Sebaceomas in a Muir-Torre-like Phenotype in a Patient with MUTYH-Associated Polyposis.

This case report describes a case of a patient with MUTYH-associated polyposis (MAP), who presented with multiple sebaceomas in a Muir-Torre-like phenotype. MAP is caused by mutations in MUTYH, a base excision repair gene responsible for detecting and repairing the 8-oxo-G:A transversion caused by reactive oxygen species. MAP is associated with an increased risk of developing adenomatous polyps and colorectal cancer. Muir-Torre syndrome is a clinical phenotype of Lynch syndrome, which presents with multiple cutaneous sebaceous neoplasms. Lynch syndrome, like MAP, increases the likelihood of developing colorectal cancer but with a different pathogenesis and mode of inheritance. This case demonstrates that in a patient presenting with multiple sebaceous neoplasms, further workup and genetic testing may be indicated, not only for Muir-Torre and Lynch syndrome but also for MAP.

Looking beyond the surface: Muir Torre syndrome.

Muir-Torre Syndrome (MTS) is associated with multiple visceral malignancies. Initial presentation may be a benign skin tumor mimicking a sebaceous cyst. This case report highlights the importance of early diagnosis, genetic testing, and multidisciplinary screening. A 67-year-old man was diagnosed with MTS following excision of a skin lesion (sebaceoma). He was declined both screening colonoscopy and genetic testing. Subsequently, advanced colon cancer was found following presentation with iron deficiency anemia, which ultimately led to palliation despite successful surgery. MTS can present insidiously with skin lesions clinically diagnosed as sebaceous cysts. Once MTS is suspected on histology, genetic testing and screening for MTS-related cancers is warranted. Better understanding of the genetic variants for MTS can aid in earlier diagnosis thus not dismissing the need for screening for MTS-related cancers.

Machine learning for classification of cutaneous sebaceous neoplasms: implementing decision tree model using cytological and architectural features.

BACKGROUND: This observational study aims to describe and compare histopathological, architectural, and nuclear characteristics of sebaceous lesions and utilized these characteristics to develop a predictive classification approach using machine learning algorithms. METHODS: This cross-sectional study was conducted on Iranian patients with sebaceous tumors from two hospitals between March 2015 and March 2019. Pathology slides were reviewed by two pathologists and the architectural and cytological attributes were recorded. Multiple decision tree models were trained using 5-fold cross validation to determine the most important predictor variables and to develop a simple prediction model. RESULTS: This study assessed the characteristics of 123 sebaceous tumors. Histopathological findings, including pagetoid appearance, neurovascular invasion, atypical mitosis, extensive necrotic area, poor cell differentiation, and non-lobular tumor growth pattern, as well as nuclear features, including highly irregular nuclear contour, and large nuclear size were exclusively observed in carcinomatous tumors. Among non-carcinomatous lesions, some sebaceoma and sebaceous adenoma cases had features like high mitotic activity, which can be misleading and complicate diagnosis. Based on multiple decision tree models, the five most critical variables for lesion categorization were identified as: basaloid cell count, peripheral basaloid cell layers, tumor margin, nuclear size, and chromatin. CONCLUSIONS: This study implemented a machine learning modeling approach to help optimally categorize sebaceous lesions based on architectural and nuclear features. However, studies of larger sample sizes are needed to ensure the accuracy of our suggested predictive model.

Borderline Malignant Sebaceoma of the Auricle: A Case Report.

Sebaceoma is a rare benign tumor arising from the sebaceous gland of the skin. Sebaceoma often occurs on the head and neck but rarely on the ears. We present the case of a 78-year-old female patient with a two-year history of a protruding mass in her left ear. Physical examination revealed a well-circumscribed plaque in the crus of the helix of the left ear. A wide local excisional biopsy was taken, and the mass was subjected to histopathologic assessment. While the mass showed cytological findings indicating sebaceoma, it also presented malignant features architecturally and immunohistochemically. Based on these findings, the tumor was regarded as a sebaceoma of borderline malignancy. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-03552-4.

Sebaceous Neoplasms.

Sebaceous neoplasms describe a group of tumors with sebaceous differentiation commonly seen in lesions located primarily in the face and neck. The majority of these lesions are benign, while malignant neoplasms with sebaceous differentiation are uncommon. Sebaceous tumors present a strong association with the Muir-Torre Syndrome. Patients suspected with this syndrome should undergo neoplasm excision, followed by histopathologic and additional immunohistochemistry and genetics examinations. Clinical and dermoscopic features of the sebaceous neoplasms, as well as management procedures collected from the literature analysis regarding sebaceous carcinoma, sebaceoma/sebaceous adenoma, and sebaceous hyperplasia are described in the current review. A special note is made for describing the Muir-Torre Syndrome in patients presenting multiple sebaceous tumors.

Carcinoid-Like Cell Arrangements in Basal Cell Carcinoma: A Study of 11 Cases.

Background. Carcinoid-like pattern in basal cell carcinoma is extremely rare and has only been documented in a textbook. The aim of this study is to reveal the characteristics of the carcinoid-like pattern in basal cell carcinoma as well as to establish the concept of the tumor pattern. Methods. Of 355 basal cell carcinoma cases (355 lesions of 308 patients), 11 tumors with histopathological features of carcinoid-like pattern were retrieved. Results. The patients included 5 males and 6 females with a median age of 73 years (range 38-86 years). Of the 11 lesions, 10 were observed on the head. Histopathologically, a carcinoid-like pattern with branching and anastomosing of trabecular structures was observed in 30% to 95% of the tumor area. No differentiation to sebocytes was observed in any of the tumors. The tumors were well-circumscribed, although 3 lesions contained an infiltrative-type component as well. The carcinoid-like pattern areas in all 11 lesions exhibited diffuse BerEP4 immunoexpression but no KIT, synaptophysin, or vimentin expression. Keratin 20-positive Merkel cells were not observed in the tumor areas. Conclusions. Basal cell carcinoma can show a carcinoid-like pattern cell arrangement. Based on the histopathological and immunohistochemical findings from our study, we collectively conclude that the carcinoid-like pattern in basal cell carcinoma does not seem to represent sebaceous mantle differentiation. Carcinoid-like pattern basal cell carcinoma can be distinguished from other tumors by the favorite site of the head, the co-existence of conventional basal cell carcinoma components, lack of sebaceous differentiation, and diffuse BerEP4 immunoexpression.

The M2 macrophages infiltration of sebaceous tumors is linked to the aggressiveness of tumors but not to the mismatch repair pathway.

PURPOSE: The immune microenvironment of sebaceous neoplasms (SNs) has been poorly explored, especially in benign lesions, and never correlated to the mismatch repair (MMR) status. METHODS: We conducted an immuno-histological study to analyze the immune microenvironment of SNs. A tissue microarray was constructed including sebaceous adenomas (SAs), sebaceomas (Ss) and sebaceous carcinomas (SCs) to performed immuno-histological analysis of T cells, B cells, macrophages, dendritic cells, and expression of Programmed Death-1 (PD-1) and Programmed Death Ligand 1 (PD-L1). An automatized count was performed using the QuPath® software. Composition of the cellular microenvironment was compared to the aggressiveness, the MMR status, and to Muir-Torre syndrome (MTS). RESULTS: We included 123 SNs (43 SAs, 19 Ss and 61 SCs) for which 71.5% had a dMMR phenotype. A higher infiltration of macrophages (CD68 +) of M2 phenotype (CD163 +) and dendritic cells (CD11c +) was noticed in SCs compared to benign SNs (SAs and Ss). Programmed cell death ligand-1 but not PD-1 was expressed by more immune cells in SCs compared to benign SNs. No difference in the immune cell composition regarding the MMR status, or to MTS was observed. CONCLUSION: In SNs, M2 macrophages and dendritic cells infiltrates are associated with the progression and the malignant transformation of tumors. High PD-L1 expression in immune cells in SCs is an argument for the use of immunotherapy by anti-PD1 or PD-L1 in metastatic patients. The lack of correlation between the composition of immune cells in SNs and the MMR status emphasizes the singularity of SNs among MMR-associated malignancies.

Sebaceoma on the nose mimicking basal cell carcinoma: Pitfalls of dermoscopy and reflectance confocal microscopy.

Sebaceoma is a rare benign sebaceous tumor that usually occurs on the face and scalp. We report a case of a 3-mm solitary pink papule on the nose in an elderly woman. Dermoscopic examination showed yellow-pinkish background with a central yellow homogeneous structure, peripheral branching vessels (crown vessels), and scattered gray or reddish-brown irregular areas. Reflectance confocal microscopy (RCM) revealed tumor islands with massive dendritic cells and scattered bright fine granules in the dermis, a suspicious palisading arrangement at the periphery, and there seemed to be peritumoral dark spaces. The combined dermoscopic and RCM examination were highly suspicious for the diagnosis of basal cell carcinoma (BCC), so the lesion was excised completely, but was eventually diagnosed as sebaceoma by histopathology. This case suggests that there are some overlaps in both dermoscopic and RCM features between sebaceoma and BCC. The application of dermoscopy and RCM to the diagnosis of sebaceoma is challenging, further studies are needed in this field.

Sebaceoma. Reporte de un caso / Sebaceoma. Case report

RESUMEN El sebaceoma es un tumor de las glándulas sebáceas. Vinculado a una posible alteración en la vía de señalización Wnt/beta-catenina. Se caracteriza clínicamente por ser una lesión exofítica, más comúnmente de aparición solitaria y amarillenta. Cuando en un mismo paciente los tumores son múltiples debemos descartar la presencia del síndrome de Muir-Torre, un trastorno asociado a la presencia de neoplasias malignas internas. En la histopatología, el diagnóstico diferencial se realizaprincipalmente con el adenoma sebáceo, teniendo en cuenta el porcentaje de células germinativas o inmaduras en los lóbulos. El tratamiento de elección es la extirpación quirúrgica, aunque también se puede emplear la electrodesecación, entre otros. Se decide reportar el caso de una paciente femenina con un tumor sebáceo de poca frecuencia, haciendo una revisión de las características clínicas e histopatológicas que nos ayuden a disminuir las dificultades en el diagnóstico.

ABSTRACT Sebaceoma is a rare sebaceous gland tumor, named by Troy and Ackerman in 1984. A possible alteration in the Wnt / beta-catenin signaling pathway has been linked to its etiology and would play an important role in genesis of some tumors, including sebaceous. It is clinically characterized by being an exophytic lesion, most commonly of a solitary, yellowish appearance, which appears in seborrheic areas, although the symptoms can be very heterogeneous. When tumors are multiple in the same patient, we must rule out the presence of Muir-Torre syndrome, an autosomal dominant disorder that is associated with the presence of internal malignancies. In Sebaceoma dermoscopy, an amorphous yellowish erythematous area is generally found, which suggests the sebaceous etiology of the lesion, but currently the definitive diagnosis can only be confirmed with histopathology. The differential diagnosis is made mainly with sebaceous adenoma, taking into account the percentage of germ cells or immature lobes, being less than 50% in sebaceous adenoma and more than 50% in sebaceoma, the latter also tends to be of greater size and depth. The treatment of choice is surgical removal, although electrodesiccation, cryotherapy, or curettage can also be used. It was decided to report the case of a female patient with an infrequent sebaceous tumor, making a review of the clinical and histopathological characteristics that help us decrease the difficulties in diagnosis.

Lynch syndrome: An unusal case of familial cancer unearthed.

Lynch syndrome or hereditary nonpolyposis colorectal cancer (HNPCC) is a type of inherited cancer syndrome with a genetic predisposition to different types of cancer. There is an increased predisposition to cancers in the endometrium, colon, stomach, ovary, uterus, skin, kidney, and brain in patients of Lynch syndrome. We are reporting a 48-year-old male who presented with a pea-sized growth in his left arm which was found to be sebaceoma on histopathology. On further detailed history, examination, and genetic study, it was proved to be a familial case of Lynch syndrome. The case is being reported to stress the importance of knowledge about clinical manifestation, associated neoplasms, and molecular genetic profile of Lynch syndrome which will enable physicians and pathologists to provide highly targeted surveillance and management for patients with high cancer risk.

Sebaceoma: Un tumor infrecuente en el conducto auditivo externo / Sebaceoma: an unusual tumor in the external auditory canal

El sebaceoma es un tumor cutáneo poco frecuente que presenta diferenciación sebácea, y se localiza en piel de cabeza y cuello. Puede asociarse con la presencia de tumores malignos, asociación conocida como síndrome de Muir-Torre, por lo que ante su diagnóstico se deben descartar. Su localización en la piel del conducto auditivo externo es muy infrecuente. Presentamos nuestra experiencia en el manejo de esta patología en un varón de 78 años de edad que presentaba una lesión nodular sólida en el conducto auditivo externo izquierdo con pérdida de audición y otorrea como síntomas asociados. Se recomienda la exéresis completa de la lesión, como tratamiento de elección con fines tanto diagnósticos como terapéuticos.

Sebaceoma is a rare benign cutaneous tumor with sebaceous differentiation and it is typically located on the skin of the head and neck. This pathology made appear in association with malignant tumors (known as Muir-Torre syndrome) and must be ruled out. The location in the external auditory canal is very unusual. We present our experience in managing this pathology in a 78-year-old man who complains of hearing loss and otorrhea and presents a solid nodule in the left external auditory canal. Complete surgical removal was performed, as the choice treatment for diagnosis and therapeutic care.

Basal Cell Carcinoma and Sebaceoma Within Nevus Sebaceous of the Scalp.

This case describes the occurrence of basal cell carcinoma (BCC) and sebaceoma within a nevus sebaceous (NV), which has not yet been previously reported. This is significant to dermatologists as it emphasizes the importance of close monitoring of benign sebaceous nevi in the event that malignant transformation occurs, although such occurrences are rare. Prompt consideration for prophylactic excision of NS is warranted prior to malignant transformation.

GLUT1 Expression in Cutaneous Sebaceous Lesions Determined by Immunohistochemical Staining Patterns.

GLUT1 is a membrane associated carrier protein that functions in the physiologic transport of glucose across cell membranes. Multiple studies have shown an increased GLUT1 expression in various tumor types and a role in cancer prognosis. The aim of this study was to determine whether cutaneous sebaceous lesions have a differential expression of GLUT1 by immunohistochemistry (IHC). GLUT1 IHC was performed on excision specimens of ten cases of sebaceous carcinoma, nine of sebaceoma, ten of sebaceous adenoma, and ten of sebaceous hyperplasia. Intense, diffuse cytoplasmic staining was observed in sebaceous carcinoma. The pattern of GLUT1 staining in sebaceomas and sebaceous adenomas consisted of a gradient of intense cytoplasmic staining in the basaloid cells with a decreased intensity to membranous staining only and absent staining in mature sebaceous cells. In lesions of sebaceous hyperplasia, GLUT1 staining outlined the basal layer of each gland; cytoplasmic staining was minimal to absent. Increased cytoplasmic staining of GLUT1 may correlate with cellular metabolic and proliferative activity. GLUT1 has potential utility in differentiating sebaceous lesions.

A Rare Occurrence of Sebaceous Carcinoma, Sebaceoma, Syringocystadenoma Papilliferum, and Trichoblastoma in a Single Nevus Sebaceous Lesion.

Nevus sebaceous (NS) is a benign tumor with the potential to develop secondary benign and malignant neoplasms. It is a rare phenomenon to develop 2 or more skin tumors in a single NS lesion. We report a case of multiple secondary tumors, such as sebaceoma, sebaceous carcinoma, syringocystadenoma papilliferum, and trichoblastoma, in a single NS lesion.

MLH1 epimutation is a rare mechanism for Lynch syndrome: A case report and review of the literature.

Endometrial carcinoma is one of the prototypical malignancies associated with Lynch syndrome, an inherited cancer syndrome most commonly caused by germline mutations in DNA mismatch repair (MMR) genes, although rare alternative mechanisms also exist. In this report, we describe a patient first diagnosed with colorectal cancer at age 33, then vulvar squamous cell carcinoma, facial sebaceous adenoma/sebaceoma, and finally endometrial carcinoma at age 52. All tumors were MLH1/PMS2-deficient by immunohistochemistry, and MLH1 promoter methylation was identified in the endometrial cancer. Germline MLH1 testing was negative for pathogenic variants, but she was subsequently diagnosed with Lynch syndrome secondary to a germline monoallelic constitutional epimutation of the MLH1 promoter. Identification of patients displaying a Lynch syndrome phenotype but lacking germline MMR mutations is important to avoid delays in the diagnosis of Lynch syndrome as well as the initiation of appropriate cancer screening and genetic counseling.

Molecular Genetics of Sebaceous Neoplasia.

Sebaceous neoplasia primarily includes sebaceous adenoma, sebaceoma, and sebaceous carcinoma (SC). Sebaceous adenoma, sebaceoma, and a subset of cutaneous SC are frequently associated with defective DNA mismatch repair resulting from mutations in MLH1, MSH2, or MSH6. These tumors can be sporadic or associated with Muir-Torre syndrome. SCs without defective DNA mismatch repair have ultraviolet signature mutation or paucimutational patterns. Ocular SCs have low mutation burdens and frequent mutations in ZNF750. Some ocular sebaceous carcinomas have TP53 and RB1 mutations similar to cutaneous SC, whereas others lack such mutations and are associated with human papilloma virus infection.

Androgen receptor expression in epidermal and adnexal tumours.

INTRODUCTION: Androgen receptor (AR) immunohistochemistry is used in general pathology and in dermatopathology, particularly for sebaceous tumours. The goal of this study was to quantify AR expression in benign and malignant epidermal tumours and adnexal tumours. METHODS: We studied AR expression in 301 skin lesions using standard immunohistochemistry and compared 10 trichoblastomas, 10 sebaceomas and 10 hidradenomas using 5 markers (cytokeratin 7 and 8, PHLDA1, BerEp4 and AR). RESULTS: The rates of AR expression were: 22% in basal cell carcinomas, 3% in squamous cell carcinomas, 92% in sebaceous tumours, 10% in follicular tumours and 22% in sweat gland tumours. Benign sebaceous tumours were AR+ in 97% of cases. Only 12% of sebaceous carcinomas showed no AR staining. The immunohistochemical profiles of the comparative study were as follows: sebaceoma: AR+, CK7-, CK8-, PHLDA1-, BerEp4-; hidradenoma: AR-, CK7+, CK8+, PHLDA1+, BerEp4+; trichoblastoma: AR-, CK7-, CK8-, PHLDA1+, BerEp4+. DISCUSSION: AR staining was positive in 92% of sebaceous tumours, including sebaceomas, in some cases indicative of Muir-Torre syndrome. AR staining is therefore highly sensitive for the diagnosis of sebaceous tumours, but it is non-specific and is best used in combination with other antibodies, notably anti-CK8 and PHLDA1, particularly to distinguish sebaceoma from hidradenoma or trichoblastoma.

Sebaceoma of a Meibomian Gland of the Upper Eyelid.

Over a period of 1 year, a 74-year-old man slowly developed a painless left upper eyelid intratarsal mass. The skin was movable over the lesion. At surgery, a well-circumscribed, yellow-white, partially cystic tumor was encountered. Histopathologically it was composed of a random mixture of basaloid and sebaceous cells arranged in interconnecting cords. Immunohistochemical evaluation disclosed epithelial membrane antigen, adipophilin, and cytokeratin 14 positivity. These findings led to the diagnosis of a sebaceoma. The tumor cells abnormally failed to express mismatch repair proteins for MLH1 and PMS2. The patient did not have a personal history of any visceral malignancy, but his father had died at the age of 46 years and a daughter at the age of 33 years from colonic carcinomas. The implications of this periocular sebaceoma for the Muir-Torre syndrome are explored.

Update on the pathology, genetics and somatic landscape of sebaceous tumours.

Cutaneous sebaceous neoplasms show a predilection for the head and neck area of adults and include tumours with benign behaviour, sebaceous adenoma and sebaceoma, and sebaceous carcinoma with potential for an aggressive disease course at the malignant end of the spectrum. The majority of tumours are solitary and sporadic, but a subset of tumours may be associated with Lynch syndrome, also known as hereditary non-polyposis colon cancer (HNPCC) and previously referred to as Muir-Torre syndrome (now known to be part of Lynch syndrome). This review provides an overview of the clinical and histological features of cutaneous sebaceous neoplasia with an emphasis on differentiating features and differential diagnosis. It also offers insights into the recently described molecular pathways involved in the development of sebaceous tumours and their association with Lynch syndrome.