|
1
|
Choi JH, Thung SN. Recent Advances in Pathology of Intrahepatic Cholangiocarcinoma. Cancers (Basel) 2024; 16:1537. [PMID: 38672619 PMCID: PMC11048541 DOI: 10.3390/cancers16081537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 04/10/2024] [Accepted: 04/16/2024] [Indexed: 04/28/2024] Open
Abstract
Intrahepatic cholangiocarcinoma (ICCA) is a malignant epithelial neoplasm characterized by biliary differentiation within the liver. ICCA is molecularly heterogeneous and exhibits a broad spectrum of histopathological features. It is a highly aggressive carcinoma with high mortality and poor survival rates. ICCAs are classified into two main subtypes: the small-duct type and large-duct types. These two tumor types have different cell origins and clinicopathological features. ICCAs are characterized by numerous molecular alterations, including mutations in KRAS, TP53, IDH1/2, ARID1A, BAP1, BRAF, SAMD4, and EGFR, and FGFR2 fusion. Two main molecular subtypes-inflammation and proliferation-have been proposed. Recent advances in high-throughput assays using next-generation sequencing have improved our understanding of ICCA pathogenesis and molecular genetics. The diagnosis of ICCA poses a significant challenge for pathologists because of its varied morphologies and phenotypes. Accurate diagnosis of ICCA is essential for effective patient management and prognostic determination. This article provides an updated overview of ICCA pathology, focusing particularly on molecular features, histological subtypes, and diagnostic approaches.
Collapse
Affiliation(s)
- Joon Hyuk Choi
- Department of Pathology, Yeungnam University College of Medicine, Daegu 42415, Republic of Korea
| | - Swan N. Thung
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, New York, NY 10029, USA;
| |
Collapse
|
|
2
|
Wei YY, Li Y, Shi YJ, Li XT, Sun YS. Primary extra-pancreatic pancreatic-type acinar cell carcinoma in the right perinephric space: A case report and review of literature. World J Clin Cases 2021; 9:5637-5646. [PMID: 34307619 PMCID: PMC8281426 DOI: 10.12998/wjcc.v9.i20.5637] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 03/30/2021] [Accepted: 05/20/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Primary extra-pancreatic pancreatic-type acinar cell carcinoma (ACC) is a rare malignancy, and has only been reported in the gastrointestinal tract, liver, and lymph nodes until now. Extra-pancreatic pancreatic-type ACC in the perinephric space has not been reported. Herein, we report the first case of ACC in the perinephric space and describe its clinical and imaging features, which should be considered when differentiating perinephric space neoplasms.
CASE SUMMARY A 48-year-old man with a 5-year history of hypertension was incidentally found to have an asymptomatic right retroperitoneal mass during a routine health check-up. Laboratory tests were normal. Abdominal computed tomography and magnetic resonance imaging showed an oval hypervascular mass with a central scar and enhanced capsule in the right perinephric space. After surgical resection of the neoplasm, the diagnosis was primary extra-pancreatic pancreatic-type ACC. The patient was alive without recurrence or metastasis during a 15-mo follow-up.
CONCLUSION This is the first report of an extra-pancreatic ACC in right perinephric space, which should be considered as a possible diagnosis in perinephric tumors.
Collapse
Affiliation(s)
- Yi-Yuan Wei
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Ying Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Yan-Jie Shi
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Xiao-Ting Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Ying-Shi Sun
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| |
Collapse
|
|
3
|
Cazacu IM, Luzuriaga Chavez AA, Nogueras Gonzalez GM, Saftoiu A, Bhutani MS. Malignant Transformation of Ectopic Pancreas. Dig Dis Sci 2019; 64:655-668. [PMID: 30415408 DOI: 10.1007/s10620-018-5366-z] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2018] [Accepted: 11/01/2018] [Indexed: 02/07/2023]
Abstract
Malignant transformation of ectopic pancreas tissue is a diagnostic challenge as clinical symptoms and radiographic features of these tumors are non-specific. Given the rarity of these lesions, it is usually neither suspected nor included in the diagnostic workup of different tumors. We conducted a comprehensive literature review regarding malignancy arising from ectopic pancreas for a better understanding of its frequency, clinicopathological features, and prognosis. A literature search was performed in three major databases: PubMed, Cochrane, and Web of Science. Fifty-four well-documented cases of malignant ectopic pancreas were identified in the published literature. Our analysis provided the following observations: (1) there was a slight predominance of males over females; (2) most patients with malignant transformation of ectopic pancreas were middle-aged; (3) most commonly, the tumor was located in the stomach; (4) most tumors were adenocarcinomas; (5) most frequently, the malignancy arose within a type I heterotopia according to Heinrich classification; (6) macroscopically, a subepithelial-like appearance was most frequently observed; and (7) improved prognosis for ectopic pancreatic malignancies in comparison with reported survival data for orthotopic pancreatic cancer. Even if the majority of cases of ectopic pancreas are incidental findings and malignant transformation is a rare event, pancreatic heterotopy should be considered as a source of potentially malignant lesions.
Collapse
Affiliation(s)
- Irina M Cazacu
- Department of Gastroenterology, Hepatology, and Nutrition, University of Texas - MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030-4009, USA
| | - Adriana Alexandra Luzuriaga Chavez
- Department of Gastroenterology, Hepatology, and Nutrition, University of Texas - MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030-4009, USA
| | - Graciela M Nogueras Gonzalez
- Department of Biomathematics and Biostatistics, University of Texas - MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030-4009, USA
| | - Adrian Saftoiu
- Department of Gastroenterology, Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy Craiova, 66 1 Mai Blvd., 200638, Craiova, Romania
| | - Manoop S Bhutani
- Department of Gastroenterology, Hepatology, and Nutrition, University of Texas - MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030-4009, USA.
| |
Collapse
|
|
4
|
Ohara Y, Oda T, Enomoto T, Hisakura K, Akashi Y, Ogawa K, Owada Y, Domoto Y, Miyazaki Y, Shimomura O, Kurata M, Ohkohchi N. Surgical resection of hepatic and rectal metastases of pancreatic acinar cell carcinoma (PACC): a case report. World J Surg Oncol 2018; 16:158. [PMID: 30075727 PMCID: PMC6091145 DOI: 10.1186/s12957-018-1457-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Accepted: 07/26/2018] [Indexed: 02/07/2023] Open
Abstract
Background Pancreatic acinar cell carcinoma (PACC), a rare variant of pancreatic malignancy, is generally managed the same way as pancreatic ductal adenocarcinoma (PDAC). Surgical resection is the gateway to curing it; however, once it metastasizes (usually to the liver, lungs, lymph nodes, or peritoneal cavity), systemic chemotherapy has been the only option, but with unfavorable results. Case presentation A 67-year-old man with symptoms of loss of appetite and weight underwent surgery for malignancy of the pancreatic tail extending into the entire pancreas. The pathological diagnosis was PACC following total pancreatectomy. Twenty-four months after the pancreatectomy, a solitary liver metastasis was treated by partial hepatectomy, and, subsequently, 4 months later, he presented with melena. Further examination revealed a type-2 rectal tumor. Histological examination following biopsy revealed it to be rectal metastasis of PACC, and it was treated by abdominoperineal resection. Subsequently, the patient did not have tumor recurrence as of 40 months after pancreatectomy. Conclusions This is a rare case of PACC presenting with metachronal metastases in the liver and rectum, and we successfully treated them by surgical resections. Since the malignant behavior of PACC is usually less than that of PDAC, surgical resection could be an option even for metastatic lesions when the number and extent of metastases are limited.
Collapse
Affiliation(s)
- Yusuke Ohara
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Tatsuya Oda
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
| | - Tsuyoshi Enomoto
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Katsuji Hisakura
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Yoshimasa Akashi
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Koichi Ogawa
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Yohei Owada
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Yu Domoto
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Yoshihiro Miyazaki
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Osamu Shimomura
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Masanao Kurata
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Nobuhiro Ohkohchi
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| |
Collapse
|
|
5
|
Takagi K, Yagi T, Tanaka T, Umeda Y, Yoshida R, Nobuoka D, Kuise T, Fujiwara T. Primary pancreatic-type acinar cell carcinoma of the jejunum with tumor thrombus extending into the mesenteric venous system: a case report and literature review. BMC Surg 2017; 17:75. [PMID: 28662660 PMCID: PMC5492367 DOI: 10.1186/s12893-017-0273-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2017] [Accepted: 06/26/2017] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Although ectopic pancreatic tissue is common in the upper gastrointestinal tract, the incidence of ectopic pancreatic tissue in the jejunum is low, and malignant transformation in ectopic pancreatic tissue is rare. Furthermore, pancreatic-type acinar cell carcinoma (ACC) developing in the jejunum and ACC accompanied by tumor thrombus are extremely rare. CASE PRESENTATION A 78-year-old-woman presented with melena. Abdominal computed tomography images and endoscopic examination revealed a submucosal jejunal mass with tumor thrombus extending into a jejunal vein. The patient underwent a curative resection combined with a partial jejunectomy and partial pancreatectomy. Histopathological examination of the resected tissue showed tumor cells with a homogeneous acinar architecture identical to pancreatic-type ACC and tumor thrombus. Postoperatively, she was followed for 10 months and had no recurrence. CONCLUSION We present an extremely rare case of pancreatic-type ACC in the jejunum with extensive tumor thrombus invading into the mesenteric venous system. This type of cancer has not been reported previously but should be considered in the differential diagnosis of a jejunal mass.
Collapse
Affiliation(s)
- Kosei Takagi
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558 Japan
| | - Takahito Yagi
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558 Japan
| | - Takehiro Tanaka
- Department of Diagnostic Pathology, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558 Japan
| | - Yuzo Umeda
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558 Japan
| | - Ryuichi Yoshida
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558 Japan
| | - Daisuke Nobuoka
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558 Japan
| | - Takashi Kuise
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558 Japan
| | - Toshiyoshi Fujiwara
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558 Japan
| |
Collapse
|
|
6
|
Kanayama K, Imai H, Yoneda M, Hayashi A, Hirokawa YS, Shiraishi T. Cytological findings of an ectopic pancreas of the stomach obtained at endoscopic ultrasound-guided fine needle aspiration, differential diagnosis from acinar cell carcinoma: a case report. Cytopathology 2016; 27:379-81. [PMID: 26786071 DOI: 10.1111/cyt.12302] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/28/2015] [Indexed: 12/12/2022]
Affiliation(s)
- K Kanayama
- Department of Oncologic Pathology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
| | - H Imai
- Department of Oncologic Pathology, Mie University Graduate School of Medicine, Tsu, Mie, Japan
| | - M Yoneda
- Department of Clinical Nutrition, Suzuka University of Medical Science, Suzuka, Mie, Japan
| | - A Hayashi
- Department of Oncologic Pathology, Mie University Graduate School of Medicine, Tsu, Mie, Japan
| | - Y S Hirokawa
- Department of Oncologic Pathology, Mie University Graduate School of Medicine, Tsu, Mie, Japan
| | - T Shiraishi
- Department of Oncologic Pathology, Mie University Graduate School of Medicine, Tsu, Mie, Japan
| |
Collapse
|
|
7
|
Abstract
Acinar cell carcinoma is an uncommon carcinoma of the exocrine pancreas. On very rare occasions it has been reported in ectopic sites, sometimes with, but usually without contiguous heterotopic pancreatic tissue. Whilst mixed and composite glandular tumours have also been described, pure pancreatic-type acinar cell carcinomas arising in the stomach are very rare.
Collapse
|
|
8
|
Terris B, Genevay M, Rouquette A, Audebourg A, Mentha G, Dousset B, Rubbia-Brandt L. Acinar cell carcinoma: a possible diagnosis in patients without intrapancreatic tumour. Dig Liver Dis 2011; 43:971-4. [PMID: 21893434 DOI: 10.1016/j.dld.2011.07.013] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2011] [Revised: 07/14/2011] [Accepted: 07/22/2011] [Indexed: 12/11/2022]
Abstract
BACKGROUND Acinar cell carcinomas of the pancreas are rare neoplasms. Usually diagnosed at an advanced stage, in general they are large solid pancreatic tumours with an average size of more than 10 cm. AIMS AND RESULTS We report 3 cases of acinar cell carcinomas involving the peripancreatic lymph nodes, the liver hilum and the colon respectively, without clinical or pathological evidence of pancreatic tumours. These highly cellular neoplasms showed a predominantly acinar cell differentiation intermingled with a ductal component, with intracellular or extracellular mucin production by at least 25% of tumour cells. In addition, one case showed endocrine differentiation. Diffuse immunoreactivity for acinar enzymes trypsin and chymotrypsin was present in all cases. CONCLUSION The occurrence of acinar cell carcinomas outside the pancreas underlines the notion that acinar cell carcinomas may originate in extrapancreatic sites and probably develop from heterotopic or metaplastic pancreatic foci present along the biliary tract.
Collapse
Affiliation(s)
- Benoît Terris
- Service d'Anatomie et Cytologie Pathologiques, Hôpital Cochin, Université Paris Descartes, Paris, France.
| | | | | | | | | | | | | |
Collapse
|
|
9
|
Pancreatic-type acinar cell carcinoma of the liver: a clinicopathologic study of four patients. Mod Pathol 2011; 24:1620-6. [PMID: 21841771 DOI: 10.1038/modpathol.2011.127] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Acinar cell carcinoma of pancreatic type rarely occurs at extra-pancreatic sites. We report four primary liver tumors with features of pancreatic acinar cell carcinoma. The patients were two males and two females with a mean age of 65 years (range, 49-72 years). They had upper abdominal pain, weight loss and/or an incidentally discovered liver mass. None had evidence of a primary pancreatic tumor. Grossly, the tumors were large (mean size, 12 cm), well circumscribed and showed a lobulated cut surface. Histologically, they showed a predominantly microacinar pattern, with occasional trabecular, solid and microcystic areas. Cellular atypia and mitotic activity varied within the same tumor and from tumor to tumor. Immunohistochemically, the tumor cells were positive for cytokeratin 18 and at least one acinar cell marker (ie, trypsin, amylase or lipase), but were negative for cytokeratins 7, 19 and 20, HepPar-1, AFP, CD10, carcinoembryonic antigen, CD56, Islet-1 and CDX2. Two tumors stained focally for synaptophysin and chromogranin A. Adjacent liver parenchyma displayed no evidence of cirrhosis. During a mean follow-up of 22 months (range, 3-38 months) no metastases occurred, but one patient developed local recurrence. Our study demonstrates that acinar cell carcinoma of pancreatic type may also originate from the liver and can be readily distinguished from other primary liver neoplasms by its distinct histological and immunohistochemical features. Because our cases were observed within a rather short period, it is likely that this tumor type is so far underrecognized and has been mistaken as a variant of hepatocellular carcinoma, cholangiocarcinoma or any other liver tumor.
Collapse
|
|
10
|
Lowery MA, Klimstra DS, Shia J, Yu KH, Allen PJ, Brennan MF, O'Reilly EM. Acinar cell carcinoma of the pancreas: new genetic and treatment insights into a rare malignancy. Oncologist 2011; 16:1714-20. [PMID: 22042785 DOI: 10.1634/theoncologist.2011-0231] [Citation(s) in RCA: 90] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Acinar cell carcinoma (ACC) of the pancreas is a rare neoplasm, accounting for 1% of all pancreatic neoplasms. There remains a lack of data regarding the use of systemic therapy in this disease. We present a series of 40 consecutive cases of ACC of the pancreas treated at Memorial Sloan-Kettering Cancer Center, with an emphasis on evaluation of activity of new therapeutic agents. METHODS Patients reviewed at our institution from January 2000 through January 2011 were identified from an institutional database with prior institutional review board approval. Pathology was confirmed in all cases as ACC or a closely related entity. RESULTS Forty patients were identified; 29 were male (73%). The median age at diagnosis was 65 years (range, 16-87 years). The median overall survival (OS) time for patients with localized, resectable disease was 56.9 months and the OS time for patients with metastatic ACC (n = 18) was 19.6 months. Six patients with metastatic or recurrent ACC had a partial response to chemotherapy and five patients had stable disease for ≥6 months on systemic chemotherapy. Clinical observation was made of a patient with ACC and hereditary nonpolyposis colorectal cancer and a patient with ACC and a BRCA1 germline mutation. CONCLUSIONS ACC is moderately chemoresponsive to agents that have activity in pancreatic adenocarcinoma and colorectal carcinoma. A potential association between germline mutations in DNA mismatch repair genes and ACC warrants further evaluation.
Collapse
Affiliation(s)
- Maeve A Lowery
- Gastrointestinal Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA
| | | | | | | | | | | | | |
Collapse
|
|
11
|
La Rosa S, Vigetti D, Placidi C, Finzi G, Uccella S, Clerici M, Bartolini B, Carnevali I, Losa M, Capella C. Localization of carboxyl ester lipase in human pituitary gland and pituitary adenomas. J Histochem Cytochem 2010; 58:881-9. [PMID: 20566755 DOI: 10.1369/jhc.2010.956169] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Carboxyl ester lipase (CEL) is an enzyme that hydrolyzes a wide variety of lipid substrates, including ceramides, which are known to show inhibitory regulation of pituitary hormone secretion in experimental models. Because no studies on CEL expression in human pituitary and pituitary adenomas have been reported in the literature, we investigated CEL expression in 10 normal pituitary glands and 86 well-characterized pituitary adenomas [12 FSH/LH cell, 17 α-subunit/null cell, 6 TSH cell, 21 ACTH cell, 11 prolactin (PRL) cell, and 19 GH cell adenomas] using IHC, immunoelectron microscopy, Western blotting, and quantitative RT-PCR. In normal adenohypophysis, CEL was localized in GH, ACTH, and TSH cells. In adenomas, it was mainly found in functioning GH, ACTH, and TSH tumors, whereas its expression was poor in the corresponding silent adenomas and was lacking in FSH/LH cell, null cell, and PRL cell adenomas. Ultrastructurally, CEL was localized in secretory granules close to their membranes. This is the first study demonstrating CEL expression in normal human pituitary glands and in functioning GH, ACTH, and TSH adenomas. Considering that CEL hydrolyzes ceramides, inactivating their inhibitory function on pituitary hormone secretion, our findings suggest a possible role of CEL in the regulation of hormone secretion in both normal and adenomatous pituitary cells.
Collapse
Affiliation(s)
- Stefano La Rosa
- Department of Pathology, Ospedale di Circolo, Varese, Italy.
| | | | | | | | | | | | | | | | | | | |
Collapse
|