PTEN Hamartoma Tumor Syndrome/Cowden Syndrome: Genomics, Oncogenesis, and Imaging Review for Associated Lesions and Malignancy
Abstract
:Simple Summary
Abstract
1. Introduction
2. Genomics and Pathophysiology
3. Clinical Presentation and Diagnostic Criteria
4. Associated Benign Pathologies
5. Lhermitte–Duclos Disease (LDD)
6. Vascular Malformations
7. Associated Malignant Pathologies
7.1. Breast Cancer
7.2. Thyroid Carcinoma
7.3. Endometrial Cancer
7.4. Renal Cell Carcinoma
8. Imaging Screening Guidelines for Cowden Syndrome
9. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Lloyd, K.M. Cowden’s disease. A possible new symptom complex with multiple system involvement. Ann. Intern. Med. 1963, 58, 136–142. [Google Scholar] [CrossRef]
- Gustafson, S.; Zbuk, K.M.; Scacheri, C.; Eng, C. Cowden Syndrome. Semin. Oncol. 2007, 34, 428–434. [Google Scholar] [CrossRef] [PubMed]
- Gammon, A.; Jasperson, K.; Champine, M. Genetic basis of Cowden syndrome and its implications for clinical practice and risk management. Appl. Clin. Genet. 2016, 9, 83–92. [Google Scholar] [CrossRef] [Green Version]
- Pilarski, R. Cowden Syndrome: A Critical Review of the Clinical Literature. J. Genet. Couns. 2008, 18, 13–27. [Google Scholar] [CrossRef] [PubMed]
- Caux, F.; Plauchu, H.; Chibon, F.; Faivre, L.; Fain, O.; Vabres, P.; Bonnet, F.; Selma, Z.B.; Laroche, L.; Gérard, M.; et al. Segmental overgrowth, lipomatosis, arteriovenous malformation and epidermal nevus (SOLAMEN) syndrome is related to mosaic PTEN nullizygosity. Eur. J. Hum. Genet. 2007, 15, 767–773. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Masmoudi, A.; Chermi, Z.M.; Marrekchi, S.; Raida, B.S.; Boudaya, S.; Mseddi, M.; Jalel, M.T.; Turki, H. Cowden syndrome. J. Dermatol. Case Rep. 2011, 5, 8–13. [Google Scholar] [CrossRef]
- Tan, M.-H.; Mester, J.L.; Ngeow, J.; Rybicki, L.A.; Orloff, M.S.; Eng, C. Lifetime Cancer Risks in Individuals with Germline PTEN Mutations. Clin. Cancer Res. 2012, 18, 400–407. [Google Scholar] [CrossRef] [Green Version]
- National Comprehensive Cancer Network. Cowden Syndrome/PTEN Hamartoma Tumor Syndrome (Version 2.2021). Available online: http://www.nccn.org/professionals/physician_gls/pdf/genetics__bop.pdf (accessed on 14 April 2021).
- Pilarski, R.; Burt, R.; Kohlman, W.; Pho, L.; Shannon, K.M.; Swisher, E. Cowden Syndrome and the PTEN Hamartoma Tumor Syndrome: Systematic Review and Revised Diagnostic Criteria. J. Natl. Cancer Inst. 2013, 105, 1607–1616. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Spaargaren, L.; Cras, P.; Bomhof, M.A.M.; Lie, S.T.; De Barsy, A.M.; Croese, P.H.; Teepen, J.L.J.M.; Duwel, V.H.J.M.; Van Goethem, J.W.; Ozsarlak, O.; et al. Contrast enhancement in Lhermitte–Duclos disease of the cerebellum: Correlation of imaging with neuropathology in two cases. Neuroradiology 2003, 45, 381–385. [Google Scholar] [CrossRef] [PubMed]
- Dubois, J.; Alison, M. Vascular anomalies: What a radiologist needs to know. Pediatr. Radiol. 2010, 40, 895–905. [Google Scholar] [CrossRef] [PubMed]
- Dubois, J.; Soulez, G.; Oliva, V.L.; Berthiaume, M.-J.; Lapierre, C.; Therasse, E. Soft-Tissue Venous Malformations in Adult Patients: Imaging and Therapeutic Issues. Radiographics 2001, 21, 1519–1531. [Google Scholar] [CrossRef] [PubMed]
- Mester, J.; Eng, C. Cowden syndrome: Recognizing and managing a not-so-rare hereditary cancer syndrome. J. Surg. Oncol. 2014, 111, 125–130. [Google Scholar] [CrossRef] [PubMed]
- Kuhl, C.K. MRI of breast tumors. Eur. Radiol. 2000, 10, 46–58. [Google Scholar] [CrossRef] [PubMed]
- Smerdel, M.P.; Skytte, A.-B.; Jelsig, A.M.; Ebbehøj, E.; Stochholm, K. Revised Danish guidelines for the cancer surveillance of patients with Cowden Syndrome. Eur. J. Med. Genet. 2020, 63, 103873. [Google Scholar] [CrossRef] [PubMed]
- Tessler, F.N.; Middleton, W.D.; Grant, E.G.; Hoang, J.K.; Berland, L.L.; Teefey, S.A.; Cronan, J.J.; Beland, M.D.; Desser, T.S.; Frates, M.C.; et al. ACR Thyroid Imaging, Reporting and Data System (TI-RADS): White Paper of the ACR TI-RADS Committee. J. Am. Coll. Radiol. 2017, 14, 587–595. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Faria, S.; Devine, C.; Rao, B.; Sagebiel, T.; Bhosale, P. Imaging and Staging of Endometrial Cancer. Semin. Ultrasound, CT MRI 2019, 40, 287–294. [Google Scholar] [CrossRef] [PubMed]
- Vikram, R.; Ng, C.S.; Tamboli, P.; Tannir, N.M.; Jonasch, E.; Matin, S.F.; Wood, C.G.; Sandler, C.M. Papillary Renal Cell Carcinoma: Radiologic-Pathologic Correlation and Spectrum of Disease. Radiographics 2009, 29, 741–754; discussion 755–757. [Google Scholar] [CrossRef] [PubMed]
- Prasad, S.R.; Humphrey, P.A.; Catena, J.R.; Narra, V.R.; Srigley, J.R.; Cortez, A.D.; Dalrymple, N.C.; Chintapalli, K.N. Common and Uncommon Histologic Subtypes of Renal Cell Carcinoma: Imaging Spectrum with Pathologic Correlation. Radiographics 2006, 26, 1795–1806; discussion 1806–1810. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Major Criteria * | Minor Criteria |
---|---|
Lhermitte–Duclos disease * | Genitourinary tumors (RCC) or malformations |
Thyroid carcinoma | Lipomas |
Macrocephaly * | Fibromas |
Breast cancer | Mental retardation |
Fibrocystic disease of breast | |
Gastrointestinal hamartomas | |
Other thyroid lesions, such as goiter | |
Mucocutaneous lesions or palmoplantar keratosis can meet the criteria for CS alone if six or more lesions are present |
Revised Clinical Diagnostic Criteria for PTEN Hamartoma Syndrome * | |
---|---|
Major Criteria | Minor Criteria |
Breast cancer | Autism disorder |
Endometrial cancer (epithelial) | Colon cancer |
Thyroid cancer | Esophageal glycogenic acanthoses |
Gastrointestinal hamartomas (includes ganglioneuromas but excludes hyperplastic polyps, ≥3) | Lipomas |
Lhermitte–Duclos disease (adult) | Intellectual disability (IQ ≤ 75) |
Macrocephaly (≥97th percentile) | Renal cell carcinoma |
Macular pigmentation of the glans penis | Testicular lipomatosis |
Multiple mucocutaneous lesions (any of the following):
| Thyroid cancer (papillary or follicular) |
Thyroid structural lesions (e.g., adenoma, multinodular goiter) | |
Vascular anomalies/malformations (including multiple developmental venous anomalies) |
Associated Cancer | Surveillance/Risk Reduction Method | Interval | Starting Age, Years | Evidence Category |
---|---|---|---|---|
Breast cancer | MRI | Yearly a,f | 30–35 e | 2A |
Mammography | Yearly a,f | 30–35 e | 2A | |
Risk-reducing surgery offered | – | – | 2A e | |
Thyroid cancer | Ultrasonography | Yearly | 7 | 2A |
Renal cancer | Ultrasonography | Every 1–2 years | 40 | 2A |
Colorectal cancer | Colonoscopy | Every 5 years b | 35 d | 2A |
Melanoma | Skin examination | Yearly | 30 | 2A |
Endometrial cancer | Imaging surveillance not recommended c | – | – | – |
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Dragoo, D.D.; Taher, A.; Wong, V.K.; Elsaiey, A.; Consul, N.; Mahmoud, H.S.; Mujtaba, B.; Stanietzky, N.; Elsayes, K.M. PTEN Hamartoma Tumor Syndrome/Cowden Syndrome: Genomics, Oncogenesis, and Imaging Review for Associated Lesions and Malignancy. Cancers 2021, 13, 3120. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13133120
Dragoo DD, Taher A, Wong VK, Elsaiey A, Consul N, Mahmoud HS, Mujtaba B, Stanietzky N, Elsayes KM. PTEN Hamartoma Tumor Syndrome/Cowden Syndrome: Genomics, Oncogenesis, and Imaging Review for Associated Lesions and Malignancy. Cancers. 2021; 13(13):3120. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13133120
Chicago/Turabian StyleDragoo, David D., Ahmed Taher, Vincenzo K. Wong, Ahmed Elsaiey, Nikita Consul, Hagar S. Mahmoud, Bilal Mujtaba, Nir Stanietzky, and Khaled M. Elsayes. 2021. "PTEN Hamartoma Tumor Syndrome/Cowden Syndrome: Genomics, Oncogenesis, and Imaging Review for Associated Lesions and Malignancy" Cancers 13, no. 13: 3120. https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13133120