- Email: [email protected]
Abnormal intrinsic brain activity patterns in leukoaraiosis with and without cognitive impairment
J AM ACAD DERMATOL
Letters 313
VOLUME 73, NUMBER 2
calibration, or processing software—all of which which are needed for spectrophotometry. This tool can be used for both adults and children with limited literacy, and therefore populations can be screened for individuals with skin cancer risk and identify those needing sun protection.
Fig 1. Color bar survey item. The participant selected the color bar that most closely matched the skin tone on the inside part of their upper arm.
descriptions (R2 ¼ 0.867; P \.0001), and Fitzpatrick sunburn propensity (R2 ¼ 0.879; P\.04). For the FST tan/darker response data, a binomial fit performed best with R2 of 0.963 compared to R2 of 0.236 for a linear model (P ¼ .6). Among this ethnically heterogeneous population, people reliably self-selected color bars as assessed by melanin index. Responses to the color bars displayed the strongest linear relationship among the survey items, with means evenly covering the range of melanin indices found in our study population. While ultraviolet radiation (UVR)erelated skin cell damage correlates linearly with skin tone, UVR is linked to DNA damage across skin types.3 Race/ ethnicity is a poor proxy for skin cancer risk because members of racial/ethnic minority groups might have individual risk factors for skin cancer (eg, lighter skin, skin that sunburns easily). In our research, the colors bars allowed discrimination between the 6 groups, and the colors correlated with melanin index and with the individual’s potential to have sunburn/skin irritation. Stern and Momtaz4 established that individuals with FSTs I and II had a greater skin cancer risk than those with FSTs III and IV. Because responses to the adapted FST discriminate among the 6 categories for all races/ethnicities, Stern and Momtaz’s work can be extended to associating high skin cancer risk with FSTs I and II, medium risk with FSTs III and IV, and low risk with FSTs V and VI. Participants understood that survey items were either explicitly or implicitly related to their skin color, and therefore cultural bias related to a preference for being either lighter or darker may have affected our results. These preferences among different ethnic groups—particularly NHBs, have been well-documented.5 Any attempt to categorize skin cancer risk by skin tone will need to be cognizant of possible shifting subconscious racial biases. Our novel, easy to use color bar tool is economical and does not need a power source,
The color bar inter- and intrarater reliability statistical analyses were performed by Mary J. Kwasny, ScD, who also consulted to the analysis of the quantitative comparisons.
Byron K. Ho and June K Robinson, MD Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois Supported by a National Cancer Institute grant (R21 CA-173196) to Dr Robinson. Conflicts of interest: None declared. Correspondence to: June K. Robinson, MD, Department of Dermatology, Northwestern University Feinberg School of Medicine, 676 St Clair St, Ste 1260, Chicago, IL 60611 E-mail: [email protected] REFERENCES 1. Rampen FH, Fleuren BA, de Boo TM, Lemmens WA. Unreliability of self-reported burning tendency and tanning ability. Arch Dermatol. 1988;124:885-888. 2. Eilers S, Bach DQ, Gaber R, et al. Accuracy of self-report in assessing Fitzpatrick skin phototypes I through VI. JAMA Dermatol. 2013;149:1289-1294. 3. Tadokoro T, Kobayashi N, Zmudzka BZ, et al. UV-induced DNA damage and melanin content in human skin differing in racial/ethnic origin. FASEB J. 2003;17:1177-1179. 4. Stern RS, Momtaz K. Skin typing for assessment of skin cancer risk and acute response to UV-B and oral methoxsalen photochemotherapy. Arch Dermatol. 1984;120:869-873. 5. Hochschild JL, Weaver V. The skin color paradox and the American racial order. Social Forces. 2007;86:643-670. http://dx.doi.org/10.1016/j.jaad.2015.05.024
Biopsies of the acral extremities: Assessing specimen (in)adequacy based on anatomic site To the Editor: Cutaneous biopsies are invaluable tools for the accurate diagnosis and treatment of skin disease in dermatologic practice. Nondiagnostic biopsy specimens as a result of inadequate sampling may cause unnecessary patient anxiety, office visits, follow-up procedures, and pathology fees and, unfortunately, are a frequent occurrence in histopathologic evaluation.1-3 The purpose of this study is to identify associations, if any, between acral sites and frequency of inadequate biopsy specimens to guide clinicians who perform these procedures.
J AM ACAD DERMATOL
314 Letters
AUGUST 2015
Fig 1. ‘‘Inadequate’’ biopsy specimens. A, Keratin, no pathologic diagnosis. B, Hypertrophic actinic keratosis, base not visualized (cannot exclude invasive squamous cell carcinoma).
Table I. Summary of inadequate biopsy specimens from acral and nonacral sites Biopsy specimen type
Cannot exclude invasive disease
Total no. (%)
42 2 44
58 0 58
100 (11.6) 2 (0.2) 102 (11.8)
10 0 10
24 0 24
34 (3.9) 0 (0) 34 (3.9)
Nondiagnostic
Acral extremities Shave Punch Total Nonacral sites Shave Punch Total
In all, 865 consecutive cutaneous biopsy specimens from the acral extremities and 864 consecutive biopsy specimens from all other sites were reviewed in our institution. Only shave and punch biopsies were included, and specimens without a specified anatomic site or those on which an alopecia protocol was performed were excluded. Full spectrums of both inflammatory and neoplastic processes were represented by both groups. The main outcome measure was whether or not the biopsy specimen established a definitive diagnosis. An ‘‘inadequate’’ biopsy specimen was defined as one in which no pathologic diagnosis could be given or where invasive disease could not be excluded or confirmed (Fig 1). In many cases, the clinician provided information indicating that the biopsy was performed for this latter purpose (eg, ‘‘hypertrophic actinic keratosis, rule out squamous cell carcinoma’’). Given the prior observation that invasive disease may be found on additional sections,4 in all cases in which no diagnosis could be given or in which invasive disease could not be excluded on initial sections, additional step sections were performed. Of the 865 specimens from the acral extremities, 102 (11.8%) specimens were inadequate (Table I). Of these, a total of 44 (43.1%) yielded no pathologic diagnosis, whereas 58 (56.9%) represented
specimens in which invasive disease could not be excluded nor confirmed. In contrast, 34 of 864 (3.9%) specimens from nonacral sites were determined to be inadequate. Ten (29.4%) yielded no pathologic diagnosis, and the remaining 24 (70.6%) specimens represented those in which invasive disease could not be excluded. In sum, acral biopsies were more likely to yield an inadequate specimen compared with other sites (P \ .0001, odds ratio ¼ 3.23). Lesions in which a keratinocytic process was suspected by the clinician appear to be overrepresented in specimens that were determined to be inadequate: although keratinocytic neoplasms composed 946 of 1729 (54.7%) of all biopsy specimens examined, they made up 116 of 136 (85.3%) of all inadequate specimens. Site-associated sampling differences may partially reflect physiologic differences in stratum corneum thickness between acral and nonacral sites,5 and a higher proportion of keratinizing neoplasms occurring on acral extremities compared with nonacral sites. Both of these factors lend to a clinical impression that adequate tissue is being obtained, but because of the degree of overlying keratin, the depth may not be sufficient to yield diagnostic results. Deeper biopsies of acral neoplasms in which a keratinizing process is suspected may yield better outcomes with decreased frequency of inadequate specimens. Because punch biopsies made up only 12.3% of all specimens in our study, there are not enough data to conclude whether improvements can be achieved through increased use of punch biopsy in this setting, or through adaptations to the shave biopsy approach (eg, saucerization). Catherine G. Chung, MD,a,b Eric E. Jung, BS,c and Klaus F. Helm, MDa,b Departments of Pathologya and Dermatology,b Penn State Hershey Medical Center, and Penn State University College of Medicine,c Hershey
J AM ACAD DERMATOL VOLUME 73, NUMBER 2
Funding sources: None. Conflicts of interest: None declared. Presented as a poster at the American Society of Dermatopathology Annual Meeting in Chicago, Illinois, on November 6-9, 2014. Correspondence to: Catherine G. Chung, MD, Department of Dermatology, HU17, Penn State Hershey Medical Center, 500 University Dr, PO Box 850, Hershey, PA 17033 E-mail: [email protected] REFERENCES 1. Sellheyer K, Nelson P, Bergfeld WF. Nonspecific histopathological diagnoses: the impact of partial biopsy and the need for a consensus guideline. JAMA Dermatol. 2014;150(1): 11-12. 2. Phelps RG, Lebwohl MG. Biopsy techniques: shave, punch, or excision? JAMA Dermatol. 2014;150(1):12-13. 3. Fernandez EM, Helm T, Ioffreda MD, Helm KF. The vanishing biopsy: the trend toward smaller specimens. Cutis. 2005;76: 335-339. 4. Carag HR, Prieto VG, Yballe LS, Shea CR. Utility of step sections: demonstration of additional pathological findings in biopsy samples initially diagnosed as actinic keratosis. Arch Dermatol. 2000;136:471-475. 5. Ya-Xian Z, Suetake T, Tagami H. Number of cell layers of the stratum corneum in normal skinerelationship to the anatomical location on the body, age, sex, and physical parameters. Arch Dermatol Res. 1999;291:555-559. http://dx.doi.org/10.1016/j.jaad.2015.04.022
Optical coherence tomography (OCT) features of nevi and melanomas and their association with intraepidermal or dermal involvement: A pilot study To the Editor: Optical coherence tomography (OCT) was shown to be an useful tool for the fast evaluation of nonmelanocytic tumors of the skin.1 There are few reports in the literature studying melanocytic lesions with OCT, with variable and sometimes contrasting results.2,3 A constant need for reducing costs and cosmetic concerns of unnecessary excisions of suspicious melanocytic lesions lead us to further investigate this new technology.4 We used OCT (Vivosight OCT Scanner, Michelson Diagnostics Ltd, Orpington, Kent, United Kingdom) to evaluate a total of 39 lesions: 19 melanomas (10 in situ and 9 invasive, with Breslow thickness \1 mm), 15 compound nevi, and 5 junctional nevi. No lesions from palms, soles, and mucosal areas were included because of the peculiarity of skin anatomy in these areas. Our first goal was to design a pattern of findings in melanocytic lesions on OCT. Secondly,
Letters 315
we aimed to explore the correlation between histopathology and OCT features through the evaluation of skin compartments, and to assess its significance in the diagnosis of melanoma. One image sequence (60 per lesion) belonging to each case was selected for assessment. Two evaluators, an experienced dermatologist in imaging in dermatology (T. C. M. P. B.) and a radiologist (M. P. C.), independently analyzed the lesions regarding the OCT features. Eleven features present in the epidermis, dermoepidermal junction, and dermis were separately evaluated, including criteria previously identified in the literature for melanocytic lesions, and newly described features (Figs 1 and 2).3,5 Findings were finally analyzed by both evaluators for all lesions and binarized as present or absent in agreement. The histopathology study first categorized melanocytic lesions as melanoma in situ, invasive melanoma, junctional nevus, or compound nevus. Anatomical compartment of tumor proliferation was reported as intraepidermal ( for in situ melanoma and junctional nevi), and within the dermis ( for invasive melanomas and compound nevi). Statistical analysis was carried out using software (SPSS, Release 20.0.0, IBM Corp, Armonk, NY). Absolute and relative frequencies were calculated. Fisher’s exact test was used to evaluate the differences in OCT features between nevi and melanoma. The significance level was set at 5% (P \ .05) (Table I). The presence of shadows correlated significantly with in situ melanoma (8 in 10 cases, P ¼ .007). Shadows and loss of bright collagen correlated with invasive melanoma, compared with compound nevi (P ¼ .002 and P \.001). Hyporeflective band was associated with compound nevi (80%), and less frequently found in melanomas (31.5%, P ¼ .007). Concerning the distinction between melanomas and nevi, the presence of dermal shadows and absence of bright collagen were the most relevant parameters to suggest malignancy. The lack of hyporeflective bands on invasive melanomas represented a distinguishing feature from compound nevi. To understand the value of OCT in the diagnosis of melanoma a larger population should be tested. We can hypothesize that OCT may help to define the tumor burden and eventual dermal infiltration of melanocytic tumors, which could influence the choice of surgical procedure between shaving or complete excision of clinically suspicious lesions. The study was approved by the institutional review board (Committee of Ethics in Research,
Letters 313
VOLUME 73, NUMBER 2
calibration, or processing software—all of which which are needed for spectrophotometry. This tool can be used for both adults and children with limited literacy, and therefore populations can be screened for individuals with skin cancer risk and identify those needing sun protection.
Fig 1. Color bar survey item. The participant selected the color bar that most closely matched the skin tone on the inside part of their upper arm.
descriptions (R2 ¼ 0.867; P \.0001), and Fitzpatrick sunburn propensity (R2 ¼ 0.879; P\.04). For the FST tan/darker response data, a binomial fit performed best with R2 of 0.963 compared to R2 of 0.236 for a linear model (P ¼ .6). Among this ethnically heterogeneous population, people reliably self-selected color bars as assessed by melanin index. Responses to the color bars displayed the strongest linear relationship among the survey items, with means evenly covering the range of melanin indices found in our study population. While ultraviolet radiation (UVR)erelated skin cell damage correlates linearly with skin tone, UVR is linked to DNA damage across skin types.3 Race/ ethnicity is a poor proxy for skin cancer risk because members of racial/ethnic minority groups might have individual risk factors for skin cancer (eg, lighter skin, skin that sunburns easily). In our research, the colors bars allowed discrimination between the 6 groups, and the colors correlated with melanin index and with the individual’s potential to have sunburn/skin irritation. Stern and Momtaz4 established that individuals with FSTs I and II had a greater skin cancer risk than those with FSTs III and IV. Because responses to the adapted FST discriminate among the 6 categories for all races/ethnicities, Stern and Momtaz’s work can be extended to associating high skin cancer risk with FSTs I and II, medium risk with FSTs III and IV, and low risk with FSTs V and VI. Participants understood that survey items were either explicitly or implicitly related to their skin color, and therefore cultural bias related to a preference for being either lighter or darker may have affected our results. These preferences among different ethnic groups—particularly NHBs, have been well-documented.5 Any attempt to categorize skin cancer risk by skin tone will need to be cognizant of possible shifting subconscious racial biases. Our novel, easy to use color bar tool is economical and does not need a power source,
The color bar inter- and intrarater reliability statistical analyses were performed by Mary J. Kwasny, ScD, who also consulted to the analysis of the quantitative comparisons.
Byron K. Ho and June K Robinson, MD Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois Supported by a National Cancer Institute grant (R21 CA-173196) to Dr Robinson. Conflicts of interest: None declared. Correspondence to: June K. Robinson, MD, Department of Dermatology, Northwestern University Feinberg School of Medicine, 676 St Clair St, Ste 1260, Chicago, IL 60611 E-mail: [email protected] REFERENCES 1. Rampen FH, Fleuren BA, de Boo TM, Lemmens WA. Unreliability of self-reported burning tendency and tanning ability. Arch Dermatol. 1988;124:885-888. 2. Eilers S, Bach DQ, Gaber R, et al. Accuracy of self-report in assessing Fitzpatrick skin phototypes I through VI. JAMA Dermatol. 2013;149:1289-1294. 3. Tadokoro T, Kobayashi N, Zmudzka BZ, et al. UV-induced DNA damage and melanin content in human skin differing in racial/ethnic origin. FASEB J. 2003;17:1177-1179. 4. Stern RS, Momtaz K. Skin typing for assessment of skin cancer risk and acute response to UV-B and oral methoxsalen photochemotherapy. Arch Dermatol. 1984;120:869-873. 5. Hochschild JL, Weaver V. The skin color paradox and the American racial order. Social Forces. 2007;86:643-670. http://dx.doi.org/10.1016/j.jaad.2015.05.024
Biopsies of the acral extremities: Assessing specimen (in)adequacy based on anatomic site To the Editor: Cutaneous biopsies are invaluable tools for the accurate diagnosis and treatment of skin disease in dermatologic practice. Nondiagnostic biopsy specimens as a result of inadequate sampling may cause unnecessary patient anxiety, office visits, follow-up procedures, and pathology fees and, unfortunately, are a frequent occurrence in histopathologic evaluation.1-3 The purpose of this study is to identify associations, if any, between acral sites and frequency of inadequate biopsy specimens to guide clinicians who perform these procedures.
J AM ACAD DERMATOL
314 Letters
AUGUST 2015
Fig 1. ‘‘Inadequate’’ biopsy specimens. A, Keratin, no pathologic diagnosis. B, Hypertrophic actinic keratosis, base not visualized (cannot exclude invasive squamous cell carcinoma).
Table I. Summary of inadequate biopsy specimens from acral and nonacral sites Biopsy specimen type
Cannot exclude invasive disease
Total no. (%)
42 2 44
58 0 58
100 (11.6) 2 (0.2) 102 (11.8)
10 0 10
24 0 24
34 (3.9) 0 (0) 34 (3.9)
Nondiagnostic
Acral extremities Shave Punch Total Nonacral sites Shave Punch Total
In all, 865 consecutive cutaneous biopsy specimens from the acral extremities and 864 consecutive biopsy specimens from all other sites were reviewed in our institution. Only shave and punch biopsies were included, and specimens without a specified anatomic site or those on which an alopecia protocol was performed were excluded. Full spectrums of both inflammatory and neoplastic processes were represented by both groups. The main outcome measure was whether or not the biopsy specimen established a definitive diagnosis. An ‘‘inadequate’’ biopsy specimen was defined as one in which no pathologic diagnosis could be given or where invasive disease could not be excluded or confirmed (Fig 1). In many cases, the clinician provided information indicating that the biopsy was performed for this latter purpose (eg, ‘‘hypertrophic actinic keratosis, rule out squamous cell carcinoma’’). Given the prior observation that invasive disease may be found on additional sections,4 in all cases in which no diagnosis could be given or in which invasive disease could not be excluded on initial sections, additional step sections were performed. Of the 865 specimens from the acral extremities, 102 (11.8%) specimens were inadequate (Table I). Of these, a total of 44 (43.1%) yielded no pathologic diagnosis, whereas 58 (56.9%) represented
specimens in which invasive disease could not be excluded nor confirmed. In contrast, 34 of 864 (3.9%) specimens from nonacral sites were determined to be inadequate. Ten (29.4%) yielded no pathologic diagnosis, and the remaining 24 (70.6%) specimens represented those in which invasive disease could not be excluded. In sum, acral biopsies were more likely to yield an inadequate specimen compared with other sites (P \ .0001, odds ratio ¼ 3.23). Lesions in which a keratinocytic process was suspected by the clinician appear to be overrepresented in specimens that were determined to be inadequate: although keratinocytic neoplasms composed 946 of 1729 (54.7%) of all biopsy specimens examined, they made up 116 of 136 (85.3%) of all inadequate specimens. Site-associated sampling differences may partially reflect physiologic differences in stratum corneum thickness between acral and nonacral sites,5 and a higher proportion of keratinizing neoplasms occurring on acral extremities compared with nonacral sites. Both of these factors lend to a clinical impression that adequate tissue is being obtained, but because of the degree of overlying keratin, the depth may not be sufficient to yield diagnostic results. Deeper biopsies of acral neoplasms in which a keratinizing process is suspected may yield better outcomes with decreased frequency of inadequate specimens. Because punch biopsies made up only 12.3% of all specimens in our study, there are not enough data to conclude whether improvements can be achieved through increased use of punch biopsy in this setting, or through adaptations to the shave biopsy approach (eg, saucerization). Catherine G. Chung, MD,a,b Eric E. Jung, BS,c and Klaus F. Helm, MDa,b Departments of Pathologya and Dermatology,b Penn State Hershey Medical Center, and Penn State University College of Medicine,c Hershey
J AM ACAD DERMATOL VOLUME 73, NUMBER 2
Funding sources: None. Conflicts of interest: None declared. Presented as a poster at the American Society of Dermatopathology Annual Meeting in Chicago, Illinois, on November 6-9, 2014. Correspondence to: Catherine G. Chung, MD, Department of Dermatology, HU17, Penn State Hershey Medical Center, 500 University Dr, PO Box 850, Hershey, PA 17033 E-mail: [email protected] REFERENCES 1. Sellheyer K, Nelson P, Bergfeld WF. Nonspecific histopathological diagnoses: the impact of partial biopsy and the need for a consensus guideline. JAMA Dermatol. 2014;150(1): 11-12. 2. Phelps RG, Lebwohl MG. Biopsy techniques: shave, punch, or excision? JAMA Dermatol. 2014;150(1):12-13. 3. Fernandez EM, Helm T, Ioffreda MD, Helm KF. The vanishing biopsy: the trend toward smaller specimens. Cutis. 2005;76: 335-339. 4. Carag HR, Prieto VG, Yballe LS, Shea CR. Utility of step sections: demonstration of additional pathological findings in biopsy samples initially diagnosed as actinic keratosis. Arch Dermatol. 2000;136:471-475. 5. Ya-Xian Z, Suetake T, Tagami H. Number of cell layers of the stratum corneum in normal skinerelationship to the anatomical location on the body, age, sex, and physical parameters. Arch Dermatol Res. 1999;291:555-559. http://dx.doi.org/10.1016/j.jaad.2015.04.022
Optical coherence tomography (OCT) features of nevi and melanomas and their association with intraepidermal or dermal involvement: A pilot study To the Editor: Optical coherence tomography (OCT) was shown to be an useful tool for the fast evaluation of nonmelanocytic tumors of the skin.1 There are few reports in the literature studying melanocytic lesions with OCT, with variable and sometimes contrasting results.2,3 A constant need for reducing costs and cosmetic concerns of unnecessary excisions of suspicious melanocytic lesions lead us to further investigate this new technology.4 We used OCT (Vivosight OCT Scanner, Michelson Diagnostics Ltd, Orpington, Kent, United Kingdom) to evaluate a total of 39 lesions: 19 melanomas (10 in situ and 9 invasive, with Breslow thickness \1 mm), 15 compound nevi, and 5 junctional nevi. No lesions from palms, soles, and mucosal areas were included because of the peculiarity of skin anatomy in these areas. Our first goal was to design a pattern of findings in melanocytic lesions on OCT. Secondly,
Letters 315
we aimed to explore the correlation between histopathology and OCT features through the evaluation of skin compartments, and to assess its significance in the diagnosis of melanoma. One image sequence (60 per lesion) belonging to each case was selected for assessment. Two evaluators, an experienced dermatologist in imaging in dermatology (T. C. M. P. B.) and a radiologist (M. P. C.), independently analyzed the lesions regarding the OCT features. Eleven features present in the epidermis, dermoepidermal junction, and dermis were separately evaluated, including criteria previously identified in the literature for melanocytic lesions, and newly described features (Figs 1 and 2).3,5 Findings were finally analyzed by both evaluators for all lesions and binarized as present or absent in agreement. The histopathology study first categorized melanocytic lesions as melanoma in situ, invasive melanoma, junctional nevus, or compound nevus. Anatomical compartment of tumor proliferation was reported as intraepidermal ( for in situ melanoma and junctional nevi), and within the dermis ( for invasive melanomas and compound nevi). Statistical analysis was carried out using software (SPSS, Release 20.0.0, IBM Corp, Armonk, NY). Absolute and relative frequencies were calculated. Fisher’s exact test was used to evaluate the differences in OCT features between nevi and melanoma. The significance level was set at 5% (P \ .05) (Table I). The presence of shadows correlated significantly with in situ melanoma (8 in 10 cases, P ¼ .007). Shadows and loss of bright collagen correlated with invasive melanoma, compared with compound nevi (P ¼ .002 and P \.001). Hyporeflective band was associated with compound nevi (80%), and less frequently found in melanomas (31.5%, P ¼ .007). Concerning the distinction between melanomas and nevi, the presence of dermal shadows and absence of bright collagen were the most relevant parameters to suggest malignancy. The lack of hyporeflective bands on invasive melanomas represented a distinguishing feature from compound nevi. To understand the value of OCT in the diagnosis of melanoma a larger population should be tested. We can hypothesize that OCT may help to define the tumor burden and eventual dermal infiltration of melanocytic tumors, which could influence the choice of surgical procedure between shaving or complete excision of clinically suspicious lesions. The study was approved by the institutional review board (Committee of Ethics in Research,