(Dysplastic) Nevi Outcomes of Surgical Excision and Association with Melanoma

Research

Original Investigation Atypical (Dysplastic) Nevi Outcomes of Surgical Excision and Association With Melanoma

Kavitha K. Reddy, MD; Michele J. Farber, MD; Jag Bhawan, MD; Roy G. Geronemus, MD; Gary S. Rogers, MD

CME Quiz at OBJECTIVE To evaluate the effect of surgical excision, performed after biopsy diagnosis of jamanetworkcme.com and dysplastic nevus, on final diagnosis, melanoma prevention, and melanoma detection. CME Questions page 1004

DESIGN, SETTING, AND PARTICIPANTS Outcome study using retrospective review conducted in an academic dermatopathology practice (Boston Medical Center Skin Pathology Laboratory) that receives specimens from community and academic practices across the United States. Consecutive patient pathology samples of dysplastic nevi and cutaneous melanomas evaluated between September 1, 1999 and March 1, 2011, and identified using systematized nomenclature of medicine codes were included.

MAIN OUTCOMES AND MEASURES In dysplastic nevi cases, the rate of clinically significant change in diagnosis and the rate of melanoma detection as a result of excision. In melanoma cases, the rate and characteristics of association with dysplastic nevus.

RESULTS Of dysplastic nevi, 196 of 580 (34%) showed a positive biopsy margin, increasing with grade of atypia (P < .001); 127 of 196 with positive biopsy margin received excision (65%), performed more often as grade of atypia increased (P < .001). Two excisions (2 of 127, 1.6%) resulted in a clinically significant change in diagnosis, from biopsy-diagnosed moderately-to-severely dysplastic nevi before excision to melanoma in situ after excision. In melanomas (n = 216), in situ and superficial spreading subtypes were more often associated Author Affiliations: Laser & Skin Surgery Center of New York, New with dysplastic nevi (20% and 18%, respectively) (P = .002), most often of York, New York (Reddy, Geronemus); moderate-to-severe or severe grade. Departments of Dermatology, Jefferson Medical College, CONCLUSIONS AND RELEVANCE Excision of biopsy-diagnosed mildly or moderately dysplastic Philadelphia, Pennsylvania (Farber); Boston University School of nevi is unlikely to result in a clinically significant change in diagnosis, and risk of Medicine, Boston, Massachusetts transformation to melanoma appears very low. Moderately-to-severely and severely (Bhawan); Tufts University School of dysplastic nevi are more often associated with melanoma, and excision may be beneficial for Medicine, Boston, Massachusetts melanoma detection or prevention. (Rogers). Corresponding Author: Kavitha K. Reddy, MD, Laser & Skin Surgery JAMA Dermatol. 2013;149(8):928-934. doi:10.1001/jamadermatol.2013.4440 Center of New York, 317 E 34th St, Published online June 12, 2013. 11th Floor, New York, NY 10016 ([email protected]).

lark et al1 described the atypical, or dysplastic, nevus plastic nevus with positive histologic margin, there is signifi- as having unusual clinical and pathologic features cant variation and lack of consensus in subsequent C found in individuals or families predisposed to management.6 melanoma. A National Institutes of Health Consensus Surgical excision of the dysplastic nevus biopsy site with Conference2 further defined atypical nevi as having diam- a 2- to 3-mm margin of normal skin is frequently performed. eter greater than 5 mm, color or border irregularity, and cer- The goal of excision is to confirm the biopsy diagnosis, to en- tain histologic features. Evidence supports observations sure complete removal due to concerns of future malignant that the presence of atypical nevi is associated with transformation, or both. These goals include melanoma de- increased overall melanoma risk.3 tection and prevention. The lifetime transformation risk of an Atypical nevi are common, with an incidence of 2% to 8% “average” dysplastic nevus into melanoma is estimated at 1 in in white patients.4,5 Many are biopsied to evaluate for 10 000, though risk likely varies with grade of atypia.7 In ad- melanoma.4 Management of a biopsy-proven dysplastic (atypi- dition, excision is sometimes performed to eliminate risk of a cal) nevus with a positive histologic margin remains ill defined.6 recurrent nevus, a benign lesion that rarely may be difficult Particularly after a biopsy finding of mildly or moderately dys- to distinguish from melanoma.8 Disadvantages of excision in-

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Table 1. Characteristics of Dysplastic Nevi on Biopsy and Excision

Dysplastic Nevi, No. (%) Dysplastic Nevus Cases, Positive Biopsy Surgical Residual Clinically Significant Grade No. Margina Excisiona Lesion Change in Diagnosis Mild 155 17 (11) 2 (12) 1 (50) 0 Mild to moderate 90 17 (19) 9 (53) 2 (22) 0 Moderate 207 83 (40) 52 (63) 20 (38) 0 Moderate to severe 109 68 (62) 55 (81) 17 (31) 2 (3.6)b Severe 13 11 (85) 9 (82) 2 (22) 0 Abbreviation: NA, not applicable. Unspecified 6 0 NA NA NA a P < .001. Total 580 196 (34) 127 (65) 42 (33) 2 (1.6) b Melanoma in situ.

were diagnosed by a board-certified dermatopathologist. Dys- Figure 1. Grades and Characteristics of Dysplastic Nevi plastic nevus grade of atypia was diagnosed using criteria summarized by Arumi-Uria et al.9 Biopsy reports dated between Excision performed after positive biopsy margin September 1, 1999, and March 1, 2011, reporting a pathologic Excision shows residual lesion diagnosis of dysplastic nevus were reviewed retrospectively Excision results in significant 90 change in diagnosis in reverse chronologic order until 580 cases were reviewed. 80 Positive biopsy margin Dysplastic nevi characteristics of gross pathologic size, grade 70 of atypia, anatomic location, and biopsy margin positivity were

60 recorded. In cases reporting a dysplastic nevus with a positive biopsy margin, records were reviewed for surgical exci- 50 sion. Surgical excision of the lesion with a 2- to 3-mm margin 40 of normal skin followed by closure of the skin is the standard 30 Dysplastic Nevi, % Dysplastic Nevi, method for removal of a biopsy-diagnosed dysplastic nevus. 20 If an excision was performed, date of excision, presence of re-

10 sidual lesion on pathologic examination, and final pathologic diagnosis were recorded. Concordance of biopsy diagnoses 0 with excision diagnoses was recorded. Clinically significant Mild Mild to Moderate Moderate to Severe Moderate Severe changes in diagnosis upon excision were recorded, defined as Degree of Dysplasia severe atypia or melanoma upon excision of biopsy- diagnosed mildly-to-moderately or moderately dysplastic nevi, Grade of dysplastic nevus and association with biopsy margin positivity, and defined as melanoma upon excision of biopsy-diagnosed frequency of excision after positive biopsy margin, frequency of residual nevus in excision specimen, and clinically significant change in diagnosis upon moderately-to-severely or severely dysplastic nevi. excision. Pathology reports dated between September 1, 1999, and March 1, 2011, reporting a diagnosis of primary cutaneous melanoma were also reviewed, until a limit of 216 cases. Mela- clude risks of scarring and surgical complications and utiliza- noma type, depth, presence of associated scar, and presence tion of health resources. of associated dysplastic nevus were recorded. If an associ- The management of dysplastic nevi significantly impacts ated dysplastic nevus was present, grade of atypia was re- individual and public health. The impact of surgical excision corded. In cases of melanoma with associated scar, records of dysplastic nevi on goals of melanoma detection and pre- were reviewed, and any history of biopsy-diagnosed dysplas- vention has not been well-studied. Our objectives were to tic nevus at the melanoma site was recorded. evaluate the impact of surgical excision of biopsy-diagnosed dysplastic nevi on final diagnosis, on melanoma detection, and Statistical Analysis on melanoma prevention through analysis of concordance of Observed characteristics of dysplastic nevi and primary cuta- biopsy and excision diagnoses and examination of the risk of neous melanomas were summarized using counts and pro- dysplastic nevus transformation to melanoma. portions. For dysplastic nevi, biopsy margin positivity, frequency of excision after positive biopsy margin, frequency of residual nevus upon excision, and clinically significant change Methods in diagnosis upon excision were summarized within categories of dysplastic nevus grade. For cases of dysplastic nevus Study Design with positive biopsy margin, anatomic location and size were Study approval was granted by the Boston Medical Center in- also summarized within categories of dysplastic nevus grade. stitutional review board. The Boston Medical Center Skin Pa- In primary cutaneous melanoma cases, presence and grade of thology Laboratory database was searched using system- associated dysplastic nevus, presence of associated scar, and atized nomenclature of medicine (SNOMED) codes for history of biopsy-proven dysplastic nevus at the melanoma site dysplastic nevi and for primary cutaneous melanoma. All cases were summarized within categories of melanoma type and

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Table 2. Association of Dysplastic Nevus Grade With Biopsy Margin Positivity, Anatomic Location, and Gross Pathologic Size

Anatomic Location, No. (%) Largest Dimension, cm Dysplastic Nevus With Grade of Atypia Positive Margin, No. Head or Neck Trunk or Extremities Mean Median Mode Mild 17 0 17 (100) 0.64 0.50 0.40 Mild to moderate 17 1 (6) 16 (94) 0.82 0.70 0.50 Moderate 83 3 (4) 80 (96) 0.67 0.60 0.60 Moderate to severe 68 3 (4) 65 (96) 0.74 0.65 0.50 Severe 11 1 (9) 10 (91) 0.80 0.70 0.70

Figure 2. Melanoma In Situ in Reexcision of a Biopsied Dysplastic Nevus

A B

C D

A and B, Initial biopsy shows moderate to severely dysplastic nevus with showing scar on the right with adjacent nested and lentiginous severely atypical predominantly nested melanocytic hyperplasia, atypical, concentric, and melanocytic hyperplasia on the left (C, hematoxylin-eosin, original lamellar fibroplasia, and mild host inflammatory infiltrate (hematoxylin-eosin, magnification ×4) consistent with melanoma in situ (D, hematoxylin-eosin, original magnifications ×10 [A] and ×20 [B]). C and D, Excision specimen original magnification ×40).

melanoma depth. The χ2 Fisher exact and Cochran-Armitage opsy margin. A positive biopsy margin was more often re- trend tests were used to compare proportions and evaluate ported as the degree of atypia worsened (mild, 11%; mild to trends. All statistical analyses were performed using the SAS moderate, 19%; moderate, 40%; moderate to severe, 62%; and statistical package, version 9.2 (SAS Institute). All P values cal- severe, 85%) (P < .001 for test of trend) (Figure 1). As a result culated are 2-sided. of this observation, further analysis for factors affecting margin positivity was conducted. In dysplastic nevi with positive biopsy margins, gross pathologic size and anatomic location Results at the head or neck were also positively correlated with grade of atypia and with biopsy margin positivity, with the excep- A total of 580 cases reporting a biopsy diagnosis of dysplastic tion of mildly-to-moderately dysplastic nevi, which showed nevus were reviewed (Table 1). Nearly all were biopsied by slightly larger size and greater frequency on the head or neck shave biopsy technique. Standard shave biopsy of atypical nevi than would be predicted according to the trend (Table 2). includes partial-thickness dermis and a 1- to 2-mm margin of Of dysplastic nevi with a positive biopsy margin, 127 of 196 normal skin. Overall, 196 of 580 (34%) reported a positive bi- (65%) received surgical excision (Table 1). As grade of atypia

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increased, frequency of excision after positive biopsy margin Table 3. Characteristics of Primary Cutaneous Melanomas increased (mild, 12%; mild to moderate, 53%; moderate, 63%; moderate to severe, 81%; severe, 82%) ( < .001 for test of trend) Melanomas, No. (%) P Melanoma Type (n = 216) (Figure 1). Of dysplastic nevi with a positive biopsy margin that Melanoma in situ (n = 44) received surgical excision, 42 of 127 (33%) showed residual ne- Associated with dysplastic nevus 9 (20)a vus. Rate of biopsy margin positivity sorted by grade of atypia Associated with scar 10 (23) and grade of atypia were not associated with the presence of History of biopsied dysplastic nevus at site 0 residual nevus upon excision (P =.68fortestoftrend).Two Superficial spreading (n = 90) of 127 surgical excisions (1.6%) led to a clinically significant Associated with dysplastic nevus 16 (18)a change in diagnosis. Both were biopsy-diagnosed moderately- Associated with scar 13 (14) to-severely dysplastic nevi that were diagnosed as mela- History of biopsied dysplastic nevus at site 0 noma in situ upon excision (Figure 2). There were not any cases Lentigo maligna (n = 21) of biopsy-diagnosed mildly or moderately dysplastic nevi that resulted in a clinically significant change in diagnosis upon Associated with dysplastic nevus 0 excision. Associated with scar 6 (29) A total of 216 primary cutaneous melanomas were also re- History of biopsied dysplastic nevus at site 0 viewed (Table 3). Sixteen of 90 superficial spreading melano- Nodular (n = 6) mas (18%) and 9 of 44 melanomas in situ (20%) were associ- Associated with dysplastic nevus 0 ated with a dysplastic nevus (Table 3 and Figure 3). The Associated with scar 0 association of melanomas in situ and superficial spreading History of biopsied dysplastic nevus at site 0 melanomas with dysplastic nevi (25 of 134, 18.7%) was signifi- Desmoplastic (n = 3) cantly higher than the association between other melanoma Associated with dysplastic nevus 0 types and dysplastic nevi (2 of 82, 2%) (P = .001). None of mela- Associated with scar 0 nomas showing associated scar without associated dysplas- History of biopsied dysplastic nevus at site 0 tic nevus revealed a history of biopsy-diagnosed dysplastic ne- Amelanotic (n = 2) vus at the site (Table 3). In melanomas associated with Associated with dysplastic nevus 0 dysplastic nevi, the most frequent grades of atypia were mod- Associated with scar 1 (50) erate-to-severe and severe (Table 4). Of 27 melanomas asso- History of biopsied dysplastic nevus at site 0 ciated with dysplastic nevi, 26 of 27 (96%) were 1 mm or less Acral lentiginous (n = 2) in depth. Melanoma association with dysplastic nevus de- Associated with dysplastic nevus 0 creased with increasing melanoma depth (P = .03 for test of Associated with scar 0 trend) (Table 5). Overall, 10.97% of invasive melanomas were History of biopsied dysplastic nevus at site 0 associated with a dysplastic nevus. Polypoid (n = 2) Associated with dysplastic nevus 0 Associated with scar 0 Discussion History of biopsied dysplastic nevus at site 0 Atypical nevi are associated with an increased risk of cutane- Unclassified (n = 46) ous melanoma, which may develop in existing nevi or de novo Associated with dysplastic nevus 2 (4) on previously normal skin. Therefore, management of the pa- Associated with scar 7 (15) tient with atypical nevi is recommended to include complete History of biopsied dysplastic nevus at site 0 skin examinations at regular intervals and patient education a Melanoma in situ and superficial spreading melanomas with significantly in melanoma prevention and early detection.4 While many phy- higher rate of association with dysplastic nevus compared with other sicians also perform surgical excision of dysplastic nevi hav- melanoma types (P = .002). ing a positive histologic margin, outcomes of atypical nevus excision have not been examined in detail, to our knowledge, residual cells after biopsy. In contrast, moderately-to- and the appropriate surgical management of dysplastic nevi severely dysplastic nevi with a positive biopsy margin dis- has remained poorly defined. played a 4% rate of melanoma in situ diagnosis upon surgical In our examination of the impact of dysplastic nevus ex- excision. Moderately-to-severely and severely dysplastic nevi cision on final diagnosis and on melanoma detection, vary- were also most often associated with melanomas. This sug- ing effects were observed for mildly and moderately dysplas- gests that in contrast to patients with mildly and moderately tic nevi compared with moderately-to-severely and severely dysplastic nevi, patients with moderately-to-severely and se- dysplastic nevi. Mildly and moderately dysplastic nevi did not verely dysplastic nevi with positive biopsy margins are more show any clinically significant change from biopsy diagnosis likely to benefit from surgical excision for confirmation of di- nor any evidence of melanoma upon surgical excision. The data agnosis, melanoma detection, and melanoma prevention. suggest that biopsied mildly and moderately dysplastic nevi In our series, 34% of dysplastic nevi showed a positive may not require subsequent surgical excision to confirm the biopsy margin, consistent with a previous report by Armour diagnosis and are unlikely to harbor associated melanoma in et al.10 Dysplastic nevus biopsy margins were more often

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Figure 3. Melanoma In Situ Associated With a Dysplastic Nevus, Without Previous Biopsy

A B

C D

A and B, A component of the lesion appears as a mildly to moderately dysplastic to severe lentiginous melanocytic hyperplasia, dyshesion, focal pagetoid nevus (hematoxylin-eosin, original magnifications ×10 [A] and ×20 [B]). C and spread, mild dermal fibrosis, and melanophages (hematoxylin-eosin, original D, The dysplastic nevus is associated with melanoma in situ showing moderate magnifications ×10 [C] and ×20 [D]).

positive as grade of atypia worsened, and as gross size and perform surgical excision of a dysplastic nevus that had a posi- frequency of head or neck location increased. Potential tive biopsy margin, with many self-writing in that the decision theoretical explanations for the increased biopsy margin would depend on the degree of atypia.6 Our findings confirm positivity observed with increasing grade of atypia include that excision frequency is positively correlated with degree of increased subclinical extension as atypia worsens, increased atypia, and we have quantified observed excision rates. gross nevus size as atypia worsens with clinician biopsies To our knowledge, the effect of dysplastic nevus excision not increasing proportionately in size, increased proportion on the final diagnosis has been examined previously in only 2 of head or neck lesions having wide atypical melanocytic small studies.10,11 Armour and colleagues10 found that 21 of 22 hyperplasia, and/or medical or legal concerns leading to shave biopsies (95%) of atypical nevi were concordant with the more thorough margin assessment as grade of atypia excision diagnosis. Study limitations include a small sample increases. Our study confirms that patients having a dys- size and lack of reporting of grades of atypia examined. Co- plastic nevus with a positive biopsy margin frequently hen and colleagues11 examined 189 excision specimens ob- receive excision, and that frequency of excision appears to tained after biopsy of atypical melanocytic lesions, many of increase with grade of atypia. The greatest variability in which were atypical nevi. Of these, 47 of 189 (25%) contained management was observed for cases of mildly-to- residual nevus cells and 1 of 189 (0.5%) contained melanoma moderately and moderately dysplastic nevi, which received (the initial biopsy diagnosis having been moderately-to- surgical excision after a positive biopsy margin finding in severely atypical nevus). Our data also support a low rate of 53% and 63% of cases, respectively. change in diagnosis upon excision (1.6%) when all grades of There have been limited reports describing practice pat- atypical nevi are considered together and confirms that mod- terns in the management of atypical nevi. In 2002, a survey of erately-to-severely atypical nevi are more likely to be associ- dermatologists reported that 67% of respondents preferred to ated with melanoma.

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Table 4. Grade of Dysplastic Nevus Associated With Primary Table 5. Melanoma Depth and Association With Dysplastic Nevus Cutaneous Melanoma Melanoma Cases, Cases Associated With a Associated Dysplastic Nevi, No. (%) Depth, mm No. Dysplastic Nevus, No. (%) Malignant Melanoma Superficial Spreading 0 (in situ) 61 10 (16) Grade of Atypia In Situ Melanoma ≤1.00 109 16 (15) Mild 001.01-2.00 27 1 (4) Mild to moderate 1 (11) 0 2.01-4.00 90 Moderate 00>4.00 10 0 Moderate to 3 (33) 3 (19) Total 216 27 (12.5) severe Severe 2 (22) 6 (38) a Melanoma depth negatively associated with dysplastic nevus (P =.03). Grade unspecified 3 (33) 7 (44) an atypical nevus retrospectively, though prospective study Total 916 of this outcome is unlikely to be conducted. Large, prospective clinical trials are encouraged in further studying out- The association of dysplastic nevi with melanoma has been comes of excision of dysplastic nevi. reported, although without sorting by grade of atypia. Stud- Overall, our data suggest 2 dysplastic nevi risk catego- ies have estimated that 60% to 80% of melanomas arise de ries: (1) mildly, mildly-to-moderately, and moderately dys- novo12 and that melanomas arise in association with an atypi- plastic nevi generally appearing as low-risk lesions, and (2) cal nevus in 0.5% to 46% of cases.4 Based on data showing that moderately-to-severely and severely dysplastic nevi appear- 11% of invasive melanomas were associated with an atypical ing to carry a higher risk for coexistent or future melanoma. nevus,Tsaoetal7 estimated the lifetime risk of an “average” This suggests that patients with biopsied mildly or moder- atypical nevus transforming to melanoma as approximately 1 ately dysplastic nevi may be observed clinically, while pa- in 10 000. Our study confirms an 11% rate of association be- tients with moderately-to-severely and severely atypical nevi tween dysplastic nevi and invasive melanoma. Several mela- have a higher risk of melanoma and may benefit from exci- noma-associated dysplastic nevi were of unspecified grade, and sion. Moderately atypical nevi, which have a large variation depending on the true level of atypia, estimated transforma- in management, appear to display similar characteristics and tion risk may vary accordingly. behavior to those of mildly atypical nevi. Together, these data Sorted by grade of atypia, our data suggest that the life- suggest that routine surgical excision of biopsied mildly or time risk of a moderately-to-severely or severely dysplastic ne- moderately atypical nevi with a positive biopsy margin for the vus transforming to melanoma is likely clinically significant. purpose of melanoma prevention or detection may not be in- In contrast, the lifetime risk of mildly or moderately atypical dicated, while surgical excision of biopsied moderately-to- nevi transforming to melanoma may be similar to that of a nor- severely or severely atypical nevi with a positive biopsy mar- mal “typical” nevus. gin may be beneficial in melanoma prevention and detection. Our findings are most generalizable to dysplastic nevi that Individual patient factors are important in medical decision have been biopsied and found to have clinically negative mar- making, which remains the responsibility of the treating phy- gins but positive histologic margins because it is standard der- sician. Given the common biopsy diagnosis of atypical ne- matologic practice to remove the entire clinically visible nevus, we encourage further study of outcomes of surgical ex- vus during a shave biopsy procedure. Study limitations include cision to promote optimum patient care and to maximize the difficulty of estimating melanoma transformation risk of melanoma prevention and detection efforts.

ARTICLE INFORMATION Conflict of Interest Disclosures: None reported. B-K mole syndrome’. Arch Dermatol. Accepted for Publication: March 28, 2013. Funding/Support: This study was supported by a 1978;114(5):732-738. Published Online: June 12, 2013. Cutting Edge Research Grant from the American 2. NIH Consensus Conference. NIH Consensus doi:10.1001/jamadermatol.2013.4440. Society for Dermatologic Surgery (Dr Reddy). Conference: diagnosis and treatment of early melanoma. JAMA. 1992;268(10):1314-1319. Author Contributions: Drs Reddy and Rogers had Role of the Sponsors: The sponsor did not have full access to the all of the data in the study, take any role in the design or conduct of the study; in the 3. Psaty EL, Scope A, Halpern AC, Marghoob AA. responsibility for the integrity of the data and the collection, analysis, or interpretation of data; or in Defining the patient at high risk for melanoma. Int J accuracy of data reporting and analysis. the preparation, review, or approval of the Dermatol. 2010;49(4):362-376. Study concept and design: Reddy, Rogers. manuscript. 4. Friedman RJ, Farber MJ, Warycha MA, Acquisition of data: Reddy, Farber. Additional Contributions: We gratefully Papathasis N, Miller MK, Heilman ER. The Analysis and interpretation of data: Reddy, Bhawan, acknowledge Robin Ruthazer, MPH, of the “dysplastic” nevus. Clin Dermatol. Geronemus, Rogers. Biostatistics Research Center, Institute for Clinical 2009;27(1):103-115. Drafting of the manuscript: Reddy, Farber, Rogers. Research and Health Policy Studies, Tufts Medical 5. Piepkorn M, Meyer LJ, Goldgar D, et al. The Critical revision of the manuscript for important Center, for her assistance with statistical analysis. dysplastic melanocytic nevus: a prevalent lesion intellectual content: Reddy, Bhawan, Geronemus, that correlates poorly with clinical phenotype. JAm Rogers. REFERENCES Acad Dermatol. 1989;20(3):407-415. Obtained funding: Reddy. 1. Clark WH Jr, Reimer RR, Greene M, Ainsworth Administrative, technical, and material support: 6. Tripp JM, Kopf AW, Marghoob AA, Bart RS. AM, Mastrangelo MJ. Origin of familial malignant Management of dysplastic nevi: a survey of fellows Bhawan. melanomas from heritable melanocytic lesions: ‘the Study supervision: Geronemus, Rogers.

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of the American Academy of Dermatology. JAm comparison with melanoma with regression. Mod 11. Cohen LM, Hodge SJ, Owen LG, Callen JP. Acad Dermatol. 2002;46(5):674-682. Pathol. 2009;22(5):611-617. Atypical melanocytic nevi: clinical and 7. Tsao H, Bevona C, Goggins W, Quinn T. The 9. Arumi-Uria M, McNutt NS, Finnerty B. Grading of histopathologic predictors of residual tumor at transformation rate of moles (melanocytic nevi) atypia in nevi: correlation with melanoma risk. Mod reexcision. J Am Acad Dermatol. 1992;27(5, pt into cutaneous melanoma: a population-based Pathol. 2003;16(8):764-771. 1):701-706. estimate. Arch Dermatol. 2003;139(3):282-288. 10. Armour K, Mann S, Lee S. Dysplastic naevi: to 12. Bevona C, Goggins W, Quinn T, Fullerton J, Tsao 8. King R, Hayzen BA, Page RN, Googe PB, Zeagler shave, or not to shave? a retrospective study of the H. Cutaneous melanomas associated with nevi. D, Mihm MC Jr. Recurrent nevus phenomenon: a use of the shave biopsy technique in the initial Arch Dermatol. 2003;139(12):1620-1624. clinicopathologic study of 357 cases and histologic management of dysplastic naevi. Australas J Dermatol. 2005;46(2):70-75.

NOTABLE NOTES

Remembering Louis Tribondeau (1872-1918)

Maria Dalamaga, MD, PhD; Antonis A. Kousoulis, MD

French physician Louis Tribondeau (1872-1918) has been an important memorative plaque lies today hidden and forgotten behind tree name in biochemical and dermatological research for 100 years. His study branches. of infectious diseases, particularly syphilis and mycoses, marks some im- Author Affiliations: Department of Clinical Biochemistry, Medical School, portant chapters in the history of dermatology. Most notably, he ame- University of Athens, “Attikon” General University Hospital, Athens, Greece liorated the Wassermann reaction and described a method for staining (Dalamaga); University of Athens Medical School, Athens (Kousoulis); Society of Treponema pallidum and other spirochetes by silver impregnation using Junior Doctors, Athens (Kousoulis). ammoniacal silver nitrate solution, named “Fontana-Tribondeau silver Corresponding Author: Antonis A. Kousoulis, MD, University of Athens Medical School, 9 Huxley Gardens, NW10 7EB, London, England (antonis.kousoulis@sni stain.”1-3 .gr). However, despite his excellent contributions, he has largely been 1. Kasai K, Kobayashi R. The stomach spirochete occurring in mammals. ignored by published literature. This is also the case in Corfu, Greece, J Parasitol. 1919;6(1):1-10. where he served as chief medical officer of the Navy and as head of 2. Gerstley L III, Morton HE. The demonstration of bacterial capsules by the department of bacteriology and infectious diseases for about 1 Fontana’s staining procedure. J Bacteriol. 1954;67(1):125-126. year until his death in the 1918 influenza pandemic. The hospital he 3. Fonseca L, de Toledo BE, Orrico SR, Elias AM, Ito IY. Determination of the worked in had been named the “Achilleion Tribondeau Hospital,” as presence of spirochetes in the subgingival plaque of Brazilian children. Braz seen on the left pillar plate of the Achilleion Palace (Figure). This com- Dent J. 1993;4(1):3-8.

Figure. Pillar Plate for Achilleion Tribondeau Hospital, Corfu, Greece

The left pillar plate in the Achilleion Palace, Corfu, Greece, stating “Achilleion Tribondeau Hospital.” (Photograph courtesy of Maria Dalamaga, MD, PhD; August 2012.)

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