Papillary‐cystic tumor of the pancreas in a young woman: Fine‐needle aspiration cytology, ultrastructure and DNA analysis

Skarda, Janet S.; Honick, Arnold B.; Gibbins, Carl; Josselson, Arnold R.; Rishi, Mazhar

doi:10.1002/dc.2840100106

Cited by 18 publications

(11 citation statements)

References 15 publications

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“…Pancreatic cancer cells have been reported to show prominent ER (Klimstra et al, 1992;Skarda et al, 1994). Here, we report for the first time that edelfosine accumulates in the ER of human pancreatic cancer cells and triggers a prolonged ER stress response, leading to apoptosis.…”

Section: Discussionmentioning

confidence: 51%

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Antitumor alkyl-lysophospholipid analog edelfosine induces apoptosis in pancreatic cancer by targeting endoplasmic reticulum

et al. 2011

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Pancreatic cancer remains as one of the most deadly cancers, and responds poorly to current therapies. The prognosis is extremely poor, with a 5-year survival of less than 5%. Therefore, search for new effective therapeutic drugs is of pivotal need and urgency to improve treatment of this incurable malignancy. Synthetic alkyl-lysophospholipid analogs (ALPs) constitute a heterogeneous group of unnatural lipids that promote apoptosis in a wide variety of tumor cells. In this study, we found that the anticancer drug edelfosine was the most potent ALP in killing human pancreatic cancer cells, targeting endoplasmic reticulum (ER). Edelfosine was taken up in significant amounts by pancreatic cancer cells and induced caspaseand mitochondrial-mediated apoptosis. Pancreatic cancer cells show a prominent ER and edelfosine accumulated in this subcellular structure, inducing a potent ER stress response, with caspase-4, BAP31 and c-Jun NH 2 -terminal kinase (JNK) activation, CHOP/GADD153 upregulation and phosphorylation of eukaryotic translation initiation factor 2 a-subunit that eventually led to cell death. Oral administration of edelfosine in xenograft mouse models of pancreatic cancer induced a significant regression in tumor growth and an increase in apoptotic index, as assessed by TUNEL assay and caspase-3 activation in the tumor sections. The ER stress-associated marker CHOP/ GADD153 was visualized in the pancreatic tumor isolated from edelfosine-treated mice, indicating a strong in vivo ER stress response. These results suggest that edelfosine exerts its pro-apoptotic action in pancreatic cancer cells, both in vitro and in vivo, through its accumulation in the ER, which leads to ER stress and apoptosis. Thus, we propose that the ER could be a key target in pancreatic cancer, and edelfosine may constitute a prototype for the development of a new class of antitumor drugs targeting the ER.

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Section: Discussionmentioning

confidence: 51%

“…Because the pancreatic cancer cells show prominent ER (Klimstra et al, 1992;Skarda et al, 1994), we wondered whether edelfosine might be active against pancreatic cancer by targeting ER. Hence, we investigated the in vitro and in vivo action of edelfosine on pancreatic cancer as well as its mechanism of action.…”

Section: Introductionmentioning

confidence: 99%

Antitumor alkyl-lysophospholipid analog edelfosine induces apoptosis in pancreatic cancer by targeting endoplasmic reticulum

et al. 2011

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“…In contrast, the nuclear appearance of SCT has been characterized by finely granular and evenly distributed chromatin. 3,5,6,8,9,15,18,20,22 It follows that the chromatin pattern may be useful for the discrimination of SCT from islet cell tumor. Although SCT is known to have less or no nuclear atypia, a prominent nuclear groove, as well as hyperchromatic giant cells, was observed in case 3.…”

Section: Discussionmentioning

confidence: 99%

“…Ultrastructural features of SCT have been reported as the presence of abundant mitochondria and/or prominent endoplasmic reticulum. 6,[10][11][12][13]15,17,18,20 Furthermore, zymogenlike granules have been observed ultrastructurally in some cases of SCT, suggesting that the cells differentiate to or derive from acinar cells of the pancreas. 6,10,12 Some other authors 13,18,20 have described not only zymogenlike granules but also neurosecretory granules in certain cases of SCT, indicative of endocrine derivation of the tumor.…”

Section: Discussionmentioning

confidence: 99%

“…To date, several investigators have described the cytologic features of SCT as papillary clusters composed of uniform tumor cells lacking apparent nuclear atypia. 3,5,6,8,9,15,18,20,22 In the present study, cytologic features and histologic, immunohistochemical and ultrastructural characteristics of SCT were reported for four cases, including a case with some degree of nuclear atypia. Furthermore, these cytologic features of SCT were compared with those of islet cell tumor of the pancreas, which resembles SCT histologically and cytologically.…”

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confidence: 99%

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Cytologic Features of Solid and Cystic Tumor of the Pancreas

Kashima

Hayashida²,

Yokoyama³

et al. 1997

Acta Cytologica

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Solid‐pseudopapillary tumor of the pancreas: A neoplasm with distinct and highly characteristic cytological features

Pettinato

Vizio

Manivel

et al. 2002

Diagnostic Cytopathology

122

108

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The solid-pseudopapillary tumor of the pancreas (SPTP) is an unusual low-grade malignant epithelial tumor affecting predominantly adolescent girls and young women. Although approximately 500 cases of SPTP have been described in the last 40 yr, its pathogenesis remains uncertain. However, the clinical features of this neoplasm are very characteristic and SPTP must be suspected in any young woman with a cystic or partially cystic pancreatic mass. In this report, we describe the cytologic features of seven cases of SPTP investigated by preoperative fine-needle aspirates. The analysis of the cytologic features in these cases and in 43 cases collected from the literature reveals that they are highly characteristic and quite distinct from those of other cystic or solid tumors of the pancreas. On this basis, a cytologic diagnosis of SPTP may be rendered with great confidence, not only in clinically typical examples, but also in unusual presentations, such as in older patients, in males, in ectopic locations, and in metastatic sites.

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Papillary‐cystic tumor of the pancreas in a young woman: Fine‐needle aspiration cytology, ultrastructure and DNA analysis

Cited by 18 publications

References 15 publications

Antitumor alkyl-lysophospholipid analog edelfosine induces apoptosis in pancreatic cancer by targeting endoplasmic reticulum

Antitumor alkyl-lysophospholipid analog edelfosine induces apoptosis in pancreatic cancer by targeting endoplasmic reticulum

Cytologic Features of Solid and Cystic Tumor of the Pancreas

Solid‐pseudopapillary tumor of the pancreas: A neoplasm with distinct and highly characteristic cytological features

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