dc.contributor.author |
Fuchs, Talia L |
|
dc.contributor.author |
Luxford, Catherine |
|
dc.contributor.author |
Clarkson, Adele |
|
dc.contributor.author |
Sheen, Amy |
|
dc.contributor.author |
Sioson, Loretta |
|
dc.contributor.author |
Elston, Marianne |
|
dc.contributor.author |
Croxson, Michael S |
|
dc.contributor.author |
Dwight, Trisha |
|
dc.contributor.author |
Benn, Diana E |
|
dc.contributor.author |
Tacon, Lyndal |
|
dc.contributor.author |
Field, Michael |
|
dc.contributor.author |
Ahadi, Mahsa S |
|
dc.contributor.author |
Chou, Angela |
|
dc.contributor.author |
Clifton-Bligh, Roderick J |
|
dc.contributor.author |
Gill, Anthony J |
|
dc.coverage.spatial |
United States |
|
dc.date.accessioned |
2024-06-10T23:03:56Z |
|
dc.date.available |
2024-06-10T23:03:56Z |
|
dc.date.issued |
2023-01 |
|
dc.identifier.citation |
(2023). American Journal of Surgical Pathology, 47(1), 25-36. |
|
dc.identifier.issn |
0147-5185 |
|
dc.identifier.uri |
https://hdl.handle.net/2292/68767 |
|
dc.description.abstract |
Up to 40% of pheochromocytomas (PCCs) and paragangliomas (PGLs) are hereditary. Germline mutations/deletions in fumarate hydratase ( FH ) cause hereditary leiomyomatosis and renal cell carcinoma syndrome which manifests predominantly with FH-deficient uterine/cutaneous leiomyomas and renal cell carcinomas (RCCs)-tumors characterized by loss of immunohistochemical (IHC) expression of FH and/or positive staining for S-(2-succino)-cysteine. Occasional patients develop PCC/PGL. We investigated the incidence, morphologic, and clinical features of FH-deficient PCC/PGL. We identified 589 patients with PCC/PGLs that underwent IHC screening for FH and/or S-(2-succino)-cysteine. Eight (1.4%) PCC/PGLs were FH deficient (1.1% in an unselected population). The median age for FH-deficient cases was 55 (range: 30 to 77 y) with 50% arising in the adrenal. All 4 with biochemical data were noradrenergic. Two (25%) metastasized, 1 dying of disease after 174 months. Germline testing was performed on 7 patients, 6 of whom had FH missense mutations. None were known to have a significant family history before presentation or developed cutaneous leiomyomas, or FH-deficient RCC at extended follow-up. The patient wild-type for FH on germline testing was demonstrated to have somatic FH mutation and loss of heterozygosity corresponding to areas of subclonal FH deficiency in her tumor. One patient did not undergo germline testing, but FH mutation was demonstrated in his tumor. We conclude that FH-deficient PCC/PGL are underrecognized but can be identified by IHC. FH-deficient PCC/PGL are strongly associated with germline missense mutations but are infrequently associated with leiomyoma or RCC, suggesting there may be a genotype-phenotype correlation. FH-deficient PCC/PGL may have a higher metastatic risk. |
|
dc.format.medium |
Print-Electronic |
|
dc.language |
eng |
|
dc.publisher |
Wolters Kluwer |
|
dc.relation.ispartofseries |
The American journal of surgical pathology |
|
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
|
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
|
dc.subject |
Humans |
|
dc.subject |
Leiomyomatosis |
|
dc.subject |
Paraganglioma |
|
dc.subject |
Pheochromocytoma |
|
dc.subject |
Carcinoma, Renal Cell |
|
dc.subject |
Adrenal Gland Neoplasms |
|
dc.subject |
Skin Neoplasms |
|
dc.subject |
Uterine Neoplasms |
|
dc.subject |
Kidney Neoplasms |
|
dc.subject |
Neoplastic Syndromes, Hereditary |
|
dc.subject |
Cysteine |
|
dc.subject |
Fumarate Hydratase |
|
dc.subject |
Immunohistochemistry |
|
dc.subject |
Adult |
|
dc.subject |
Aged |
|
dc.subject |
Middle Aged |
|
dc.subject |
Female |
|
dc.subject |
32 Biomedical and Clinical Sciences |
|
dc.subject |
3211 Oncology and Carcinogenesis |
|
dc.subject |
Genetics |
|
dc.subject |
Cancer |
|
dc.subject |
Kidney Disease |
|
dc.subject |
Rare Diseases |
|
dc.subject |
Clinical Research |
|
dc.subject |
2.1 Biological and endogenous factors |
|
dc.subject |
2 Aetiology |
|
dc.subject |
Science & Technology |
|
dc.subject |
Life Sciences & Biomedicine |
|
dc.subject |
Pathology |
|
dc.subject |
Surgery |
|
dc.subject |
FH |
|
dc.subject |
2SC |
|
dc.subject |
CELL-CARCINOMA SYNDROME |
|
dc.subject |
HEREDITARY LEIOMYOMATOSIS |
|
dc.subject |
DEHYDROGENASE |
|
dc.subject |
MUTATIONS |
|
dc.subject |
SOCIETY |
|
dc.subject |
UTILITY |
|
dc.subject |
SDHB |
|
dc.subject |
PREDISPOSITION |
|
dc.subject |
GUIDELINE |
|
dc.subject |
1103 Clinical Sciences |
|
dc.subject |
3202 Clinical sciences |
|
dc.title |
A Clinicopathologic and Molecular Analysis of Fumarate Hydratase-deficient Pheochromocytoma and Paraganglioma |
|
dc.type |
Journal Article |
|
dc.identifier.doi |
10.1097/pas.0000000000001945 |
|
pubs.issue |
1 |
|
pubs.begin-page |
25 |
|
pubs.volume |
47 |
|
dc.date.updated |
2024-05-01T20:51:01Z |
|
dc.rights.holder |
Copyright: The authors |
en |
dc.identifier.pmid |
35993574 (pubmed) |
|
pubs.author-url |
https://www.ncbi.nlm.nih.gov/pubmed/35993574 |
|
pubs.end-page |
36 |
|
pubs.publication-status |
Published |
|
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RetrictedAccess |
en |
pubs.subtype |
Research Support, Non-U.S. Gov't |
|
pubs.subtype |
research-article |
|
pubs.subtype |
Journal Article |
|
pubs.elements-id |
917713 |
|
pubs.org-id |
Medical and Health Sciences |
|
pubs.org-id |
School of Medicine |
|
pubs.org-id |
Medicine Department |
|
dc.identifier.eissn |
1532-0979 |
|
dc.identifier.pii |
00000478-202301000-00003 |
|
pubs.record-created-at-source-date |
2024-05-02 |
|
pubs.online-publication-date |
2022-08-22 |
|