- Case report
- Open Access
Diagnostic challenge for ovarian malignant melanoma in premenopausal women: Primary or metastatic?
© Sbitti et al; licensee BioMed Central Ltd. 2011
- Received: 7 October 2010
- Accepted: 17 June 2011
- Published: 17 June 2011
In the ovary, metastatic malignant melanoma may be confused with primary malignant melanoma and presents a diagnosis challenge. Most cases are associated with disseminated diseases and poor prognosis. We present this case report of a metastatic ovarian malignant melanoma simulating primary ovarian cancer.
A 45-year-old premenopausal woman was incidentally found to have an abdominal mass, 3 years after removal of a cutaneous melanoma lesion. Ultrasound and CT scan revealed left two solid masses, which were found to be an ovarian tumor at laparotomy. Left oophorectomy was performed. Histopathology and immunohistochemistry showed melanoma metastasis to the ovary. Nine months later, the patient developed epilepsy and confusion. Magnetic Resonance Imaging showed unique Wright frontal lobe lesion. She underwent stereotactic radio surgery and dacarbazine monotherapy. For months later, the patient is died from disseminate disease progression.
Ovarian metastasis is an unusual presentation of cutaneous melanoma and the prognosis was dismal. As illustrated by this case report, a differential diagnosis of a metastatic malignant melanoma must be considered.
- ovarian neoplasm
- differential diagnosis
The ovary is a frequent site of secondary spread from extra-ovarian malignancies. Approximately 6-7% of the patients presenting with suspected ovarian neoplasm will prove to suffer from metastatic disease to the ovary (1). Ovarian involvement by metastatic malignant melanoma is relatively uncommon and it is rare for melanoma to present clinically as an ovarian mass (2). Solitary metastatic malignant melanoma to the ovary may be confused with primary ovarian carcinoma. We present this case report of metastatic ovarian malignant melanoma simulating primary ovarian cancer.
Melanoma affects usually the skin, adrenal glands and ocular choroids with frequent sites of metastasis to the skin, brain and lung and rarely to the ovary . However, once the diagnosis of malignant melanoma of the ovary has been established; the distinction of a primary ovarian malignant melanoma from a metastatic tumor must be made. Some authors [2, 3] have restricted the diagnosis of primary ovarian malignant melanoma to those cases with no history of malignant melanoma at any other site, where the tumor is confined to the ovary, and where it arises in association with ovarian cystic teratomas. Metastatic ovarian malignant melanomas are more common than primary ovarian malignant melanomas; to date, about 77 cases of malignant melanoma metastatic to the ovary [4–7] compared to only about 31 cases of primary ovarian malignant melanoma including a compilation of 20 cases and individual case reports [8–11] have been reported in the world literature. Although approximately 20% of patients dying of malignant melanoma have ovarian involvement at postmortem examination, the diagnosis of ovarian malignant melanoma is seldom made before autopsy . This is because most of these patients have multiorgan metastases so the involvement of the ovary is not clinically significant. However premortem diagnosis is uncommon and sufficiently symptomatic to be diagnosed in living patients. The time interval between the diagnosis of the primary melanoma and ovarian metastasis has ranged from months up to 18 years . Our patient had an intermediate, stage III melanoma, thus a 36% risk of death at 10 years . She developed ovarian mass three years after melanoma diagnosis. Ovarian metastases from melanoma are mostly unilateral , as in our patient. Women of reproductive age are more prone to metastatic ovarian involvement, which may be attributed to the higher blood flow to the premenopausal ovary . The extremities are the most frequent primary localization of melanoma, secondarily involving the ovaries , as in our patient. Metastatic melanoma to the ovary can mimic a primary ovarian malignancy and may pose a diagnostic challenge. The majority of ovarian metastasis from melanoma published so far has been almost invariably diagnosed following surgical treatment [4, 13, 15, 16]. Levels of tumor markers are non discriminatory and Ultrasound and CT scan were unable to characterize the lesion as in our patient . However Magnetic resonance imaging of the lesion can raise suspicion of its nature because of a hyper-intense signal in T1-weighted images. This hyper-intense signal is related to the amount of melanin in the lesion and is finally present in about a third of cases [15, 16]. In our patient, the possibility of the cutaneous melanoma metastasizing to the ovary was not considered being very rare and MRI was not performed. The pathological diagnosis is also difficult, since the morphology of the lesion is often nonspecific. An achromic or poorly pigmented lesion often leads to several biopsies before the tumor is clearly defined. Diagnostic difficulties also arise histologically as the tumors do not have a consistent appearance and they can be mistaken for germ cell and sex cord stromal tumors or granulosa tumor . Hence, definite diagnosis relies on immunohistochemistry. S-100 is expressed in both the nucleus and the cytoplasm and has been found to be the most sensitive marker, present in 95% of cases [3, 5–7]. HMB-45 and Melan A are expressed in the cytoplasm. In our patient's, history of cutaneous melanoma, the absence of cystic teratomas lesion and tumor positive stain for PS100 and Melan A markers (Figure 2) and negative stain for of alpha-inhibin and CD99 confirmed the diagnosis of metastatic ovarian melanoma. The management of ovarian tumor is surgical, with removal of the tumor and evaluation for local, regional and distant spread. Initial staging should evaluate thoroughly disease extent and obtain pathologic diagnosis to guide further treatment. Metastatic melanoma is associated with poor prognosis with 11% 5-year survival . Surgical treatment for abdominal metastases of melanoma in one report significantly prolonged survival; however complete resection was only possible in one-third of the patients . Unilateral salpingo-oophorectomy has been proposed as an appropriate treatment for metastatic melanoma involving the ovary, if there is no evidence of controlateral ovarian involvement or extra ovarian spread [4, 12]. In such cases of apparently resectable metastatic disease, preoperative screening for metastatic disease in other sites is crucial, either with conventional imaging or with PET scanning . In disseminated diseases, chemotherapy (single-agent or combined) generally only yields a response rate of up to 25%. Though early studies of bio-chemotherapy and immunotherapy were promising, most randomized trials have failed to demonstrate a significant increase in response rate or overall survival.. More targeted approaches that capitalize on recent advances in our understanding of melanoma pathogenesis have emerged. Pro-apoptotic agents 'Oblimersen', an antisense inhibitor of Bcl-2, and 'Sorafenib', an orally active small molecule inhibitor of wild type and mutant BRAF or PLX4032 a potent inhibitor of BRAF with the V600E mutation are at the forefront of novel therapies developed for advanced metastatic disease [19, 20]. In our case the no evidence of right lesion and abdominal spread, left unilateral oophorectomy was performed without adjuvant chemotherapy. The patient had a good postoperative recovery with good health at nine months. She developed unique cerebral metastases lesion treated with radio surgery followed by dacarbazine. 4 months later, the patients died from disseminate disease progression.
In conclusion, this case illustrate that ovarian melanoma is a rare disease, associated with a poor prognosis. Also imaging modalities may be non conclusive and immunohistochemistry must be relied upon to make the final definitive diagnosis. Metastatic presentation is more common than primary ovarian melanoma and should be suspected in any patient who presents a history of malignant melanoma with an ovarian mass without benign cystic teratomas, even if the remission period is long and the ovary is the initial site of relapse. Surgical interventions may be undertaken only in limited metastatic disease, where complete resection is expected.
Written informed consent was obtained from the patient's husband for publication of this case report and any accompanying images.
- Moore RG, Chung M, Granai CO, Gajewski W, Steinhoff MM: Incidence of metastasis to the ovaries from nongenital tract primary tumors. GynecolOncol. 2004, 93: 87-91.Google Scholar
- Afonso JF, Martin GM, Nisco FS, de Alvarez RR: Melanogenic ovarian tumors. Am J Obstet Gynecol. 1962, 84: 667-676.View ArticlePubMedGoogle Scholar
- Remadi S, McGee W, Egger JF, Ismail A, Ovarian metastatic melanoma: A diagnostic pitfall in histopathologic examination. Arch Anat Cytol Pathol. 1997, 45 (1): 43-6.PubMedGoogle Scholar
- Piura B, Kedar I, Ariad S, Meirovitz M, Yanai-Inbar I: Malignant Melanoma Metastatic to the Ovary. Gynecol Oncol. 1998, 68: 201-205. 10.1006/gyno.1997.4919.View ArticlePubMedGoogle Scholar
- Jeremić K, Berisavac M, Argirović R, Gojnić M, Bosković V, Milenković V, Mostić T: Solitary ovarian metastasis from cutaneous melanoma--case report. Eur J Gynaecol Oncol. 2006, 27 (4): 443-4. Melanoma secondairePubMedGoogle Scholar
- Boutis A, Valeri R, Korantzis I, Valoukas D, Andronikidis I, Andreadis C: Delayed malignant melanoma recurrence simulating primary ovarian cancer: case report. World J Surg Oncol. 2008, 6: 124-10.1186/1477-7819-6-124. Melanoma secondairePubMed CentralView ArticlePubMedGoogle Scholar
- Vukomanovic P, Karanikolic A, Stefanoviic M, Mihajlovic D, Djordjevic B, Kutlesic R: Late recurrence of malignant melanoma mimicking ovarian malignancy. Eur J Gynaecol Oncol. 2010, 31 (5): 590-2. Melanoma secondairePubMedGoogle Scholar
- Suneja A, Yadav P, Sharma A, Vaid NB, Singh B, Grover RK: Primary malignant melanoma in cystic teratoma of ovary. Indian J Cancer. 2009, 46 (4): 340-2.View ArticlePubMedGoogle Scholar
- Watanabe Y, Ueda H, Nakajima H, Minoura R, Hoshiai H, Noda K: Amelanotic malignant melanoma arising in an ovarian cystic teratoma: a case report. Acta Cytol. 2001, 45 (5): 756-60. 10.1159/000328299.View ArticlePubMedGoogle Scholar
- McCluggage WG, Bissonnette JP, Young RH: Primary malignant melanoma of the ovary: a report of 9 definite or probable cases with emphasis on their morphologic diversity and mimicry of other primary and secondary ovarian neoplasms. Int J Gynecol Pathol. 2006, 25 (4): 321-9. 10.1097/01.pgp.0000215301.39900.07.View ArticlePubMedGoogle Scholar
- Ueng SH, Pinto MM, Alvarado-Cabrero I, Lee LY, Tavassoli FA: Ovarian malignant melanoma: a clinicopathologic study of 5 cases. Int J Surg Pathol. 2010, 18 (3): 184-92. 10.1177/1066896908320834.View ArticlePubMedGoogle Scholar
- Ayhan A, Guvenal T, Salman MC, Ozyuncu O, Sakinci M, Basaran M: The role of cytoreductive surgery in nongenital cancers metastatic to the ovaries. Gynecol Oncol. 2005, 98: 235-241. 10.1016/j.ygyno.2005.05.028.View ArticlePubMedGoogle Scholar
- Gupta D, Deavers MT, Silva EG, Malpica A: Malignant Melanoma Involving the Ovary: a Clinicopathologic and Immunohistochemical Study of 23 Cases. Am J SurgPathol. 2004, 28: 771-780.View ArticleGoogle Scholar
- Thompson JF, Scolyer RA, Kefford RF: Cutaneous melanoma. Lancet. 2005, 365: 687-701.View ArticlePubMedGoogle Scholar
- Oliver R, Dasgupta C, Coker A, Al-Okati D, Weekes ARL: Ovarian malignant melanoma: Unusual presentation of a solitary metastasis. Gynecol Oncol. 2005, 99: 412-4. 10.1016/j.ygyno.2005.06.066.View ArticlePubMedGoogle Scholar
- Moselhi M, Spencer J, Lane G: Malignant Melanoma Metastatic to the Ovary: Presentation and Radiological Characteristics. Gynecol Oncol. 1998, 69: 165-168. 10.1006/gyno.1998.4992.View ArticlePubMedGoogle Scholar
- Gutman H, Hess KR, Kokotsakis JA, Ross MI, Guinee VF, Balch CM": Surgery for abdominal metastases of cutaneous melanoma. World J Surg. 2001, 25: 750-758. 10.1007/s00268-001-0027-2.View ArticlePubMedGoogle Scholar
- Eigtved A, Andersson AP, Dahlstrom K: Use of fluorine-18 fluorodeoxyglucose positron emission tomography in the detection of silent metastases from malignant melanoma. Eur J Nucl Med. 2000, 27: 70-75. 10.1007/PL00006666.View ArticlePubMedGoogle Scholar
- Puzanov I, Flaherty KT: Targeted molecular therapy in melanoma. Semin Cutan Med Surg. 2010, 29 (3): 196-201. 10.1016/j.sder.2010.06.005.View ArticlePubMedGoogle Scholar
- Flaherty KT, Puzanov I, Kim KB, Ribas A, McArthur GA, Sosman JA, O'Dwyer PJ, Lee RJ, Grippo JF, Nolop K, Chapman PB: Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med. 2010, 363 (9): 809-19. 10.1056/NEJMoa1002011.PubMed CentralView ArticlePubMedGoogle Scholar
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