Journal of the American Academy of DermatologyVolume 28, Number 6

patterns in patients with cutaneous melanoma [Abstract].Clin Res 1979;27:563A.

12, Lopransi S, Mihm MC Jr. Clinical and pathological corre­lation of malignant melanoma. J Cutan PathoI1979;6:180­94.

13. Koh HK. Cutaneous melanoma. N Engl J Med 1991;325:171-82.

14. Mastrangelo MJ, Baker AR, Katz HR. Cutaneous mela­noma. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.Cancer, principles and practice of oncology. 2nd ed. Phil­adelphia: lB Lippincott, 1985:1371-422.

15. Foster HM, Webb SJ. Skin cancer in the North Solomons.Aust N Z J Surg 1988;58:397-401.

16. Harsanyi ZP, Post PW, Brinkmann JW, et al. Mutagenic­ity of melanin from human red hair. Experimentia 1980;36:291-2.

17. Kukita A, Ishihara K. Clinical features and distribution ofmalignant melanoma and pigmented nevi on the soles of thefeet in Japan. J Invest Dermatol 1989;92(suppl 5):2IOS­13S.

[8. Isaacson C, Spector 1. Malignant melanomas in the Eur­African-Malay population of South Africa. Am J Derma­tohistopathol 1987;9: 109-10.

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19. Black WC, Wiggins C. Melanoma among southwesternAmerican Indians. Cancer 1985;55:2899-902. .

20. Reintgen DS, McCarty KM Jr, Cox E, et al. Malignantmelanoma in black American and white American popula­tions: a comparative review. lAMA 1982;248:1856-9.

21. Collins RJ. Melanoma in the Chinese of Hong Kong: em­phasis on volar andsubungualsites. Cancer 1984;54:I482-8.

22. Lever WF, Schaumburg-Lever G. Histopathology of theskin. 6th ed. Philadelphia: JB Lippincott, 1983:703-18.

23. Efron B, Tibshirani R. Statistical data analysis in the com­puter age. Science 1991 ;253:390-5.

24. Efron B, Tibshirani R. Bootstrap methods for standard er­rors, confidence intervals, and other measures of statisticalaccuracy. Stat Sci 1986;1:54-77.

25. Efron B. Why isn't everyone Bayesian? Am Stat 1986;40:1-5.

26. Breslow A. Prognosis in cutaneous melanoma: tumorthickness as a guide to treatment. In: Sommers SS, RosenPP, eds. Pathology annual; part 1, vol 15. New York: Ap­pleton-Century-Crofts, 1980:1-22.

27. Breslow A. Thickness, cross-sectional area and depth of in­vasion in prognosis of cutaneous melanoma. Ann Surg1970;172:902-8.

Rombo syndrome: A second case report and review

Robin Ashinoff, MD, Mark Jacobson, MD, and Donald V. Belsito, MDNew York, New York

Rombo syndrome is inherited as an autosomaldominant trait. Patients have agrainy appearance tothe skin, multiple basal cell carcinomas, trichoepi­theliomas, hypotrichosis, and a peculiar cyanosis ofthe hands and feet. We report the second case ofthissyndrome.

CASE REPORT

A 92-year-old white woman had multiple lesions on herface. The patient had mild dementia; her only medicationwas a phenothiazine. She was otherwise well. The patientand the patient's family were poor historians, althoughthey reported no one else in the family with any skinproblems. There was no history of x-irradiation.

Physical examination revealed ulcerated pearly pap­ules and plaques on the patient's left cheek, left side of theneck, right cheek, and right side of her upper lip. In ad-

From the Ronald 0, Perelman Department of Dermatology, New YorkUniversity Medical Center.

Reprint requests: Robin Ashinoff, MD, Ronald 0. Perelman Depart­mentofDermatology, NYU Medical Center, 566 First Avenue, NewYork, NY 10016.

JAM ACAD DBRMATOL 1993;28:1011-4.Copyright @ 1993 by the American Academy of Denllatology, lnc.0190-9622/93 $1.00 +.10 16/54/43970

dition, she had severe ectropion of both upper and lowereyelids with overflow tearing (Fig. I). There were no eye­lashes of the upper and lower lids. She had no other mu­cosallesions. The skin of her entire face was coarse andgrainy with a distinct yellow tone. The patient had nopalmar pits or jaw abnormalities. Her son and daughterhad normal skin. A facial photograph of the patient takenat age 35 revealed an apparently normal skin texture.

The ulcerated lesions were basal cell carcinomas as di­agnosed histologically. Indirect immunofluorescence forcicatricial pemphigoid was negative. An ophthalmologistbelieved her ectropion was secondary to fibrosis of the pe­riocular tissues.

The patient was referred for Mohs micrographic sur­gery. At the periphery of sections containing basal cellcarcinoma and in biopsy specimens from "normal"­appearing skin at the orbital rims, there were milia-likecysts and small nests and strands of basaloid epithelialcells surrounded by rims of compact collagen. These his­tologic features are similar to those seen in desmoplastictrichoepithelioma (Fig. 2), a follicular hamartoma thathas also been termed sclerosingepithelialhamartoma. I, 2

DISCUSSION

The Rombo syndrome was first described byMichaelsson et al.3 in 1981. Itwas named for the

1012 Brief communicationsJournal of the American Academy of Dermatology

June 1993

Fig. 1. Severe ectropion involves both eyes and multiple scars from surgical procedures forbasal cell carcinomas.

Fig. 2. High-power view of "normaI"-appearing skin. (Hematoxylin-eosin stain; XIOO.)

oldest family member in the pedigree. The syndromeseemed to be inherited in an autosomal dominantfashion. The patients described had skin with acoarse, grainy appearance with yellow papules, oftenfollicular, distributed on the entire face. The patientsalso had hypotrichosis with missing eyelashes on theupper and lower lids as well as pronounced cyanoticredness of the lips, hands, and feet. Our patient hadmost of these features except for the peripneral cy­anosis. The vermicular atrophoderma described in

the original patients resembles the coarse, grainyskin texture in our patient.

The differential diagnoses include the Bazex syn­drome,4 which consists of follicular atrophoderma,hypotrichosis, and basal cell carcinomas that de­velop in adolescence and Rasmussen's syndrome,swhich consists of milia, trichoepithelioma, and cy­lindroma. In addition, multiple trichoepitheliomas,follicular hamartomas, folliculobasaloid prolifera­tion, and generalized hair follicle hamartomas also

Journal of the American Academy of DermatologyVolume 28, Number 6

need to be considered. We believe that our patient'sconstellation of findings is best represented by theRombo syndrome, although no other family mem­ber seemed to be affected.

Multiple trichoepitheliomas or epithelioma ade­noides cysticum was first described by Brooke6 andthen by Fordyce7; both stressed that these lesionswere benign. Subsequent to this, several authorssuggested that basal cell carcinomas could arisefrom these benign lesions.8-l2 In addition, somelesions have had features of basal cell carcinoma inassociation with trichoepithelioma, and it can bedifficult to differentiate between the two lesions.

The recognition of patients with this syndrome orsimilar syndromes is especially important when per­forming surgical procedures such as Mohs micro­graphic surgery because excised trichoepithelioma­tous proliferations can be mistaken for basal Gel!carcinoma. In addition, these patients should be o'b­served closely because these trichoepitheliomas cangive rise to basal cell carcinomas as seen in our pa­tient and other patients.12 After this patient hadbeen observed for almost I year, it became apparentthat clinically recognizable basal cell carcinomasquickly develop from "normal"-appearing skin.

Histologically, it can also be difficult to differen­tiate a desmoplastic trichoepithelioma from a mor­pheaform basal cell carcinoma, especially when thefollicle-like structures penetrate into the reticulardermis. Desmoplastic trichoepithelioma has someareas of follicular differentiation, calcification ofcornified cells, and solar elastosis usually situatedabove an eosinophilic stroma. Morpheaform basalcell carcinoma is more likely to have clefts betweenbizarre aggregations of neoplastic cells and thestroma, foci of necrotic neoplastic cells, and solarelastosis mixed in with a fibrotic, amphophilic­staining stroma. Desmoplastic trichoepitheliomasare also more likely to have rims of compact colla­gen around aggregations of epithelial cells, which isnot seen in morpheaform basal cell carcinomal3

(Fig. 2).The severe ectropion in this patient was appar­

ently caused by traction exerted by the fibrosis in theproliferations resembling desmoplastic trichoepithe­liomas in both orbital rims.

Mohs micrographic surgery has been establishedas extremely efficacious in the treatment of reCUf­rent or problematic skin tumors. 14, IS Inherent in thetechnique is the preservation of normal tissue adja-

Briefcommunications 1013

cent to tumors. In certain areas of the face, this canbe difficult. Leshin and White l6 reported the casesof 22 patients undergoing Mohs micrographic sur­gery for nasal or perinasal basal cell carcinoma inwhom horizontal frozen sections showed folliculo­centric basaloid proliferation. This is benign, but canbe easily confused with basal cell carcinoma.

Follicular hamartomas l5- l9 can also be confusedwith basal cell carcinoma and folliculocentric pro­liferation. However, follicular hamartomas are usu­ally associated with myasthenia gravis and clinicallyusually appear as alopecia or infiltrated plaques onthe face. ls Our patient did not have myastheniagravis or indurated plaques. In addition, our pa­tient's lesions contained many keratin cysts thathave not been described in folliculocentric basaloidproliferation. 16 Generalized hair follicle hamarto­mas show prominent keratin cysts, but they are sur­rounded by a dense basophilic connective tissuestroma, l7, 18 whereas our patient's lesions showedmarked fibrosis around the follicular and sebaceouselements.

REFERENCES

1. Brownstein M, Shapiro L. Desmoplastic trichoepithelioma.Cancer 1977;40:2979-86.

2. MacDonald DM, Jones EW, Marks R. Sclerosing epithe­lial hamartoma. Clin Exp Dermatol 1977;2:153-60.

3. Michaelsson G, Olsson E, Westermark P. The Rombosyndrome: a familial disorder with vermiculate atropho­derma, milia, hypotrichosis, trichoepitheliomas, basal cellcarcinomas and peripheral vasodilation with cyanosis. ActaDerm Venereol (Stockh) 1981;61:497-50l

4. Viksnins P, Berlin A. Follicular atrophoderma and basalcell carcinomas: the Bazex syndrome. Arch Dermatol1977;113:948-51.

5. Rasmussen JE. A syndrome of trichoepilheliomas, miliaand cylindroma. Arch Dermatol 1975;111 :610-4.

6. Fordyce JA. Multiple benign cystic epitheliomas of theskin. J Cutan Dis 1892;10:459-73.

7. Brooke HG. Epithelioma adenoides cysticum. Dr J Der­matol 1892;4:269-86.

8. White Jc. Multiple benign cystic epitheliomas. J Cutan Dis1894; I2:477-84.

9. Adamson HG. Two cases of multiple rodent ulcers with anote on the possible relationship between multiple rodentulcer and epithelioma adenoides cysticum of Brooke. Lan­cet 1908;2:1133-8.

10. Savatoid L. Epithelioma adenoides cysticum. Br J Derma­tol 1922;43:381-96.

II. Howell JB, Anderson DE. Transformation of epitheliomaadenoides cysticulTI into multiple rodent ulcers: fact or fal­lacy. Dr J Dermatol 1976;95:233-41.

l2. Pariser RJ. Multiple hereditary trichoepitheliomas andbasal cell carcinomas. J Cutan Pathol 1986;13:111-7.

13. Ackerman AB, Troy .JL, Rosen LB, et al. Differential di­agnosis in dermatopathology II. Philadelphia: Lea &Febiger, 1988:154-5.

1014 Briefcommunications

14. Cottell WI, Proper S. Mobs surgery, fresh-tissue technique:our technique with a review. J Dermatol Surg Oneal1982;8:576-87.

15. Robins P. Chemosurgery: my 15 years of experience. JDermatol Surg Oneol 1981;7:779-89.

16. Leshin B, White WL. Folliculocentric basaloid prolifera­tion: the bulge (der Wulst) revisited. Arch Dermatol1990;126:900-6.

Journal of the American Academy of DermatologyJune 1993

17. Brown A, Crounse R, Winkelmann R. Generalized hair­follicle hamartoma. Arch Dermatol [969;99:478-93.

18. Ridley C, Smith N. Generalized hair follicle hamartomaassociated with alopecia and myasthenia gravis: report of asecond case. Clin Exp Dermatol 1981;6:283-9.

19. Mehregan W, Baker S. Basaloid follicular hamartoma:three cases with localized and systematized unilaterallesions. J Cutan PathoI1985;12:189-95.

Efficacy of cyclosporine in two patients with dermatitis herpetiformisresistant to conventional therapy

Harma J. Stenveld, MD,a Theo M. Starink, MD,a Theodoor van Joost, MD,b andTom 1. Stoof, MD, PhDa Amsterdam and Rotterdam, The Netherlands

Dapsone is the treatment of choice in dermatitisherpetiformis (DH) and is usually successful. In re­sistant cases other drugs, as well as a gluten-free diet,may be of value.1·3 We report the efficacy of cyclo­sporine in two patients with DH resistant to conven­tional therapy.

CASE REPORTSCase 1

A 46-year-old woman had a blistering eruption on herelbows, knees, and face for 13 years. A diagnosis of DHwas confirmed by histologic examination and direct im­munofluorescence. Multiple biopsy specimens of thejejunal mucosa revealed no evidence of a gluten-sensitiveenteropathy.

Treatment with dapsone, 200 mg/day, controlled herdisease, but a severe hemolytic anemia and methemoglo­binemia developed. For the past 13 years the patient hadalso been given a gluten-free diet as well as many otherdrugs, either as a monotherapy, or in combination withdapsone. These included cholestyramine, salazopyrine,colchicine, sulfamethoxypyridazine, and prednisone.Apart from sulfamethoxypyridazine, which had to bediscontinued because of a drug eruption, and prednisone,none of these treatments was successful.

After prolonged therapy with prednisone, 40 mg daily,and dapsone, 50 mg/day, serious side effects developed

From the Departments of Dermatology of the Academic Hospital FreeUniversity Amsterdam." and the Dijkzigt Ziekenhuis, Erasmus Uni­versity, Rotterdam.b

Reprint requests: Harma J. Stenveld, Department of Dermatology,Academic Hospital Free University, de Boelelaan 1117, NL·l081HV Amsterdam, The Netherlands.

JAMACAD DERMATOL1993;28:1014·5.Copyright@ 1993 by the American Academy of Dermatology, Inc.0190·9622/93 + $1.00 +.10 16/54/44102

and cyclosporine, 5 mg/kg/day, was added. After a shorttime prednisone could be discontinued. The dapsone dosewas reduced to 50 mg on alternate days, and stopped af­ter 3 months.

After 4 months of cyclosporine treatment, the serumcreatinine and blood pressure became elevated and theglomerular filtration rate fell to 30% of the initial value.Therefore we reduced the cyclosporine dose to 3mg/kg/day and added nifedipine (lOmg twice daily) as well asfish oil (6 gm/day) to protect renal function. After thedose reduction the patient had a few new blisters, butthese cleared spontaneously in a few days.

After the dose reduction the blood pressure and renalfunction normalized and remained so. Eighteen monthsafter the start ofcyclosporine therapy the patient was freeof symptoms. However, direct immunofluorescencestudies still showed granular IgA deposits and fibrinogenin the dermal papillae.

Case 2

A 63-year-old man had a 17-year history of a blister­ing eruption on his face, scalp, shoulders, arms, and legs.The diagnosis of DR was confirmed by histologic exam­ination and direct immunofluorescence. Biopsyspecimensof the jejunal mucosa revealed no evidence of a gluten­sensitive enteropathy. Treatment with dapsone, up to 300mg/day, was unable to control his disease. Salazopyrine,a gluten-free diet, and an iodine-free diet were ineffective.Cyclosporine was given at a dose of 7 mg/kg/day. Thiswas followed by the disappearance of the blisters within3weeks. Direct immunofluorescence studies still revealedIgA and fibrinogen deposits in the dermal papillae. Thishigh dose of cyclosporine was well tolerated, and the pa­tient remained free of symptoms, apart from a few minor"flare-ups". After 3 months a tumor on the scalp devel­oped. Histologically it was not possible to exclude a cuta·neous B-cell1ymphoma, and treatment with cyclosporine