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Health professionals have jobs that are inherently stressful and most have had little opportunity or encouragement to focus on self-care. Over the past 10 years, professional development programs such as the 'Courage to Teach' have been developed for teachers in primary and secondary schools. Reported outcomes include personal and professional growth, increased satisfaction and well-being, and renewed passion and commitment for teaching. Based on this model of transformational professional development, a program was developed for health professionals, the Inner Life Renewal Program. Four cohorts of health professionals have completed the program. This brief report provides descriptive information regarding the structure, format, and process of the program and evaluative data based on program evaluations and participant interviews. Outcomes reported by participants include an increase in self-awareness, improved listening skills and relationships with colleagues, and an increased ability to manage or cope with stress. [ABSTRACT FROM AUTHOR]

Context.--Slide review has been advocated as a means to reduce diagnostic error in surgical pathology and is considered an important component of a total quality assurance program. Blinded review is an unbiased method of error detection, and this approach may be used to determine the diagnostic discrepancy rates in surgical pathology. Objective.--To determine the diagnostic discrepancy rate for skin biopsies reported by general pathologists. Design.--Five hundred eighty-nine biopsies from 500 consecutive cases submitted by primary care physicians and reported by general pathologists were examined by rapid-screen, blinded review by 2 dermatopathologists, and the original diagnosis was compared with the review interpretation. Results.--Agreement was observed in 551 (93.5%) of 589 biopsies. Blinded review of these skin biopsies by experienced dermatopathologists had a sensitivity of 100% (all lesions originally reported were detected during review). False-negative errors were the most common discrepancy, but false positives, threshold discrepancies, and differences in type or grade were also observed. Only 1.4% of biopsies had discrepancies that were of potential clinical importance. Conclusions.--Blinded review demonstrates that general pathologists reporting skin biopsies submitted by primary care physicians have a low diagnostic error rate. The method detects both false-negative and false-positive cases and identifies problematic areas that may be targeted in continuing education activities. Blinded review is a useful component of a dermatopathology quality improvement program. [ABSTRACT FROM AUTHOR]

Improvisation represents the spontaneous and real-time conception and execution of a novel response to an unanticipated situation. In order to benefit from the positive safety potential of this phenomenon, it is necessary to understand what influences its appropriateness and effectiveness. This study has applied the system-based methodology Impromaps to analysing accounts of improvisation aimed at mitigating adverse safety outcomes. These accounts were obtained from led outdoor activity (LOA) leaders through critical decision method interviews. Influencing factors and interactions have been identified across all system levels. The factors most influential to leaders' ability to improvise are 'Policy, procedures and rules', 'Organisation culture', 'Training', 'Role responsibilities', 'Communication/instruction/demonstration', 'Situation awareness', 'Leader experience', 'Mental simulation', 'Equipment, clothing & PPE' and 'Terrain/physical environment'. To enhance the likelihood of effective, appropriate improvisation, LOA providers are recommended to focus on higher level factors over which they are able to exert greater control. Practitioner Summary: To enhance resilience in safety-critical situations, organisations need to understand what influences appropriate, effective improvisation. To elucidate this, the Impromaps methodology is applied to in-depth interview data. The Impromap affords a graphical depiction of the influencing factors and interactions across the system, providing a basis for the development of interventions.

Context: -Dermatologists and subspecialty dermatopathologists, working together over many years, develop a common understanding of clinical information provided on the requisition and of terminology used in the pathology report. Challenges arise for pathologists without additional subspecialty training in dermatology/dermatopathology, and for any pathologist reporting skin biopsies for nondermatologists such as general practitioners or surgeons., Objective: -To provide practical strategies to improve efficiency of dermatopathology sign-out, at the same time providing the clinician with clear diagnostic and prognostic information to guide patient management., Data Sources: -The information outlined in this review is based on our own experiences with routine dermatopathology and dermatology practice, and review of English-language articles related to the selected topics discussed., Conclusions: -Using generic diagnoses for some benign lesions, listing pertinent negatives in the pathology report, and using logical risk management strategies when reporting on basal cell carcinoma, partial biopsies, or specimens with incomplete clinical information allow the pathologist to convey relevant and useful diagnostic information to the treating clinician.

Cellular blue nevomelanocytic lesions (CBNLs) frequently pose diagnostic problems to pathologists, and their biological potential may be difficult to establish. In this study, the authors have analyzed the clinical, histological, and outcome data of 37 cellular blue nevomelanocytic lesions and the molecular characteristics of 4 lesions. The cohort of cases comprised 8 cellular blue nevi (CBNs), 17 atypical cellular blue nevi (ACBNs), and 12 blue-nevus-like melanomas (BNLMs) with a mean follow-up of 5 years. The average age at diagnosis was 25.9 years for patients with ACBN, versus 30.4 years for CBN, and 44.6 years for BNLM. Both CBN and ACBN occurred most frequently on the trunk or extremities, whereas BNLM primarily involved the scalp. Histologically, CBN and ACBN were characterized by a mean diameter of <1 cm, absence of necrosis, low mitotic rate (mean: 1-2 mitotic figures/mm), little or no infiltrative properties, and usually low-grade cytologic atypia. In contrast, BNLM had a mean diameter of 1.6 cm, necrosis, tissue infiltration, greater mitotic activity (mean: 6 mitotic figures/mm), and high-grade cytologic atypia. ACBNs often were larger, more densely cellular, exhibited higher mitotic counts, and were cytologically more atypical than CBN. Seven CBN cases with follow-up had a benign clinical course (average follow-up of 4.7 years). Among 6 patients with ACBN who underwent sentinel lymph node (SLN) biopsy, 3 were positive, and a single additional case had 1 positive non-SLN (this patient did not have a SLN biopsy performed). All 14 cases of ACBN with follow-up were alive and without recurrence with mean follow-up of 5 years. Of the 9 melanoma cases with follow-up, 3 patients with SLN and non-SLN involvement died from their disease (average follow-up of 4.8 years). Array comparative genomic hybridization was performed on 2 ACBNs and 1 BNLM: One of the 2 ACBNs showed chromosomal aberrations and 1 BNLM showed multiple chromosomal gains and losses. Multiplex polymerase chain reaction was performed on 1 ACBN, and no mutations were found. From these results, the authors conclude that ACBN occupy an intermediate position within the spectrum of CBN and BNLM, yet many lesions cannot be reliably distinguished from either CBN or BNLM because of overlapping histologic features. However, in general, ACBNs seem to aggregate more closely with CBN in terms of clinical, histological, molecular profile (limited data), and biological behavior.

The study aim was to evaluate the implementation of group- and home-based exercise falls prevention programs delivered through community health agencies to community-dwelling older people. Interviews with program staff were guided by the Diffusion of Innovations theory. Highly consistent themes emerged for the two types of programs. Both had high overall compatibility, high relative advantage, good observability and high inherent trialability--all factors known to strengthen implementation. The level of complexity and low financial compatibility emerged as the strongest potential inhibitors to program implementation in the context examined. The two main factors contributing to complexity were the need to challenge balance safely across a broad range of capability, and practical considerations associated with program delivery. A range of strategies to provide more technical support for exercise program leaders to tailor balance challenge for exercise program leaders may enhance implementation of falls prevention exercise programs.

Background: Drug-induced subacute cutaneous lupus erythematosus is an uncommon disorder associated with the use of pharmacological agents including systemic chemotherapy., Case Presentation: We report a case of docetaxel-induced subacute cutaneous lupus erythematosus in a 60-year-old Caucasian female with Sjögren's syndrome diagnosed 2 months after receiving docetaxel as part of the adjuvant FEC-D (5-fluorouracil, epirubicin, cyclophosphamide, docetaxel) chemotherapy protocol for early stage breast cancer. Although the exact mechanisms behind the autoimmune response elicited by docetaxel are unclear, the involvement of anti-SSA/Ro antibodies has been implicated., Conclusion: This case highlights the symptom severity and clinical course of docetaxel-induced subacute cutaneous lupus erythematosus, and highlights the importance of recognizing this uncommon but potentially severe chemotherapy-associated cutaneous reaction.

Rationale, Aims and Objectives: The extent to which best practice for falls prevention is being routinely delivered by health care providers for community-dwelling older adults is unclear. We investigated falls prevention practice among Hospital Admission Risk Programs (HARP) that provide and coordinate specialized health care for people at high risk of hospitalization., Method: Cross-sectional survey of all HARP services in Victoria, excluding one paediatric programme (n = 34). The questionnaire focused upon medication review and exercise prescription, as these are the evidence-based falls interventions with a good fit with HARP services., Results: Completed questionnaires were received from 24 programmes (70.6%) that service 15,250 older clients (60+ years). All except one programme screened for medicine use; however, a lower proportion (65% of those that screen) target falls risk medications. Among the 17 programmes responding to the exercise prescription question, all routinely include strengthening exercises, and almost all (n = 15) include flexibility, endurance training and movement of the centre of gravity. A lesser proportion (71%) includes reducing the need for upper limb support. The majority of services (88%) undertake falls risk assessments, and all of these either make referral appointments for clients or refer to other services that make referral appointments for clients. Follow-up of appointments and the resulting recommendations was high., Conclusion: Screening for falls risk medications could be improved and staff training in exercise prescription for balance challenge in this high-risk group may be needed. Although evidence-based falls prevention practice within Victorian HARP services appears strong, the effect on falls risk may not be as high as that achieved in randomized trials., (© 2014 John Wiley & Sons, Ltd.)

An accurate and complete pathology report is critical for the optimal management of cutaneous melanoma patients. Protocols for the pathologic reporting of melanoma have been independently developed by the Royal College of Pathologists of Australasia (RCPA), Royal College of Pathologists (United Kingdom) (RCPath), and College of American Pathologists (CAP). In this study, data sets, checklists, and structured reporting protocols for pathologic examination and reporting of cutaneous melanoma were analyzed by an international panel of melanoma pathologists and clinicians with the aim of developing a common, internationally agreed upon, evidence-based data set. The International Collaboration on Cancer Reporting cutaneous melanoma expert review panel analyzed the existing RCPA, RCPath, and CAP data sets to develop a protocol containing "required" (mandatory/core) and "recommended" (nonmandatory/noncore) elements. Required elements were defined as those that had agreed evidentiary support at National Health and Medical Research Council level III-2 level of evidence or above and that were unanimously agreed upon by the review panel to be essential for the clinical management, staging, or assessment of the prognosis of melanoma or fundamental for pathologic diagnosis. Recommended elements were those considered to be clinically important and recommended for good practice but with lesser degrees of supportive evidence. Sixteen core/required data elements for cutaneous melanoma pathology reports were defined (with an additional 4 core/required elements for specimens received with lymph nodes). Eighteen additional data elements with a lesser level of evidentiary support were included in the recommended data set. Consensus response values (permitted responses) were formulated for each data item. Development and agreement of this evidence-based protocol at an international level was accomplished in a timely and efficient manner, and the processes described herein may facilitate the development of protocols for other tumor types. Widespread utilization of an internationally agreed upon, structured pathology data set for melanoma will lead not only to improved patient management but is a prerequisite for research and for international benchmarking in health care.

Immunohistochemistry (IHC) is considered a valuable ancillary tool for dermatopathology diagnosis, but few studies have measured IHC utilization by dermatopathologists or assessed its diagnostic utility. In a regionalized, community-based dermatopathology practice, we measured IHC utilization (total requests, specific antibodies requested, and final diagnosis) over a 12-month period. Next, we assessed diagnostic utility by comparing a preliminary "pre-IHC" diagnosis based on routine histochemical staining with the final diagnosis rendered after consideration of IHC results. The dermatopathology IHC utilization rate was 1.2%, averaging 3.6 stains requested per case. Melanocytic, hematolymphoid, and fibrohistiocytic lesions made up 23%, 18%, and 16%, respectively, of the total cases requiring IHC. S100 and Melan A were the most frequently requested stains, ordered on 50% and 34% of IHC cases, respectively. The utility study revealed that IHC changed the diagnosis in 11%, confirmed a diagnosis, or excluded a differential diagnosis in 77%, and was noncontributory in 4% of cases. Where IHC results prompted a change in diagnosis, 14% were a change from a benign to malignant lesion, whereas 32% changed from one malignant entity to another. IHC is most commonly used in cutaneous melanocytic and hematolymphoid lesions. In 11% of dermatopathology cases in which IHC is used, information is provided that changes the H&E diagnosis. Such changes may have significant treatment implications. IHC is noncontributory in only a small percentage of cases.

The Canadian Medical Association Journal (CMAJ) is a high-impact multidisciplinary medical journal. We have observed instances in which a pathology diagnosis, documented with gross or microscopic images, forms an integral part of a CMAJ article, but a pathologist is neither an author nor acknowledged as a contributor. To examine the hypothesis that pathologist contributions are underrecognized and/or underdocumented, we reviewed all CMAJ articles over a 6-year period (September 2003-2009), and correlated the use of pathology images with pathologist authorship or contribution. For each article containing pathology images, department affiliations of authors were determined, and acknowledgments were assessed. Although only 1.7% of articles contained pathology images, 47% (26/55) of these articles did not include a pathologist as either an author or a contributor. We conclude that important intellectual contributions of pathologists are underrecognized and suggest that the scientific credibility of pathology data is in doubt when pathologists do not take on full responsibility of authorship or are not acknowledged as contributors.

Background: Pemphigus vegetans is a rare variant of pemphigus vulgaris, comprising 1 to 2% of all pemphigus cases. Exposures to oral agents such as captopril and penicillamine and, less commonly, physical or chemical factors have been implicated in the development of pemphigus., Methods: We report a 42-year-old white male with a 12-month history of hypertrophic, vegetative plaques affecting primarily his external nares and upper lips. The patient had a history of alcoholism and intermittent drug abuse, primarily intranasal cocaine, since his youth. He had been using cocaine heavily three to four times/week for 1 month prior to and 1 month following the onset of the eruption but has since ceased use. His clinical features and histopathologic findings were consistent with a diagnosis of pemphigus vegetans. Treatment with high-dose prednisone (80 mg/d) and mycophenolate mofetil (1.5 g/d) resulted in resolution of the lesions after 18 months., Results and Conclusions: To our knowledge, this is the second report proposing an association between intranasal cocaine use and the pemphigus family of disorders. Although the relationship between illicit drug use and the development of pemphigus is unclear, we postulate that intranasal cocaine abuse is operative in our patient's disease. Herein we discuss drug and other external precipitants of pemphigus and review previous case reports of pemphigus associated with illicit drugs.

Primary cutaneous melanoma is treated by excisional surgery and careful histologic assessment of the specimen margins is a crucial component of pathology reporting. Surgical margins may be assessed by conventional transverse (bread-loaf) vertical sections, by en face vertical sections, or by en face oblique sections. Transverse techniques only sample a small percentage of the surgical margin. En face techniques are technically challenging but allow assessment of close to 100% of the margin. Margin assessment for melanoma removed from chronically sun-damaged skin is difficult. Melanoma in situ shows contiguous melanocyte growth, nesting, or intraepidermal pagetoid spread. Pitfalls include solar melanocytic hyperplasia, solar lentigines, melanocytic hyperplasia secondary to previous biopsy, lichenoid reactions, and invasive melanoma mimicking scar or benign nevus. En face sections can be used to assess margins for melanoma on sun-damaged skin, and evidence suggests that frozen sections may also be employed by experienced clinicians. Immunohistochemistry is a useful ancillary technique, enabling more accurate identification of in situ melanoma within a surgical margin., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Interface design is an important factor in assessing the potential effects on safety of interacting with an in-vehicle information system while driving. In the current study, the layout of information on a visual display was manipulated to explore its effect on driving performance in the context of music selection. The comparative effects of an auditory-verbal (cognitive) task were also explored. The driving performance of 30 participants was assessed under both baseline and dual task conditions using the Lane Change Test. Concurrent completion of the music selection task with driving resulted in significant impairment to lateral driving performance (mean lane deviation and percentage of correct lane changes) relative to the baseline, and significantly greater mean lane deviation relative to the combined driving and the cognitive task condition. The magnitude of these effects on driving performance was independent of layout concept, although significant differences in subjective workload estimates and performance on the music selection task across layout concepts highlights that potential uncertainty regarding design use as conveyed through layout concept could be disadvantageous. The implications of these results for interface design and safety are discussed., (Copyright © 2010 Elsevier Ltd and The Ergonomics Society. All rights reserved.)

Immunohistochemistry (IHC) is an important part of the diagnostic work-up in surgical pathology, but the use of IHC in autopsy pathology is poorly defined. We measured IHC utilization by pathologists performing 609 consecutive non-medicolegal, hospital-based, adult autopsies over a three-year period. IHC requests on non-neurologic and neurologic material were analyzed separately. Total stains, number of tissue blocks, specific antibody requests, resident trainee involvement, and ordering pathologist were recorded. For all autopsies on which IHC was requested, the final autopsy report was reviewed. IHC was requested on 345 cases (57%), and a total of 4612 stains were performed (mean 13.5 per autopsy). For non-neurologic autopsy tissues, IHC was used most commonly for the accurate diagnosis of malignancy. For neuropathologic autopsy examinations, IHC was employed most commonly to exclude neurodegenerative conditions and correlate ante-mortem clinical neurologic findings. Resident involvement did not significantly impact utilization. Individual pathologists demonstrated a wide variation in IHC utilization. We conclude that IHC is used extensively in Canadian non-medicolegal autopsy pathology reflecting the complexity, extent, and severity of disease in patients dying in a tertiary-care, academic hospital setting. Utilization is strongly influenced by the neuropathology component of these autopsies. The results provide a point of reference for IHC utilization in autopsy pathology., (Copyright © 2011 Elsevier GmbH. All rights reserved.)

Immunohistochemistry results for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 are used to guide breast carcinoma patient management and it is essential to monitor these tests in external quality assurance (EQA) programs. Canadian Immunohistochemistry Quality Control is a web-based program with novel approach to EQA. Canadian Immunohistochemistry Quality Control RUN2 included tissue microarray slides with 38 samples tested by 18 immunohistochemical laboratories. Deidentified results were posted for viewing at www.ciqc.ca including all used protocols matched with scanned slides for virtual microscopy and garrattograms. Sensitivity, specificity, Kendall W test (concordance between laboratories), and kappa statistics (agreement with designated reference values) were calculated. Kappa values were within the target range (>0.8, or "near perfect" agreement) for 85% results. Kendall coefficient was 0.942 for estrogen receptor, 0.930 for progesterone receptor, and 0.958 for human epidermal growth factor receptor 2. The anonymous participation, quick feedback, and unrestricted full access in EQA results provides rapid insight into technical or interpretive deficiencies, allowing appropriate corrective action to be taken whereas the use of tissue microarrays enables meaningful statistical analysis.

Primary cutaneous melanoma is treated by excisional surgery and careful histologic assessment of the specimen margins is a crucial component of pathology reporting. Surgical margins may be assessed by conventional transverse (bread-loaf) vertical sections, by en face vertical sections, or by en face oblique sections. Transverse techniques only sample a small percentage of the surgical margin. En face techniques are technically challenging but allow assessment of close to 100% of the margin. Margin assessment for melanoma removed from chronically sun-damage skin is difficult. Melanoma in situ shows contiguous melanocyte growth, nesting, or intraepidermal pagetoid spread. Pitfalls include solar melanocytic hyperplasia, solar lentigines, melanocytic hyperplasia secondary to previous biopsy, lichenoid reactions, and invasive melanoma mimicking scar or benign nevus. En face sections can be used to assess margins for melanoma on sun-damaged skin, and evidence suggests that frozen sections may also be employed by experienced clinicians. Immunohistochemistry is a useful ancillary technique, enabling more accurate identification of in situ melanoma within a surgical margin., (Copyright © 2009 Elsevier Inc. All rights reserved.)

Background: Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma and typically affects older adults. It is estimated that less than 5% of MF cases are of juvenile onset. An uncommon hypopigmented variant of MF exists, which has been more commonly observed in dark-skinned individuals and predominantly in juvenile-onset cases., Methods: We describe an 8-year-old otherwise healthy Hispanic male who, by 6 months of age, had developed asymptomatic hypopigmented patches on the lower legs, thighs, and buttocks, which have evolved over the past 7 years. This condition had previously been misdiagnosed as vitiligo. Recent immunohistologic and molecular biology studies are consistent with MF., Results and Conclusions: Given that hypopigmented MF is an uncommon condition, it may not be clinically suspected in the pediatric population. Histopathologic, immunophenotypic, and/or molecular biologic studies are sometimes equivocal, with findings similar to inflammatory dermatoses or autoimmune vitiligo, which may initially lead to a misdiagnosis, as in this patient's case.

We describe a detailed, cross-sectional, self-report time study of laboratory physician tasks in a regionalized, multisite academic setting, using custom data collection templates programmed into personal digital assistants (PDAs). The 7-week study was completed by 56 medical and scientific staff (86% participation rate). Participants recorded 12,781 PDA entries of specific tasks completed during the study period. The mean number of entries per worked day per participant was 8.14 (range, 1.96-14.33). Study results demonstrated that professional staff worked, on average, 53.5 hours per week. Percentage work time spent in each activity area was as follows: clinical, direct, 50.6%; administration, 18.5%; clinical, indirect, 9.5%; research, 8.2%; learning/continuing education, 5.3%; teaching, 4.9%; and quality assurance, 3.1%. These percentages varied significantly by laboratory medicine subspecialty and by type of academic appointment. The findings confirm that activities not directly involved with patient care, such as administration, quality assurance, teaching, research, and professional development, typically occupy 40% to 50% of a laboratory physician's time.

Aim: To measure pathologist workload in subspecialty dermatopathology., Methods: Three subspecialty dermatopathologists, working in a university-affiliated laboratory, participated in a time-motion study during which they reported 2891 consecutive skin cases received from community-based dermatologists. All pathology reports were retrospectively reviewed and workload measured using the Royal College of Pathologists (RCPath) guidelines and the level 4 equivalent (L4E) method., Results: The majority of dermatopathology cases were scored as low (32%) or intermediate (52%) complexity using the RCPath matrix. Only 16% of cases were considered high or very high complexity. The mean RCPath score per case was 2.68 units. Using L4E complexity levels, 83% of specimens were level 3, 15% were level 4, and only 2% were higher complexity (levels 5 and 6). Mean values for specimens/case, blocks/case, and slides/case were 1.31, 1.52, and 2.92, respectively. Time-motion analysis demonstrated a mean workload per hour of 16.3 cases, 21.3 specimens, 45.1 slides, 43.0 RCPath units, and 12.2 L4E. All three dermatopathologists reported >35 RCPath units per hour., Conclusions: The RCPath histopathology workload guidelines underestimate the workload achievable by an experienced dermatopathologist, and thus are not directly applicable to subspecialty dermatopathology practice. Hourly work rates 3-4 times that recommended by the RCPath workload matrix are routinely achievable, but extrapolation to yearly workload estimates requires detailed knowledge of practice pattern and time required for non-clinical duties such as teaching, research and administration.

BACKGROUND Products instilled within or beneath the skin to improve its physical features are known as fillers. The position of the filler within the skin is one determinant of the end cosmetic result. OBJECTIVE The objective was to histologically determine the anatomic location of injected hyaluronic acid (HA) filler within nasolabial fold (NLF) skin. METHODS AND MATERIALS Sixteen patients (12 females, 4 males; median age, 59 years) undergoing Mohs micrographic surgery for basal cell carcinoma of the NLF area consented to injection of Burow's triangle or dog-ear redundant skin with HA gel (Juvederm), ex vivo, in vivo, or in vivo with delayed (1-4 weeks) removal. Sections of alcohol-fixed, paraffin-embedded tissue specimens were stained with hematoxylin and eosin and with Hale's colloidal iron for detection of acid mucins. Dermal thickness was measured and HA distribution assessed. RESULTS NLF dermal thickness was 1.37+/-0.27 mm (mean+/-SD), with a range of 1.04 to 1.86 mm. All 16 patients showed HA filler localized to the subcutis. In 9/16 tissue samples, some HA was present in the deep dermis, but filler was only observed in more superficial dermis in 1 patient. The thickness of injected filler was 2.11+/-0.63 mm, but filler was often transected at the specimen base. CONCLUSION The predominant localization of injected HA filler is within the subcutis. A relatively thin NLF dermal thickness, typically <1.50 mm, likely precludes accurate injection of filler into dermal collagen. The results suggest that dermal localization of HA filler products is not required for an excellent cosmetic result.

The distinction of cellular blue nevi (CBN) with atypical features ["atypical" CBN (ACBN)] from conventional CBN and malignant melanomas related to or derived from CBN remains a difficult problem. Here, we report on the diagnosis of various cellular blue melanocytic neoplasms by 14 dermatopathologists who routinely examine melanocytic lesions. Three parameters were assessed: (1) for between rater analyses, we calculated interobserver agreement by the kappa statistic (regardless of whether the diagnosis was correct). (2) For each individual lesion, we reported whether a majority agreement (>50%) was reached and, if so, whether the majority agreed with the gold standard diagnosis, derived from standardized histopathologic criteria for melanoma, definitive outcome such as metastatic event or death of disease, or disease-free follow-up for > or =4 years. (3) For the individual pathologists, we calculated sensitivity and specificity for each type of lesion. The study set included 26 melanocytic lesions: (1) 6 malignant melanomas developing in or with attributes of CBN; (2) 11 CBN with atypical features and indeterminate biologic potential (ACBN); (3) 8 conventional CBN; and (4) 1 common BN. The kappa values for interrater agreement varied from 0.52 (95% confidence interval 0.45, 0.58) for melanoma to 0.02 (0.05, 0.08) for ACBN and 0.20 (0.13, 0.28) for CBN. The kappa for all lesions was 0.25 (0.22, 0.28). The pathologists' sensitivities were 68.6% (61.0%, 76.1%) for melanoma, 33.1% (21.0%, 45.2%) for ACBN, and 44.6% (29.0%, 60.3%) for CBN. The specificities were 65.7% (55.8%, 75.6%) for melanoma, 84.7% (77.3%, 92.2%) for ACBN, and 89.9% (82.7%, 97.1%) for CBN. Overall, greater than 50% of the pathologists agreed and were correct in their diagnosis 38.5% (10 lesions) of the time. There was a majority agreement, but with an incorrect diagnosis, another 26.9% (7 lesions) of the time. Six of the 7 majority agreements with an incorrect diagnosis were for ACBN lesions. In summary, the results of our study indicate that there is substantial confusion and disagreement among experienced histopathologists about the definitions and biologic nature of cellular blue melanocytic neoplasms particularly those thought to have atypical features ("atypical" CBN).

Background: In addition to an established role in the repair of postreplicative DNA errors, DNA mismatch repair (MMR) proteins also contribute to cellular responses to exogenous DNA damage. Previously, we have shown that Msh2-null mice display increased sensitivity to ultraviolet (UV) B-induced tumorigenesis, but squamous cell carcinomas (SCC) generated are microsatellite stable, suggesting a role for MMR other than postreplicative repair in UV-induced cutaneous tumour formation., Objectives: We questioned whether there was evidence of MMR dysfunction in human SCC, thus validating the mouse models of MMR-dependent UVB-induced skin cancer., Methods: Using tissue microarrays we examined both nuclear and cytoplasmic levels of MMR proteins MSH2, MSH6, MSH3, MLH1 and PMS2 in more than 200 cases of cutaneous SCC and basal cell carcinoma (BCC)., Results: We found that subsets of these 10 MMR protein measures were increased in nonmelanoma skin cancer (NMSC) compared with normal epidermal samples; this was particularly true of SCC. In fact, based on post hoc tests and MMR protein distribution patterns, BCC was distinct from SCC. With the exception of nuclear MSH2, the BCC had lower levels of identified MMR protein measures than SCC. We believe this to be important because not only is SCC more aggressive than BCC, but evidence suggests that these two NMSC subtypes arise through different molecular pathways., Conclusions: In combination with previously established roles for MMR proteins in response to UVB-induced DNA damage, our data point towards an expanded perspective of the importance of MMR proteins in the suppression of UVB-induced tumorigenesis and, potentially, tumour behaviour.

Background: The pathogenesis of seborrheic keratosis (SK) is not well understood. SKs are slow growing, but the details of cell cycle control in these lesions are not known. We hypothesized that cyclin-dependent kinase inhibitors would be strongly expressed in SKs and that the proliferation rate would be low., Objectives: To quantify the expression of Ki67, p16(INK4a), p21(WAF1), and p27(KIP1 )in SK., Methods: We assessed acanthotic SKs (n=10) and irritated SKs (n=10) for Ki67, p16(INK4a), p21(WAF1), and p27(KIP1 )expression using immunohistochemistry., Results: For nonirritated acanthotic pattern SKs, the Ki67 index was 3.4% (range 0.6-6.5%), confirming a low proliferation rate. The p16(INK4A) index was 6.0% (range 0-16%), and the p21(WAF1) index was 4.8% (range 0-25%). p27(KIP1) was strongly and diffusely expressed in all SKs, with a labeling index of 78% (range 75-85%). The labeling indices were similar in irritated SK lesions with a slightly increased proliferation rate and corresponding decrease in p27(KIP1) expression., Conclusions: We conclude that in SKs, strong expression of the cyclin-dependent kinase inhibitor p27(KIP1) appears to be a major mechanism controlling keratinocyte proliferation.

Background: The histology of melanocytic nevi removed from older patients often differs from that of nevi from younger adults. According to the literature, the most common nevus in older individuals is the intradermal nevus, and purely junctional nevi are rare and should alert the pathologist to a possible melanoma precursor., Objective: To evaluate the histologic features of melanocytic nevi removed from patients > 60 year of age., Methods: Biopsies of nevi (N=215) from 172 patients > 60 years (mean age 69+/-7 years) were examined retrospectively by three dermatopathologists, a consensus diagnosis was rendered, and the spectrum of histologic features was documented., Results: Junctional melanocytic nevi were frequently diagnosed in older patients (21% of cases) and a lentiginous, often heavily pigmented growth pattern was common (12% of nevi). Severely atypical (dysplastic) changes were found in 6% of nevi removed from older patients., Conclusions: We conclude that benign junctional nevi are relatively common in older patients and that a lentiginous, heavily pigmented growth pattern, traditionally associated with younger individuals, is often seen in both junctional and compound nevi in this older age group. This pattern must be differentiated from dysplastic nevus and melanoma in situ, which they may clinically resemble.

Background: The risk of malignant melanoma associated with histologically dysplastic naevi (HDN) has not been defined. While clinically atypical naevi appear to confer an independent risk of melanoma, no study has evaluated the extent to which HDN are predictive of melanoma., Objectives: To estimate the risk of melanoma associated with HDN. Secondarily, the risk associated with number of naevi and large naevi is estimated., Methods: We enrolled 80 patients with newly diagnosed melanoma along with 80 spousal controls. After obtaining information on melanoma risk factors and performing a complete cutaneous examination, the most clinically atypical naevus was biopsied in both cases and controls. Histological dysplasia was then assessed independently by 13 dermatopathologists (0, no dysplasia; 1, mild dysplasia; 2, moderate dysplasia; 3, severe dysplasia). The dermatopathologists were blinded as to whether the naevi were from melanoma subjects or controls. Multivariate analyses were performed to determine if there was an independent association between the degree of histological dysplasia in naevi and a personal history of melanoma., Results: In persons with naevi receiving an average score of > 1 (i.e. naevi considered to have greater than mild histological dysplasia), there was an increased risk of melanoma [odds ratio (OR) 2.60, 95% confidence interval (CI) 0.99-6.86] which persisted after adjustment for confounders (OR 3.99, 95% CI 1.02-15.71). Very few dermatopathologists reliably graded naevi of subjects with melanoma as being more dysplastic than naevi of control subjects. Among the entire group, the interobserver reliability associated with grading histological dysplasia in naevi was poor (weighted kappa 0.28)., Conclusions: HDN do appear to confer an independent risk of melanoma. However, this result may add more to our biological understanding of melanoma risk than to clinical assessment of risk, because HDN assessed by a single pathologist generally cannot be used to assess risk of melanoma. Future studies should be directed at establishing reproducible, predictive criteria for grading naevi.

Lentigo maligna (LM) and lentigo maligna melanoma (LMM) represent a character, histogenetic subclass of melanocytic malignancies. They often present with a prolonged phase of slow growth but once invasion has occurred, the prognostic features are identical to all other melanomas. These lesions occur primarily on the head and neck where they evolve from areas of pigmented staining to the more typical features identifiable with malignant melanomas on other skin surfaces. The treatment options and recent advances in management are reviewed., (Copyright 2004 Wiley-Liss, Inc.)

Squamous cell carcinoma in situ (SCCIS) of the skin is a problem commonly dealt with by dermatologists. The classic presentation, originally described by Bowen, is easily recognized, but presentation on some anatomical surfaces may be associated with less than typical features. Major aetiological factors for this disease are UV light, human papillomavirus infection and immunosuppression. The natural course of SCCIS is usually prolonged, with treatment being appropriate, but not urgent. The choice of therapy requires consideration of the location of the lesion, and a desire for a high cure rate without causing loss of form, function or cosmesis. The immunomodulatory agent imiquimod has offered a significant advance for the topical treatment of SCCIS. Our improved understanding of the underlying biology of SCCIS permits us to make rational choices of treatment. In the future we may be able to determine which of these lesions may progress to invasive disease, and help us select the most effective therapy.

To assess the diagnostic accuracy of margin evaluation of melanocytic lesions using en face frozen sections compared with standard paraffin-embedded sections, we studied 2 sets of lesions in which en face frozen sections were used for analysis of surgical margins (13 from malignant melanomas [MMs] and 10 from nonmelanocytic lesions [NMLs]). Routine permanent sections were cut after routine processing. The slides were mixed and coded randomly. Fifteen dermatopathologists examined the cases separately. Margin status was categorized as positive, negative, or indeterminate. Kappa statistics were calculated per dermatopathologist and per case. One case from each group was excluded because epidermis was not available in the routine sections. Of 330 evaluations (22 cases, 15 dermatopathologists), there were 132 diagnostic discrepancies (40.0%): 66 each for MM and NML (mean per case for both diagnoses, 6). In 9 instances (6.8%), the change was from positive (frozen) to negative (permanent) and in 43 (32.6%), from negative (frozen) to positive (permanent). There was poor agreement between frozen and permanent sections (kappa range per dermatopathologist, -0.1282 to 0.6615). If permanent histology is considered the "gold standard" for histologic evaluation, en face frozen sections are not suitable for accurate surgical margin assessment of melanocytic lesions.

Background: Malignant cutaneous spindle cell lesions with marked sclerosis are uncommon. Only a few cases of cutaneous leiomyosarcoma and dermatofibrosarcoma protuberans with sclerosis have been published., Methods: We report a case of atypical fibroxanthoma (AFX) with prominent sclerosis and hyalinization occurring on the scalp of an 81-year-old male., Results: Histopathologic examination revealed an exophytic, well-delineated, focally ulcerated tumor arising in sun-damaged skin. The lesion was composed of atypical spindle cells arranged in a fascicled and vaguely storiform pattern. Occasional multinucleated giant cells were present. The tumor cells were strongly positive for CD99 (O13), vimentin, and smooth muscle actin, and focally positive for CD68. There was striking sclerosis with hyalinization throughout the lesion., Conclusions: Rarely, AFX may exhibit marked sclerosis with areas of complete replacement of tumor by hyalinized collagen. In a small biopsy, such hyalinization may be a diagnostic pitfall leading to an erroneous diagnosis.

Background: Thrombospondins (TSPs) are recognized as important glycoproteins that regulate a wide variety of cell functions and interactions. TSPs in malignant tumors can both enhance and inhibit tumor progression, invasion, and metastasis, depending on cell type, stromal interactions, and microenvironment. These proteins are potential targets for anticancer therapy., Objective: The aim of our article is to review the role of thrombospondin-1 (TSP1) in cutaneous melanoma., Conclusions: TSP1 expression is variable in melanoma cell lines and tumors. Similar to findings in other human cancers, expression of TSP1 by melanoma cells usually inhibits tumor progression via the antiangiogenic effect of TSP1. Conversely, stromal TSP1 overexpression in melanoma is a poor prognostic factor associated with decreased survival. Understanding the interactions of TSP1 with other melanoma- and matrix-associated proteins should provide new prognostic indices and possible therapeutic targets for melanoma treatment.

Background: The treatment of cutaneous malignant melanoma of the face presents a challenge to ensure eradication of disease with maximum preservation of tissue. Mohs micrographic surgery provides a means for histologically controlled removal of malignant melanoma., Objective: This study evaluates the efficacy of Mohs micrographic surgery, at a single institution, for the treatment of facial melanoma and assesses the accuracy of margin control by frozen section techniques., Methods: Ninety-seven patients with biopsy-confirmed melanoma in situ or invasive melanoma of the face were treated by Mohs micrographic surgery over a 6-year period. In 25 patients, tissue margins defined as negative for melanoma at the time of frozen section were re-evaluated on permanent section histology of formalin-fixed, paraffin-embedded tissue., Results: Ninety-two of 97 patients had followup information available (8-72 months; mean 33 months). There were no cases of local recurrence. Eighty-nine of the 92 patients were alive and well with no evidence of disease. One patient died of metastatic melanoma. In situ or invasive melanoma was not identified on permanent sections of 117 tissue margins which had been interpreted as negative on frozen section., Conclusion: Mohs micrographic surgery appears to be an effective treatment for facial melanomas. Our study showed complete correlation between frozen section tissue margins and permanent section controls.

Background: The histopathologic features of dermatofibroma vary remarkably, and this diversity may occasionally cause problems in differentiating between benign and malignant mesenchymal lesions, including smooth muscle neoplasms. Immunohistochemical stains are sometimes necessary to clarify the histogenesis of a lesion., Objective: To evaluate dermatofibromas for expression of desmin and smooth muscle myosin heavy chain (SM-MHC) antigens, which are commonly used as evidence of smooth muscle differentiation., Methods: We studied 100 consecutive cases of dermatofibroma using hematoxylin-eosin-stained sections and immunoperoxidase staining with antibodies against desmin, SM-MHC, and smooth muscle actin., Results: We found focal positivity for desmin in 9 cases, and in 2 of these cases, at least 10% of lesional cells showed strong expression. We found focal staining for SM-MHC in 10 cases, and in 2 of these cases, at least 10% of the lesional cells were positive. Regions positive for desmin and/or SM-MHC did not show definite histologic features of myogenous differentiation on hematoxylin-eosin-stained sections. All dermatofibromas expressing desmin and SM-MHC were also strongly positive for smooth muscle actin., Conclusions: About 10% of dermatofibromas show focal expression of desmin and SM-MHC, and this expression may be present in up to 10% to 15% of lesional cells. Thus, in dermal spindle cell lesions, focal expression of these muscle antigens, like that of smooth muscle actin, is not diagnostic of a smooth muscle tumor.

Background: p53 is a key regulator of the cellular stress response. p53 modulates the transcription of several genes., Objectives: To examine the influence of p53 on expression of heat shock protein 72 (HSP72)., Methods: Two model systems were used. (i) HSP72 expression was studied by Western blot on extracts from p53-proficient or p53-deficient primary mouse keratinocytes, and (ii) archival human anogenital skin from fibroepithelial polyps, human papillomavirus (HPV) 16/18-associated lesions or squamous cell carcinomas (SCCs) was subjected to immunostaining for HSP72., Results: Basal HSP72 expression was higher in keratinocytes from p53-deficient than from p53-proficient mice. Immunostaining for HSP72 was higher in HPV 16/18 lesions and SCCs, which have reduced p53 protein., Conclusions: p53 status may influence the basal level of HSP72.

Background: Criteria for distinguishing between cutaneous lymphoid hyperplasia (CLH) and low-grade B-cell lymphoma are not well defined. We examined the hypothesis that the presence of a clonal B-cell population in heavy multinodular lymphoid infiltrates correlates with clinical presentation and outcome., Methods: We identified 29 patients with skin lesions characterized histologically by a heavy dermal lymphocytic infiltrate with a multinodular architecture and extension into deep dermis and subcutaneous fat. Clonality was assessed immunophenotypically by light-chain restriction and also by analysis for IgH-gene rearrangement using PCR on DNA extracted from paraffin blocks., Results: Follow-up (mean 80 months; median 45 months) was obtained in all patients. Twenty-four patients (83%) presented with a solitary lesion: only four had solitary recurrences, and none developed multiple synchronous lesions or systemic B-cell lymphoma. However, 9/24 of these solitary lesions (38%) were clonal by light-chain restriction or IgH PCR; 5/29 patients (17%) presented with multiple recurrent lesions and continued to develop lesions during the period of follow-up; 3/5 patients (60%) with multiple lesions demonstrated a B-cell clone. No patient developed systemic B-cell lymphoma., Conclusions: Heavy, multinodular cutaneous lymphoid infiltrates have an excellent prognosis. Multiple lesions at presentation are the best predictor of recurrent multiple lesions confined to the skin. The presence of a clonal B-cell population does not correlate with clinical presentation or histology, nor does it predict development of further lesions or systemic lymphoma.

Pseudopelade is a rare self-limited hair disorder, resulting in cicatricial alopecia. It presents with skin-colored alopecic patches primarily involving the parietal and vertex portions of the scalp. This is a case report of a patient with pseudopelade that involves both his scalp and beard area.

Background: Epithelial elements, such as trichoepithelioma, are occasionally associated with melanocytic nevi., Objective: A case of trichoepithelioma in association with cellular blue nevus is reported., Methods and Results: A solitary, pigmented nodule was removed from the scalp of a middle-aged woman. Histopathologic examination demonstrated a circumscribed cellular blue nevus within which were embedded epithelial strands and cystic structures consistent with trichoepithelioma., Conclusion: Trichoepitheliomas have been described in relation to common acquired nevi, but an association with a blue nevus is rare. The intimate admixture of trichoepithelioma within the nodule of a nevus supports the concept of epithelial induction by melanocytic nevi.

Background: The tumour suppressor, p53, is recognized as a crucial molecule in regulating cellular responses to various DNA-damaging agents. Very early on in the development of nonmelanoma cancers p53 is mutated or lost, suggesting that p53 is crucial in protecting normal keratinocytes from the harmful effects of ultraviolet (UV) radiation., Objective: Using two mouse models, one with multiple copies of mutant p53 and the other a p53 "knockout," our laboratory has examined a role for p53 in UV-induced DNA damage and determined if these effects are differentiation dependent., Conclusion: We outline in this review a proposed model reflecting differentiation-dependent p53 regulation of UV-induced responses in keratinocytes. After exposure to UV, basal keratinocytes repair damaged DNA, whereas differentiating keratinocytes undergo cell death, both processes are regulated by p53.