioma, angiofibroma, hemangiopericytoma, myofibroma and leiomyosarcoma. Immunohistochemical staining such as muscle specific actin, desmin, myoglobin, S-100 protein, vimentin can be of additional value [2, 12]. There was no characteristic image finding for preoperative diagnosis, but CT and magnetic resonance imaging (MRI) could provide the information about the extent of the lesion, bony erosion and sometimes differentiate the neoplasm from inflammatory changes [13]. A tissue biopsy might be performed before surgery, but the accuracy of preoperative diagnosis seemed to be doubtful. In three cases with preoperative biopsy, the results turned out to be the hemangiopericytoma, inflammatory tissue and hemangioma [2, 14, 15]. Therefore, the final diagnosis depended on surgical excision with histopathological study Int J Clin Exp Pathol 2014;7(3):
4 Table 1. Sex hormone receptor expression in vascular leiomyoma of sinonasal cavity Authors Sex Age (yr) Location Side Size (cm) Symptoms PR ER Marioni et al. (2002) F 70 NVe R 1.5 N-O, N-B + - Kim et al. (2004) F 60 IT R 2 N-D, Sneezing - - Chen et al. (2007) M 88 IT R 0.9 N-D, right hearing impairment - - He et al. (2009) M 58 IT R 1.3 N-O, N-B + - Onesti et al. (2012) F 46 NT L 1.45 P-M, skin color change at high temperature - - Present case F 48 IT R 1 N-D, N-B + - Abbreviations: ER: estrogen receptor; F: female; IT: inferior turbinate; L: left; M: male; N-B: nasal bleeding or bloody discharge; N-D: nasal discharge; N-O: nasal obstruction; NT: nasal tip; NVe: nasal vestibule; PR: progesterone receptor; P-M: protruding mass; R: right. The most satisfactory treatment for sinonasal leiomyoma is complete surgical excision. The surgical approach depends on the size, location, the extension of tumor and the experience of the surgeon. In most cases, transnasal endoscopic excision can be performed successfully because many of them were limited in sinonasal cavity. For case in certain site or larger and more extended one, transpalatal, Caldwell-Luc, lateral rhinotomy, external ethmoidotomy with medial maxillectomy or Craniofacial resection is also of the choice. The prognosis of sinonasal leiomyoma is favorable. No malignant transformation of sinonasal leiomyoma had been published before. The recurrence is rare after complete excision. Yang et al mentioned one patient with recurrent leiomyoma two years after surgery which was probably due to incomplete excision of tumor margin and adjacent bony shell [13]. The patient then received further surgical excision with no evidence of recurrence for 5 years. Thus, the chance of local recurrence is mainly related to incomplete excision at first surgery. In conclusion, sinonasal leiomyoma is a middleaged disease with a female predominance. Patients usually have nonspecific symptoms like nasal obstruction, epistaxis and nasal discharge. Mostly, they are vascular subtype and the tumor growth may be hormone-dependant. For those with immunopositivity to PR, there is a chance that symptom like epistaxis developed. CT and MRI provide useful information about the tumor and the surrounding structure. Complete surgical excision is recommended either by endoscopic or open procedure. The prognosis is favorable with rare local recurrence. Currently, no patient has been reported to have malignant change in previous surgical site after definite surgery. Disclosure of conflict of interest None. Address correspondence to: Dr. Pao-Yu Tseng, Department of Otorhinolaryngology, Head and Neck Surgery, Changhua Christian Hospital, 135 Nanxiao St., Changhua City, Changhua County 500, Taiwan. Tel: ; Fax: ; @cch.org.tw References [1] Barens L. Surgical pathology of the head and neck. vol 1. New York: Marcel Dekker; pp: [2] Nicolai P, Radaelli de Zinis LO, Facchetti F, Maroldi R, Antonelli AR. Craniofacial resection for vascular leiomyoma of the nasal cavity. Am J Otolaryngol 1996; 17: [3] Marioni G, Marchese-Ragona R, Fernandez S, Bruzon J, Marino F, Staffieri A. Progesterone receptor expression in angioleiomyoma of the nasal cavity. Acta Otolaryngol 2002; 122: [4] Campelo VE, Neves MC, Nakanishi M, Voegels RL. Nasal cavity vascular leiomyoma: case report and literature review. Braz J Otorhinolaryngol 2008; 74: [5] Vafiadis M, Kantas I, Panopoulou M, Sivridis E, Exarchakos G. Vascular leiomyoma of the nasal vestibule. Case report and literature review. B-ENT 2008; 4: [6] He J, Zhao LN, Jiang ZN, Zhang SZ. Angioleiomyoma of the nasal cavity: a rare cause of epistaxis. Otolaryngol Head Neck Surg 2009; 141: [7] Kim SJ, Hong SH, Roh MS. Angioleiomyoma of the nasal cavity: a case report. Korean J Pathol 2004; 38: [8] Chen CJ, Lai MT, Chen CY, Fang CL. Vascular leiomyoma of the nasal cavity: case report. Chin Med J (Engl) 2007; 120: [9] Onesti MG, Maruccia M, Carella S, Rossi A, Soda G, Scuderi N. Subcutaneous angioleio Int J Clin Exp Pathol 2014;7(3):
5 myoma of the nasal tip. Report of a rare case. In Vivo 2012; 26: [10] Batsakis JG. Tumors of the head and neck: Clinical and Pathological Considerations. 2nd ed. Baltimore: Williams and Wilkins; pp: [11] Barr GD, More IAR, McCallum HM. Leiomyoma of the nasal septum. J Laryngol Otol 1990; 104: [12] Duhig JT, Ayer JP. Vascular leiomyoma: a study of sixty-one cases. Arch Pathol Lab Med 1959; 68: [13] Yang BT, Wang ZC, Xian JF, Hao DP, Chen QH. Leiomyoma of the sinonasal cavity: CT and MRI findings. Clin Radiol 2009; 64: [14] LaBruna A, Reagan B, Papageorge A. Leiomyoma of the maxillary sinus: A diagnostic dilemma. Otolaryngol Head Neck Surg 1995; 112: [15] Ikeda K, Kuroda M, Sakaida N, Maehara M, Ohmura N, Sawada S. Cellular leiomyoma of the nasal cavity: findings of CT and MR imaging. AJNR Am J Neuroradiol 2005; 26: Int J Clin Exp Pathol 2014;7(3):
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