127G.Y. Wu et al. (eds.), Atlas of Dermatological Manifestations of Gastrointestinal Disease, DOI 10.1007/978-1-4614-6191-3_52, © Springer Science+Business Media New York 2013

Clinical signs and features include: Sebaceous neoplasms: particularly sebaceous adenomas, • epitheliomas, and carcinomas Sebaceous adenomas are the most common sebaceous • neoplasm associated with Muir–Torre syndrome (MTS) and appear as yellowish circumscribed papules or nod-ules, which most commonly present on the face but in MTS they are more often on the trunk [ 1 ] Sebaceous epitheliomas (sebaceoma): appear as yellow • papules or nodules or plaques occasionally with rolled borders; usually are solitary; commonly ulcerate and bleed; some experts believe basal cell carcinoma with sebaceous differentiation is the same entity as sebaceous epithelioma [ 2 ] Sebaceous hyperplasia may be associated with MTS but • is not speci fi c for MTS and is very common in general population ( see Fig. 52.1 ) Sebaceous carcinoma, except in patients with MTS, is • usually periocular and may appear as a subcutaneous nod-ule, thickening of skin, or pedunculated tumor and often mimics chalazion; sebaceous carcinoma is more typically extraocular in MTS [ 3 ] May also see keratoacanthomas with sebaceous differen-• tiation: fi rm, dome-shaped, erythematous nodule with a

central keratin plug that grows rapidly and can be several centimeters in diameter ( see Fig. 52.2 ) Visceral malignancy: nearly one half of patients have two • or more visceral malignancies; the most common fi rst malignancy is colon cancer accounting for nearly half of cancers; nearly one fourth of patients with MTS have colonic polyps; MTS can also be associated with other digestive tract cancers; genitourinary cancers account for nearly one fourth of visceral cancers; breast cancer, 12%; hematologic cancer, 9% [ 1, 2 ] Median age at diagnosis of cancer: 55 years; 22–32% of • patients present with sebaceous neoplasm before the internal cancer; 9–12% are diagnosed simultaneously with sebaceous neoplasm and internal cancer; 56–59% are diagnosed with internal cancer before the sebaceous neoplasm [ 2 ]

Pathogenesis of this disease involves: Autosomal dominant with high penetrance but variable • expression DNA mismatch repair gene is defective leading to micro-• satellite instability (MSI) [ 4 ] Appears to be a component of hereditary nonpolyposis • coli cancer syndrome (Lynch syndrome), with loss of MSH-2 more common than MLH-1 and rarely MSH-6 mutations [ 4 ]

Histopathological features include: Sebaceous adenoma: well-circumscribed multilobulated • neoplasm often in continuity with overlying squamous epithelium composed of predominantly (>50%) mature sebocytes centrally in addition to basaloid seboblastic cells noted in multiple layers at the periphery of each lob-ule. The distribution of the seboblastic cells and sebocytes as well as transitional cells can vary from within lobules ( see Fig. 52.3 ) Sebaceous epithelioma or sebaceoma has a more • irregularly shaped lobules or masses of cells with a

Muir–Torre Syndrome: Dermatological Features

Liam Zakko , Justin Finch , Marti J. Rothe , and Jane M. Grant-Kels

52

L. Zakko (*) Yale Department of Internal Medicine , 20 York Street, Yale New Haven Hospital , New Haven, CT 05610 , USA e-mail: liam.zakko@yale.edu

J. Finch • M. J. Rothe • J. M. Grant-Kels Department of Dermatology , University of Connecticut Health Center , 21 South Road , Farmington , CT 06030 , USA e-mail: fi nch@uchc.edu; rothe@uchc.edu; grant@uchc.edu

128 L. Zakko et al.

preponderance (>50%) of undifferentiated germinative seboblastic cells plus scattered transitional cells and aggregates of central mature sebocytes

Sebaceous carcinoma: asymmetrical, poorly circum-• scribed, in fi ltrating neoplasm composed of germinative cells plus some cells demonstrating sebaceous differentia-tion, evidence of mitotic fi gures as well as cellular/nuclear pleomorphism/hyperchromatism; more likely MTS if periocular Keratoacanthoma: atypical squamous neoplasm with an • exo- and endophytic architecture and a central horn fi lled crater; if contains sebaceous differentiation more likely to be MTS ( see Fig. 52.4 )

The diagnosis is made using a combination of: One of A and B or all of C with no other etiology of the • fi ndings [ 5 ] :

Group A: sebaceous adenoma, sebaceous epithelioma, –sebaceous carcinoma, keratoacanthoma with seba-ceous differentiation Group B: a visceral malignancy – Group C: multiple keratoacanthomas, multiple visceral –malignancies, family history of MTS

Fig. 52.1 Extensive sebaceous hyperplasia

Fig. 52.2 Keratoacanthoma. Crateriform nodule on the dorsal hand, with hyperkeratotic core

Fig. 52.3 Sebaceous adenoma. Circumscribed lobular tumor compris-ing sebaceous cells and basaloid cells (40×)

Fig. 52.4 Keratoacanthoma. Well-circumscribed keratin- fi lled crater ( arrow ) surrounded by pale, glassy keratinocytes (10×)

12952 Muir–Torre Syndrome: Dermatological Features

The identi fi cation of a sebaceous neoplasm on the trunk • or extremities in a patient younger than 50 years old war-rants additional work-up [ 4 ]

If immunohistochemistry testing of the neoplasm –shows absence of expression of MSH-2, MSH-1, or MSH-6, then MSI analysis is recommended. If MSI is detected, then the proband and family should –have cancer surveillance If MSI is not detected but there is a positive family his- –tory for MTS, then germline mutation analysis should be performed and, if positive, the proband and family should have cancer surveillance If MSI is not detected and family history is negative –for MTS, then no further testing is recommended

The differential diagnosis should include: Sebaceous hyperplasia • Cowden’s disease • Multiple trichoepitheliomas • Basal cell nevus syndrome • Ferguson–Smith syndrome • Tuberous sclerosis • Extramammary Paget’s disease • Metastatic renal clear cell carcinoma • Balloon cell melanoma •

Metastatic sebaceous carcinoma of the parotid gland • Treatment options include [ 1, 6 ] :

Sebaceous adenoma and epithelioma: excision/• cryosurgery Sebaceous carcinoma: wide excision or Mohs surgery • Keratoacanthoma: excision or Mohs surgery • Oral isotretinoin alone or in combination with interferon-• a may prevent or partially treat cutaneous lesions

References

1. Ponti G, Ponz de Leon M. Muir–Torre syndrome. Lancet Oncol. 2005;6:980–7.

2. Eisen DB, Michael DJ. Sebaceous lesions and their associated syn-dromes: part II. J Am Acad Dermatol. 2009;61:563–78.

3. Shalin SC, Lyle S, Calonje E, Lazar AJF. Sebaceous neoplasia and the Muir–Torre syndrome: important connections with clinical implications. Histopathology. 2010;56:133–47.

4. Abbas O, Mahalingam M. Cutaneous sebaceous neoplasms as markers of Muir–Torre syndrome: a diagnostic algorithm. J Cutan Pathol. 2009;36:613–9.

5. Schwartz RA, Torre DP. The Muir–Torre syndrome: a 25 year ret-rospective. J Am Acad Dermatol. 1995;33:90–104.

6. Eisen DB, Michael DJ. Sebaceous lesions and their associated syn-dromes: part I. J Am Acad Dermatol. 2009;61:549–60.