Papillomatous Papules Research Articles

Use of Topical Minocycline for Treatment of Confluent and Reticulated Papillomatosis

Confluent and reticulated papillomatosis (CRP) is a rare dermatosis initially that typically affects young adults and is characterized by scaly, hyperpigmented macules or papillomatous papules combining into patches typically involving the upper trunk and neck. Herein, we report two cases of CRP successfully treated with topical minocycline. The most widely accepted treatment of CRP to date is oral minocycline. Due to the chronic nature of CRP, topical minocycline could be considered a better first-line treatment option. This alternative treatment offers the advantage of a targeted, local application for enhanced skin bioavailability and efficacy. This case supports the possibility of topical minocycline use as an alternative to long-term oral antibiotics for treatment of CRP.

A rare case report of the Cowden syndrome

Cowden syndrome (CS) is a rare autosomal dominant genodermatosis caused by a heterozygous germline mutation in the PTEN gene, found in nearly 80% of cases. It is characterized by multiple benign hamartomas which manifest across various organs. This condition is further distinguished by its association with macrocephaly, facial trichilemmomas, acral keratoses, papillomatous papules, and a heightened susceptibility to certain malignant neoplasms, particularly affecting the thyroid, endometrium, and the breast (OMIM no. 58350).In this report, we detail the case of an Indian patient presenting with macrocephaly and multiple blackish pigmented areas on the face, alongside several small papules on the dorsum of the hands, and the presence of gastric and duodenal polyps, among other symptoms. Genetic analysis through Sanger sequencing of the PTEN gene revealed a heterozygous nonsense pathogenic variant (ENST00000371953.8: c.388C > T, p.Arg130Ter), thereby confirming a CS diagnosis. The report encompasses a comprehensive review of the existing literature, emphasizing the significance of genetic evaluation and discussing the intricacies of managing patients diagnosed with CS.

Dermatological manifestations in Costello syndrome: A prospective multicentric study of 31 HRAS-positive variant patients.

Data on dermatological manifestations of Costello syndrome (CS) remain heterogeneous and lack in validated description. To describe the dermatological manifestations of CS; compare them with the literature findings; assess those discriminating CS from other RASopathies, including cardiofaciocutaneous syndrome (CFCS) and the main types of Noonan syndrome (NS); and test for dermatological phenotype-genotype correlations. We performed a 10-year, large, prospective, multicentric, collaborative dermatological and genetic study. Thirty-one patients were enrolled. Hair abnormalities were ubiquitous, including wavy or curly hair and excessive eyebrows, respectively in 68% and 56%. Acral excessive skin (AES), papillomas and keratotic papules (PKP), acanthosis nigricans (AN), palmoplantar hyperkeratosis (PPHK) and 'cobblestone' papillomatous papules of the upper lip (CPPUL), were noted respectively in 84%, 61%, 65%, 55% and 32%. Excessive eyebrows, PKP, AN, CCPUL and AES best differentiated CS from CFCS and NS. Multiple melanocytic naevi (>50) may constitute a new marker of attenuated CS associated with intragenic duplication in HRAS. Oral acitretin may be highly beneficial for therapeutic management of PPHK. No significant dermatological phenotype-genotype correlation was determined between patients with and without HRAS c.34G>A (p.G12S). This validated phenotypic characterization of a large number of patients with CS will allow future researchers to make a positive diagnosis, and to differentiate CS from CFCS and NS.

EP062: Clinically significant goiters as the initial presentation of PTEN hamartoma tumor syndrome

PTEN hamartoma tumor syndrome (PHTS) is a multi-systemic tumor predisposition syndrome driven by PTEN germline pathogenic variant. Syndromes previously categorized based on clinical features, such as Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome, share overlapping features and are now categorized as part of the PHTS spectrum. Its estimated prevalence is 1:200,000, however we believe it is underrecognized due to its rarity and low recognition rates. Patients may present with progressive hamartomas occurring in multiple tissues or organs: polyposis in GI tract, complex vascular malformation such as cavernous hemangiomas, cerebellar dysplastic gangliocytomas, as well as excessive quantity of various types of cutaneous lesions such as skin tags, trichilemmomas, and papillomatous papules.

Characterizing dermatologic findings among patients with PTEN hamartoma tumor syndrome: Results of a multicenter cohort study

BackgroundDermatologic phenotypes in PTEN hamartoma tumor syndrome (PHTS) are heterogeneous and poorly documented. ObjectiveTo characterize dermatologic findings among PHTS and conduct an analysis of genotype-dermatologic phenotype associations. MethodsMucocutaneous findings were reviewed in a multicenter cohort study of PHTS. Genotype-dermatologic phenotype associations were tested using multivariable regression. ResultsA total of 201 patients were included. Children were significantly less likely than adults to have oral papillomas, vascular malformations, benign follicular neoplasms, and acral keratoses. There were no cases of skin cancer among children. Basal cell carcinoma, cutaneous squamous cell carcinoma, and melanoma developed in 5%, 2%, and 1% of White adults, respectively. After adjusting for age, missense mutations were associated with 60% lower odds of developing cutaneous papillomatous papules (odds ratio: 0.4; 95% confidence interval [0.2, 0.7]), oral papillomas (0.4; 95% confidence interval [0.2, 0.9]), and vascular malformations (0.4; 95% confidence interval [0.2, 0.8]). LimitationsPartly retrospective data. ConclusionChildren are less likely than adults to have certain dermatologic findings, likely due to age-related penetrance. The risk of pediatric melanoma and the lifetime risk of nonmelanoma skin cancer in PHTS may not be elevated. Missense variants may be associated with the development of fewer dermatologic findings but future validation is required.

Asymptomatic Hyperpigmented Rash in a Healthy Adolescent Female.

Asymptomatic Hyperpigmented Rash in a Healthy Adolescent Female.

Verrucous Epidermal Nevus: Dermoscopy, Reflectance Confocal Microscopy, and Histopathological Correlation.

Citation: VerzAE, Lacarrubba F, Quattrocchi E, Micali G. Verrucous epidermal nevus: dermoscopy, reflectance confocal microscopy, and histopathological correlation. Dermatol Pract Concept.2019;9(3):230-231. DOI: https://doi.org/10.5826/dpc.0903a16

COWDEN'S SYNDROME DIAGNOSED BY ORAL LESIONS: CASE REPORT AND REVIEW OF THE LITERATURE

Cowden's syndrome (CS), also known as multiple hamartoma syndrome, is a rare genodermatosis of autosomal dominant inheritance and variable phenotype. Its origin is a PTEN (phosphatase and tensin homologue) gene mutation, resulting in the development of multiple hamartomatous lesions and an increased risk of malignancy. Clinically, it is characterized by multiple mucocutaneous lesions, including oral and labial papillomatous papules. Oral manifestations in CS are frequent and usually precede the establishment of malignant tumours. Their correct diagnosis may improve early recognition of this entity, leading to an appropriate genetic counselling and close surveillance for the early detection of malignant processes associated with SC. We report a case of a 58-year-old male patient who was referred to the Oral Pathology Department of Andres Bello University, Vina del Mar, Chile, with a presumptive diagnosis of “multiple papules” in the oral cavity. Extraoral examination revealed macrocephaly, facial trichilemomas and acral keratosis. Upon intraoral examination, multiple papillomatous lesions were observed. A biopsy of the oral lesions was taken, which revealed fibro-epithelial hyperplasia. Endoscopy of the upper digestive tract showed acanthosis of the oesophagus and multiple polyps on the antrum of the stomach and duodenum. Thyroid ultrasound showed uninodular goitre. The patient was diagnosed with Cowden's syndrome and has been followed up closely by a multidisciplinary team in order to diagnose any development of malignant tumours.

Clinical and Histopathologic Study of Confluent and Reticulated Papillomatosis by Anatomic Site and Age.

BackgroundConfluent and reticulated papillomatosis (CRP) is an uncommon dermatosis characterized by hyperpigmented scaly macules or papillomatous papules coalescing into confluent patches or plaques centrally with a reticular pattern peripherally. Few studies regarding this have been reported in the literature.ObjectiveThe purpose of this study was to investigate the clinical and histologic characteristics of CRP in Korean patients according to anatomic site and age.MethodsWe retrospectively reviewed the medical records, clinical photographs, and 40 histopathologic slides of 29 patients diagnosed with CRP.ResultsSixteen adults and 13 adolescents were included. The predominantly involved anatomic sites were the trunk (89.7%) and axillae (27.6%); flexural area involvement was mainly found in the adolescent group. The mean disease duration was 2.3 times longer in the adult group than in the adolescent group. The histopathologic features included hyperkeratosis (95.0%), acanthosis (87.5%), and papillomatosis (77.5%) in the epidermis. In the adult group, only 10 specimens (52.6%) showed mild to moderate papillomatosis. There was no relationship between the histologic findings and disease duration; however, the former was associated with the anatomic site.ConclusionThe present study is the first to present the clinical and histologic features of CRP according to age and anatomic site in Korean patients. The patients in this study more frequently had fungal infections (31%) than patients in a previous study (12.8%). Histologic changes were more prominent in the adolescent group than in the adult group and in the flexural area than in the non-flexural area.

Focal Dermal Hypoplasia Syndrome with Distinct Clinical and Pathological Features

A 17-year-old male presented with multiple linear distributed erythema and papules which first appeared since birth. The erythema was fragile, easily traumatized, and often healed with hypopigmented atrophic scars. The right first and second fingers and nails were hypoplastic. Generalized linear or whorled hyperpigmented patches gradually developed and multiple papillomatous papules emerged during childhood, which were mainly distributed in the perioral region. A skin biopsy found epidermal parakeratosis, diminished dermal thickness, increased vasculatures in dermal papillae, and upward migration of subcutaneous fat layer known as “fat herniation”. A diagnosis of focal dermal hypoplasia was thus established.

When Should Patients Undergo Genetic Testing for Hereditary Colon Cancer Syndromes?

When Should Patients Undergo Genetic Testing for Hereditary Colon Cancer Syndromes?

歯肉乳頭腫様丘疹を伴ったCowden病の1例

Cowden's disease is an autosomal dominant disorder caused by mutation of the phosphatase and tensin homologue deleted on chromosome 10 (PTEN). Cowden's disease is characterized by symptoms such as hamartomas developing in multiple organs, papillomatous hyperplasia, and papules on the face or limbs. We describe a 69-year-old woman with a chief complaint of gingival swelling who was found to have multiple papillomatous hyperplastic lesions of the maxillary and mandibular gingiva within the oral cavity and small papules on the skin of the neck. Upper gastrointestinal endoscopy revealed multiple polyps in the esophagus and stomach. Cowden's disease was diagnosed after detection of the PTEN mutation on genetic analysis. Caution is required in differential diagnosis when multiple papillomatous papules are present within the oral cavity, because this could be an oral symptom of a disorder such as Cowden's disease.

Genodermatosis Affecting the Skin and Mucosa of the Head and Neck: Clinicopathologic, Genetic, and Molecular Aspect--PTEN-Hamartoma Tumor Syndrome/Cowden Syndrome.

PTEN hamartoma tumor syndrome refers to a spectrum of disorders caused by mutations in the phosphatase and tensin homolog (PTEN) gene. Cowden syndrome, the principal PTEN-related disorder is characterized by multiple neoplasms and hamartomas, mucosal papillomatosis, and skin lesions, trichilemmomas. Trichilemmomas and mucocutaneous papillomatous papules are one of the first signs of the disease. Early recognition of these skin lesions may help on diagnosing an underlying malignancy and early cancer screening.

Phosphatase and Tensin Homolog Immunohistochemical Staining and Clinical Criteria for Cowden Syndrome in Patients With Trichilemmoma or Associated Lesions

Trichilemmomas and mucocutaneous papillomatous papules are associated with Cowden syndrome (CS). Germline Phosphatase and tensin homolog (PTEN) mutations have been identified in 34% to 80% of those meeting clinical criteria for CS. PTEN expression has not been well evaluated in large numbers of trichilemmoma. We investigated clinical criteria for CS in trichilemmoma patients and studied PTEN staining to determine how often patients with trichilemmoma have CS and whether PTEN staining is useful. About 102 cases of trichilemmoma or associated lesions from 95 patients were collected. Clinical histories were reviewed to investigate the incidence of CS using International Cowden Consortium operational criteria for diagnosis of CS, version 2000. PTEN staining was performed and graded for intensity and percentage. Although 1 patient had 3 trichilemmoma or associated lesions, and 5 had 2 trichilemmoma or associated lesions, none of 95 patients met clinical criteria for a diagnosis of CS. Twelve of the 89 cases available for staining (13.5%) showed decreased PTEN. Of these, the demographic, clinical, and pathological features were not significantly different compared with PTEN intact cases. None of the cases from the 6 patients with more than 1 trichilemmoma or associated lesions showed decreased PTEN staining. We thus conclude that the likelihood of a clinical diagnosis of CS among patients with a solitary or only a few trichilemmoma is extremely low. PTEN expression is decreased in some sporadic trichilemmomas or associated lesions. This is the largest study investigating clinical history and PTEN staining in patients with trichilemmoma or associated lesions. Because none of our patients met clinical diagnostic criteria for CS, the direct correlation of PTEN in CS and sporadic trichilemmoma remains unclear.

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.

Multiple hamartoma syndrome with characteristic oral and cutaneous manifestations.

Aim. To present a case of Cowden's syndrome and emphasize the importance of continued cancer surveillance in these patients. Cowden syndrome is an inherited autosomal dominant trait with incomplete penetrance and a range of expressivity. It is characterized by multiple hamartomas and neoplasms. Mucocutaneous features include trichilemmomas, oral mucosal papillomatosis, acral keratosis, and palmoplantar keratosis. Here, we report a case of Cowdens syndrome of a 30-year-old female patient who came with a complaint of multiple growths in the oral cavity of a three-month duration. On examination, multiple skin-colored, flat-topped papules over her forehead and right malar bone and multiple papillomatous papules involving all the mucosal surfaces intraorally were observed. This syndrome is associated with the development of several types of malignancies, especially breast carcinoma and thyroid carcinoma, which is why early recognition and regular and vigilant surveillance of individuals with the syndrome are important.

Predicting PTEN mutations: an evaluation of Cowden syndrome and Bannayan–Riley–Ruvalcaba syndrome clinical features

BackgroundCowden syndrome (CS) is associated with benign hamartomatous lesions and risks for thyroid, breast and endometrial cancers. Bannayan–Riley–Ruvalcaba syndrome is an allelic disorder characterised by macrocephaly, intestinal polyps, lipomas, and...

Le syndrome de Cowden ou syndrome des hamartomes multiples en endocrinologie clinique

Cowden syndrome (CS) is the prototypic PTEN hamartoma tumor syndromes (PHTS), rare clinical syndromes characterized by germline mutations of the tumor suppressor PTEN. CS is characterized by association of macrocephaly, facial trichilemmomas, acral keratoses, papillomatous papules, with increased risk for breast, thyroid and endometrial cancer. PTEN, which is located on chromosome 10q23, regulates negatively the prosurvival PI3K/Akt/mTOR pathway through a lipid phosphatase activity. Loss of PTEN activates this pathway and leads to increased cellular growth, migration, proliferation, and survival. CS diagnosis is clinical, based on the association of pathognomonic, major and minor criteria. The association in a patient with thyroid cancer, rarely with multinodular goiter, of typical dermatological manifestations, easily identifiable by clinical examination (papillomatous papules, acral keratoses, trichilemmomas), with a history of breast, endometrial, or renal cancer, or hamartomatous tumors presence, should alert the clinician. Clinical management of patients with CS is multidisciplinary, to include early and frequent screening, surveillance, and preventive care for associated malignancies. The development of antineoplastic agents targeting PI3K/Akt/mTOR pathway, such as rapamycin, may be the opportunity of treatment in PHTS and CS patients, for whom no specific medical treatment exist.

P45 Erythroplasia Queyrat s.Bowen disease of the glans penis

Introduction Erytroplasia Queyrat EQ is a rare disease which arises from the squamous epithelial cells of the glans penis or inner lining of the prepuce. It is seen in uncircumcised men aged 20–80 years and represents an in situ form of squamous cell carcinoma. Progresion to invasive carcinoma may occur a variable period of time. 10% of patients with EQ may have invasive squamous cells carcinoma in the primary lesion. Multiple factors have been implicated as causative agents in this process: chronic irritation, inflammation, infection as herpes simplex, humanpapilloma virus, urine, smegma, poor hygiene, trauma, immunosuppression… Characteristic lesions of EQ are solitary or multiple erythematous plaques with variable texture: smooth, velvety, scaly, crusty or verrucous. Ulceration or distinct papillomatous papules within a plaque may indicate progression in invasive squamous cells carcinoma. Case Report We present a 73-years-old man with typically erythematous plaques,well-delinited, with smooth texture and velvety surface,which is bleeding at the minimale touch. The biopsy of the lesion showed a squamous cells carcinoma in sity. EQ is usually treated with creams such as imiquimed or 5-fluorouracil, but we decided to treat the lesion with surgical treatment. No inguinal lymphadenopathy was found.

Mucocutaneous papillomatous papules in Cowden’s syndrome

Cowden syndrome (CS; also known as multiple hamartoma syndrome) is a rare autosomal dominant disorder characterized by multiple hamartomas and a high risk of development of thyroid, breast, endometrial and other cancers. The cardinal features of the disease, which often lead to diagnosis, include mucocutaneous papillomatous papules and trichilemmomas. Most affected people develop these characteristic lesions by the age of 20 years. Once diagnosed, gene identification can be offered to family members of affected patients. We report a case of the disease and briefly review the current literature.