Practical Strategies to Improve the Clinical Utility of the Dermatopathology Report.

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: Analysis of Clinical, Histological, and Outcome Data in 37 Cases.

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.

Drug-induced subacute cutaneous lupus erythematosus associated with docetaxel chemotherapy: a case report.

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.

Data set for pathology reporting of cutaneous invasive melanoma: recommendations from the international collaboration on cancer reporting (ICCR).

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.

Utilization and utility of immunohistochemistry in dermatopathology.

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.

Underrecognition of pathologist contributions to articles published in a major multidisciplinary medical journal.

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.

Pemphigus vegetans associated with intranasal cocaine abuse.

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.

Melanoma margin assessment.

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.

Immunohistochemistry utilization in autopsy pathology: a Canadian experience.

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.

Juvenile-onset hypopigmented mycosis fungoides mimicking vitiligo.

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.

Time study of clinical and nonclinical workload in pathology and laboratory medicine.

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.

Implementation of a Canadian external quality assurance program for breast cancer biomarkers: an initiative of Canadian Quality Control in immunohistochemistry (cIQc) and Canadian Association of Pathologists (CAP) National Standards Committee/Immunohistochemistry.

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.

Melanoma Margin Assessment.

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.

Anatomic location of hyaluronic acid filler material injected into nasolabial fold: a histologic study.

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.

Intraoperative consultation/final diagnosis correlation: relationship to tissue type and pathologic process.

CONTEXT: The correlation of the diagnosis made at intraoperative consultation (IC) with the final diagnosis is one of the cornerstones of quality assurance in the anatomic pathology laboratory. OBJECTIVE: To review correlation of IC diagnoses with final diagnoses during a 1-year period in a regionalized, multisite hospital setting in a major Canadian city. DESIGN: One pathologist reviewed all surgical pathology cases at Calgary Laboratory Services from June 2004 through May 2005 that had an IC to extract the following data points: intraoperative diagnoses, final diagnoses, correlation between the two, anatomic site of the tissue on which the IC was requested, pathologic procedure requested of the IC, types of disagreements encountered, reasons for disagreement, and deferrals. RESULTS: Intraoperative consultations occurred for 2812 specimens, of which 87 were discordant and 135 were deferred. Percent agreement was 96.75% (95% confidence interval, 96.08-97.42) with a kappa statistic of 0.94 (95% confidence interval, 0.92-0.95). Lymph nodes for evaluation for metastases (427), thyroid/parathyroid (401), and central/peripheral nervous system (378) specimens were sent most frequently for IC, and the latter 2 tissue types accounted for the greatest number of disagreements. The most common assessments requested were the presence/typing of a neoplasm (1161) and assessment of margins (730), which also accounted for the largest number of disagreements. Disagreements were most frequently due to interpretive (53) and gross sampling (23) errors; false-negative disagreements were nearly 3 times as common as false positives. CONCLUSIONS: The IC was an excellent diagnostic test. Agreement and deferral rates varied by specimen site and by type of assessment requested.

Atypical cellular blue nevi (cellular blue nevi with atypical features): lack of consensus for diagnosis and distinction from cellular blue nevi and malignant melanoma ("malignant blue nevus").

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).