Case Report Vaginal Primary Malignant Melanoma Complicating Cervical Carcinoma in Situ: a Case Report and Review of Literature

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Int J Clin Exp Pathol 2016;9(4):4555-4559 www.ijcep.com /ISSN:1936-2625/IJCEP0021903

Case Report Vaginal primary malignant melanoma complicating cervical carcinoma in situ: a case report and review of literature

Fei-Fei Liu1, Quan Tian1, Yan Xue1, Mei-Li Pei1, Chun-Bao Wang2, Rui-Fang An1

Departments of 1Gynecology and Obstetrics, 2Pathology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shanxi, P. R. China Received December 14, 2015; Accepted February 25, 2016; Epub April 1, 2016; Published April 15, 2016

Abstract: Vaginal primary malignant melanoma (VPMM) is a rare and extremely aggressive tumor. Because of hidden location and lack of early symptoms, it usually develops at advanced stage and has very high mortality rate. Moreover, the etiology of this tumor is largely unknown. Therefore, it is important for improving prognosis to early diagnosis of VPMM. In the present study, we describe a 35-year-old female patient who was diagnosed as VPMM combined with CIN3 before any report not mentioned. The patient presented to our hospital with abnormal vaginal bleeding of 2 months. Preoperative colposcopic-directed biopsy and physical examination suggested malignant lesions occurred in the upper third of anterior vaginal wall. Then a wide local excision of the lesion was first performed. Postoperative pathological results confirmed and metastasis to left internal iliac lymphnodes. She underwent adjuvant radiotherapy and immunotherapy as further therapeutic measures. Although the patient could not complete a cycle due to intolerable toxicity of immunotherapy, she is still alive 14 months after diagnose.

Keywords: VPMM, etiology, treatment, surgery, radiotherapy

Introduction cm diameter in the upper third of anterior vaginal wall. There were no palpable lymph nodes, Vaginal melanoma is a rare malignant tumor. It and the rest of pelvic and physical examination accounts for 2%-5% of all female genital tract was normal. The patient was originally consid- melanomas, for less than 3% of all vaginal ered as vaginal tumor, thus the patient under- malignant tumors [1]. Cervical carcinoma in went colposcopy with lesion biopsy for diagno- situ is a common kind of cervical intraepithelial sis. Postoperative pathological results were neoplasm III (CIN3) level. However, VPMM com- some atypical cells, with indication of a malig- plicated with CIN3 is a particularly rare event. nant tumor. The patient was presented to the There has been no relevant report. Here we Department of Medical the University of Xi’an report a case of VPMM with cervical carcinoma Jiao tong for further diagnosis and treatment. in situ and review the literature. Further pathological analyses of the specimen Case presentation hinted that the neoplasm may be malignant melanoma or botryoid sarcoma. Preoperative The patient, a 35-year-old female, Gravid 1 and Thin Prep cytology test (TCT) was HSIL and HPV Para 1, and previously had regular menstrua- 33 and 35 are positive. tion, menstrual cycle 30 days, period 5 days. She was admitted to local hospital with a com- She underwent a wide hysterectomy, part vagi- plaint of abnormal vaginal bleeding for 2 nectomy, bilateral adnexectomy and pelvic months. Her previous and familial histories lymphadenectomy. Pathological results showed were unremarkable. plenty of atypical cells invading deep muscles with infiltrating cervical fornix, cervix labium On pelvic examination, there was a lobulated, anterius local squamous cell carcinoma in situ raised, part ulcerated, and irregular lesion 3×3 (Figure 1), left internal iliac lymph node was Vaginal primary malignant melanoma complicating cervical cancer in situ

Figure 1. Hematoxylin&eosin (H&E) staining from sample of the tumor of vagina by surgical resection. A. The tumor consisted of cervical squamous cells carcinoma in situ (H&E staining, ×200). B. Vaginal melanoma tumor (H&E staining, ×200).

Figure 2. Immunohistochemical staining of the vagina tumor cells was detected different antibodies. (A) Posi- tive for HMB-45; (B) Positive for Melan-A; (C) S-100 was positive expression in the vaginal tumor (A-C: IHC. ×400).

involved, and without tumor tissue in the surgi- The patient received pelvic linear accelerator cal margins and other lymph nodes. Immuno- radiation, immunotherapy with interferon (IFN), chemical results indicated the tumorous cells intra-vaginal radiotherapy. But our patient did were positive for HMB-45, S-100 protein, not tolerate immunotherapy on account of Melan-A, vimentin, Ki-67, and CK (Figure 2). fever, so breaking off this therapy. She has mul- The final diagnosis was VPMM and carcinoma tiple organ metastases and refuses further in situ of cervix. therapy 14 months of follow-up after diagnose.

4556 Int J Clin Exp Pathol 2016;9(4):4555-4559 Vaginal primary malignant melanoma complicating cervical cancer in situ

Discussion Its diagnosis rely on pathological examination, typical melanoma that are commonly pigment- Malignant melanoma of the vagina is a rare ed is easy to diagnose. However, amelanotic cancer and its behavior is aggressive. There appearance is rare and makes diagnosis even have been less than 300 VPMM cases report- more difficult [21]. Consequently, immuno- ed worldwide up to now and accounts for less chemical staining should often be used to sup- than 4% of all vaginal malignant tumors [2]. The plement the diagnosis, such as protein S-100, incidence of VPMM is 0.46 cases per one mil- HMB-45, Melan-A, Mart-1 and vimentin. In our lion women per year [3]. The age of VPMM has case, the pathological results only showed a been reported ranging from 22 to 90 years, malignant melanoma, and immunochemical with most commonly being diagnosed in post- analysis demonstrated HMB-45, S-100 protein, menopausal period [4]. The overall 5-year sur- Melan-A and vimentin staining positive which vival rate for women with VPMM ranges from further confirmed the diagnosis. 0% to 25% [5]. It is primarily found in the lower third of vaginal wall [6], secondly located in Although the management of the vaginal mela- mid-upper and total of vagina. Its symptoms nomas has many options including local wide commonly present as vaginal bleeding and dis- excision, radical surgery, radiotherapy, chemo- charge, mass lesion and less commonly dys- therapy and immunotherapy, the most effective uria or ulceration [7, 8]. Macroscopically it often treatment protocol has not reached consensus presents like pigmented lesion. In present [22]. In these recommendations surgical resec- case, the lobulated and brown pigmented tu- tion remains the mainstay of melanoma and mor is found in the upper of vagina, and mainly can improves OS, as compared with a primary complaining of abnormal vaginal bleeding. radiotherapy [23]. Nevertheless, there has been controversial concerning surgical range, VPMM is one type of mucosal melanomas that early studies advised radical surgery (vaginec- stems from melanocytes and does not exposed tomy and pelvic exenteration), but recent publi- to ultraviolet rays. Compared to cutaneous mel- cations support conservative treatment (wide anomas, mucosal melanomas are rare, and the local excision) [24]. Tcheung WJ et al. [5] con- risk factors have not been identified [9-11]. In sidered that conservative surgery can not only recent study, a family history of melanoma was reduce local recurrence, but also decrease an important risk factor for mucosal melano- complication resulted from radical surgery. mas [12]. Seifreid S deduced that cervical screening may lead to earlier diagnosis of vul- On account of the rate of lymph node metasta- vo-vaginal melanoma with exception of its pri- sis lower, the value of local lymph node dissec- mary aim [4]. Some reports [13, 14] verified tion is not still certainty. Miner et al. [23] per- that vulva melanoma links with HPV infection, formed a systematic lymphadenectomy on 26 and a case report found the positive of HPV6 patients and found two lymph node metasta- and 11 with in situ hybridization (ISH) in benign ses. But we were to clear away if there should melanosis lesions of the vagina which may be a be suspicious lymph nodes during operation. precursor of malignant melanoma [15]. And The current case underwent lymph node dis- Rohwedder et al. reported that cutaneous HPV section. Recently, the feasibility of the tech- and epidermodysplasia verruciformis (EV) nique of the sentinel lymph node biopsy has could play a role in the pathogenesis of genital been shown [25, 26]. Frumovitz et al. [27, 28] melanoma [13, 14]. The theory that HPV infec- recommends its use. tion is necessary for progression to CIN-2/3 is to known [16, 17]. However, there is no clear Radiotherapy can be applied as adjuvant treat- whether HPV infection status is related to ment for patients who are unable to surgery or VPMM or CIN is associated with VPMM. We who the surgery cannot completely remove or found two kinds of HPV infections (HPV33, 35) pelvic metastasis is possible. Our patient in our case. underwent a wide local excision, and received pelvic linear accelerator radiation and intra- It is of crucial importance for VPMM to early vaginal radiotherapy. diagnose due to its appearing at an advanced stage and poor prognosis, with relation to its Bio-immunotherapy is recently a new adjuvant hidden location and the rich vascular [18-20]. treatment, and randomized clinical trial demon-

4557 Int J Clin Exp Pathol 2016;9(4):4555-4559 Vaginal primary malignant melanoma complicating cervical cancer in situ strate interferon (IFN) α2b is first medicine that [6] Terzakis E, Androutsopoulos G, Adonakis G, is beneficial for advanced malignant melano- Zygouris D, Grigoriadis C and Decavalas G. ma, whose treatment can improve the total of Vaginal primary malignant melanoma: report survival time and disease-free survival time of four cases and review of the literature. Eur J [29, 30]. However, toxicity is important [6, 31, Gynaecol Oncol 2011; 32: 122-124. [7] Reid GC, Schmidt RW, Roberts JA, Hopkins MP, 32]. In our patient, she did not receive immuno- Barrett RJ and Morley GW. Primary melanoma therapy due to fever. However, she is still alive of the vagina: a clinicopathologic analysis. 14 months after initial diagnosis. Obstet Gynecol 1989; 74: 190-199. [8] Verschraegen CF, Benjapibal M, Supakara- In summary, Our patient illustrates that CIN3 pongkul W, Levy LB, Ross M, Atkinson EN, could be a cause of VPMM or VPMM may bring Bodurka-Bevers D, Kavanagh JJ, Kudelka AP, about CIN3, via directly or indirectly oncogenic Legha SS. Vulvar melanoma at the M.D. interactions, or as a cofactor, via activation of Anderon Cancer Center: 25 years later. Int J melanocytes, and whether VPMM be associat- Gynecol Cancer 2001; 11: 359-364. ed with HPV33 and 35 infections remains to be [9] McLaughlin CC, Wu XC, Jemal A, Martin HJ, a further in-depth study. Roche LM and Chen VW. Incidence of noncuta- neous melanomas in the U.S. Cancer 2005; Acknowledgements 103: 1000-1007. [10] Cazenave H, Maubec E, Mohamdi H, Grange F, This work was supported by all authors and Bressac-de Paillerets B, Demenais F and Avril Department of Pathology, The First Affiliated MF. Genital and anorectal mucosal melanoma Hospital of Xi’an Jiaotong University. is associated with cutaneous melanoma in patients and in families. Br J Dermato 2013; 169: Disclosure of conflict of interest 594-599. [11] Hussein MR. Extracutaneous malignant mela- None. nomas. Cancer Invest 2008; 26: 516-534. [12] Cazenave H, Maubec E, Mohamdi H, Grange F, Address correspondence to: Dr Rui-Fang An, De- Bressac-de Paillerets B, Demenais F and Avril partment of Gynecology and Obstetrics, The First MF. Genital and anorectal mucosal melanoma Affiliated Hospital of Xi’an Jiaotong University, 277 is associated with cutaneous melanoma in pa- Yanta West Road, Xi’an 710061, Shanxi, P. R. China. tients and in families. Br J Dermatol 2013; Tel: +86-29-85323845; Fax: +86-29-85323845; 169: 594-599. E-mail: [email protected] [13] Rohwedder A, Philips B, Malfetano J, Kredentser D and Carlson JA. Vulvar malignant References melanoma associated with human papillomavirus DNA: report of two cases and review of [1] Piura B. Management of primary melanoma of literature. Am J Dermatopathol 2002; 24: 230- the female urogenital tract. Lancet Oncol 240. 2008; 9: 973-981. [14] Rohwedder A, Slominski A, Wolff M, Kredentser [2] Creasman WT, Phillips JL and Menck HR. The D and Carlson JA. Epidermodysplasia verruci- National Cancer Data Base report on cancer of formis and cutaneous human papillomavirus the vagina. Cancer 1998; 83: 1033-1040. DNA, but not genital human papillomavirus [3] Hu DN, Yu GP and Mccormick SA. Population- DNAs, are frequently detected in vulvar and based incidence of vulvar and vaginal mela- vaginal melanoma. Am J Dermatopathol 2007; noma in various races and ethnic groups with 29: 13-17. comparisons to other site-specific melanomas. [15] Nunez-Troconis J, Delgado M, Gonzalez G, Melanoma Res 2010; 20: 153-158. Rivas A and Molero K. Melanosis of the vagina [4] Seifried S, Haydu LE, Quinn MJ, Scolyer RA, and human papillomavirus infection, an un- Stretch JR and Thompson JF. Melanoma of the common pathology: case report. Invest Clin vulva and vagina: principles of staging and 2011; 52: 268-273. their relevance to management based on a [16] Winer RL, Kiviat NB, Hughes JP, Adam DE, Lee clinicopathologic analysis of 85 cases. Ann SK, Kuypers JM and Koutsky LA. Development Surg Oncol 2015; 22: 1959-1966. and duration of human papillomavirus lesions, [5] Tcheung WJ, Selim MA, Herndon JE 2nd, after initial infection. J Infect Dis 2005; 191: Abernethy AP and Nelson KC. Clinicopathologic 731-738. study of 85 cases of melanoma of the female [17] Humans IWGotEoCRt. Human papillomavirus- genitalia. J Am Acad Dermatol 2012; 67: 598- es. IARC Monogr Eval Carcinog Risks Hum 605. 2007; 90: 1-636.

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