Not All Ductal Carcinomas In Situ Are Created IDLE (Indolent Lesions of Epithelial Origin).

CONTEXT.­: Mammographic screening has increased the incidence of ductal carcinoma in situ (DCIS), but this has not been accompanied by a decline in the incidence of invasive carcinoma (IC). Consequently, the surgical treatment of DCIS has recently been questioned, with some advocating only surveillance (with or without neoadjuvant endocrine therapy) after a core biopsy diagnosis of DCIS. OBJECTIVES.­: To examine the predictive value of a core biopsy diagnosis of DCIS, particularly the upgrade rate to IC, and to identify associated factors. DESIGN.­: Using the pathology database, we identified 2943 cases of DCIS diagnosed on core biopsy from 2000 to 2015, of which 229 cases (8%) later had the stage upgraded to IC. RESULTS.­: Ages ranged from 25 to 90 years (mean, 59 years). The DCIS presented with calcifications in 151 of 229 cases (65.9%), was widespread in 26 of 151 cases (17%), had a mass or density present in 70 of 229 cases (31%), with heterogeneous echogenic features in 44 of those 70 cases (63%), and an enhancement upon magnetic resonance imaging in 8 of 229 cases (3.5%). Of the 229 cases, the DCIS grades were as follows: low in 29 cases (13%), intermediate in 79 cases (36%), and high in 121 cases (53%). Of the 229 cases, necrosis was present in 152 (66.4%) and was comedo necrosis in 99 cases (43%). Of the 229 cases of IC, the tumor stage was as follows: microIC in 36 (16%), T1a in 119 (52%), T1b in 35 (15%), T1c in 28 (12%), T2 in 8 (3%), and T3 in 3 cases (1%). Axillary lymph nodes were staged in 167 patients as follows: N0, 141 cases (84%); N0(i+), 14 cases (8%); and N1, 12 cases (7%). The 12 N1 cases were subclassified by T stage as follows: T1a, 1 case (8%); T1b, 4 cases (33%); T1c, 2 cases (17%); T2, 4 cases (33%); and T3, 1 case (8%). The IC cases of stage upgrading were predominantly smaller than 2 cm (218 of 229; 95%), and more than two-thirds were smaller than 0.5 cm (155 of 229; 95%), most of which were accompanied by extensive DCIS. CONCLUSIONS.­: Approximately one-half of the upgrades were associated with high-grade DCIS, especially with comedo necrosis; nevertheless, the other one-half of the upgrades were due to low- and intermediate-grade DCIS and should not be underestimated. There were few positive results from axillary lymph node biopsies, but they occurred in 3% (7 of 218) of the carcinomas smaller than 2 cm. Our findings indicate that caution is needed when DCIS cases diagnosed by core biopsy are treated nonsurgically with surveillance (with or without neoadjuvant endocrine therapy), given the number of cases (229 of 2943; 8%) that are upgraded to IC and those with axillary lymph node metastases (12 of 167; 7%).

Clinical performance of a next-generation sequencing assay (ThyroSeq v2) in the evaluation of indeterminate thyroid nodules.

BACKGROUND: Molecular testing with the Thyroseq v2 next generation sequencing panel ("Thyroseq") is used to estimate the risk of cancer in indeterminate thyroid nodules. METHODS: We analyzed 156 indeterminate thyroid nodules evaluated with Thyroseq, across 3 institutions. Thyroseq data and surgical pathology were matched via pathologic re-review. A result was considered Thyroseq positive if molecular alterations were annotated on the report with malignancy probability >30%. Performance characteristics were estimated using Bayes theorem. RESULTS: The Thyroseq-negative call rate was 65% (102/156). On surgical pathology, 16% (10/63) of nodules were malignant. The positive predictive value of a Thyroseq-positive result was 22% (8/37; if 2 noninvasive follicular thyroid neoplasm with papillary-like nuclear features are counted as malignant, 27%, 10/37). There was 1 false-negative result (negative predictive value 96%, 22/23). The most common mutation was NRAS (19/37) with a positive predictive value of 7% (1/15). The positive predictive value of all RAS mutations (HRAS, KRAS, NRAS) was 9% (2/22). The second most common mutation, BRAF V600E, had positive predictive value of 100% (3/3). CONCLUSION: We report an external analysis of Thyroseq performance in the evaluation of indeterminate thyroid nodules. These data indicate that Thyroseq is likely to offer high negative predictive value but low positive predictive value. Many genetic alterations appear to be nonspecific for malignancy, and positive results should be interpreted with caution. These findings have implications for the management of indeterminate thyroid nodules profiled with Thyroseq.

Extracapsular extension is associated with worse distant control and progression-free survival in patients with lymph node-positive human papillomavirus-related oropharyngeal carcinoma.

OBJECTIVES: To determine the prognostic utility of pathologic extracapsular extension (ECE) in human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC). MATERIALS AND METHODS: Retrospective analysis was performed on patients who underwent surgery for primary HPV-related OPSCC and received adjuvant radiotherapy (RT) between 2006 and 2015. Locoregional control (LRC), distant control (DC), progression-free survival (PFS) and overall survival (OS) were compared between the groups with and without ECE using univariate Kaplan-Meier and multivariate Cox regression survival analyses. RESULTS: 75 patients were identified and ECE was demonstrated on the surgical pathology of 26 patients. ECE(+) patients more frequently received chemotherapy (76.9% vs. 32.7%; p<0.0001) and RT doses>66Gy (76.9% vs. 16.3%; p<0.001). With a median follow-up of 29months, patients with ECE had a significantly worse 5-year DC rate than those without ECE (76.7% vs. 97.9%; p=0.046), and patients with ECE had a significantly worse 5-year PFS (54.5% vs. 93.6%; p=0.021) than those without ECE. On multivariate Cox regression analysis, ECE was independently prognostic of worse DC (hazard ratio: 8.26; 95% confidence interval: 1.24-55.21; p=0.029) and worse PFS(HR: 4.64; 95% CI: 1.18-18.29; p=0.028). There was no statistically significant difference in 5-year LRC (93.3% vs. 95.7%) or OS (66.9% vs. 97.0%) between ECE(+) and ECE(-) patients, respectively. CONCLUSION: This study suggests that ECE is independently prognostic of worse DC and PFS in patients who undergo surgery prior to adjuvant RT for primary HPV-related OPSCC.

Cutaneous/subcutaneous mesenchymal proliferations of the breast.

Cutaneous mesenchymal "spindle cell" lesions arising in the vicinity of the breast represent a complex clinical and diagnostic scenario which may overlap histopathologically and immunohistochemically with mammary spindle cell proliferations, potentially impacting management and overall prognostication. In this review, we suggest a pattern-based approach to assist in the evaluation of these lesions. A comprehensive description of each entity is accompanied by a cutaneous and mammary differential diagnosis.