Case Report Open Access
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Nov 15, 2020; 12(11): 1372-1380
Published online Nov 15, 2020. doi: 10.4251/wjgo.v12.i11.1372
Cutaneous metastases of pancreatic carcinoma to the labia majora: A case report and review of literature
Ying Shi, Yan Yu, Department of Dermatology, First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Shan-Shan Li, Department of Dermatology and Venereology, First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Dan-Yan Liu, Department of Radiology, First Hospital of Jilin University, Changchun 130021, Jilin Province, China
ORCID number: Ying Shi (0000-0002-3249-6632); Shan-Shan Li (0000-0001-5745-7835); Dan-Yan Liu (0000-0001-5631-6387); Yan Yu (0000-0003-1227-7448).
Author contributions: All authors contributed equally to this paper with the conception and design of the study, literature review and analysis, manuscript drafting, critical revision, and editing, and approval of the final version.
Informed consent statement: Informed consent was obtained from the patient.
Conflict-of-interest statement: All the authors are aware of the content of the manuscript and have no conflict of interest to disclose.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yan Yu, MD, Chief Doctor, Department of Dermatology, First Hospital of Jilin University, No. 71 Xinmin Street, Changchun 130021, Jilin Province, China. yuyan741206@126.com
Received: August 12, 2020
Peer-review started: August 12, 2020
First decision: September 16, 2020
Revised: September 29, 2020
Accepted: October 19, 2020
Article in press: October 19, 2020
Published online: November 15, 2020

Abstract
BACKGROUND

Cutaneous metastases originating from pancreatic cancer are relatively rare. The most common reported site of metastasis is the umbilicus, and this manifestation is known as the Sister Mary Joseph’s nodule. Non-umbilical cutaneous metastases are far less common, with only a few cases reported in the literature. Our case is the first case report, to our knowledge, on metastasis involving the labia majora and flat papules.

CASE SUMMARY

A 49-year-old Chinese female patient presented with a number of red, swollen papules on the vulva for 2 mo. Histological examination of the labia majora lesion revealed metastatic adenocarcinoma. The serum levels of tumor biomarkers CA199, CA242, and CA125 were significantly elevated. B-mode ultrasound-guided needle biopsy of the pancreas demonstrated moderately and poorly differentiated adenocarcinoma. The patient finally declined treatment for financial reasons and died 3 mo later.

CONCLUSION

Metastatic cutaneous lesions could indicate pancreatic cancer. Serum levels of tumor biomarkers may aid in diagnosing metastatic pancreatic adenocarcinoma.

Key Words: Pancreatic cancer, Cutaneous, Metastasis, Non-umbilical, Biomarker, Case report

Core Tip: Cutaneous metastasis from pancreatic cancer is uncommon. The most common site of the skin lesion is the umbilicus. The majority of skin lesions are singular, particularly in patients exhibiting the Sister Mary Joseph’s nodule. We describe an unusual case of flat papules on the labia majora that metastasized from pancreatic cancer. The lesion was the first sign of metastatic disease, and serum levels of CA199, CA242, and CA125 were also elevated. We report this case to improve the understanding of cutaneous metastasis of pancreatic cancer and emphasize the importance of serum levels of CA199, CA242, and CA125 in diagnosing pancreatic cancer.



INTRODUCTION

Pancreatic cancer is one of the most lethal human malignancies and is often diagnosed late in the course of the disease. Cutaneous metastases originating from pancreatic cancer are relatively rare. The most common reported site of metastasis is the umbilicus, and this manifestation is known as the Sister Mary Joseph’s nodule. Non-umbilical cutaneous metastases are far less common, with only a few cases reported in the literature. To our knowledge, there are no previous reports on metastasis involving the labia majora and flat papules. This report describes a case of cutaneous pancreatic metastases on the labia majora in a Chinese woman, and a review of previously reported non-umbilical cutaneous pancreatic carcinoma metastases (by conducting a detailed PubMed search). Furthermore, an analysis of 34 reported cases of non-umbilical cutaneous metastasis from pancreatic cancer was conducted with regard to the clinical characteristics.

CASE PRESENTATION
Chief complaints

A 49-year-old female patient with a number of red, swollen papules on the vulva for 2 mo was referred to our department.

History of present illness

The patient had developed red, swollen papules on the vulva 3 mo previously. She attended a local hospital, where she was diagnosed with contact dermatitis and took regular anti-allergy treatment. There was no obvious improvement in her symptoms. Erythema gradually affected the abdomen and lower extremities. The patient had experienced intermittent shortness of breath and coughed up white sputum during this period.

History of past illness

The patient had experienced hypertension for 2 years and had a history of sulfonamide allergy.

Personal and family history

There was not a personal or family history of pancreatic cancer.

Physical examination

Physical examination revealed diffuse erythema and swelling on the chest, abdomen, and vulva; right leg edema; and a number of flat skin-colored or gray papules on the labia majora (Figure 1).

Figure 1
Figure 1 Photographs of our patient. A: Diffuse erythema and swelling on the chest, abdomen, and right leg; B: Edema and a number of flat skin-colored or gray papules on the labia majora.
Laboratory examinations

Routine laboratory testing revealed that the patient was human immunodeficiency virus (HIV) negative; the results of blood and urine tests and levels of renal and hepatic markers and antinuclear antibodies were within the normal ranges. There was a remarkable elevation in the serum concentrations of tumor markers, comprising cytokeratin 19 (8.98 g/L; normal: < 5 µg/L), CA242 (> 500 U/mL; normal: < 20 U/mL), CA125 (52.41 U/mL; normal: < 35 U/mL), and CA199 (726.54 U/mL; normal: < 37 U/mL).

Imaging examinations

An ultrasound scan showed bilateral mammary gland hyperplasia, no other gynecological abnormalities, and right leg lymphedema. A chest computerized tomography (CT) scan revealed inflammation, with patterns of interstitial change scattered across both lungs and a little pleural effusion in the left lung. An abdominal CT scan demonstrated many enlarged lymph nodes, associated with the abdominal aorta, bilateral iliac artery, and bilateral inguinal region, as well as changes in the pancreatic and peripancreatic morphology. A positron emission tomography (PET)-CT scan showed increased metabolic activity in the tail of the pancreas and multiple enlarged lymph nodes throughout the body, as well as subcutaneous tissue edema (Figure 2).

Figure 2
Figure 2 Positron emission tomography-computed tomography scan showing increased metabolic activity. A: The tail of the pancreas; B: Mediastinum, hilus of the lung, and postperitoneal lymph nodes.
Further diagnostic work-up

A punch biopsy was performed on the abdomen and labia majora lesions. The abdominal epidermis was normal, and there were dilated small blood vessels and lymph vessels in the dermis, and small quantities of infiltrating lymphocytes. Histological examination of the labia majora papules showed nests of moderately differentiated atypical cells partly forming adenomatous structures in the collagen bundles of the dermis and lymphangiectasia (pathologic dilation of the lymph vessels) in the dermis (Figure 3). The immunohistochemical staining results (Figure 4) were as follows: CK7 (+), panCK (+), CK19 (+), CA19-9 (+), CDX-2 (+), CK20 (+), D2-40 (-), and P63 (-), which is consistent with a possible pancreatic source of the metastasis.

Figure 3
Figure 3 Pathology of cutaneous metastasis. A: Histological examination of the labia majora papule showing nests of moderately differentiated atypical cells partly forming adenomatous structures in the collagen bundle of the dermis and lymphangiectasis in the dermis [hematoxylin-eosin (HE) staining, × 40]; B: Dermis occupied by mass of numerous tumor cells (HE staining, × 200).
Figure 4
Figure 4 Neoplastic glands showing a positive reaction to immunohistochemical staining (100 ×). A: CK7 (+); B: panCK (+); C: CK19 (+); D: CA199 (+); E: CK20 (+); F: CDX-2 (+).

In addition, a large amount of milky fluid was drained from the skin biopsy sites. While the serum triglyceride level was normal, the level in the fluid was 1.55 mmol/L, indicating lymphocytosis. Neither bacteria (including Mycobacterium tuberculosis) nor fungi were found in the fluid. According to the laboratory and histopathologic findings, a diagnosis of chylous reflux fluid was made.

Thereafter, B-mode ultrasound-guided needle biopsy of the pancreas demonstrated moderately and poorly differentiated adenocarcinoma (Figure 5).

Figure 5
Figure 5 B-mode ultrasound-guided needle biopsy of the pancreas showing the moderately and poorly differentiated adenocarcinoma (hematoxylin-eosin staining, × 200).
FINAL DIAGNOSIS

According to the clinical manifestations and histopathologic findings, a diagnosis of metastatic pancreatic carcinoma was established.

TREATMENT

The patient declined treatment for financial reasons.

OUTCOME AND FOLLOW-UP

The patient died 3 mo later.

DISCUSSION

Cutaneous metastases are rare, occurring in 0.7%-9.0% of all patients with cancer[1]. Breast, lung, and colon cancer are the most frequent origins of cutaneous metastases.

Pancreatic cancer is one of the most lethal cancers, with a 5 year survival rate of 5%. Owing to a lack of early clinical features and the fulminant disease course, early diagnosis is difficult and the metastasis rate is high, with a median overall survival of 5 mo[2]. Pancreatic cancer is often known to metastasize via the lymphatic system, with direct invasion at an early stage and hematogenous dissemination at a later stage. The incidence of cutaneous metastases is significantly more frequent for cancers of the pancreatic body and tail than for pancreatic head cancer[3].

The most frequent organs involved in the metastasis are the liver, peritoneum, lungs, bones, and brain[2]. Indeed, only 2% of the first metastases from pancreatic cancer are cutaneous metastases, making cutaneous metastases relatively rare[4]. The most common site of cutaneous metastasis from the pancreas is the umbilicus, and this manifestation is known as Sister Mary Joseph’s nodule[5]. Horino et al[6] reviewed 42 reported cases of pancreatic metastasis from 1950 to 2011, and included only 14 cases of non-umbilical cutaneous metastasis, involving the head, neck, and truncal region. The patients with pancreatic metastasis had such symptoms as subcutaneous nodules (in 26 patients) and inflammatory erythema (in 3 patients).

We collected all case reports of non-umbilical metastatic skin cancer from 1950 to 2020 on the electronic PubMed database (www.ncbi.nlm.nih.gov/pubmed; up to July 2020) by searching using Medical Subject Headings (www.nlm.nih. gov/mesh) and keywords, and by limiting the search to human studies (Table 1)[1-4,6-30]. The terms pancreatic cancer, pancreatic neoplasm, pancreatic carcinoma, cutaneous metastasis, and skin metastasis were used. The abstracts were reviewed, and articles that were associated with umbilical metastasis were excluded. Duplicate references as well as repeated publications were discarded. All of the studies that were considered to be eligible were retrieved and the final selection was based on the full article.

Table 1 Review of case reports of nonumbilical cutaneous metastasis from pancreatic cancer.

Ref.
Age (yr)
Sex
Appearance
Metastatic site
Primary
Year
1Edelstein et al[10]60MCellulitisFace, neckNA1950
2Sakai et al47MHerpes zoster-likeNo detailsHead1969
3Sironi et al[12]72MNoduleRight thighHead1991
4Lookingbill et al[13]No detailsNo detailsNoduleAbdomenNo details1993
5Taniguchi et al[4]63FErythematousplaques, noduleLeft axilla, chestNo details1994
6Ohashi et al79MNoduleNeck, chest, abdomenNo details1995
7Ohashi et al65MNoduleBackNo details1995
8Fukui et al49MNoduleFace, chestNo details1995
9Puri et al[14]45MNoduleScalp, face, neck, backNo details1995
10Nakano et al[15]80MNoduleOccipital scalpTail1996
11Miyahara et al[16]43MNoduleScalpUncus1996
12Miyahara et al[16]65MNoduleMentumUncus1996
13Horino et al[17]65FNoduleChest wallHead1999
14Flórez et al[18]48MNoduleButtockHead2000
15Gawrieh et al[19]45FNoduleTemporal scalpNo details2002
16Takeuchi et al[3]77MNoduleLeft axillaTail2003
17Otegbayo et al[20]59MNoduleFace, chest, abdomen, backNo details2005
18Jun et al[21]68MNoduleRight forearm, chestBody, tail2005
19Ambro et al[22]63MNoduleScalpDuctal2006
20Takemura et al[23]85MNoduleLeft templeNo details2007
21Hafez et al[24]55FNoduleNeckHead2008
22Kimura et al50MNoduleLateral abdomenBody2008
23van Akkooi et al[25]59MNoduleScalpNo details2010
24Bdeiri et al[1]59FNoduleScalpTail2010
25Pontinen et al[26]67FNoduleLower abdomenTail2010
26Saif et al[27]46FNoduleChest, abdomen, right supraclavicular areaNo details2011
27Horino et al[6]58FNoduleLower abdomenBody2012
28Horino et al[6]65FNoduleLower abdomenTail2012
29Bdeiri et al[1]70FNoduleScalpTail2013
30Kaoutzanis et al[28]43MNoduleScalpHead2013
31Zhou et al[2]76FNoduleScalp, chest, abdomenTail2014
32Shin et al[29]60MMassLeft hipBody2015
33Kotsantis et al[11]62MEdemaScrotum, trunk, chest wallHead2017
34Ito et al[30]71FUlcerScalpTail2020

Our case is unique in that the cutaneous pancreatic cancer metastases were found on the labia majora. Our patient had papules on the labia majora, with diffuse swelling on the skin of the chest, abdomen, and vulva. In addition, there was oozing of chyle from the skin biopsy sites.

Chyle originates in the bowel lacteals (lymphatic capillaries that absorb dietary fats), is absorbed by the intestinal lymphatic vessels, passes through the collecting lymphatic vessels into the intestinal trunk (truncus intestinalis), and then passes through the cisterna chyli and thoracic duct to the bloodstream. If the reflux is obstructed, chylous reflux occurs; the chyle flows backward or leaks into the serosal cavity, external genitalia, lower limbs, etc. Chylous reflux is divided into primary and secondary types. Secondary chylous reflux is usually caused by neoplasia, trauma, inflammation, or surgery[7]. According to the PET-CT scan, the metastatic cancer cells may have traveled to the labia majora via the lymphatic pathways. The abnormal lymphatic system, caused by tumor metastasis, may have been the underlying cause for the backflow of chyle to the skin. The patient was advised to undergo lymphangiography to confirm this, but declined for financial reasons.

The serum levels of tumor biomarkers CA199, CA242, and CA125 were significantly elevated in our case. It has been shown that the sensitivity and specificity of CA199 for diagnosing pancreatic cancer are 77% and 88%, respectively. Ozkan et al[8] revealed that CA242 was significantly increased in 75% of pancreatic cancer patients. To sum up, Mao et al[9] suggested that assessment of the combination of CA199, CA242, CEA, and CA125 levels is a simple, noninvasive, and effective method for early diagnosis of pancreatic cancer.

We present a case of pancreatic adenocarcinoma metastasizing to the vulva, with a number of flat papules. This condition is extremely rare and easy to misdiagnose.

CONCLUSION

Cutaneous metastasis from pancreatic carcinoma is a rare finding and mostly occurs around the umbilicus. Subcutaneous nodules are the most common clinical manifestation. To our knowledge, we describe the first case of cutaneous pancreatic metastasis to the vulva, with a number of flat papules. Clinicians should be aware of the possibility of metastatic cutaneous lesions in pancreatic adenocarcinoma and screen for tumor markers as promptly as possible.

Footnotes

Manuscript source: Unsolicited manuscript

Specialty type: Oncology

Country/Territory of origin: China

Peer-review report’s scientific quality classification

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P-Reviewer: Buanes T S-Editor: Gao CC L-Editor: Wang TQ P-Editor: Li JH

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