Use of modifying phrases in surgical pathology reports: is there a different understanding between pathologists and treating physicians?

When not all the histopathologic and clinical features necessary for a pathology diagnosis are present in a particular specimen, pathologists may use modifying phrases to convey various degrees of certainty, e.g., "consistent with…" and "suggestive of…." However, it is unclear whether pathologists use such phrases consistently or whether treating physicians fully understand their intended meaning. A questionnaire concerning six common modifying phrases ("consistent with, suggestive of, suspicious for, highly consistent with, highly suggestive of, some features of") was sent to all physicians from a single institution who either issued or routinely received surgical pathology reports. Physicians were asked to rank their understanding of each phrase on a printed scale between 1 ("no evidence of") and 10 ("diagnostic of"). One hundred sixty physicians (74.3%) responded. Despite wide variation, there was a hierarchy (from more to less diagnostic): highly consistent > highly suspicious > consistent > suspicious > suggestive > some features (p < 1 × 10-7). There were no significant differences between pathologists and treating physicians (p = 0.72) or attendings and residents (p = 0.9). Pathologists and treating physicians share an overall common understanding of their hierarchical relationship, albeit with wide ranges. Based upon our results, we propose to use only three qualifying phrases to convey the degree of certainty for a particular diagnosis: "suggestive of" (> 25 ≤ 50% certainty), "suspicious for" (> 50 ≤ 75%), and "consistent with" (> 75%). The phrase "no evidence of" should probably be used only when there is ≤ 5% confidence in a diagnosis, and conversely, "diagnostic of" should probably be used only when there is ≥ 95% confidence in a diagnosis.

Histopathologic features predictive of metastasis and survival in 230 patients with cutaneous squamous cell carcinoma of the head and neck and non-head and neck locations: a single-center retrospective study.

BACKGROUND: Staging systems for cutaneous squamous cell carcinoma (cSCC) produce inconsistent risk stratification. OBJECTIVE: The aim of this study was to identify further prognostic parameters for better stratification. METHODS: We retrospectively analysed the prognostic significance of clinicopathologic parameters of 230 patients who underwent primary excision of invasive cSCC of the head and neck (n = 115) and non-head and non-neck (n = 115) locations. In addition to known high-risk features, we analysed tumour nest shape, invasion pattern, lymphoid response pattern and tumour budding. RESULTS: On multivariable analysis, lymphovascular invasion (LVI) and high tumour budding predicted worse disease-specific survival, and ulceration, LVI and high tumour budding predicted worse overall survival. Only ulceration was independently associated with risk of nodal metastasis. CONCLUSION: High tumour budding, LVI and ulceration are independently associated with poor outcome in cSCC and may be used to refine cSCC prognostic stratification, which is crucial to optimize clinical decision and to identify patients who are more likely to benefit from more aggressive interventions or clinical trials.

Spitzoid melanoma with histopathological features of ALK gene rearrangement exhibiting ALK copy number gain: a novel mechanism of ALK activation in spitzoid neoplasia.

Spitzoid neoplasms pose diagnostic difficulties because their morphology is not consistently predictive of their biological potential. Recent advances in the molecular characterization of these tumours provides a framework by which they can now begin to be categorized. In particular, spitzoid lesions with ALK rearrangement have been specifically associated with a characteristic plexiform growth pattern of intersecting fascicles of amelanotic spindled melanocytes. We report the case of an 87-year-old man with a 3-cm nodule on his mid-upper back comprised of an intradermal proliferation of fusiform amelanotic melanocytes arranged in intersecting fascicles with occasional peritumoral clefts. Immunohistochemical studies demonstrated diffuse, strong expression of SOX10 and S100 by the tumour cells and diffuse, weak-to-moderate cytoplasmic positivity for anaplastic lymphoma kinase (ALK), suggestive of ALK rearrangement. Fluorescence in situ hybridization revealed no ALK rearrangements but instead revealed at least three intact ALK signals in 36% of the tumour cells, confirming ALK copy number gain. To our knowledge, this is the first reported case of a plexiform spitzoid neoplasm exhibiting ALK copy number gain instead of ALK rearrangement. This case suggests that ALK copy number gain is a novel mechanism of ALK activation but with the same characteristic histopathological growth pattern seen among ALK-rearranged spitzoid neoplasms.

Pathological assessment of resection specimens after neoadjuvant therapy for metastatic melanoma.

Background: Clinical trials have recently evaluated safety and efficacy of neoadjuvant therapy among patients with surgically resectable regional melanoma metastases. To capture informative prognostic data connected to pathological response in such trials, it is critical to standardize pathologic assessment and reporting of tumor response after this treatment. Methods: The International Neoadjuvant Melanoma Consortium meetings in 2016 and 2017 assembled pathologists from academic centers to develop consensus guidelines for pathologic examination and reporting of surgical specimens from AJCC (8th edition) stage IIIB/C/D or oligometastatic stage IV melanoma patients treated with neoadjuvant-targeted or immune therapy. Patterns of pathologic response are provided context to inform these guidelines. Results: Based on our collective experience and guided by efforts in well-established neoadjuvant settings like breast cancer, procedures directing handling of pre- and post-neoadjuvant therapy-treated melanoma specimens are provided to facilitate comparison of findings across different trials and centers. Definitions of pathologic response are provided together with guidelines for reporting and quantifying the extent of pathologic response. Finally, the spectrum of histopathologic responses observed following neoadjuvant-targeted and immune-checkpoint therapy is described and illustrated. Conclusions: Standardizing pathologic evaluation of resected melanoma metastases following neoadjuvant-targeted or immune-checkpoint therapy allows more robust stratification of patient outcomes. This includes recognizing the spectrum of histopathologic response patterns to neoadjuvant therapy and a standard approach to grading pathologic responses. Such an approach will facilitate comparison of results across clinical trials and inform ongoing correlative studies into the mechanisms of response and resistance to agents applied in the neoadjuvant setting.

Benchmarking en la identificación de pacientes: una oportunidad para aprender / Benchmarking in patient identification: an opportunity to learn

Objetivo. Realizar benchmarking sobre la identificación segura de los pacientes en los hospitales integrantes del Club de las 3 «C» (calidez, calidad y cuidados) y elaboración de una ficha común del proceso. Material y métodos. Se trata de un estudio descriptivo de las actividades llevadas a cabo en el proceso de identificación de pacientes en 5 hospitales de media estancia en las unidades de cuidados paliativos y de ictus. Se han seguido las siguientes etapas: recogida de datos en cada hospital, organización y análisis de los datos y elaboración de una ficha común de proceso. Resultados. Los datos obtenidos para el proceso de ictus, del total de pacientes identificados de forma segura fueron: hospital n.° 1 (93%), hospital n.° 2 (93,1%), hospital n.° 3 (100%) y hospital n.° 5 (93,4%). Para el proceso de cuidados paliativos: hospital n.° 1 (93%), hospital n.° 2 (92,3%), hospital n.° 3 (92%), hospital n.° 4 (98,3%) y hospital n.° 5 (85,2%). Conclusiones. El objetivo del trabajo se ha cumplido satisfactoriamente. Se han desarrollado las actividades de benchmarking y compartido conocimientos sobre el proceso de identificación de pacientes. Todos los hospitales han tenido buenos resultados. El hospital n.° 3 destaca en la identificación del proceso de ictus. La identificación de un benchmark es difícil, pero entre los 5hospitales se ha identificado una ficha común útil que recoge las mejores prácticas. Es importante incorporar a la sistemática de las organizaciones la práctica del benchmarking (AU)

Objective. To perform a benchmarking on the safe identification of hospital patients involved in 'Club de las tres C' (Calidez, Calidad y Cuidados) in order to prepare a common procedure for this process. Material and methods. A descriptive study was conducted on the patient identification process in palliative care and stroke units in 5medium-stay hospitals. The following steps were carried out: Data collection from each hospital; organisation and data analysis, and preparation of a common procedure for this process. Results. The data obtained for the safe identification of all stroke patients were: hospital 1 (93%), hospital 2 (93.1%), hospital 3 (100%), and hospital 5 (93.4%), and for the palliative care process: hospital 1 (93%), hospital 2 (92.3%), hospital 3 (92%), hospital 4 (98.3%), and hospital 5 (85.2%). Conclusions. The aim of the study has been accomplished successfully. Benchmarking activities have been developed and knowledge on the patient identification process has been shared. All hospitals had good results. The hospital 3 was best in the ictus identification process. The benchmarking identification is difficult, but, a useful common procedure that collects the best practices has been identified among the 5 hospitals (AU)

[Benchmarking in patient identification: An opportunity to learn]. / Benchmarking en la identificación de pacientes: una oportunidad para aprender.

OBJECTIVE: To perform a benchmarking on the safe identification of hospital patients involved in "Club de las tres C" (Calidez, Calidad y Cuidados) in order to prepare a common procedure for this process. MATERIAL AND METHODS: A descriptive study was conducted on the patient identification process in palliative care and stroke units in 5medium-stay hospitals. The following steps were carried out: Data collection from each hospital; organisation and data analysis, and preparation of a common procedure for this process. RESULTS: The data obtained for the safe identification of all stroke patients were: hospital 1 (93%), hospital 2 (93.1%), hospital 3 (100%), and hospital 5 (93.4%), and for the palliative care process: hospital 1 (93%), hospital 2 (92.3%), hospital 3 (92%), hospital 4 (98.3%), and hospital 5 (85.2%). CONCLUSIONS: The aim of the study has been accomplished successfully. Benchmarking activities have been developed and knowledge on the patient identification process has been shared. All hospitals had good results. The hospital 3 was best in the ictus identification process. The benchmarking identification is difficult, but, a useful common procedure that collects the best practices has been identified among the 5 hospitals.

Use of New Techniques in Addition to IHC Applied to the Diagnosis of Melanocytic Lesions, With Emphasis on CGH, FISH, and Mass Spectrometry.

Melanoma remains one of the most aggressive forms of cutaneous malignancies. While its diagnosis based on histologic parameters is usually straight forward in most cases, distinguishing a melanoma from a melanocytic nevus can be challenging in some instances, especially when there are overlapping clinical and histopathologic features. Occasionally, melanomas can histologically mimic other tumors and even demonstration of melanocytic origin can be challenging. Thus, several ancillary tests may be employed to arrive at the correct diagnosis. The objective of this review is to summarize these tests, including the well-established and commonly used ones such as immunohistochemistry, with specific emphasis on emerging techniques such as comparative genomic hybridization, fluorescence in situ hybridization and imaging mass spectrometry.

Active animal health surveillance in European Union Member States: gaps and opportunities.

Animal health surveillance enables the detection and control of animal diseases including zoonoses. Under the EU-FP7 project RISKSUR, a survey was conducted in 11 EU Member States and Switzerland to describe active surveillance components in 2011 managed by the public or private sector and identify gaps and opportunities. Information was collected about hazard, target population, geographical focus, legal obligation, management, surveillance design, risk-based sampling, and multi-hazard surveillance. Two countries were excluded due to incompleteness of data. Most of the 664 components targeted cattle (26·7%), pigs (17·5%) or poultry (16·0%). The most common surveillance objectives were demonstrating freedom from disease (43·8%) and case detection (26·8%). Over half of components applied risk-based sampling (57·1%), but mainly focused on a single population stratum (targeted risk-based) rather than differentiating between risk levels of different strata (stratified risk-based). About a third of components were multi-hazard (37·3%). Both risk-based sampling and multi-hazard surveillance were used more frequently in privately funded components. The study identified several gaps (e.g. lack of systematic documentation, inconsistent application of terminology) and opportunities (e.g. stratified risk-based sampling). The greater flexibility provided by the new EU Animal Health Law means that systematic evaluation of surveillance alternatives will be required to optimize cost-effectiveness.

Merkel cell polyomavirus and human papilloma virus in proliferative skin lesions arising in patients treated with BRAF inhibitors.

The potential role of oncogenic viruses mediating development of proliferative skin lesions in patients treated with RAF inhibitors is poorly understood. The objective of this study was to investigate human papilloma virus (HPV) and Merkel cell polyomavirus (MCPyV) in skin lesions among patients treated with RAF inhibitors with the help of a case series describing prevalence of HPV, MCPyV, and RAS mutations in skin biopsies obtained from patients receiving RAF inhibitors and developing cutaneous lesions. HPV-DNA was amplified by PCR utilizing multiple nested primer systems designed for detection of a broad range of HPV types. MCPyV copy number determination with real time PCR technology was performed by a "Quantification of MCPyV, small t region" kit. Thirty-six patients were tested (squamous cell carcinoma (SCC) = 14; verruca vulgaris = 15; other = 11). Nine of 12 SCCs (75 %) and eight of 13 verruca vulgaris lesions (62 %) tested positive for MCPyV whereas none of the normal skin biopsies obtained from nine of these patients tested positive for MCPyV (p = 0.0007). HPV incidence in cutaneous SCCs was not different compared to normal skin (50 vs. 56 %, p = 0.86). The association between MCPyV and proliferative skin lesions after RAF inhibitor therapy merits further investigation.

Identification of Suitable Areas for African Horse Sickness Virus Infections in Spanish Equine Populations.

African horse sickness (AHS) is one of the most important vector-borne viral infectious diseases of equines, transmitted mainly by Culicoides spp. The re-emergence of Culicoides-borne diseases in Europe, such as the recent bluetongue (BT) or Schmallenberg outbreaks, has raised concern about the potential re-introduction and further spread of AHS virus (AHSV) in Europe. Spain has one of the largest European equine populations. In addition, its geographical, environmental and entomological conditions favour AHSV infections, as shown by the historical outbreaks in the 1990s. The establishment of risk-based surveillance strategies would allow the early detection and rapid control of any potential AHSV outbreak. This study aimed to identify the areas and time periods that are suitable or at high risk for AHS occurrence in Spain using a GIS-based multicriteria decision framework. Specifically risk maps for AHS occurrence were produced using a weighted linear combination of the main risk factors of disease, namely extrinsic incubation period, equine density and distribution of competent Culicoides populations. Model results revealed that the south-western and north-central areas of Spain and the Balearic Islands are the areas at the highest risk for AHSV infections, particularly in late summer months. Conversely, Galicia, Castile and Leon and La Rioja can be considered as low-risk regions. This result was validated with historical AHS and BT outbreaks in Spain, and with the Culicoides vector distribution area. The model results, together with current Spanish equine production features, should provide the foundations to design risk-based and more cost-effective surveillance strategies for the early detection and rapid control potential of AHS outbreaks in Spain.

Constant Hepatitis E Virus (HEV) Circulation in Wild Boar and Red Deer in Spain: An Increasing Concern Source of HEV Zoonotic Transmission.

Hepatitis E is a viral zoonosis that affects multiple hosts. The complete dynamics of infection in wildlife are still unknown, but the previous fact facilitates the maintenance and circulation of the virus, posing a risk to human health in the case of meat consumption from susceptible animals. In Spain, it has been shown how domestic pigs, cattle and wildlife (i.e. wild boar and red deer) clearly interact in hunting farms, generating a complex epidemiological situation in terms of interspecies pathogen transmission. Therefore, in this study, we aimed to (i) evaluate the circulation of the virus in geographically close domestic (Iberian pigs) and wild animals (wild boar and deer) living in hunting areas from central Spain over an 8-year period (2003-2010) and (ii) to determine whether HEV could be used as a marker of domestic-wildlife contact. For these purposes, a longitudinal analysis of Iberian pig, wild boar and red deer samples (n = 287) through virological and serological tests was conducted to shed light upon the circulation events of HEV. Regarding HEV RNA detection by real-time RT-PCR, 10.12% samples (95% CI: 5.44-14.8) from wild boar and 16.05% samples (95% CI: 8.06-24.04) from red deer were positive. As for the Iberian pigs, none of the 48 samples was positive for HEV RNA detection. In the serological analysis, 43.75% (95% CI: 29.75-57.75) from Iberian pig, 57.40% (95% CI: 48.10-66.70) from wild boar and 12.85% (95% CI: 5.01-20.69) samples from red deer presented anti-HEV antibodies. Positive samples were distributed among all study years (2003-2010). These results depict the urgent need to improve the inspection and surveillance of these species and their products. In the case of HEV, it is clear that the stable and constant presence of the virus in wildlife and its contact with Iberian pigs pose a risk for human health as they are all destined for human consumption.

Natural Immunity of Sheep and Lambs Against the Schmallenberg Virus Infection.

Since the first reports of the Schmallenberg disease (SBD) outbreaks in late 2011, the disease has spread across Europe, affecting cattle and sheep farms. While Schmallenberg virus (SBV) causes a mild clinical disease in adults, infection of pregnant females may lead to the production of typical congenital malformations (CMFs) in their offspring. It is speculated that the immunity acquired after a SBV infection is effective in preventing further infections. However, this has not been proven in naturally infected sheep, especially if they are pregnant when reinfected. The aim of this study was to monitor the natural immunity in SBV-infected sheep. Twenty-four ewes from the only Spanish farm with a SBV OIE-notified outbreak were sampled. Subsequently, nine pregnant ewes were inoculated with SBV infectious plasma under controlled conditions. Six of them were euthanized before delivery, and their fetuses were inspected for lesions indicative for the SBV infection. The three remaining ewes were allowed to deliver one lamb each. Inoculation of the lambs was scheduled at approx. 3 months after birth. All samples were analyzed for viral RNA by RT-PCR, and for antibodies by an indirect ELISA and a virus neutralization test (VNT). The majority of the 24 ewes showed a serological reaction against SBV. The three ewes that were allowed to lamb down demonstrated variable degrees of seroconversion which corresponded to the levels of immune reaction observed in their lambs. Moreover, no viral RNA was detected, no lesions were observed in the fetuses, and no clinical signs were detected in the inoculated animals. These findings suggest that the immunity acquired by sheep following a natural SBV infection could be sufficient to stop SBV reinfection. However, vaccination could be a valuable tool to control SBV infections and associated economic losses as it affords a more uniform and predictable protection at the flock/herd level.

Systematic review of surveillance systems and methods for early detection of exotic, new and re-emerging diseases in animal populations.

In this globalized world, the spread of new, exotic and re-emerging diseases has become one of the most important threats to animal production and public health. This systematic review analyses conventional and novel early detection methods applied to surveillance. In all, 125 scientific documents were considered for this study. Exotic (n = 49) and re-emerging (n = 27) diseases constituted the most frequently represented health threats. In addition, the majority of studies were related to zoonoses (n = 66). The approaches found in the review could be divided in surveillance modalities, both active (n = 23) and passive (n = 5); and tools and methodologies that support surveillance activities (n = 57). Combinations of surveillance modalities and tools (n = 40) were also found. Risk-based approaches were very common (n = 60), especially in the papers describing tools and methodologies (n = 50). The main applications, benefits and limitations of each approach were extracted from the papers. This information will be very useful for informing the development of tools to facilitate the design of cost-effective surveillance strategies. Thus, the current literature review provides key information about the advantages, disadvantages, limitations and potential application of methodologies for the early detection of new, exotic and re-emerging diseases.

Farm-level risk factors for the occurrence, new infection or persistence of tuberculosis in cattle herds from South-Central Spain.

Eradication of tuberculosis (TB) in cattle is a priority in the EU. However, and despite the resources invested, TB eradication is still a goal yet to be accomplished. As a consequence, the identification of risk factors contributing to TB transmission and persistence is key to a better understand and, ultimately, more cost-effectively control and eradicate this complex zoonotic disease worldwide. This study aimed to identify the factors contributing to the TB occurrence, new infection, and persistence in one of the most TB-prevalent regions in the South-Central part of Spain (SCS), Ciudad Real (CR), and for which high quality and detailed information on cattle and wild ungulate demographics, management, and sanitary status was available for up to 5 years (2007-2011). Multilevel logistic modeling was used for this purpose. Results of this study revealed that the risk for TB (occurrence, new infection, and/or persistence) in cattle herds from CR is related to TB-persistence on farm in previous years, extensive production systems (beef and bullfighting being more risky that dairy) and large farm in terms of cattle number. Also, the presence and proximity of fenced hunting estates (which are usually intensively managed) significantly contributed to the risk of TB occurrence and persistence in CR. This association suggests that wild ungulates may play a role as TB-reservoirs and transmit TB to cattle in the CR, a region where TB is endemic and is associated with extensive farming of beef cattle. To the best of author's knowledge this is the first study to (i) evaluate the wild ungulate-domestic interface at a farm level using detailed information over an extensive region and period of time (2007-2011) and (ii) to identify a direct association between TB in cattle and the proximity and management practices of wild ungulates. Methods and results presented here may support policies to better prevent and control TB in the SCS and in other regions/countries with similar epidemiological conditions.

Interspecific introgression and changes in population structure in a flatfish species complex after the Prestige accident.

Oil spills cause aggressive impacts on marine ecosystems affecting immense areas and the species inhabiting them. If wastes are not cleaned up properly, the remnants may affect local populations for a long time. This work focuses on the long-term impacts of the Prestige spillage that occurred off Galician coast (Spain) in November 2002. Model species were two sympatric flatfish, the megrims Lepidorhombus whiffiagonis and Lepidorhombus boscii. Samples obtained before and nine years after the Prestige accident from affected and unaffected areas were genotyped for six hypervariable nuclear markers and for the mitochondrial D-loop sequence. The results revealed a high proportion of post-F1 interspecific hybrids in the area affected, and also increased intraspecific population differentiation likely due to such localized introgression of foreign genes. These changes suggest the appearance of a hybrid zone following the accident and emphasize the need of paying special attention to potential evolutionary impacts of oil spills.

Thickness of superficial basal cell carcinoma (sBCC) predicts imiquimod efficacy: a proposal for a thickness-based definition of sBCC.

BACKGROUND: Basal cell carcinoma (BCC) is the most common malignancy in the white population. It is an important driver of healthcare costs and causes significant morbidity. Topical imiquimod is a good noninvasive treatment alternative for surgical excision in superficial BCC (sBCC). However, there are currently no uniform histological definitions of sBCC. A definition based on tumour thickness might be a good alternative. OBJECTIVES: To determine whether tumour thickness in sBCC is a predictor of treatment failure. METHODS: We retrospectively examined 127 histological biopsy specimens of sBCC treated primarily with imiquimod five times a week for 6 weeks. Mean follow-up was 34 months (range 3-91). Recurrence was evaluated clinically with histological verification. RESULTS: Among nonrecurrent cases the median tumour thickness was 0·26 mm (range 0·09-0·61), while for recurrent cases the median tumour thickness was 0·57 mm (range 0·41-1·41, P < 0·0001). Among lesions ≤ 0·40 mm in thickness, none recurred, whereas for lesions > 0·40 mm the recurrence rate was 58% (P < 0·0001). CONCLUSIONS: We recommend the use of tumour thickness to define the superficial pattern in pathology reports for BCC as this can help to determine treatment response of sBCC to imiquimod.

Spitzoid and non-spitzoid melanoma in children: a prognostic comparative study.

BACKGROUND: Spitzoid melanoma is a rare melanoma subtype often developing in children with unknown biological potential. OBJECTIVES: To compare the clinical and histopathological factors that influence the biological behaviour between spitzoid and non-spitzoid childhood melanoma, to establish if the spitzoid subset of melanoma has different prognosis than other types of childhood melanomas. METHODS: A comparison of the prognostic significance of clinical and pathological findings between 38 spitzoid (SM) and 99 non-spitzoid melanomas (N-SM) in children and teenagers younger than 18 years referred to UT - MD Anderson Cancer Center during the period 1992-2007. RESULTS: Children with SM were significantly younger than those with N-SM, had more frequently multiple melanocytic nevi, nodular melanoma subtype with vertical growth phase, high Breslow thickness and mitotic rate, positive sentinel lymph node biopsy and more advanced stage. N-SM had more often associated nevus. However, the mortality rate in the SM group was lower (5.9%) than in the N-SM group (12.0%). This study has two major limitations. Small size of both groups does not allow reaching statistically significant differences regarding mortality. Using metastatic potential as an inclusion criterion for SM could result in a sample selection bias of the most aggressive group of SM. CONCLUSIONS: Although SM patients had poorer prognostic factors than N-SM patients, slightly lower mortality rate was detected in the SM group. This less aggressive behaviour could be due to lower potential for widespread distant metastases than conventional melanomas or younger age of children with SM.

GHEP-ISFG proficiency test 2011: Paper challenge on evaluation of mitochondrial DNA results.

The GHEP-ISFG Working Group performed a collaborative exercise to monitor the current practice of mitochondrial (mt)DNA reporting. The participating laboratories were invited to evaluate a hypothetical case example and assess the statistical significance of a match between the haplotypes of a case (hair) sample and a suspect. A total of 31 forensic laboratories participated of which all but one used the EMPOP database. Nevertheless, we observed a tenfold range of reported LR values (32-333.4), which was mainly due to the selection of different reference datasets in EMPOP but also due to different applied formulae. The results suggest the need for more standardization as well as additional research to harmonize the reporting of mtDNA evidence.

Agreement of dermatopathologists in the evaluation of clinically difficult melanocytic lesions: how golden is the 'gold standard'?

BACKGROUND: The 'gold standard' for the diagnosis of melanocytic lesions is dermatopathology. Although most of the diagnostic criteria are clearly defined, the interpretation of histopathology slides may be subject to interobserver variability. OBJECTIVES: The aim of this study was to determine the variability among dermatopathologists in the interpretation of clinically difficult melanocytic lesions. METHODS: This study used the database of MelaFind®, a computer-vision system for the diagnosis of melanoma. All lesions were surgically removed and sent for independent evaluation by four dermatopathologists. Agreement was calculated using kappa statistics. RESULTS: A total of 1,249 pigmented melanocytic lesions were included. There was a substantial agreement among expert dermatopathologists: two-category kappa was 0.80 (melanoma vs. non-melanoma) and three-category kappa was 0.62 (malignant vs. borderline vs. benign melanocytic lesions). The agreement was significantly greater for patients ≥40 years (three-category kappa = 0.67) than for younger patients (kappa = 0.49). In addition, the agreement was significantly lower for patients with atypical mole syndrome (AMS) (kappa = 0.31) than for patients without AMS (kappa = 0.76). LIMITATIONS: The data were limited by the inclusion/exclusion criteria of the MelaFind® study. This might represent a selection bias. The agreement was evaluated using kappa statistics. This is a standard method for evaluating agreement among pathologists, but might be considered controversial by some statisticians. CONCLUSIONS: Expert dermatopathologists have a high level of agreement when diagnosing clinically difficult melanocytic lesions. However, even among expert dermatopathologists, the current 'gold standard' is not perfect. Our results indicate that lesions from younger patients and patients with AMS may be more problematic for the dermatopathologists, suggesting that improved diagnostic criteria are needed for such patients.