Cowden syndrome in children caused by a new mutation of PTEN gene: a case report and literature review / 中华实用儿科临床杂志

Objective:To summarize the clinical and gene mutation characteristics of a child with Cowden syndrome and review the literature.Methods:The clinical data of a child with Cowden syndrome treated in the First Affiliated Hospital of Xinxiang Medical University in June 2020 were analyzed retrospectively.Taking " Cowden syndrome" , " PTEN gene" , " hamartoma polyps" , "child" , " Cowden syndrome and child" and " PTEN and child" as key words, literature was retrieved from Chinese databases (China National Knowledge Internet database and Wanfang database) and the PubMed database from the establishment of the database to March 2021. Results:A 13-year-old male had intermittent abdominal pain and abdominal distension for 5 months.Electron microscopic gastroenteroscopy showed multiple polyps, and focal lymphocyte aggregation and infiltration were found in tissue biopsy.Whole exon sequencing revealed a hemizygous mutation of c. 475 (exon5) A>T in PTEN gene, which led to the transformation of the 159 th amino acid from arginine to tryptophan.The prediction results of the tertiary structure of the protein indicated that the variation might affect the spatial structure of the protein and damage the protein function.According to the clinical characteristics, Cowden syndrome was diagnosed.The pedigree confirmed that the variation was inherited from the mother, who had a similar phenotype.No qualified Chinese report was retrieved.Among 41 English studies on PTEN gene mutation in children, there were only two reports related to pediatric Cowden syndrome.The hemizygous mutation of PTEN gene was not reported. Conclusions:The missense mutation of c. 475 (exon5) A>T in PTEN gene in this study is a novel cause of Cowden syndrome, and the case is the first case report in China.

A Rare WHO Grade I Lesion of the Posterior Fossa with Recurrence Biological Behavior ­ Dysplastic Gangliocytoma of the Cerebellum: Case Report

Dysplastic gangliocytoma of the cerebellum (DGC) or Lhermitte-Duclos Disease is a rare lesion (World Health Organization [WHO] grade I) characterized by thickened folia and replacement of the internal granular layer by abnormal ganglion cells. More commonly, the compromised patients are young adults presenting ataxia, seizures, obstructive hydrocephalus, and increased intracranial pressure. Dysplastic gangliocytoma of the cerebellum is intimately associated with Cowden syndrome, a hereditary disorder caused by a germline mutation in the PTEN tumor suppressor gene on chromosome 10q23. Large neurons of DCG show vesicular nuclei with prominent nucleoli. Expansion of the internal granular layer determines vacuolization of the molecular layer and white matter, which can be related to the bright stripes identified on T2-weighted magnetic resonance imaging. Herein, the authors report a female patient who developed long- time recurrence of DGC and discuss pathological findings and differential diagnosis of this rare cerebellar lesion.

Lhermitte-Duclos Disease and Cowden Syndrome: A Case Report and Literature Review

Lhermitte-Duclos disease (LDD), also known as dysplastic gangliocytoma of the cerebellum, is a rare, usually benign, slow-growing tumor, that commonly affects patients aged 30 to 50 years-old. The manifestations of dysplastic cerebellar gangliocytoma are nonspecific and are related both to the mass effect produced by its growth and to the location of the lesion. Cerebellar symptoms such as ataxia are often present. In 40% of cases, the tumor is associated with Cowden syndrome, which is part of a group ofgenetic disorders called polypoid hamartoma complex. In this case report, the patient presented expansive lesion in the posterior fossa, compatible with LDD, associated with macrocephaly. These findings are consideredmajor criteria for Cowden syndrome. When together, they confirm the diagnoses. To our knowledge, this is the first report of the association of LDD and Cowden syndrome in Brazil.

Síndrome de Cowden / Cowden syndrome

El síndrome de Cowden es una enfermedad hereditaria, de transmisión autosómica dominante, caracterizada por la presencia de múltiples hamartomas y nódulos en la piel y la mucosa oral, junto con anomalías en mamas, tiroides y pólipos en el tracto gastrointestinal, con un riesgo incrementado de tumores malignos. Se reporta un caso de una paciente con diagnóstico de bocio tóxico nodular, y que presentaba -por los antecedentes y estudios realizados- manifestaciones compatibles con el síndrome de Cowden. El síndrome de Cowden es el síndrome hamartomatoso tumoral del phosphatase and tensinhomolog mejor descrito hasta el momento. Los pacientes con él tienen lesiones mucocutáneas características y un elevado riesgo de cáncer de mama, tiroides, endometrio, colorrectal y renal, así como varias manifestaciones benignas como macrocefalia y gangliocitomadisplásico del cerebelo. Es importante el diagnóstico precoz de este síndrome y el seguimiento a largo plazo, dado el alto riesgo de desarrollar tumores malignos(AU)

Cowden syndrome is a hereditary disease, of autosomal dominant transmission, and characterized by the presence of multiple hamartomas and nodules in the skin and oral mucosa, and also with abnormalities in the breast, thyroid, and polyps in the gastrointestinal tract with an increased risk of malignant tumors. It is reported a case of a patient with a diagnosis of toxic nodular goiter, and who presented -due to the antecedents and studies carried out- manifestations compatible with the Cowden syndrome. Cowden syndrome is the hamartomatous tumor syndrome of phosphatase and tensin homolog which is better described so far. Patients having it present characteristic mucocutaneous lesions and a high risk of breast, thyroid, endometrial, colorectal and renal cancers, as well as several benign manifestations such as macrocephaly and gangliocytoma of the cerebellum. Early diagnosis of this syndrome and long-term follow-up are important given the high risk of developing malignant tumors(AU)

Synchronous Bilateral Breast Carcinoma in a Patient with Cowden Syndrome with PTEN Mutation: A Case Report

Cowden syndrome (CS), also known as multiple hamartomas syndrome, is a rare hereditary autosomal dominant disorder caused by a germline mutation in the phosphatase and tensin homolog (PTEN) gene mapped on chromosome 10. The clinical features of CS are variable, primarily presenting as mucocutaneous lesions (99%). A mucocutaneous lesion, such as trichilemmoma of the face or keratosis of the extremities, is an important diagnostic marker for CS. CS has been reported to increase the incidence of benign and malignant neoplasms in the breast, thyroid, and gastrointestinal tract. The risk of developing malignancy in individuals with CS is up to 10 times higher than general population throughout an entire life time.

Dysplastic cerebellar gangliocytoma/Lhermitte-Duclos disease: report of 6 cases and review of the literatures / 临床与实验病理学杂志

Purpose To investigate the clinicopthologic features of dysplastic cerebellar gongliocytoma/Lhermitte-Duclos disease (LDD) and to discuss the diagnosis and differential diagnosis of the tumor.Methods Histopathological characteristics and immunohistochemical of SP results of 6 cases of LDD were studied and the relevant literatures were reviewed.Results 6 cases ranged in age from 23 to 56 years old,with an average of 34 years.The clinical manifestations were intracranial hypertension with or without cerebellar signs.MRI manifestations were characteristic by "tiger spots".Histology showed local cerebellar structure disorders,granulocytes and Purkinje cells decreased and replaced by a large number of abnormal ganglion cells.2 cases were followed up for 5 to 8 years recurrence,the remaining 4 cases recovered well.Conclusion LDD is a rare primary benign lesions of the cerebellum.Diagnosis depends on imaging and histopathological examination.The gross total resection is the best treatment choice.

Síndrome de Cowden. Presentación de un caso infrecuente / Cowden syndrome. Presentation of an infrequent case

El síndrome de Cowden es una enfermedad hereditaria, de transmisión autosómica dominante, caracterizada por la presencia de múltiples hamartomas y nódulos en piel y mucosa oral, junto con anomalías en mama, tiroides y pólipos en el tracto gastrointestinal, tendiendo a malignizarse sobre todo en mama y tiroides. El diagnóstico precoz a partir de las lesiones en piel y alteraciones digestivas pueden redirigir el estudio buscando malignidades en tiroides y en caso que sea una fémina en mama. Se presenta un caso clínico que debuta por trastornos digestivos que se interpretan como un sangramiento digestivo alto, al realizar la endoscopia se observan múltiples pólipos duodenales que junto a las alteraciones de la piel hacen el diagnóstico. La presencia de pápulas faciales cutáneas y la papilomatosis de la mucosa oral son los criterios clínicos mayores para establecer el diagnóstico del síndrome de Cowden debiendo alertar al clínico ante la posibilidad de otras lesiones neoplásicas, a veces ocultas, sobre todo en mama, tiroides y tubo digestivo con carácter maligno.

Cowden syndrome is an inherited disease, of dominant auto somatic transmission, characterized by the presence of multiple hamartomas and nodules in skin and oral mucosa, together with anomalies in breasts and thyroids, and polyps in the gastrointestinal tract; they tend to become malignant, above all in breast and thyroids. The precocious diagnosis after finding skin lesions and digestive disturbances should redirect the study, looking for malignancy in thyroids and, in cases of women patients, in breast. We presented a clinical case debuting with digestive disturbances interpreted as upper digestive bleeding. During the endoscopy, several duodenal polyps were observed that together with skin disturbances led to the diagnosis. The presence of skin facial papules and the oral mucosa papillomatosis are the bigger clinical criteria to stablish the Cowden syndrome diagnosis; they should raise the clinician alert toward the possibility of other neoplastic lesions, sometimes hidden, especially in the breast, thyroids and alimentary canal, with malignant character.

The importance of the dentist in the diagnosis of cowden syndrome – Case report

Cowden Syndrome is an autosomal dominant disorder characterized by the development of several hamartomas in a variety of tissues, including the skin, gastrointestinal tract, adipose tissue, and bone and connective tissues. This syndrome is associated with a high risk of developing malignancies, especially breast, thyroid and endometrium cancers. This report presents a case of a 53-year-old patient who sought assistance at the Dentistry Department of the University Hospital of Brasilia (HUB) to receive basic dental treatment. The current and past medical history and oral and facial manifestations led to the diagnosis of Cowden syndrome. This case report aims to highlight the importance of a dental surgeon in the diagnosis of this syndrome, based on the observation of oral manifestations and medical history.

A Síndrome de Cowden é uma desordem hereditária autossômica dominante, caracterizada pelo desenvolvimento de diversos hamartomas em vários tipos de tecidos, incluindo a epiderme, trato gastrointestinal, tecido adiposo e tecidos ósseo e conjuntivo. Essa síndrome é associada a um risco elevado de desenvolvimento de malignidades, especialmente câncer de mama, tireoide e endométrio. Esse relato apresenta o caso de um paciente de 53 anos de idade que procurou o Departamento de Odontologia do Hospital Universitário de Brasília (HUB) para tratamento dental básico. História médica atual e passada e manifestações orais e faciais levaram ao diagnóstico de síndrome de Cowden. Este relato de caso apresenta a importância do cirurgião-dentista no diagnóstico desta síndrome, com base na observação das manifestações orais e história médica.

A Case of Cowden Syndrome Associated with Tumor of the Follicular Infundibulum / 대한피부과학회지

Cowden Syndrome (CS) is a rare genodermatosis of autosomal-dominant inheritance, with variable expressivity and multiple types of hamartomas. The most consistent features of CS are small wart-like papillomatous papules on the face, hands, and mouth. A 31-year-old woman presented with a history of pearly papules on the face, hand, and foot for several years. The lesions were initially diagnosed as warts, and treated accordingly, but they did not subside. There was a history of endometrial cancer, breast cancer, and thyroid nodule, and her father had a history of thyroid cancer. A biopsy specimen from the facial papule showed plate-like growth of anastomosing epithelial cords, extending parallel to the epidermis. It was diagnosed as a tumor of the follicular infundibulum (TFI). The patient refused further treatment. Here, we report a rare case of CS presenting with TFI.

Cowden Syndrome with a Novel Germline PTEN Mutation and an Unusual Clinical Course

Here, we report a case of Cowden syndrome with an unusual clinical course of late-onset oral papillomatosis and a novel germline PTEN mutation. Cowden syndrome is the most common phosphatase and tensin homolog hamartomatous tumor syndrome. It is characterized by multiple hamartomas in the gastrointestinal tract and mucocutaneous lesions such as trichilemmomas, oral papillomatosis, facial papules, and acral keratoses. Patients with Cowden syndrome have a higher risk of malignancies, especially breast, colon, and thyroid cancers. A 53-year-old female presented with cobblestone-like papillomatous papules on the lower gums that developed 1 year earlier. She had no other mucocutaneous lesions besides oral papillomatosis. Gastrointestinal endoscopy and colonoscopy revealed multiple hamartomas in the stomach and colon. The patient had a history of breast cancer and multinodular goiter diagnosed 4 and 5 years ago, respectively. She was diagnosed with Cowden syndrome and a novel PTEN mutation was confirmed by direct sequencing.

Cowden Syndrome Presenting as Breast Cancer: Imaging and Clinical Features

Cowden syndrome is an uncommon, autosomal dominant disease which is characterized by multiple hamartomas of the skin, mucous membrane, brain, breast, thyroid, and gastrointestinal tract. The diagnosis of Cowden syndrome implicates an increased risk of developing breast cancer. We report a case of a 22-year-old woman with Cowden syndrome that presented as breast cancer with concomitant bilateral exuberant benign masses in both breasts.

A Case of Multiple Eyelid Trichilemmoma Associated with Cowden Syndrome

PURPOSE: To report a case of multiple eyelid trichilemmomas associated with Cowden syndrome. CASE SUMMARY: A 27-year-old woman presented with multiple upper and lower eyelid skin masses that developed over several years. The masses were as large as whitish millet, and were around the upper and lower eyelid margin and the face. The patient had previously undergone subtotal thyroidectomy for a thyroid mass and a mass excision for extremity hemangioma. Excisional biopsy was performed for the diagnosis, and trichilemmoma was diagnosed based on histopathologic examination. Consequently, multiple trichilemmoma associated with Cowden syndrome was diagnosed, and breast evaluations for existence of further masses were recommended. On breast examinations, intraductal papilloma and fibroadenoma were detected. CONCLUSIONS: The trichilemmoma was a hair-follicle benign tumor that also appeared on the skin around the eyelid. If multiple trichilemmoma is diagnosed, an association with Cowden syndrome should be considered as well as presence of masses in other organs.

Cowden syndrome.

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.

Cowden Syndrome Accompanied by Multiple Sclerotic Fibroma on the Face / 대한피부과학회지

Cowden syndrome (CS) is a rare genodermatosis that is characterized by multiple hamartomatous tumors of an ectodermal, mesodermal and endodermal origin. CS is associated with an increased risk of malignancy and especially breast cancer, thyroid cancer, uterine cancer and renal cell carcinoma. The characteristic features of the disease are mucocutaneous findings, including multiple facial trichilemmomas, oral mucosal papillomatosis and acral keratoses. Multiple sclerotic fibroma is also known to be a clue to diagnose CS. We herein emphasize that multiple sclerotic fibromas of the skin are an important marker of CS, which may also be helpful for making an early diagnosis.

Clinical approach of hereditary cancer in gynecology / 대한산부인과학회지

Hereditary cancer syndrome is a genetic condition that causes and increases the risk for specific type of cancers. Recent advances in genetics have identified a number of genes associated with inherited susceptibility to cancer, and this rapid development of knowledge about cancer genetics have implications for all aspects of cancer management, including prevention, screening, and treatment. Hereditary patterns of cancer are often characterized by early age at onset, high penetrance, bilaterality in paired organs, vertical transmission through either parent, and an association with other types of tumors. Most representative hereditary cancer syndromes in gynecologic field are hereditary breast/ovarian cancer syndrome (HBOC), hereditary non-polyposis colorectal cancer (HNPCC), Li-Fraumeni syndrome, and Cowden syndrome. Several familial mutations of specific genes, such as BRCA1, 2, TP53, PTEN, MMR, CHEK2, are linked to hereditary cancer syndrome, which are responsible for hereditary gynecologic cancers. It would be very important for gynecologic doctors to know the inclusion criteria for the genetic assessment, taking family history, clinical evaluation, genetic testing, screening guideline and risk reduction strategies for women with hereditary high risk factor. The morbidity and mortality of gynecologic malignancies related to these syndromes could be reduced by the adequate clinical approach, although recent guidelines were developed with an acute awareness of the preliminary nature of much of our knowledge regarding the clinical application of the rapidly emerging field of molecular genetics, and with an appreciation for the need for flexibility when applying these guidelines to individual families.

Candida Esophagitis in a Patient with Cowden's Syndrome: A Case Report / 대한소아소화기영양학회지

Cowden's syndrome is a harmatomatous polyposis syndrome with characteristic mucocutaneous lesions and among the spectra of clinical disorders that has been attributed to germline mutations in the PTEN gene. Although Cowden's syndrome has rarely been reported, immunologic studies have revealed that patients with this syndrome have humoral and/or cellular immune abnormalities. We recently identified a 21-year-old woman with Cowden's syndrome who was diagnosed with candida esophagitis without a history of diabetes, carcinoma, or steroid therapy. We report the immunologic status of this patient and the relationship with candida esophagitis on the basis of a literature review.

Enfermedad de Lhermitte-Duclos: Informe de un caso y revisión de la literatura / Lhermitte-Duclos disease: Case report and review of literature

Introducción. El gangliocitoma displásico del cerebelo fue descrito originalmente en 1920 por Lhermitte y Duelos, autores a quienes se les debe el epónimo de esta enfermedad. Es una entidad rara, caracterizada por ser una masa tumoral unilateral de la corteza cerebelosa, de crecimiento muy lento, que produce un aumento de la presión intracraneana. En 1991 Padberg y col. describieron la asociación de la enfermedad Lhermitte-Duclos y el síndrome de Cowden (SC). Aún no se ha comprendido completamente la biología molecular que asocia a estas enfermedades, sin embargo se ha comprobado en estudios modelos animales (ratones) mutaciones del gen homólogo de fosfatasa y tensina suprimido del cromosoma 10 (PTEN). Las imágenes de resonancia magnética son características de esta entidad, de tal manera que permiten hacer el diagnóstico preoperatorio sin la necesidad de estudios histopatológicos, permitiendo una evaluación y manejo neuroquirúrgico adecuados. Caso clínico. Se informa el caso de una mujer de 17 años con enfermedad de Lhermitte-Duclos del hemisferio cerebeloso derecho no asociado a SC, en quien el diagnóstico se estableció en el transoperatorio con improntas de la lesión cerebelosa. Conclusión. No existen publicaciones previas que describan las características cito lógicas de la lesión, y en este caso sí fue posible estudiarlas.

Introduction. Dysplastic cerebellar gangliocytoma was first described in 1920 by Lhermitte and Duelos, authors who gave their name to the entity. It is a rare condition, which is characterized by a very slowly growing unilateral tumor mass of the cerebellar cortex, producing increased intracranial pressure. In 1991 Padberg et al. described the association of Lhermitte-Duclos disease and Cowden syndrome. The relationship between these 2 entities has been associated with mutations of the phosphatase and tensin homolog deleted on chromosome (PTEN) gene. Magnetic resonance imaging findings are the hallmark of this entity, and the diagnosis is established without hystopathologic studies. Case report. We inform a case of a 17 years old girl with Lhermitte-Duclos of the right cerebellar hemisphere without Cowden syndrome.

A Case of Cowden Syndrome Associated with Breast Cancer and Thyroid Cancer / 대한소화기내시경학회지

Cowden syndrome, which is also known as 'multiple hamartoma syndrome', is an autosomal dominant condition with variable expression resulting from a mutation in the PTEN gene on the chromosome arm, 10q23. Cowden syndrome causes hamartomatous neoplasms of the skin and mucosa, breast, thyroid, and gastrointestinal tract, and is associated with the development of several types of malignancy. In particular, a marked increase in the incidence of breast carcinoma in women and of thyroid carcinoma in both men and women has been reported. We report a case of Cowden syndrome associated with both carcinomas with a review of the relevant literature.

Long-term Follow-up of a Case of Cowden Syndrome / 대한소아소화기영양학회지

Cowden syndrome is very rare clinical condition with characteristic mucocutaneous lesions associated with abnormalities of the breast, thyroid, and gastrointestinal tract. Here, the case of a 16-year-old girl with diverse gastrointestinal polyposis with breast and thyroid lesions is reported as a definite case of Cowden syndrome. During follow up for 4 years, changes in the characteristic lesions were observed; Esophageal acanthosis and oropharyngeal polyps were newly developed. Gastric, duodenal, rectal and ileal polyps were noted at the first visit when she was 12 years of age and revealed histologically hyperplastic polyps. Mucocutaneous lesions, the pathognomonic finding of Cowden syndrome, were not noted at the first visit or during the follow up period. Breast and thyroid masses were noted at the first visit. Breast aspiration showed highly cellular ductal epithelial fragments and fibroblastic stromal cell fragments, and a thyroid biopsy shows proliferation of irregular sized follicles, with variable colloid contents. Macrocephaly was also noted at the first visit. The characteristic lesions of Cowden syndrome change with the patient's age, and the long-term follow up is recommended in cases suspected with this syndrome.

A Case of Cowden's Syndrome / 대한소화기내시경학회지

A 17-year-old man was referred to our hospital because of dizziness and mild dyspnea. He had a history of partial thyroidectomy due to benign mass when he was 10 year-old. His conjunctiva was anemic and acral keratosis was noted. He had a goiter and a previous surgical scar on the anterior neck just below the thyroid cartilage. Blood counts were as follows; Hb was 4.3 g/dL, WBC 5,500/mm3, PLT 366,000/ mm3. Esophagogastroduodenoscopy and colonoscopy showed esophageal acanthosis and numerous variable sized polyps in the stomach, duodenum and colon. The small bowel series showed numerous polypoid lesions in the entire small bowel. Gastric polyps revealed hamartoma and colon polyps revealed inflammatory polyp with lymphoid hyperplasia by pathologic examination. Thyroid ultrasonograph showed multiple nodules and cysts and I131 scintigraphy showed multiple cold and hot nodules in his remnant thyroid gland. We diagnosed the patient as Cowden's syndrome.