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A Distinctive Adnexal (Usually Paratubal) Neoplasm Often Associated with Peutz-Jeghers Syndrome and Characterized by STK11 Alterations (STK11 Adnexal Tumor) : A Report of 22 Cases

Bennett, Jennifer A. ; Young, Robert H. ; Howitt, Brooke E. ; Croce, Sabrina ; Wanjari, Pankhuri ; Zhen, Chaojie ; Da Cruz Paula, Arnaud ; Meserve, Emily ; Schoolmeester, J. Kenneth and Westbom-Fremer, Sofia LU orcid , et al. (2021) In American Journal of Surgical Pathology 45(8). p.1061-1074
Abstract

We describe 22 examples of a novel, usually paratubal, adnexal tumor associated with Peutz-Jeghers syndrome in nearly 50% of cases that harbored STK11 alterations in all tested (n=21). The patients ranged from 17 to 66 years (median=39 y) and the tumors from 4.5 to 25.5 cm (median=11 cm). Most (n=18) were paratubal, with metastases noted in 11/22 (50%) and recurrences in 12/15 (80%). Morphologically, they were characterized by interanastomosing cords and trabeculae of predominantly epithelioid cells, set in a variably prominent myxoid to focally edematous stroma, that often merged to form tubular, cystic, cribriform, and microacinar formations, reminiscent of salivary gland-type tumors. The tumor cells were uniformly atypical, often... (More)

We describe 22 examples of a novel, usually paratubal, adnexal tumor associated with Peutz-Jeghers syndrome in nearly 50% of cases that harbored STK11 alterations in all tested (n=21). The patients ranged from 17 to 66 years (median=39 y) and the tumors from 4.5 to 25.5 cm (median=11 cm). Most (n=18) were paratubal, with metastases noted in 11/22 (50%) and recurrences in 12/15 (80%). Morphologically, they were characterized by interanastomosing cords and trabeculae of predominantly epithelioid cells, set in a variably prominent myxoid to focally edematous stroma, that often merged to form tubular, cystic, cribriform, and microacinar formations, reminiscent of salivary gland-type tumors. The tumor cells were uniformly atypical, often with prominent nucleoli and a variable mitotic index (median=9/10 HPFs). The tumors were usually positive to a variable extent for epithelial (CAM5.2, AE1/AE3, cytokeratin 7), sex cord (calretinin, inhibin, WT1), and mesothelial (calretinin, D2-40) markers, as well as hormone receptors. PAX8, SF1, and GATA-3 were rarely positive, while claudin-4, FOXL2, and TTF-1 were consistently negative. All sequenced tumors (n=21) harbored alterations in STK11, often with a loss of heterozygosity event. There were no other recurrently mutated genes. Recurrent copy number alterations included loss of 1p and 11q, and gain of 1q, 15q, and 15p. Despite an extensive morphologic, immunohistochemical, and molecular evaluation, we are unable to determine with certainty the histogenesis of this unique tumor. Wolffian, sex cord stromal, epithelial, and mesothelial origins were considered. We propose the term STK11 adnexal tumor to describe this novel entity and emphasize the importance of genetic counseling in these patients as a significant number of neoplasms occur in association with Peutz-Jeghers syndrome.

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type
Contribution to journal
publication status
published
subject
keywords
adnexal, paratubal, Peutz-Jeghers syndrome, salivary gland-like, sex cord-like, STK11
in
American Journal of Surgical Pathology
volume
45
issue
8
article number
001677
pages
1061 - 1074
publisher
Lippincott Williams & Wilkins
external identifiers
  • scopus:85102477759
  • pmid:33534223
ISSN
0147-5185
DOI
10.1097/PAS.0000000000001677
language
English
LU publication?
yes
id
dad871a0-51c6-451d-8d46-bd0c17c282ba
date added to LUP
2021-03-30 06:52:44
date last changed
2024-06-30 12:24:36
@article{dad871a0-51c6-451d-8d46-bd0c17c282ba,
  abstract     = {{<p>We describe 22 examples of a novel, usually paratubal, adnexal tumor associated with Peutz-Jeghers syndrome in nearly 50% of cases that harbored STK11 alterations in all tested (n=21). The patients ranged from 17 to 66 years (median=39 y) and the tumors from 4.5 to 25.5 cm (median=11 cm). Most (n=18) were paratubal, with metastases noted in 11/22 (50%) and recurrences in 12/15 (80%). Morphologically, they were characterized by interanastomosing cords and trabeculae of predominantly epithelioid cells, set in a variably prominent myxoid to focally edematous stroma, that often merged to form tubular, cystic, cribriform, and microacinar formations, reminiscent of salivary gland-type tumors. The tumor cells were uniformly atypical, often with prominent nucleoli and a variable mitotic index (median=9/10 HPFs). The tumors were usually positive to a variable extent for epithelial (CAM5.2, AE1/AE3, cytokeratin 7), sex cord (calretinin, inhibin, WT1), and mesothelial (calretinin, D2-40) markers, as well as hormone receptors. PAX8, SF1, and GATA-3 were rarely positive, while claudin-4, FOXL2, and TTF-1 were consistently negative. All sequenced tumors (n=21) harbored alterations in STK11, often with a loss of heterozygosity event. There were no other recurrently mutated genes. Recurrent copy number alterations included loss of 1p and 11q, and gain of 1q, 15q, and 15p. Despite an extensive morphologic, immunohistochemical, and molecular evaluation, we are unable to determine with certainty the histogenesis of this unique tumor. Wolffian, sex cord stromal, epithelial, and mesothelial origins were considered. We propose the term STK11 adnexal tumor to describe this novel entity and emphasize the importance of genetic counseling in these patients as a significant number of neoplasms occur in association with Peutz-Jeghers syndrome.</p>}},
  author       = {{Bennett, Jennifer A. and Young, Robert H. and Howitt, Brooke E. and Croce, Sabrina and Wanjari, Pankhuri and Zhen, Chaojie and Da Cruz Paula, Arnaud and Meserve, Emily and Schoolmeester, J. Kenneth and Westbom-Fremer, Sofia and Benzi, Eduardo and Patil, Ninad M. and Kooreman, Loes and El-Bahrawy, Mona and Zannoni, Gian Franco and Krausz, Thomas and McCluggage, W. Glenn and Weigelt, Britta and Ritterhouse, Lauren L. and Oliva, Esther}},
  issn         = {{0147-5185}},
  keywords     = {{adnexal; paratubal; Peutz-Jeghers syndrome; salivary gland-like; sex cord-like; STK11}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{1061--1074}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{American Journal of Surgical Pathology}},
  title        = {{A Distinctive Adnexal (Usually Paratubal) Neoplasm Often Associated with Peutz-Jeghers Syndrome and Characterized by STK11 Alterations (STK11 Adnexal Tumor) : A Report of 22 Cases}},
  url          = {{http://dx.doi.org/10.1097/PAS.0000000000001677}},
  doi          = {{10.1097/PAS.0000000000001677}},
  volume       = {{45}},
  year         = {{2021}},
}