Clinical Perineural Invasion of Cutaneous SCC May Warrant Adjuvant Treatment

MedicalResearch.com Interview with:
Dr. Chrysalyne D. Schmults, MD, MSCE
Associate Professor of Dermatology, Harvard Medical School
Director, Mohs and Dermatologic Surgery Center and
Mr. Pritesh S. Karia, MPH
Department of Epidemiology
Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

Department of Dermatology
Brigham and Women’s Faulkner Hospital
Harvard Medical School, Boston, Massachusetts
Jamaica Plain, MA 02130-3446 

MedicalResearch.com: What is the background for this study?

Response: Perineural nerve invasion (PNI) is a well-recognized risk factor for poor prognosis in patients with cutaneous squamous cell carcinoma (CSCC). Most cases of CSCC with PNI are identified on histologic examination at the time of surgery and the patient has no clinical symptoms or radiologic evidence of PNI. These cases are classified as incidental PNI (IPNI). However, some patients with PNI present with clinical symptoms and/or radiologic evidence of PNI. These cases are classified as clinical PNI (CPNI). A few studies have shown differences in disease-related outcomes between CSCC patients with IPNI and CPNI but consensus regarding adjuvant treatment and detailed guidelines on follow-up schedules have not yet materialized.

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When Interpreting Skin Biopsies, Pathologists Often Disagree

MedicalResearch.com Interview with:

Joann G. Elmore M.D., M.P.H. Professor of Medicine,  Adjunct Professor of Epidemiology, University of Washington School of Medicine Harborview Medical Center Seattle, WA 98104-2499

Dr. Elmore

Joann G. Elmore M.D., M.P.H.
Professor of Medicine,
Adjunct Professor of Epidemiology,
University of Washington School of Medicine
Harborview Medical Center
Seattle, WA 98104-2499

MedicalResearch.com: What is the background for this study?

JE: Previous studies on diagnostic accuracy in interpreting melanocytic lesions exist but have small sample size, inclusion of experts only, or small numbers of specimens. We sought to examine accuracy and reproducibility in melanocytic skin lesions by improving upon the methodological limitations of previous studies. Specifically, we recruited a large national sample of practicing community and academic pathologists with a wide range of experience, and we utilized a large sample of biopsy cases that were carefully selected. Given that diagnostic errors can lead to patient deaths and invasive melanoma kills more than 9,000 Americans each year, we wanted to study the issue of diagnostic accuracy in interpreting melanocytic skin lesions in a very robust fashion.

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Mitotic Rate Correlates With Sentinel Lymph Node Status and Outcome in Cutaneous Melanoma

MedicalResearch.com Interview with:
Dr. Mario Mandalà, MD

Division of Oncology, Department of Oncology and Hematology
Papa Giovanni XXIII Hospital
Bergamo, Italy. 

MedicalResearch.com: What is the background for this study?

Response: The 7th edition of the TNM AJCC classification incorporated mitotic rate (MR) only for primary cutaneous melanoma with Breslow thickness ≤1 mm. We investigated whether and to what extent MR is able to predict sentinel lymph node (SLN) status and clinical outcome of  primary cutaneous melanoma (PCM) patients with BT >1 mm.

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Storage Time Can Effect Plasma Biomarker Results

MedicalResearch.com Interview with:
Stefan Enroth, Associate Professor, PhD
Dept. of Immunology, Genetics & Pathology
Uppsala University

MedicalResearch.com: What is the background for this study?

Response: One basic requirement of life science research is the quality of samples. Proper handling and rigorous biobanking of clinical samples is very important when for instance collecting samples for rare diseases, for monitoring individual variation in longitudinal studies and when conducting prospective studies of biomarkers and risk of developing for instance cardiovascular disease. In epidemiological studies using case and control cohorts, great care is taken to ensure that the cases and controls are matched in terms of for instance age, anthropometrics and lifestyle exposures such as smoking or alcohol consumption. Technical factors and sampling handling history are not as commonly used. There has been a lack of studies that systematically investigated the effects of for instance storage-time on a larger set of plasma proteins. With emerging high-throughput technologies enabling measurements of a high number of proteins simultaneously on a population level, biomarker research will enter a new era and the more knowledge we have on what factors that influence circulating biomarker levels – such as plasma proteins, the higher the chances are of finding new clinically important biomarkers for disease.

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Patients With Newly Diagnosed DCIS Breast Cancer May Not Need Their Core Needle Biopsy Tested for Hormone Receptors

MedicalResearch.com Interview with:

Pedram Argani, M.D. Professor of Pathology and Principal consultant of the Breast Pathology Service Johns Hopkins Medicine

Dr. Pedram Argani

Pedram Argani, M.D.
Professor of Pathology and
Principal consultant of the Breast Pathology Service
Johns Hopkins Medicine

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Most pathology laboratories, at the request if clinicians, automatically (reflexively) test needle core biopsies containing ductal carcinoma in situ (DCIS) for estrogen receptor (ER) and progesterone receptor (PR). The logic for testing DCIS for these hormone receptors is that, for patients who have pure DCIS that is ER positive after surgical excision, treatment with estrogen blockers like Tamoxifen can decrease the recurrence of DCIS by a small amount, though overall survival (which is excellent) is not impacted.

However, there are several factors which suggest that this reflex testing unnecessarily increases costs.
• First, the ER/PR results on core needle biopsy do not impact the next step in therapy; namely, surgical excision.
• Second, a subset of excisions performed for DCIS diagnosed on core needle biopsy will harbor invasive breast carcinoma, which would than need to be retested for ER/PR.
• Third, because ER and PR labeling is often variable in DCIS, negative results for ER/PR in a small core biopsy specimen should logically be repeated in a surgical excision specimen with larger amounts of DICS to be sure that the result is truly negative.
• Fourth, many patients with pure DCIS which is ER/PR positive after surgical excision will decline hormone therapy, so any ER/PR testing of their DCIS is unnecessary.
• Fifth, PR status in DCIS has no independent value.

We reviewed the Johns Hopkins experience with reflex ER/PR testing of DCIS on core needle biopsies over 2 years. We found that reflex core needle biopsy specimen testing unnecessarily increased costs by approximately $140.00 per patient. We found that ER/PR testing in the excision impacted management in only approximately one third of cases, creating an unnecessary increased cost of approximately $440.00 per patient. Extrapolating the increased cost of reflex ER/PR testing of DCIS to the 60,000 new cases of DCIS in the United States each year, reflex core needle biopsy ER/PR testing unnecessarily increased costs by approximately 35 million dollars.

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Pathologists Don’t Always Agree On Breast Biopsy Atypia or DCIS

Joann G. Elmore M.D., M.P.H. Professor of Medicine, Adjunct Professor of Epidemiology, University of Washington School of Medicine Harborview Medical Center Seattle, WA 98104-2499MedicalResearch.com Interview with:
Joann G. Elmore M.D., M.P.H.
Professor of Medicine,
Adjunct Professor of Epidemiology,
University of Washington School of Medicine
Harborview Medical Center
Seattle, WA 98104-2499

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Elmore: It is estimated that 1.6 million women in the United States each year undergo a breast biopsy. By interpreting these biopsies under the microscope, pathologists provide diagnoses on a spectrum from benign, to atypia, to ductal carcinoma in situ (DCIS), to invasive cancer. Using these diagnostic classifications, clinical doctors work with their patients to decide if they are at increased risk of developing breast cancer in the future, which can lead to additional surveillance, or how to treat them when the diagnosis is invasive breast cancer. As misclassification of breast lesions by pathologists may contribute to overtreatment and undertreatment of breast disease, we decided to study the accuracy of breast pathology diagnoses in the U.S.

In the Breast Pathology (B-Path) Study, we used a set of 240 breast biopsy cases to evaluate the interpretive accuracy of 115 U.S. pathologists who were actively interpreting breast biopsies in their clinical practices. Their diagnoses were compared with reference diagnoses established by a consensus panel of experienced breast pathologists. When the panel members each independently diagnosed the slides pre-consensus, they agreed unanimously on 75 percent of their diagnoses; ninety percent of the panel members’ initial independent diagnoses agreed with the final consensus-derived reference diagnoses.

When comparing participating pathologists’ diagnoses to the reference diagnoses, we found overall agreement for 75 percent of interpretations. The concordance rate for invasive breast cancer was reassuringly high at 96 percent, and fairly high for benign findings without atypia at 87 percent. However, concordance was lower for atypia at 48 percent and for DCIS at 84 percent. This means that nearly one out of five pathologists disagreed on the diagnosis of DCIS. We found disagreement with the reference diagnosis to be statistically more frequent when pathologists had lower weekly case volumes or worked in smaller labs. Disagreement was also statistically significantly more likely when the patient had dense breast tissue on mammogram; however, the absolute difference was small. Our accuracy findings were not altered when we used different methods of defining the reference diagnosis.

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