Background
Synoptic reporting is recommended by many guideline committees to encourage the thorough histologic documentation necessary for optimal management of patients with melanoma.
Methods
One ...hundred fifty‐one pathologists from 40 US states interpreted 41 invasive melanoma cases. For each synoptic reporting factor, the authors identified cases with “complete agreement” (all participants recorded the same value) versus any disagreement. Pairwise agreement was calculated for each case as the proportion of pairs of responses that agreed, where paired responses were generated by the comparison of each reviewer's response with all others.
Results
There was complete agreement among all reviewers for 22 of the 41 cases (54%) on Breslow thickness dichotomized at 0.8 mm, with pairwise agreement ranging from 49% to 100% across the 41 cases. There was complete agreement for “no ulceration” in 24 of the 41 cases (59%), with pairwise agreement ranging from 42% to 100%. Tumor transected at base had complete agreement for 26 of the 41 cases (63%), with pairwise agreement ranging from 31% to 100%. Mitotic rate, categorized as 0/mm2, 1/mm2, or 2/mm2, had complete agreement for 17 of the 41 cases (41%), with pairwise agreement ranging from 36% to 100%. Regression saw complete agreement for 14 of 41 cases (34%), with pairwise agreement ranging from 40% to 100%. Lymphovascular invasion, perineural invasion, and microscopic satellites were rarely reported as present. Respectively, these prognostic factors had complete agreement for 32 (78%), 37 (90%), and 18 (44%) of the 41 cases, and the ranges of pairwise agreement were 47% to 100%, 70% to 100%, and 53% to 100%, respectively.
Conclusions
These findings alert pathologists and clinicians to the problem of interobserver variability in recording critical prognostic factors.
Lay Summary
This study addresses variability in the assessment and reporting of critical characteristics of invasive melanomas that are used by clinicians to guide patient care.
The authors characterize the diagnostic variability among pathologists and their reporting methods in light of recently updated national guidelines. Results demonstrate considerable variability in the diagnostic reporting of melanoma with regard to the following: Breslow thickness, mitotic rate, ulceration, regression, and microscopic satellites.
This work serves to alert pathologists and clinicians to the existence of variability in reporting these prognostic factors.
This work serves to alert pathologists and clinicians alike to an existing problem of interobserver variability in reporting critical histopathological prognostic factors, including Breslow thickness, ulceration, and others, that are requisite to the optimal management of patients with melanoma.
Clinical guidelines for the treatment of melanoma are based largely on the behavior of thicker tumors. As a result, little is known about survival differences among patients with thinner tumors.
To ...investigate the variability in survival for American Joint Committee on Cancer stage T1 thin melanoma tumors, defined as tumors less than 1 mm thick at diagnosis.
This population-based series included 43,008 non-Hispanic whites in whom cutaneous melanoma was diagnosed between 2004 and 2013 from the California Cancer Registry. Survival outcomes were estimated using the Kaplan-Meier method. Cox proportional hazard models were used to estimate risk of death.
Survival for patients with thin ulcerated tumors was comparable to that for patients with stage II tumors, who are currently treated more aggressively. At 12 months, patients with thin ulcerated tumors had approximately 6% lower survival (92.5% 95% confidence interval (CI), 90.6%-93.9%) compared with patients with thin nonulcerated tumors (98.2% 95% CI, 98.0%-98.3%). At 24 months, this survival difference increased (85.2% 95% CI, 82.8%-87.4% vs 96.1% 95% CI, 95.8-96.3% for those with thin ulcerated and thin nonulcerated tumors, respectively) and a greater than 15% survival difference was seen at 60 months.
Previous reports of cancer registry data have noted some evidence of miscoding of thin tumors.
The poorer survival in patients with ulcerated tumors less than 1 mm thick implies the need for additional studies to determine potential benefits of more aggressive treatment.
Background
Evidence exists that escalating melanoma incidence is due in part to overdiagnosis, the diagnosis of lesions that will not lead to symptoms or death. The authors aimed to characterize ...subsets of melanoma patients with very‐low risk of death that may be contributing to overdiagnosis.
Methods
Melanoma patients diagnosed in 2010 and 2011 with stage I lesions ≤1.0 mm thick and negative clinical lymph nodes from the Surveillance, Epidemiology, and End Results database were selected. Classification and regression tree and logistic regression models were developed and validated to identify patients with very‐low risk of death from melanoma within 7 years. Logistic models were also used to identify patients at higher risk of death among this group of stage I patients.
Results
Compared to an overall 7‐year mortality from melanoma of 2.5% in these patients, a subset comprising 25% had a risk below 1%. Younger age at diagnosis and Clark level II were associated with low risk of death in all models. Breslow thickness below 0.4 mm, absence of mitogenicity, absence of ulceration, and female sex were also associated with lower mortality. A small subset of high‐risk patients with >20% risk of death was also identified.
Conclusion
Patients with very‐low risk of dying from melanoma within 7 years of diagnosis were identified. Such cases warrant further study and consensus discussion to develop classification criteria, with the potential to be categorized using an alternative term such as “melanocytic neoplasms of low malignant potential.”
Lay summary
Although melanoma is the most serious skin cancer, most melanoma patients have high chances of survival.
There is evidence that some lesions diagnosed as melanoma would never have caused symptoms or death, a phenomenon known as overdiagnosis.
In this study, we used cancer registry data to identify a subset of early‐stage melanoma patients with almost no melanoma deaths.
Using two statistical approaches, we identified patients with <1% risk of dying from melanoma in 7 years.
Such patients tended to be younger with minimal invasion into the skin.
We also identified a very small patient subset with higher mortality risk.
This Surveillance, Epidemiology, and End Results analysis identified subsets of stage I melanoma patients with <1% risk of death from melanoma within 7 years of diagnosis. Clark level II invasion and younger patient age were associated with lower risk of death from melanoma.
The incidence of melanoma diagnoses has been increasing in recent decades, and controlled studies have indicated high histopathologic discordance across the intermediate range of melanocytic lesions. ...The respective causes for these phenomena remain incompletely understood.
To identify pathologist characteristics associated with tendencies to diagnose melanocytic lesions as higher grade vs lower grade or to diagnose invasive melanoma vs any less severe diagnosis.
This exploratory study used data from 2 nationwide studies (the Melanoma Pathology M-Path study, conducted from July 2013 to May 2016, and the Reducing Errors in Melanocytic Interpretations REMI study, conducted from August 2018 to March 2021) in which participating pathologists who interpreted melanocytic lesions in their clinical practices interpreted study cases in glass slide format. Each pathologist was randomly assigned to interpret a set of study cases from a repository of skin biopsy samples of melanocytic lesions; each case was independently interpreted by multiple pathologists. Data were analyzed from July 2022 to February 2023.
The association of pathologist characteristics with diagnosis of a study case as higher grade (including severely dysplastic and melanoma in situ) vs lower grade (including mild to moderately dysplastic nevi) and diagnosis of invasive melanoma vs any less severe diagnosis was assessed using logistic regression. Characteristics included demographics (age, gender, and geographic region), years of experience, academic affiliation, caseload of melanocytic lesions in their practice, specialty training, and history of malpractice suits.
A total of 338 pathologists were included: 113 general pathologists and 74 dermatopathologists from M-Path and 151 dermatopathologists from REMI. The predominant factor associated with rendering more severe diagnoses was specialist training in dermatopathology (board certification and/or fellowship training). Pathologists with this training were more likely to render higher-grade diagnoses (odds ratio OR, 2.63; 95% CI, 2.10-3.30; P < .001) and to diagnose invasive melanoma (OR, 1.95; 95% CI, 1.53-2.49; P < .001) than pathologists without this training interpreting the same case. Nonmitogenic pT1a diagnoses (stage pT1a melanomas with no mitotic activity) accounted for the observed difference in diagnosis of invasive melanoma; when these lesions, which carry a low risk of metastasis, were grouped with the less severe diagnoses, there was no observed association (OR, 0.95; 95% CI, 0.74-1.23; P = .71). Among dermatopathologists, those with a higher caseload of melanocytic lesions in their practice were more likely to assign higher-grade diagnoses (OR for trend, 1.27; 95% CI, 1.04-1.56; P = .02).
The findings suggest that specialty training in dermatopathology is associated with a greater tendency to diagnose atypical melanocytic proliferations as pT1a melanomas. These low-risk melanomas constitute a growing proportion of melanomas diagnosed in the US.
Pathologic assessment to diagnose skin biopsies, especially for cutaneous melanoma, can be challenging, and immunohistochemistry (IHC) staining has the potential to aid decision-making. Currently, ...the temporal trends regarding the use of IHC for the examination of skin biopsies on a national level have not been described.
To illustrate trends in the use of IHC for the examination of skin biopsies in melanoma diagnoses.
A retrospective cross-sectional study was conducted to examine incident cases of melanoma diagnosed between January 2000 and December 2017. The analysis used the SEER-Medicare linked database, incorporating data from 17 population-based registries. The study focused on incident cases of in situ or malignant melanoma of the skin diagnosed in patients 65 years or older. Data were analyzed between August 2022 and November 2023.
The main outcomes encompassed the identification of claims for IHC within the month of melanoma diagnoses and extending up to 14 days into the month following diagnosis. The SEER data on patients with melanoma comprised demographic, tumor, and area-level characteristics.
The final sample comprised 132 547 melanoma tumors in 116 117 distinct patients. Of the 132 547 melanoma diagnoses meeting inclusion criteria from 2000 to 2017, 43 396 cases had accompanying IHC claims (33%). Among these cases, 28 298 (65%) were diagnosed in male patients, 19 019 (44%) were diagnosed in patients aged 65 years to 74 years, 16 444 (38%) in patients aged 75 years to 84 years, and 7933 (18%) in patients aged 85 years and older. In 2000, 11% of melanoma cases had claims for IHC at or near the time of diagnosis. This proportion increased yearly, with 51% of melanoma cases having associated IHC claims in 2017. Increasing IHC use is observed for all stages of melanoma, including in situ melanoma. Claims for IHC in melanomas increased in all 17 SEER registries but at different rates. In 2017, the use of IHC for melanoma diagnosis ranged from 39% to 68% across registries.
Considering the dramatically rising and variable use of IHC in diagnosing melanoma by pathologists demonstrated in this retrospective cross-sectional study, further investigation is warranted to understand the clinical utility and discern when IHC most improves diagnostic accuracy or helps patients.
Background
Persistent controversy exists with regard to how and when patients with head and neck cancer should undergo imaging after definitive therapy. The current study was conducted to evaluate ...whether the type of imaging modality used in posttreatment imaging impacts cancer‐specific survival for patients with advanced head and neck squamous cell carcinoma.
Methods
A retrospective study of National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program–Medicare‐linked data in patients with an advanced stage of the 3 most common head and neck malignancies (oral cavity, oropharynx, and larynx) was conducted. Hazard ratios and 95% CIs for cancer‐specific survival were estimated for patients diagnosed with any of these cancers between 2006 and 2015.
Results
Significant improvement with regard to cancer‐specific survival was observed among patients with American Joint Committee on Cancer stage III and stage IVA laryngeal cancer who underwent positron emission tomography (PET) and/or computed tomography (CT) imaging during the first 6 months after receipt of definitive treatment (hazard ratio, 0.517; 95% CI, 0.33‐0.811) compared with those who underwent CT. There was a trend toward an improvement in cancer‐specific survival among patients with oral cavity or oropharyngeal malignancies who underwent PET/CT imaging, but it did not reach statistical significance.
Conclusions
Compared with CT imaging, posttreatment imaging with PET was associated with improved survival in patients with advanced laryngeal carcinoma.
Persistent controversy exists regarding how and when patients with head and neck cancer should undergo imaging after receiving definitive therapy. The current study evaluates whether the type of imaging modality used in posttreatment imaging impacts cancer‐specific survival for patients with advanced head and neck squamous cell carcinoma and finds that, compared with computed tomography imaging, posttreatment imaging using positron emission tomography is associated with improved survival in patients with advanced laryngeal carcinoma.
Despite evidence of overdiagnosis of in situ and invasive melanoma, neither the perceptions of practicing dermatopathologists about overdiagnosis nor possible associations between perceptions of ...overdiagnosis and diagnostic practices have been studied.
To examine practicing US dermatopathologists' perceptions of melanoma overdiagnosis as a public health issue, and to associate diagnostic behaviors of dermatopathologists with perceptions of melanoma overdiagnosis.
This survey study included 115 board-certified and/or fellowship-trained dermatopathologists and their diagnostic interpretations on a set of 18 skin biopsy cases (5 slide sets comprising 90 melanocytic skin lesions). Participants interpreted cases remotely using their own microscopes. Survey invitations occurred during 2018 to 2019, with data collection completed 2021. Data analysis was performed from June to September 2021.
Agreement vs disagreement that overdiagnosis is a public health issue for atypical nevi, melanoma in situ, and invasive melanoma. Associations between perceptions regarding overdiagnosis and interpretive behavior on study cases.
Of 115 dermatopathologists, 68% (95% CI, 59%-76%) agreed that overdiagnosis is a public health issue for atypical nevi; 47% (95% CI, 38%-56%) for melanoma in situ; and 35% (95% CI, 26%-43%) for invasive melanoma. Dermatopathologists with more years in practice were significantly less likely to perceive that atypical nevi are overdiagnosed, eg, 46% of dermatopathologists with 20 or more years of experience agreed that atypical nevi are overdiagnosed compared with 93% of dermatopathologists with 1 to 4 years of experience. Compared with other dermatopathologists, those who agreed that all 3 conditions are overdiagnosed were slightly more likely to diagnose study cases as mild to moderately dysplastic nevi (odds ratio, 1.26; 95% CI, 0.97-1.64; P = .08), but the difference was not statistically significant. Dermatopathologists who agreed that invasive melanoma is overdiagnosed did not significantly differ in diagnosing invasive melanoma for study cases compared with those who disagreed (odds ratio, 1.10; 95% CI, 0.86-1.41; P = .44).
In this survey study, about two-thirds of dermatopathologists thought that atypical nevi are overdiagnosed, half thought that melanoma in situ is overdiagnosed, and one-third thought that invasive melanoma is overdiagnosed. No statistically significant associations were found between perceptions about overdiagnosis and interpretive behavior when diagnosing skin biopsy cases.
Medical second opinions are common, although little is known about the best processes for obtaining them. This study assesses whether knowledge of a prior physician's diagnosis influences consulting ...physicians' diagnoses.
To measure the extent to which dermatopathologists' diagnoses are influenced by prior diagnostic information from another dermatopathologist.
Dermatopathologists were randomly assigned to interpret 1 slide set of 18 melanocytic skin biopsy specimens in 2 phases (5 slide sets totaling 90 cases). Phase 1 interpretations were conducted without prior diagnostic information. After a washout period of 12 or more months, dermatopathologists' phase 2 interpretations were conducted with their identical slide set; for a random subset of cases in phase 2, participants were shown prior diagnoses by other dermatopathologists that were either more or less severe than their own phase 1 diagnosis of the case. Using the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis tool, cases ranged from class I (benign) to class V (≥pT1b invasive melanoma). Data collection took place from August 2018 to March 2021, and data analysis was performed from March to December 2021.
Prior diagnoses were actual diagnoses from board-certified and/or fellowship-trained dermatopathologists. A prior diagnosis was always in a more severe or less severe diagnostic class than the participant's phase 1 interpretation; more or less severe was determined by the randomization scheme. In the control condition of no prior diagnostic information, the participants were told that a prior diagnosis was not available.
When exposure was to a prior diagnosis in a higher diagnostic class, the primary study outcome was whether a participant's diagnosis in phase 2 was in a higher diagnostic class than the participant's diagnosis in phase 1. When exposure was to a prior diagnosis in a lower diagnostic class, the primary study outcome was whether a participant's diagnosis in phase 2 was in a lower diagnostic class than the participant's diagnosis in phase 1. The effect of prior diagnostic information was measured using the relative risk (RR) of each outcome relative to the control condition of no prior diagnostic information, adjusted for the diagnostic class of the phase 1 diagnosis. Prior to data collection, it was hypothesized that participants would be swayed in the direction of prior diagnostic information.
A total of 149 dermatopathologists (median range age, 47 years 34-76 years; 101 68% were male) provided 5322 interpretations of study cases. Participants were more likely to increase the severity of their diagnosis when the prior diagnosis was of greater severity compared with when no prior diagnosis was provided (RR, 1.52; 95% CI, 1.34-1.73); likewise, participants gave less severe diagnoses when prior diagnoses were of lesser severity (RR, 1.38; 95% CI, 1.19-1.59). Trends were similar among dermatopathologists who had previously stated they were "not at all influenced" by prior diagnoses. Prior diagnoses also swayed dermatopathologists away from correct diagnoses.
In this randomized controlled trial, despite the preference of most dermatopathologists to receive prior diagnoses when providing second opinions, this information swayed them away from a correct diagnosis to an incorrect diagnosis.
Diagnostic error can be defined as deviation from a gold standard diagnosis, typically defined in terms of expert opinion, although sometimes in terms of unexpected events that might occur in ...follow-up (such as progression and death from disease). Although diagnostic error does exist for melanoma, deviations from gold standard diagnosis, certainly among appropriately trained and experienced practitioners, are likely to be the result of uncertainty and lack of specific criteria, and differences of opinion, rather than lack of diagnostic skills. In this review, the concept of diagnostic error will be considered in relation to diagnostic uncertainty, and the concept of overdiagnosis in melanoma will be presented and discussed.
Background
The optimal imaging for the staging of oropharyngeal cancer is not well defined.
Methods
The linked Surveillance, Epidemiology, and End Results (SEER)–Medicare database for 2006 through ...2011 was used to compare patient characteristics and hospital region by the initial imaging modality used for patients with oropharyngeal cancer. The primary outcome was 3‐year cancer‐specific survival (CSS). Cox proportional hazards models were adjusted for imaging, age, sex, region, education, race, American Joint Committee on Cancer stage of disease, and treatment, which were examined using backward elimination. The authors also explored how initial imaging use varied by patient characteristics and hospital region.
Results
A total of 1765 patients underwent initial diagnostic imaging. Of those, approximately 11.4% (202 patients) received computed tomography (CT) alone as their initial imaging modality, 5.2% (91 patients) underwent magnetic resonance imaging (MRI) without positron emission tomography (PET), and 83.3% (1472 patients) had initial imaging that included PET. The overall 3‐year CSS rate for the entire population was 63.7%. In the adjusted survival models compared by initial imaging modality, patients who underwent a PET examination were found to have higher survival than those who underwent CT alone or MRI, respectively (hazard ratio, 1.337 95% CI, 1.001‐1.785; P = .0491; and hazard ratio, 1.748 95% CI, 1.2‐2.545; P = .0036).
Conclusions
Among patients with oropharyngeal cancer, initial staging with PET imaging was associated with improved 3‐year CSS compared with initial staging with MRI or CT.
The optimal imaging for the staging of oropharyngeal cancer is not well defined. In the current study, Surveillance, Epidemiology, and End Results‐Medicare analysis demonstrates an association between initial staging with positron emission tomography and improved cancer‐specific survival for patients with squamous cell carcinoma of the oropharynx compared with initial staging using magnetic resonance imaging alone.
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