Establishing molecular pathology curriculum for pathology trainees and continued medical education: a collaborative work from the Molecular Pathology Study Group of the Korean Society of Pathologists

Background@#The importance of molecular pathology tests has increased during the last decade, and there is a great need for efficient training of molecular pathology for pathology trainees and as continued medical education. @*Methods@#The Molecular Pathology Study Group of the Korean Society of Pathologists appointed a task force composed of experienced molecular pathologists to develop a refined educational curriculum of molecular pathology. A 3-day online educational session was held based on the newly established structure of learning objectives; the audience were asked to score their understanding of 22 selected learning objectives before and after the session to assess the effect of structured education. @*Results@#The structured objectives and goals of molecular pathology was established and posted as a web-based interface which can serve as a knowledge bank of molecular pathology. A total of 201 pathologists participated in the educational session. For all 22 learning objectives, the scores of self-reported understanding increased after educational session by 9.9 points on average (range, 6.6 to 17.0). The most effectively improved items were objectives from next-generation sequencing (NGS) section: ‘NGS library preparation and quality control’ (score increased from 51.8 to 68.8), ‘NGS interpretation of variants and reference database’ (score increased from 54.1 to 68.0), and ‘whole genome, whole exome, and targeted gene sequencing’ (score increased from 58.2 to 71.2). Qualitative responses regarding the adequacy of refined educational curriculum were collected, where favorable comments dominated. @*Conclusions@#Approach toward the education of molecular pathology was refined, which would greatly benefit the future trainees.

Effective Timing of Introducing an Inpatient Smoking Cessation Program to Cancer Patients

Purpose@#We aimed to identify factors influencing smoking cessation success among cancer patients registered in an inpatient smoking cessation program at a single cancer center. @*Materials and Methods@#The electronic medical records of enrolled patients with solid cancer were retrospectively reviewed. We evaluated factors associated with 6-month smoking cessation. @*Results@#A total of 458 patients with cancer were included in this study. Their mean age was 62.9±10.3 years, and 56.3% of the participants had lung cancer. 193 (42.1%) had not yet begun their main treatment. The mean number of counseling sessions for the participants was 8.4±3.5, and 46 (10.0%) patients were prescribed smoking cessation medications. The 6-month smoking cessation success rate was 48.0%. Multivariate analysis showed that younger age (<65 years), cohabited status, early stage, and the number of counseling sessions were statistically significant factors affecting 6-month smoking cessation success (p<0.05). Initiation of a cessation program before cancer treatment was significantly associated with cessation success (odds ratio, 1.66; 95% confidence interval, 1.02–2.70; p=0.040). @*Conclusion@#Smoking cessation intervention must be considered when establishing a treatment plan immediately after a cancer diagnosis among smokers.

Isolated Intracranial Rosai–Dorfman Disease Mimicking Meningioma: A Case Report

Rosai–Dorfman Disease (RDD) is a rare lymphoproliferative disease, and the occurrence of isolated intracranial RDD is extremely rare. Most cases of intracranial RDDs present as dural masses showing homogenous enhancement on MRI, which makes it difficult to differentiate these masses from meningiomas before surgery unless massive cervical lymphadenopathy is observed. We herein report a rare case of isolated intracranial RDD in a 65-year-old male. Brain MRI revealed a well-defined enhancing mass-like lesion involving the right frontal convexity and subtle diffusion restriction. However, only a subtle blush was observed on the preoperative cerebral angiogram. Although instances of isolated intracranial RDD are rare, it should be considered as a potential differential diagnosis when a dural mass with hypovascularity is visualized on the cerebral angiogram.

Peripheral T-Cell Lymphoma Presenting as a Scalp Mass

Peripheral scalp T-cell lymphoma is a very rare disease. We report a case of a 22-year-old man who presented an indolent large scalp mass in the right frontal scalp region. The patient’s physical examination demonstrated no palpable mass in the chest, abdomen, and extremities. The brain CT revealed a high-density large scalp mass of the subgaleal layer in the right frontal and a small scalp mass of the subgaleal layer in the left frontal. The brain MRI showed multifocal enhancing masses in the bilateral dura, the subgaleal layer of the scalp, and the skull. The patient underwent removal of the tumor found in the right frontal scalp. The histologic diagnosis was peripheral T-cell lymphoma. Bone marrow aspiration showed the involvement of T-cell lymphoma. The patient received chemotherapy with cyclophosphamide, vincristine, doxorubicin, and prednisolone (CHOP protocol) for 3 cycles. The patient was discharged without neurological deficit. The patient showed no evidence of recurrence 15 months after surgery. We report a rare case of peripheral T-cell lymphoma mimicking benign scalp tumors.

Predictors of intubation and mechanical ventilation in patients with acute respiratory failure treated with high flow nasal cannula in emergency room: the usefulness of arterial blood gas analysis

Objective@#The use of a high flow nasal cannula (HFNC) might cover the gap between conventional oxygen therapy andmechanical ventilation in the management of acute respiratory failure patients and could be a significant factor in determiningpatient outcomes. Early predictors of HFNC failure may help a clinician decide whether to shift the patient to amechanical ventilator. We aimed at identifying the predictors associated with HFNC failure and the application of amechanical ventilator using arterial blood gas analysis (ABGA). @*Methods@#We retrospectively analyzed patients who were admitted to the emergency room at a single center with respiratorydistress and a PaO2/FiO2 ratio (ratio of arterial partial pressure of oxygen to fraction of inspired oxygen) of less than300. Comparing keeping and weaning HFNC groups with the escalation group, we sought to identify a few discriminatingfactors. Initial ABGA was done when the patients entered the emergency room and this was followed up within 2 hoursafter HFNC therapy. @*Results@#Two hundred and eighteen patients were enrolled and of these HFNC therapy succeeded in 153 and failed in65. At baseline Glasgow Coma Scale, follow-up (F/U) pH, ΔpH, and F/U respiratory rate-oxygenation index were lowerand pro-brain natriuretic peptide, initial lactate, F/U lactate, ΔPCO2, heart rate, acidosis, consciousness, oxygenation,respiratory rate score, Acute Physiology And Chronic Health Evaluation score, Simplified Acute Physiology Score, andSequential Organ Failure Assessment score were significantly higher in the HFNC failure group. The results of the multivariateanalysis indicated that initial lactate (odds ratio [OR], 1.215; 95% confidence interval [CI], 1.081-1.366; P=0.001)and ΔpH (OR, 0.000; 95% CI, 0.000-0.018; P<0.001) were independently associated with the prediction of application ofthe mechanical ventilator. @*Conclusion@#Patients who had higher initial lactate levels and insufficiently corrected pH after HFNC therapy may needto be monitored carefully and escalation of oxygen therapy may need to be considered.

Standardization of the pathologic diagnosis of appendiceal mucinous neoplasms

Although the understanding of appendiceal mucinous neoplasms (AMNs) and their relationship with disseminated peritoneal mucinous disease have advanced, the diagnosis, classification, and treatment of AMNs are still confusing for pathologists and clinicians. The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists (GPSG-KSP) proposed a multicenter study and held a workshop for the “Standardization of the Pathologic Diagnosis of the Appendiceal Mucinous Neoplasm” to overcome the controversy and potential conflicts. The present article is focused on the diagnostic criteria, terminologies, tumor grading, pathologic staging, biologic behavior, treatment, and prognosis of AMNs and disseminated peritoneal mucinous disease. In addition, GPSG-KSP proposes a checklist of standard data elements of appendiceal epithelial neoplasms to standardize pathologic diagnosis. We hope the present article will provide pathologists with updated knowledge on how to handle and diagnose AMNs and disseminated peritoneal mucinous disease.

Predictors of intubation and mechanical ventilation in patients with acute respiratory failure treated with high flow nasal cannula in emergency room: the usefulness of arterial blood gas analysis

Objective@#The use of a high flow nasal cannula (HFNC) might cover the gap between conventional oxygen therapy andmechanical ventilation in the management of acute respiratory failure patients and could be a significant factor in determiningpatient outcomes. Early predictors of HFNC failure may help a clinician decide whether to shift the patient to amechanical ventilator. We aimed at identifying the predictors associated with HFNC failure and the application of amechanical ventilator using arterial blood gas analysis (ABGA). @*Methods@#We retrospectively analyzed patients who were admitted to the emergency room at a single center with respiratorydistress and a PaO2/FiO2 ratio (ratio of arterial partial pressure of oxygen to fraction of inspired oxygen) of less than300. Comparing keeping and weaning HFNC groups with the escalation group, we sought to identify a few discriminatingfactors. Initial ABGA was done when the patients entered the emergency room and this was followed up within 2 hoursafter HFNC therapy. @*Results@#Two hundred and eighteen patients were enrolled and of these HFNC therapy succeeded in 153 and failed in65. At baseline Glasgow Coma Scale, follow-up (F/U) pH, ΔpH, and F/U respiratory rate-oxygenation index were lowerand pro-brain natriuretic peptide, initial lactate, F/U lactate, ΔPCO2, heart rate, acidosis, consciousness, oxygenation,respiratory rate score, Acute Physiology And Chronic Health Evaluation score, Simplified Acute Physiology Score, andSequential Organ Failure Assessment score were significantly higher in the HFNC failure group. The results of the multivariateanalysis indicated that initial lactate (odds ratio [OR], 1.215; 95% confidence interval [CI], 1.081-1.366; P=0.001)and ΔpH (OR, 0.000; 95% CI, 0.000-0.018; P<0.001) were independently associated with the prediction of application ofthe mechanical ventilator. @*Conclusion@#Patients who had higher initial lactate levels and insufficiently corrected pH after HFNC therapy may needto be monitored carefully and escalation of oxygen therapy may need to be considered.

Standardization of the pathologic diagnosis of appendiceal mucinous neoplasms

Although the understanding of appendiceal mucinous neoplasms (AMNs) and their relationship with disseminated peritoneal mucinous disease have advanced, the diagnosis, classification, and treatment of AMNs are still confusing for pathologists and clinicians. The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists (GPSG-KSP) proposed a multicenter study and held a workshop for the “Standardization of the Pathologic Diagnosis of the Appendiceal Mucinous Neoplasm” to overcome the controversy and potential conflicts. The present article is focused on the diagnostic criteria, terminologies, tumor grading, pathologic staging, biologic behavior, treatment, and prognosis of AMNs and disseminated peritoneal mucinous disease. In addition, GPSG-KSP proposes a checklist of standard data elements of appendiceal epithelial neoplasms to standardize pathologic diagnosis. We hope the present article will provide pathologists with updated knowledge on how to handle and diagnose AMNs and disseminated peritoneal mucinous disease.

A Case of Syringocystadenoma Papilliferum of External Auditory Canal / 대한이비인후과학회지

Ceruminous glands are specialized sudoriferous glands located in the external auditory canal (EAC). Tumors originating from these ceruminous glands are rare lesions of EAC; in particular, syringocystadenoma papilliferum (SCAP) is an extremely rare ceruminous glands neoplasm to occur in the EAC. Although it is rare, the association of SCAP with tubular apocrine adenoma in the background of nevus sebaceous on the body, extremities, and scalp is well documented. In this article, we report on a 60-year-old male who presented a mass in EAC, which was surgically removed. The final diagnosis of SCAP was determined by histological analysis and the patient has been well without recurrence.

A Case of Follicular Lymphoma of Sphenoid Sinus and Orbit / 대한이비인후과학회지

Malignant lymphoma is a tumor of the immune system. It mainly occurs in the lymph node, but it can also originate from extranodal organs such as the gastrointestinal tract, salivary gland and the sinonasal tract. A primary malignant lymphoma in the paranasal sinuses is rare and usually occurs in the maxillary or ethmoid sinus. The sphenoid sinus is a rare primary site for extranodal lymphomas. Moreover, follicular lymphoma involving paranasal sinuses rarely occurs. Recently, we experienced a patient who complained of facial swelling, exophthalmos, reduced visual acuity, and diplopia for a month, and she was diagnosed with follicular lymphoma of the sphenoid sinus and orbit. Here we report a rare case of follicular lymphoma of the sphenoid sinus and orbit, along with a literature review.

Postpartum Galactocele in Augmented Breast after Using Breast Pump Mimicking Breast Implant-Associated Anaplastic Large Cell Lymphoma: A Case Report

Post-partum galactocele is a common benign disease among breastfeeding women, whereas retromammary and peri-implant galactocele are relatively rare conditions. Herein, a 34-yearold, 1 month-postpartum female, who had augmentation mammoplasty and a 1-month history of breast pump use, presented with left breast enlargement for 2 weeks. An initial left breast US revealed hyperechoic peri-implant fluid collection. Additional US-guided fine needle aspiration was done using a 21G-needle, draining the milk component in the process, and cytologic results revealed numerous crystals, suggestive of galactocele. Various diseases, especially breast implant-associated anaplastic large cell lymphoma, can cause peri-implant fluid collection in an augmented breast. Thus, correlating imaging features with clinical information and cytologic analysis plays an important role in appropriate management.

A Case of Adrenal Myelolipoma Associated with Hereditary Spherocytosis / 임상소아혈액종양

Hereditary spherocytosis is the most common hereditary red blood cell membrane disorder. It results from a deficiency in certain proteins that are part of the red blood cell membrane cytoskeleton. We report a case of adrenal myelolipoma in a 23-yearold patient with hereditary spherocytosis. She was diagnosed with hereditary spherocytosis at 7 months of age. As she grew older, hemoglobin level was low, so splenectomy was recommended, but continuous follow up was not possible due to the circumstances of the patient, so the splenectomy was delayed. Adrenal myelolipoma was discovered incidentally at the age of 23 with abdominal pain and cholecystitis with gallstones at the time. Myelolipoma is a benign tumor of the mesenchymal origin;its etiology remains unclear. Myelolipoma is composed of adipose and hematopoietic tissues and mainly arises from adrenal tissues. The mass is often detected during routine radiologic examinations because myelolipoma is usually asymptomatic and not generally associated with hematologic diseases. The prevalence of myelolipoma appears to be increasing due to the increased use of imaging modalities. The association of myelolipoma with hereditary spherocytosis has rarely been reported in the literature. To our best knowledge, this is the first report of adrenal myelolipoma associated with hereditary spherocytosis in the Korean population.

Bilateral Triple Negative Invasive Ductal Breast Carcinoma in a BRCA1 Mutation Carrier with Discrepant Pathologic Response to Neoadjuvant Chemotherapy

Herein, we report a case of synchronous bilateral triple negative invasive ductal breast carcinoma in a patient with discrepant pathologic response to neoadjuvant chemotherapy. Right and left breast cancer stages at the initial diagnosis were T1cN0M0 and T4dN3aM0, respectively. The patient was identified as a BRCA1 mutation carrier and treated with four cycles of adriamycin and cyclophosphamide, followed by four cycles of docetaxel. Bilateral breast cancer stages decreased with the first regimen. However, the bilateral breast cancers showed discrepant responses to chemotherapy with docetaxel. The right breast cancer showed a continuous tumor volume reduction while the left breast cancer showed marked progression. Finally, the tumor size was 0.3 cm and 12 cm in the right and left mastectomy specimens, respectively. As bilateral breast cancers of the same subtype may show discrepant responses to neoadjuvant chemotherapy, close monitoring and follow-up imaging are required to avoid delayed surgery.

Mucinous Breast Carcinoma Presenting as a Coarse and Densely Calcified Mass on Mammography: A Case Report

We report herein a 46-year-old woman who presented with mucinous breast carcinoma that appeared as a coarse and densely calcified mass on mammography. The lesion was a 4.6-cmsized palpable, hyperechoic, calcified mass with posterior shadowing on ultrasonography. This finding is a unique feature of mucinous breast carcinoma and is also observed in unusual breast cancer variants such as metaplastic breast cancer with chondroid differentiation, extraosseous osteosarcoma, and breast chondrosarcoma. The lesion showed a slow-growing pattern throughout the 4-year observation period. Mammography performed 4 years ago revealed faint, grouped microcalcifications; the lesion increased in size over 2 years, presenting as a well-circumscribed, calcified mass, mimicking dystrophic calcification. As several unusual variants of breast cancer, including mucinous carcinoma, may present as coarse and densely calcified masses on mammography, immediate biopsy should be considered when they are observed.

Trends in the prevalence of chronic liver disease in theKorean adult population, 1998–2017

Background/Aims@#Data on the trends in the prevalence of chronic liver disease (CLD) in Korea are scarce. This study aimed to evaluate whether the CLD prevalence changed between 1998–2001 and 2016–2017. @*Methods@#Data were extracted from the Korea National Health and Nutrition Examination Survey (1998–2001 to 2016– 2017; n=25,893). Non-alcoholic fatty liver disease (NAFLD) was defined as a hepatic steatosis index >36 in the absence of any other evidence of CLD. The definition of alcohol-related liver disease (ALD) was excessive alcohol consumption (≥210 g/week for men and ≥140 g/week for women) and an ALD/NAFLD index >0. @*Results@#The prevalence of NAFLD increased from 18.6% (95% confidence interval [CI], 17.8–19.5%) in 1998–2001 to 21.5% (95% CI, 20.6–22.6%) in 2016–2017. During the same time period, increases were observed in the prevalence of obesity (27.0 vs. 35.1%), central obesity (29.4 vs. 36.0%), diabetes (7.5 vs. 10.6%), and excessive drinking (7.3 vs. 10.5%). ALD prevalence also increased from 3.8% (95% CI, 3.4–4.2%) to 7.0% (95% CI, 6.4–7.6%). In contrast, chronic hepatitis B decreased from 5.1% (95% CI, 4.6–5.5%) to 3.4% (95% CI, 3.0–3.8%). The prevalence of chronic hepatitis C was approximately 0.3% in 2016–2017. @*Conclusions@#The prevalence of NAFLD and ALD increase among Korean adults. Our results suggest potential targets for interventions to reduce the future burden of CLD.

Bilateral Triple Negative Invasive Ductal Breast Carcinoma in a BRCA1 Mutation Carrier with Discrepant Pathologic Response to Neoadjuvant Chemotherapy

Herein, we report a case of synchronous bilateral triple negative invasive ductal breast carcinoma in a patient with discrepant pathologic response to neoadjuvant chemotherapy. Right and left breast cancer stages at the initial diagnosis were T1cN0M0 and T4dN3aM0, respectively. The patient was identified as a BRCA1 mutation carrier and treated with four cycles of adriamycin and cyclophosphamide, followed by four cycles of docetaxel. Bilateral breast cancer stages decreased with the first regimen. However, the bilateral breast cancers showed discrepant responses to chemotherapy with docetaxel. The right breast cancer showed a continuous tumor volume reduction while the left breast cancer showed marked progression. Finally, the tumor size was 0.3 cm and 12 cm in the right and left mastectomy specimens, respectively. As bilateral breast cancers of the same subtype may show discrepant responses to neoadjuvant chemotherapy, close monitoring and follow-up imaging are required to avoid delayed surgery.

A Case of Myeloid Sarcoma in the Nasal Cavity Occurred in the Patient with Leukemic Transformation in Myelodysplastic Syndrome / 대한이비인후과학회지

Myeloid sarcoma is characterized by the presence of myeloid blasts at an extramedullar site that disrupts the normal architecture of the organ. Many of these cases are associated with acute myeloid leukemia, chronic myeloid leukemia, myelodysplastic syndrome, or occur in de novo. It occurs most commonly in skin, lymph node, gastrointestinal tract, bone, soft tissue but, rarely in head and neck; especially in nasal cavity. Therefore, it is often misdiagnosed as a different disease: most commonly as lymphoma. Here we report a rare case of myeloid sarcoma in the nasal cavity that occurred in a patient with leukemic transformation with myelodysplastic syndrome, provided with literature review.

Concordance of Programmed DeathLigand 1 Expression between SP142 and 22C3/SP263 Assays in Triple-Negative Breast Cancer / 한국유방암학회지

Purpose@#Triple-negative breast cancer (TNBC) represents a major clinical challenge due to its aggressive and metastatic behavior and the lack of available targeted therapies. Therefore, therapeutic strategies are needed to improve TNBC patient management. Recently, atezolizumab and nab-paclitaxel chemotherapy has been approved by the Food and Drug Administration for the first-line treatment of patients with locally advanced and metastatic TNBC. The programmed death-ligand 1 (PD-L1) immunohistochemical SP142 assay was also approved as a companion diagnostic device for selecting TNBC patients for atezolizumab treatment. This study aimed to evaluate and compare the analytical performance of the PD-L1 22C3/SP263 assays in comparison with the SP142 assay for ≥ 1% immune cells (ICs). @*Methods@#Immunohistochemical expression for the PD-L1 22C3/SP263 assays, in comparison with the SP142 assay, was analyzed for the ≥ 1% ICs in 95 TNBCs. @*Results@#At the 1% cut-off value, the proportions of positive cases were 52.6% for the SP142 assay in infiltrating ICs and 50.5% and 52.6% for the 22C3 and SP263 assays in tumor cells, respectively. The PD-L1 SP263 assay had the highest while the PD-L1 22C3 assay had the lowest total positive expression rate at all cut-off values. The concordance rate between the assays was highest at a 1% cut-off value and decreased when the cut-off value increased.The concordance rate between the SP142 and SP263 assays at 1% cut-off was high, while in comparison, the concordance rate between the SP142 and 22C3 assays at 1% cut-off was relatively lower. @*Conclusion@#This study demonstrates that although the 22C3 assay at a 1% cut-off value compared with the PD-L1 SP142 assay at the clinically relevant cut-off shows comparable but not interchangeable analytical performance, the analytical performance of the SP263 assay at a 1% cut-off value shows interchangeable performance with the PD-L1 SP142 assay at the clinically relevant cut-off.

Clinical Characteristics of Korean Patients with Lung Cancer Who Have Programmed Death-Ligand 1 Expression / 결핵

BACKGROUND: Programmed death-ligand 1 (PD-L1), a transmembrane protein, binds to the programmed death-1 (PD-1) receptor, and anti-PD-1 therapy enables immune responses against tumors. This study aimed to assess clinical characteristics of PD-L1 expression using immunohistochemistry among Korean patients with lung cancer. METHODS: We retrospectively reviewed the data of patients with pathologically proven lung cancer from a single institution. PD-L1 expression determined by Tumor Proportion Score (TPS) was detected using 22C3 pharmDx (Agilent Technologies) and SP263 (Ventana Medical Systems) assays. RESULTS: From July 2016 to July 2017, 267 patients were enrolled. The main histologic type was adenocarcinoma (69.3%). Most participants were smokers (67.4%) and had clinical stage IV disease (60.7%). In total, 116 (42%) and 58 (21%) patients had TPS ≥1% and ≥50%, respectively. The patients were significantly older in TPS ≥1% group than in TPS <1% group (64.83±9.38 years vs. 61.73±10.78 years, p=0.014), not in TPS ≥50% cutoff value (64.69 ± 9.39 vs. 62.36 ± 10.51, p= 0.178). Regarding histologic grade, higher proportions of poorly differentiated tumor were observed in the TPS ≥1% (40.8% vs. 25.8%, p=0.020) and TPS ≥50% groups (53.2% vs. 27.2%, p=0.004). Among 34 patients examined with 22C3 and SP263 assays, 27 had positive results in both assays, with a cutoff of TPS ≥1% (r=0.826; 95% confidence interval, 0.736–0.916). CONCLUSION: PD-L1 expression, defined as TPS ??%, was related to older age and poorly differentiated histology. There was a similar distribution of PD-L1 expression in both 22C3 and SP263 results.

Development of Koreans Gut Quotient Measurement Scales / 대한소화기학회지

BACKGROUND/AIMS: The aim of this study was to develop ‘Koreans Gut Quotient Measurement Scales (GQ)’, in which Koreans respond to questionnaires about the subjective feelings and symptoms of their intestinal health status.METHODS: Among 66 items pooled from previous studies and 4 items that were added following a focus group interview, 15 items were chosen using the Delphi survey. The content validity was evaluated using the content validity ratio. Data collected from 1,120 people from the general public in Korea were analyzed to verify the reliability and validity of GQ.RESULTS: The finalized GQ consisted of 17 items (including two exploratory measurement items) that were classified into three independent factors based on exploratory factor analysis (EFA): ‘perceived intestine discomfort’, ‘bowel movement discomfort’, and ‘bowel movement control discomfort’. The discriminant and convergent validity of GQ were identified using EFA, reliability test, and confirmatory factor analysis. In addition, the criterion-related validity of GQ was identified using correlation and multiple regression analysis.CONCLUSIONS: The GQ, which is a simplified intestinal health index developed based on an easy questionnaire for the public to understand, can be used as a tool for the public to evaluate their own intestinal health and determine when to visit clinics.