J AM ACAD DERMATOL
Letters 589
VOLUME 71, NUMBER 3
lesions require no margin for complete excision. Malignant lesions should be excised with margins that completely remove the visible lesion along with any subclinical extension. This concept has shaped the accepted surgical margin of 1 cm for most melanomas. There is no intermediate margin for lesions of uncertain behavior, or for diagnostic ambiguity. Clinicians are faced with 2 options: no further treatment, as for a benign lesion; or to treat as if malignant. If we excise a lesion for disagreement among pathologists in classification as benign or malignant, it is an all-or-none margin, but not in between. Landon E. Stigall, MD, and John A. Zitelli, MD University of Pittsburgh Medical Center, and Zitelli & Brodland PC, Pittsburgh, Pennsylvania Funding sources: None. Conflicts of interest: None declared. Correspondence to: Landon E. Stigall, MD, Zitelli & Brodland PC, 5200 Centre Ave, Suite 303, Pittsburgh, PA 15232 E-mail: [email protected] REFERENCES 1. Piepkorn MW, Barnhill RL, Elder DE, Knezevich SR, Carney PA, Reisch LM, et al. The MPATH-Dx reporting schema for melanocytic proliferations and melanoma. J Am Acad Dermatol 2014;70:131-41. 2. Comfere N, Chakraborty R, Peters M. Margin comments in dermatopathology reports on dysplastic nevi influence re-excision rates. J Am Acad Dermatol 2013;69:687-92. http://dx.doi.org/10.1016/j.jaad.2014.04.073
Reply to ‘Surgical margins for possibly malignant melanocytic lesions’ To the Editor: We would like to thank Drs Stigall and Zitelli for their perspective on the management of melanocytic lesions, with reference to our study, ‘‘Margin comments in dermatopathology reports on dysplastic nevi influence re-excision rates.’’1 We applaud efforts by Piepkorn et al2 to develop a set of standardized diagnostic risk groups and corresponding treatment recommendations. However, interobserver agreement in histopathological diagnoses of melanocytic proliferations continues to be a major problem,3 because of multiple factors including the nature of the specimen submitted (partial vs complete samples) and unquantifiable tendency of pathologists to modify histopathological interpretations, including upgrading of atypia, depending on their experience with the clinical consequences of their reports. Thus, although
the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) scheme and the 2-tiered management proposal of Drs Stigall and Zitelli are valuable endeavors in the right direction, a major limitation is partial biopsy specimens: even if interobserver variability is improved, the MPATH-Dx or any other diagnostic scheme cannot surmount the justifiable influence of incomplete biopsy on how pathologists formulate their diagnoses and recommendations. A simplified scheme that only considers benign or malignant diagnoses does not fully address the need for re-excision of partially sampled lesions,4 given the known heterogeneity of melanocytic lesions,5 and does not offer specific recommendations for such scenarios. Therefore, although standardized 2-tiered (benign vs malignant) treatment recommendations are the most desirable direction, unless and until the ambiguities, poor reproducibility, and risks associated with partial samples that currently characterize diagnosis of melanocytic lesions are resolved, attempts to develop prognostic subgroups will be problematic. Thus, the recommendation of Drs Stigall and Zitelli that ‘‘benign lesions require no margin for complete excision’’ is correct in theory but ignores the practical reality that many ‘‘benign’’ lesions are incompletely removed and, as Elston et al6 so succinctly summarized, ‘‘one dermatopathologist’s moderately atypical nevus may be another’s melanoma.’’ Diagnostic uncertainty begets therapeutic ambiguity, hence the need for specific recommendations to guide clinicians. Given this current state of the art, complete biopsy with distinct margin of normal-appearing skin is needed to protect patients against the risks inherent in diagnostic uncertainty. Nneka I. Comfere, MD, and Margot S. Peters, MD Departments of Dermatology and Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota Funding sources: None. Conflicts of interest: None declared. Correspondence to: Nneka I. Comfere, MD, Department of Dermatology, Mayo Clinic, 200 First St SW, Rochester, MN 55905 E-mail: [email protected]
REFERENCES 1. Comfere N, Chakraborty R, Peters M. Margin comments in dermatopathology reports on dysplastic nevi influence re-excision rates. J Am Acad Dermatol 2013;69:687-92. 2. Piepkorn MW, Barnhill RL, Elder DE, Knezevich SR, Carney PA, Reisch LM, et al. The MPATH-Dx reporting schema for
J AM ACAD DERMATOL
590 Letters
3.
4.
5.
6.
SEPTEMBER 2014
melanocytic proliferations and melanoma. J Am Acad Dermatol 2014;70:131-41. Brochez L, Verhaeghe E, Grosshans E, Haneke E, Pierard G, Ruiter D, et al. Inter-observer variation in the histopathological diagnosis of clinically suspicious pigmented skin lesions. J Pathol 2002;196:459-66. Hocker TL, Alikhan A, Comfere NI, Peters MS. Favorable long-term outcomes in patients with histologically dysplastic nevi that approach a specimen border. J Am Acad Dermatol 2013;68:545-51. Barr RJ, Linden KG, Rubinstein G, Cantos KA. Analysis of heterogeneity of atypia within melanocytic nevi. Arch Dermatol 2003;139:289-93. Elston D, McNiff J, Maize J Sr. Histologically dysplastic nevi that extend to a specimen border. J Am Acad Dermatol 2013;68:682-3. http://dx.doi.org/10.1016/j.jaad.2014.05.030
Reply: Surgical margins for possibly malignant melanocytic lesions and the overdiagnosis of melanoma To the Editor: We welcome the thoughts of Drs Stigall and Zitelli. Although their remarks could be interpreted in different ways, they seem to take the position that either there is no such thing as an intermediate melanocytic lesion (being simply diagnostic disagreement), or that, if there is, there is no need for an intermediate margin for lesions of uncertain behavior. Either way, we disagree.1 Many choose to believe that melanocytic tumors are either indubitably benign or clearly malignant. Regardless of whether or not a simple binary dichotomy exists as such in nature, the practical reality of histologic diagnosis is less simple. The reliability of histologic diagnosis tends to break down in the gray zone between benign and malignant. The reasons are complex and poorly understood; suffice it to say that criteria differ in sensitivity and specificity, are often subjective, and often have not been vetted to rigorous standards. In short, histologic diagnosis is a crude surrogate for disease biology. Not surprisingly, many, if not most, dermatopathologists who practice long enough will render a false-negative diagnosis from partial biopsy specimen. Sampling limitations, low sensitivity of criteria in ‘‘borderline’’ lesions, observer variability, and ‘‘lives of lesions’’ are potentially contributory. This common experience, in concert with concern for patient safety and the medicolegal climate, promotes defensive overdiagnosis; this is likely a major, if not THE major, contributor to the perceived melanoma epidemic, which to some investigators is more pseudo than actual.2-5 Overdiagnosis, and underdiagnosis, is to be assiduously avoided. Faced with a reality in which a binary diagnosis cannot always be reliably determined, we must endeavor to manage uncertainty in a way that will protect patients and all involved parties.
Without transformative advances in molecular diagnostics, one alternative to forcing binary diagnoses is standardized schemata that stratify intermediate diagnoses by degree of perceived risk and corresponding management. Indeed, this is already what has happened de facto in practice, but in a nonstandardized way that can lead to miscommunication and harm. Our MPATH-Dx (Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis) scheme is a modest proposal to manage uncertainty created by lesions that are neither conclusively benign nor malignant. It will be important to obtain consensus and appropriate modifications of our schema from the community before it is put into practice. Whether such schemata will mitigate the propensity of dermatopathologists to overdiagnose melanocytic lesions as melanoma merits future study.2-5 Michael W. Piepkorn, MD, PhD,a,b Raymond L. Barnhill, MD,c and David E. Elder, MBChB, FRCPAd Division of Dermatology, Department of Medicine, University of Washington School of Medicine, Seattlea; Dermatopathology Northwest, Bellevue, Washingtonb; Department of Pathology and Laboratory Medicine, University of California at Los Angelesc; and Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphiad Funding sources: None. Conflicts of interest: None declared. Correspondence to: Michael W. Piepkorn, MD, PhD, Division of Dermatology, Department of Medicine, University of Washington School of Medicine, Box 356524, Seattle, WA 98195 E-mail: [email protected] REFERENCES 1. Piepkorn MW, Barnhill RL, Elder DE, Knezevich SR, Carney PA, Reisch LM, et al. The MPATH-Dx reporting schema for melanocytic proliferations and melanoma. J Am Acad Dermatol 2014;70:131-41. 2. Criscione VD, Weinstock MA. Melanoma thickness trends in the United States, 1988-2006. J Invest Dermatol 2010;130:793-7. 3. Welch HG, Woloshin S, Schwartz LM. Skin biopsy rates and incidence of melanoma: population based ecological study. BMJ 2005;331:481. 4. Levell NJ, Beattie CC, Shuster S, Greenberg DC. Melanoma epidemic: a midsummer night’s dream? Br J Dermatol 2009; 161:630-4. 5. Frangos JE, Duncan LM, Piris A, Nazarian RM, Mihm MC Jr, Hoang MP, et al. Increased diagnosis of thin superficial spreading melanomas: A 20-year study. J Am Acad Dermatol 2012;67:387-94. http://dx.doi.org/10.1016/j.jaad.2014.05.031
Letters 589
VOLUME 71, NUMBER 3
lesions require no margin for complete excision. Malignant lesions should be excised with margins that completely remove the visible lesion along with any subclinical extension. This concept has shaped the accepted surgical margin of 1 cm for most melanomas. There is no intermediate margin for lesions of uncertain behavior, or for diagnostic ambiguity. Clinicians are faced with 2 options: no further treatment, as for a benign lesion; or to treat as if malignant. If we excise a lesion for disagreement among pathologists in classification as benign or malignant, it is an all-or-none margin, but not in between. Landon E. Stigall, MD, and John A. Zitelli, MD University of Pittsburgh Medical Center, and Zitelli & Brodland PC, Pittsburgh, Pennsylvania Funding sources: None. Conflicts of interest: None declared. Correspondence to: Landon E. Stigall, MD, Zitelli & Brodland PC, 5200 Centre Ave, Suite 303, Pittsburgh, PA 15232 E-mail: [email protected] REFERENCES 1. Piepkorn MW, Barnhill RL, Elder DE, Knezevich SR, Carney PA, Reisch LM, et al. The MPATH-Dx reporting schema for melanocytic proliferations and melanoma. J Am Acad Dermatol 2014;70:131-41. 2. Comfere N, Chakraborty R, Peters M. Margin comments in dermatopathology reports on dysplastic nevi influence re-excision rates. J Am Acad Dermatol 2013;69:687-92. http://dx.doi.org/10.1016/j.jaad.2014.04.073
Reply to ‘Surgical margins for possibly malignant melanocytic lesions’ To the Editor: We would like to thank Drs Stigall and Zitelli for their perspective on the management of melanocytic lesions, with reference to our study, ‘‘Margin comments in dermatopathology reports on dysplastic nevi influence re-excision rates.’’1 We applaud efforts by Piepkorn et al2 to develop a set of standardized diagnostic risk groups and corresponding treatment recommendations. However, interobserver agreement in histopathological diagnoses of melanocytic proliferations continues to be a major problem,3 because of multiple factors including the nature of the specimen submitted (partial vs complete samples) and unquantifiable tendency of pathologists to modify histopathological interpretations, including upgrading of atypia, depending on their experience with the clinical consequences of their reports. Thus, although
the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) scheme and the 2-tiered management proposal of Drs Stigall and Zitelli are valuable endeavors in the right direction, a major limitation is partial biopsy specimens: even if interobserver variability is improved, the MPATH-Dx or any other diagnostic scheme cannot surmount the justifiable influence of incomplete biopsy on how pathologists formulate their diagnoses and recommendations. A simplified scheme that only considers benign or malignant diagnoses does not fully address the need for re-excision of partially sampled lesions,4 given the known heterogeneity of melanocytic lesions,5 and does not offer specific recommendations for such scenarios. Therefore, although standardized 2-tiered (benign vs malignant) treatment recommendations are the most desirable direction, unless and until the ambiguities, poor reproducibility, and risks associated with partial samples that currently characterize diagnosis of melanocytic lesions are resolved, attempts to develop prognostic subgroups will be problematic. Thus, the recommendation of Drs Stigall and Zitelli that ‘‘benign lesions require no margin for complete excision’’ is correct in theory but ignores the practical reality that many ‘‘benign’’ lesions are incompletely removed and, as Elston et al6 so succinctly summarized, ‘‘one dermatopathologist’s moderately atypical nevus may be another’s melanoma.’’ Diagnostic uncertainty begets therapeutic ambiguity, hence the need for specific recommendations to guide clinicians. Given this current state of the art, complete biopsy with distinct margin of normal-appearing skin is needed to protect patients against the risks inherent in diagnostic uncertainty. Nneka I. Comfere, MD, and Margot S. Peters, MD Departments of Dermatology and Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota Funding sources: None. Conflicts of interest: None declared. Correspondence to: Nneka I. Comfere, MD, Department of Dermatology, Mayo Clinic, 200 First St SW, Rochester, MN 55905 E-mail: [email protected]
REFERENCES 1. Comfere N, Chakraborty R, Peters M. Margin comments in dermatopathology reports on dysplastic nevi influence re-excision rates. J Am Acad Dermatol 2013;69:687-92. 2. Piepkorn MW, Barnhill RL, Elder DE, Knezevich SR, Carney PA, Reisch LM, et al. The MPATH-Dx reporting schema for
J AM ACAD DERMATOL
590 Letters
3.
4.
5.
6.
SEPTEMBER 2014
melanocytic proliferations and melanoma. J Am Acad Dermatol 2014;70:131-41. Brochez L, Verhaeghe E, Grosshans E, Haneke E, Pierard G, Ruiter D, et al. Inter-observer variation in the histopathological diagnosis of clinically suspicious pigmented skin lesions. J Pathol 2002;196:459-66. Hocker TL, Alikhan A, Comfere NI, Peters MS. Favorable long-term outcomes in patients with histologically dysplastic nevi that approach a specimen border. J Am Acad Dermatol 2013;68:545-51. Barr RJ, Linden KG, Rubinstein G, Cantos KA. Analysis of heterogeneity of atypia within melanocytic nevi. Arch Dermatol 2003;139:289-93. Elston D, McNiff J, Maize J Sr. Histologically dysplastic nevi that extend to a specimen border. J Am Acad Dermatol 2013;68:682-3. http://dx.doi.org/10.1016/j.jaad.2014.05.030
Reply: Surgical margins for possibly malignant melanocytic lesions and the overdiagnosis of melanoma To the Editor: We welcome the thoughts of Drs Stigall and Zitelli. Although their remarks could be interpreted in different ways, they seem to take the position that either there is no such thing as an intermediate melanocytic lesion (being simply diagnostic disagreement), or that, if there is, there is no need for an intermediate margin for lesions of uncertain behavior. Either way, we disagree.1 Many choose to believe that melanocytic tumors are either indubitably benign or clearly malignant. Regardless of whether or not a simple binary dichotomy exists as such in nature, the practical reality of histologic diagnosis is less simple. The reliability of histologic diagnosis tends to break down in the gray zone between benign and malignant. The reasons are complex and poorly understood; suffice it to say that criteria differ in sensitivity and specificity, are often subjective, and often have not been vetted to rigorous standards. In short, histologic diagnosis is a crude surrogate for disease biology. Not surprisingly, many, if not most, dermatopathologists who practice long enough will render a false-negative diagnosis from partial biopsy specimen. Sampling limitations, low sensitivity of criteria in ‘‘borderline’’ lesions, observer variability, and ‘‘lives of lesions’’ are potentially contributory. This common experience, in concert with concern for patient safety and the medicolegal climate, promotes defensive overdiagnosis; this is likely a major, if not THE major, contributor to the perceived melanoma epidemic, which to some investigators is more pseudo than actual.2-5 Overdiagnosis, and underdiagnosis, is to be assiduously avoided. Faced with a reality in which a binary diagnosis cannot always be reliably determined, we must endeavor to manage uncertainty in a way that will protect patients and all involved parties.
Without transformative advances in molecular diagnostics, one alternative to forcing binary diagnoses is standardized schemata that stratify intermediate diagnoses by degree of perceived risk and corresponding management. Indeed, this is already what has happened de facto in practice, but in a nonstandardized way that can lead to miscommunication and harm. Our MPATH-Dx (Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis) scheme is a modest proposal to manage uncertainty created by lesions that are neither conclusively benign nor malignant. It will be important to obtain consensus and appropriate modifications of our schema from the community before it is put into practice. Whether such schemata will mitigate the propensity of dermatopathologists to overdiagnose melanocytic lesions as melanoma merits future study.2-5 Michael W. Piepkorn, MD, PhD,a,b Raymond L. Barnhill, MD,c and David E. Elder, MBChB, FRCPAd Division of Dermatology, Department of Medicine, University of Washington School of Medicine, Seattlea; Dermatopathology Northwest, Bellevue, Washingtonb; Department of Pathology and Laboratory Medicine, University of California at Los Angelesc; and Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphiad Funding sources: None. Conflicts of interest: None declared. Correspondence to: Michael W. Piepkorn, MD, PhD, Division of Dermatology, Department of Medicine, University of Washington School of Medicine, Box 356524, Seattle, WA 98195 E-mail: [email protected] REFERENCES 1. Piepkorn MW, Barnhill RL, Elder DE, Knezevich SR, Carney PA, Reisch LM, et al. The MPATH-Dx reporting schema for melanocytic proliferations and melanoma. J Am Acad Dermatol 2014;70:131-41. 2. Criscione VD, Weinstock MA. Melanoma thickness trends in the United States, 1988-2006. J Invest Dermatol 2010;130:793-7. 3. Welch HG, Woloshin S, Schwartz LM. Skin biopsy rates and incidence of melanoma: population based ecological study. BMJ 2005;331:481. 4. Levell NJ, Beattie CC, Shuster S, Greenberg DC. Melanoma epidemic: a midsummer night’s dream? Br J Dermatol 2009; 161:630-4. 5. Frangos JE, Duncan LM, Piris A, Nazarian RM, Mihm MC Jr, Hoang MP, et al. Increased diagnosis of thin superficial spreading melanomas: A 20-year study. J Am Acad Dermatol 2012;67:387-94. http://dx.doi.org/10.1016/j.jaad.2014.05.031
