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Is a cystic sebaceous neoplasm always marker for Muir-Torre syndrome?

  • Author(s): Arsenovic, Nebojsa
  • Ramaiya, Arjun
  • et al.
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Is a cystic sebaceous neoplasm always marker for Muir-Torre syndrome?
Nebojsa Arsenovic MD SpecPath1, Arjun Ramaiya MBBS FRCPath2
Dermatology Online Journal 15 (11): 11

1. Section for Skin Pathology, Department of Cellular Pathology, PathLinks Pathology Services, Lincoln County Hospital, Lincoln, UK
2. Department of Cellular Pathology, Norfolk and Norwich University Hospitals, Norwich, UK


Abstract

Cystic sebaceous neoplasms are uncommon and almost always regarded as a consistent marker for Muir-Torre syndrome. We present a 73-year-old man with a cystic sebaceous neoplasm on his arm, clinically not associated with Muir-Torre syndrome.


A number of cutaneous lesions have been reported as markers of internal malignancy. Muir-Torre syndrome (MTS) describes sebaceous neoplasia in individuals with internal malignancy, especially colorectal adenocarcinoma [1, 2]. MTS is considered a subtype of a hereditary nonpolyposis colorectal cancer syndrome, characterized by familial truncating germline mutations involving one of the DNA mismatch repair genes, most often hMSH2. The genetic defect is inherited in an autosomal dominant fashion with a high degree of penetrance, variable expression and a slight male predominance. Rütten et al. [3] studied 19 cases of Muir-Torre syndrome and found 8 patients who presented with a cystic variant of sebaceous neoplasms. They concluded that cystic sebaceous neoplasms are a marker for Muir-Torre syndrome. We report a case of a cystic sebaceous neoplasm arising on the forearm of a 73-year-old male with no clinical evidence for Muir-Torre syndrome.


Figure 1Figure 2
Figure 1. A 13 mm multilobular fleshy nodule

Figure 2. Low power view of a solid cystic sebaceous neoplasm

In 2008, a 73-year-old male presented with a skin tag on the right forearm. This was clinically diagnosed as a fibroepithelioma and excised. Macroscopically, it appeared to be a 13 mm well defined nodular, multilobular fleshy lesion (Fig. 1). Microscopic examination revealed a well-circumscribed dermal solid-cystic neoplasm (Fig. 2) composed of peripheral basaloid cells, which showed central maturation into well differentiated sebocytes with mild atypia (Fig. 3). Focally the neoplasm contained a collapsed cyst lined by similar sebocytes (Fig. 4). The immunohistochemistry for the DNA mismatch repair gene hMSH2 revealed no expression. The appearance was typical of a cystic sebaceous neoplasm.


Figure 3Figure 4
Figure 3. High power view of the solid part showing well-differentiated sebocytes with mild atypia

Figure 4. High power view of the cystic wall lined by sebocytes with similar morphology

The patient did not have a history of colorectal, genitourinary or other malignancy. Clinical investigations including endoscopy, random biopsies, and CT scan were normal. His follow up had been uneventful until his death during an unrelated surgical procedure (cardiac valve replacement). Clinical assessment of the family did not reveal evidence suggestive of Muir-Torre syndrome. Consent for further genetic/molecular studies could not be obtained.

Cystic sebaceous neoplasms are uncommon. Recently, there has been debate about their biology and classification [4, 5, 6]. Rütten et al. were one of the first to suggest cystic sebaceous neoplasms as markers of the mismatch repair-deficient subtype of Muir-Torre syndrome. In their study, molecular analysis of 10 cystic sebaceous neoplasms revealed microsatellite instability in 100 percent of cases [3]. Further investigation is required to explain the predisposition for development of sebaceous neoplasms in Muir-Torre syndrome and their characteristic cystic appearance [7]. Recognition of this association is of clinical importance because cutaneous neoplasms may coincide or precede visceral malignancies. Individuals presenting with sebaceous neoplasms can undergo genetic tests and those with the inherited mutation can be screened for internal malignancies. These include malignancies with a strong association with Muir-Torre syndrome such as those arising in the gastrointestinal, genitourinary, and female genital tract. Individuals with Muir-Torre syndrome may have a positive family history of malignancy, which is of relevance for genetic counseling and family screening.

The present case highlights this uncommon neoplasm and reflects on its association with Muir-Torre syndrome. This is limited by the constraints on further investigations including genetic studies and molecular analysis and stain of the tumor for expression of two other common DNA mismatch repair genes (MLH1 and MSH6) on available tissue. It is likely that there is a strong etiological relationship between Muir Torre syndrome and cystic sebaceous neoplasia. However, cystic sebaceous neoplasms may not be consistent markers for Muir-Torre syndrome. Cystic sebaceous neoplasms are uncommon and reviews of the syndrome may be prone to observational bias. Studies involving larger numbers of cystic sebaceous neoplasms may be required to elucidate the precise relationship between this uncommon adnexal neoplasm and genetic predisposition to visceral malignancy.

References

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