Diagnostic Assessment of Deep Learning Algorithms for Frozen Tissue Section Analysis in Women with Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Assessing the metastasis status of the sentinel lymph nodes (SLNs) for hematoxylin and eosin–stained frozen tissue sections by pathologists is an essential but tedious and time-consuming task that contributes to accurate breast cancer staging. This study aimed to review a challenge competition (HeLP 2019) for the development of automated solutions for classifying the metastasis status of breast cancer patients. @*Materials and Methods@#A total of 524 digital slides were obtained from frozen SLN sections: 297 (56.7%) from Asan Medical Center (AMC) and 227 (43.4%) from Seoul National University Bundang Hospital (SNUBH), South Korea. The slides were divided into training, development, and validation sets, where the development set comprised slides from both institutions and training and validation set included slides from only AMC and SNUBH, respectively. The algorithms were assessed for area under the receiver operating characteristic curve (AUC) and measurement of the longest metastatic tumor diameter. The final total scores were calculated as the mean of the two metrics, and the three teams with AUC values greater than 0.500 were selected for review and analysis in this study. @*Results@#The top three teams showed AUC values of 0.891, 0.809, and 0.736 and major axis prediction scores of 0.525, 0.459, and 0.387 for the validation set. The major factor that lowered the diagnostic accuracy was micro-metastasis. @*Conclusion@#In this challenge competition, accurate deep learning algorithms were developed that can be helpful for making a diagnosis on intraoperative SLN biopsy. The clinical utility of this approach was evaluated by including an external validation set from SNUBH.

Intentional Death Caused by the Overdose of Nonprescription Drugs: An Autopsy Case of Acetaminophen Poisoning / 대한법의학회지

Acetaminophen or paracetamol (N-acetyl-para-aminophenol [APAP]) is a safe and effective antipyretic and analgesic drug and is a representative nonprescription drug. However, APAP is one of the most common nonprescription drugs used for intentional overdose or suicide, thereby resulting in hundreds of deaths annually in the United States. Moreover, the misuse of nonprescription drugs is a cause of increasing concern in Korea with the revision of the Pharmaceutical Affairs Law in 2012. Generally, the mortality rate of APAP overdose is extremely low due to the well-established treatment guidelines and availability of antidotes. However, it should not be overlooked because of the high number of either accidental or intentional APAP overdose cases recorded every day. To achieve a good prognosis, individuals with APAP overdose must be immediately identified and brought to the hospital. Herein, we report an autopsy case of an individual with APAP overdose who died due to acute liver injury.

Cytologic Diagnosis of Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features and Its Impact on the Risk of Malignancy in the Bethesda System for Reporting Thyroid Cytopathology: An Institutional Experience

BACKGROUND: This study was performed to analyze cytologic diagnosis of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and its impact on the risk of malignancy (ROM) in the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). METHODS: Five thousand five hundred and forty-nine cases of thyroid fine-needle aspiration cytology (FNAC) diagnosed between 2012 and 2014 were included in this study. Diagnostic categories based on TBSRTC were compared with final surgical diagnoses, and the ROM in each category was calculated both when NIFTP was included in malignant lesions and when excluded from malignant lesions. RESULTS: Of the 5,549 thyroid FNAC cases, 1,891 cases underwent surgical resection. In final diagnosis, 1,700 cases were revealed as papillary thyroid carcinoma (PTC), and 25 cases were reclassified as NIFTP. The cytologic diagnoses of NIFTP were non-diagnostic in one, benign in five, atypia of undetermined significance (AUS) in 14, follicular neoplasm in two, and suspicious for malignancy in three cases. Collectively, NIFTP/encapsulated follicular variant of PTC (EFVPTC) were more frequently classified as benign, AUS, or follicular neoplasm and less frequently categorized as malignant compared to conventional PTCs. Exclusion of NIFTP from malignant diagnoses resulted in a slight decrease in malignancy rates in non-diagnostic, benign, AUS, follicular neoplasm, and suspicious for malignancy categories without any statistical significance. CONCLUSIONS: The decrease in the ROM was not significant when NIFTP was excluded from malignant lesions. In thyroid FNACs, NIFTP/EFVPTCs were mostly classified into indeterminate categories. Therefore, it might be feasible to separate NIFTP/EFVPTC from conventional PTC on FNAC to guide clinicians to conservative management for patients with NIFTP/EFVPTC.

Benign Intraductal Papilloma without Atypia on Core Needle Biopsy Has a Low Rate of Upgrading to Malignancy after Excision / 한국유방암학회지

PURPOSE: The management of benign intraductal papilloma (IDP) without atypia diagnosed on core needle biopsy (CNB) remains controversial. This study was performed to evaluate the rate of upgrading to malignancy or high-risk lesions after excision and to identify factors associated with upgrading using a large series of benign IDP cases without atypia. METHODS: We included patients who were diagnosed as having benign IDP without atypia on CNB and underwent surgical or vacuum-assisted excision between 2010 and 2015. We analyzed the clinical, radiologic, and histopathologic features of IDPs that were upgraded to malignancy or high-risk lesions after excision. RESULTS: A total of 511 benign IDPs without atypia diagnosed via CNB were identified, of which 398 cases were treated with excision. After reviewing these cases, four cases of high-risk lesions in adjacent tissue on CNB, two cases which were revealed as papilloma with atypia, and nine cases of malignancy in the same breast were excluded. In the remaining 383 cases, the rate of upgrading to malignancy and high-risk lesions after excision was 0.8% and 4.4%, respectively. The presence of concurrent contralateral breast cancer, the presence of symptoms, and multifocality were factors significantly associated with upgrading to malignancy on subsequent excision. Surgical excision rather than vacuum-assisted excision was significantly associated with upgrading to high-risk lesions or malignancy. CONCLUSION: The rate of upgrading to malignancy for benign IDP without atypia was very low, suggesting that close clinical and radiologic observation may be sufficient for patients with benign IDP without atypia on CNB under proper settings.

Negative Conversion of Progesterone Receptor Status after Primary Systemic Therapy Is Associated with Poor Clinical Outcome in Patients with Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Alteration of biomarker status after primary systemic therapy (PST) is occasionally found in breast cancer. This study was conducted to clarify the clinical implications of change of biomarker status in breast cancer patients treated with PST. MATERIALS AND METHODS: The pre-chemotherapeutic biopsy and post-chemotherapeutic resection specimens of 442 breast cancer patients who had residual disease after PST were included in this study. The association between changes of biomarker status after PST and clinicopathologic features of tumors, and survival of the patients, were analyzed. RESULTS: Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status changed after PST in 18 (4.1%), 80 (18.1%), and 15 (3.4%) patients,respectively. ER and PR mainly underwent positive to negative conversion,whereas HER2 status underwent negative to positive conversion. Negative conversion of ER and PR status after PST was associated with reduced disease-free survival. Moreover, a decline in the Allred score for PR in post-PST specimens was significantly associated with poor clinical outcome of the patients. HER2 change did not have prognostic significance. In multivariate analyses, negative PR status after PST was found to be an independent adverse prognostic factor in the whole patient group, in the adjuvant endocrine therapy-treated subgroup, and also in pre-PST PR positive subgroup. CONCLUSION: ER and HER2 status changed little after PST, whereas PR status changed significantly. In particular, negative conversion of PR status was revealed as a poor prognostic indicator, suggesting that re-evaluation of basic biomarkers is mandatory in breast cancer after PST for proper management and prognostication of patients.

Microinvasive Carcinoma versus Ductal Carcinoma In Situ: A Comparison of Clinicopathological Features and Clinical Outcomes / 한국유방암학회지

PURPOSE: Although microinvasive carcinoma is distinct from ductal carcinoma in situ (DCIS), the clinical significance of microinvasion in DCIS remains elusive. The purpose of this study is to evaluate the clinicopathological features and clinical outcomes of microinvasive carcinoma compared with pure DCIS. METHODS: We assessed 613 cases of DCIS and microinvasive carcinoma that were consecutively resected from 2003 to 2014 and analyzed clinicopathological variables, expression of standard biomarkers such as the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), p53, and Ki-67, and tumor recurrence. RESULTS: Among the 613 cases, 136 (22.2%) were classified as microinvasive carcinoma. Microinvasive carcinoma was significantly associated with DCIS with a large extent, high nuclear grade, necrosis, and comedotype architectural pattern. ER and PR expressions were dominantly observed in pure DCIS, whereas positive HER2 status, p53 overexpression, and high Ki-67 proliferation indices were more frequently observed in microinvasive carcinoma. Lymph node metastasis was found in only four cases of microinvasive carcinoma with multifocal microinvasion. In the multivariate analysis, DCIS with a large extent, comedo-type architectural pattern, and negative ER status were found to be independent predictors of microinvasion. During follow-up, 12 patients had ipsilateral breast recurrence, and no differences in recurrence rates were observed between patients with DCIS and those with microinvasive carcinoma. The triple-negative subtype was the only factor that was associated with tumor recurrence. CONCLUSION: Microinvasive carcinomas are distinct from DCIS in terms of clinicopathological features and biomarker expressions but are similar to DCIS in terms of clinical outcomes. Our results suggest that microinvasive carcinoma can be treated and followed up as pure DCIS.

Mammary Carcinoma Arising in Microglandular Adenosis: A Report of Five Cases

Mammary carcinoma arising in microglandular adenosis (MGA) is extremely rare, and MGA is regarded as a non-obligate precursor of triple-negative breast cancer. We report five cases of carcinoma arising in MGA of the breast. All cases showed a spectrum of proliferative lesions ranging from MGA to atypical MGA, ductal carcinoma in situ or invasive carcinoma. Immunohistochemically, all cases were triple-negative and expression of S-100 protein gradually decreased as the lesions progressed from MGA to atypical MGA and carcinoma. Three cases showed acinic cell differentiation with reactivity to α1-antitrypsin, and one case was metaplastic carcinoma. During clinical follow-up, one patient developed local recurrence. Carcinoma arising in MGA is a rare but distinct subset of triple-negative breast cancer with characteristic histologic and immunohistochemical findings.

Adaptive Iterative Dose Reduction Algorithm in CT: Effect on Image Quality Compared with Filtered Back Projection in Body Phantoms of Different Sizes

OBJECTIVE: To evaluate the impact of the adaptive iterative dose reduction (AIDR) three-dimensional (3D) algorithm in CT on noise reduction and the image quality compared to the filtered back projection (FBP) algorithm and to compare the effectiveness of AIDR 3D on noise reduction according to the body habitus using phantoms with different sizes. MATERIALS AND METHODS: Three different-sized phantoms with diameters of 24 cm, 30 cm, and 40 cm were built up using the American College of Radiology CT accreditation phantom and layers of pork belly fat. Each phantom was scanned eight times using different mAs. Images were reconstructed using the FBP and three different strengths of the AIDR 3D. The image noise, the contrast-to-noise ratio (CNR) and the signal-to-noise ratio (SNR) of the phantom were assessed. Two radiologists assessed the image quality of the 4 image sets in consensus. The effectiveness of AIDR 3D on noise reduction compared with FBP were also compared according to the phantom sizes. RESULTS: Adaptive iterative dose reduction 3D significantly reduced the image noise compared with FBP and enhanced the SNR and CNR (p < 0.05) with improved image quality (p < 0.05). When a stronger reconstruction algorithm was used, greater increase of SNR and CNR as well as noise reduction was achieved (p < 0.05). The noise reduction effect of AIDR 3D was significantly greater in the 40-cm phantom than in the 24-cm or 30-cm phantoms (p < 0.05). CONCLUSION: The AIDR 3D algorithm is effective to reduce the image noise as well as to improve the image-quality parameters compared by FBP algorithm, and its effectiveness may increase as the phantom size increases.