Stevan R. Knezevich

The MPATH-Dx reporting schema for melanocytic proliferations and melanoma.

BACKGROUND The histologic diagnosis of melanoma and nevi can be subject to discordance and errors, potentially leading to inappropriate treatment and harm. Diagnostic terminology is not standardized, creating confusion for providers and patients and challenges for investigators. OBJECTIVE We sought to describe the development of a pathology reporting form for more precise research on melanoma and a diagnostic-treatment mapping tool for improved patient care and consistency in treatment. METHODS Three dermatopathologists independently reviewed melanocytic lesions randomly selected from a dermatopathology database. Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) reporting schema evolved from iterative case review and form revision. RESULTS Differences in diagnostic thresholds, interpretation, and nomenclature contributed to development of the MPATH-Dx histology reporting form, which groups lesions by similarities in histogenesis and degrees of atypia. Because preliminary results indicate greater agreement regarding suggested treatments than for specific diagnoses, the diverse terminologies of the MPATH-Dx histology reporting form were stratified by commonalities of treatments in the MPATH-Dx diagnostic-treatment mapping scheme. LIMITATIONS Without transformative advances in diagnostic paradigms, the interpretation of melanocytic lesions frequently remains subjective. CONCLUSIONS The MPATH-Dx diagnostic-treatment mapping scheme could diminish confusion for those receiving reports by categorizing diverse nomenclature into a hierarchy stratified by suggested management interventions.

Pathologists’ diagnosis of invasive melanoma and melanocytic proliferations: observer accuracy and reproducibility study

Objective To quantify the accuracy and reproducibility of pathologists’ diagnoses of melanocytic skin lesions. Design Observer accuracy and reproducibility study. Setting 10 US states. Participants Skin biopsy cases (n=240), grouped into sets of 36 or 48. Pathologists from 10 US states were randomized to independently interpret the same set on two occasions (phases 1 and 2), at least eight months apart. Main outcome measures Pathologists’ interpretations were condensed into five classes: I (eg, nevus or mild atypia); II (eg, moderate atypia); III (eg, severe atypia or melanoma in situ); IV (eg, pathologic stage T1a (pT1a) early invasive melanoma); and V (eg, ≥pT1b invasive melanoma). Reproducibility was assessed by intraobserver and interobserver concordance rates, and accuracy by concordance with three reference diagnoses. Results In phase 1, 187 pathologists completed 8976 independent case interpretations resulting in an average of 10 (SD 4) different diagnostic terms applied to each case. Among pathologists interpreting the same cases in both phases, when pathologists diagnosed a case as class I or class V during phase 1, they gave the same diagnosis in phase 2 for the majority of cases (class I 76.7%; class V 82.6%). However, the intraobserver reproducibility was lower for cases interpreted as class II (35.2%), class III (59.5%), and class IV (63.2%). Average interobserver concordance rates were lower, but with similar trends. Accuracy using a consensus diagnosis of experienced pathologists as reference varied by class: I, 92% (95% confidence interval 90% to 94%); II, 25% (22% to 28%); III, 40% (37% to 44%); IV, 43% (39% to 46%); and V, 72% (69% to 75%). It is estimated that at a population level, 82.8% (81.0% to 84.5%) of melanocytic skin biopsy diagnoses would have their diagnosis verified if reviewed by a consensus reference panel of experienced pathologists, with 8.0% (6.2% to 9.9%) of cases overinterpreted by the initial pathologist and 9.2% (8.8% to 9.6%) underinterpreted. Conclusion Diagnoses spanning moderately dysplastic nevi to early stage invasive melanoma were neither reproducible nor accurate in this large study of pathologists in the USA. Efforts to improve clinical practice should include using a standardized classification system, acknowledging uncertainty in pathology reports, and developing tools such as molecular markers to support pathologists’ visual assessments.

Variability in mitotic figures in serial sections of thin melanomas

BACKGROUND T1 melanoma staging is significantly affected by tissue sampling approaches, which have not been well characterized. OBJECTIVE We sought to characterize presence of mitotic figures across a minimum of 5 sequential sections of T1 melanomas. METHODS A cohort of T1 melanomas with either 5 (single section per slide) or 10 (2 sections per slide) sequential sections (5-μm thickness) per case were prepared and examined for mitotic figures. RESULTS In all, 44 of 82 T1 melanomas (54%) were classified as T1b. The number of sections with a mitotic figure present ranged from only 1 of 5 sections (n = 5 of 44 cases, 11.4%) to all 5 (n = 20 of 44 cases, 45.5%). A sequential approach versus a nonsequential approach did not appear to matter. LIMITATION Cases were taken from a single pathology practice in the Pacific Northwest, which may not generalize to other populations in the United States. CONCLUSION The variation in the presence of mitotic figures within sequential sections supports reviewing 3 to 5 sections to fulfill American Joint Committee on Cancer recommendations. The prognostic significance of a T1b melanoma with a rare mitotic figure on a single section versus a T1b melanoma with mitotic figures on multiple sections deserves more attention to see if further subclassification is possible or even necessary.

Teledermatology in the diagnosis of melanoma.

Summary We conducted a retrospective chart review of US Veterans in the Pacific Northwest area to compute melanoma incidence and Breslow depth at diagnosis. We compared Veterans with access to teledermatology (TD) and those without (non-TD). We identified pathology-confirmed primary melanomas in Veterans who had had at least one encounter at a VA facility during a 3-year study period. The age-adjusted melanoma incidence for all, TD and non-TD Veterans was 36, 15 and 57 per 100,000, respectively. The mean Breslow depth was significantly greater in the TD group (P = 0.03). Although a higher proportion of thin (Breslow depth ≤1 mm) TD melanomas were mitotically active, this difference was not significant. We also found that 180 (40%) of the non-TD (face-to-face) diagnosed melanomas were from Veterans living in areas where TD was available. This suggests that the higher melanoma incidence in the non-TD group was mainly due to under-utilization of TD services. The study demonstrated that the TD service was not fully utilized in the VISN20 region, although the reasons for this are not clear. Where TD was utilized it tended to diagnose more advanced melanomas with worse initial prognosis.

Achieving consensus for the histopathologic diagnosis of melanocytic lesions: use of the modified Delphi method.

To understand the sophisticated nature of coming to consensus when diagnosing complex melanocytic lesions among a panel of experienced dermatopathologists.

The utilization of spitz‐related nomenclature in the histological interpretation of cutaneous melanocytic lesions by practicing pathologists: results from the M‐Path study

Spitz nevi, atypical Spitz tumors and spitzoid melanomas (‘spitzoid lesions’) represent controversial and poorly understood cutaneous melanocytic lesions that are difficult to diagnose histologically. It is unknown how these terms are used by pathologists.

The self-reported use of immunostains and cytogenetic testing in the diagnosis of melanoma by practicing U.S. pathologists of 10 selected states.

The diagnosis of melanoma can be challenging, especially in lesions for which the histopathologic criteria bridge two or more taxonomic categories. Newer genomic analytical methods of fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH) have been introduced as ancillary techniques to differentiate benign and malignant melanocytic proliferations.

THE UTILIZATION OF SPITZ‐RELATED NOMENCLATURE IN THE HISTOLOGICAL INTERPRETATION OF CUTANEOUS MELANOCYTIC LESIONS BY PRACTICING PATHOLOGISTS

Spitz nevi, atypical Spitz tumors and spitzoid melanomas (‘spitzoid lesions’) represent controversial and poorly understood cutaneous melanocytic lesions that are difficult to diagnose histologically. It is unknown how these terms are used by pathologists.

Eruptive seborrheic keratoses associated with adalimumab use

BACKGROUND Seborrheic keratoses are common, benign cutaneous growths, however in rare situations they can acutely erupt in large numbers. Eruptive seborrheic keratoses can be associated with internal malignancy (sign of Leser-Trelat), but may also appear in conjunction with inflammatory dermatoses and adverse drug reactions. MAIN OBSERVATION A 71-year-old Caucasian man presented with acute onset of a pruritic, burning papular erythematous rash on his chest, upper extremities and lower extremities after a routine adalimumab injection for rheumatoid arthritis. Two skin biopsies obtained showed findings diagnostic of seborrheic keratoses. Spontaneous resolution of the diffuse eruptive seborrheic keratoses was achieved within 3 months of discontinuing adalimumab therapy. CONCLUSIONS We believe the development of eruptive seborrheic keratoses due to adalimumab therapy is rare, and because our patient responded promptly to discontinuation of the drug we suggest this should be the preferred course of action in future cases.

Complexities of perceived and actual performance in pathology interpretation: A comparison of cutaneous melanocytic skin and breast interpretations

Little is known about how pathologists process differences between actual and perceived interpretations.