Prognostic modeling of cutaneous melanoma stage I patients using cancer registry data identifies subsets with very-low melanoma mortality.

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.

Characterization of multiple diagnostic terms in melanocytic skin lesion pathology reports.

BACKGROUND: Histopathologically ambiguous melanocytic lesions lead some pathologists to list multiple diagnostic considerations in the pathology report. The frequency and circumstance of multiple diagnostic considerations remain poorly characterized. METHODS: Two hundred and forty skin biopsy samples were interpreted by 187 pathologists (8976 independent diagnoses) and classified according to a diagnostic/treatment stratification (MPATH-Dx). RESULTS: Multiple diagnoses in different MPATH-Dx classes were used in n = 1320 (14.7%) interpretations, with 97% of pathologists and 91% of cases having at least one such interpretation. Multiple diagnoses were more common for intermediate risk lesions and are associated with greater subjective difficulty and lower confidence. We estimate that 6% of pathology reports for melanocytic lesions in the United States contain two diagnoses of different MPATH-Dx prognostic classes, and 2% of cases are given two diagnoses with significant treatment implications. CONCLUSIONS: Difficult melanocytic diagnoses in skin may necessitate multiple diagnostic considerations; however, as patients increasingly access their health records and retrieve pathology reports (as mandated by US law), uncertainty should be expressed unambiguously.

Segmenting Skin Biopsy Images with Coarse and Sparse Annotations using U-Net.

The number of melanoma diagnoses has increased dramatically over the past three decades, outpacing almost all other cancers. Nearly 1 in 4 skin biopsies is of melanocytic lesions, highlighting the clinical and public health importance of correct diagnosis. Deep learning image analysis methods may improve and complement current diagnostic and prognostic capabilities. The histologic evaluation of melanocytic lesions, including melanoma and its precursors, involves determining whether the melanocytic population involves the epidermis, dermis, or both. Semantic segmentation of clinically important structures in skin biopsies is a crucial step towards an accurate diagnosis. While training a segmentation model requires ground-truth labels, annotation of large images is a labor-intensive task. This issue becomes especially pronounced in a medical image dataset in which expert annotation is the gold standard. In this paper, we propose a two-stage segmentation pipeline using coarse and sparse annotations on a small region of the whole slide image as the training set. Segmentation results on whole slide images show promising performance for the proposed pipeline.

Histopathologic synoptic reporting of invasive melanoma: How reliable are the data?

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.

Terminology for melanocytic skin lesions and the MPATH-Dx classification schema: A survey of dermatopathologists.

BACKGROUND: Diagnostic terms used in histopathology reports of cutaneous melanocytic lesions are not standardized. We describe dermatopathologists' views regarding diverse diagnostic terminology and the utility of the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) for categorizing melanocytic lesions. METHODS: July 2018-2019 survey of board-certified and/or fellowship-trained dermatopathologists with experience interpreting melanocytic lesions. RESULTS: Among 160 participants, 99% reported witnessing different terminology being used for the same melanocytic lesion. Most viewed diverse terminology as confusing to primary care physicians (98%), frustrating to pathologists (83%), requiring more of their time as a consultant (64%), and providing necessary clinical information (52%). Most perceived that adoption of the MPATH-Dx would: improve communication with other pathologists and treating physicians (87%), generally be a change for the better (80%), improve patient care (79%), be acceptable to clinical colleagues (68%), save time in pathology report documentation (53%), and protect from malpractice (51%). CONCLUSIONS: Most dermatopathologists view diverse terminology as contributing to miscommunication with clinicians and patients, adversely impacting patient care. They view the MPATH-Dx as a promising tool to standardize terminology and improve communication. The MPATH-Dx may be a useful supplement to conventional pathology reports. Further revision and refinement are necessary for widespread clinical use.

Pathologists' agreement on treatment suggestions for melanocytic skin lesions.

BACKGROUND: Although treatment guidelines exist for melanoma in situ and invasive melanoma, guidelines for other melanocytic skin lesions do not exist. OBJECTIVE: To examine pathologists' treatment suggestions for a broad spectrum of melanocytic skin lesions and compare them with existing guidelines. METHODS: Pathologists (N = 187) completed a survey and then provided diagnoses and treatment suggestions for 240 melanocytic skin lesions. Physician characteristics associated with treatment suggestions were evaluated with multivariable modeling. RESULTS: Treatment suggestions were concordant with National Comprehensive Cancer Network guidelines for the majority of cases interpreted as melanoma in situ (73%) and invasive melanoma (86%). Greater variability of treatment suggestions was seen for other lesion types without existing treatment guidelines. Characteristics associated with provision of treatment suggestions discordant with National Comprehensive Cancer Network guidelines were low caseloads (invasive melanoma), lack of fellowship training or board certification (melanoma in situ), and more than 10 years of experience (invasive melanoma and melanoma in situ). LIMITATIONS: Pathologists could not perform immunohistochemical staining or other diagnostic tests; only 1 glass side was provided per biopsy case. CONCLUSIONS: Pathologists' treatment suggestions vary significantly for melanocytic lesions, with lower variability for lesion types with national guidelines. Results suggest the need for standardization of treatment guidelines for all melanocytic lesion types.

Factors associated with use of immunohistochemical markers in the histopathological diagnosis of cutaneous melanocytic lesions.

BACKGROUND: Melanocytic tumors are often challenging and constitute almost one in four skin biopsies. Immunohistochemical (IHC) studies may assist diagnosis; however, indications for their use are not standardized. METHODS: A test set of 240 skin biopsies of melanocytic tumors was examined by 187 pathologists from 10 US states, interpreting 48 cases in Phase I and either 36 or 48 cases in Phase II. Participant and diagnosis characteristics were compared between those who reported they would have ordered, or who would have not ordered IHC on individual cases. Intraobserver analysis examined consistency in the intent to order when pathologists interpreted the same cases on two occasions. RESULTS: Of 187 participants interpreting 48 cases each, 21 (11%) did not request IHC tests for any case, 85 (45%) requested testing for 1 to 6 cases, and 81 (43%) requested testing for ≥6 cases. Of 240 cases, 229 had at least one participant requesting testing. Only 2 out of 240 cases had more than 50% of participants requesting testing. Increased utilization of testing was associated with younger age of pathologist, board-certification in dermatopathology, low confidence in diagnosis, and lesions in intermediate MPATH-Dx classes 2 to 4. The median intraobserver concordance for requesting tests among 72 participants interpreting the same 48 cases in Phases I and II was 81% (IQR 73%-90%) and the median Kappa statistic was 0.20 (IQR 0.00, 0.39). CONCLUSION: Substantial variability exists among pathologists in utilizing IHC.

Impact on clinical practice of a non-invasive gene expression melanoma rule-out test: 12-month follow-up of negative test results and utility data from a large US registry study.

The Pigmented Lesion Assay (PLA, sensitivity 91-95%, specificity 69-91%, negative predictive value ?99%) is a commercially available, non-invasive gene expression test that helps dermatologists guide pigmented lesion management decisions and rule out melanoma. Earlier studies have demonstrated high clinical utility and no missed melanomas in a 3-6-month follow-up period. We undertook the current investigations to provide 12-month follow-up data on PLA(-) tests, and to further confirm utility. A 12-month chart review follow-up of 734 pigmented lesions that had negative PLA results from 5 US dermatology centers was performed. Thirteen of these lesions (1.8%) were biopsied in the follow-up period and submitted for histopathologic review. None of the lesions biopsied had a histopathologic diagnosis of melanoma. The test's utility was studied further in a registry (N=1575, 40 US dermatology offices, 62 participating providers), which demonstrated that 99.9% of PLA(-) lesions were clinically monitored, thereby avoiding a surgical procedure, and 96.5% of all PLA(+) lesions were appropriately biopsied, most commonly with a tangential shave. This long-term follow-up study confirms the PLA's high negative predictive value and high utility in helping guide the management of pigmented lesions to avoid unnecessary surgical procedures.

Corrigendum: Impact on clinical practice of a non-invasive gene expression melanoma rule-out test: 12-month followup of negative test results and utility data from a large US registry study.

The revised version of the article corrected Figure 2. This change appears in the revised online PDF copy of this article.

Pathologist characteristics associated with accuracy and reproducibility of melanocytic skin lesion interpretation.

BACKGROUND: Diagnostic interpretations of melanocytic skin lesions vary widely among pathologists, yet the underlying reasons remain unclear. OBJECTIVE: Identify pathologist characteristics associated with rates of accuracy and reproducibility. METHODS: Pathologists independently interpreted the same set of biopsy specimens from melanocytic lesions on 2 occasions. Diagnoses were categorized into 1 of 5 classes according to the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis system. Reproducibility was determined by pathologists' concordance of diagnoses across 2 occasions. Accuracy was defined by concordance with a consensus reference standard. Associations of pathologist characteristics with reproducibility and accuracy were assessed individually and in multivariable logistic regression models. RESULTS: Rates of diagnostic reproducibility and accuracy were highest among pathologists with board certification and/or fellowship training in dermatopathology and in those with 5 or more years of experience. In addition, accuracy was high among pathologists with a higher proportion of melanocytic lesions in their caseload composition and higher volume of melanocytic lesions. LIMITATIONS: Data gathered in a test set situation by using a classification tool not currently in clinical use. CONCLUSION: Diagnoses are more accurate among pathologists with specialty training and those with more experience interpreting melanocytic lesions. These findings support the practice of referring difficult cases to more experienced pathologists to improve diagnostic accuracy, although the impact of these referrals on patient outcomes requires additional research.