Figure - available via license: Creative Commons Attribution 2.0 Generic
Content may be subject to copyright.
CT scan showing enlarged head of pancreas with heterogeneous soft tissue mass measuring 5 × 5 cm. with multiple porta hepatis and paraaortic lymph nodes with no evidence of hepatic focal lesions
Source publication
Pancreatic cancer is one of the most dangerous human cancers and will continue to be a major unsolved health problem as we enter the 21(st) century. This is the case despite advances in imaging technology and surgical management. Indeed, 80% to 90% of pancreatic cancers are diagnosed either at the locally advanced or metastatic stage. Cutaneous met...
Similar publications
Sister Mary Joseph's nodule is a metastatic tumor deposit in the umbilicus and often represents advanced intra-abdominal malignancy with dismal prognosis. There is a paucity of published data on this subject in our setting. This study was conducted to describe the clinicopathological presentation and treatment outcome of this condition in our envir...
The patient was a 66-year-old woman. An induration of approximately 15 mm in size that accompanied redness was palpable in the umbilical fossa. She did not respond to 1-month antibiotic treatment provided by the previous physician. For this reason, a biopsy of the site was performed with the possibility of neoplastic disease in mind, resulting in t...
Sister Mary Joseph's nodule refers to palpable nodules bulging into the umbilicus as a result of metastasis from malignancy in the abdomen or pelvis. The most common primaries are in the gastrointestinal or genital tract, while other origins are considered rare. We recently treated a 71-year-old man who presented with painless umbilical swelling. F...
Sister Mary Joseph’s nodule refers to a palpable nodule bulging into the umbilicus as result of a malignant cancer in the abdomen or pelvis. It is associated with multiple peritoneal metastases and usually indicates an advanced stage of disease with a poor prognosis. Most cases are metastatic adenocarcinoma malignancies. The most common primary sit...
Sister Mary Joseph's periumbilical metastatic nodule is an ominous harbinger of an internal malignancy usually originating from gastrointestinal or genital system primary cancers. At the time of diagnosis, they are inoperable and therefore deemed incurable, suggesting an invariably dismal prognosis. Periumbilical neoplastic deposits from primary no...
Citations
... 4 Our understanding of the pathobiology of PC and cutaneous metastases is primarily based on single case descriptions in the literature. [6][7][8][9][10][11] The most common site of cutaneous metastasis of PC is the umbilicus, also referred to as 'Sister Mary Joseph's nodule'. 12 There is disagreement as to whether these lesions represent cutaneous or deeperseated peritoneal lesions that spread to the umbilicus. ...
... Cutaneous metastases from PC have been reported in multiple case reports in the literature. [6][7][8][9][10][11] Horino et al. reviewed 42 cases of pancreatic metastasis in the literature from 1950 to 2011, with the majority of patients presenting with umbilical cutaneous metastases and presenting predominantly with subcutaneous nodules, 19 consistent with the results from our study. Horino also noted that the incidence of umbilical metastases from cancers of the pancreatic body and tail was significantly more frequent than from the pancreatic head. ...
Background:
Cutaneous metastases in pancreatic cancer (PC) are rare. Herein, we evaluate the clinical, genomic, and other descriptors of patients with PC and cutaneous metastases.
Methods:
Institutional databases were queried, and clinical history, demographics, PC cutaneous metastasis details, and overall survival (OS) from cutaneous metastasis diagnosis were abstracted. OS was estimated using Kaplan-Meier methods.
Results:
Forty patients were identified, and median age (Q1-Q3, IQR) of PC diagnosis was 66.0 (59.3-72.3, 12.9) years. Most patients had Stage IV disease at diagnosis (n = 26, 65%). The most common location of the primary tumor was the tail of the pancreas (n = 17, 43%). The most common cutaneous metastasis site was the abdomen (n = 31, 78%), with umbilical lesions occurring in 74% (n = 23) of abdominal lesions. The median OS (95% CI) was 11.4 months (7.0, 20.4). Twenty-three patients had umbilical metastases (58%), and 17 patients had non-umbilical metastases (43%). The median OS (95% CI) was 13.7 (7.0, 28.7) months in patients with umbilical metastases and 8.9 (4.1, Not reached) months in patients with non-umbilical metastases (p = 0.1). Sixteen of 40 (40%) patients underwent somatic testing, and findings were consistent with known profiles. Germline testing in 12 (30%) patients identified pathogenic variants in patients: CHEK2, BRCA1, and ATM.
Conclusion:
Cutaneous metastases from PC most frequently arise from a pancreas tail primary site and most frequently occur in the umbilicus. Cutaneous metastases may generally be categorized as umbilical or non-umbilical metastases.
... This could be related to the tendency of tail of pancreas cancers to remain asymptomatic until the advanced stage of the disease, when distant metastasis has already occurred. In contrast, non-umbilical cutaneous metastases are more common in adenocarcinoma involving the head of the pancreas [12] -perhaps due to a predominantly different route of metastatic spread. In general, pancreatic cancers with cutaneous metastases tend to be moderately or poorly differentiated [3], possibly due to these tumor cells expressing a more aggressive, invasive phenotype [13]. ...
Umbilical metastasis [Sister Mary Joseph Nodule (SMJN)] is a rare presentation of visceral abdominal/pelvic malignancy. It is less commonly seen in metastatic pancreatic adenocarcinoma and there are only over a hundred cases to date in the literature on this topic. This article highlights a case of metastatic pancreatic adenocarcinoma presenting as SMJN and concomitant pancreatitis (which to the best of our knowledge is the first such report to date) with discussions regarding the etiopathogenesis of this phenomenon and presents a brief literature review on pancreatic adenocarcinoma presenting as SMJN.
... It is considered to be an aggressive cancer with <5% survival after 5 years [3]. Approximately 80% of patients are diagnosed with pancreatic cancer at a locally advanced or metastatic stage [4]. The response to conventional therapies, such as chemotherapy and radiotherapy, is limited and these treatments have little effect on the natural progress of this malignancy [5]. ...
Here we explore the effect of grape seed proanthocyanidins (GSPs) on pancreatic cancer cell migration and the molecular mechanisms underlying these effects. Treatment of human pancreatic cancer cell lines Miapaca-2, PANC-1 and AsPC-1 with GSPs resulted in inhibition of cell migration (19-82%, P<0.01-0.001), which was associated with decreased phosphorylation of ERK1/2 and inactivation of NF-κB. Treatment of cells with UO126, an inhibitor of MEK, and caffeic acid phenethyl ester, an inhibitor of NF-κB, also inhibited the migration of cells (40-80%, P<0.01-0.001). Inhibition of cell migration by GSPs was associated with reversal of the epithelial-to-mesenchymal transition. This was associated with upregulation of E-cadherin and desmoglein-2 and down-regulation of fibronectin, N-cadherin and vimentin.
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 Clinical Message
Herein, we present the case of a patient with pancreatic cancer and nonumbilical cutaneous metastasis. Patients with pancreatic adenocarcinomas can develop extensive cutaneous metastases involving not only abdominal skin but also other unusual sites such as the scrotum.
Background:
Tumor metastasis is driven by malignant cells and stromal cell components of the tumor microenvironment. Cancer stem cells (CSCs) are thought to be responsible for metastasis by altering the tumor microenvironment. Epithelial-mesenchymal transition (EMT) processes contribute to specific stages of the metastatic cascade, promoted by cytokines and chemokines secreted by stromal cell components in the tumor microenvironment. C-C chemokine receptor 7 (CCR7) interacts with its ligand, chemokine ligand 21(CCL21), to mediate metastasis in some cancer cells lines. This study investigated the role of CCL21/CCR7 in promoting EMT and metastasis of cluster of differentiation 133+ (CD133+) pancreatic cancer stem-like cells.
Methods:
Panc-1, AsPC-1, and MIA PaCa-2 pancreatic cancer cells were selected because of their aggressive invasive potentials. CCR7 expression levels were examined in total, CD133+ and CD133- cell fractions by Immunofluorescence analysis and real time-quantitative polymerase chain reaction (RT-qPCR). The role of CCL21/CCR7 in mediating metastasis and survival of CD133+ pancreatic cancer stem-like cells was detected by Transwell assays and flow cytometry, respectively. EMT and lymph node metastasis related markers (E-cadherin, N- cadherin, LYVE-1) were analyzed by western blot. CCR7 expression levels were analyzed by immunohistochemical staining and RT-qPCR in resected tumor tissues, metastatic lymph nodes, normal lymph nodes and adjacent normal tissues from patients with pancreatic carcinoma.
Results:
CCR7 expression was significantly increased in CD133+ pancreatic cancer stem-like cells, resected pancreatic cancer tissues, and metastatic lymph nodes, compared with CD133- cancer cells, adjacent normal tissues and normal lymph nodes, respectively. CCL21/CCR7 promoted metastasis and survival of CD133+ pancreatic cancer stem-like cells and regulated CD133+ pancreatic cancer stem-like cells metastasis by modulating EMT and Erk/NF-κB pathway.
Conclusions:
These results indicate a specific role for CCL21/CCR7 in promoting EMT and metastasis in CD133+ pancreatic cancer stem-like cells. Furthermore the data also indicated the potential importance of developing therapeutic strategies targeting cancer stem-like cells and CCL21/CCR7 for reducing metastasis.
Epithelial-to-mesenchymal transition (EMT) facilitates the escape of pancreatic cancer cells from the primary tumor site, which is a key early event in metastasis. In the present study, we examined if intermittent hypoxia facilitates the invasiveness of human pancreatic cancer cell lines (Panc-1 and BxPC-3) by Transwell assay. We used western blotting and flow cytometry analysis to quantify stem-like cells in the migratory cells during intermittent hypoxia in the human pancreatic cancer cells. Under normoxia or intermittent hypoxia, the expression of autophagy-related proteins (LC3-II and Beclin), hypoxia-inducible factor-1α (HIF-1α) and EMT-related markers (E-cadherin, Vimentin and N-cadherin) was examined by western blotting. siRNA and the autophagic inhibitor were used to access the role of HIF-1α and autophagy in promoting metastasis and EMT. Under intermittent hypoxia, pancreatic cancer cells demonstrated enhanced invasive ability and enriched stem-like cells. The migratory cells displayed stem-like cell characteristics and elevated the expression of LC3-II and Beclin-1, HIF-1α, E-cadherin, Vimentin and N-cadherin under intermittent hypoxia conditions. Moreover, enhanced autophagy was induced by the elevated level of HIF-1α. The metastatic ability and EMT of pancreatic cancer stem cells was associated with HIF-1α and autophagy. This novel finding may indicate the specific role of HIF-1α and autophagy in promoting the metastatic ability of pancreatic cancer stem cells. Additionally, it emphasizes the importance of developing therapeutic strategies targeting cancer stem cells and autophagy to reduce metastasis.
With an overall mortality approaching nearly 100 %, pancreatic cancer is still a challenging disease. A major proportion of pancreatic cancers are still diagnosed at the locally advanced or metastatic stage. Tumors originating from tail region present very late due to the absence of specific symptoms and signs. The usual sites of metastases are the liver, peritoneum and lungs, with occasional reports of metastases in other sites. There are very few documented cases of gastrointestinal cancers manifesting as metastases to muscle. This is a report on a case of pancreatic cancer presenting as metastases to skeletal muscle and multiple other viscera and review of literature for pancreatic cancer metastases.
Pancreatic adenocarcinoma is one of the deadliest human malignancies with the majority of cases diagnosed late in the course of the disease. Cutaneous metastases originating from pancreatic cancer are rare. The most common site reported is the umbilicus. Non-umbilical cutaneous metastases are far less common with only a few cases reported in the literature. Our case involved a 43-year-old man with pancreatic carcinoma who was offered resection and a Whipple procedure was planned. Intraoperatively, the patient was found to have a widely metastatic disease not seen on preoperative imaging. Postoperatively, cutaneous metastasis in the scalp was discovered. Although rare, the recognition of non-umbilical cutaneous metastases of pancreatic adenocarcinoma can be of value because they can not only detect an underlying tumour but also guide management.
