Existence of the sign of Leser-Trélat

Volume 23 Number 1 July 1990 study of a series of cases of scrotal calcinosis I revealed calcifying cystssimilarin appearanceto thoseillustrated by Song et al. The cysts, which occasionally communicated. with eccrineducts, wereconfirmed. as eccrine duct milia by the immunoperoxidase technique for the demonstration of carcinoembryonic antigen. Immunoreactivity of the cystcontentsand cytoplasm of periluminal cells was strong. This stainingpattern is typically seenin normal eccrineducts and structuresderived from them. Further unpublished. findings withpregnancy-specific f31-g1ycoprotein,anothermarker ofeccrineducts,demonstrated a similar but less intense pattern of immunoreactivity. These results were not seen in cysts of epidermal and pilar types. Ultrastructural examination of one case revealed surface microvilli, a periluminal band of tonofilaments, and numerous multivesicular bodies. These findings are characteristic of eccrineductal epithelium. In the photomicrographs and diagrams Song et al. designate those cysts with a granular layer as epidermal and thosewithouta granular layeras pilar.Themere absence of a granular layer is not sufficient evidence to establish the diagnosis of pilarcyst.Pilar cysts,which occur most commonly on the scalp, displaydistinctpalisading ofperipheral cells withswollen, glassycytoplasmicchange in periluminal cells. No such palisading or cytoplasmic change isseenin the cystsassociated withscrotalcalcinosis. The absence of a granular layerin cystsderived from eccrine sweat ducts is not surprising, becausethere is no granular layer in the intradermal portion of the normal eccrine duct. The presence of a granular layerin someof the cysts may reflect a recapitulationof the intraepidermal portion of the eccrine duct where a granular layer appears. Terms such as "idiopathic calcinosis of the scrotum" and "scrotalcalcinosis" providean inadequatedescription of thisdistinctive pathologic process. The term "hidrocalcinosis" has been proposed for this form of calcinosis cutis, in which the initialsite of calciumsalt accumulation is withinstructuresderived fromthe eccrinesweatglands. Anthony J. Dare, MBBS, FRCPA M'aryborough, Queensland, Australia

REFERENCE 1. Dare Al, Axelsen RA. Scrotal calcinosis: origin from dystrophic calcification of eccrine duct milia. 1 Cntan Pathol

1988;15:142-9.

Reply To the Editor: I thank Dr. Dare for his interest in and comments on our article.Dare's opinion is that our case may not bederived from epidermal, pilar, or hybridcysts but may be from eccrineduct milia, and he proposed the

Correspondence 151 term "hydrocalcinosis." There is an overlap between glandular and keratinizingmaturation in eccrineand pilosebaceous cysts. Sometimes the cysts show combinations of both patterns.' However, I disagree with Dare that scrotal calcinosis in our case may be derived from eccrine duct milia for the following reasons: I. The communication between the eccrine duct and the cyst wall was not observed. in all cysts and the contentsand cytoplasms ofperiluminalcellsofcysts showed all negativeimmunoperoxidase stainingfor carcinoembryonic antibody. 2. In one pilar cyst the cells of the cyst wall gotlarger toward the lumen and underwent abrupt keratinization without formation of keratohyalin. These cells showedno clearlyvisible intercellular bridges. Part of the cyst wall showed a distinct palisading arrangement of the peripheral layer cells, and the content of the cysts consisted of homogeneous eosinophilic material. Thus weinterpreted this cyst as a pilar cyst.

Won Hyoung Kang, MD Seoul. Korea

REFERENCE 1. Mehregan AH . Pinkus' guide todermatohistopathology. 4th ed. Norwalk, Conn: Appleton-Century-Crofts, 1986:483 .

Existence of the sign of Leser-Trelat To the Editor: I take the opportunity to respond to a number of points raisedin Rampen and Schwengle's recent article (J AM ACAD DERMATOL 1989;21:50-5). Specifically, I disagree with their conclusions that evidence for existence of the sign of Leser-Trelat is meager. When only a limited number of cases are available, surely controversy will arise; however, this provides a forum for discussion fromwhichallphysicians may benefit. First, I believe errors of interpretation of the literature were made on the authors' behalfthat would not necessarily exclude some of the cases. As opposed to the authors', Gougerot and Duperrant' did histologically examine the skin lesions and determinedthat they were seborrheic keratoses. Various histologic types of seborrheickeratoses occurandhavebeen describedelsewhere.' In recent publicationsv' I have strongly suggested that clinical correlation of this sign would be strengthened if all persons had biopsies of the skin lesions to confirm whether seborrheic keratoses occur. Certainly, eczematouscutaneouschangescan present a problem withinterpretation;thus careful evaluation of the previous state of the skin is necessary? However, I disagree with Rampen and Schwengle

Journal of the American Academy of Dermatology

152 Correspondence concerning the unreliability of "anamnestic data in elderly patients" and haveresponded to thisin publication." Even though their Spearmanrank correlationcoefficient may appear impressive withshorter historyof eruption of cutaneous lesions with advancing age, I believe that it is of minor significance.' A number of olderpublications have beenvagueabout the occurrence of pruritus and acanthosis nigricans and about its correlation withthis sign. Although these phenomena occur frequently, it doesnot appear to be an absolute requirementforclassification of this entity? By my observation, acanthosis nigricans alone is observed in 35%,pruritus alonein 43%, and both acanthosisnigricans and pruritus in 16%. 6 Another point of contention is that of the parallel course of the seborrheic keratoses and the progression of the malignancy. The data I haveexamineddo not support this hypothesis, at least not in this case. I do not have a good answer for this, but here are my observations; Curth's criteria are fine and dandy, but these criteria in themselves are stillonlyhypotheses and not laws of physics. The authors themselves use malignant acanthosis nigricans as an example of an "ideal paraneoplastic syndrome"; however, the literature certainly proves that a parallel does not always exist for the tumor and cutaneous lesions. In addition, malignant acanthosis nigricans has been found to be associated with cancers other than adenocarcinoma of the gastrointestionaltract. The exact association of seborrheic keratoseswith differenttypes of cancers is not clearat this time; however, the tumors apparentlysecretea similarhormoneor othersubstancethat produces the cutaneous Iesions.s 3 Although their points are welltaken, thesecriteria do not have a 100%correlation withmost paraneoplastic syndromes, as is welldemonstrated in the literature.Seborrheic keratosescertainly are common,yetthe dynamics of which theyerupt should arouse one's suspicion that a malignancy may be the underlyingcause.Astimegoesonand moreobservations are made, and if some of my prior suggestions are applied, maybe then we can obtain a better understanding and correlation of this cutaneousmanifestation.' As a last point,I believe the prior study performed by these authors"hasminimalapplicationtoward the sign of Leser-Trelat, The authors basically observed a static population on a one-time basis. From the information examined,the signis a dynamicprocesswith evolution of the cutaneous lesions over time. Thus the study of Schwengleet a1. 4 demonstrated little utility in the classification of this dermatoses. Mack R. Holdiness, MD, PhD Metairie [New Orleans], Louisiana

REFERENCES 1. Gougerout H, Duperrat B. Dermatose verruquese "monitrice" d'un cancer visceral. Ann Dermatol Syph (Paris) 1942; 19: 193-9.

2. Holdiness MR. On the classification of the sign of LeserTrelat [Editorial]. JAM ACAD DERMATOL 1988;19:754-7. 3. Holdiness MR. On the signof Leser-Trelat: a review. Int J DermatoI1986;25:564-72. 4. Schwengle LEM, Rampen FHJ, Wobbes TH. Seborrheic keratoses and internalmaligancies: a casecontrolstudy. Clin Exp Dermatol 1989;13:177-9. 5. Holdiness MR. Seborrhoeic keratoses and internal malignancies: a rebuttal. Clin Exp Dermatol (in press). 6. Holdiness MR. Pruritusand the Leser-Trelat sign, [Letter]. JAM ACAD DERMATOL 1988;18:149.

The sign of Leser-Trelat To the Editor: We read with great interest the article "The Sign of Leser-Trelat: Does It Exist?" by Rampen and Schwengle (J AM ACAD DERMATOL 1989;21:50-5). The authors concluded that the evidence for association of eruptive seborrheic keratoses with an underlying malignant process is scant and that it is barely sufficient to regard such lesions as a valid warning sign. Their table, which showed the reported cases of the sign of LeserTrelat with evidence of a parallel course of seborrheic keratoses and malignancy, failed to mention our previouslyreported case of a patient with Leser-Trelat sign associatedwith malignant melanoma.' Not only did we find the parallel course of seborrheic keratoses and malignancy, but we isolated alpha-transforming growth factor (TGF-a) in the patient's urine and also showed a parallel course between TGF-a: and increased cutaneous growth factor receptors.These findings suggest an important role for growth factors in the cutaneous manifestation of paraneoplastic syndromes. Not many patients with multiple seborrheic keratoses have internal malignancies.However, the sudden appearance of multiple pruritic seborrheickeratosesshould alert physicians to the possible presence of an underlying malignancy that may be cutaneous or that may originate from moreclassicinternal sourcessuch as the gastrointestinal tract. We believethat, instead of statistical analysis such as the authors suggested, that guidelines for documenting cutaneous paraneoplastic syndromes should be followed as outlined in our previous publication, entitled "Melanoma Growth Factors and Cutaneous Paraneeplastic Syndromes.'? Jim C. Chow, MD, Darrel L. Ellis, MD, Michael E. McCadden, MD, and Lloyd E. King, MD, PhD Division oj Dermatology Vanderbilt University Veterans Administration Medical Center Nashville, Tennessee

REFERENCES 1. EllisDL, Kafka SP, ChowJ C, et al. Melanoma,growth factors, acanthosis nigricans, the signof Leser-Trelat, and mul-