Peutz-Jeghers syndrome with ovarian sex cord tumor with annular tubules and cervical adenoma malignum

Podczaski, Edward S.; Kaminski, Paul F.; Pees, Richard C.; Singapuri, Kishor; Sorosky, Joel I.

doi:10.1016/0090-8258(91)90234-v

Cited by 41 publications

(21 citation statements)

References 11 publications

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“…A markedly increased incidence of carcinomas of the gastrointestinal tract including stomach, small bowel, colon and pancreatic cancer, as well as breast, ovary, uterus, cervix, lung and testis cancer has been observed through longitudinal studies of affected kindreds (Giardiello et al, 1987(Giardiello et al, , 2000Spigelman et al, 1989;Gruber et al, 1998;Lim et al, 2004;Hearle et al, 2006). In addition, rare tumors have been associated with PJS including those of a reproductive origin-including testicular and ovarian sex cord tumors, Sertoli cell tumors and adenoma malignum of the cervix-as well as non-adenocarcinoma pancreatic tumors, including pancreatic intraductal papillary mucinous neoplasia and serous cystadenomas (Podczaski et al, 1991;Young et al, 1995;Tomlinson and Houlston, 1997;Su et al, 1999;Sato et al, 2001;Yee et al, 2003).…”

Section: Peutz-jeghers Syndrome and Human Cancer Geneticsmentioning

confidence: 99%

LKB1; linking cell structure and tumor suppression

2008

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Germ line mutations in the LKB1 tumor suppressor gene are associated with the Peutz-Jeghers polyposis and cancer syndrome. Somatic mutations in Lkb1 are observed in sporadic pulmonary, pancreatic and biliary cancers and melanomas. The LKB1 serine-threonine kinase functionally and biochemically links control of cellular structure and energy utilization through activation of the AMPK family of kinases. Lkb1 regulates cell polarity through downstream kinases including AMPKs, MARKs and BRSKs, and nutrient utilization and cellular metabolism through the AMPK-mTOR pathway. LKB1 has been shown to affect normal chromosomal segregation, TGF-b signaling in the mesenchyme and WNT and p53 activity. Although each of the LKB1-dependent processes and downstream pathways have been individually delineated through work across a range of experimental systems, how they relate to Lkb1's role as a tumor suppressor remains to be fully explored and elucidated. The recent development of mouse cancer models harboring engineered mutations in Lkb1 have offered insights into how LKB1 may be functioning to restrain tumorigenesis and how its role as a master regulator of polarity and metabolism could contribute to its tumor suppressor function.

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Section: Peutz-jeghers Syndrome and Human Cancer Geneticsmentioning

confidence: 99%

LKB1; linking cell structure and tumor suppression

2008

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“…In addition to an elevated risk of gastrointestinal cancers, an increased risk of cancers at other sites, such as breast, ovary, uterus, cervix, lung, and testis, has been described (3 -7). Rare tumors have also been attributed to Peutz-Jeghers syndrome, including testicular sex cord and Sertoli cell tumors, leading to sexual precocity and gynecomastia (8 -10), ovarian sex cord tumors with annular tubules, and adenoma malignum of the cervix (1,2,11,12).…”

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confidence: 99%

Frequency and Spectrum of Cancers in the Peutz-Jeghers Syndrome

Hearle

Schumacher

Menko³

et al. 2006

Clinical Cancer Research

702

476

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Background: Although an increased cancer risk in Peutz-Jeghers syndrome is established, data on the spectrum of tumors associated with the disease and the influence of germ-line STK11/ LKB1 (serine/threonine kinase) mutation status are limited. Experimental Design: We analyzed the incidence of cancer in 419 individuals with PeutzJeghers syndrome, and 297 had documented STK11/LKB1 mutations. Results: Ninety-six cancers were found among individuals with Peutz-Jeghers syndrome. The risk for developing cancer at ages 20, 30, 40, 50, 60, and 70 years was 2%, 5%, 17%, 31%, 60%, and 85%, respectively. The most common cancers represented in this analysis were gastrointestinal in origin, gastroesophageal, small bowel, colorectal, and pancreatic, and the risk for these cancers at ages 30, 40, 50, and 60 years was 1%, 9%, 15%, and 33%, respectively. In women with Peutz-Jeghers syndrome, the risk of breast cancer was substantially increased, being 8% and 31% at ages 40 and 60 years, respectively. Kaplan-Meier analysis showed that cancer risks were similar in Peutz-Jeghers syndrome patients with identified STK11/LKB1 mutations and those with no detectable mutation (log-rank test of difference m 2 = 0.62; 1 df ; P = 0.43). Furthermore, the type or site of STK11/LKB1 mutation did not significantly influence cancer risk. Conclusions:The results from our study provide quantitative information on the spectrum of cancers and risks of specific cancer types associated with Peutz-Jeghers syndrome.

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“…In females, it is in the form of sex cord tumor with annular tubules whereas in males, the lesion has features that are often intermediate between those of a sex cord tumor with annular tubules and a large cell calcifying Sertoli cell tumor [65,66]. Adenoma malignum of the uterine cervix is also much more common in PJS than in control population [67]. PJS patients have increased risk of esophageal, gastrointestinal, and pancreatic cancer, and the risk for these cancers markedly increases with age.…”

Section: Peutz-jeghers Syndromementioning

confidence: 89%

Pathology of the hereditary colorectal carcinoma

Gatalica

Torlakovic

2007

Familial Cancer

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Positive familial history (first or second degree relative) for colorectal carcinoma (CRC) can be found in approximately 30% of all newly diagnosed cases, but less than 5% will be due to a defined genetic category of hereditary CRC. Pathologic examination of the biopsy or resection specimen can help in identification of unsuspected cases of certain forms of hereditary CRC due to the characteristic morphologic findings. Additional immunohistochemical and molecular studies can then provide a definitive diagnosis. The most common form of hereditary CRC is Lynch syndrome (hereditary non-polyposis colorectal cancer, HNPCC) which is characterized by proximally located tumors frequently showing mucinous and medullary type histologic features. The syndrome results from a germline mutation in genes for mismatch repair (MMR) proteins leading to insufficient DNA repair and development of tumors characterized by high levels of instability in short tandem repeat DNA sequences (microsatellites) or "microsatellite instability-high" (MSI-H). The presence of intra-epithelial lymphocytes is single most helpful morphologic feature in identification of CRC caused by deficiency in MMR proteins, for which MSI-H status is a good marker but morphologic features and MSI-H do not differentiate tumors caused by germline mutations in one of the MMR genes (Lynch syndrome) from sporadic CRC due to inactivation of MLH-1 through promoter methylation. Hereditary CRC may also arise in various familial polyposis syndromes which include familial adenomatous polyposis (FAP), attenuated FAP and other multiple adenomas syndromes as well as various hamartomatous polyposis syndromes. All of these rare conditions have characteristic clinical presentation and histopathologic features of polyps and most of them have defined genetic abnormality. Furthermore, due to the germline nature of mutations in these syndromes, various extracolonic manifestations may be the first sign of the disease and knowledge of such associations can greatly improve the quality of care for these patients. The role of pathologist is to recognize these characteristics and initiate appropriate follow up with clinicians and genetic counselors.

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Peutz-Jeghers syndrome with ovarian sex cord tumor with annular tubules and cervical adenoma malignum

Cited by 41 publications

References 11 publications

LKB1; linking cell structure and tumor suppression

LKB1; linking cell structure and tumor suppression

Frequency and Spectrum of Cancers in the Peutz-Jeghers Syndrome

Pathology of the hereditary colorectal carcinoma

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