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Painful clitoromegaly caused by rare epithelioid hemangioma
Gynecologic Oncology Reports 4 (2013) 60–62
Contents lists available at SciVerse ScienceDirect
Gynecologic Oncology Reports journal homepage: www.elsevier.com/locate/gynor
Case Report
Painful clitoromegaly caused by rare epithelioid hemangioma Heidi J. Gray a, b,⁎, Mara H. Rendi c, Maria Holmes d a
Division of Gynecologic Oncology, University of Washington, Seattle, WA, USA Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA c Department of Pathology, University of Washington, Seattle, WA, USA d Issaquah Women's Clinic, Issaquah, WA, USA b
a r t i c l e
i n f o
Article history: Received 31 October 2012 Accepted 18 December 2012 Available online 31 December 2012 Keywords: Clitoromegaly Hemangioma Benign vulvar tumor
Introduction Clitoromegaly due to tumor infiltration is exceptionally rare. When women present with an enlarging clitoris, it is commonly secondary to hyperandrogenism from ovarian secreting tumors. In the setting of normal androgen levels, clitoromegaly due to primary tumors such as schwannomas have been reported (Yüksel et al., 2003). Epithelioid hemangiomas, also known as angiolymphoid hyperplasia with eosinophilia, are benign vascular tumors that usually arise in the skin, subcutis, and less frequently, in the bone (Olsen and Helwig, 1985; Calonje and Fletcher, 2000). We present here the first reported case of a premenopausal woman presenting with painful clitoromegaly secondary to an infiltrating epithelioid hemangioma. Case A 44 year old G0 patient presented with increasing vulvar pain for several months. She had menarche at age 14 with regular periods every 30 days lasting 4–5 days. She denied any increase in facial or body hair or deepening of her voice. Her past medical history was
⁎ Corresponding author at: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington Medical Center, PO Box 356460, Seattle, WA 98195, USA. Fax: +1 206 543 3915. E-mail address: [email protected] (H.J. Gray). 2211-338X/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.gynor.2012.12.007
significant for recent diagnosis of insulin-dependent type 2 diabetes mellitus. Over a 2 month period, her vulvar pain and swelling had increased to the point of needing to take anti-inflammatory and narcotic pain medications round the clock with little effect. On presentation to her OB/Gyn, she was mildly hypertensive without temporal balding or hirsutism. On pelvic exam, her external genitalia was significant for marked clitoromegaly measuring 4.5 × 1.5 cm that was firm and very painful to examination (Fig. 1A). The remainder of the pelvic exam was normal with no pelvic masses appreciated. Laboratory exam was significant for normal testosterone, free testosterone and DHEAS. Pelvic MRI showed a 4.5 cm enlarged clitoris extending down the right crura and mildly enlarged right inguinal lymph node. The uterus was normal and the right ovary measured 3.5 cm×2.6 cm×3.5 cm and the left ovary 4.8 cm×4.6 cm×3.7 cm with heterogeneous morphology consistent with endometriosis (Fig. 1B). On referral to a gynecologic oncologist, an exam under anesthesia with intraoperative ultrasound was performed showing no fluid collection, cyst or vascular malformation. Fine needle aspiration performed was negative for pus or blood. Biopsies returned as an epithelioid neoplasm and she was recommended to undergo radical surgical resection. She was taken to the operating room and a radical resection of the clitoris and partial vulvectomy were performed with reconstruction of the vulva, clitoral hood and labia minora. Final pathology revealed a well-circumscribed mass involving the erectile tissue of the clitoris. The lesion was composed of wellformed vascular channels with open lumina lined by plump epithelioid cells with abundant eosinophilic cytoplasm and centrally located, bland appearing oval nuclei. Some cells contained intracytoplasmic vacuoles recapitulating vascular lumens (Fig. 1C and D). In addition, the lesion was associated with an abundant mixed inflammatory infiltrate with prominent eosinophils. Although small areas of necrosis and foci of neoplasm within lymphovascular spaces were identified, there was no significant mitotic activity and the tumor was wellcircumscribed. Immunohistochemical staining demonstrated that the lesional cells focally expressed smooth muscle actin, estrogen receptor, and CD34 and did not express pan-cytokeratin, MELAN-A, or S-100, consistent with the histologic impression of epithelioid hemangioma. All resection margins were negative. The patient had immediate relief of pain postoperatively. In follow-up one week after surgery, she was taking minimal over the counter pain medications and healing remarkably well. The patient gave informed consent for publication of her unusual case.
H.J. Gray et al. / Gynecologic Oncology Reports 4 (2013) 60–62
A
B
C
D
61
Fig. 1. Epithelioid hemangioma of clitoris. A) Gross appearance of clitoral mass. B) T1 MRI image showing 4 cm clitoral mass extending to public bone. C) Epithelioid hemangioma, 40× magnification, hematoxylin and eosin. Note the lobulated appearance of the lesion and the abundant open vascular lumens. D) Epithelioid hemangioma, 400× magnification, hematoxylin and eosin. The lesion is composed of bland epithelioid endothelial cells with intracytoplasmic lumens recapitulating vascular lumens and a prominent eosinophilic inflammatory infiltrate.
Discussion Most causes of clitoromegaly in menarchal women are due to excess androgen stimulation either from steroid producing ovarian tumors or late presentation of congenital defects in the cortisol synthesis pathway. In the setting of normal androgen levels, there are reports describing painful clitoromegaly due to abscess, especially in premenarchal patients (Lara-Torre et al., 2004). Clitoral priapism as a rare cause of painful clitoromegaly has also been reported (Medina, 2002). As in male patients, clitoral priapism can be treated by alpha adrenergic agonists to promote vasoconstriction either by direct injection into the corpus or oral treatment with imipramine hydrochloride (Medina, 2002). Primary clitoral neoplasms are rare. Most commonly reported in the literature are schwannomas seen in patients with neurofibromatosis (Yüksel et al., 2003). Other tumor types reported are transitional cell, melanoma and lymphoma (DiGiorgi et al., 2004; Kost'álová et al., 2007; Ferrando-Marco et al., 1992). We performed a biopsy prior to excision to rule out non-surgical management. As the pathology returned an epithelioid neoplasm, we recommended primary radical clitoral resection, yet with extensive counseling that this would lead to loss of function and clitoral sensation. The final pathology revealed epithelioid hemangioma. Epithelioid hemangiomas, first described in 1969, are rare, slow growing, benign vascular lesions that typically occur during early and mid-adult life in the skin and sub-cutis. The lesions are wellcircumscribed with abundant, well-formed vascular spaces with open lumina and a distinctive eosinophilic inflammatory infiltrate. The characteristic feature of epithelioid hemangioma is the epithelioid endothelial cells with large oval nuclei and abundant eosinophilic cytoplasm. On immunohistochemical staining, epithelioid hemangiomas are positive for CD31, CD34, and factor VIII-related antigen and negative for keratins and epithelial membrane antigens. The differential diagnosis of epithelioid hemangioma includes the more aggressive epithelioid
hemangioendothelioma and epithelioid angiosarcoma. It is important to differentiate epithelioid hemangioma from both of these lesions as the later two lesions often recur and metastasize (Calonje and Fletcher, 2000; Mentzel et al., 1997; Tsang and Chan, 1993). The typical features of epithelioid hemangioendothelioma including an infiltrative border, nuclear atypia, a distinctive chondroid matrix, and a cording/ clustering of cells were not seen in the present case. Epithelioid angiosarcoma is a malignant vascular tumor, characterized by cells with prominent nuclear atypia, a high mitotic index, and abundant necrosis (Tsang and Chan, 1993). These are highly aggressive neoplasms with an aggressive clinical course. Most cases of epithelioid hemangiomas have been described occurring in the skin, soft tissue, bone, as well as parenchymal lesions in the liver and lung. Our case is the first reported arising in the erectile tissue of the clitoris. Although epithelioid hemangiomas have a much more benign course than epithelioid hemangioendothelioma or epithelioid angiosarcoma, surgical management with close clinical follow-up for local recurrence is essential. Conflict of interest statement The authors report no conflicts of interest.
References Yüksel, H., Odabaşi, A.R., Kafkas, S., et al., 2003. Clitoromegaly in type 2 neurofibromatosis: a case report and review of the literature. Eur. J. Gynaecol. Oncol. 24 (5), 447–451. Lara-Torre, E., Hertweck, S.P., Kives, S.L., Perlman, S., 2004. Premenarchal recurrent periclitoral abscess: a case report. J. Reprod. Med. 49 (12), 983–985 (Dec). Medina, C.A., 2002. Clitoral priapism: a rare condition presenting as a cause of vulvar pain. Obstet. Gynecol. 100 (5 Pt 2), 1089–1091 (Nov). DiGiorgi, S., Schnatz, P.F., Mandavilli, S., Greene, J.F., Curry, S.L., 2004. Transitional cell carcinoma presenting as clitoral priapism. Gynecol. Oncol. 93 (2), 540–542 (May). Kost'álová, M., Kost'ál, M., Ettler, K., et al., 2007. Melanoma clitoridis. Int. J. Dermatol. 46 (4), 393–395 (Apr). Ferrando-Marco, J., Martorell, M.A., Carrato, A., Navarro, J.T., 1992. Primary vulvar lymphoma presenting as a clitoral tumor. Acta Obstet. Gynecol. Scand. 71 (7), 543–546 (Oct).
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H.J. Gray et al. / Gynecologic Oncology Reports 4 (2013) 60–62
Olsen, T.G., Helwig, E.B., 1985. Angiolymphoid hyperplasia with eosinophilia. A clinicopathologic study of 116 patients. J. Am. Acad. Dermatol. 12, 781–796. Calonje, E., Fletcher, C.D.M., 2000. Tumors of blood vessels and lymphatics. In: Fletcher, C.D.M. (Ed.), Diagnostic Histopathology of Tumors. Hartcourt Publishers Limited, London, UK, pp. 55–56.
Mentzel, T., Beham, A., Calonje, E., Katenkamp, D., Fletcher, C.D., 1997. Epithelioid hemangioendothelioma of skin and soft tissues: clinicopathologic and immunohistochemical study of 30 cases. Am. J. Surg. Pathol. 21, 363–374. Tsang, W.Y., Chan, J.K., 1993. The family of epithelioid vascular tumors. Histol. Histopathol. 8, 187–212.
Contents lists available at SciVerse ScienceDirect
Gynecologic Oncology Reports journal homepage: www.elsevier.com/locate/gynor
Case Report
Painful clitoromegaly caused by rare epithelioid hemangioma Heidi J. Gray a, b,⁎, Mara H. Rendi c, Maria Holmes d a
Division of Gynecologic Oncology, University of Washington, Seattle, WA, USA Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA c Department of Pathology, University of Washington, Seattle, WA, USA d Issaquah Women's Clinic, Issaquah, WA, USA b
a r t i c l e
i n f o
Article history: Received 31 October 2012 Accepted 18 December 2012 Available online 31 December 2012 Keywords: Clitoromegaly Hemangioma Benign vulvar tumor
Introduction Clitoromegaly due to tumor infiltration is exceptionally rare. When women present with an enlarging clitoris, it is commonly secondary to hyperandrogenism from ovarian secreting tumors. In the setting of normal androgen levels, clitoromegaly due to primary tumors such as schwannomas have been reported (Yüksel et al., 2003). Epithelioid hemangiomas, also known as angiolymphoid hyperplasia with eosinophilia, are benign vascular tumors that usually arise in the skin, subcutis, and less frequently, in the bone (Olsen and Helwig, 1985; Calonje and Fletcher, 2000). We present here the first reported case of a premenopausal woman presenting with painful clitoromegaly secondary to an infiltrating epithelioid hemangioma. Case A 44 year old G0 patient presented with increasing vulvar pain for several months. She had menarche at age 14 with regular periods every 30 days lasting 4–5 days. She denied any increase in facial or body hair or deepening of her voice. Her past medical history was
⁎ Corresponding author at: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington Medical Center, PO Box 356460, Seattle, WA 98195, USA. Fax: +1 206 543 3915. E-mail address: [email protected] (H.J. Gray). 2211-338X/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.gynor.2012.12.007
significant for recent diagnosis of insulin-dependent type 2 diabetes mellitus. Over a 2 month period, her vulvar pain and swelling had increased to the point of needing to take anti-inflammatory and narcotic pain medications round the clock with little effect. On presentation to her OB/Gyn, she was mildly hypertensive without temporal balding or hirsutism. On pelvic exam, her external genitalia was significant for marked clitoromegaly measuring 4.5 × 1.5 cm that was firm and very painful to examination (Fig. 1A). The remainder of the pelvic exam was normal with no pelvic masses appreciated. Laboratory exam was significant for normal testosterone, free testosterone and DHEAS. Pelvic MRI showed a 4.5 cm enlarged clitoris extending down the right crura and mildly enlarged right inguinal lymph node. The uterus was normal and the right ovary measured 3.5 cm×2.6 cm×3.5 cm and the left ovary 4.8 cm×4.6 cm×3.7 cm with heterogeneous morphology consistent with endometriosis (Fig. 1B). On referral to a gynecologic oncologist, an exam under anesthesia with intraoperative ultrasound was performed showing no fluid collection, cyst or vascular malformation. Fine needle aspiration performed was negative for pus or blood. Biopsies returned as an epithelioid neoplasm and she was recommended to undergo radical surgical resection. She was taken to the operating room and a radical resection of the clitoris and partial vulvectomy were performed with reconstruction of the vulva, clitoral hood and labia minora. Final pathology revealed a well-circumscribed mass involving the erectile tissue of the clitoris. The lesion was composed of wellformed vascular channels with open lumina lined by plump epithelioid cells with abundant eosinophilic cytoplasm and centrally located, bland appearing oval nuclei. Some cells contained intracytoplasmic vacuoles recapitulating vascular lumens (Fig. 1C and D). In addition, the lesion was associated with an abundant mixed inflammatory infiltrate with prominent eosinophils. Although small areas of necrosis and foci of neoplasm within lymphovascular spaces were identified, there was no significant mitotic activity and the tumor was wellcircumscribed. Immunohistochemical staining demonstrated that the lesional cells focally expressed smooth muscle actin, estrogen receptor, and CD34 and did not express pan-cytokeratin, MELAN-A, or S-100, consistent with the histologic impression of epithelioid hemangioma. All resection margins were negative. The patient had immediate relief of pain postoperatively. In follow-up one week after surgery, she was taking minimal over the counter pain medications and healing remarkably well. The patient gave informed consent for publication of her unusual case.
H.J. Gray et al. / Gynecologic Oncology Reports 4 (2013) 60–62
A
B
C
D
61
Fig. 1. Epithelioid hemangioma of clitoris. A) Gross appearance of clitoral mass. B) T1 MRI image showing 4 cm clitoral mass extending to public bone. C) Epithelioid hemangioma, 40× magnification, hematoxylin and eosin. Note the lobulated appearance of the lesion and the abundant open vascular lumens. D) Epithelioid hemangioma, 400× magnification, hematoxylin and eosin. The lesion is composed of bland epithelioid endothelial cells with intracytoplasmic lumens recapitulating vascular lumens and a prominent eosinophilic inflammatory infiltrate.
Discussion Most causes of clitoromegaly in menarchal women are due to excess androgen stimulation either from steroid producing ovarian tumors or late presentation of congenital defects in the cortisol synthesis pathway. In the setting of normal androgen levels, there are reports describing painful clitoromegaly due to abscess, especially in premenarchal patients (Lara-Torre et al., 2004). Clitoral priapism as a rare cause of painful clitoromegaly has also been reported (Medina, 2002). As in male patients, clitoral priapism can be treated by alpha adrenergic agonists to promote vasoconstriction either by direct injection into the corpus or oral treatment with imipramine hydrochloride (Medina, 2002). Primary clitoral neoplasms are rare. Most commonly reported in the literature are schwannomas seen in patients with neurofibromatosis (Yüksel et al., 2003). Other tumor types reported are transitional cell, melanoma and lymphoma (DiGiorgi et al., 2004; Kost'álová et al., 2007; Ferrando-Marco et al., 1992). We performed a biopsy prior to excision to rule out non-surgical management. As the pathology returned an epithelioid neoplasm, we recommended primary radical clitoral resection, yet with extensive counseling that this would lead to loss of function and clitoral sensation. The final pathology revealed epithelioid hemangioma. Epithelioid hemangiomas, first described in 1969, are rare, slow growing, benign vascular lesions that typically occur during early and mid-adult life in the skin and sub-cutis. The lesions are wellcircumscribed with abundant, well-formed vascular spaces with open lumina and a distinctive eosinophilic inflammatory infiltrate. The characteristic feature of epithelioid hemangioma is the epithelioid endothelial cells with large oval nuclei and abundant eosinophilic cytoplasm. On immunohistochemical staining, epithelioid hemangiomas are positive for CD31, CD34, and factor VIII-related antigen and negative for keratins and epithelial membrane antigens. The differential diagnosis of epithelioid hemangioma includes the more aggressive epithelioid
hemangioendothelioma and epithelioid angiosarcoma. It is important to differentiate epithelioid hemangioma from both of these lesions as the later two lesions often recur and metastasize (Calonje and Fletcher, 2000; Mentzel et al., 1997; Tsang and Chan, 1993). The typical features of epithelioid hemangioendothelioma including an infiltrative border, nuclear atypia, a distinctive chondroid matrix, and a cording/ clustering of cells were not seen in the present case. Epithelioid angiosarcoma is a malignant vascular tumor, characterized by cells with prominent nuclear atypia, a high mitotic index, and abundant necrosis (Tsang and Chan, 1993). These are highly aggressive neoplasms with an aggressive clinical course. Most cases of epithelioid hemangiomas have been described occurring in the skin, soft tissue, bone, as well as parenchymal lesions in the liver and lung. Our case is the first reported arising in the erectile tissue of the clitoris. Although epithelioid hemangiomas have a much more benign course than epithelioid hemangioendothelioma or epithelioid angiosarcoma, surgical management with close clinical follow-up for local recurrence is essential. Conflict of interest statement The authors report no conflicts of interest.
References Yüksel, H., Odabaşi, A.R., Kafkas, S., et al., 2003. Clitoromegaly in type 2 neurofibromatosis: a case report and review of the literature. Eur. J. Gynaecol. Oncol. 24 (5), 447–451. Lara-Torre, E., Hertweck, S.P., Kives, S.L., Perlman, S., 2004. Premenarchal recurrent periclitoral abscess: a case report. J. Reprod. Med. 49 (12), 983–985 (Dec). Medina, C.A., 2002. Clitoral priapism: a rare condition presenting as a cause of vulvar pain. Obstet. Gynecol. 100 (5 Pt 2), 1089–1091 (Nov). DiGiorgi, S., Schnatz, P.F., Mandavilli, S., Greene, J.F., Curry, S.L., 2004. Transitional cell carcinoma presenting as clitoral priapism. Gynecol. Oncol. 93 (2), 540–542 (May). Kost'álová, M., Kost'ál, M., Ettler, K., et al., 2007. Melanoma clitoridis. Int. J. Dermatol. 46 (4), 393–395 (Apr). Ferrando-Marco, J., Martorell, M.A., Carrato, A., Navarro, J.T., 1992. Primary vulvar lymphoma presenting as a clitoral tumor. Acta Obstet. Gynecol. Scand. 71 (7), 543–546 (Oct).
62
H.J. Gray et al. / Gynecologic Oncology Reports 4 (2013) 60–62
Olsen, T.G., Helwig, E.B., 1985. Angiolymphoid hyperplasia with eosinophilia. A clinicopathologic study of 116 patients. J. Am. Acad. Dermatol. 12, 781–796. Calonje, E., Fletcher, C.D.M., 2000. Tumors of blood vessels and lymphatics. In: Fletcher, C.D.M. (Ed.), Diagnostic Histopathology of Tumors. Hartcourt Publishers Limited, London, UK, pp. 55–56.
Mentzel, T., Beham, A., Calonje, E., Katenkamp, D., Fletcher, C.D., 1997. Epithelioid hemangioendothelioma of skin and soft tissues: clinicopathologic and immunohistochemical study of 30 cases. Am. J. Surg. Pathol. 21, 363–374. Tsang, W.Y., Chan, J.K., 1993. The family of epithelioid vascular tumors. Histol. Histopathol. 8, 187–212.