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Muir-Torre Syndrome: a Rare but Important Disorder

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Muir-Torre Syndrome: a Rare but Important Disorder CONTINUING MEDICAL EDUCATION Muir-Torre Syndrome: A Rare But Important Disorder Holly H. Hare, MD; Neetu Mahendraker, MD; Sandhya Sarwate, MD; Krishnarao Tangella, MD GOAL To understand Muir-Torre syndrome (MTS) to better manage patients with the condition LEARNING OBJECTIVES Upon completion of this activity, dermatologists and general practitioners should be able to: 1. Identify diagnostic criteria for MTS. 2. Interpret the inheritance pattern of MTS. 3. Propose treatments for MTS. CME Test on page 265. This article has been peer reviewed and approved Einstein College of Medicine is accredited by by Michael Fisher, MD, Professor of Medicine, the ACCME to provide continuing medical edu- Albert Einstein College of Medicine. Review date: cation for physicians. September 2008. Albert Einstein College of Medicine designates This activity has been planned and imple- this educational activity for a maximum of 1 AMA mented in accordance with the Essential Areas PRA Category 1 CreditTM. Physicians should only and Policies of the Accreditation Council for claim credit commensurate with the extent of their Continuing Medical Education through the participation in the activity. joint sponsorship of Albert Einstein College of This activity has been planned and produced in Medicine and Quadrant HealthCom, Inc. Albert accordance with ACCME Essentials. Drs. Hare, Mahendraker, Sarwate, and Tangella report no conflict of interest. The authors report no discussion of off-label use. Dr. Fisher reports no conflict of interest. Muir-Torre syndrome (MTS) is a rare disorder char- malignancy. Sebaceous adenomas, sebaceous acterized by the presence of at least one seba- carcinomas, and sebaceomas (sebaceous epi- ceous gland neoplasm and at least one visceral theliomas) are all characteristic glandular tumors of MTS. The most common visceral malignancies Accepted for publication October 1, 2007. associated with MTS are colorectal, followed by Dr. Hare is a dermatology resident, Department of Dermatology, genitourinary. These visceral malignancies fre- University of Missouri, Columbia. Dr. Mahendraker is Visiting quently have a more indolent course in patients Clinical Associate, Department of Internal Medicine, University of Illinois, Urbana. Dr. Sarwate is a pathologist, Christie Clinic with MTS than they would otherwise. Muir-Torre Department of Pathology, Urbana, and Clinical Associate syndrome is an autosomal dominant disorder; Professor, Department of Pathology, University of Illinois, Urbana. however, sporadic cases are known to develop. Dr. Tangella is a pathologist, Christie Clinic Department of It often is associated with germ-line mutations in Pathology, Urbana, and Clinical Assistant Professor, Department of the mutS homolog 2, colon cancer, nonpolyposis Pathology, University of Illinois, Urbana. Correspondence: Holly H. Hare, MD, Department of Dermatology type 1 (Escherichia coli) gene, MSH2, and the at the University of Missouri, 1 Hospital Dr, MA111, Columbia, MO mutL homolog 1, colon cancer, nonpolyposis 65212 ([email protected]). type 2 (E coli) gene, MLH1 (similar to hereditary 252 CUTIS® Muir-Torre Syndrome nonpolyposis colon cancer [HNPCC]). The diag- sent to pathology for evaluation. On microscopic nosis of MTS currently is based on clinical crite- examination, a well-differentiated sebaceous carcinoma ria; however, immunohistochemical staining for was noted. Immunoperoxidase studies were performed. MSH2 and MLH1 can confirm the diagnosis. We The stain for the mutS homolog 2, colon cancer, non- report 2 patients with MTS who developed colon polyposis type 1 (Escherichia coli) gene, MSH2, showed adenocarcinomas in conjunction with sebaceous loss of expression in tumor cells. Expression of the carcinomas. Both patients demonstrated loss of mutL homolog 1, colon cancer, nonpolyposis type 2 MSH2 expression in tumor cells on immunohis- (E coli) gene, MLH1, was intact. tochemical staining. One of these patients later The patient’s medical history included sebaceous developed gastric carcinoma, a very uncommon hyperplasia of the left naris in 1993, and the right malignancy associated with MTS. We conclude naris and right temple in 1994. In December 1995, that the diagnosis of rare sebaceous lesions at 41 years of age, the patient was diagnosed with associated with MTS may represent a marker of Dukes C node-positive colon adenocarcinoma and visceral disease and warrants further investiga- underwent subtotal colectomy and subsequent adju- tion for internal malignancies in the individual and vant chemotherapy. In 1999, she had a sebaceous ade- GOAL at-risk family members. noma removed from her right forehead and a sebaceous To understand Muir-Torre syndrome (MTS) to better manage patients with the condition Cutis. 2008;82:252-256. lesion, with differential including sebaceous hyperpla- LEARNING OBJECTIVES sia and adenoma, removed from her mid forehead. The Upon completion of this activity, dermatologists and general practitioners should be able to: patient underwent total hysterectomy and bilateral uir-Torre syndrome (MTS) was first described salpingo-oophorectomy in 2000 for leiomyomas. 1. Identify diagnostic criteria for MTS. by Muir et al1 in 1967 and Torre2 in 1968 as The patient’s family history was equally complex. 2. Interpret the inheritance pattern of MTS. M a disorder characterized by the association of Her mother had a history of colon, gastric, uterine, and 3. Propose treatments for MTS. sebaceous gland neoplasms and visceral malignancies, urethral cancer. Two brothers died from colon cancer, most commonly colon cancer. Diagnostic criteria for one at 16 and the other at 39 years of age. The patient’s CME Test on page 265. MTS are the synchronous or metachronous occur- maternal grandfather, maternal uncle, and a maternal rence of at least one sebaceous gland neoplasm and first cousin were all diagnosed with colon cancer. One at least one visceral malignancy.3,4 The sebaceous maternal aunt was diagnosed with uterine cancer and gland neoplasms include adenomas, carcinomas, and another with ovarian cancer. One maternal cousin sebaceomas (sebaceous epitheliomas). The visceral was diagnosed with both breast and colon cancer and malignancies are most commonly colorectal and geni- another was diagnosed with renal cell carcinoma. tourinary but can include a variety of other visceral Patient 2—A 55-year-old man presented in 2005 cancers. Diagnosis of MTS also can be established with an indurated, elevated, smooth, dome-shaped if the patient has multiple keratoacanthomas with papule approximately 4 mm on the right supraclavic- multiple visceral malignancies and a family history of ular region. Results of shave excision showed poorly MTS.5 It is a rare autosomal dominant genodermatosis differentiated sebaceous carcinoma. Immunoperoxi- of variable expressivity that is thought to result from dase stains were performed using antibodies directed a mutation in mismatch repair genes and associated against DNA mismatch repair proteins MLH1, MSH2, microsatellite instability. mutS homolog 6 (E coli) MSH6, and postmeiotic seg- Muir-Torre syndrome represents a genetic predis- regation PMS2. Neoplastic cells showed aberrant loss position to visceral neoplasia and the diagnosis can of MSH2 and MSH6 gene expression with retention be suggested based on a cutaneous finding. In some of MLH1 and PMS2 gene expression. The patient cases, the histopathologic findings of a sebaceous had a medical history of moderately differentiated neoplasm may serve as the first clue to the diagnosis. adenocarcinoma of the cecum at 35 years of age. Thus, the pathologist may play an important role in A diagnosis of MTS was made. Since 2005, several the initial diagnosis. sites of actinic keratoses, a moderately differentiated According to Curry et al,6 more than 200 cases squamous cell carcinoma on the left cheek and right of MTS have been described since 1982. We report aspect of the neck, and a malignant melanoma in situ 2 patients with MTS; the pathologist first suggested (superficial spreading type) on the right side of the the diagnosis in both patients. flank were found and removed. In September 2006, the patient presented with Case Reports concerns of worsening epigastric pain and belching. Patient 1—A 52-year-old woman with a history of Endoscopic evaluation demonstrated a large ulcer in colon adenocarcinoma and multiple skin lesions the fundus of stomach. A biopsy specimen of the ulcer presented to the dermatologist in 2006 for a lesion showed poorly differentiated adenocarcinoma. The on the left lower eyelid. The lesion was excised and patient later died from complications of gastric surgery. VOLUME 82, OCTOBER 2008 253 Muir-Torre Syndrome The patient’s family history included uterine and fallopian tube tumors in his mother. Several other Diagnostic Criteria for relatives died from unknown cancers. Muir-Torre Syndrome Comment At least one visceral malignancy plus at least Muir-Torre syndrome is the association of at least one one of the following: sebaceous gland neoplasm and at least one visceral malignancy (Table).3,5,7-10 Colonic polyps and kerato- Sebaceous adenoma 3,4 acanthomas also are frequent findings. We diagnosed Sebaceous carcinoma both our patients with MTS based on their histories of colon adenocarcinomas in conjunction with sebaceous Sebaceoma carcinomas. Genetic testing supported this diagnosis. Keratoacanthoma with sebaceous The most common visceral malignancies associ- differentiation ated with MTS are colorectal, followed by genito- urinary.3,4,7,11-15
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