Syndrome of the Month Dermal Eccrine Cylindromatosis

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Med Genet 1994;31:321-324 321 Syndrome of the month J Med Genet: first published as 10.1136/jmg.31.4.321 on 1 April 1994. Downloaded from Dermal eccrine cylindromatosis

I D C van Balkom, R C M Hennekam

In 1842 Ancell' first described an entity char- acterised by a striking clinical picture of multiple disfiguring tumours located on the face and scalp, which rapidly recurred after excision, had a distinctive histology, and showed familial occurrence. Differences of opinion as to the pathogenesis of the lesion and especially the various names used (including epithelioma adenoides cysticum, multiple benign cystic epithelioma, multiple trichoepithelioma, turban tumour, tomato tumour, Spiegler's cylindroma, or dermal cylindroma) have led to considerable confusion. An extensive study by Figure 1 Small dermal eccrine cylindromata around Cotton and Braye2 strongly supported earlier the nose and on the nasal bridge in an adult male. reports3 4 of evidence for an eccrine intradermal origin. Therefore, we have adopted the term "dermal eccrine cylindroma" to include dermal eccrine cylindroma develop chiefly in the origin of the tumours. A rare subtype of the frontal and tempoparietal regions of the dermal eccrine cylindroma is called turban scalp2 (fig 2). The larger dermal eccrine cylin- tumour, a highly descriptive label for the clas- dromata are hairless, firm, and nodular, resis- sical total involvement of the scalp with tent to the touch and mobile on the underlying tumours covering the head and causing gross galea, while being firmly attached to the skin. disfigurement.51'0 They may occur in such numbers as to cover the scalp more or less completely3 6 7 10 11 which http://jmg.bmj.com/ are called turban tumours. Incidence Tumours usually become apparent during The frequency of (multiple) eccrine dermal adolescence and initially grow slowly.6 " As cylindroma is still uncertain, although most they continue to develop and grow during life authors consider it rare. In the Netherlands the disfigurement worsens with progression of reports of two families have been published" 12 the disease.2043 Individual tumours may vary in and two others are known to us; in total they size from a few millimetres to 4 or 5 centi- have 45 affected members. Some studies have metres, the latter size probably representing on September 27, 2021 by guest. Protected copyright. indicated a higher incidence in females.7 13-15 coalescences of smaller lesions.6 16 Internal One study even mentions a female preponder- tumours of the parotid gland35 and lung'9 have ance of 10:1,2 while others have reported equal been reported. sex distribution. Anderson and Howell'6 sug- Crain and Helwig3 reported five patients in gested that this higher incidence in females which injury preceded the development of the may be explained by reduced penetrance in tumour. However, the significance of this find- males. ing is doubtful.' The lesions do not usually Dermal eccrine cylindromata are mostly seem to be associated with pain, although the reported in white races, but may be found in patient reported by Evans6 did complain of other ethnic groups as well.'7 intense irritation at night, Sherman et al'8

Free University Hospital, Amsterdam, Clinical features Locations of dermal eccrine cylindromata described in The Netherlands published reports and in personally known patients, I D C van Balkom The majority of dermal eccrine cylindroma according to frequency (n = 74) arise as small, solitary lesions on the head or Site % Institute of Human neck2 3 18 (fig 1). The mean age of first appear- Genetics and ance of lesions in published and personally Scalp 96 Department of Nasolabial area 70 Pediatrics, Academic known cases was 23.2 years (range 1.5 to 69 Back 43 Medical Centre, years). The locations of the cylindromata are Chest 42 Meibergdreef 15, Forehead 29 1105 AZ Amsterdam, shown according to their frequency in the Eyelids 18 table. Approximately 10 to 15% occur on sites Extremities 15 The Netherlands Chin 11 R C M Hennekam other than the head or neck, such as the trunk Abdomen 9 and extremities.'5 Six percent are reported to External genitalia 9 Correspondence to Ears 6 Dr Hennekam be related to the ear.'9 The giant forms of 322 van Balkom, Hennekam

reported pain in a patient during rapid growth, and Blandy et all reported stinging in the lesions. J Med Genet: first published as 10.1136/jmg.31.4.321 on 1 April 1994. Downloaded from

Complications Deafness may occur owing either to tumours in the external ear or to occlusion of the auditory canal14 18 21 22 (fig 3). Growth of the tumours may be so extensive as to cover both eyes and ears necessitating a total resection of tumour bearing skin.6892' Iftumours reach this size, the risk of infection increases because the patients have difficulty in keeping their head v clean.' In late presentations ulceration and macera- tion of the tumour or tumours may occur, leading to unpleasant fetor and anae- p,amia.212224r + 0>EpisodesI!tE1_g of depression related to the disfigurement caused by the tumours have been reported in three instances.102024 Multiple _,_3 ^eccrine cylindromata are known to be associated with both trichoepitheliomata and milia,'9383942 pointing to a common histogene- &1 _l .,sis(see Histopathology). Possibly this is a separate entity. Malignant transformation of multiple or solitary dermal eccrine cylindroma is con- sidered to be rare. One report described der- Figure 2 Large dermal eccrine cylindromata on the mal cylindromata of the parotid glands in a scalp of an affectedfemale. patient without malignant degeneration during 18 years of follow up.25 However, Lin et aP6 and Tsamboas et aP7 reported histological changes, consisting of loss of hyaline sheath and atypical mitotic figures, indicative of possible malignant transformation. Lin et aP6 also reported a greater tendency towards malignant transformation in multiple dermal eccrine http://jmg.bmj.com/ cylindromata compared to solitary lesions, but no well documented evidence to support this view was given. Crain and Helwig3 stated that dermal eccrine cylindromata seldom undergo malignant transformation: Urbanski et a14I encountered 11 cases with a malignancy. Crain

and Helwig' caution that in the case described on September 27, 2021 by guest. Protected copyright. by Lugeri8 the picture could have been com- plicated by repeated and massive radiation therapy over a period of years before the malignant transformation occurred. Bourland et aP9 described the transformation to a baso- cellular epithelioma of a previously diagnosed solitary cylindroma in a 90 year old male. Blandy et all suggested that until long term results are known and documented it would be wise to consider the lesions to be potentially malignant.

Differential diagnosis Dermal eccrine cylindroma should be differ- entiated from malignant syndromes such as basal naevoid cell carcinoma or metastases from a distant primary tumour, to which a close resemblance may exist.5 16 Sometimes dermal eccrine cylindromata are confused with neurofibromata, even necessitating a biopsy for reliable differentiation.'0 Cylindromata Figure 3 Nearly complete occlusion of the auditory may also occur as solitary, non-hereditary canal by coalescing dermal eccrine cylindromata. lesions."' Dermal eccrine cyclindromatosis 323

Histopathology some anomaly. A remarkable finding has been The origin of dermal eccrine cylindromata has that dermal eccrine cylindromata overex- long been controversial. Fusaro and Goltz32 pressed type VII collagen, which is the major

and Hashimoto and Lever33 favoured an apo- structural protein of the anchoring fibrils.0 J Med Genet: first published as 10.1136/jmg.31.4.321 on 1 April 1994. Downloaded from crine differentiation because their electron However, it is uncertain whether this has any microscopic findings showed two types of pathogenetic relevance. granules similar to the secretory cells of apo- As mentioned before, a preponderance of crine glands. In addition, these authors felt affected females has been reported.2 Anderson that this view was supported by the common and Howell,'6 however, reported in their ex- association of trichoepithelioma and dermal tensive analysis of 19 previously published eccrine cylindroma, both originating from pedigrees and one newly ascertained pedigree cells of the primary epithelial germ, and by the (in total 175 cases) that there was no indication fact that no dermal cylindroma has been of an excess of affected females, but, rather, a reported on the palm or sole where tumours of marked deficit of affected males. They found a eccrine origin would be expected. high penetrance level when the males belonged However, studies by Crain and Helwig,3 to the proband's sibship, a small sibship, or Munger et al,4 and especially Cotton and had early birth order but found a reduced Braye2 supplied evidence that the dermal disease frequency in males when sibship or cylindroma is derived from the eccrine sweat pedigree size was large, birth order late, or gland. Cotton and Braye2 studied 10 examples when the males belonged to a sibship not ofcylindromata taken from their routine histo- containing the proband. Furthermore, they pathology files, using histological, ultrastruc- found no evidence ofreduced viability in males tural, and immunocytochemical techniques. or of sex linkage, suggesting that the dif- The eccrine origin of the cylindromata was ferences in affected rates between males and supported mainly by their derivation from the females can be best explained by a combination coiled segment of intradermal eccrine ducts.2 of a different penetrance and detection rate. Further evidence has been provided by the Less overt expression and diminished pene- coexistence of cylindromata and eccrine spir- trance in males may imply that generally the adenomata in the same patients20 23 24 34 35 45 and disorder is more variable and less expressed in the coexistence of dermal eccrine cylindromata males compared to females, resulting in fewer and multiple trichoepitheliomata of the face and smaller tumours, later development of (rarely in the same clinical lesion), suggesting a multiple tumours, or location of tumours in common histogenesis from a pluripotent stem unobtrusive areas. Anderson and Howell'6 cell.420 23 36 Recently, it was shown that both concluded that endocrine influences could be a dermal eccrine cylindromata and trichoepithe- factor in the different expression in both sexes. liomata stained positively with type IV and 1 Ancell H. History of a remarkable case of tumours, de- type VII collagen antibodies, which consti- veloped on the head and face, accompanied with a similar tutes further evidence of a common disease in the abdomen. Med Chir Trans R Med Chir Soc

origin.37 http://jmg.bmj.com/ Lond 1842;25:227-46. The primary histological features of cylin- 2 Cotton DWK, Braye SG. Dermal, cylindromas originate dromata are cystic and duct-like structures from the eccrine sweat gland. BrJ Dermatol 1984;1 11:53- 61. with cords of basophilic cells and a prominent 3 Crain RC, Helwig EB. Dermal cylindroma (dermal eccrine acidophilic hyaline basement membrane. Mi- cylindroma). Am J Clin Pathol 1961;35:504-15. 4 Munger BL, Graham JH, Helwig EB. Ultrastructure and croscopic examination shows multiple foci of histochemical characteristics of dermal eccrine cylin- closely clustered epithelial cells with uniform droma (turban tumor). J Invest Dermatol 1962;39:577-95. 5 Blandy JP, Gammie WFP, Stovin PGI, Swettenham K. size and shape and a pallisading arrangement Turban in J tumours brother and sister. Br Surg on September 27, 2021 by guest. Protected copyright. within nodules surrounded by a hyaline wall.'3 1961;49:136-40. 6 Evans CD. Turban tumour. BrJ Dermatol 1954;66:434-43. The oval to round islands of basophilic cells 7 Freedman AM, Woods JE. Total scalp excision and auricu- may have the appearance of an assembled lar resurfacing for dermal cylindroma (turban tumor). Ann Plast Surg 1989;22:50-7. jigsaw puzzle 2 7 12 26 34 The cystic spaces in 8 Gabarro P, Baker SL. An enormous epithelioma adenoides almost all cases are lined by squamous, cuboi- cysticum of the scalp with a pathological report. BrJ Surg 1945;33:188-90. dal, or columnar epithelium and in some in- 9 Goldman B. Total excision of the scalp and portions of the stances resemble sweat ducts.34 3 Small units face; restoration by skin grafting: the surgical manage- ment of massive cylindroma of the scalp and face. Ann of tumour are invariably present at the margins Surg 1951;133:555-60. and may account for the high recurrence rate 10 Harper PS. Turban tumors (cylindromatosis). Birth Defects 1977;VII(8):338-41. after excision. 11 Rogge CWL, Oeseburg HB, van Andel P. Turban tumors and tricho-epitheliomata in a Groningen family. Chir Plast 1975;3:75-83. 12 Spauwen PHM, Molenaar WM, Dhar BK. Cylindroma of Genetics the scalp. Neth J Surg 1987;39:101-3. 13 Given K, Pickrell K, Smith D. Dermal cylindroma (turban A decimal eccrine cylindroma may occur tumor). Plast Reconstr Surg 1977;59:582-7. either in a solitary or a multiple form. The 14 Irwin LR, Bainbridge LC, Reid CA, Piggot TA, Brown HG. Dermal eccrine cylindroma (turban tumor). Br J more frequent solitary form is a sporadic Plast Surg 1990;43:702-5. event,3 but multiple dermal eccrine cylindro- 15 Schuermann H, Weber K. Beitrag zur Kenntnis der Spieg- lerschen Tumoren (Cylindroma) nebst einigen Bemer- mata are inherited as an autosomal dominant kungen zum Epithelioma adenoides cysticum. Arch Der- trait with incomplete penetrance which has matol Syph 1937;175:682-95. 16 Anderson DE, Howell JB. Epithelioma adenoides cysticum: been estimated to be 60% to 75%.1439 Welch et genetic update. Br J Dermatol 1976;95:225-32. al'9 reported a higher percentage approaching 17 Sachs W, Sachs PM. Turban tumors. Report of a case with unusual pathologic findings, including both epidermal 100% in a family with both cylindromata and and dermal nevi. Arch Dermatol Syph 1940;42:15-22. trichoepitheliomata. There is no clue what- 18 Sherman JE, Hoffman S, Goulian D. Dermal cylindroma: surgical approach. Plast Reconstr Surg 1981;68:596-602. soever available about a chromosomal location 19 Welch JP, Wells RS, Kerr CB. Ancell-Spiegler cylindromas as no patient has been reported with a chromo- (turban tumours) and Brooke-Fordyce trichoepithelio- 324 van Balkom, Hennekam

mas: evidence for a single genetic entity. J Med Genet 34 Goette DK, McConnell MA, Fowler VR. Cylindroma and 1968;5:29-35. eccrine spiradenoma coexistent in the same lesion. Arch 20 Berberian BJ, Sulica VI, Kao GF. Familial multiple eccrine Dermatol 1982;118:273-4. spiradenomas with cylindromatous features associated 35 Headington JT, Batsakis JG, Beals TF, Campbell TE, with epithelioma adenoides cysticum of Brooke. Cutis Simmons JL, Stone WD. Membranous basal cell aden-

1990;46:46-50. oma of parotid gland, dermal cylindromas, and tricho- J Med Genet: first published as 10.1136/jmg.31.4.321 on 1 April 1994. Downloaded from 21 Pfaltz M, Schnyder UW. A case of familial cylindromas and epitheliomas. Comparative histochemistry and ultrastruc- trichoepitheliomas. Dermatologica 1989;179:106-9. ture. Cancer 1977;39:2460-9. 22 Vernon HJ, Olsen EA, Vollmer RT. Autosomal dominant 36 Dupre A, Bonafe JL, Lassere J. Hamartome epithelial multiple cylindromas associated with solitary lung cylin- sclerosant: forme clinique du tricho-epitheliome. A pro- droma. J Am Acad Dermatol 1988;19:397-400. pos de 3 cas. Ann Dermatol Venereol (Paris) 1980; 23 Gottschalk HR, Graham JH, Aston EE. Dermal eccrine 107:649-54. cylindroma, epithelioma adenoides cysticum of Brooke, 37 Pfaltz M, Bruckner-Tuderman L, Schnyder UW. Type and eccrine spiradenoma. Arch Dermatol 1974;110:473-9. VII collagen is a component of cylindroma basement 24 Regan WJ, Hunt A. Turban tumours. Proc R Soc Med membrane zone. J Cutan Pathol 1989;16:388-95. 1956;49:337-9. 38 Rasmussen JE. A syndrome of trichoepitheliomas, milia 25 Reingold IM, Keasbey LE, Graham JH. Multicentric der- and cylindromas. Arch Dermatol 1975;111:610-4. mal-type cylindromas of the parotid glands in a patient 39 Guggenheim W, Schnyder UW. Zur Nosologie der with florid turban tumors. Cancer 1977;40:1702-10. Spiegler-Brook'schen Tumoren. Dermatologica 1961;122: 26 Lin PY, Fatteh SM, Lloyd KM. Malignant transformation 274-8. in a solitary dermal cylindroma. Arch Pathol Lab Med 40 Bruckner-Tuderman L, Pfaltz M, Schnyder UW. Cylin- 1987;1 1 1:765-7. droma overexpresses collagen VII, the major anchoring 27 Tsamboas D, Greither A, Orfanos, CE. Multiple malignant fibril protein. J Invest Dermatol 1991;96:729-34. Spiegler tumors with brachydactyly and racket-nails. 41 Urbanski SJ, From L, Abramowicz A. Metamorphosis of Light and electron microscopic study. J Cutan Pathol dermal cylindroma: possible relation to malignant trans- 1979;6:31-41. J 28 Luger A. Das cylindrom der Haut und seine maligne formation. Am Acad Dermatol 1985;12: 188-95. Degeneration. Arch Dermatol Syph 1949;188:155-80. 42 Guillot B, Buffiere I, Barneon G, Bensadoun D, Guilhou JJ, 29 Bourlond A, Clerens A, Sigart H. Cylindrome Malin. Meynadier J. Tricho-epitheliomes multiples cylin- Dermatologica 1979;158:203-7. dromes, grains de milium. Une entite. Ann Dermatol 30 Baden HP. Cylindromatosis simulating neurofibromatosis. Venereol 1987;114:175-82. N Engl J Med 1962;267:296-7. 43 Rubin MG, Mitchell AJ. Generalized cutaneous cylindro- 31 Nerad JA, Folberg R. Multiple cylindromas. The "turban matosis. Cutis 1984;33:568-9. tumor". Arch Ophthalmol 1987;105:1137. 44 Wolf BA, Gluckman JL, Wirman JA. Benign dermal cylin- 32 Fusaro RM, Goltz RW. Histochemically demonstrable car- droma of the external auditory canal: a clinicopathological bohydrates of appendageal tumors of the skin. II. Benign report. Am J Otolaryngol 1985;6:35-8. apocrine gland tumors. J Invest Dermatol 1962;38:137-42. 45 Wright S, Ryan J. Multiple familial eccrine spiradenoma 33 Hashimoto K, Lever WL. Histogenesis of skin appendage with cylindroma. Acta Derm Venereol (Stockh) 1990; tumors. Arch Dermatol 1969;100:356-69. 70:79-82. http://jmg.bmj.com/ on September 27, 2021 by guest. Protected copyright.