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Sebaceous Adenoma of the Eyelid in Muir-Torre Syndrome

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Sebaceous Adenoma of the Eyelid in Muir-Torre Syndrome CLINICOPATHOLOGIC REPORTS, CASE REPORTS, AND SMALL CASE SERIES SECTION EDITOR: W. RICHARD GREEN, MD Recent investigations into the mo- of local tumor recurrence or metas- Sebaceous Adenoma lecular genetics of Muir-Torre tasis. There was no family history of of the Eyelid syndrome have revealed genomic any ocular disease or malignancy. in Muir-Torre Syndrome replication errors, known as micro- On examination, the patient’s cor- satellite instabilities, due to muta- rected visual acuity was 20/20 OU. tions in the mismatch repair genes, External examination revealed an Muir-Torre syndrome is a rare can- hMSH2 and hMLH1.6 In this report, 8ϫ5ϫ4-mm, yellowish-pink, warty cer predisposition syndrome char- we present the clinical and histo- growth of the left upper eyelid close acterized by unusual cutaneous tu- logic features of a patient with Muir- to the margin (Figure 1A). The sur- mors and internal malignancy.1,2 The Torre syndrome who had multiple face of the lesion had fine papillary cutaneous tumors associated with facial lesions, some of which in- projections without vascularity, Muir-Torre syndrome include volved the eyelid, in association with crusting, or ulceration, and no sur- mainly sebaceous gland neoplasms an internal malignancy. rounding induration was present. (sebaceous adenoma and seba- Numerous yellow-white, slightly ceous carcinoma), keratoacan- Report of a Case. A 59-year-old man raised lesions that ranged in size thoma, and basal cell carcinoma.1-3 sought care in July 2003 for a pro- from 3 to 10 mm were distributed Colorectal and genitourinary carci- gressively enlarging exophytic le- on the face in the central forehead noma are the common types of in- sion that involved the left upper eye- region, nose, and adjacent cheek area ternal malignancies that occur in lid for the last 6 months. He had a (Figure 1B). Each lesion appeared to Muir-Torre syndrome.3 Although history of biopsy-proven basal cell be a conglomeration of many smaller Muir-Torre syndrome is character- carcinoma of the right temple re- nodular lesions. The results of an- ized by autosomal dominant inher- gion, which had been treated with terior segment examination and fun- itance, sporadic cases are known external beam radiotherapy in 1996. dus evaluation of both eyes were un- to occur. Significant variation can He had also been treated for biopsy- remarkable. The eyelid lesion and occur in the phenotypic manifesta- proven advanced rectal adenocarci- one of the facial lesions were ex- tions of Muir-Torre syndrome, noma with preoperative combined cised and submitted for histopatho- and in some cases Muir-Torre syn- chemoradiotherapy followed by an logic evaluation. drome may resemble hereditary non- abdominoperineal resection and sig- Macroscopically, the eyelid lesion polyposis colorectal carcinoma.4,5 moid colostomy in 1996. He was free was composed of a 10ϫ8ϫ5-mm A B Figure 1. Sebaceous adenomas on the face in a patient with Muir-Torre syndrome. A, External appearance of the left eye. Note a yellowish-pink warty growth arising from the anterior lamella of the left upper eyelid. B, Multiple yellow nodular lesions involving the central forehead, nose, and adjacent cheek area (arrow). (REPRINTED) ARCH OPHTHALMOL / VOL 123, APR 2005 WWW.ARCHOPHTHALMOL.COM 562 ©2005 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/02/2021 A B C D E F Figure 2. Histopathologic features of Muir-Torre syndrome. A, Eyelid (upper panel) and face (lower panel) sebaceous adenomas (original magnification ϫ10). B, Higher-power images of the eyelid (upper panel) and face (lower panel) sebaceous adenomas, demonstrating the mitotically active, cytologically atypical basaloid germinative cells layer (arrows) with adjacent mature vacuolated sebocytes (arrowheads) (original magnification ϫ100). C, Rectal adenocarcinoma. Note the malignant glandular profiles with a surrounding desmoplastic response (original magnification ϫ50). D, Sebaceous adenoma stained immunohistochemically with an antibody to the MLH1 protein. Note the presence of brown nuclear staining (original magnification ϫ50). E, Sebaceous adenoma stained immunohistochemically with an antibody to the MSH2 protein. Note the absence of nuclear staining (original magnification ϫ50). F, Normal sebaceous lobules adjacent to the sebaceous adenoma stained immunohistochemically with an antibody to the MSH2 protein. Note the presence of brown nuclear staining (original magnification ϫ50). pentagonal piece of skin, with a 5ϫ4- maturing to vacuolated sebocytes sence of aberrant mitotic figures, and mm, firm, yellow exophytic nodule. centrally, with transitional forms necrosis of both lesions supported The facial lesion was composed of a seen (Figure 2B). The mature, cen- the diagnosis of benign sebaceous 10ϫ6ϫ3-mm elliptical-shaped piece tral sebocytes comprised most of the adenomas. of skin with a 6ϫ4ϫ3-mm, central lesional tissue. Variable eosino- The rectal biopsy results from yellow nodule. philic holocrine degeneration was 1996 were reviewed, and a diagno- Microscopy of the eyelid lesion seen. No convincing cystic change sis of primary adenocarcinoma demonstrated an exophytic neo- was identified. There was no evi- was confirmed (Figure 2C). The se- plasm situated principally within the dence of an infiltrative growth pat- baceous adenoma and rectal cutaneous compartment that was tern, pagetoid lesions, mitotic fig- adenocarcinoma underwent immu- composed of multiple, irregularly ures, or lymphovascular space nohistochemical analysis with anti- shaped, closely packed, circum- invasion. The eyelid tissue adja- bodies directed at MLH1 (PharM- scribed sebaceous lobules, sepa- cent to the lesion exhibited patchy, ingen, Oxford, England) and MSH2 rated by compressed, dermal con- focal lipogranulomatous inflamma- (Cambridge Bioscience Ltd, Cam- nective tissue septa (Figure 2A). tion, constituting secondary chala- bridge, England) proteins, using a The lobules communicated with the zion formation. The cheek lesion conventional diaminobenzidine epidermal surface via several open- demonstrated histologic features detection method, with a brown ings. Each lobule was composed of identical to those described herein chromogen. The sebaceous ad- a peripheral, mitotically active ba- (Figure 2A and 2B). The circum- enoma (Figure 2D) exhibited saloid germinative layer, which ex- scription, mature sebaceous pheno- consistent nuclear positivity for hibited moderate cytologic atypia type, lack of infiltrative borders, ab- MLH1 but was negative for MSH2 (REPRINTED) ARCH OPHTHALMOL / VOL 123, APR 2005 WWW.ARCHOPHTHALMOL.COM 563 ©2005 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/02/2021 Table. Various Eyelid and Adnexal Tumors That Are Markers of Benign and Malignant Visceral Tumors Entity Eyelid or Adnexal Tumors Visceral Tumors Associated Abnormalities Locus and Gene Neurofibromatosis type 17 Neurofibroma Pheochromocytoma Café au lait spots, Lisch 17q, nodules NF1 gene Gardner syndrome8 Epidermoid cyst, fibroma, Colorectal polyps or Congenital hypertrophy of 5q21, orbital osteoma carcinoma retinal pigment epithelium APC gene Gorlin syndrome9 Basal cell carcinoma Ovarian fibroma or Odontogenic cysts, bifid ribs, 9q22, fibrosarcoma palmar pits PTC gene Cowden syndrome10 Tricholemmoma Breast fibroadenoma, Thyroid adenoma or 10q23, adenocarcinoma adenocarcinoma, PTEN gene oral papilloma Carney complex11 Myxoma Testicular tumor Spotty mucocutaneous 17q, pigmentation, schwannoma, PRKAR1A gene, endocrine overactivity chromosome 2 MEN 2B12 Conjunctival neuroma Mucocutaneous neuroma, Thyroid carcinoma, 10q11.2, thickened corneal nerves pheochromocytoma RET protooncogene Muir-Torre syndrome Sebaceous adenoma, Colororectal 2p, sebaceous adenocarcinoma, adenocarcinoma, hMLH1, keratoacanthoma, basal cell genitourinary, malignancy hMSH2 carcinoma Abbreviation: MEN, multiple endocrine neoplasia. (Figure 2E). As an internal control, around a single central dilated duct, individuals is not associated with the normal background sebaceous which is often filled with debris. Se- Muir-Torre syndrome. Although se- lobules showed positive nuclear baceous adenoma shows irregu- baceous gland carcinoma of the eye- staining for both MLH1 and MSH2 larly shaped, closely packed seba- lid and extraocular sites17 has been proteins (Figure 2F). ceous glands that communicate with reported in patients with Muir- 1 or more dilated infundibula or di- Torre syndrome, such patients also Comment. Various eyelid and rectly to the surface. There are more had sebaceous adenomas.18 Seba- adnexal tumors are known to be basaloid germinative cells than nor- ceous gland carcinoma of the eye- markers of benign and malignant mal sebaceous glands, together with lid by itself is not suggestive of Muir- visceral tumors. Some of the well- transitional forms, but there still Torre syndrome.19,20 Similarly, recognized entities include neuro- tends to be a majority of mature keratoacanthoma and basal cell car- fibromatosis type 1,7 Gardner syn- vacuolated sebocytes, as described cinoma without sebaceous ad- drome,8 Gorlin syndrome,9 Cowden in the lesions in this case report. Se- enoma are not diagnostic of Muir- syndrome,10 Carney complex,11 mul- baceous carcinoma is usually asym- Torre syndrome. tiple endocrine neoplasia type 2B,12 metric, infiltrative, and composed of In a review of 120 patients with and Muir-Torre syndrome (Table).3 lobules, nests, and sheets of princi- Muir-Torre syndrome,
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