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CASE REPORT Table of Contents   
Year : 2010  |  Volume : 21  |  Issue : 3  |  Page : 439-442
Cowden syndrome


Department of Oral Medicine and Radiology, Kothiwal Dental College and Research Centre, Mora Mustaqueem, Moradabad (U.P.), India

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Date of Submission19-Jul-2009
Date of Decision17-Sep-2009
Date of Acceptance23-Jan-2010
Date of Web Publication29-Sep-2010
 

   Abstract 

Cowden syndrome or multiple hamartoma syndrome is an autosomal dominant condition with variable expressions that result mainly from mutation in the PTEN gene on arm 10q. It is characterized by multiple hamartomatous neoplasms of the skin, oral mucosa, gastrointestinal tract, bones, CNS, eyes, and genitourinary tract. Mucocutaneous features include trichilemmomas, oral mucosal papillomatosis, acral keratosis, and palmoplantar keratosis. Here we present a case of Cowden syndrome in a 14-year-old female patient with the chief complaint of multiple oral papillomatous lesions.

Keywords: Cowden syndrome, hamartomas, malignancies, oral papillomatosis, trichilemmomas

How to cite this article:
Ravi Prakash S M, Suma G N, Goel S. Cowden syndrome. Indian J Dent Res 2010;21:439-42

How to cite this URL:
Ravi Prakash S M, Suma G N, Goel S. Cowden syndrome. Indian J Dent Res [serial online] 2010 [cited 2018 Sep 22];21:439-42. Available from: http://www.ijdr.in/text.asp?2010/21/3/439/70803
Eyes can only see what the brain knows. Importance of this adage is realized in our lives time and time again. Many lethal diseases leave their footmarks in oral cavity as an early sign. Dentist play a major role in recognizing these oral signs so that measures can be taken at an early stage to prevent the morbidity and mortality associated with these conditions.

Cowden syndrome (CD), also termed as multiple hamartoma syndrome, was first described in 1940 by Costello. [1] In 1963, Llyod and Dennis defined and named the syndrome after their patient Rachel Cowden, a 20-year-old female. [2] It is an autosomal dominant condition with variable expressions that result most commonly from the mutation in the PTEN gene on the arm 10q. [1],[3],[4]


   Case Report Top


A 16-year-old female patient came to our department with chief complain of swollen hard gums. Presence of occasional rectal bleeding was noted in her medical history. Her parents and other siblings were normal. On general examination, patient appeared thin built and anemic. Dorsal surface of her hands showed acral keratosis [Figure 1].
Figure 1: Acral keratosis on dorsal surface of hands

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Extraoral examination revealed the presence of multiple skin colored, flat-topped papules on and around her nose measuring around 1-5 mm in diameter [Figure 2]. These papules were diagnosed as trichilemmomas on biopsy.
Figure 2: Multiple skin colored, flat topped trichilemmomas on and around the nose of the patient

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Intraoral examination showed enlarged gingiva, which was firm to hard in consistency [Figure 2]. Probing depth was less than 3 cm in diameter with minimal bleeding on probing. Flex of subgingival calculus was seen with the molar teeth. Smooth, whitish surfaced papillomatous lesions, ranging from 1 to 3 mm in diameter, were present on gingiva [Figure 2], buccal mucosa, and tongue. The presence of multiple, confluent lesions produced a cobblestone appearance on the tongue [Figure 3] and gingiva [Figure 4]. On the basis of history and clinical examination, patient was diagnosed as a case of Cowden syndrome.
Figure 3: Cobblestone appearance of multiple confluent papules on the tongue

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Figure 4: Enlarged gingiva having smooth, whitish surfaced papillomatous lesions in all the four quadrants

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We performed several investigations in this patient to rule out other hamartomas and malignancies. Laboratory investigations performed were complete hematological tests, thyroid functions test, urine analysis and mucosal lesions biopsy. Hematological investigation showed the presence of anemia, while thyroid function tests and urine analysis were normal. Biopsy specimen of papules from tongue, buccal mucosa, and gingiva showed hyperkeratinized stratified squamous hyperplastic epithelium with no inflammatory evidence in the connective tissue suggestive of non-inflammatory epithelial hyperplasia [Figure 5].
Figure 5: H and E stained section of oral papillomatous lesions showing noninflammatory epithelial hyperplasia

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Imaging studies performed were orthopantomogram [Figure 6], mammogram, CT scan, and MRI of brain along with upper and lower gastrointestinal endoscopy. Mammography findings were unremarkable although firm masses were clinically palpable on gynaecological examination. Multiple intestinal lymphoid polyps were seen on GI endoscopy [Figure 7], which were excised and histologically confirmed. CT scan and MRI of the brain showed no posterior cerebellar hamartomas.
Figure 6: Orthopantomogram of the patient showing incipient interdental bone loss

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Figure 7: Intestinal lymphoid polyp on GI endoscopy

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Patient was referred to various specialists like gynecologist, neurologist, gastroenterologist, and general surgeon for opinion. She is under regular follow up and care.


   Discussion Top


Cowden syndrome is an inherited autosomal dominant trait with incomplete penetrance and a range of expressivity. It is characterized by multiple hamartomas and neoplasms of ectodermal, endodermal, and mesodermal origin affecting skin, oral mucosa, GI tract, bones, CNS, eyes, and genitourinary tract. Mucocutaneous features include trichilemmomas, oral mucosal papillomatosis, acral keratosis, and palmoplantar keratosis. This syndrome is associated with the development of several types of malignancies, especially breast carcinoma and thyroid carcinoma, which is why recognition of individuals with the syndrome is important. [1],[4],[5]

It is a rare syndrome with over 300 published cases internationally. The passage of this disease to offspring has been reported to be 1 in 200,000 births. CD is caused by a mutation in the PTEN tumor suppressor gene (also termed as MMAC1 or TEP1) on band 10q23. The PTEN protein product is believed to promote cell death and the mutation that causes loss of protein's function that may lead to over proliferation of cells, resulting in hamartomatous growths. [3],[4],[6]

Diagnosis of this disease is typically established between ages 13-64 with average 22 years. A slight female predilection is noted. In 90-100% patients, one of four types of mucocutaneous lesions is present that include flesh-colored flat-topped lichenoid or elongated verrucoid cutaneous facial papules ranging from 1 to 5 mm in diameter, most of which are trichilemmomas. Oral lesions in the form of papules, measuring around 1-3 mm, with smooth whitish surface present on gingival, labial, and palatal surfaces of oral cavity. These lesions often coalesce into confluents sheets, which are described as having cobblestone appearance. Histologically, they are benign fibromas. Acral keratosis is present on the dorsal hands and feet, and there can also be the presence of palmoplantar keratosis. [4],[6] In this case, all the above mucocutaneous lesions are present except for palmoplantar keratosis.

Less frequently noted lesions include lipomas, neuromas, and hemangiomas. Multiple mucosal neuromas as the presenting sign of Cowden syndrome have also been reported. Other facial and oral features include macrocephaly, adenoid facies, micrognathia, and high arched palate. [1],[4],[6],[7]

Abnormalities of thyroid are present in approximately 60% of the cases manifested as goiter, benign adenomas, and follicular adenocarcinomas. There is increased tendency of development of thyroid carcinoma. Fibrocystic disease and fibroadenomas of breast are present in approximately 75% of cases, while carcinoma of breast occurs in 20-36% of cases. GI abnormalities are present in most of the patients in the form of polyps that can occur in the oesophagus, stomach, intestine, or anus but are most common in the colon. [4],[8],[9] These polyps are sessile or pedunculated and can be hyperplastic, lipomatous, ganglioneuromatous, lymphoid, or rarely adenomatous. [9]

Genitourinary manifestations that are common include ovarian cysts, leiyomyomas, adenocarcinomas of cervix, and benign urethral polyps. [4],[10] Skeletal abnormalities include bone cysts, thoracic kyphosis, as well as one reported case of osteosarcoma. [4] Lhermitte duclos disease is considered currently as part of CD and is caused by hamartomatous growths of cerebellum. [4],[10] This case showed the presence of GI lymphoid polyp and initial fibrocystic disease of breast.

The international Cowden syndrome consortium has proposed operational criteria for the diagnosis of Cowden syndrome. [1],[4] This case report fulfilled the pathognomic criteria and can be placed under diagnostic criteria 1 [Table 1].
Table 1: International Cowden consortium operational diagnostic criteria 2000

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Because of multitude of pathologic manifestations in Cowden syndrome, its differential diagnosis based on lesional appearances includes a long list of conditions like bannayan riley ruvalcaba syndrome, proteus syndrome, tuberous sclerosis, fragile x syndrome, Hecks disease, Darier's disease, epidermolysis bulosa, Goltz syndrome, and juvenile polyposis syndrome. [1],[4],[11]

Laboratory investigations that are essential at baseline and as indicated clinically in subsequent years are complete blood count, thyroid function tests, urinalysis, and lesion biopsy. Imaging modalities include annual or biannual mammograms to screen for breast cancer, chest radiograph, thyroid scans, upper and lower GI endoscopy or barium swallow for GI hamartomas, intravenous pyelogram, and MRI of head if symptoms are present to exclude Lhermitte duclos disease. [4],[10]

Treatment is complicated by high risk of cancers of various organ systems. [1] The mucocutaneous lesions can be treated with five fluorouracil, retinoids, electrosurgery, cryosurgery, dermabrasion, laser abrasion, interferon-2 alfa, bleomycin, and surgery. [4] Future treatment options to help control the increased cancer risk of patients may focus on restoration of PTEN-associated molecular pathways. [1] The overall prognosis of this syndrome is guarded owing to high risk of cancer and frequent follow up being the key to survival. [1],[4]


   Conclusion Top


The oral physician play an important role in identifying oral and head and neck manifestations of this syndrome as in this case, allowing for close surveillance for early detection of malignant process.

 
   References Top

1.Scheper MA, Nikitakis NG, Sarlani E, Sauk JJ, Meiller TF. Cowden syndrome: report of a case with immunohistochemical analysis and review of literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;101:625-31.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]  
2.Lloyd KM 2nd, Dennis M. Cowden′s disease- A possible new symptom complex with multiple system involvement. Ann Intern Med 1963;58:136-42.  Back to cited text no. 2  [PUBMED]    
3.Takenoshite Y, Kubo S, Takenchi T, Lida M. Oral and facial lesions in Cowden syndrome. J Oral Maxillofac Surg 1993;57:682-7.  Back to cited text no. 3      
4.Miller C. Cowden syndrome. eMedicine. [Homepage on the Internet]. Available from: http://www.emedicine.com/neuro/topic399.htm . [last updated on 2007 16 Feb]  Back to cited text no. 4      
5.Mignogna M, Muzio LL, Ruocio V, Bucci E. Early diagnosis of multiple hamartomas and neoplasia syndrome. The role of dentist. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1995;79:295-9.  Back to cited text no. 5      
6.Greenberg MS, Glick M, Ship JA. Burkett′s textbook of oral medicine. 11 TH edition. BC Becker Inc: 2008. p. 131-2.  Back to cited text no. 6      
7.Shafer, Hine, Levy. Textbook of oral pathology. 5 th edition: Elsiever Publication; 2006. p. 994-7.  Back to cited text no. 7      
8.Usha V, Nair GT. Cowden syndrome report of 2 cases. Indian J Dermatol Venereol Leprol 1999;65:42-3.  Back to cited text no. 8    Medknow Journal  
9.Goulas SS, Papanoannou DG. Cowden′s disease: a case report and review of literature. Ann Gastroenterol 2003;16:70-3.  Back to cited text no. 9      
10.Blanco V, Keochgerián V. Cowden′s syndrome. Case report, with reference to an affected family. Med Oral Patol Oral Cir Bucal 2006;11:E2-6.  Back to cited text no. 10      
11.Segura Saint-Gerons R, Ceballos Salobreña A, Toro Rojas M, Gándara Rey JM. Oral manifestations of Cowden′s disease. Presentation of a clinical case. Med Oral Patol Oral Cir Bucal 2006;11:E421-4.  Back to cited text no. 11      

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Correspondence Address:
S M Ravi Prakash
Department of Oral Medicine and Radiology, Kothiwal Dental College and Research Centre, Mora Mustaqueem, Moradabad (U.P.)
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0970-9290.70803

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
 
 
    Tables

  [Table 1]

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