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Metastatic Melanoma of Uncertain Primary with 5-Year Durable Response after Conventional Therapy: A Case Report with Literature Review

Metastatic Melanoma of Uncertain Primary with 5-Year Durable Response after Conventional Therapy:... Hindawi Case Reports in Oncological Medicine Volume 2018, Article ID 7289896, 5 pages https://doi.org/10.1155/2018/7289896 Case Report Metastatic Melanoma of Uncertain Primary with 5-Year Durable Response after Conventional Therapy: A Case Report with Literature Review 1 2 Jomjit Chantharasamee and Jitsupa Treetipsatit Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand Department of Pathology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand Correspondence should be addressed to Jomjit Chantharasamee; jomjit025@hotmail.com Received 3 March 2018; Accepted 8 May 2018; Published 31 May 2018 Academic Editor: Jose I. Mayordomo Copyright © 2018 Jomjit Chantharasamee and Jitsupa Treetipsatit. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. A 51-year-old Thai woman presented with bilateral leg edema and painful left inguinal mass for 6 months. Physical examination revealed matted bilateral inguinal lymph nodes up to 9 cm in size. Otherwise, physical examinations including skin were unremarkable. The result of the lymph node incisional biopsy is consistent with that of metastatic melanoma. The extensive investigation demonstrated multiple intra-abdominal and inguinal lymph nodes without detectable primary tumor. Palliative radiation and conventional chemotherapy were prescribed. The CT scan between treatments showed that the response was stable disease, but the following CT scan demonstrated a gradual decrease in size from August 2012 to November 2017 including the lesions outside radiation fields. Moreover, she developed vitiligo during a follow-up visit. The previous data reported the median overall survival among the patients who were treated with conventional chemotherapy ranging from 9.1 to 9.3 months and whose 5-year survival was less than 10%. This case represented a metastatic melanoma of unknown primary who achieved a durable response by conventional treatment. The clinical features including nodal-only disease, vitiligo, and abscopal effect of radiation were considered to be the favorable factors. 1. Introduction A 5-year overall survival of MUP before the era of the immune checkpoint inhibitor was reported to range from Malignant melanoma is an uncommon skin malignancy 8 to 18% [3, 4, 7]. The most common metastatic site is the accounting for about 4% of skin cancer [1, 2]. An incidence lymph node and GI tract [2, 3]. Many hypotheses were documented in relation to the etiology of MUP including rate of melanoma is increasing worldwide but varies between different studies ranging from 0.3 to 3.6% [1] depending on spontaneous regression of primary melanoma, undiagnosed excised melanoma, small primary in the visceral site, and pri- the predominant skin type and geographical location. The prevalence for men and women varies with the highest preva- mary melanoma in the lymph node [2, 8, 9]. This study was lence at the fifth decade of age [2, 3]. Malignant melanoma of aimed at reporting a patient with metastatic melanoma of uncertain primary who achieved durable response longer than unknown primary (MUP) was reported to be 2–2.4% of mela- noma [2, 4]. Compared to the other areas, Asian populations expected after being treated with conventional treatments. have a significantly lower incidence rate that was estimated about 0.2 to 0.5 per 100,000 patient-years; this incidence rate 2. Case Report is mostly of melanoma of known primary (MKP), so that makes MKP in Asian population extremely rare [1, 2]. Most A 51-year-old Thai woman was hospitalized in July 2012 of the literatures in the different geographic regions demon- with edema at the left lower extremities and painful left strated better overall survival of MUP than of MKP [2, 5, 6]. inguinal mass for 6 months. 2 Case Reports in Oncological Medicine conventional chemotherapy and palliative radiation. When Physical examination revealed matted bilateral inguinal lymph nodes up to 9 cm in size with hard consistency, ery- comparing prognosis, MUP tends to have a better prognosis thema, and tenderness without fluctuation or ulcer. Marked than MKP as reported in previous studies [2, 4–6, 8, 12]. The swelling at both lower extremities was observed. There was aforementioned hypotheses of unknown primary including no other superficial lymphadenopathy. Otherwise, physical an immunological response that leads to spontaneous regres- examinations were normal. sion of primary tumor, unrecognized primary tumor, and the Incisional biopsy of the left inguinal lymph node revealed occurrence of malignant ectopic nevus cells in the lymph metastatic round cell tumor which is immunohistochemistry node itself can be considered the etiology of MUP in this positive for vimentin, S100, and HMB-45. The immunophe- patient, who denied previous removal of cutaneous lesion notype is consistent with malignant melanoma (Figure 1). [2, 8, 9]. The data from Dana-Farber Institute reported that Therefore, primary tumors in the lower extremities, the nodal-only metastasis was an independent favorable abdominal cavity, and anogenital organ were suspected. By prognostic factor of MUP compared to metastasis at other complete skin examination, no cutaneous lesion was identi- sites [3]. This patient had nodal-only metastasis, which fied. Ophthalmoscopy, gastroscopy, colonoscopy, and cys- explains that this is a favorable clinical feature. The survival toscopy were completely normal. Genital and pelvic outcome of metastatic melanoma according to the molecular examinations did not show any evidence of lesion. She alteration was reported in many literatures. For Asian popu- denied previous abnormal or removal of cutaneous lesion. lation, the study reported by Kong et al. [13] showed that KIT Computer tomography of the whole abdomen showed multi- mutation was an independent prognostic factor for a shorter ple enlarged lymph nodes throughout the abdominal and survival compared to KIT wild type (30 versus 58 months). pelvic cavity up to 9.5 cm, along with compression of both Another study by Si et al. [14] reported that BRAF and NRAS iliac veins without an organ-specific lesion (Figure 2). CT mutation was associated with worse overall survival com- chest was unremarkable. The patient was diagnosed with pared to wild-type melanoma (33 versus 53 months). metastatic melanoma of unknown primary. The molecular Regarding the effect of palliative chemotherapy, the recent testing had not been done due to the patient’s reimbursement studies showed that the response rate was 10–30% [10, 11, issue, and the specimen was poor in quality for further 15] consistent with the response rate of this patient. After testing. During the investigation, she developed severe pain completion of chemotherapy, the tumors still had a detect- requiring high-dose opioid, so she has undergone 20 Gy of able size as same as previous, but after regular visits, the palliative radiotherapy for bilateral inguinal lymph nodes. tumors gradually decreased in size based on the interval CT scan. The possibility of clinical response from the conven- Despite radiotherapy, the remaining tumors were up to 7.4 cm based on the CT scan. For the subsequent systemic tional chemotherapy can be explained by the genomic pro- therapy, according to a national reimbursement policy, she file. The correlation of somatic mutations with the clinical could not access an immune checkpoint inhibitor or targeted outcome of melanoma patients treated with carboplatin/pac- drug. Chemotherapy was prescribed with carboplatin litaxel either with or without sorafenib was reported by (AUC5) and paclitaxel 175 mg/m for 6 cycles. After comple- Melissa et al. The patients harboring BRAF mutation and tion of the planned chemotherapy, the symptom was slightly wild type seemed to have longer survival than those harbor- ing NRAS mutation (15.6 versus 5.6 months) in a chemo- improved. The CT scan at the first 3 months showed that the response was stable disease, but the following CT scan dem- therapy arm [16]. Another study from Jilaveanu et al. [17] onstrated a gradual decrease in size over time from August reported the association between marker expression and response to sorafenib plus chemotherapy. This study 2012 to November 2017 (Figure 3). During the follow-up period, the patient developed multiple depigmented patches revealed that the patients with high VEGFR-R2/low ERK1/ around the lips, trunk, and periorbital and inguinal area, 2 expression correlated with a higher response rate compared which are typical of vitiligo. to those with low VEGFR-R2/high ERK1/2. However, we could not demonstrate the molecular alteration in our patient due to the unaffordable cost of testing at the time of diagnosis 3. Discussion and the poor quality of the 5-year archival specimen. In addition to the chemotherapy treatment, the tumors outside Systemic treatments of metastatic melanoma were developed for many decades since conventional chemotherapy has been the radiation field also decreased in size which could be either considered a standard approach until the emergence of new the effect of chemotherapy or the abscopal effect of radiation [18]. This late-response phenomenon could be the effect of drugs such as targeted therapy and immunotherapy over the last 10 years. The dramatic and durable response the immune response rather than of the chemotherapy itself. occurred by taking targeted therapy or immunotherapy but According to the effect of radiotherapy, irradiation can not by taking chemotherapy. In the patients who did not induce the host antitumor immune response resulting in have access to those drugs, chemotherapy is a mainstay treat- the late response after treatment as presented in this case [19]. The hypotheses of presentation of vitiligo concomitant ment. Previous data reported the median overall survival among the patients who were treated with conventional with melanoma by the process of autoimmune-related chemotherapy ranging from 7.7 to 16 months and whose vitiligo were published in many literatures. The several 5-year survival was 8–18% [4, 6, 7, 10, 11]. data-reported specific antigens of melanoma such as TRP1 This case report represents a patient with metastatic and TRP2 that were shared by normal melanocytes caused immune response to both melanoma and normal melanoma of unknown primary with durable response by Case Reports in Oncological Medicine 3 (a) (b) (c) (d) (e) Figure 1: Metastatic malignant melanoma in the left inguinal lymph node: (a) H&E at ×40 and (b) H&E at ×400. The tumor cells are positive for vimentin (c), S100 (d), and HMB-45 (e). 52 YEAR 9/8/2555 15:23:56 57 YEAR 30/11/2560 9:12:48 F 22647157 F 24897934 OMNIPAQUE350 = 70 ULTRAVIST370 = 85 LOC: −228.50 LOC: −127.38 THK: 1.25 THK: 1.25 FFS FFS 24.61 mm RL RL RD: 349 RD: 347 Tilt: 0 Z: 1 Z: 1 Tilt: 0 mA: 341 C: 55 mA: 500 C: 55 KVp: 120 W: 426 Figure 2: Abdominal CT scan at the time of diagnosis demonstrated Figure 3: The following CT scan revealed a marked decrease in size matted paraaortic nodes. of intra-abdominal lymph nodes. melanocytes [20–22]. In addition, some preclinical evidence T-cell infiltration within the melanoma and vitiligo lesion. supported the role of CD8 T-cell-mediated melanoma in All those theories can explain the correlation between mela- vitiligo. The result from an ex vivo study demonstrated that noma and vitiligo. The evidence supports that the presence melanoma cells can be killed by CD8 T-cells taken from a of vitiligo may be a favorable prognostic factor for survival vitiligo lesion and T-cells taken from melanoma that caused theoretically due to the immune mechanism responsible for apoptosis of melanocytes [21, 23, 24]. Moreover, the report melanocytic proliferation causing depigmentation of skin from Becker et al. [25] showed the clonotypically identical and spontaneous regression of primary melanoma which 4 Case Reports in Oncological Medicine Open Access Macedonian Journal of Medical Sciences, vol. 5, were reported [26–28]. One of the studies reported by no. 7, pp. 970–973, 2017. Nordlund et al. [28] showed that a 10-year survival rate among patients with nonmetastatic melanoma with vitiligo [10] S. Aamdal, I. Wolff, S. Kaplan et al., “Docetaxel (Taxotere) in advanced malignant melanoma: a phase II study of the was 49%. This patient who has vitiligo may benefit from this EORTC early clinical trials group,” European Journal of mechanism in terms of disease control. This patient had a Cancer, vol. 30, no. 8, pp. 1061–1064, 1994. tumor response along with vitiligo later after the complete [11] M. B. Atkins, J. Hsu, S. Lee et al., “Phase III trial comparing treatment which was probably from the effect of the immune concurrent biochemotherapy with cisplatin, vinblastine, process. The molecular basis in this patient was not yet dacarbazine, interleukin-2, and interferon alfa-2b with cis- known to be a prognostic marker for survival. platin, vinblastine, and dacarbazine alone in patients with met- astatic malignant melanoma (E3695): a trial coordinated by 4. Conclusion the eastern cooperative oncology group,” Journal of Clinical Oncology, vol. 26, no. 35, pp. 5748–5754, 2008. Metastatic melanoma can achieve durable response by [12] F. Egberts, I. Bergner, S. Krüger et al., “Metastatic melanoma of conventional chemotherapy and radiotherapy in patients unknown primary resembles the genotype of cutaneous mela- with some clinical characteristics. The presence of the nomas,” Annals of Oncology, vol. 25, no. 1, pp. 246–250, 2014. nodal-only disease, vitiligo, and effect of radiation seemed [13] Y. Kong, L. Si, Y. Zhu et al., “Large-scale analysis of KIT aber- to be the favorable factors for better survival. rations in Chinese patients with melanoma,” Clinical Cancer Research, vol. 17, no. 7, pp. 1684–1691, 2011. [14] L. Si, Y. Kong, X. Xu et al., “Prevalence of BRAF V600E muta- Conflicts of Interest tion in Chinese melanoma patients: large scale analysis of BRAF and NRAS mutations in a 432-case cohort,” European The authors declare that they have no conflicts of interest. Journal of Cancer, vol. 48, no. 1, pp. 94–100, 2012. [15] E. Bajetta, M. del Vecchio, P. Nova et al., “Multicenter phase References III randomized trial of polychemotherapy (CVD regimen) ver- sus the same chemotherapy (CT) plus subcutaneous [1] F. Erdmann, J. Lortet-Tieulent, J. Schüz et al., “International interleukin-2 and interferon-α2b in metastatic melanoma,” trends in the incidence of malignant melanoma 1953– Annals of Oncology, vol. 17, no. 4, pp. 571–577, 2006. 2008—are recent generations at higher or lower risk?,” Inter- [16] M. A. Wilson, F. Zhao, R. Letrero et al., “Correlation of national Journal of Cancer, vol. 132, no. 2, pp. 385–400, 2013. somatic mutations and clinical outcome in melanoma [2] J. F. Scott, R. Z. Conic, C. L. Thompson, M. R. Gerstenblith, patients treated with carboplatin, paclitaxel, and sorafenib,” and J. S. Bordeaux, “Stage IV melanoma of unknown primary: Clinical Cancer Research, vol. 20, no. 12, pp. 3328–3337, a population-based study in the United States from 1973 to 2014,” Journal of the American Academy of Dermatology, [17] L. Jilaveanu, C. Zito, S. J. Lee et al., “Expression of sorafenib vol. 18, pp. 30472–30479, 2018. targets in melanoma patients treated with carboplatin, pacli- [3] K. A. Katz, E. Jonasch, F. S. Hodi et al., “Melanoma of taxel and sorafenib,” Clinical Cancer Research, vol. 15, no. 3, unknown primary: experience at Massachusetts general hospi- pp. 1076–1085, 2009. tal and Dana-Farber Cancer Institute,” Melanoma Research, [18] M. A. Postow, M. K. Callahan, C. A. Barker et al., “Immuno- vol. 15, no. 1, pp. 77–82, 2005. logic correlates of the abscopal effect in a patient with mela- [4] A. E. Chang, L. H. Karnell, and H. R. Menck, “The National noma,” The New England Journal of Medicine, vol. 366, Cancer Data Base report on cutaneous and noncutaneous no. 10, pp. 925–931, 2012. melanoma,” Cancer, vol. 83, no. 8, pp. 1664–1678, 1998. [19] C. A. Perez, A. Fu, H. Onishko, D. E. Hallahan, and L. Geng, [5] J. M. Bae, Y. Y. Choi, D. S. Kim et al., “Metastatic melanomas “Radiation induces an antitumour immune response to mouse of unknown primary show better prognosis than those of melanoma,” International Journal of Radiation Biology, known primary: a systematic review and meta-analysis of vol. 85, no. 12, pp. 1126–1136, 2010. observational studies,” Journal of the American Academy of Dermatology, vol. 72, no. 1, pp. 59–70, 2015. [20] A. Houghton, M. Eisinger, A. P. Albino, J. Cairncross, and L. Old, “Surface antigens of melanocytes and melanomas. [6] C. C. Lee, M. B. Faries, L. A. Wanek, and D. L. Morton, Markers of melanocyte differentiation and melanoma subsets,” “Improved survival for stage IV melanoma from an unknown Journal of Experimental Medicine, vol. 156, no. 6, pp. 1755– primary site,” Journal of Clinical Oncology, vol. 27, no. 21, 1766, 1982. pp. 3489–3495, 2009. [21] M. J. Turk, J. D. Wolchok, J. A. Guevara-Patino, S. M. Gold- [7] G. Vijuk and A. S. Coates, “Survival of patients with visceral berg, and A. N. Houghton, “Multiple pathways to tumor metastatic melanoma from an occult primary lesion: a retro- immunity and concomitant autoimmunity,” Immunological spective matched cohort study,” Annals of Oncology, vol. 9, Reviews, vol. 188, no. 1, pp. 122–135, 2002. no. 4, pp. 419–422, 1998. [22] H. Uchi, R. Stan, M. J. Turk et al., “Unraveling the complex [8] P. Savoia, P. Fava, S. Osella-Abate et al., “Melanoma of relationship between cancer immunity and autoimmunity: les- unknown primary site: a 33-year experience at the Turin sons from melanoma and vitiligo,” Advances in Immunology, Melanoma Centre,” Melanoma Research, vol. 20, no. 3, vol. 90, pp. 215–241, 2006. pp. 227–232, 2010. [9] G. Tchernev, A. Chokoeva, and L. V. Popova, “Primary soli- [23] A. Anichini, C. Maccalli, R. Mortarini et al., “Melanoma cells tary melanoma of the lymphatic nodes or a single metastasis and normal melanocytes share antigens recognized by HLA- of unknown melanoma: do we need a new staging system?,” A2-restricted cytotoxic T cell clones from melanoma patients,” Case Reports in Oncological Medicine 5 Journal of Experimental Medicine, vol. 177, no. 4, pp. 989–998, [24] K. Oyarbide-Valencia, J. G. van den Boorn, C. J. Denman et al., “Therapeutic implications of autoimmune vitiligo T cells,” Autoimmunity Reviews, vol. 5, no. 7, pp. 486–492, 2006. [25] J. C. Becker, P. Guldberg, J. Zeuthen, E.-B. Bröcker, and P. t. Straten, “Accumulation of identical T cells in melanoma and vitiligo-like leukoderma,” Journal of Investigative Dermatol- ogy, vol. 113, no. 6, pp. 1033–1038, 1999. [26] E. A. Cho, M. A. Lee, H. Kang, S. D. Lee, H. O. Kim, and Y. M. Park, “Vitiligo-like depigmentation associated with metastatic melanoma of an unknown origin,” Annals of Dermatology, vol. 21, no. 2, pp. 178–181, 2009. [27] P. Quaglino, F. Marenco, S. Osella-Abate et al., “Vitiligo is an independent favourable prognostic factor in stage III and IV metastatic melanoma patients: results from a single- institution hospital-based observational cohort study,” Annals of Oncology, vol. 21, no. 2, pp. 409–414, 2010. [28] J. J. Nordlund, J. M. Kirkwood, B. M. Forget, G. Milton, D. M. Albert, and A. B. Lerner, “Vitiligo in patients with metastatic melanoma: a good prognostic sign,” Journal of the American Academy of Dermatology, vol. 9, no. 5, pp. 689–696, 1983. 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Metastatic Melanoma of Uncertain Primary with 5-Year Durable Response after Conventional Therapy: A Case Report with Literature Review

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Hindawi Case Reports in Oncological Medicine Volume 2018, Article ID 7289896, 5 pages https://doi.org/10.1155/2018/7289896 Case Report Metastatic Melanoma of Uncertain Primary with 5-Year Durable Response after Conventional Therapy: A Case Report with Literature Review 1 2 Jomjit Chantharasamee and Jitsupa Treetipsatit Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand Department of Pathology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand Correspondence should be addressed to Jomjit Chantharasamee; jomjit025@hotmail.com Received 3 March 2018; Accepted 8 May 2018; Published 31 May 2018 Academic Editor: Jose I. Mayordomo Copyright © 2018 Jomjit Chantharasamee and Jitsupa Treetipsatit. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. A 51-year-old Thai woman presented with bilateral leg edema and painful left inguinal mass for 6 months. Physical examination revealed matted bilateral inguinal lymph nodes up to 9 cm in size. Otherwise, physical examinations including skin were unremarkable. The result of the lymph node incisional biopsy is consistent with that of metastatic melanoma. The extensive investigation demonstrated multiple intra-abdominal and inguinal lymph nodes without detectable primary tumor. Palliative radiation and conventional chemotherapy were prescribed. The CT scan between treatments showed that the response was stable disease, but the following CT scan demonstrated a gradual decrease in size from August 2012 to November 2017 including the lesions outside radiation fields. Moreover, she developed vitiligo during a follow-up visit. The previous data reported the median overall survival among the patients who were treated with conventional chemotherapy ranging from 9.1 to 9.3 months and whose 5-year survival was less than 10%. This case represented a metastatic melanoma of unknown primary who achieved a durable response by conventional treatment. The clinical features including nodal-only disease, vitiligo, and abscopal effect of radiation were considered to be the favorable factors. 1. Introduction A 5-year overall survival of MUP before the era of the immune checkpoint inhibitor was reported to range from Malignant melanoma is an uncommon skin malignancy 8 to 18% [3, 4, 7]. The most common metastatic site is the accounting for about 4% of skin cancer [1, 2]. An incidence lymph node and GI tract [2, 3]. Many hypotheses were documented in relation to the etiology of MUP including rate of melanoma is increasing worldwide but varies between different studies ranging from 0.3 to 3.6% [1] depending on spontaneous regression of primary melanoma, undiagnosed excised melanoma, small primary in the visceral site, and pri- the predominant skin type and geographical location. The prevalence for men and women varies with the highest preva- mary melanoma in the lymph node [2, 8, 9]. This study was lence at the fifth decade of age [2, 3]. Malignant melanoma of aimed at reporting a patient with metastatic melanoma of uncertain primary who achieved durable response longer than unknown primary (MUP) was reported to be 2–2.4% of mela- noma [2, 4]. Compared to the other areas, Asian populations expected after being treated with conventional treatments. have a significantly lower incidence rate that was estimated about 0.2 to 0.5 per 100,000 patient-years; this incidence rate 2. Case Report is mostly of melanoma of known primary (MKP), so that makes MKP in Asian population extremely rare [1, 2]. Most A 51-year-old Thai woman was hospitalized in July 2012 of the literatures in the different geographic regions demon- with edema at the left lower extremities and painful left strated better overall survival of MUP than of MKP [2, 5, 6]. inguinal mass for 6 months. 2 Case Reports in Oncological Medicine conventional chemotherapy and palliative radiation. When Physical examination revealed matted bilateral inguinal lymph nodes up to 9 cm in size with hard consistency, ery- comparing prognosis, MUP tends to have a better prognosis thema, and tenderness without fluctuation or ulcer. Marked than MKP as reported in previous studies [2, 4–6, 8, 12]. The swelling at both lower extremities was observed. There was aforementioned hypotheses of unknown primary including no other superficial lymphadenopathy. Otherwise, physical an immunological response that leads to spontaneous regres- examinations were normal. sion of primary tumor, unrecognized primary tumor, and the Incisional biopsy of the left inguinal lymph node revealed occurrence of malignant ectopic nevus cells in the lymph metastatic round cell tumor which is immunohistochemistry node itself can be considered the etiology of MUP in this positive for vimentin, S100, and HMB-45. The immunophe- patient, who denied previous removal of cutaneous lesion notype is consistent with malignant melanoma (Figure 1). [2, 8, 9]. The data from Dana-Farber Institute reported that Therefore, primary tumors in the lower extremities, the nodal-only metastasis was an independent favorable abdominal cavity, and anogenital organ were suspected. By prognostic factor of MUP compared to metastasis at other complete skin examination, no cutaneous lesion was identi- sites [3]. This patient had nodal-only metastasis, which fied. Ophthalmoscopy, gastroscopy, colonoscopy, and cys- explains that this is a favorable clinical feature. The survival toscopy were completely normal. Genital and pelvic outcome of metastatic melanoma according to the molecular examinations did not show any evidence of lesion. She alteration was reported in many literatures. For Asian popu- denied previous abnormal or removal of cutaneous lesion. lation, the study reported by Kong et al. [13] showed that KIT Computer tomography of the whole abdomen showed multi- mutation was an independent prognostic factor for a shorter ple enlarged lymph nodes throughout the abdominal and survival compared to KIT wild type (30 versus 58 months). pelvic cavity up to 9.5 cm, along with compression of both Another study by Si et al. [14] reported that BRAF and NRAS iliac veins without an organ-specific lesion (Figure 2). CT mutation was associated with worse overall survival com- chest was unremarkable. The patient was diagnosed with pared to wild-type melanoma (33 versus 53 months). metastatic melanoma of unknown primary. The molecular Regarding the effect of palliative chemotherapy, the recent testing had not been done due to the patient’s reimbursement studies showed that the response rate was 10–30% [10, 11, issue, and the specimen was poor in quality for further 15] consistent with the response rate of this patient. After testing. During the investigation, she developed severe pain completion of chemotherapy, the tumors still had a detect- requiring high-dose opioid, so she has undergone 20 Gy of able size as same as previous, but after regular visits, the palliative radiotherapy for bilateral inguinal lymph nodes. tumors gradually decreased in size based on the interval CT scan. The possibility of clinical response from the conven- Despite radiotherapy, the remaining tumors were up to 7.4 cm based on the CT scan. For the subsequent systemic tional chemotherapy can be explained by the genomic pro- therapy, according to a national reimbursement policy, she file. The correlation of somatic mutations with the clinical could not access an immune checkpoint inhibitor or targeted outcome of melanoma patients treated with carboplatin/pac- drug. Chemotherapy was prescribed with carboplatin litaxel either with or without sorafenib was reported by (AUC5) and paclitaxel 175 mg/m for 6 cycles. After comple- Melissa et al. The patients harboring BRAF mutation and tion of the planned chemotherapy, the symptom was slightly wild type seemed to have longer survival than those harbor- ing NRAS mutation (15.6 versus 5.6 months) in a chemo- improved. The CT scan at the first 3 months showed that the response was stable disease, but the following CT scan dem- therapy arm [16]. Another study from Jilaveanu et al. [17] onstrated a gradual decrease in size over time from August reported the association between marker expression and response to sorafenib plus chemotherapy. This study 2012 to November 2017 (Figure 3). During the follow-up period, the patient developed multiple depigmented patches revealed that the patients with high VEGFR-R2/low ERK1/ around the lips, trunk, and periorbital and inguinal area, 2 expression correlated with a higher response rate compared which are typical of vitiligo. to those with low VEGFR-R2/high ERK1/2. However, we could not demonstrate the molecular alteration in our patient due to the unaffordable cost of testing at the time of diagnosis 3. Discussion and the poor quality of the 5-year archival specimen. In addition to the chemotherapy treatment, the tumors outside Systemic treatments of metastatic melanoma were developed for many decades since conventional chemotherapy has been the radiation field also decreased in size which could be either considered a standard approach until the emergence of new the effect of chemotherapy or the abscopal effect of radiation [18]. This late-response phenomenon could be the effect of drugs such as targeted therapy and immunotherapy over the last 10 years. The dramatic and durable response the immune response rather than of the chemotherapy itself. occurred by taking targeted therapy or immunotherapy but According to the effect of radiotherapy, irradiation can not by taking chemotherapy. In the patients who did not induce the host antitumor immune response resulting in have access to those drugs, chemotherapy is a mainstay treat- the late response after treatment as presented in this case [19]. The hypotheses of presentation of vitiligo concomitant ment. Previous data reported the median overall survival among the patients who were treated with conventional with melanoma by the process of autoimmune-related chemotherapy ranging from 7.7 to 16 months and whose vitiligo were published in many literatures. The several 5-year survival was 8–18% [4, 6, 7, 10, 11]. data-reported specific antigens of melanoma such as TRP1 This case report represents a patient with metastatic and TRP2 that were shared by normal melanocytes caused immune response to both melanoma and normal melanoma of unknown primary with durable response by Case Reports in Oncological Medicine 3 (a) (b) (c) (d) (e) Figure 1: Metastatic malignant melanoma in the left inguinal lymph node: (a) H&E at ×40 and (b) H&E at ×400. The tumor cells are positive for vimentin (c), S100 (d), and HMB-45 (e). 52 YEAR 9/8/2555 15:23:56 57 YEAR 30/11/2560 9:12:48 F 22647157 F 24897934 OMNIPAQUE350 = 70 ULTRAVIST370 = 85 LOC: −228.50 LOC: −127.38 THK: 1.25 THK: 1.25 FFS FFS 24.61 mm RL RL RD: 349 RD: 347 Tilt: 0 Z: 1 Z: 1 Tilt: 0 mA: 341 C: 55 mA: 500 C: 55 KVp: 120 W: 426 Figure 2: Abdominal CT scan at the time of diagnosis demonstrated Figure 3: The following CT scan revealed a marked decrease in size matted paraaortic nodes. of intra-abdominal lymph nodes. melanocytes [20–22]. In addition, some preclinical evidence T-cell infiltration within the melanoma and vitiligo lesion. supported the role of CD8 T-cell-mediated melanoma in All those theories can explain the correlation between mela- vitiligo. The result from an ex vivo study demonstrated that noma and vitiligo. The evidence supports that the presence melanoma cells can be killed by CD8 T-cells taken from a of vitiligo may be a favorable prognostic factor for survival vitiligo lesion and T-cells taken from melanoma that caused theoretically due to the immune mechanism responsible for apoptosis of melanocytes [21, 23, 24]. Moreover, the report melanocytic proliferation causing depigmentation of skin from Becker et al. [25] showed the clonotypically identical and spontaneous regression of primary melanoma which 4 Case Reports in Oncological Medicine Open Access Macedonian Journal of Medical Sciences, vol. 5, were reported [26–28]. One of the studies reported by no. 7, pp. 970–973, 2017. Nordlund et al. [28] showed that a 10-year survival rate among patients with nonmetastatic melanoma with vitiligo [10] S. Aamdal, I. Wolff, S. Kaplan et al., “Docetaxel (Taxotere) in advanced malignant melanoma: a phase II study of the was 49%. 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