Background: Non-melanocytic benign skin tumours encompass a diverse group of lesions, classified based on their cellular origin, such as epidermal, vascular, fibrous, neural, muscle, and adnexal tumours. Though they often reveal solitary lesions, multiple skin tumours focus on genodermatoses. Each syndrome exhibits distinct clinical characteristics and potential complications, including cutaneous and extra-cutaneous malignancies, some of which are potentially life-threatening. Diagnosing genetic syndromes is complex and requires numerous histopathological and immunohistochemistry tests due to similarities between the adnexal tumours and basal cell carcinoma upon pathology. Methods: To illustrate the clinical practice, we conducted a retrospective case study that included eleven patients with genodermatoses referred to a tertiary dermatology clinic from September 2018 to April 2024. We have also conducted a research study on available treatment modalities in this setting. Results: Five patients with excellent aesthetic results were treated using a recently approved FDA plasma device. After searching SCOPUS and PubMed database records, we assessed 96 original articles to present current knowledge regarding the dermato-surgical approach. Conclusions: Multiple skin tumours, especially on the face, may significantly affect patients\' quality of life and have psychological consequences. An appropriate treatment selection tailored to the patient\'s needs should be provided. There is no standardised treatment for multiple benign tumours in genodermatoses, and selected methods with varying efficacy are employed. We presented the utility of a new plasma device in these settings.

Aim of the report: Brooke-Spiegler syndrome (BSS) is a rare autosomal dominant disease characterized by the growth of cylindromas, spiradenomas, trichoepitheliomas, or their combination. These neoplasms usually begin in the second decade and progressively increase in number and size over the years. Diagnosis necessitates consideration of family history, clinical examination, histological findings, and genetic analysis. The aim of this paper is to explore the clinical overlap between Brooke-Spiegler syndrome (BSS) and neurofibromatosis type 1 (NF1). We aim to highlight the challenges associated with their differential diagnosis and emphasize the lack of standardized diagnostic criteria and treatment approaches. Case presentation: Hereby, we introduce the case of a 28-year-old male referred for suspicion of neurofibromatosis type 1 (NF1) who initially declined the recommended surgical excision for a scalp mass. After four years, he returned with larger masses of the scalp, and underwent excision of multiple masses, revealing cylindromas, spiradenomas, and spiradenocylindromas. Family history reported similar tumors in his father, who was also diagnosed with NF1 for the presence of multiple subcutaneous lesions on the scalp. Clinical overlap led to a genetic consultation, but testing for CYLD mutations yielded no significant variations. Despite this, the strong family history and consistent findings led to a revised diagnosis of Brooke-Spiegler syndrome, correcting the initial misdiagnosis of NF1 syndrome. Conclusions: Thanks to the evolving landscape of BSS research over the past two decades, its molecular underpinnings, clinical presentation, and histopathological features are now clearer. However, a thorough family history assessment is mandatory when BSS is suspected. It is our belief that a multidisciplinary approach and cooperation between specialists are essential when dealing with BSS. By sharing this case, we hope to underscore the importance of considering BSS as a differential diagnosis, especially in cases with atypical presentations or overlapping features with other syndromes like NF1.

BACKGROUND: Brooke-Spiegler syndrome is a rare autosomal dominant disorder characterized by the continuous development of multiple benign skin appendage tumors. It is treated usually by repeated standard surgery. Here, we present a case study where electrochemotherapy (ECT) with bleomycin was used as an effective alternative approach in treating advanced dermal cylindromatosis of the head and neck in a patient with Brooke-Spiegler syndrome.
METHODS: A 45-year-old woman presented with multiple recurrent dermal cylindroma lesions on her scalp. Previous treatment consisted of several surgical excisions that resulted in psychological deterioration due to the formation of numerous scars and extensive alopecic areas. ECT was offered to provide tumor removal and disease control and to improve the patient\'s quality of life.
RESULTS: The treatment was well tolerated, and a significant reduction in neoplastic tissue was achieved. Importantly, scalp skin condition significantly improved, regaining a fair follicular density on the margins.
CONCLUSIONS: This report suggests the feasibility of bleomycin ECT as a less invasive alternative option for controlling multiple scalp cylindroma lesions with cosmetically acceptable results, and improving quality of life.

Surgical treatment of large and multiple lesions of irradiated scalp may require subtotal scalp exeresis and reconstruction in two-stage free flap surgery: harvesting and placing the flap first, then scalp removing and defect covering in a second step. This strategy raises the question of how to care the flap between the two surgeries. We report an original technique of free latissimus dorsi flap lacing. A 70-year-old male, afflicted with familial cylindromatosis and treated by brachytherapy 18years ago, received a free latissimus dorsi myocutaneous flap in two-stage surgery, allowing 25×25cm pathological scalp exeresis. During first step, suture clips were fixed in two rows around the future scalp defect, in order to be used as anchors for the flap lacing. Braided wire were chosen for a better steerability, and to prevent knots untightening. Thus, the flap were placed in \"anatomical\" place, next to the scalp, pending secondary procedure. This situation permitted to avoid flap or pedicle compression or plication, and to ease flap care. The wires were tighten as shoelaces, allowing them to be undone and done as desired. The two-stage free latissimus dorsi flap reconstruction of scalp large defect permitted us to assess the flap reliability before final reconstruction. The lacing solution allowed us regular local care and convenient flap handling, while favoriting its optimal placing next to its future location.

Mutations in the tumor suppressor gene CYLD underlie phenotypically heterogeneous hereditary tumor disorders of the skin appendages. These diseases are inherited autosomal dominantly and include Brooke-Spiegler syndrome (BSS; OMIM 605041), familial cylindromatosis (FC; OMIM 132700) and multiple familial trichoepithelioma (MFT; OMIM 601606). Clinically, cylindromas, trichoepitheliomas and spiradenomas can be found in affected individuals. We sought to elucidate the molecular genetic basis in individuals with newly diagnosed cylindromas, trichoepitheliomas and/or spiradenomas. Mutation analysis using polymerase chain reaction (PCR)-based techniques was performed in seven German patients and one Turkish patient. We detected two missense, two nonsense, two deletions and two duplication mutations in the CYLD gene, of which seven have not yet been reported. No genotype-phenotype correlation was detected amongst the patients. Our data provide additional information on the clinical and molecular genetic heterogeneity of disorders associated with CYLD mutations.

Brooke-Spiegler Syndrome (BSS) is a rare genodermatosis characterized by the progressive formation of adnexal skin tumors in the scalp and face, mainly trichoepitheliomas, cylindromas, and spiradenomas. It has also been associated with salivary glands neoplasms. It is due to mutations in the tumor suppressor gene cylindromatosis (CYLD gene) localized on chromosome 16q12-q13. Around 93 mutations have been described. The study of CYLD gene in patients and their relatives is of vital importance to establish the molecular diagnosis and offer appropriate genetic counseling. There is a low risk of malignancy and patients require long-term follow-up. A case of BSS in a family is described. The existence of the genetic mutation at the CYLD gene c. 1628_1629delCT in three of the women affected was demonstrated. This mutation has only been described once in a previous study.

Cylindroma is a benign skin adnexal tumor of eccrine differentiation. Clinically, they are disfiguring lesions that can mimic a malignancy. Cylindromas can be single or multiple and commonly involve the scalp (turban tumor) and face. Multiple cylindromas can have a syndromic association as seen in Brooke-Spiegler syndrome and familial cylindromatosis. We present a case of non familial cylindroma of the face that clinically mimicked a basal cell carcinoma. The histopathology was confirmatory. Herein we also highlight the utility of a simple and inexpensive histochemical stain Periodic Acid Schiff in supporting the diagnosis.

A young male patient presented with multiple swellings on his chest and the nape of his neck. Physical examination revealed multiple small papulonodular swellings measuring 0.5 × 0.5 cm to 2 × 2 cm, that were soft without discharge with no surrounding skin changes or induration. Skin biopsy samples were diagnosed as benign adnexal neoplasm consistent with eccrine spiradenoma, trichoepithelioma, and cylindroma, i.e., Brooke-Spiegler syndrome. Having confirmed this to be a case of eccrine spiradenoma, surgical excision was performed and the raw area was covered with a split thickness skin graft taken from the right thigh and sutured over the raw area. The sternal lesion was circumferentially excised and the wound was primarily closed by Z-plasty. Surgical excision is considered the gold standard for the treatment of these cases, with low rates of recurrence. Around 50 such cases have been reported in the literature to date. Although eccrine spiradenomas are usually solitary and small, the findings in our case underscore the fact that a variety of presentations are possible. With strict clinical suspicion and histological criteria, the correct diagnosis can be achieved, especially when combined with pertinent clinical information and laboratory studies.
METHODS: Level V, therapeutic study.

OBJECTIVE: Brooke-Spiegler syndrome (BSS, familial cylindromatosis) is a rare hereditary disease characterized by multiple tumors of the skin appendages predominantly located in the head and neck region, such as cylindromas, trichoepitheliomas, or spiradenomas. It is caused by an autosomal dominant mutation in the CYLD gene, mapped on chromosome 16q12-13. Association with secondary malignant neoplasms has been reported. Until now 51 different mutations in 73 families have been reported; 41 % of them constitute frameshift mutations, resulting in an interruption of the expression of the gene product CYLD. CYLD is a deubiquitinating enzyme and plays an important role in (NF)-κB pathway signaling, a central pathway for apoptosis regulation. Mutation-induced loss of function leads to constitutive activation of NF-κB.
METHODS: Here, we report the case of a 48-year-old female patient diagnosed with an abdominal aggressive non-Hodgkin\'s lymphoma. The patient presented with multiple cylindromas of the capillitium. The patient\'s mother also has a mild form of late-onset cylindromas. Due to the typical clinical features indicating BSS, genotyping from peripheral blood was performed. A c.2465insAACA mutation in exon 17 of the CYLD gene, leading to a frameshift, was detected in the patient and in the patient\'s mother.
CONCLUSIONS: This is the first description of this hereditary mutation in exon 17 of the CYLD gene. There have been several reports on patients with CYLD mutations and different types of malignancies. However, a coincidence with aggressive non-Hodgkin\'s lymphoma has not been reported yet.