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Open Access 27.05.2019 | Case Report

Isolated pancreatic metastasis from malignant melanoma: a case report and literature review

verfasst von: Yoshifumi Nakamura, Reiko Yamada, Maki Kaneko, Hiroaki Naota, Yu Fujimura, Masami Tabata, Kazuhiko Kobayashi, Kyosuke Tanaka

Erschienen in: Clinical Journal of Gastroenterology | Ausgabe 6/2019

Abstract

Isolated pancreatic metastasis from malignant melanoma is rare. Pancreatic metastasis is difficult to diagnose in patients with unknown primary malignant melanoma. Endoscopic ultrasound-guided fine-needle aspiration plays an important role in confirming the diagnosis. A 67-year-old woman was referred to our institution because of a mass in her pancreas. Computed tomography and magnetic resonance imaging revealed a 35-mm mass localized on the pancreatic tail, with low attenuation, surrounded by a high-attenuation rim. Endoscopic ultrasonography revealed a hypoechoic mass with central anechoic areas. Endoscopic ultrasound-guided fine-needle aspiration of the mass was performed, and the pathological diagnosis was malignant melanoma. Intense fluorodeoxyglucose uptake was observed in the pancreatic tail on positron emission tomography–computed tomography. No other malignant melanoma was found. Distal pancreatectomy was performed. Six months postoperatively, positron emission tomography–computed tomography revealed high uptake in the left nasal cavity, and biopsy revealed the mass to be a malignant melanoma, indicating that the primary site of the malignant melanoma was the left nasal cavity and that the pancreatic mass and peritoneal lesion were metastases. The patient had survived > 2 years after the distal pancreatectomy. Pancreatic resection of isolated pancreatic metastasis can possibly prolong survival; however, metastatic melanoma usually has poor prognosis.
Hinweise

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Introduction

Pancreatic metastases are rare, ranging from 2 to 5% of pancreatic malignancies [1, 2]. The most common primary malignancies that metastasize to the pancreas are renal, lung, breast, and colon cancer, with sarcoma and melanoma observed less commonly [24]. Metastatic melanoma has a poor prognosis; the median survival for patients with stage IV melanoma ranges from 8 to 18 months after diagnosis [5]. Isolated pancreatic metastasis is a rare event that represents about less than 1% of metastatic melanomas [6].
Pancreatic metastases can resemble primary pancreatic malignancies, such as ductal carcinoma or neuroendocrine tumors. Thus, it can be difficult to differentiate pancreatic metastases from primary tumors based only on imaging findings. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) plays an important role in confirming the diagnosis [1]. There are only a few reports on surgically resected pancreatic metastasis of malignant melanoma diagnosed by EUS-FNA [3, 7, 8]. Here, we present a unique case of malignant melanoma with isolated pancreatic metastasis diagnosed by EUS-FNA and was treated with distal pancreatectomy.

Case report

A 67-year-old woman, who had been healthy all her life, presented to the referring hospital with left upper quadrant abdominal pain. Her ultrasonogram and computed tomography (CT) showed a mass in the pancreas, and the patient was referred to our institution for further examination.
Enhanced CT revealed that the mass was localized to the tail of the pancreas, with pancreatic ductal dilatation. The mass was a rounded, well-defined lesion with low attenuation, surrounded by a high-attenuation rim (Fig. 1a). Magnetic resonance imaging (MRI) showed that the center of the mass was hyperintense on T1-weighted image and hypointense on T2-weighted image (Fig. 1b, c). The diffusion-weighted image showed a hyperintense peripheral rim of the mass (Fig. 1d). Endoscopic retrograde cholangiopancreatogram demonstrated smooth narrowing and displacement of the pancreatic duct with upstream dilatation (Fig. 2). EUS revealed the 35-mm mass to be hypoechoic and heterogeneous with central anechoic areas (Fig. 3a, b). Contrast-enhanced EUS (CE-EUS) was conducted using an electronic radial-type endoscope (GF-UE260; Olympus, Japan) and perflubutane as ultrasound contrast agent. CE-EUS showed isoenhancement during the 20-s phase (Fig. 3c) and hypoenhancement during the 120-s phase (Fig. 3d) of the peripheral rim of the mass with central non-enhancement.
Cytological analysis obtained by EUS-FNA with a 22-gauge needle (Fig. 4a) revealed a large nucleus and a high nuclear/cytoplasmic ratio in the cells, with brown pigmentation (Fig. 4b). The cells were positive for Melan A and Human Melanoma Black 45 (HMB-45) and were negative for S100 on cell-block immunocytochemical analysis (Fig. 4c, d). Thus, the patient was diagnosed as having malignant melanoma.
Since primary pancreatic malignant melanoma has never been reported before, we suspected metastatic malignant melanoma of the pancreas. However, intense fluorodeoxyglucose uptake was observed only in the tail of the pancreas on positron emission tomography–CT (PET-CT) (Fig. 5). Esophagogastroduodenoscopy and colonoscopy did not reveal any specific findings. The primary site could not be identified by dermatological, ophthalmological, or gynecological examination.
Distal pancreatectomy was performed. Histological examination of the surgical specimen revealed malignant melanoma with central necrosis (Figs. 6, 7). The resection specimen stained for Melan A and HMB-45, but not for S100. The patient underwent interferon-alfa treatment as an adjuvant therapy. Six months postoperatively, the follow-up PET-CT showed high uptake in the left nasal cavity, left infraclavicular lymph, and peritoneum (Fig. 8). On fiber-optic laryngoscopy, a whitish mass was detected in the left nasal cavity, which was determined to be a malignant melanoma. Although melanin was unclear in the nasal cavity biopsy specimen, cell shape and immunohistochemistry findings were the same as those in the resected surgical specimen. The primary site of the malignant melanoma was the left nasal cavity, and the pancreatic mass, left infraclavicular lymph, and peritoneal lesion were metastases. Nivolumab was started; thereafter, the treatment was switched to pembrolizumab. The patient had survived for more than 2 years after the distal pancreatectomy.

Discussion

Malignant melanoma usually metastasizes to the gastrointestinal tract, and metastatic malignant melanoma usually affects multiple sites. Isolated organ metastasis is unusual; specifically, metastasis to the pancreas is extremely rare (< 1%) [6]. There are 76 cases of pancreatic metastasis from malignant melanoma reported in English (Table 1). The major primary site is cutaneous and ocular. Meanwhile, there are only three cases of pancreatic metastasis from nasal cavity malignant melanoma, including our case [9, 10]. Sometimes, the primary lesion of melanoma is difficult to identify during pretreatment evaluation. In our case, the primary site was identified by PET-CT 6 months postoperatively, even though PET-CT is only effective for detecting primary tumors or cancers of unknown primary.
Table 1
Metastatic malignant melanoma of pancreas reported in the English literature
Authors
Year of publication
Age
Sex
Case
Primary site
Location in the pancreas
Tumor size (cm)
Diagnostic modality
Surgery
Follow-up (month)
Outcome
Das Gupta et al. [21]
1964
44
Female
2
Cutaneous
Body and tail
NR
Exploratory laparotomy
No operation
2
Dead
28
Male
 
Cutaneous
Body and tail
NR
Exploratory laparotomy
DP
10
Dead
Johansson et al. [22]
1970
67
Female
1
Ocular
Head
NR
Biopsy
PD
11
Alive
Bianca et al. [23]
1991
48
Male
1
Unknown
Head
3
FNA
PD
12
Alive
Brodish et al. [24]
1993
75
Female
1
Cutaneous
Tail
5
CT
DP
12
Alive
Rütter et al. [9]
1994
55
Male
1
Unknown (1 year after surgery, melanoma detected in nasal cavity and nasopharynx)
Head
2.5
ERCP
DP
12
Alive
Sobesky et al. [25]
1997
32
Female
1
Thoracic melanoma
Diffuse infiltration
NR
ERCP, biopsy
No operation
1.5
Dead
Harrison et al. [26]
1997
NR
NR
1
NR
NR
NR
NR
NR
NR
NR
Medina-Franco et al. [27]
1999
60
Male
1
Unknown
Head
8
CT, US
PD
6
Dead
Wood et al. [19]
2001
NR
NR
8
NR
NR
NR
NR
Curative resection or palliative resection
Median 23.8
 
NR
NR
20
NR
NR
NR
NR
no operation
Median 15.2
 
Hiotis et al. [28]
2002
NR
NR
1
NR
NR
NR
NK
PD
NR
Dead
Camp et al. [29]
2002
62
Female
1
Ocular
Body
5
CT, PET-CT
DP
20
Alive
Dewitt et al. [30]
2003
33
Male
2
Unknown
Head
5
EUS-FNA
Palliative gastrojejunostomy
6
Dead
83
Female
 
Unknown
Tail
3
EUS-FNA
No operation
10
Alive
Mizushima et al. [31]
2003
51
Female
1
Cutaneous
Head
5
Biopsy
No operation
NR
NR
Nikfarjam et al. [32]
2003
45
Male
2
Ocular
Head
3
CT, MRI, PET-CT etc.
PD
6
Alive
55
Male
 
Ocular
Head, body, tail
NR
CT, PET-CT etc.
TP
7
Alive
Carboni et al. [33]
2004
55
Female
1
Cutaneous
Head
8
Biopsy
PD
4
Dead
Crippa et al. [34]
2006
36
Female
1
NR
Head
NR
NR
PD
14
Dead
Belágyi et al. [35]
2006
28
Female
1
Ocular
Body
NR
CT
Pancreatic enucleation etc.
4
Dead
Eidt et al. [36]
2007
NR
NR
4
NR
NR
8
NR
PD
76
Alive
NR
NR
 
NR
NR
5
NR
PD
30
Alive
NR
NR
 
NR
NR
7
NR
PD
12
Dead
NR
NR
 
NR
NR
5
NR
PD
25
Dead
Reddy et al. [37]
2008
NR
NR
3
NR
NR
Median size 4
NR
NR
Median 10.8
 
Dumitraşcu et al. [7]
2008
43
Female
1
Ocular
Body
2
EUS-FNA
CP
12
Alive
Lanitis et al. [38]
2010
69
Male
1
Cutaneous
Head
4.5
CT
PD
96
Alive
He et al. [39]
2010
39
Male
1
Ocular
Tail
18
CT, MRI, ERCP etc.
DP
25
Alive
Vagefi et al. [8]
2010
57
Female
1
Ocular
Tail
2.2
EUS-FNA
DP
NR
NR
Portale et al. [4]
2011
43
Female
1
Unknown
Tail
1.7
US, CT, PET-CT
DP
NR
NR
Moszkowicz et al. [40]
2011
44
Female
1
Cutaneous
Uncinate process, Cephalo-isthmic junction
1.3, 0.9
Biopsy under EUS
PD
NR
NR
Sperti et al. [41]
2011
48
Male
1
Unknown
Body
2.9
CT
DP
24
Dead
Goyal et al. [18]
2012
47
Female
5
Cutaneous
Head
3
ERCP-assisted biopsy
PD
15
Dead
73
Female
 
Cutaneous
Head
4
CT
PD
3
Dead
58
Female
 
Unknown
Head
10
CT-guided biopsy
PD
11.4
Dead
28
Female
 
Cutaneous
Head
2
PET-CT
PD
4.5
Dead
69
Male
 
Unknown
Tail
4.5
Biopsy
DP
26
Dead
Larsen et al. [2]
2013
32
Female
1
Cutaneous
Head
NR
CT
PD
228
Alive
Birnbaum et al. [5]
2013
45
Female
1
Cutaneous
Head
6
Biopsy
PD
19
Alive
Sugimoto et al. [10]
2013
46
Male
1
Nasal cavity
Body
3.3
CT, PET-CT
DP
10
Dead
Solmaz et al. [42]
2014
59
Male
1
Cutaneous
Head
3.8
Biopsy
No operation
NR
NR
Jana et al. [1]
2015
75
Male
1
Cutaneous
Head, body
2.4, 1.4, 1, 0.6
EUS-FNA
No operation
NR
NR
De Moura et al. [3]
2016
58
Female
1
Ocular
Head, neck
3.1
EUS-FNA
PD
NR
NR
Nadal et al. [43]
2016
57
Female
1
Ocular
Tail
2
EUS-FNA
NR
NR
NR
Ben Slama et al. [44]
2017
55
Female
1
Unknown
Head
5.5
CT, MRI
PD
15
Alive
Liu et al. [45]
2018
54
Male
1
Cutaneous
Head
3.1
CT
PD
6
Alive
Current
2019
67
Female
1
Nasal cavity
Body
3.5
EUS-FNA
DP
24
Alive
NR not reported, PD pancreatoduodenectomy, DP distal pancreatectomy, TP total pancreatectomy, CP central pancreatectomy
Despite technological advances, preoperative diagnosis of metastatic pancreatic tumor is sometimes difficult [11]. Metastatic lesions from malignant melanoma have hypervascularity on contrast-enhanced CT and MRI [12]. The blood supply to metastatic lesions is carried from the surrounding organs; therefore, the surrounding tissue of the large lesion receives more blood supply than the central area, resulting in rim enhancement, especially in lesions larger than 1.5 cm. The same could be said in our case, as a high-attenuation rim was revealed on enhanced CT. EUS provided us with high-quality images to examine the pancreas and nearby structures. In general, pancreatic metastases on EUS have regular margins and appear as homogenous structures that are hypoechoic compared with the surrounding pancreas [13]. In our case, EUS revealed the mass to be hypoechoic and homogenous with the central anechoic areas. Few studies have reported on CE-EUS findings of pancreatic metastatic lesion. Pancreatic metastasis of renal cell carcinoma tends to show hyperenhancement, whereas malignant melanoma may or may not show hyperenhancement [1315]. The lack of characteristic findings makes diagnosis of metastatic malignant melanoma by CE-EUS difficult.
To confirm the diagnosis of pancreatic metastatic lesions, pathological examination is necessary. EUS-FNA plays an important role in providing cytological/histological diagnosis, and it is extremely useful in identifying pancreatic metastases. To distinguish pancreatic metastases from a primary carcinoma accurately, effective sampling and immunocytochemistry are needed [1, 3, 6]. EUS-FNA with rapid on-site evaluation provides effective sampling, because a cytopathologist can ensure that the samples are adequate for assessment [16]. Immunohistochemical analysis has been shown to be useful in identifying metastatic melanoma; the sensitivity of S100, Melan A, and HMB-45 are reported to be 97–100%, 75–92%, and 69–93%, respectively. The specificity of S100 and Melan A is reported to be 75–87% and 95–100%, respectively [17]. In our case, Melan A and HMB-45 were positive.
The prognosis of patients with malignant melanoma metastatic to the pancreas is unknown, although metastatic melanoma usually indicates poor prognosis [5]. There are few experiences with pancreatic resection for isolated pancreatic metastases, and pancreatic resection is controversial. Some studies have shown that complete surgical resection of a localized metastatic disease can prolong survival [5, 18]. However, Wood et al. [19] reported 28 patients with isolated pancreatic metastases from malignant melanoma and found that the 5-year survival rate of pancreatic resection (performed in 8 patients) was 37.5% (median survival, 23.8 months), as compared with 23% (median survival, 15.2 months) of the 20 patients treated with non-resection. It is critical that surgery should be performed only when a complete resection is possible. Therefore, exhaustive preoperative staging is needed to confirm both the absence of local invasion of the major vasculature and the absence of distant metastasis. PET scan has a high sensitivity and specificity for detecting metastasis from malignant melanoma [20]. In our case, PET-CT also had an important role; preoperative PET-CT identified the pancreatic tail mass, and the 6-month postoperative PET-CT showed high uptake in the left nasal cavity and peritoneum.
In conclusion, this unique case of isolated pancreatic metastasis from malignant melanoma was conclusively proven with EUS-FNA prior to the diagnosis of the primary lesion. Broad differential diagnoses should be considered when faced with inconclusive imaging studies of pancreatic tumors. In such cases, EUS-FNA is useful in providing a definitive diagnosis.

Acknowledgements

We are grateful to Dr. Hiroko Sugimoto from the Department of Pathology, Matsusaka Chuo General Hospital, Matsusaka, Mie, Japan, for helpful discussions.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest or financial arrangement with any company.

Human rights

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008(5).
Written informed consent was obtained from the patient for publication of this case report and accompanying images.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://​creativecommons.​org/​licenses/​by/​4.​0/​), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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Metadaten
Titel
Isolated pancreatic metastasis from malignant melanoma: a case report and literature review
verfasst von
Yoshifumi Nakamura
Reiko Yamada
Maki Kaneko
Hiroaki Naota
Yu Fujimura
Masami Tabata
Kazuhiko Kobayashi
Kyosuke Tanaka
Publikationsdatum
27.05.2019
Verlag
Springer Japan
Erschienen in
Clinical Journal of Gastroenterology / Ausgabe 6/2019
Print ISSN: 1865-7257
Elektronische ISSN: 1865-7265
DOI
https://doi.org/10.1007/s12328-019-00996-6

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