- Email: [email protected]
Ganglioneuroma of the uterine cervix—a case report
Human Pathology (2011) 42, 1573–1575
www.elsevier.com/locate/humpath
Case study
Ganglioneuroma of the uterine cervix—a case report Sung-Im Do a,b , Gou Young Kim a,b , Kyung-Do Ki a,b , Chu-Yeop Huh a,b , Youn-Wha Kim c , Juhie Lee c , Yong-Koo Park c , Sung-Jig Lim a,⁎ a
Department of Pathology, East-West Neo Medical Center, College of Medicine, Kyung Hee University, College of Medicine, Seoul 134-727, Korea b Department of Obstetrics & Gynecology, East-West Neo Medical Center, College of Medicine, Kyung Hee University, Seoul 134-727, Korea c Department of Pathology, Kyung Hee Medical Center, College of Medicine, Kyung Hee University, 130-702 Korea Received 17 September 2009; revised 2 March 2010; accepted 16 March 2010
Keywords: Ganglioneuroma; Neuroblastoma; Cervix; Uterus
Summary Ganglioneuroma is a rare, benign tumor usually found in the mediastinum, retroperitoneum, or adrenal glands. We present a case of ganglioneuroma arising in the uterine cervix. A 65-year-old woman (gravida 3, para 3, abortus 0) showed vaginal spotting. The clinician observed a mild erosive lesion of her cervix and performed a biopsy and then conization. Histopathology revealed ganglioneuroma arising in the cervix. To our knowledge, this is the first report of a ganglioneuroma in the uterine cervix. Although ganglioneuroma is normally benign, a few malignant changes have been reported. Regular follow-up is necessary. © 2011 Elsevier Inc. All rights reserved.
1. Introduction Ganglioneuromas are rare benign neuroblastoma tumors. They are fully differentiated tumors composed of mature ganglion cells, nerve fibers, and Schwann cells. These tumors are usually located in the posterior mediastinum, retroperitoneum, or adrenal glands [1] but also rarely occur in the presacral space, intestine, and skin [2-4]. We report here the first case of ganglioneuroma in the uterine cervix.
2. Case report A 65-year-old woman (gravida 3, para 3, abortus 0) presented with a 3-year history of vaginal bleeding that occurred once or twice a year. She had no other medical ⁎ Corresponding author. E-mail address: [email protected] (S. -J. Lim). 0046-8177/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.humpath.2010.03.013
history and did not take any medicine. On gynecologic examination, the cervix had only a mild erosive lesion, and biopsy was performed. After histologic diagnosis by biopsy, conization was performed. The patient shows no recurrence 6 months after conization.
3. Pathologic findings The biopsy specimen was routinely formalin-fixed and paraffin-embedded and then stained with hematoxylin and eosin for histopathology. Microscopic examination revealed a nonencapsulated lesion that was not well circumscribed, with a collection of large oval to round cells with abundant basophilic to eosinophilic cytoplasm and large vesicular nuclei with prominent nucleoli characteristic of ganglion cells under the cervical epithelium (Fig. 1). Interspersed spindle cell proliferation was also noted. The overlying
1574
S. -I. Do et al.
cervix epithelium was intact and showed some interstitial lymphocytic infiltration (Fig. 1). Immunohistochemical studies revealed that spindle cells and ganglion cells were positive for S-100, glial fibrillary acidic protein (GFAP), and synaptophysin but negative for epithelial membrane antigen (EMA) and Human Melanoma Black-45 (HMB-45) (Fig. 2). The specimen from conization showed nodular collection of ganglion cells and spindle cells. There was no additional tumor component, and the resection margins were negative for the tumor.
4. Discussion Ganglioneuroma is a well-differentiated benign tumor from the neuroblastoma series that evolves from the sympathetic nervous system. Weiss [1] showed that in 88 patients with ganglioneuroma, 52% developed in the abdomen, 39% in the mediastinum, and 9% in the neck or
Fig. 2 A and B, S-100 immunohistochemical stain highlighting staining of ganglion cells and Schwann cells (A, ×100). Also, these ganglion cells and Schwann cells show positive synaptophysin immunohistochemical stain (B, ×200).
Fig. 1 A and B, Under the cervix epithelium, there are round to oval mature ganglion cells having large nuclei, prominent eosinophilic nucleoli and abundant granular cytoplasm within wavy, spindle Schwann cells (A: H&E ×200, B: H&E ×400). H&E indicates hematoxylin and eosin.
pelvic cavity. This tumor can also be observed in the central nervous system and the periphery of the sympathetic system [5]. Other sites of origin are much less common, and primary ganglion cell tumors in the uterine cervix have never been reported. Fingerland [6] described ganglioneuroma of the cervix uteri in a 46-year-old woman in 1938, but their microscopic findings showed ganglioneuroma with endometrial stroma and glands, indicating that the lesion might not be ganglioneuroma arising in the cervix but probably an endometrial ganglioneuroma protruding into the cervix. Ganglioneuroma consists of sympathetic ganglion cells and mature Schwann cells. Our case showed histologic features of ganglioneuroma in the biopsy and conization specimens. Because there were no other components except ganglion cells and Schwann cells, we excluded the possibility of teratoma. In addition, melanoma could be ruled out because HMB-45 was negative. Ganglioneuromas are mostly sporadic but also can be associated with neurofibromatosis type I and multiple endocrine neoplasia [7]. They also may occur spontaneously or during chemotherapy or radiation therapy
Ganglioneuroma of the uterine cervix for neuroblastomas [8]. This patient had no history of neurofibromatosis or cancer. The pathogenesis of ganglioneuroma in the uterine cervix is unclear because the uterus has no sympathetic innervation. Similarly, ganglion cells are not normal components of the skin, but cutaneous ganglioneuroma may arise from immature precursors derived from neural crest, or they may be choristomas [9]. Glial polyps of the cervix or glial tissues in the cervix can exist [10,11] as a polypoid lesion composed of finely eosinophilic tissue with fully differentiated astrocytic glial tissue. However, these lesions do not show ganglion cell aggregation but only astrocytes. These lesions may result from ectopic glial tissue from fetal brain, because most patients had a medical history of abortion and curettage. However, there are also patients with cervical glioma with no coital history [12]. Our case also had no history of abortion, so the ganglioneuroma of our case did not arise from implanted neural tissue or fetal brain. Therefore, because ganglion cells are not normally in the uterine cervix, our case is probably a choristomatous lesion. Although ganglioneuroma is mostly a well-circumscribed mass, our case was not a circumscribed mass. Some ganglioneuroma in skin and colon were not a circumscribed mass [4,9]. It is possible that ganglioneuroma, especially in the choristomatous lesion, cannot form a circumscribed mass. To our knowledge, this is the first ganglioneuroma reported in the uterine cervix. Surgical excision is usually sufficient treatment, but metastasis has been reported in ganglioneuromas, representing maturation of neuroblastoma [13]. Rarely, ganglioneuroma may reveal malignant transformation, most commonly malignant peripheral nerve sheath tumor, considering de novo ganglioneuroma or that derived from maturation in a neuroblastoma [14,15]. Thus, regular follow-up is necessary.
1575
References [1] Weiss SW. Soft tissue tumors. In: Schmitt W, editor. Soft tissue tumors. Philadelphia: Elsevier; 2008. p. 960-3. [2] Murphy M, Hoss D, Berke A, Kerr P, Gart G, Grant-Kels J. Cutaneous ganglioneuroma. Int J Dermatol 2007;46:861-3. [3] Cerullo G, Marrelli D, Rampone B, et al. Presacral ganglioneuroma: a case report and review of literature. World J Gastroenterol 2007;13: 2129-31. [4] Mendez IM, Pereda T, Rodriguez FJ, Funez R, Sanchez A. Solitary colonic polypoid ganglioneuroma. Diagn Pathol 2008;3:20. [5] Preidler KW, Ranner G, Szolar D, Walch C, Anderhuber W. Retropharyngeal ganglioneuroma: ultrasound, CT and MRI findings in a 57-year-old patient. Eur J Radiol 1995;19:108-10. [6] Fingerland A. Ganglioneuroma of the cervix uteri. J Pathol Bacteriol 1938;47:631-4. [7] Thway K, Fisher C. Diffuse ganglioneuromatosis in small intestine associated with neurofibromatosis type 1. Ann Diagn Pathol 2009;13: 50-4. [8] Hayes FA, Green AA, Rao BN. Clinical manifestations of ganglioneuroma. Cancer 1989;63:1211-4. [9] Furmanczyk PS, Hughes SR, Walsh JS, Bass J, McFarlane JR, Argenyi ZB. Cutaneous ganglioneuroma associated with overlying hyperkeratotic epidermal changes: a report of 2 cases. Am J Dermatopathol 2008;30:600-3. [10] Guo LX. Glial polyp of the cervix. A case report. Chin Med J 1992;105:518-9. [11] Roca AN, Guajardo M, Estrada WJ. Glial polyp of the cervix and endometrium. Report of a case and review of the literature. Am J Clin Pathol 1980;73:718-20. [12] Young RH, Kleinman GM, Scully RE. Glioma of the uterus. Report of a case with comments on histogenesis. Am J Surg Pathol 1981;5: 695-9. [13] Geoerger B, Hero B, Harms D, Grebe J, Scheidhauer K, Berthold F. Metabolic activity and clinical features of primary ganglioneuromas. Cancer 2001;91:1905-13. [14] Drago G, Pasquier B, Pasquier D. Malignant peripheral nerve sheath tumour arising in a de nova ganglioneuroma: a case report and review of the literature. Med Pediatr Oncol 1997;28:216-22. [15] Malignant peripheral nerve sheath tumor arising from an adrenal ganglioneuroma in a 6-year-old boy. Ped Dev Pathol 2004;7:277-84.
www.elsevier.com/locate/humpath
Case study
Ganglioneuroma of the uterine cervix—a case report Sung-Im Do a,b , Gou Young Kim a,b , Kyung-Do Ki a,b , Chu-Yeop Huh a,b , Youn-Wha Kim c , Juhie Lee c , Yong-Koo Park c , Sung-Jig Lim a,⁎ a
Department of Pathology, East-West Neo Medical Center, College of Medicine, Kyung Hee University, College of Medicine, Seoul 134-727, Korea b Department of Obstetrics & Gynecology, East-West Neo Medical Center, College of Medicine, Kyung Hee University, Seoul 134-727, Korea c Department of Pathology, Kyung Hee Medical Center, College of Medicine, Kyung Hee University, 130-702 Korea Received 17 September 2009; revised 2 March 2010; accepted 16 March 2010
Keywords: Ganglioneuroma; Neuroblastoma; Cervix; Uterus
Summary Ganglioneuroma is a rare, benign tumor usually found in the mediastinum, retroperitoneum, or adrenal glands. We present a case of ganglioneuroma arising in the uterine cervix. A 65-year-old woman (gravida 3, para 3, abortus 0) showed vaginal spotting. The clinician observed a mild erosive lesion of her cervix and performed a biopsy and then conization. Histopathology revealed ganglioneuroma arising in the cervix. To our knowledge, this is the first report of a ganglioneuroma in the uterine cervix. Although ganglioneuroma is normally benign, a few malignant changes have been reported. Regular follow-up is necessary. © 2011 Elsevier Inc. All rights reserved.
1. Introduction Ganglioneuromas are rare benign neuroblastoma tumors. They are fully differentiated tumors composed of mature ganglion cells, nerve fibers, and Schwann cells. These tumors are usually located in the posterior mediastinum, retroperitoneum, or adrenal glands [1] but also rarely occur in the presacral space, intestine, and skin [2-4]. We report here the first case of ganglioneuroma in the uterine cervix.
2. Case report A 65-year-old woman (gravida 3, para 3, abortus 0) presented with a 3-year history of vaginal bleeding that occurred once or twice a year. She had no other medical ⁎ Corresponding author. E-mail address: [email protected] (S. -J. Lim). 0046-8177/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.humpath.2010.03.013
history and did not take any medicine. On gynecologic examination, the cervix had only a mild erosive lesion, and biopsy was performed. After histologic diagnosis by biopsy, conization was performed. The patient shows no recurrence 6 months after conization.
3. Pathologic findings The biopsy specimen was routinely formalin-fixed and paraffin-embedded and then stained with hematoxylin and eosin for histopathology. Microscopic examination revealed a nonencapsulated lesion that was not well circumscribed, with a collection of large oval to round cells with abundant basophilic to eosinophilic cytoplasm and large vesicular nuclei with prominent nucleoli characteristic of ganglion cells under the cervical epithelium (Fig. 1). Interspersed spindle cell proliferation was also noted. The overlying
1574
S. -I. Do et al.
cervix epithelium was intact and showed some interstitial lymphocytic infiltration (Fig. 1). Immunohistochemical studies revealed that spindle cells and ganglion cells were positive for S-100, glial fibrillary acidic protein (GFAP), and synaptophysin but negative for epithelial membrane antigen (EMA) and Human Melanoma Black-45 (HMB-45) (Fig. 2). The specimen from conization showed nodular collection of ganglion cells and spindle cells. There was no additional tumor component, and the resection margins were negative for the tumor.
4. Discussion Ganglioneuroma is a well-differentiated benign tumor from the neuroblastoma series that evolves from the sympathetic nervous system. Weiss [1] showed that in 88 patients with ganglioneuroma, 52% developed in the abdomen, 39% in the mediastinum, and 9% in the neck or
Fig. 2 A and B, S-100 immunohistochemical stain highlighting staining of ganglion cells and Schwann cells (A, ×100). Also, these ganglion cells and Schwann cells show positive synaptophysin immunohistochemical stain (B, ×200).
Fig. 1 A and B, Under the cervix epithelium, there are round to oval mature ganglion cells having large nuclei, prominent eosinophilic nucleoli and abundant granular cytoplasm within wavy, spindle Schwann cells (A: H&E ×200, B: H&E ×400). H&E indicates hematoxylin and eosin.
pelvic cavity. This tumor can also be observed in the central nervous system and the periphery of the sympathetic system [5]. Other sites of origin are much less common, and primary ganglion cell tumors in the uterine cervix have never been reported. Fingerland [6] described ganglioneuroma of the cervix uteri in a 46-year-old woman in 1938, but their microscopic findings showed ganglioneuroma with endometrial stroma and glands, indicating that the lesion might not be ganglioneuroma arising in the cervix but probably an endometrial ganglioneuroma protruding into the cervix. Ganglioneuroma consists of sympathetic ganglion cells and mature Schwann cells. Our case showed histologic features of ganglioneuroma in the biopsy and conization specimens. Because there were no other components except ganglion cells and Schwann cells, we excluded the possibility of teratoma. In addition, melanoma could be ruled out because HMB-45 was negative. Ganglioneuromas are mostly sporadic but also can be associated with neurofibromatosis type I and multiple endocrine neoplasia [7]. They also may occur spontaneously or during chemotherapy or radiation therapy
Ganglioneuroma of the uterine cervix for neuroblastomas [8]. This patient had no history of neurofibromatosis or cancer. The pathogenesis of ganglioneuroma in the uterine cervix is unclear because the uterus has no sympathetic innervation. Similarly, ganglion cells are not normal components of the skin, but cutaneous ganglioneuroma may arise from immature precursors derived from neural crest, or they may be choristomas [9]. Glial polyps of the cervix or glial tissues in the cervix can exist [10,11] as a polypoid lesion composed of finely eosinophilic tissue with fully differentiated astrocytic glial tissue. However, these lesions do not show ganglion cell aggregation but only astrocytes. These lesions may result from ectopic glial tissue from fetal brain, because most patients had a medical history of abortion and curettage. However, there are also patients with cervical glioma with no coital history [12]. Our case also had no history of abortion, so the ganglioneuroma of our case did not arise from implanted neural tissue or fetal brain. Therefore, because ganglion cells are not normally in the uterine cervix, our case is probably a choristomatous lesion. Although ganglioneuroma is mostly a well-circumscribed mass, our case was not a circumscribed mass. Some ganglioneuroma in skin and colon were not a circumscribed mass [4,9]. It is possible that ganglioneuroma, especially in the choristomatous lesion, cannot form a circumscribed mass. To our knowledge, this is the first ganglioneuroma reported in the uterine cervix. Surgical excision is usually sufficient treatment, but metastasis has been reported in ganglioneuromas, representing maturation of neuroblastoma [13]. Rarely, ganglioneuroma may reveal malignant transformation, most commonly malignant peripheral nerve sheath tumor, considering de novo ganglioneuroma or that derived from maturation in a neuroblastoma [14,15]. Thus, regular follow-up is necessary.
1575
References [1] Weiss SW. Soft tissue tumors. In: Schmitt W, editor. Soft tissue tumors. Philadelphia: Elsevier; 2008. p. 960-3. [2] Murphy M, Hoss D, Berke A, Kerr P, Gart G, Grant-Kels J. Cutaneous ganglioneuroma. Int J Dermatol 2007;46:861-3. [3] Cerullo G, Marrelli D, Rampone B, et al. Presacral ganglioneuroma: a case report and review of literature. World J Gastroenterol 2007;13: 2129-31. [4] Mendez IM, Pereda T, Rodriguez FJ, Funez R, Sanchez A. Solitary colonic polypoid ganglioneuroma. Diagn Pathol 2008;3:20. [5] Preidler KW, Ranner G, Szolar D, Walch C, Anderhuber W. Retropharyngeal ganglioneuroma: ultrasound, CT and MRI findings in a 57-year-old patient. Eur J Radiol 1995;19:108-10. [6] Fingerland A. Ganglioneuroma of the cervix uteri. J Pathol Bacteriol 1938;47:631-4. [7] Thway K, Fisher C. Diffuse ganglioneuromatosis in small intestine associated with neurofibromatosis type 1. Ann Diagn Pathol 2009;13: 50-4. [8] Hayes FA, Green AA, Rao BN. Clinical manifestations of ganglioneuroma. Cancer 1989;63:1211-4. [9] Furmanczyk PS, Hughes SR, Walsh JS, Bass J, McFarlane JR, Argenyi ZB. Cutaneous ganglioneuroma associated with overlying hyperkeratotic epidermal changes: a report of 2 cases. Am J Dermatopathol 2008;30:600-3. [10] Guo LX. Glial polyp of the cervix. A case report. Chin Med J 1992;105:518-9. [11] Roca AN, Guajardo M, Estrada WJ. Glial polyp of the cervix and endometrium. Report of a case and review of the literature. Am J Clin Pathol 1980;73:718-20. [12] Young RH, Kleinman GM, Scully RE. Glioma of the uterus. Report of a case with comments on histogenesis. Am J Surg Pathol 1981;5: 695-9. [13] Geoerger B, Hero B, Harms D, Grebe J, Scheidhauer K, Berthold F. Metabolic activity and clinical features of primary ganglioneuromas. Cancer 2001;91:1905-13. [14] Drago G, Pasquier B, Pasquier D. Malignant peripheral nerve sheath tumour arising in a de nova ganglioneuroma: a case report and review of the literature. Med Pediatr Oncol 1997;28:216-22. [15] Malignant peripheral nerve sheath tumor arising from an adrenal ganglioneuroma in a 6-year-old boy. Ped Dev Pathol 2004;7:277-84.