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Multiple Hereditary Infundibulocystic Basal Cell Carcinomas a Genodermatosis Different from Nevoid Basal Cell Carcinoma Syndrome

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Multiple Hereditary Infundibulocystic Basal Cell Carcinomas a Genodermatosis Different from Nevoid Basal Cell Carcinoma Syndrome OBSERVATION Multiple Hereditary Infundibulocystic Basal Cell Carcinomas A Genodermatosis Different From Nevoid Basal Cell Carcinoma Syndrome Luis Requena, MD; Maria del Carmen Farin˜a, MD; Mercedes Robledo, MD; Omar P. Sangueza, MD; Evaristo Sanchez Yus, MD; Aurora Villanueva, MD; Amparo Marquina, MD; Roser Tamarit, MD Background: Infundibulocystic basal cell carcinoma is 2 was performed using polymorphic markers (D9S196, a recently described distinctive clinicopathologic vari- D9S280, D9S287, and D9S180), and the affected mem- ant of basal cell carcinoma. Histopathologic differential bers shared the same haplotype. Loss of heterozygosity diagnosis among infundibulocystic basal cell carci- analysis was performed in 2 affected members of this fam- noma, trichoepithelioma, and basaloid follicular hamar- ily from whom tumoral DNA was available, and al- toma has generated controversy in the literature. though these individuals were constitutively heterozy- gous for D9S196, they did not show loss of heterozygosity Observations: Members of 2 families with multiple in- for this marker in their neoplasms. fundibulocystic basal cell carcinomas are described. Each patient showed multiple papular lesions, mostly located Conclusions: Multiple hereditary infundibulocystic basal on the face. No patient showed palmar pits or jaw cysts. cell carcinomas represent a distinctive genodermatosis Forty-two cutaneous lesions from 5 patients were stud- different from multiple hereditary trichoepitheliomas and ied histopathologically. Thirty-nine lesions were infun- nevoid basal cell carcinoma syndrome. We propose clini- dibulocystic basal cell carcinomas. This clinicopatho- cal and histopathologic criteria to distinguish infundibu- logic variant of basal cell carcinoma consists of a relatively locystic basal cell carcinoma from trichoepithelioma, ba- well-circumscribed basaloid neoplasm composed of buds saloid follicular hamartoma, and folliculocentric basaloid and cords of neoplastic cells arranged in anastomosing proliferation. fashion and with scant stroma. Some of the neoplastic cords contain tiny infundibular cysts filled by cornified cells with abundant melanin. Linkage analysis in family Arch Dermatol. 1999;135:1227-1235 N 1987, TOZAWA and Ackerman1 We herein describe 2 families in described a new clinicopatho- which several members have multiple in- logic variant of basal cell carci- fundibulocystic basal cell carcinomas. noma that they named basal cell None of the patients had palmar pits or jaw carcinoma with follicular differen- cysts. Furthermore, results of linkage Itiation. Their report generated consider- analysis demonstrated that the affected From the Departments of able controversy in the literature, mainly members shared the same haplotype, but Dermatology (Drs Requena and concerning the difference between this loss of heterozygosity (LOH) for D9S196 Farin˜a) and Genetics basal cell carcinoma with follicular differ- could not be demonstrated in 2 patients (Dr Robledo), Fundacio´n entiation and trichoepithelioma.2-9 Later, from whom tumoral DNA was available. Jime´nez Dı´az, Universidad 10 Auto´noma, and the Department in 1990, Walsh and Ackerman pro- Therefore, a diagnosis of nevoid basal cell of Dermatology, Hospital posed a new name for this variant of basal carcinoma syndrome could be elimi- Clı´nico San Carlos, cell carcinoma, ie, infundibulocystic basal nated. We believe that multiple heredi- Universidad Complutense cell carcinoma, on the basis of the main his- tary infundibulocystic basal cell carcino- (Dr Yus), Madrid, Spain; the topathologic characteristics of the neo- mas represent a distinctive genodermatosis Departments of Dermatology plasm. These authors stated that infun- different from nevoid basal cell carci- and Pathology, Medical College dibulocystic basal cell carcinoma was found noma syndrome. We discuss the histo- of Georgia, Augusta (Dr frequently in patients with nevoid basal cell pathologic differential diagnosis with that Sangueza); and the carcinoma syndrome (Gorlin syn- of lesions that look like infundibulocys- Departments of Pathology (Dr Villanueva) and drome). More recently, debate has ensued tic basal cell carcinoma, namely follicu- Dermatology (Drs Marquina again as to whether this infundibulocys- locentric basaloid proliferation, basaloid and Tamarit), Hospital tic basal cell carcinoma and basaloid fol- follicular hamartoma, and trichoepithe- Universitario Dr Peset, licular hamartoma are the same or differ- lioma. We review the literature about the Valencia, Spain. ent entities.11-13 subject, giving our interpretation for each ARCH DERMATOL / VOL 135, OCT 1999 WWW.ARCHDERMATOL.COM 1227 ©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 Figure 1. Multiple pearly, small papules involving the face, mostly the nasolabial folds. Figure 3. Pearly papules on the anterior aspect of the legs. Figure 2. Papules involving the labia majora of the vulva. Figure 4. A pedunculated lesion with eroded surface on the left shoulder. one of the previously described cases on the basis of the cised from the face and neck, mostly for cosmetic rea- histopathologic illustrations provided in the reports and sons. All lesions showed histopathologic features of in- the histopathologic criteria that we propose herein. fundibulocystic basal cell carcinoma. REPORT OF CASES Patient 2 FAMILY 1 A 45-year-old sister of patient 1 was seen with multiple small papules scattered over the back and the anterior Patient 1 aspect of the legs (Figure 3) that had been present for many years. A larger lesion with pedunculated shape and A 50-year-old woman presented with multiple pearly, eroded surface was present on the left shoulder small papules involving the face (Figure 1), scalp, neck, (Figure 4). There were no facial lesions. The eroded le- chest, and vulva (Figure 2) that had been present for sion on the left shoulder was excised, and it showed his- several years, but had increased in number and size dur- topathologic features of nodular basal cell carcinoma with ing the last few years. During physical examination, more areas of infundibulocystic basal cell carcinoma. Three small than 100 lesions were counted. Clinical diagnosis was papules excised from the back were stereotypical ex- multiple trichoepitheliomas, and 28 lesions were ex- amples of infundibulocystic basal cell carcinoma. ARCH DERMATOL / VOL 135, OCT 1999 WWW.ARCHDERMATOL.COM 1228 ©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 Figure 5. Pearly papules, some of them with annular shapes, on the upper Figure 6. A papular lesion with eroded surface was seen in the left external lip and chin. The scar of the nose tip resulted from a lesion previously auditory canal. excised in another center. lesion from the right nasolabial fold showed histo- Other Family Members pathologic features of infundibulocystic basal cell car- cinoma. In accord with these siblings, a younger sister showed the same facial lesions as patient 1, but this third patient Other Family Members could not be examined by us because she lives in an- other country. The parents of the 3 siblings had died of Patient 1’s father had died of unrelated causes, but ac- unrelated causes, but according to both patients, they had cording to both siblings seen by us, their father had mul- no cutaneous lesions. tiple pearly small papules scattered over the face. Two brothers and 2 sons of patient 1 were examined in our FAMILY 2 department, and they showed no cutaneous lesions. In the 5 patients examined by us, no palmar or plan- Patient 1 tar pits were seen, and results of the radiographic sur- vey demonstrated that jaw cysts or other bone anoma- A 51-year-old woman presented with multiple pearly pap- lies were not present. ules scattered over the face, mostly located on the upper lip, nasolabial folds, and chin (Figure 5). Some of the RESULTS lesions showed an annular shape, with delled centers and raised borders. A papular lesion with identical shape was HISTOPATHOLOGIC CHARACTERISTICS present in the left external auditory canal (Figure 6), OF INFUNDIBULOCYSTIC and another lesion had been excised previously (in an- BASAL CELL CARCINOMAS other center) from the tip of the nose and interpreted as trichoepithelioma. Four lesions from the face and the le- Forty-two specimens from the 5 patients were studied sion from the left external auditory canal were excised histopathologically. Except for a nodular basal cell car- for histopathologic study. One lesion showed features of cinoma in patient 1, family 2, and 2 superficial basal nodular basal cell carcinoma; the other 4 lesions exhib- cell carcinomas in patient 2, family 2, the remaining 39 ited characteristic findings of infundibulocystic basal cell specimens showed essentially the same histopathologic carcinoma. features, ie, relatively well-circumscribed basaloid neo- plasms. Some neoplasms were superficial with no Patient 2 involvement of the deep reticular dermis, whereas in other specimens, neoplastic aggregations of basaloid A 54-year-old sister of patient 1 was seen with multiple cells extended throughout the full thickness of the der- translucent papules on the face and back. The lesions were mis and involved the skeletal muscle to the base of the predominantly located on the upper lip and nasolabial folds. specimen (Figure 7). Neoplastic aggregations con- Two lesions on the back were eroded and covered by crusts. sisted of buds and cords
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