Cancer and Lhermitte-Duclos disease are common in Cowden syndrome patients

Riegert–Johnson, Douglas L.; Gleeson, Ferga C.; Roberts, Maegan E.; Tholen, Krysta; Youngborg, Lauren; Bullock, Melvin; Boardman, Lisa A.

doi:10.1186/1897-4287-8-6

Cited by 155 publications

(133 citation statements)

References 14 publications

Supporting

Mentioning

123

Contrasting

Unclassified

Order By: Relevance

“…These findings are also comparable with previous literature (2). We used standard criteria for calling pathogenic mutations, ranging from bioinformatic algorithms (SIFT, PolyPhen, Mutation Taster) to functional studies.…”

supporting

confidence: 75%

Lifetime Cancer Risks of PTEN Mutation Carriers—Response

Tan

Mester

Eng³

2012

Clinical Cancer Research

View full text Add to dashboard Cite

We thank Daniels and colleagues for their comments on our report (1). Given that the Cleveland Clinic is the main referral center of patients with germline PTEN mutations in the United States, it is certainly possible that ascertainment bias may exist, an issue we acknowledged in our report. Referral bias is an inherent challenge for the study of rare genetic disorders, but clearly a population-based approach for evaluating such a rare syndrome would be impractical. We also agree that this bias would be ideally addressed by prospective follow-up of affected individuals, an effort we are currently undertaking. The Kaplan-Meier method was selected because of its widespread use in other studies evaluating lifetime cancer risks in genetic syndromes. The other methods referenced by Daniels and colleagues require either long-term follow-up or recruitment of several members within each family, making these models incompatible with this study's design and patient population.As noted in the original article, our cohort has been prospectively ascertained. Thus, not all the cancers reported are prevalent. For example, renal cell carcinoma is a minor criterion and colon cancer and melanoma are not criteria at all. Yet, increased standardized incidence ratio (SIR) and age-related penetrances are noted for these cancers. These findings are also comparable with previous literature (2). We used standard criteria for calling pathogenic mutations, ranging from bioinformatic algorithms (SIFT, PolyPhen, Mutation Taster) to functional studies. We only used for this study mutations and promoter variants that have been shown to be pathogenic. There are many more variants in the promoter that our laboratory is struggling to functionally characterize. To be conservative, these have not been included in this study.Daniels and colleagues suggest that it would be premature to recommend changes in clinical practice based on data from our series. Existing clinical practice and NCCN recommendations derive primarily from previous retrospective observations, many of which were contributed by our group. Our approach has identified colorectal carcinoma, melanoma, pediatric thyroid cancer, and papillary renal cell carcinoma as features of germline PTEN mutations, observations which are beginning to be confirmed by other investigators (3, 4). The adult and pediatric testing criteria we have developed are also superior to existing NCCN criteria (5). Together with the fact that this data set is derived from the largest known series of patients with PTEN mutations, we believe the recommendations outlined in our article represent current best practice for counseling and follow-up of these patients. Disclosure of Potential Conflicts of InterestNo potential conflicts of interest were disclosed.

show abstract

supporting

confidence: 75%

Lifetime Cancer Risks of PTEN Mutation Carriers—Response

Tan

Mester

Eng³

2012

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…Its significance arises from its association with colorectal, mammary, thyroidal, and genitourinary cancers. Overall, the lifetime risk of cancer in patients with CS was reported to be at approximately 89% with the largest portion of the patients presenting with breast and/or thyroid carcinomas [4]. CS also remains relevant to dental professionals because of the overwhelming prevalence of hamartomatous oral nodules observed in over 99% of patients [1,3].…”

Section: Discussionmentioning

confidence: 99%

“…The lesion was interpreted to clinically and histologically resemble previously reported oral lesions in CS and no further intraoral surgical intervention was recommended or indicated, unless the lesions were to become symptomatic or presented hygienic challenges. The patient was 4 Gingival pebbly papulonodular lesion at low magnification. Surface epithelium demonstrates hyperparakeratosis, irregular acanthosis, papillomatosis, and patchy atrophy.…”

Section: Diagnosismentioning

confidence: 97%

“…Microscopy revealed a pebbly papulonodular lesion displaying surface stratified squamous epithelium accompanied by hyperparakeratosis, papillomatosis, acanthosis with elongated broad and slender rete processes, and mild suprapapillary epithelial atrophy (Figs. 4,5,6). Physiologic pigmentation (melanin pigment) was seen in the cytoplasm of the basal keratinocytes.…”

Section: Diagnosismentioning

confidence: 99%

See 1 more Smart Citation

Multiple Oral Mucosal Hamartomas in a 34-Year Old Female

Elo

Sun

Laudenbach

et al. 2017

Head and Neck Pathol

View full text Add to dashboard Cite

reported first noticing these lesions approximately 10 years prior. She also denied any history of oral surgery, facial trauma, and alcohol, tobacco, or recreational drug use. The patient's past medical history was significant for left and right mastectomy for bilateral ductal carcinoma and partial thyroidectomy for microcarcinoma. She received blood transfusions at multiple points during her surgical journey but her current medical regimen included only levothyroxine. Clinical FindingsIntraoral examination (Fig. 1) revealed generalized multiple white-pink round/oval papules on the patient's lips. She was noted to have a distinct 6 mm × 5 mm × 3 mm papillary lesion on the facial gingiva between teeth #25 and 26 with smaller lesions extending slightly inferiorly to the distal of teeth #27 and 28. Similar small patches of lesions were noted on her contralateral mandibular quadrant. Also noted was a 7 mm × 3 mm white lesion on her right buccal mucosa just superior to the occlusal plane on the distobuccal cusp of tooth #31. In addition, pink papillary growths were found on the palatal gingiva of teeth #1, 2, 3, 6, 7, 9, 10, and 11 (Fig. 2) along with a similar but white papillary lesion on the attached buccal gingiva of tooth #15 measuring 5 mm × 5 mm × 5 mm. Another 3 mm × 7 mm papillary cluster was noted on the lingual mandibular gingiva near teeth #21 and 22. White gingival tissue was noted on the crest of her #14 edentulous ridge site (Fig. 3). None of these lesions were removable with gauze. The tongue was otherwise normal, as was the floor of her mouth. Radiographic imaging of the maxillomandibular region was otherwise unremarkable.Abstract A case of Cowden syndrome (CS) is described in a 34-year-old African American female who reported a history of breast and thyroid malignancies. Clinical examination demonstrated multiple soft, white-pink papules across multiple mucosal surfaces of the oral cavity. Microscopy of the lesions revealed hyperkeratotic surface squamous epithelium with papillomatosis and acanthosis along with elongated rete processes. A genomic polymerase chain reaction direct sequencing using the patient's blood was positive for mutations of the PTEN gene typical of CS.

show abstract

“…Cowden sydrome (autosomal dominant inherited multiple hamartoma syndrome) should be kept in mind in patients with LDD (14). LDD is one of the major diagnostic criteria for Cowden syndrome and these patients should be scanned for phosphatase and tensin homolog gene mutations and cancers (15).…”

Section: Discussionmentioning

confidence: 99%

Lhermitte-Duclos Disease with Orthostatic Hypotension

Yılmaz¹,

Şeker²,

Omaygenç³

et al. 2016

tnd

View full text Add to dashboard Cite

130Lhermitte-Duclos disease is a rare cerebellar dysplastic gangliocytoma. The most common symptoms include headache, nausea, vomiting, blurred vision, and imbalance. The typical appearance on cranial magnetic resonance imaging is hyper-intensity on T2-weighted images and hypo-intensity on T1-weighted images. The disease generally presents with benign progress. Development of obstructive hydrocephalus is an indication for urgent surgical intervention and surgery outcomes are satisfactory. Orthostatic hypotension is a very rare clinical presentation of this syndrome and ours is the second case of orthostatic hypotension to be reported in the literature.

show abstract

Cancer and Lhermitte-Duclos disease are common in Cowden syndrome patients

Cited by 155 publications

References 14 publications

Lifetime Cancer Risks of PTEN Mutation Carriers—Response

Lifetime Cancer Risks of PTEN Mutation Carriers—Response

Multiple Oral Mucosal Hamartomas in a 34-Year Old Female

Lhermitte-Duclos Disease with Orthostatic Hypotension

Contact Info

Product

Resources

About