Med Genet 1994;31:321-324

Syndrome of the month

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 multi-ple disfiguring tumours located on the face andscalp, which rapidly recurred after excision,had a distinctive histology, and showed fami-lial occurrence. Differences of opinion as to thepathogenesis of the lesion and especially thevarious names used (including epitheliomaadenoides cysticum, multiple benign cysticepithelioma, multiple trichoepithelioma, tur-ban tumour, tomato tumour, Spiegler's cylin-droma, or dermal cylindroma) have led toconsiderable confusion. An extensive study byCotton and Braye2 strongly supported earlierreports3 4 of evidence for an eccrine intrader-mal origin. Therefore, we have adopted theterm "dermal eccrine cylindroma" to includethe origin of the tumours. A rare subtype ofdermal eccrine cylindroma is called turbantumour, a highly descriptive label for the clas-sical total involvement of the scalp withtumours covering the head and causing grossdisfigurement.51'0

IncidenceThe frequency of (multiple) eccrine dermalcylindroma is still uncertain, although mostauthors consider it rare. In the Netherlandsreports of two families have been published" 12and two others are known to us; in total theyhave 45 affected members. Some studies haveindicated a higher incidence in females.7 13-15One study even mentions a female preponder-ance of 10:1,2 while others have reported equalsex distribution. Anderson and Howell'6 sug-

gested that this higher incidence in femalesmay be explained by reduced penetrance inmales.Dermal eccrine cylindromata are mostly

reported in white races, but may be found inother ethnic groups as well.'7

Figure 1 Small dermal eccrine cylindromata around

the nose and on the nasal bridge in an adult male.

dermal eccrine cylindroma develop chiefly inthe frontal and tempoparietal regions of thescalp2 (fig 2). The larger dermal eccrine cylin-dromata are hairless, firm, and nodular, resis-tent to the touch and mobile on the underlyinggalea, while being firmly attached to the skin.They may occur in such numbers as to cover

the scalp more or less completely3 6 7 10 11 whichare called turban tumours.Tumours usually become apparent during

adolescence and initially grow slowly.6 " Asthey continue to develop and grow during lifethe disfigurement worsens with progression ofthe disease.2043 Individual tumours may vary insize from a few millimetres to 4 or 5 centi-metres, the latter size probably representingcoalescences of smaller lesions.6 16 Internaltumours of the parotid gland35 and lung'9 havebeen reported.

Crain and Helwig3 reported five patients inwhich injury preceded the development of thetumour. However, the significance of this find-ing is doubtful.' The lesions do not usuallyseem to be associated with pain, although thepatient reported by Evans6 did complain ofintense irritation at night, Sherman et al'8

Free UniversityHospital, Amsterdam,The NetherlandsI D C van Balkom

Institute of HumanGenetics andDepartment ofPediatrics, AcademicMedical Centre,Meibergdreef 15,1105 AZ Amsterdam,The NetherlandsR C M Hennekam

Correspondence toDr Hennekam

Clinical featuresThe majority of dermal eccrine cylindromaarise as small, solitary lesions on the head orneck2 3 18 (fig 1). The mean age of first appear-ance of lesions in published and personallyknown cases was 23.2 years (range 1.5 to 69years). The locations of the cylindromata areshown according to their frequency in thetable. Approximately 10 to 15% occur on sitesother than the head or neck, such as the trunkand extremities.'5 Six percent are reported tobe related to the ear.'9 The giant forms of

Locations of dermal eccrine cylindromata described inpublished reports and in personally known patients,according to frequency (n = 74)

Site %

Scalp 96Nasolabial area 70Back 43Chest 42Forehead 29Eyelids 18Extremities 15Chin 11Abdomen 9External genitalia 9Ears 6

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reported pain in a patient during rapid growth,and Blandy et all reported stinging in thelesions.

ComplicationsDeafness may occur owing either to tumoursin the external ear or to occlusion of theauditory canal14 18 21 22 (fig 3). Growth of thetumours may be so extensive as to cover botheyes and ears necessitating a total resection oftumour bearing skin.6892' If tumours reach thissize, the risk of infection increases because thepatients 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,a r + 0> I! t E1 _gmia.212224 Episodes of depression related tothe disfigurement caused by the tumours havebeen reported in three instances.102024 Multiple

_,_3^eccrine cylindromata are known to beassociated with both trichoepitheliomata andmilia,'9383942 pointing to a common histogene-

&1 _l .,sis(see Histopathology). Possibly this is aseparate entity.

Malignant transformation of multiple orsolitary 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 ascalp of an affected female. patient without malignant degeneration during

18 years of follow up.25 However, Lin et aP6and Tsamboas et aP7 reported histologicalchanges, consisting of loss of hyaline sheathand atypical mitotic figures, indicative of pos-sible malignant transformation. Lin et aP6 alsoreported a greater tendency towards malignanttransformation in multiple dermal eccrinecylindromata compared to solitary lesions, butno well documented evidence to support thisview was given. Crain and Helwig3 stated thatdermal eccrine cylindromata seldom undergomalignant transformation: Urbanski et a14Iencountered 11 cases with a malignancy. Crainand Helwig' caution that in the case describedby Lugeri8 the picture could have been com-plicated by repeated and massive radiationtherapy over a period of years before themalignant transformation occurred. Bourlandet aP9 described the transformation to a baso-cellular epithelioma of a previously diagnosedsolitary cylindroma in a 90 year old male.Blandy et all suggested that until long termresults are known and documented it would bewise to consider the lesions to be potentiallymalignant.

Differential diagnosisDermal eccrine cylindroma should be differ-entiated from malignant syndromes such asbasal naevoid cell carcinoma or metastasesfrom a distant primary tumour, to which aclose resemblance may exist.5 16 Sometimesdermal eccrine cylindromata are confused withneurofibromata, even necessitating a biopsyfor reliable differentiation.'0 Cylindromata

Figure 3 Nearly complete occlusion of the auditory may also occur as solitary, non-hereditarycanal by coalescing dermal eccrine cylindromata. lesions."'

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Dermal eccrine cyclindromatosis

HistopathologyThe origin of dermal eccrine cylindromata haslong been controversial. Fusaro and Goltz32and Hashimoto and Lever33 favoured an apo-crine differentiation because their electronmicroscopic findings showed two types ofgranules similar to the secretory cells of apo-crine glands. In addition, these authors feltthat this view was supported by the commonassociation of trichoepithelioma and dermaleccrine cylindroma, both originating fromcells of the primary epithelial germ, and by thefact that no dermal cylindroma has beenreported on the palm or sole where tumours ofeccrine origin would be expected.However, studies by Crain and Helwig,3

Munger et al,4 and especially Cotton andBraye2 supplied evidence that the dermalcylindroma is derived from the eccrine sweatgland. Cotton and Braye2 studied 10 examplesof cylindromata taken from their routine histo-pathology files, using histological, ultrastruc-tural, and immunocytochemical techniques.The eccrine origin of the cylindromata wassupported mainly by their derivation from thecoiled segment of intradermal eccrine ducts.2Further evidence has been provided by thecoexistence of cylindromata and eccrine spir-adenomata in the same patients20 23 24 34 35 45 andthe coexistence of dermal eccrine cylindromataand multiple trichoepitheliomata of the face(rarely in the same clinical lesion), suggesting acommon histogenesis from a pluripotent stemcell.420 23 36 Recently, it was shown that bothdermal eccrine cylindromata and trichoepithe-liomata stained positively with type IV andtype VII collagen antibodies, which consti-tutes further evidence of a common origin.37The primary histological features of cylin-

dromata are cystic and duct-like structureswith cords of basophilic cells and a prominentacidophilic hyaline basement membrane. Mi-croscopic examination shows multiple foci ofclosely clustered epithelial cells with uniformsize and shape and a pallisading arrangementwithin nodules surrounded by a hyaline wall.'3The oval to round islands of basophilic cellsmay have the appearance of an assembledjigsaw puzzle 2 7 12 26 34 The cystic spaces inalmost all cases are lined by squamous, cuboi-dal, or columnar epithelium and in some in-stances resemble sweat ducts.34 3 Small unitsoftumour are invariably present at the marginsand may account for the high recurrence rateafter excision.

GeneticsA decimal eccrine cylindroma may occureither in a solitary or a multiple form. Themore frequent solitary form is a sporadicevent,3 but multiple dermal eccrine cylindro-mata are inherited as an autosomal dominanttrait with incomplete penetrance which hasbeen estimated to be 60% to 75%.1439 Welch etal'9 reported a higher percentage approaching100% in a family with both cylindromata andtrichoepitheliomata. There is no clue what-soever available about a chromosomal locationas no patient has been reported with a chromo-

some anomaly. A remarkable finding has beenthat dermal eccrine cylindromata overex-pressed type VII collagen, which is the majorstructural protein of the anchoring fibrils.0However, it is uncertain whether this has anypathogenetic relevance.As mentioned before, a preponderance of

affected females has been reported.2 Andersonand Howell,'6 however, reported in their ex-tensive analysis of 19 previously publishedpedigrees and one newly ascertained pedigree(in total 175 cases) that there was no indicationof an excess of affected females, but, rather, amarked deficit of affected males. They found ahigh penetrance level when the males belongedto the proband's sibship, a small sibship, orhad early birth order but found a reduceddisease frequency in males when sibship orpedigree size was large, birth order late, orwhen the males belonged to a sibship notcontaining the proband. Furthermore, theyfound no evidence of reduced viability in malesor of sex linkage, suggesting that the dif-ferences in affected rates between males andfemales can be best explained by a combinationof a different penetrance and detection rate.Less overt expression and diminished pene-trance in males may imply that generally thedisorder is more variable and less expressed inmales compared to females, resulting in fewerand smaller tumours, later development ofmultiple tumours, or location of tumours inunobtrusive areas. Anderson and Howell'6concluded that endocrine influences could be afactor in the different expression in both sexes.

1 Ancell H. History of a remarkable case of tumours, de-veloped on the head and face, accompanied with a similardisease in the abdomen. Med Chir Trans R Med Chir SocLond 1842;25:227-46.

2 Cotton DWK, Braye SG. Dermal, cylindromas originatefrom the eccrine sweat gland. BrJ Dermatol 1984;1 11:53-61.

3 Crain RC, Helwig EB. Dermal cylindroma (dermal eccrinecylindroma). Am J Clin Pathol 1961;35:504-15.

4 Munger BL, Graham JH, Helwig EB. Ultrastructure andhistochemical characteristics of dermal eccrine cylin-droma (turban tumor). J Invest Dermatol 1962;39:577-95.

5 Blandy JP, Gammie WFP, Stovin PGI, Swettenham K.Turban tumours in brother and sister. Br J Surg1961;49:136-40.

6 Evans CD. Turban tumour. BrJ Dermatol 1954;66:434-43.7 Freedman AM, Woods JE. Total scalp excision and auricu-

lar resurfacing for dermal cylindroma (turban tumor).Ann Plast Surg 1989;22:50-7.

8 Gabarro P, Baker SL. An enormous epithelioma adenoidescysticum of the scalp with a pathological report. BrJ Surg1945;33:188-90.

9 Goldman B. Total excision of the scalp and portions of theface; restoration by skin grafting: the surgical manage-ment of massive cylindroma of the scalp and face. AnnSurg 1951;133:555-60.

10 Harper PS. Turban tumors (cylindromatosis). Birth Defects1977;VII(8):338-41.

11 Rogge CWL, Oeseburg HB, van Andel P. Turban tumorsand tricho-epitheliomata in a Groningen family. ChirPlast 1975;3:75-83.

12 Spauwen PHM, Molenaar WM, Dhar BK. Cylindroma ofthe scalp. Neth J Surg 1987;39:101-3.

13 Given K, Pickrell K, Smith D. Dermal cylindroma (turbantumor). Plast Reconstr Surg 1977;59:582-7.

14 Irwin LR, Bainbridge LC, Reid CA, Piggot TA, BrownHG. Dermal eccrine cylindroma (turban tumor). Br JPlast Surg 1990;43:702-5.

15 Schuermann H, Weber K. Beitrag zur Kenntnis der Spieg-lerschen Tumoren (Cylindroma) nebst einigen Bemer-kungen zum Epithelioma adenoides cysticum. Arch Der-matol Syph 1937;175:682-95.

16 Anderson DE, Howell JB. Epithelioma adenoides cysticum:genetic update. Br J Dermatol 1976;95:225-32.

17 Sachs W, Sachs PM. Turban tumors. Report of a case withunusual pathologic findings, including both epidermaland dermal nevi. Arch Dermatol Syph 1940;42:15-22.

18 Sherman JE, Hoffman S, Goulian D. Dermal cylindroma:surgical approach. Plast Reconstr Surg 1981;68:596-602.

19 Welch JP, Wells RS, Kerr CB. Ancell-Spiegler cylindromas(turban tumours) and Brooke-Fordyce trichoepithelio-

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mas: evidence for a single genetic entity. J Med Genet1968;5:29-35.

20 Berberian BJ, Sulica VI, Kao GF. Familial multiple eccrinespiradenomas with cylindromatous features associatedwith epithelioma adenoides cysticum of Brooke. Cutis1990;46:46-50.

21 Pfaltz M, Schnyder UW. A case of familial cylindromas andtrichoepitheliomas. Dermatologica 1989;179:106-9.

22 Vernon HJ, Olsen EA, Vollmer RT. Autosomal dominantmultiple cylindromas associated with solitary lung cylin-droma. J Am Acad Dermatol 1988;19:397-400.

23 Gottschalk HR, Graham JH, Aston EE. Dermal eccrinecylindroma, epithelioma adenoides cysticum of Brooke,and eccrine spiradenoma. Arch Dermatol 1974;110:473-9.

24 Regan WJ, Hunt A. Turban tumours. Proc R Soc Med1956;49:337-9.

25 Reingold IM, Keasbey LE, Graham JH. Multicentric der-mal-type cylindromas of the parotid glands in a patientwith florid turban tumors. Cancer 1977;40:1702-10.

26 Lin PY, Fatteh SM, Lloyd KM. Malignant transformationin a solitary dermal cylindroma. Arch Pathol Lab Med1987;1 1 1:765-7.

27 Tsamboas D, Greither A, Orfanos, CE. Multiple malignantSpiegler tumors with brachydactyly and racket-nails.Light and electron microscopic study. J Cutan Pathol1979;6:31-41.

28 Luger A. Das cylindrom der Haut und seine maligneDegeneration. Arch Dermatol Syph 1949;188:155-80.

29 Bourlond A, Clerens A, Sigart H. Cylindrome Malin.Dermatologica 1979;158:203-7.

30 Baden HP. Cylindromatosis simulating neurofibromatosis.N Engl J Med 1962;267:296-7.

31 Nerad JA, Folberg R. Multiple cylindromas. The "turbantumor". Arch Ophthalmol 1987;105:1137.

32 Fusaro RM, Goltz RW. Histochemically demonstrable car-bohydrates of appendageal tumors of the skin. II. Benignapocrine gland tumors. J Invest Dermatol 1962;38:137-42.

33 Hashimoto K, Lever WL. Histogenesis of skin appendagetumors. Arch Dermatol 1969;100:356-69.

34 Goette DK, McConnell MA, Fowler VR. Cylindroma andeccrine spiradenoma coexistent in the same lesion. ArchDermatol 1982;118:273-4.

35 Headington JT, Batsakis JG, Beals TF, Campbell TE,Simmons JL, Stone WD. Membranous basal cell aden-oma of parotid gland, dermal cylindromas, and tricho-epitheliomas. Comparative histochemistry and ultrastruc-ture. Cancer 1977;39:2460-9.

36 Dupre A, Bonafe JL, Lassere J. Hamartome epithelialsclerosant: forme clinique du tricho-epitheliome. A pro-pos de 3 cas. Ann Dermatol Venereol (Paris) 1980;107:649-54.

37 Pfaltz M, Bruckner-Tuderman L, Schnyder UW. TypeVII collagen is a component of cylindroma basementmembrane zone. J Cutan Pathol 1989;16:388-95.

38 Rasmussen JE. A syndrome of trichoepitheliomas, miliaand cylindromas. Arch Dermatol 1975;111:610-4.

39 Guggenheim W, Schnyder UW. Zur Nosologie derSpiegler-Brook'schen Tumoren. Dermatologica 1961;122:274-8.

40 Bruckner-Tuderman L, Pfaltz M, Schnyder UW. Cylin-droma overexpresses collagen VII, the major anchoringfibril protein. J Invest Dermatol 1991;96:729-34.

41 Urbanski SJ, From L, Abramowicz A. Metamorphosis ofdermal cylindroma: possible relation to malignant trans-formation. J Am Acad Dermatol 1985;12: 188-95.

42 Guillot B, Buffiere I, Barneon G, Bensadoun D, Guilhou JJ,Meynadier J. Tricho-epitheliomes multiples cylin-dromes, grains de milium. Une entite. Ann DermatolVenereol 1987;114:175-82.

43 Rubin MG, Mitchell AJ. Generalized cutaneous cylindro-matosis. Cutis 1984;33:568-9.

44 Wolf BA, Gluckman JL, Wirman JA. Benign dermal cylin-droma of the external auditory canal: a clinicopathologicalreport. Am J Otolaryngol 1985;6:35-8.

45 Wright S, Ryan J. Multiple familial eccrine spiradenomawith cylindroma. Acta Derm Venereol (Stockh) 1990;70:79-82.

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