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Sebaceous carcinoma (SC) is a rare, aggressive malignancy. Most lesions occur in the periocular region, with few cases presenting with extraocular lesions. Here, we report a case of an 89-year-old woman with a 3-month history of a rapidly growing giant extraocular SC. The diagnosis was based on skin biopsy findings. We advised the patient to undergo surgical excision of the carcinoma. However, the patient and her family rejected our proposed surgical treatment, opting for topical traditional Chinese medicine as alternative treatment. The patient subsequently died of unknown causes at home, four months after the first visit. This case of treatment failure emphasizes the importance of early detection and treatment for these aggressive tumors.

Keratoacanthoma (KA) and well-differentiated cutaneous squamous cell carcinoma (cSCC) are hardly distinguishable clinically and histologically. They both can be seen in patients with hereditary non-polyposis colorectal cancer (HNPCC) or Lynch Syndrome, corresponding to DNA microsatellite instability. In our case, a young man had the excision of two rapidly growing skin tumours for which distinction between KA and cSCC was initially clinically and pathologically challenging. The diagnosis of well-differentiated cSCCs was made and the patient was treated with surgery. Ten years after the first cSCC, he was diagnosed with Muir-Torre syndrome, a variant of Lynch syndrome, with an heterozygote mutation of the MSH2 gene. This later diagnosis allowed to screen his family members for the same mutation and to adopt an appropriate follow-up regarding the risk of digestive tumours for him and his family. Furthermore, it is important to know that, in case of non-resectable cSCC occurring in this patient, immunotherapy using anti-PD1 antibody would probably be effective due to the known increased immunogenicity of MMR deficient tumours.

Lynch syndrome (LS) is an autosomal dominant inherited disorder due to pathogenic variations in the mismatch repair genes, which predisposes to malignancies, most commonly colon and endometrial carcinoma. Muir-Torre syndrome is a subset of LS with cutaneous sebaceous adenoma and keratoacanthoma in addition to the malignancies. Renal cell carcinoma (RCC) in patients with LS is extremely rare. Only 26 cases have been reported and among them, only two cases of papillary RCC. We report a case of synchronous papillary RCC and colonic adenocarcinoma in an 85-year-old male with Lynch/Muir-Torre syndrome. The LS was diagnosed when he presented with multiple sebaceous adenomas and genetic testing showed a pathogenic variant in MSH6 mismatch repair gene. A colonoscopy at that time showed multiple tubular adenomas with high-grade dysplasia. He was lost to follow-up and presented with gastrointestinal bleeding after 20 years. A right colonic mass, and a solid mass in the lower pole of the right kidney, was detected by imaging. Right Colectomy showed a T3N0 mucin-producing adenocarcinoma. Right nephrectomy showed a T3a papillary RCC which was microsatellite stable with MSH6, and KRAS mutation. The 36-month follow-up exams showed additional sebaceous neoplasms, and an absence of metastatic carcinoma. Analysis of the reported cases of RCC in LS show clear cell RCC as the most common type. These tumors showed MLH1 mutation most commonly, unlike the urothelial malignancies in LS which involve MSH2. Among the 4 cases of RCC with MSH6 mutation, three were in females, indicating some gender differences.

Muir–Torre syndrome combines skin tumors with sebaceous differentiation with malignant tumors of the gastrointestinal tract, which is caused by hereditary mutations in the genes of the mismatched nucleotide repair system. The article presents a clinical case of a 42-year old man who complained of an exophytic skin tumor on the back measuring 2.3 × 1.8 cm. At histological examination, the tumor was presented primarily with sebaceous differentiatied cells, which corresponded to adenoma of the sebaceous glands. From the patient’s history it became known that at the age of 37 he underwent hemicolectomy for high-differentiated adenocarcinoma. An immunohistochemical study with antibodies to proteins of the mismatched nucleotide repair system in a tumor sample revealed the absence of a nuclear reaction in tumor cells with antibodies to MLH1 and MSH2 proteins, which indicates the presence of germline mutations in these genes. High-throughput semiconductor parallel DNA sequencing revealed a variant of the nucleotide sequence in exon 12 of the MSH2 gene (c.1797_1801 del), leading to a shift in the reading frame (NM_000251: p.L599fs). Keywords: Muir–Torre syndrome, colorectal cancer, repair system, wrong-paired bases

El sebaceoma es una neoplasia benigna, papulonodular, amarillenta, que suele aparecer en rostro, piel cabelluda o en áreas con abundantes glándulas sebáceas. Se ha descrito en la literatura la asociación de neoplasias sebáceas con el síndrome de Muir Torre. Se presenta el caso de un paciente masculino con antecedente de cáncer de colon y presencia de lesión cutánea única en tórax, dos años después del primer diagnóstico.

Muir-Torre syndrome is an autosomal-dominant disorder caused by germline mutations in 1 of the 4 key DNA mismatch repair (MMR) genes, MSH2, MSH6, PMS2, and MLH1. Patients with Muir-Torre syndrome present with skin lesions, which play an important role in early detection of the disease and are considered cutaneous markers. The diagnostic criteria for Muir-Torre syndrome are at least 1 skin neoplasm with sebaceous differentiation, at least 1 visceral malignancy, and germline mutation of the MMR genes.1,2 Sebaceous adenoma is rare and is considered the most significant cutaneous marker for Muir-Torre syndrome.3 Abbas and Mahalingam4 suggested that when a young patient presents with a sebaceous neoplasm outside the head and neck area, immunohistochemical analysis of the MMR genes should be conducted for Muir-Torre syndrome screening. If loss of any MMR proteins is identified, microsatellite instability study or germline analysis is warranted for further diagnosis. In addition, presence of multiple keratoacanthomas should also prompt immunostaining studies for screening.3 In Muir-Torre syndrome, the keratoacanthoma usually presents with sebaceous differentiation.3 For a specific patient, loss of MMR proteins in the skin lesions and in the visceral tumors should be in concordance because of the presence of germline mutation. However, here we examined a visceral tumor and all 16 skin lesions from a patient with Muir-Torre syndrome and found genetic heterogeneity among several samples. All 13 sebaceous adenomas and the visceral tumor showed the same expression pattern of the MMR genes in line with the germline mutation, whereas other skin lesions such as keratoacanthoma and squamous cell carcinoma (SCC) showed aberrant expression patterns. To our knowledge, this is the first study reporting the phenomenon of genetic heterogeneity in a Muir-Torre syndrome patient.

Immune checkpoint blockade therapy provides substantial benefits for subsets of patients with advanced cancer, but its utility for cancer prevention is unknown. Lynch syndrome (MIM 120435) is characterized by defective DNA mismatch repair and predisposition to multiple cancers. A variant of Lynch syndrome, Muir–Torre syndrome (MIM 158320), is characterized by frequent gastrointestinal tumors and hyperplastic or neoplastic skin tumors. We report the case of a man with Muir–Torre syndrome who had 136 cutaneous or visceral hyperplastic or neoplastic lesions over a period of 19 years (mean 7.5 neoplasms/year, range 2–26) prior to receiving pembrolizumab immunotherapy as part of multi-modality treatment for invasive bladder cancer. He not only had a complete response of the bladder cancer, but also was noted to have an absence of new cancers during a 22-month follow-up period. This case adds to the rationale for exploring the utility of immune checkpoint blockade for cancer prevention, particularly for patients with DNA repair deficits.

Over several months, a painless, multinodular, non-erythematous swelling of the deep tissues of his left upper eyelid developed in a 63-year-old man. An excisional biopsy with histopathologic evaluation disclosed a unique sebaceous papilloma within a cyst lined by non-keratinizing squamous epithelium that focally displayed a variably thick, superficial, eosinophilic cuticular layer. Immunohistochemical staining demonstrated that the tumor and its epithelial cystic lining had a profile consistent with Meibomian gland duct epithelium. Adipophilin highlighted cytoplasmic vacuolar lipid positivity. The encapsulation of the lesion, absence of nuclear atypia, and Ki-67 nuclear positivity restricted to the basilar cells established its intrinsically benign nature. The patient's clinical history was remarkable for pulmonary and colonic carcinomas resected, respectively, 20 years and 8 years earlier. DNA mismatch repair protein expression studies disclosed loss of nuclear immunostaining of MSH6 protein, pointing to the possibility of an underlying rare MSH6 variant of the Muir-Torre syndrome, not yet described in the ophthalmic literature. p16 nuclear positivity was also found in the tumor cells, indicating the possible role of high-risk human papillomavirus as an additional factor in the genesis of the tumor. Genetic evaluation of normal and tumoral tissues in future similar cases will detect if there is an underlying germline mutation versus a somatic mutation limited to the tumor. This will be required to fully establish a predictable linkage with this new subtype of the Muir-Torre syndrome.

Background: Muir-Torre syndrome (MTS) is defined clinically as the association of cutaneous sebaceous neoplasm and visceral malignancy. Ancillary tests are considered crucial for diagnosis. Although screening guidelines for MTS, including the Mayo MTS scoring system, have been proposed, there are no ophthalmic site-specific guidelines. Summary: A literature review conducted by PubMed search for articles describing patients with periocular sebaceous neoplasm and MTS disclosed 31 publications describing 60 patients, 36 (60%) of whom fulfilled clinical criteria for MTS, 6 (10%) whose diagnosis was based on screening ancillary studies, 14 (23%) who fulfilled clinical criteria and had supporting screening ancillary studies, and 4 (7%) who fulfilled clinical criteria and had supporting diagnostic genetic testing. Most patients were male (34 vs. 15 females), with a median age of 59 years (range 37–79 years). The most common diagnosis was sebaceous carcinoma (40/60, 67%), followed by sebaceous adenoma (16/60, 27%), followed by other tumors with sebaceous differentiation (4/60, 6%). The periocular lesions were identified prior to visceral malignancy in 10 out of 45 (22%) cases, after visceral malignancy in 34 out of 45 (76%) cases, and concurrently with visceral malignancy in 1 out of 45 (2%) cases. Immunohistochemistry for mismatch repair proteins was performed in 41 out of 60 (68%) and 14 out of 38 (37%) of the tumors had lost MSH2. Based on Mayo-MTS scores of 2 or greater, and after removing visceral malignancies not included in their scoring algorithm, 26 out of 30 of patients (87%) with complete data were considered to be appropriate candidates for further work-up. A survey of current practice was conducted by questionnaires, distributed to ophthalmic pathologists, ocular oncologists, and oculoplastic surgeons from national and international professional societies. Of the 103 physicians who participated in the survey, 91 (88%) felt that MTS evaluation guidelines were not sufficiently clear. Key Messages: Our findings suggest that Mayo MTS screening guidelines may be applicable to periocular sebaceous neoplasms. The uncertainty of ophthalmic specialists about optimal screening guidelines for MTS reflects the heterogeneity of defining criteria for MTS and limited molecular genetic data. Larger studies with detailed clinical, histopathologic, and molecular genetic data are required to formally assess screening guidelines for MTS in patients with periocular sebaceous neoplasms.

Highlights • Sebaceous carcinoma is a rare adnexal tumour. • It occurs sporadically or in association with Muir-Torre Syndrome (MTS). • MTS is a rare genetic disorder that predisposes patients to visceral and skin malignancies. • Chest wall is rare site of sebaceous carcinoma. • Surgical excision with wide margins is the standard treatment., Background Sebaceous carcinoma (SC) is a rare aggressive cutaneous malignant tumour. It accounts for less than 1 % of all cutaneous malignant tumours. Sebaceous carcinomas are divided into ocular and extraocular constituting 75 % and 25 % respectively. The most common extraocular site is parotid gland. Chest wall is a rare site of this tumour. Case presentation In line with SCARE criteria (Agha et al., 2018 [1]), this report is a case of a 45-year-old African male patient who presented with a two-year history of a large right anterior chest wall tumour. He reported that the tumour started as a small lump, which grew gradually over a two-year period. The patient reported no history of visceral malignancy and radiation exposure. However, his risk factors were age and immunosuppression in the form of Human Immunodeficiency Virus (HIV). The tumour was initially diagnosed as sebaceous adenocarcinoma by incisional biopsy before the patient had been referred to the treating team a year before. Excision of the tumour with wide margins was undertaken, and histology results confirmed sebaceous carcinoma. Discussion Sebaceous carcinoma is a rare and aggressive adnexal tumour. It is categorized as ocular and extraocular. Of these two, the more common is extraocular. The chest wall is a rare site for this tumour. The definitive diagnosis of this kind of tumour is done by tissue biopsy. In dealing with this tumour, surgical excision with wide margins is the standard treatment. Conclusion Sebaceous carcinoma is a rare aggressive malignant tumour originating from sebaceous gland. Early diagnosis and wide excision with negative margins improves survival.

Muir-Torre syndrome (MTS) a genetic disorder characterized by predisposition to cutaneous neoplasms. Lipedematous scalp is characterized by the presentation of a thick, sponge-like scalp due to the altered and increased deposition of adipose tissue. We present a case of Muir-Torre-associated sebaceous carcinoma of the scalp consistent with a lipedematous scalp.

Muir-Torre syndrome is a rare, autosomal dominant genodermatosis, characterized by sebaceous neoplasms and visceral carcinomas. The authors describe the case of a patient who, 16 years after the diagnosis of colon carcinoma, presented a verrucous plaque on the pubic region, histopathologically compatible with sebaceous adenoma. The need to investigate this syndrome is emphasized, especially in cases of sebaceous neoplasms located outside the head, face, and neck. Screening for neoplasms in these patients and their families is mandatory.

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.

Sebaceomas of the external auditory canal (EAC) are extremely rare. The recognition of sebaceoma is important as this benign tumor can be be part of the spectrum of the Muir-Torre syndrome (MTS), which is associated with visceral malignancy and multiple adenomatous polyps. Proper histological identification is thus important for further investigation. We describe a rare case of a sebaceoma that was confined to the EAC. Subsequent immunohistochemical (IHC) staining analysis of the mismatch repair genes (MLH1, MSH2, MSH6, and PMS2) was needed to investigate MTS. Even though the patient has had the history of colon cancer, the result was negative. Otorhinolaryngologists should be aware of rare sebaceoma and its potential association with the internal malignancy, besides the limitation of IHC screening test.

Muir-Torre Syndrome (MTS) is a rare autosomal-dominant genetic condition linked to germline mutations in DNA mismatch repair (MMR) genes, resulting in microsatellite instability. It is considered a variant of Lynch syndrome characterized by the association of at least one sebaceous skin tumor and at least one internal malignancy. In addition, it has been shown that a latent phenotype of MTS might be unmasked in transplant organ recipients and immunosuppressed patients. The diagnosis and treatment of such cases require a multidisciplinary approach. Here, we present a case of a kidney transplant recipient who developed multiple sebaceous carcinomas 16 years after kidney transplantation and daily immunosuppressive medication. The patient then developed multiple contemporaneous internal malignancies in the esophagus and colon with metastases to the lung, thyroid, and lymph nodes, all of which were eventually linked to MTS. To our knowledge, this is the first reported case of MTS in the Arab world and the first reported case of esophageal cancer in relation to MTS in a transplant recipient. Because patients with MTS have a high tendency of developing malignancies, patients with a strong family history of malignancies, any known mutations, or an immunocompromised status should be included in an extensive screening program.

Muir–Torre syndrome (MTS), a rare subtype of Lynch syndrome, is mostly autosomal dominant, which is caused by germline mutations in DNA mismatch repair (MMR) genes, the resulting microsatellite instability (MSI) of which increases the risk of developing sebaceous and other visceral tumors. Several reports have showed an association between immunosuppressive agents and the progression of latent MTS. In this report, we described a 41-year-old man with a history of kidney transplantation, having a rapid growth of the nodule on the anterior chest under immunosuppressive therapy, which was histologically proved to be sebaceous carcinoma. Systemic evaluation for visceral malignancies revealed sigmoid adenocarcinoma. These findings were consistent with the clinical diagnosis of MTS. Histological findings showed an absence of MMR proteins, including MSH2 and MSH6 both in the sebaceous carcinoma and sigmoid adenocarcinoma on immunohistochemical (IHC) analysis. A frame-shift mutation of c.229_230delAG (p. Ser77fs) in the MSH2 exon 2 in the lesion was detected by next-generation sequencing (NGS) analysis. This case report not only reveals a new site of MSH2 mutation in this family of East Asian descent but also highlights the importance of adequate diagnosis for Muir–Torre syndrome, as well as further prevention of the development of latent visceral tumors in kidney transplant recipients.

Preimplantation genetic diagnosis (PGD) offers patients with heritable conditions undergoing in vitro fertilization (IVF) the ability to identify specific genetic anomalies in their embryos prior to implantation. A patient with a past medical history of Lynch syndrome presented to her dermatologist for a cutaneous sebaceous carcinoma and her diagnosis was subsequently further classified as Muir Torre syndrome (MTS). This patient’s family member, who also tested positive for the mutation, used IVF with PGD to identify a mutation-free embryo for implantation and prevent her future child from carrying the same diagnosis. This family’s experience is described, and relevant reproductive technologies available to similar patients are reviewed. Physicians diagnosing and treating heritable genetic conditions should be aware of this reproductive technology and its ethical implications that vary based on individual belief systems.

The presence of sebaceous neoplasm should alert physicians to thoroughly investigate for underlying malignancies. Awareness on MTS should be raised within physicians, since this may be just the thin end of the wedge.

Background Sebaceous carcinoma is a rare but progressive malignant skin cancer, and the incidence is approximately five times higher in post-transplant patients than in people who have not received kidney transplants. Sebaceous carcinoma is sometimes found concurrently with visceral cancers and a genetic abnormality, Muir–Torre syndrome. We report the case of a female kidney transplant recipient with sebaceous carcinoma concurrent with colon cancer 10 years after transplantation. Case presentation A 43-year-old woman was admitted due to a rapidly progressive tumor on her head. Histologically, the tumor was diagnosed as sebaceous carcinoma. We diagnosed her with Muir–Torre syndrome based on the following evidence: 1) high prevalence of microsatellite instability in gene locus assay, 2) absence of mismatch repair proteins in the sebaceous carcinoma on immunohistochemical analysis, and 3) a genetic mutation of 1226_1227delAG in the MSH2 exon 7 in the lesion detected by DNA sequencing analysis. Several reports have shown an association between immunosuppressive agents and latent Muir–Torre syndrome progression. Therefore, the progression of colon cancer in this case originated from her genetic mutation for Muir–Torre syndrome and long-term use of immunosuppressive agents. Conclusion This case report not only highlights the importance of adequate diagnosis and therapy for Muir–Torre syndrome, but also suggests the further prevention of the development of malignant tumors in kidney transplant recipients. Physicians should be mindful that sebaceous carcinoma in kidney transplant recipients is highly concurrent with Muir–Torre syndrome.

Background/Aims: We present a case of 2 concomitant tumours, i.e., a sebaceous carcinoma (SC) and a small lymphocytic lymphoma (SLL), in the lacrimal gland of a patient with Muir-Torre syndrome. Methods: Clinical history, orbital examination, diagnostic biopsy, excisional biopsy, and histopathologic analysis were utilized. Results: An 89-year-old female presented to the eye casualty with corneal ulcer, anterior uveitis, proptosis, and restricted ocular motility. She has a clinical history of breast cancer, colon carcinoma, and SC of the eyelid, which had been resected completely 2 years before. Clinical examination, imaging, and diagnostic biopsy confirmed orbital SC recurrence. Exenteration and subsequent histopathologic analysis of the specimen revealed lymphocytic infiltrates consistent with SLL within the lacrimal gland. Conclusion: We report for the first time a case of a patient with Muir-Torre syndrome who developed an orbital recurrent SC with an incidental finding of a lacrimal gland B non-Hodgkin lymphoma consistent with SLL. Clinicians should be aware of the possibility of this coexistence of multiple cancer types in patients with sebaceous carcinoma and Muir-Torre syndrome.

Muir-Torre syndrome, a variant of Lynch syndrome or hereditary nonpolyposis colorectal cancer, is an autosomal dominant disease characterized by skin neoplasms (sebaceous or keratoacanthomas) and visceral malignancies. Due to the rarity of the syndrome there are no firm guidelines on how and when to test patients with its typical skin lesions. We describe a case that highlights the importance of a detailed family history.

Lynch syndrome (LS) is an autosomal-dominant inherited disorder characterized by a predisposition to colorectal cancer and extracolonic cancers (particularly endometrium, ovary, stomach, small bowel, hepatobiliary tract, pancreas, urothelial tract, brain, and skin). Muir-Torre syndrome (MTS) is considered a phenotypical variant of LS, where patients develop sebaceous neoplasms and keratoacanthomas. Currently, only few studies and case reports suggest an association between LS and other skin cancers, such as Bowens' disease, melanoma and squamous cell carcinoma (SCC). In this case-report we describe the case of a 33-year-old woman with LS and a proven MSH2 germline mutation, presenting with a SCC on the right cheek. Immunohistochemistry lacked MSH2 and MSH6 protein staining. The tumor showed a discordance between immunohistochemistry and micro-satellite instability status, for which a clear explanation cannot be provided yet. To conclude whether this pattern is indicative for SCC occurring in LS patients, further analyses of other LS patients presenting with SCC should be carried out. Our patient's young age and skin type (Fitzpatrick phototype VI) suggest a possible link between LS and cutaneous SCC.

BACKGROUND/OBJECTIVES: Loss of expression of mismatch repair (MMR) proteins is frequently observed in sebaceous skin lesions and can be a herald for Lynch syndrome. The aim of this study was to identify clinico-pathological predictors of MMR deficiency in sebaceous neoplasia that could aid dermatologists and pathologists in determining which sebaceous lesions should undergo MMR immunohistochemistry (IHC). METHODS: An audit of sebaceous skin lesions (excluding hyperplasia) where pathologist-initiated MMR IHC was performed between January 2009 to December 2016 was undertaken from a single pathology practice identifying 928 lesions from 882 individuals. Lesions were further analysed for differences in gender, age at diagnosis, lesion type and anatomic location, stratified by MMR status. RESULTS: The 882 individuals (67.7% male) had a mean (SD) age of diagnosis of 68.4 ± 13.3 years. Nearly two-thirds of the lesions were sebaceous adenomas, with 82.6% of all lesions occurring on the head and neck. MMR deficiency, observed in 282 of the 919 lesions (30.7%), was most common in sebaceous adenomas (210/282; 74.5%). MMR-deficient lesions occurred predominantly on the trunk or limbs (64.7%), compared with 23.2% in head or neck (P

Background Muir–Torre syndrome (MTS), which accounts for a small subset (1–3 %) of Lynch syndrome (LS), is an autosomal dominant genetic disorder characterized by sebaceous gland or keratoacanthoma associated with visceral malignancies. Most families with MTS have pathogenic germline variants (PGV) in MSH2. Sarcomas are not common on the LS tumor spectrum, and sarcomas associated with MTS are extremely rare. Case presentation Here we report a myxofibrosarcoma of the abdominal wall in a 73-year-old man with a sebaceoma that occurred synchronically, leading to a diagnosis of MTS. The loss of MLH1 and PMS2 protein expression was detected in immunohistochemistry, and high-frequency microsatellite instability (MSI-H) was also confirmed. A germline genetic analysis revealed that he harbored the MLH1 PGV. Conclusions This is the first case of MSI-H myxofibrosarcoma with MTS in an MLH1 PGV carrier. Although rare, we should recognize that sarcomas can be part of the spectrum of LS and MTS.

Background: We investigated the mutational landscape of skin tumors in patients with Muir-Torre Syndrome (MTS) a hereditary autosomal dominant mismatch repair disorder of increased cancer susceptibility, and examined mutations other than in the DNA mismatch repair (MMR) genes. Methods: This retrospective single-center case series included seven patients with the diagnosis of Muir-Torre Syndrome with precise medical history and family history. Mutational analysis of tumor samples Formalin-fixed paraffin-embedded tissue blocks of skin lesions associated with Muir-Torre Syndrome were used for further analysis. All skin tumors were analyzed with the Oncomine Comprehensive Assay v3 (Life Technologies), which includes 161 of the most relevant cancer driver genes. Results: Eleven skin neoplasms (nine sebaceous tumors, one melanoma, one cutaneous squamous cell carcinoma) were diagnosed in seven patients. In two patients, visceral malignancies preceded the diagnosis of the skin tumors and one patient was diagnosed with a visceral malignancy after a sebaceous tumor. History of familial cancer of Lynch Syndrome (LS) was reported in three patients. The most frequently detected mutation was in the MSH2 gene, followed by mutations in the NOTCH1/2 and TP53 gene. Conclusion, this study provides a molecular analysis of Muir-Torre Syndrome associated and non-associated skin tumors in patients with Muir-Torre Syndrome. Patients with sebaceous lesions should undergo microsatellite instability analysis and accurate evaluation of personal and family history to detect a possible Muir-Torre syndrome. As secondary malignancies may appear years after the first occurrence of sebaceous tumors, lifelong screening is mandatory.

Muir-Torre syndrome (MTS) is an autosomal dominant condition characterized by dermatological tumors along with visceral malignancies. The dermatological manifestations include recurrent sebaceous adenomas and keratoacanthomas. The commonly seen visceral malignancies are colorectal, gynecological, and urological. It is a variant of hereditary non-polyposis colorectal carcinoma syndrome (HNPCC). The underlying genetic mechanism is germline mutations in the DNA mismatch repair (MMR) genes leading to microsatellite instability (MSI), conferring an increased risk of developing malignancies. This is a case of a 57-year-old male patient with a history of colon cancer diagnosed at age 32 and multiple sebaceous adenomas. The patient also has a strong family history of cancer. They were referred to oncology after the immunohistochemical staining of a sebaceous adenoma showed loss of expression for MSH2 and MSH6. Next-generation sequencing identified a mutation in the MSH2 gene. These patients require genetic testing, counseling, and close follow-up with regular screening for cancer.

Sebaceous carcinoma is a malignant neoplasm of the sebaceous glands, which is most often found in the periocular region. Periocular sebaceous carcinoma is frequently found arising from the meibomian glands within the tarsus, especially on the upper eyelid. Other ocular sites include the caruncle, Zeiss glands, eyebrow, and conjunctiva. The most common presentation of periocular sebaceous carcinoma is a fixed, non-painful eyelid nodule. Diagnosis of sebaceous carcinoma requires biopsy and histopathological examination. Given the neoplasm’s ability to undergo subclinical pagetoid spread, conjunctival map biopsies are recommended to help guide treatment of sebaceous carcinoma. The mainstay of treatment for sebaceous carcinoma is surgical excision of the primary lesion. Both wide local excision and Mohs micrographic surgery have been successfully employed for surgical management of the ocular neoplasm. This chapter takes an in-depth look at ocular adnexal sebaceous carcinoma including its epidemiology, pathogenesis, origins, clinical presentation, differential diagnoses, histology, diagnosis, management strategies, and prognosis.

Description Simpson-Golabi-Behmel syndrome is a rare, X-linked recessive syndrome associated with mutations in the genes encoding glypican 3 (GPC3). The majority of cases have been described in pediatric males, with those affected showing manifestations of overgrowth, congenital heart defects, and increased incidence of neoplasia. Due to the X-linked nature of this disorder, penetrance is not well understood in female cases. Very few cases of female presentations of Simpson-Golabi-Behmel syndrome have been described, and this case highlights that there may be an association between mutated GPC3 carrier status and other cancers. We present a case of GPC3 gene mutation suggestive of Simpson-Golabi-Behmel syndrome in an adult female patient, diagnosed based on genetic testing performed due to a diagnosis of sebaceous carcinoma.

Muir-Torre syndrome is a hereditary condition characterized by occurrence of sebaceous neoplasms or keratoacanthomas and visceral tumors. The most common mechanism for this syndrome is a constitutional defect in the mismatch repair genes. We report the case of a 67-year-old woman with a mutator L homologue 1 (MLH1) mutation. She had a history of endometrial and colorectal cancers. The patient presented with a typical keratoacanthoma on the right cheek and numerous sebaceous neoplasms on the face and trunk. Seven sebaceous adenomas and a low-grade sebaceous carcinoma were excised. Most sebaceous adenomas showed dermoscopic features such as some yellow comedo-like globules and curved vessels in creamy-white areas. Moreover, they revealed pathological features such as keratoacanthoma-like architecture and peritumoral or intratumoral lymphocytes. One of these sebaceous adenomas indicated histopathologically spontaneous regression and another was continuous with the hair follicle. Immunohistochemical staining for mismatch repair proteins revealed loss of expression for MLH1 and postmeiotic segregation increased 2 (PMS2) proteins in tumor cells nuclei in both keratoacanthoma and sebaceous adenoma. Nuclei in overhanging epithelial lips of the keratoacanthoma were also negative. These findings suggest that the type of Muir-Torre syndrome-related cutaneous tumor may have been affected by mismatch repair protein deficient sites in the pilosebaceous unit.

The therapeutic options for disease modification in relapsing-remitting multiple sclerosis (RRMS) have expanded remarkably in the last 15 years. Although intravenous immunoglobulins (IVIg) have shown some therapeutic effects in multiple sclerosis, reducing global supplies, restriction of treatment to essential indications and availability of effective alternative treatments for MS currently exclude IVIg from being an accepted therapy for MS, other than for some exceptional considerations. We report the case of a female patient with RRMS who was diagnosed with Ehlers-Danlos syndrome (EDS) and Muir-Torre syndrome (MTS) soon after the diagnosis of active RRMS was made. The coexisting conditions precluded the use of available disease-modifying treatments. She benefited from monthly and then bi-monthly IVIg, with a single mild relapse over 10 years. Discontinuation of IVIg due to reduced availability with a brief aborted course of subcutaneous PEGylated interferon-beta was followed by significant relapses. Five months after the first ocrelizumab infusion, she developed caecal cancer requiring colectomy. Reinstitution of IVIg is contemplated.

Importance Risk of sebaceous carcinoma (SC), a rare skin cancer associated with Muir-Torre syndrome, is elevated among solid organ transplant recipients (SOTRs). However, population studies evaluating this association and assessing survival for posttransplant cases are lacking, and further understanding of SC epidemiology in this immunosuppressed population could provide etiologic and clinical insights. Objective To assess SC incidence and patient survival after solid organ transplantation. Design, Setting, and Participants This cohort study, conducted from January 1, 1987, to December 31, 2017, used data from the Transplant Cancer Match Study, which links transplant and cancer registry data for 17 states and 1 metropolitan area in the United States. Altogether, these registries account for approximately 46% of all US transplants. Data on demographic and transplant characteristics as well as induction and initial maintenance immunosuppressive therapies were obtained from the transplant registry. Standardized incidence ratios (SIRs) comparing SC incidence among SOTRs to the general population were calculated. Incidence rate ratios (IRRs) comparing SC risk between SOTR subgroups were calculated using multivariate Poisson regression. Cox regression was used to compare overall survival between SC cases in SOTRs and other individuals. Main Outcomes and Measures Sebaceous carcinoma incidence and overall patient survival after transplantation compared with the general population. Results A total of 326 282 transplant procedures were performed for 301 075 patients (No. [%] age at transplant, 126 550 [38.8%] aged 0-44 years; 82 394 [25.3%] aged 45-54 years; 82 082 [25.5%] aged 55-64 years; 35 256 [10.8%] aged ≥65 years; 201 354 male patients [61.7%]; 202 557 White patients [62.1%]). A total of 102 SCs were diagnosed in 301 075 SOTRs, corresponding to a 25-fold increased incidence (SIR, 24.8; 95% CI, 20.2-30.1). Incidence was especially elevated among lung recipients (SIR, 47.7; 95% CI, 20.6-94.0) and after a posttransplant diagnosis of cutaneous squamous cell carcinoma (SIR, 104.0; 95% CI, 62.8-163.0). Among SOTRs, factors independently associated with SC risk included male sex (IRR, 2.46; 95% CI, 1.48-4.07; P

Muir-Torre syndrome (MTS) is a rare autosomal dominant condition characterized by the presence of at least one cutaneous sebaceous tumor and one visceral malignancy, arising mostly from the gastrointestinal tract. We present the case of a 63-year-old man with several cutaneous and visceral neoplasias in the context of MTS, and a pelvic lymph node lesion diagnosed initially as metastatic sebaceous carcinoma, but later identified as metastasis from a newly diagnosed prostatic adenocarcinoma. Histological similarities between these 2 lesions are discussed. A systematic literature review was conducted evaluating all published cases of patients with MTS in which metastases were reported. Eighteen articles were included in the final synthesis, representing 20 patients with a total of 26 metastases. Seventeen patients (85%) exhibited metastases originating from MTS-related neoplasms, whereas only 2 patients (11%) exhibited metastases from concomitant malignancies. Of the 85% of patients with metastases from MTS-related malignancies, most originated from noncutaneous sources (78% from visceral neoplasms and 22% from sebaceous carcinomas). When stratifying according to metastases, 23 cases (88%) originated from MTS-related lesions, whereas only 3 (12%) originated from unrelated malignancies. Our findings thus demonstrate that most metastases found in MTS patients (88%) do indeed originate from MTS-related neoplasms. Nevertheless, it remains imperative that a broad differential diagnosis is maintained when assessing a novel lesion, to avoid misdiagnoses, as in the present case, with significant therapeutic and prognostic implications.

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.

Cancer immune-interception for prevention of recurrence in patients with high-risk familial cancer like Muir–Torre syndrome or Lynch syndrome using immune checkpoint blockade inhibitors is a promising approach. Albeit, as described in a case report by Pollak and colleagues in the April 2020 issue of Cancer Prevention Research, it has the potential to be used as immune-interceptive with alternative dosing regimens for cancers with microsatellite instability. The combination of additional cancer preventive and immunopreventive approaches, such as vaccines and minimal dose of immune checkpoint blockade inhibitors, is another unexplored modality for cancer interception in high-risk individuals.

A 68-year-old woman developed an asymptomatic left caruncular multilobular lesion over one year. Excision of the lesion displayed a benign sebaceous neoplasm taking origin from the surface squamous epithelium which invaginated into the stroma to create crypts resembling the conjunctival pseudoglands of Henle or the glands of Lieberkuhn of the small intestine. Scattered sebaceous cells were also discovered in the surface squamous epithelium. The cryptal walls spawned lateral sebaceous gland lobules that were adipophilin positive. p16 was positive in the surface epithelium, the cryptal walls, and in the basal cells of the sebaceous lobules. No defects in nuclear mismatch repair protein expression were identified, which together with the absence of a familial cancer history, rendered unlikely an association with the Muir-Torre syndrome.

Muir-Torre syndrome is a rare subtype of Lynch syndrome characterized by coincidence of skin neoplasm and visceral malignancies. Here, we report a case of this rare disease, whose diagnosis of the syndrome was first suspected by the pathologist. This was a 60-yr-old woman who presented with an axillary skin nodule, which was diagnosed as basal cell carcinoma. Further inquiry revealed that she was hospitalized for evaluation of a recurrent vaginal stump endometrial carcinoma. Histologic workup and immunohistochemistry for mismatch repair proteins of both the skin and vaginal tumor suggested the possibility of Muir-Torre syndrome. NexGen sequencing identified a frame-shift mutation in the MSH2 gene. The patient was found to have a metachronous colorectal carcinoma, uterine endometrial carcinoma, and skin cancer from 1998 to 2016. Five family members had also suffered from colorectal cancer or glioma. This case report illustrates the importance of the multidisciplinary care approach, mismatch repair protein and gene testing, and detailed medical history taking into consideration the diagnosis of Muir-Torre syndrome.

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.

BACKGROUND Sebaceous neoplasms (SN) may appear sporadically in the general population but may also be part of the Muir-Torre variant of Lynch syndrome (MT-LS). There are few studies in southern Europe on the incidence of MT-LS in the population of patients with SN. AIM To retrospectively review patients with SN and to analyse their clinical features and the incidence of MT-LS. METHODS Patients with SN diagnosed between 1995 and 2015 were enrolled in the study. The diagnosis of MT-LS was made according to established clinical criteria and, whenever possible, was confirmed by germline mutation analysis. RESULTS In 60 patients (32 men, 28 women, mean age 69.22 years), 96 SN were diagnosed: 65 adenomas (67.7%), 16 sebaceomas (16.7%) and 15 carcinomas (15.6%). Of the 60 patients, 50 (83.3%) had a single SN and 10 (16.7%) had multiple lesions. Patients diagnosed with MT-LS (12 patients, 20%) were younger (63.25 years vs. 70.71 years), and had a higher incidence of extrafacial SN (4/12 patients, 33.3%), and were significantly (P

Sebaceous carcinomas are rare tumors, with the majority of described cases occurring within the eyelid. To date, there are nine documented reports of sebaceous carcinoma arising within a mature cystic teratoma of the ovary. Although the majority of cases originate from idiopathic mutations, there exists a strong association between this rare tumor and hereditary syndromes of DNA mismatch repair deficiency, such as Lynch syndrome and the lesser-known Muir-Torre syndrome. Here we present the case of a 67 year-old woman with a longstanding history of a small left ovarian cyst with sonographic features of an ovarian dermoid. After nine years, the left adnexal mass was noted to have enlarged, and she underwent a laparoscopic bilateral salpingo-oophorectomy. The final pathology was reported as sebaceous carcinoma arising within a mature cystic teratoma. The patient underwent subsequent surgical staging and has been followed for eight months without evidence of disease. This report includes a review of the current literature, as well as a brief discussion of the clinical management of women with sebaceous carcinoma arising within a mature teratoma. Additionally, we comment on the broader, hereditary significance of a diagnosis of sebaceous carcinoma, and use this case to demonstrate the thorough histologic and genetic evaluation that is recommended for patients diagnosed with this rare tumor. Keywords: Sebaceous carcinoma, Mature cystic teratoma, Dermoid cyst, Lynch syndrome, Muir-Torre syndrome, Hereditary nonpolyposis colorectal cancer (HNPCC)

Sebaceous neoplasms with an organoid pattern (rippled, labyrinthine/sinusoidal, carcinoid-like, and petaloid) are rare. Previous studies suggested that the above patterns likely represent variations along a morphological continuum. The objectives of this study were to (1) validate this proposition by studying a large number of cases, (2) determine whether there are specific associations with clinical features, (3) establish their frequency, and (4) determine whether they have any association with Muir-Torre syndrome. Fifty-seven sebaceous neoplasms (54 sebaceomas and 3 sebaceous carcinomas) with organoid growth patterns were studied. These occurred in 36 men and 18 women (sex unknown in 3), with ages at diagnosis ranging from 22 to 89 years (mean, 63 years). All patients presented with a solitary nodule (mean size, 11 mm) on the head and neck area. Of the 57 tumors, 24 manifested a single growth pattern, 23 had a combination of 2 patterns, and 10 a combination of 3 patterns, indicating that these patterns are part of a morphological continuum of changes. The carcinoid-like pattern was the most frequent in the "monopatterned" neoplasms (13 cases), whereas the labyrinthine/sinusoidal pattern comprised most of the "polypatterned" lesions, in which various combinations occurred. Immunohistochemically, mismatch repair protein deficiency was detected in 3 of the 22 cases studied, whereas 5 of the 33 patients with available follow-up had an internal malignancy/premalignancy. In conclusion, sebaceous neoplasms with organoid growth patterns are predominantly sebaceomas having a predilection for the scalp, occurring as solitary lesions in elderly patients (male to female ratio of 2:1). Such patterns are expected to be found in a quarter of sebaceomas. In most cases, more than one of the organoid patterns is present. These lesions do not appear to be associated with internal malignancy or mismatch repair deficiency in most cases. However, confirmation of the absence of any significant association with Muir-Torre syndrome syndrome will require genetic studies.

Sebaceous carcinoma of the breast (SCB) is a rare variant of ductal carcinoma arising within the mammary gland and containing at least 50% of malignant cells with sebaceous differentiation. Only 11 cases that adjust to the criteria delineated in the WHO classification have been published in the English literature, to the best of our knowledge. Here, we present the first SCB arising in the context of a deleterious BRCA2 mutation, focusing on the histopathologic and immunohistochemical features of this exceedingly rare tumor.

Muir Torre syndrome is an autosomal dominant disorder characterised by germline mutations in mismatch repair genes involved in DNA repair, leading to microsatellite instability and a propensity to tumour formation. We report a case of a 67-year-old gentleman who underwent biopsy of a smooth nodular lesion on the nasal tip, histopathologically consistent with sebaceous adenoma. Immunohistochemistry suggested a loss of MSH6. Subsequent colonoscopy identified a poorly differentiated adenocarcinoma, with loss of staining for MSH6 and a germline mutation identified on genetic analysis. These findings were consistent with a diagnosis of Muir Torre syndrome. Whilst there is controversy in the literature regarding universal screening for Muir Torre syndrome, the early detection of visceral neoplasms is crucial. The authors strongly support screening for Muir Torre syndrome (with patient consent) upon discovery of a cutaneous sebaceous neoplasm, even in the absence of a personal or family history of visceral malignancy.

Sebaceous differentiation is commonly seen in cutaneous neoplasms, both in the context of lesions showing predominantly sebaceous differentiation (e.g., sebaceous adenoma, sebaceoma and sebaceous carcinoma), or as more focal sebaceous components in neoplasms with other primary lines of differentiation. Sebaceous changes can also be a component of benign cystic lesions or epidermal tumours, and sebaceous hyperplasia is commonly encountered. This review is intended to provide an overview of the cutaneous lesions with sebaceous differentiation, with a particular emphasis on facilitating histological diagnosis of neoplasms. In addition, the role of immunohistochemical studies is outlined, as well as the evaluation of potential cases of Muir-Torre syndrome.