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 DOI: 10.1177/0194599813490888

2013 149: 513 originally published online 21 May 2013Otolaryngology -- Head and Neck SurgeryAinhoa García-Lliberós, María-José Gómez and Miguel Armengot-Carceller

Rare Sinonasal and Laryngeal Manifestations of Cowden's Disease  

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Case Report

Rare Sinonasal and LaryngealManifestations of Cowden’s Disease

Otolaryngology–Head and Neck Surgery149(3) 513–514� American Academy ofOtolaryngology—Head and NeckSurgery Foundation 2013Reprints and permission:sagepub.com/journalsPermissions.navDOI: 10.1177/0194599813490888http://otojournal.org

Ainhoa Garcıa-Lliberos, MD1, Marıa-Jose Gomez, MD1, andMiguel Armengot-Carceller, MD, PhD1

No sponsorships or competing interests have been disclosed for this article.

Keywords

nasal tumors, dysphonia, hamartoma, inherited, nasalobstruction, PTEN

Received January 28, 2013; revised April 4, 2013; accepted April 25,

2013.

Cowden’s disease (CD), or multiple hamartoma syn-

drome, is characterized by various ecto-, meso-, and

endodermal benign and malignant tumors. It is

inherited in an autosomal dominant manner with 80% of

patients having a germ-line mutation of the PTEN tumor

suppressor gene. The estimated incidence is 1/200,000.1

We present herein a rare case of CD with sinonasal and

laryngeal manifestations. To our knowledge, this is the

second reported case of CD involving the vocal folds. This

study has been approved by the Ethics Committee of the

General and University Hospital of Valencia, Spain.

Case Report

A 52-year-old woman presented with unilateral nasal obstruc-

tion and dysphonia for the past 20 months. She had been diag-

nosed with CD in her youth and had experienced multiple

tissue involvement over the past 30 years. Verrucoid papules

on the face and hands, gum hyperplasia, intestinal polyps,

fibrocystic breast disease, hip synovial cysts, thyroid cysts, and

vaginal fibroids were part of the disease. A mutation of the

PTEN gene was confirmed. The genetic study was performed

using PCR-SSCP (polymerase chain reaction–single-strand

conformation polymorphism from cutaneous lesions cells

DNA). No malignant neoplasms had been found to date. Her

family history included 1 brother and 1 sister with CD. Nasal

endoscopy revealed a white fibrous mass with cobblestone

appearance blocking the right nostril. Flexible laryngoscopy

showed a nodular, irregular white lesion of the posterior third

of the right vocal cord (Figure 1A).

Computed tomography revealed a large mass in the max-

illary sinus destroying its medial wall and filling the entire

right nasal cavity (Figure 1B).

Given the high risk of malignancies in patients with this

syndrome,2 we decided to perform a transnasal endoscopic

medial maxillectomy and direct laryngoscopy. The sinonasal

and laryngeal lesions were completely removed.

Pathology report described a fibrous tissue embedded in

fibrinoid material with necrotic debris. No atypia or mitotic

activity was seen in any of the specimens. There were no

signs of inflammatory polyp as interstitial edema or eosino-

philic infiltration. These features were consistent with a

fibrous lesion of hamartomatous origin (Figure 2).

The patient had recurrence of her sinonasal and vocal

cord masses 1 year postoperatively, and we elected a non-

surgical approach.

Discussion

Cowden’s disease is a hereditary multiple hamartoma syn-

drome very commonly affecting the head and neck regions.

Mucocutaneous hamartomas of the buccal, gingival, and

pharyngeal spaces are found in almost 100% of cases, and

they have a cobblestone appearance.2,3

Thyroid cancer, following breast cancer, is the second

most common malignancy associated with CD. In addition,

benign multinodular goiter, adenomatous nodules, and folli-

cular adenomas appear in up to 75% of patients. The geni-

tourinary and gastrointestinal tracts are also frequently

affected.3

As previously mentioned, to our knowledge this is the

second reported case of CD involving a vocal fold2 and one

of the few described cases of CD involving the maxillary

sinus and nasal cavity. These cases have been described as

respiratory epithelial adenomatoid hamartoma: this is a sub-

group of hamartomas that more often involves the nasal

cavity or nasopharynx and is not part of CD but appears in

isolation with no other hamartomatous lesions.4

Definitive diagnosis depends on recognizing the pattern of

the clinical features and the histology of the corresponding

lesions. In our case, the predominant tissue was of fibrous

origin. This is also observed in hamartomatous polyps in colon

1Rhinology Unit, ENT Department, General and University Hospital,

Valencia, Spain

Corresponding Author:

Miguel Armengot-Carceller, MD, PhD, ENT Department, General and

University Hospital, Surgery Department, Valencia University, Valencia,

Spain.

Email: miguel.armengot@gmail.com

CD, in which the glands exhibit dilatation of the lumen and

stromal predominance.5 Therefore, the changes seen, although

not pathognomonic, are within the range of lesions described

in patients with CD (Figure 2).

The treatment of the head and neck manifestations of CD

remains primarily surgical despite the risk of recurrences. 5-

Fluorouracil has been used to treat selected mucocutaneous

lesions.3 In this case, surgical excision was selected to clear the

patient’s nasal cavity, improve her voice, and enable a histo-

pathologic examination with the purpose of ruling out malig-

nancy. However, the rapid recurrence of the lesions in this

patient suggests that surgical treatment of CD in these locations

should be primarily directed to discard malignancy. The genetic

basis of this disease probably determines its specific evolution.

The diagnosis of CD remains a challenge because of its

paucity, and the otolaryngologist should be familiar with

this entity and its head and neck manifestations.

Author Contributions

Ainhoa Garcıa-Lliberos, drafting the article, article design, analysis

of data, language translation; Marıa-Jose Gomez, drafting the article,

article design, analysis of data; Miguel Armengot-Carceller, final

approval of the version to be published, article design.

Disclosures

Competing interests: None.

Sponsorships: None.

Funding source: None.

References

1. Conti S, Condo M, Posar A, et al. Phosphatase and tensin

homolog (PTEN) gene mutations and autism: literature review

and a case report of a patient with Cowden syndrome, autistic

disorder, and epilepsy. J Child Neurol. 2012;27:392-397.

2. To EW, Tsang WM, Pak MW, Cheng JH, Tse GM, van Hasselt

CA. Cowden’s disease with vocal fold involvement. Ear Nose

Throat J. 2001;80:754-756.

3. Farooq A, Walker LJ, Bowling J, Audisio RA. Cowden syn-

drome. Cancer Treat Rev. 2010;36:577-583.

4. Di Carlo R, Rinaldi R, Ottaviano G, Pastore A. Respiratory

epithelial adenomatoid hamartoma of the maxillary sinus: case

report. Acta Otorhinolaryngol Ital. 2006;26:225-227.

5. Hamilton SR, Aaltonen LA. Cowden Syndrome in Pathology

and Genetics of Tumor of the Digestive System. Lyon, France:

IARC Press; 2000:132-133.

Figure 1. (A) A fibromatous nodular lesion on the right vocal cord (arrow). (B) Maxillofacial computed tomography views show a massoccupying the right maxillary sinus and nostril, with disruption of the left maxillary sinus medial wall.

Figure 2. The proliferation of spindle eosinophilic cells with anelongated core and loose chromatin without atypia or mitosis.Necrosis can be seen in the upper left corner (arrows).

514 Otolaryngology–Head and Neck Surgery 149(3)