Apocrine carcinoma with marked sebocyte-like cytological features: A report of two cases.

Apocrine carcinoma cases with sebaceous differentiation have not been reported and can be misdiagnosed as sebaceous carcinoma. We present two cases of apocrine carcinoma with marked sebocyte-like cytological features. Tumors were observed in the left axilla of a 68-year-old man (Case 1) and the right axilla of a 72-year-old man (Case 2). Both patients presented with multiple lymph node metastases. Histopathology revealed densely distributed solid nests of tumor cells containing foamy cytoplasm and enlarged round nuclei with prominent nucleoli. The tumor cells diffusely expressed adipophilin, PRAME (cytoplasmic pattern), androgen receptor, BerEP4, and GCDFP15 but did not express p63 in both cases. PIK3CA E726K and H1047R mutations were detected in Cases 1 and 2, respectively. Tumor location in the axilla, the presence of eosinophilic granular cytoplasm, prominent nucleoli, and PIK3CA mutations, immunoreactivity for BerEP4 and GCDFP15, and lack of p63 immunoexpression findings matched apocrine carcinoma characteristics, but not sebaceous carcinoma. Thus, apocrine carcinoma can demonstrate intracytoplasmic lipid accumulation and rarely exhibit sebocyte-like cytological features. Apocrine carcinoma should be distinguished from sebaceous carcinoma due to the former's higher metastatic potential and lack of association with Muir-Torre syndrome.

Mosaic Muir Torre Syndrome: Keratoacanthoma as a Piece of the Puzzle.

ABSTRACT: Lynch syndrome is an inherited condition, which increases the risk of numerous visceral malignancies and cutaneous tumors such as keratoacanthomas and sebaceous tumors. It is typically identified by immunohistochemistry of tissue taken from tumors or through genetic testing with next-generation sequencing. Diagnosing Lynch syndrome becomes more complex when the individual is mosaic for the relevant pathogenic variant. There are very few cases of this reported in the medical literature. It is even more unusual for the diagnosis to be made based on testing of a keratoacanthoma lesion. We report a case where immunohistochemistry of a keratoacanthoma helped make a diagnosis of mosaic Lynch syndrome. We will explore how mosaicism should be considered when a phenotype is strong, even if next-generation sequencing reports no pathogenic or likely pathogenic variant and how lesions such as keratoacanthomas can have a role in the early detection and treatment of future malignancies.

Androgen Receptor Immunohistochemistry is Superior to PRAME for the Differentiation of Sebaceous Carcinoma From Primary Cutaneous Basaloid Mimics.

ABSTRACT: Cutaneous sebaceous neoplasia comprises a spectrum of disease ranging from benign adenomas to malignant carcinomas. The hallmark of these lesions is sebaceous differentiation. However, poorly-differentiated sebaceous carcinoma (SC), which lacks significant overt sebaceous differentiation, can show morphologic overlap with a variety of other basaloid cutaneous neoplasms. The accurate classification of SC is essential not only for diagnosis, but also because of the potential association with Muir-Torre syndrome. Androgen receptor (AR) is a sensitive, but not entirely specific immunohistochemical marker that has been used for the diagnosis of SC. PReferentially expressed Antigen in MElanoma (PRAME) demonstrates strong cytoplasmic labeling of mature sebocytes and has been reported to be expressed in a variety of sebaceous neoplasms, including in the basaloid cell component. Therefore, we sought to compare the diagnostic use of cytoplasmic PRAME expression with that of AR for the distinction of SC from a cohort of basaloid cutaneous mimics; namely basal cell carcinoma, basaloid squamous cell carcinoma, pilomatricoma, cutaneous lymphadenoma, and extra-mammary Paget disease. We report that cytoplasmic PRAME expression is uncommon in poorly differentiated SC, and although specific, it shows very low sensitivity (22%). In contrast, AR was moderately sensitive (66%) and highly specific (92%) for the distinction of SC from basaloid mimics. These attributes, in addition to the nuclear expression of AR in the sebocytic and basaloid components of SC, suggest that AR is superior to PRAME for the diagnosis of SC.

S1-Guideline Sebaceous Carcinoma.

Sebaceous gland carcinomas are rare malignant cutaneous adnexal tumors with sebocytic differentiation. The typical predilection area is the head and neck region, where sebaceous gland carcinomas are the most common malignant adnexal tumors of the skin. According to their localization a distinction is made between periocular and extraocular sebaceous gland carcinomas. Muir-Torre syndrome (MTS) should always be ruled out if it is suspected. In terms of prognosis, sebaceous gland carcinomas are potentially aggressive tumors with a clear tendency to recur and metastasize. Only small extraocular sebaceous gland carcinomas that have been completely resected have a very good prognosis. Sebaceous gland carcinomas most frequently metastasize lymphogenously to regional or distant lymph nodes; organ metastasis occurs less frequently. Periocular sebaceous gland carcinomas have a higher metastasis rate (up to 15%) than extraocular sebaceous gland carcinomas (up to 2%). Complete micrographically controlled surgery (MCS) of the primary tumor is the therapy of first choice, regardless of periocular or extraocular localization. Adjuvant or therapeutic radiotherapy may be considered. There is currently no established standard therapy for advanced, inoperable, or metastatic sebaceous gland carcinomas. Local procedures and systemic therapies such as chemotherapy or immunotherapy can be considered. The procedure should be determined individually by an interdisciplinary tumor board. Close follow-up care is recommended for these potentially aggressive carcinomas.

Patients with a new-onset cutaneous sebaceous neoplasm following immunosuppression should be evaluated for Muir-Torre syndrome with germline mismatch repair gene mutation analysis: case reports.

Patients with Muir-Torre syndrome may have a systemic malignancy and a sebaceous neoplasm such as an adenoma, epithelioma, and/or carcinoma. The syndrome usually results from a germline mutation in one or more mismatch repair genes. Iatrogenic or acquired immunosuppression can promote the appearance of sebaceous tumors, either as an isolated event or as a feature of Muir-Torre syndrome and may unmask individuals genetically predisposed to the syndrome. Two iatrogenically immunosuppressed men with Muir-Torre syndrome features are described. Similar to these immunocompromised men, Muir-Torre syndrome-associated sebaceous neoplasms have occurred in solid organ transplant recipients, human immunodeficiency virus-infected individuals, and patients with chronic diseases who are treated with immunosuppressive agents. Muir-Torre syndrome-associated sebaceous neoplasms occur more frequently and earlier in kidney recipients, who are receiving more post-transplant immunosuppressive agents, than in liver recipients. The development of sebaceous neoplasms is decreased by replacing cyclosporine or tacrolimus with sirolimus or everolimus. Specific anti-cancer vaccines or checkpoint blockade immunotherapy may merit exploration for immune-interception of Muir-Torre syndrome-associated sebaceous neoplasms and syndrome-related visceral cancers. We suggest germline testing for genomic aberrations of mismatch repair genes should routinely be performed in all patients-both immunocompetent and immunosuppressed-who develop a Muir-Torre syndrome-associated sebaceous neoplasm.

[Analysis of gene mutation in a family with Muir-Torre syndrome accompanied with extraorbital cystic sebaceous carcinoma].

This study reported a family of MLH1 mutation-induced Muir-Torre syndrome (MTS) and evaluated it's clinical and genetic characteristics. A 51 year-old patient with extraorbital cystic sebaceous and colon adenocarcinoma diagnosed in November 2021 in Zhongshan Hospital of Xiamen University was included. The clinical data of the family were collected and a pedigree chart was drawn, which was in line with the Chinese Lynch syndrome diagnostic criteria and was a typical MTS family. NM_000249.4:c.298C>T(p.R100*) of MLH1 gene in exon 3 was detected by whole exome sequencing and multiplex ligation dependent amplification, which is a pathogenic mutation. After the pathogenic mutation was identified, Sanger sequencing was performed on 4 direct members of the family for MLH1 gene, and 3 family members were found to have detected the mutation and included in MTS risk control. Until December 25 2023, follow-up showed the proband patients were not suffered from recurrence or new occurrence of skin or gastrointestinal tumors. The study reported a typical MTS family and found a possible pathogenic nonsense mutation in the MLH1 gene, which provides new evidence for the pathogenicity of this mutation.

Muir-Torre syndrome and recent updates on screening guidelines: The link between colorectal tumors and sebaceous adenomas in unusual locations.

BACKGROUND: Muir-Torre syndrome (MTS) is a rare genetic disorder that is caused by mismatch repair (MMR) protein mutations. MTS increases the risk of developing skin and gastrointestinal tumors such as sebaceous adenomas (SAs), sebaceous carcinomas, colorectal cancer, endometrial cancer, and ovarian cancer. The risk of developing these types of tumors varies depending on the involved mutation and the individual's family history risk. CASE PRESENTATION: A 47-year-old male presented with multiple skin lesions on the scalp, face, flank, and back. The examination revealed well-circumscribed, dome-shaped papules with a yellowish appearance with white oily material in the center. Histopathologic examination showed a well-circumscribed sebaceous neoplasm consistent with a mixture of basaloid cells and lobules of bland-appearing mature adipocytes that communicate directly to the surface epithelium. Focal cystic changes and peritumoral lymphocytic infiltrate were noted. Increased mitotic figures were seen in the basaloid cell component. The overall findings were consistent with the diagnosis of SAs. MMR staining showed preserved expression in MLH1 and PMS2 proteins, while MSH2 and MSH6 staining showed loss of protein expression. A screening colonoscopy showed numerous colon and rectal tumors, prompting concerns about the likelihood of MTS. Surgical intervention was pursued for complete resection. Histology revealed a diagnosis of mucinous adenocarcinoma/adenocarcinoma with mucinous features of the colon. The diagnosis of MTS was supported by molecular testing that revealed MSH2 germline mutation. The increased likelihood of MTS was attributed to the occurrence of SAs in unusual locations of the head and neck regions, unlike typical cases. CONCLUSION: MTS is a rare clinical condition that necessitates prompt thorough evaluation and periodic surveillance. When SA is encountered in atypical locations, it is important to consider additional testing supported by immunohistochemical staining, molecular testing, and regular screening to exclude the likelihood of MTS.

Sebaceous carcinoma epidemiology, associated malignancies and Lynch/Muir-Torre syndrome screening in England from 2008 to 2018.

BACKGROUND: Sebaceous carcinomas (SC) may be associated with the cancer predisposition syndrome Muir-Torre/Lynch syndrome (MTS/LS), identifiable by SC mismatch repair (MMR) screening; however, there is limited data on MMR status of SC. OBJECTIVE: To describe the epidemiology of SC, copresentation of other cancers, and population level frequency of MMR screening in SC. METHODS: A population-based retrospective cohort study of SC patients in the National Cancer Registration and Analysis Service in England. RESULTS: This study included 1077 SC cases (739 extraocular, 338 periocular). Age-standardized incidence rates (ASIR) were higher in men compared with women, 2.74 (95% CI, 2.52-9.69) per 1,000,000 person-years for men versus 1.47 person-years (95% CI, 1.4-1.62) for women. Of the patients, 19% (210/1077) developed at least one MTS/LS-associated malignancy. MMR immunohistochemical screening was performed in only 20% (220/1077) of SC tumors; of these, 32% (70/219) of tumors were MMR deficient. LIMITATIONS: Retrospective design. CONCLUSIONS: Incorporation of MMR screening into clinical practice guidelines for the management of SC will increase the opportunity for MTS/LS diagnoses, with implications for cancer surveillance, chemoprevention with aspirin, and immunotherapy treatment targeted to MTS/LS cancers.

Comparison of clinicopathologic features, survival, and demographics in sebaceous carcinoma patients with and without Muir-Torre syndrome.

BACKGROUND: Visceral malignancies in patients with Lynch syndrome behave less aggressively than in those without Lynch syndrome. The behavior of sebaceous carcinoma (SC) in Muir-Torre syndrome (MTS), a variant of Lynch syndrome, is incompletely investigated. OBJECTIVE: To investigate features and survival of SC patients with and without MTS. METHODS: Retrospective cohort study in the Surveillance, Epidemiology, and End Results 17 database from 2000 to 2019 of patients with SC. Patients were classified as MTS or non-MTS cases based on a threshold score of 2 on the Mayo MTS risk score. RESULTS: We identified 105 (2.8%) MTS cases and 3677 (97.2%) non-MTS cases. On univariate analysis, MTS patients were younger, had a higher proportion of tumors outside the head/neck, and had fewer high-grade tumors. On Kaplan-Meier analysis, MTS patients trended toward having better SC-specific survival. On multivariate Cox proportional hazards analysis adjusting for other covariates, MTS status was an independent predictor of worse overall survival. However, there was no association between MTS status and SC-specific survival. LIMITATIONS: Given relatively high disease-specific survival in SC, our study may have been underpowered to detect a difference on Kaplan-Meier analysis. CONCLUSIONS: Our study suggests SC does not behave more aggressively in patients with MTS.

Immunohistochemistry, Molecular Biology, and Clinical Scoring for the Detection of Muir-Torre Syndrome in Cutaneous Sebaceous Tumors: Which Strategy?

BACKGROUND: Sebaceous neoplasms (SNs) always raise the possibility of an association with Muir-Torre syndrome (MTS) and permit to screen internal malignancies, colorectal and endometrial carcinomas, before they become symptomatic. Immunohistochemistry (IHC), molecular biology, and clinical examination are different approaches for detection of MTS. We conducted a retrospective analysis of non-selected SNs in order to determine the optimal tools to implement for MTS screening. METHODS: Deficient MMR phenotype (dMMR) was determined by either IHC using antibodies directed to four mismatch repair (MMR) antigens on tissue microarray or molecular biology using pentaplex PCR. The Mayo Clinic risk score of MTS was calculated from medical records. Sensibility and specificity of each test for the detection of MTS were determined. RESULTS: We included 107 patients, 8 with multiple SNs, for a total of 123 SNs (43 sebaceous adenomas, 19 sebaceomas, and 61 sebaceous carcinomas (SC)). Loss of at least one MMR protein was observed in 70.7% of tumors, while 48% had a microsatellite instable phenotype. Concordance between both techniques was 92.9%, with a 0.85 Cohen's kappa coefficient. Nineteen patients (20.2%) had a ≥2 points Mayo Clinic risk score, one having a pMMR SC. Among the 13 patients with confirmed MTS, 2 had a low Mayo Clinic risk score (1 point). IHC had the highest sensitivity for MTS screening (100%) with a specificity of 34.1%, while a >2-point Mayo Clinic risk score had a lower sensitivity (92%) but a higher specificity (89%). CONCLUSION: To detect MTS in SN patients, the first-line Mayo Clinic risk score followed by IHC appears to be the most accurate strategy with lower cost for society. This strategy should be adapted to the medico-economic resources of each country.

Clinical Outcomes in Sebaceous Carcinoma: A Retrospective Two-Center Cohort Study.

BACKGROUND: Sebaceous carcinoma (SC) is a rare, potentially recurrent, and life-threatening cutaneous malignancy that can be associated with Muir-Torre syndrome (MTS), a DNA mismatch repair-driven genodermatosis. Earlier studies examining factors associated with recurrence have focused on periocular tumors only. OBJECTIVE: Examine outcomes of SC and identify factors associated with recurrence. MATERIALS AND METHODS: Retrospective study from 2 tertiary care centers. RESULTS: Sixty-seven cases from 63 patients were identified, including 7 cases of MTS and 13 arising in the context of immunosuppression. Fifty-five cases (82.1%) were treated with complete circumferential peripheral and deep margin assessment (CCPDMA) methods. Five recurrences developed during the postoperative period. On univariate analysis, periocular location (odds ratio [OR] 7.6, p = .0410), and lesion size ≥2 cm (OR 9.6, p = .005) were associated with recurrence, whereas CCPDMA (OR 0.052, p = .0006) was inversely associated with recurrence. On multivariate analysis, only lesion size ≥2 cm (OR 9.6, p = .0233) and CCPDMA approaches (OR 0.052, p = .007) were significant. CONCLUSION: Non-complete circumferential peripheral and deep margin assessment methods and large lesion size were independent risk factors predicting recurrence, whereas anatomic subtype and MTS status were not. These findings can assist in identifying SC cases that may benefit from more aggressive treatment and closer surveillance.

Sebaceous Carcinoma Arising in Ovarian Teratoma: First Report Associated With Germline Mismatch Repair Gene Mutation.

Sebaceous carcinoma is an uncommon primary cutaneous neoplasm which may be associated with mismatch repair (MMR) abnormalities and sometimes with Muir-Torré syndrome. These neoplasms rarely arise in the ovary within a teratoma/ dermoid cyst. We report a sebaceous carcinoma arising in an ovarian teratoma in a 49-yr old (the 14th case reported in the literature) which exhibited loss of expression of MMR proteins MSH2 and MSH6. A germline mutation c.1102C>T was present in exon 7 of the MSH2 gene, the first report of a germline mutation associated with this tumor type. In reporting this case, we review prior reports of primary ovarian sebaceous carcinoma. We recommend that all sebaceous carcinomas of the ovary undergo immunohistochemistry for MMR proteins for investigation of possible Lynch syndrome.

Muir-Torre syndrome: a case of unusual coexisting genetic mutations.

Patients with Muir-Torre syndrome (MTS) commonly have germline mismatch repair mutations in MLH1, MSH2 or MSH6, with a strong predominance in MSH2. A subset of approximately one-third of patients will instead have an autosomal recessive base excision repair mutation in MUTYH called MUTYH polyposis. To the best of our knowledge, this is the first report of coexisting germline MSH2 and MUTYH mutations in a patient with MTS.

Clinical Features and Prognosis of Young and Middle-Aged Adults With Skin Sebaceous Adenocarcinoma.

BACKGROUND: Sebaceous adenocarcinoma (SAC) mostly occurs in the elderly, and SAC in young and middle-aged population is inadequately investigated. OBJECTIVE: To explore the clinical features and prognosis of young and middle-aged adults with SAC. MATERIALS AND METHODS: Patients with skin SAC between ages 18 and 59 years from the Surveillance, Epidemiology, and End Results database (1975-2016) were eligible for this study. RESULTS: Seven hundred thirty-nine cases were identified. The proportion of extraocular SAC in the nonelderly increased from 1975-2005 to 2006-2016 ( p = .001), male predominance was observed in overall patients whereas female predominance in Asian population, and young patients had more head and neck SAC than middle-aged patients ( p = .014). The prognosis of young patients was better than middle-aged patients ( p = .004). Other independent prognostic factors included sex, marital status, tumor size, surgery, chemotherapy, and multiple primary cancer history. CONCLUSION: An increasing proportion of extraocular SAC was observed in young and middle-aged patients, and the young developed more head and neck SAC than the middle-aged. Female predominance was found in Asian population, and female patients had better prognosis. Younger age and married status indicated better prognosis, and around 20% of young and middle-aged patients might have poorer survival because of Muir-Torre syndrome.

In Vivo Reflectance Confocal Microscopy of Adnexal Tumors: Evaluation of Trichoepithelioma, Sebaceoma, and Fibrofolliculoma.

ABSTRACT: Cutaneous adnexal tumors are benign and malignant neoplasms that undergo morphological differentiation into cutaneous adnexa, comprising pilosebaceous, eccrine, or apocrine units. Reflectance confocal microscopy is a noninvasive diagnostic method that enables in vivo visualization of tissues at a similar resolution as conventional histopathology. The use of this method in skin imaging over the past several years has improved dermatological diagnoses, potentiating its wide application, especially for benign and malignant skin tumors. We describe the use of reflectance confocal microscopy in cases of trichoepithelioma, sebaceoma, and fibrofolliculoma and correlate the resulting clinical, histopathological, and confocal microscopy images.

Keratoacanthoma or cutaneous squamous cell carcinoma revealing a DNA mismatch repair default (Muir-Torre Syndrome).

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.

Seborrheic Keratosis With Sebaceous Differentiation, a Series of 8 Cases and Critical Review of the Literature.

ABSTRACT: Seborrheic keratosis with sebaceous differentiation (SKSD) can sometimes raise uncertainty, confuse with other even malignant entities, and lead to overestimation of this harmless variant. Retrospective analysis of the cases diagnosed as SKSD and a search of the pertaining literature were conducted. Eight cases of SKSD were found. Histologically, these lesions show a flat to plate-like outgrowth of basaloid cells with solitary or clustered sebocytes at the bottom of the rete ridges and variable sebaceous ducts with luminal cuticula. The lesions differed in the outgrowth subpattern: flat/macular, acanthotic, or reticulated. No association was found with Muir-Torre syndrome, and no malignant transformation was seen in these lesions. Literature search revealed confusingly designated lesions that simply represented SKSD. SKSD can show several growth patterns as classic SK. This entity is either underreported or even underrecognized. This entity is benign; however, according to the literature, exclusion of an associating Muir-Torre syndrome should be warranted. The published literature about this lesion is confusing and inconsistent. We suggest the avoidance of confusing terminology and particularly the terminus epithelioma for such lesions.

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.

Muir-Torre Syndrome With a Frame-shift Mutation in the MSH2 Gene: A Rare Case Report and Literature Review.

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.

Metastatic Prostatic Adenocarcinoma in Patient With Muir-Torre Syndrome Misdiagnosed as Metastatic Sebaceous Carcinoma: Case Report and Systematic Literature Review.

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.