Diagnostic accuracy of whole slide imaging for cutaneous, soft tissue, and melanoma sentinel lymph node biopsies with and without immunohistochemistry.

BACKGROUND: Diagnostic accuracy with whole slide imaging (WSI) for complex inpatient and outpatient dermatopathology cases with immunohistochemistry (IHC) is unknown. METHODS: WSI (Leica Aperio AT2 Digital Pathology scanner, N = 151 cases) was performed for Emory inpatient and outpatient skin (N = 105), soft tissue (N = 30), and melanoma sentinel lymph node biopsies (N = 16) collected between 2000 and 2016. Resultant images were uploaded to an online cloud storage system for review by 2 board-certified dermatopathologists (reviewers 1 and 2) with greater than 5 years of dermatopathology experience and 1 dermatopathology fellow (reviewer 3). RESULTS: Reviewers 1 (diagnostic accuracy = 97%) and 2 (diagnostic accuracy = 95%) demonstrated high diagnostic accuracy with WSI. Diagnostic accuracy was greater than 90% for inpatient biopsies, melanocytic lesions, melanoma sentinel lymph node biopsies, and cases with immunohistochemistry, but was slightly lower for soft tissue cases (reviewer 1 = 89%; reviewer 2 = 89%). The dermatopathology fellow (reviewer 3) demonstrated lower diagnostic accuracy (84%). CONCLUSIONS: Diagnostic accuracy with WSI for skin, soft tissue, and melanoma sentinel lymph node biopsies with and without immunohistochemistry was greater than 95% for 2 reviewers with greater than 5 years of dermatopathology experience. Professional experience signing out dermatopathology cases may impact diagnostic accuracy with WSI.

Tumor stage mycosis fungoides: a single-center study on clinicopathologic features, treatments, and patient outcome.

BACKGROUND: Tumor stage mycosis fungoides (MF) is a subtype of cutaneous T-cell lymphoma (CTCL). Tumor stage MF is rarely curable. Treatment is aimed towards controlling the disease and minimizing side effects from therapy. OBJECTIVE: To characterize clinicopathologic features of tumor stage MF and the impact of clinical characteristics and treatment modalities on patient outcome. METHODS: A retrospective chart review was conducted on 39 patients with tumor stage MF followed at Vanderbilt University between July 1995 and July 2010. RESULTS: The median age of diagnosis was 61 years (IQR: 54-70). Sixty-nine percent of the patients were male (27/39). The median follow-up time was 13.6 months (IQR: 5.5-35.9). Among the patients younger than 60 years at the time of initial diagnosis (n = 19), median overall survival (OS) was 7.0 years (95% CI: 2.1-17.9), compared with 3.3 years (95% CI: 2.4-9.3) in patients who were 60 years or older at initial diagnosis. Ten patients with T1/T2 stage at diagnosis had median OS of 5.0 years (95% CI 3.2-7.0). Twenty-eight patients with T3 stage at diagnosis had median OS of 5.8 years (95% CI 2.4-14.2). Median OS for patients with large cell transformation (LCT) and without LCT was 3.3 and 7.7 years, respectively. LIMITATIONS: This is a retrospective study with the bias of a tertiary-care referral center. CONCLUSION: Although LCT and older age at diagnosis were not statistically significant negative prognostic indicators of OS, there was a trend towards statistical significance for LCT. Clinical stage at diagnosis may not affect OS in patients who develop tumor stage MF.

Discordance of histopathologic parameters in cutaneous melanoma: Clinical implications.

BACKGROUND: Histopathologic analysis remains the gold standard for the diagnosis of melanoma, however previous studies have shown a substantial rate of interobserver variability in the evaluation of melanocytic lesions. OBJECTIVE: We sought to evaluate discordance in the histopathological diagnosis and microstaging parameters of melanoma and subsequent impact on clinical management. METHODS: This was a retrospective review of 588 cases of cutaneous melanoma and melanoma in situ from January 2009 to December 2014 that were referred to Emory University Hospital, Atlanta, GA, for treatment. Per institutional policy, all outside melanoma biopsy specimens were reviewed internally. Outside and institutional reports were compared. RESULTS: Disagreement between outside and internal reports resulted in a change in American Joint Committee on Cancer pathologic stage in 114/588 (19%) cases, resulting in a change in management based on National Comprehensive Cancer Network guidelines in 105/588 (18%) cases. LIMITATIONS: Given the retrospective nature of data collection and the bias of a tertiary care referral center, cases in this study may not be representative of all melanoma diagnoses. CONCLUSION: These findings confirm consistent subjectivity in the histopathologic interpretation of melanoma. This study emphasizes that a review of the primary biopsy specimen may lead to significant changes in tumor classification, resulting in meaningful changes in clinical management.

Benign colonic metaplasia at a previous stoma site in a patient without adenomatous polyposis.

There are few reported cases of cutaneous intestinal metaplasia or primary adenocarcinoma arising at the ileostomy site following panproctocolectomy. These complications have been seen almost exclusively in patients with familial adenomatous polyposis and inflammatory bowel disease (IBD). However, benign intraepidermal colonic mucosa at a reversed ileostomy site in a patient without familial adenomatous polyposis or IBD has not been documented. We report a case of a 51-year-old female with a history of colonic adenocarcinoma who presented with pruritic, erythematous, scaly plaques on the right lower abdomen, present since reversal of her ileostomy in 2007. Skin biopsy revealed benign foci of colonic epithelium with no evidence of adenomatous change. Benign intraepidermal colonic mucosa was diagnosed based on histopathologic findings and immunohistochemistry. To our knowledge, this is the first case of intraepidermal benign colonic metaplasia forming in a patient following ostomy reversal. The case emphasizes the importance of patient education and physical examination of the stoma or stoma remnants for detection of unusual or changing lesions due to the risk for malignant transformation. It also demonstrates that benign colonic mucosa should be considered in the differential diagnosis when evaluating lesions near ileostomy sites, regardless of whether the patient has a history of familial adenomatous polyposis or IBD.

Percutaneous stereotactic radiofrequency lesioning for trigeminal neuralgia: determination of minimum clinically important difference in pain improvement for patient-reported outcomes.

BACKGROUND: The Visual Analog Scale (VAS) and the Barrow Neurological Institute Pain Scale (BNI-PS) are 2 patient-reported outcome (PRO) tools frequently used to rate pain from trigeminal neuralgia (TN). Outcomes studies often use these patient-reported outcomes to assess treatment effectiveness, but it is unknown exactly what degree of change in the numerical scores constitutes the minimum clinically important difference (MCID). MCID remains uninvestigated for percutaneous stereotactic radiofrequency lesioning (RFL), a common surgical procedure for TN. OBJECTIVE: To determine MCID values for the VAS and BNI-PS in patients undergoing RFL. METHODS: Forty-three consecutive patients with TN who underwent RFL by a single surgeon were prospectively assessed with the VAS and BNI-PS preoperatively and 3 years postoperatively. Three anchors were used to assign each patient's outcome: satisfaction, willingness to have the surgery again, and Health Transition Index. We then used 3 well-established, anchor-based methods to calculate MCID: average change, minimum detectable change, and change difference. RESULTS: Patients experienced substantial improvement in both VAS (9.81 vs 3.35; P < .001) and BNI-PS (4.95 vs 2.44; P < .001) after RFL. The 3 MCID calculation methods generated a range of MCID values for each of the PROs (VAS, 4.13-8.20; BNI-PS, 1.03-3.30). The area under the receiver-operating characteristic curve was greater for BNI-PS compared with VAS for all 3 anchors, indicating that BNI-PS is probably better suited for calculating MCID. CONCLUSION: RFL-specific MCID is variable on the basis of the calculation technique. With the use of the minimum detectable change calculation method with the Health Transition Index anchor, the minimum clinically important difference is 4.49 for VAS and 1.16 for BNI-PS after RFL for TN. ABBREVIATIONS: AUC, area under the receiver-operating characteristic curveBNI-PS, Barrow Neurological Institute Pain ScaleHTI, Health Transition IndexMCID, minimum clinically important differenceMDC, minimum detectable changePRO, patient-reported outcomeRFL, percutaneous stereotactic radiofrequency lesioningTN, trigeminal neuralgiaVAS, Visual Analog Scale.

Microvascular decompression for classic trigeminal neuralgia: determination of minimum clinically important difference in pain improvement for patient reported outcomes.

BACKGROUND: Outcomes studies use patient-reported outcome (PRO) measurements to assess treatment effectiveness, but can lack direct clinical meaning. Minimum clinically important difference (MCID) calculation provides a point estimate of the critical threshold needed to achieve clinically relevant treatment effectiveness. MCID remains uninvestigated for microvascular decompression (MVD), a common surgical procedure for trigeminal neuralgia. OBJECTIVE: We aimed to determine MCID for the most commonly used PRO measures of pain after MVD: Visual Analog Scale (VAS) and Barrow Neurological Institute Pain Scale (BNI-PS). METHODS: Sixty consecutive patients with classic trigeminal neuralgia who decided to undergo MVD by a single surgeon were prospectively assessed with VAS and BNI-PS preoperatively and 2 years postoperatively. Three anchors were used to assign each patient's outcome. We then used 3 well-established, anchor-based methods to calculate MCID. RESULTS: Patients experienced significant improvement in both VAS (9.9 vs. 2.0, P < .001) and BNI-PS (5.0 vs. 1.9, P < .001) after MVD. The area under the receiver-operating characteristic curve was greater for BNI-PS than for VAS for all 3 anchors, indicating that BNI-PS is probably better suited for calculating MCID. The 3 MCID calculation methods generated a range of MCID values for each of the PROs (VAS: 1.40-8.87, BNI-PS: 0.95-3.26). CONCLUSION: MVD-specific MCID is highly variable based on calculation technique. Some of these calculations appear to either overestimate or underestimate the patients' preoperative expectations. When the different MCID methods are averaged, the results are clinically appropriate and consistent with preoperative expectations. The average MCID for VAS is 6.25 and for BNI-PS is 2.44.

Vemurafenib (RG67204, PLX4032): a potent, selective BRAF kinase inhibitor.

Vemurafenib is a potent inhibitor of the mutated BRAF kinase. Phase I and II clinical trials of vemurafenib showed response rates of more than 50% in patients with metastatic melanoma and BRAF mutation. A Phase III study comparing vemurafenib with dacarbazine in 675 previously untreated patients revealed overall survival to be 84% (95% CI: 78-89) in the vemurafenib group and 64% (95% CI: 56-73) in the dacarbazine group. Vemurafenib was associated with a relative reduction of 63% in the risk of death and 74% in the risk of either death or disease progression, as compared with dacarbazine (p < 0.001). Progression-free survival was longer in those treated with vemurafenib (median: 5.3 vs 1.6 months; hazard ratio: 0.26; 95% CI: 0.20-0.33). Response rates were 48% for vemurafenib and 5% for dacarbazine. After review of the interim analysis by an independent data and safety monitoring board, crossover from dacarbazine to vemurafenib was recommended.

S-Methylidene Agents: Preparation of Chiral Non-Racemic Heterocycles.

Reaction of sulfur ylide with aldehyde, imine, and ketone functionality affords the desired three-membered heterocycle in excellent yield. The sulfur ylide is generated in situ upon decarboxylation of carboxymethylsulfonium betaine functionality. Of the seven carboxymethylsulfonium betaine derivatives surveyed, the highest level of conversion of π-acceptor to heterocycle was obtained having S-methyl and S-phenyl functionality bound to a thioacetate derivative. Methylene aziridinations and epoxidations involving the decarboxylation of carboxymethylsulfonium betaine functionality complements existing technologies with the advantages of the reaction protocol, levels of conversion and scope. While moderate levels of diastereocontrol were observed in the aziridination of imine functionality, the four oxiranes resolved using Jacobsen's Co(II)-salen complex were obtained in both high yield and enantioselectivity. The isolated chiral non-racemic oxiranes constitute the formal synthesis of chelonin-B and combretastatin starting from 3-bromo-4-methoxybenzaldehyde and 3,4,5-trimethoxybenzaldehyde respectively.