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.

Follicular thyroid carcinoma metastatic to skin: a small papule and a big diagnostic change

Abstract: Cutaneous metastases are uncommon in daily practice, although very important, since they may be the first manifestation of an undiscovered primary neoplasm or the first indication of recurrence. Cutaneous metastases from the breast are the most frequent in women and cutaneous metastases from the lung are the most frequent in men. Thyroid carcinoma, despite representing the most frequent endocrine neoplasm, is considered a rare neoplasm, corresponding to 1% of malignant neoplasms diagnosed. Cutaneous metastases from follicular carcinoma are rare and occur mainly in the head and neck area. We report a case of cutaneous metastasis in a patient with follicular thyroid carcinoma and breast carcinoma. Because of the association of these two neoplasms, the possibility of Cowden Syndrome - multiple hamartoma syndrome - was raised, but was excluded by genetic analysis of PTEN gene.

PTEN Mutation Identified in Patient Diagnosed with Simultaneous Multiple Cancers / Journal of the Korean Cancer Association, 대한암학회지

PTEN hamartoma tumor syndrome is a spectrum of disorders characterized by unique phenotypic features including multiple hamartomas caused by mutations of the tumor suppressor gene PTEN. Cowden syndrome and Bannayan–Riley–Ruvalcaba syndrome are representative diseases, and both have several common clinical features and differences. Because PTEN mutations are associated with an increased risk of malignancy including breast, thyroid, endometrial, and renal cancers, cancer surveillance is an important element of disease management. We report a germline mutation of the PTEN (c.723dupT, exon 7) identified in a young woman with a simultaneous occurrence of breast cancer, dermatofibrosarcoma protuberans, and follicular neoplasm. This case suggests that it is critical for clinicians to recognize the phenotypic features associated with these syndromes to accurately diagnose them and provide preventive care.

Current understanding of the genetics of extracranial arteriovenous malformation / 中华整形外科杂志

Arteriovenous malformation (AVM) is defined as a congenital vascular anomaly that shunts blood from arteries to veins with no capillary perfusion. In some rare hereditary diseases, including capillary malformation-arteriovenous malformation (CM-AVM), hereditary hemorrhagic telangiectasia (HHT), PTEN hamartoma-tumor syndrome (PHTS), AVM is generally considered the characteristic clinic presentation. This review primarily focused on the mechanisms of genetic regulation during embryonic vasculature development, genetic mutations in TGF-beta signaling pathway of HHT, PTEN mutations in PHTS and genetic screening of CM-AVM. In addition, current findings in somatic mutations of extracranial AVM were discussed as well. This review aimed to provide insight into the etiology to help the diagnosis and treatment of extracranial AVM in clinic.

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.

Benign follicular tumors

Abstract: Benign follicular tumors comprise a large and heterogeneous group of neoplasms that share a common histogenesis and display morphological features resembling one or several portions of the normal hair follicle, or recapitulate part of its embryological development. Most cases present it as clinically nondescript single lesions and essentially of dermatological relevance. Occasionally, however, these lesions be multiple and represent a cutaneous marker of complex syndromes associated with an increased risk of visceral neoplasms. In this article, the authors present the microscopic structure of the normal hair follicle as a basis to understand the type and level of differentiation of the various follicular tumors. The main clinicopathological features and differential diagnosis of benign follicular tumors are then discussed, including dilated pore of Winer, pilar sheath acanthoma, trichoadenoma, trichilemmoma, infundibuloma, proliferating trichilemmal cyst/tumor, trichoblastoma and its variants, pilomatricoma, trichodiscoma/fibrofolliculoma, neurofollicular hamartoma and trichofolliculoma. In addition, the main syndromes presenting with multiple follicular tumors are also discussed, namely Cowden, Birt-Hogg-Dubé, Rombo and Bazex-Dupré-Christol syndromes, as well as multiple tumors of follicular infundibulum (infundibulomatosis) and multiple trichoepitheliomas. Although the diagnosis of follicular tumors relies on histological examination, we highlight the importance of their knowledge for the clinician, especially when in presence of patients with multiple lesions that may be the cutaneous marker of a cancer-prone syndrome. The dermatologist is therefore in a privileged position to recognize these lesions, which is extremely important to provide further propedeutic, appropriate referral and genetic counseling for these patients.

Syndrome In Question

The authors describe a case of Cowden´s syndrome in a female patient with classic cutaneous lesions, plus papillomatous lesions in the gastrointestinal tract and a previous history of thyroid carcinoma. Mucocutaneous lesions occur in 90% of Cowden's syndrome cases and are characterized by facial trichilemmomas, oral mucosal papillomas and benign acral keratoses. Sites of extracutaneous involvement include: the thyroid, gastrointestinal tract, breast and endometrial tissue. There is risk of malignancies in these organs and they need to be monitored with imaging tests. The early diagnosis of the syndrome by a dermatologist through mucocutaneous lesions enables the investigation and diagnosis of extracutaneous involvement. .

Cowden Syndrome: report of a case and brief review of literature / Sindrome de Cowden: Relato de caso e uma breve revisao da literatura

We present the case of a female patient with facial cutaneous lesions, a cobblestone-like pattern of the oral mucosa, and verruciform lesions on the hand since her youth. She reported a history of breast cancer, endometrial cancer, melanoma and multiple benign tumors and cysts. PTEN gene analysis was performed and confirmed Cowden Syndrome, a rare genodermatosis with an autosomal dominant pattern of inheritance, characterized by multiple hamartomas. The phosphatase and tensin homolog (PTEN) gene negatively regulates cell proliferation and cell cycle progression. Loss of PTEN function contributes to an increased risk of cancer. We emphasize the importance of early detection and accurate management of Cowden Syndrome.

Apresentamos o caso de uma paciente com lesões cutâneas faciais, mucosa oral com aparência de paralelepípedo, e lesões de aspecto verrucoso na mão desde a sua juventude. Ela relatou uma história de câncer de mama, câncer de endométrio, melanoma e múltiplos tumores benignos e cistos. A análise genética PTEN foi realizada e confirmou a Síndrome de Cowden, uma genodermatose rara, com um padrão de herança autossômica dominante, caracterizada por múltiplos hamartomas. O gene homólogo de fosfatase e angiotensina (PTEN) regula negativamente a proliferação celular e a progressão do ciclo celular. A perda da função PTEN contribui para um aumento do risco de câncer. Ressaltamos a importância da detecção precoce e tratamento preciso da Síndrome de Cowden.

Bannayan-Riley-Ruvalcaba syndrome with deforming lipomatous hamartomas in infant - Case report / Sindrome de Bannayan-Riley-Ruvalcaba com hamartomas lipomatosos deformantes em lactente - Relato de caso

Bannayan-Riley-Ruvalcaba Syndrome is a rare condition caused by mutations in the PTEN gene. It displays association of multiple lipomas, macrocephaly, hemangiomas, hamartomatous intestinal polyposis, developmental delay and speckled pigmented maculae on the male genitalia. We report the case of a nine-month-old boy who had fast growing and progressive tumors for three months, macrocephaly and lentigines on the penis. Imaging tests showed extensive lipomatosis with invasion of paraspinal muscles, enlargement of the spinal canal and spinal cord compression; after surgical excision of the mass, the pathology was consistent with lipoma. Adipocyte culture karyotype demonstrated PTEN mutation. We present this case for its rarity and exuberance.

A síndrome de Bannayan-Riley-Ruvalcaba é afecção rara, causada por mutações no gene PTEN. Apresenta associação de múltiplos lipomas, macrocefalia, hemangiomas, polipose hamartomatosa intestinal, atraso do desenvolvimento e máculas salpicadas na genitália masculina. Relatamos o caso de um menino de nove meses com lesões tumorais de crescimento rápido e progressivo em três meses de evolução, macrocefalia e lentigos no pênis. Exames de imagem demonstraram extensa lipomatose com invasão da musculatura paraespinhal, alargamento do canal vertebral e compressão medular. Depois da excisão cirúrgica da massa, o anatomopatológico foi compatível com lipoma. A análise do cariótipo em cultura de adipócitos demonstrou mutação do PTEN. Apresentamos este caso por sua exuberância e raridade.

Do you know this syndrome? / Voce conhece esta sindrome?

Cowden's disease or multiple hamartoma syndrome is an autosomal dominant inherited disease and the main dermatological features are facial trichilemmomas (hamartomas of the follicular infundibula), oral fibroma and benign acral keratoses. The importance of this disease lays in the increased susceptibility to malignization of some lesions, especially breast, thyroid and genitourinary tract. Despite its varied phenotypic expression, this disease is generally unknown. Consequently, many cases are undiagnosed or diagnosis comes at a late stage, which reinforces the importance of an early investigation of the disease so the patient may have periodic check-ups to discover and treat malignancies.

A doença de Cowden ou síndrome dos hamartomas múltiplos é de transmissão autossômica dominante cuja tríade dermatológica compõem-se de triquilemomas faciais múltiplos (hamartomas do infundíbulo folicular), fibromas orais e queratoses acrais benignas. A importância desta doença está no aumento da susceptibilidade a malignização de algumas lesões, especialmente de mama, tireóide e trato genito-urinário. Apesar da expressão fenotípica variada, esta doença é geralmente desconhecida. Consequentemente, muitos casos não são diagnosticados ou o diagnóstico vem tardiamente, o que ressalta a importância do diagnóstico precoce da doença para que o paciente possa ser monitorado periodicamente para diagnóstico e tratamento precoce de doenças malignas.

Autosomal Dominant Inherited Cowden's Disease in a Family

Cowden's disease, also known as a kind of phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome, is an uncommon autosomal dominant inherited complex disorder with various hamartomatous growths of multiple organs involving all three germ cell layers. It usually manifests with polyps throughout the gastrointestinal tract, ranging anywhere from 30% to 85%, and more common extra intestinal findings. Mucocutaneous lesions like facial trichilemmomas, acral keratoses, papillomatous papules and macrocephaly, and malignancies including breast, thyroid and endometrial carcinoma are the hallmark of the disease. Here we report on familial Cowden's diseases case of a 52-year-old male proband with mucocutaneous lesions and mutation on the PTEN gene obtained by extrapolating from gastrointestinal polyposis as a starter and his daughter who developed thyroid cancer.

A Case of Familial Basaloid Follicular Hamartoma Syndrome / 대한피부과학회지

Basaloid follicular hamartoma is a benign adnexal tumor consisting of basaloid cells with follicular differentiation. It can present as a solitary lesion, multiple lesions, or an autosomal dominant inherited syndrome (basaloid follicular hamartoma syndrome). Basaloid follicular hamartoma syndrome is a rare adnexal tumor genodermatosis, which is characterized by autosomal dominant inheritance, histologically proven basaloid follicular hamartomas and associated findings including hypotrichosis, palmar/plantar pitting and hypohidrosis, etc. Herein, we report a case of 4-year-old girl with familial generalized basaloid follicular hamartoma syndrome.