Search

Lymphovascular invasion (LVI) is one of the most important prognostic factors in gastric cancer as it indicates a higher likelihood of lymph node metastasis and poorer overall outcome for the patient. Despite its importance, the detection of LVI(+) in histopathology specimens of gastric cancer can be a challenging task for pathologists as invasion can be subtle and difficult to discern. Herein, we propose a deep learning-based LVI(+) detection method using H&E‐stained whole‐slide images. The ConViT model showed the best performance in terms of both AUROC and AURPC among the classification models (AUROC: 0.9796; AUPRC: 0.9648). The AUROC and AUPRC of YOLOX computed based on the augmented patch-level confidence score were slightly lower (AUROC: -0.0094; AUPRC: -0.0225) than those of the ConViT classification model. With simple averaging of the patch-level confidence scores, the ensemble model exhibited the best AUROC, AUPRC, and F1 scores of 0.9880, 0.9769, and 0.9280, respectively. The proposed model is expected to contribute to precision medicine by potentially saving examination-related time and labor and reducing disagreements among pathologists.

BACKGROUND Acral skin tumours are common, but information in the literature regarding their incidence is scarce. AIM To investigate the clinical characteristics and differences in incidence of benign and malignant acral tumours by anatomical site. METHODS A retrospective review was conducted of 802 patients with acral skin tumours confirmed by skin biopsy between January 2010 and December 2019. Age, sex, duration, symptoms and sites were obtained from medical records and photographs. RESULTS The mean age of onset was 43.8 years, the male/female ratio was 1 : 1.41, and the mean duration was 68.8 months. Most tumours were asymptomatic (66.7%). In total, 802 acral tumours were identified: 512 (63.8%) were benign and 290 (36.2%) were malignant. The most common benign tumours were benign melanocytic lesions (n = 239), and the most common malignant tumours were melanoma (n = 234). The most common site was the sole (n = 408). Benign melanocytic lesions, melanoma and epidermal cysts were more frequent on the foot, whereas pyogenic granuloma, glomus tumours, haemangiomas and mucous cysts were more frequent on the hand. Glomus tumours, fibromas, mucous cysts and osteomas were more frequent on the nail portion, and benign melanocytic lesions and epidermal cysts were more frequent on the non-nail portion. CONCLUSION This study reports the incidence of various benign and malignant acral tumours according to site, and we believe the results will be helpful in making a clinical diagnosis.

Little is known regarding the effect of hyperuricaemia on the progression of kidney function in patients with lupus nephritis (LN). Thus, we investigated the effect of uric acid (UA) on the long-term outcome of patients with biopsy-proven LN.Data were obtained from KORNET, a prospective longitudinal systemic lupus erythematosus registry in the Republic of Korea. All 137 patients with LN included in this study had undergone a kidney biopsy and were subsequently treated with immunosuppressants. The patients were divided into two groups: UA ≤7 mg/dL and7 mg/dL; their sociodemographic, clinical, treatment-related data, and outcomes were compared. Cox-proportional regression analyses were performed to identify independent predictors of renal outcome in patients with LN.Among the 137 patients, 37 (27.0%) had UA7 mg/dL. This higher UA group included fewer women, but more patients with hypertension, proliferative type LN, and a chronicity index12. The 24-h urinary protein excretion and the creatinine level were higher in this group; haemoglobin, platelet, and albumin levels were lower. During 85.0 months of follow-up, complete remission at 1 year was less frequent in the higher UA group, whereas chronic kidney disease (CKD) and end-stage renal disease were more prevalent. In the Cox proportional hazards regression analysis, UA7 mg/dL was a signi cant predictor of progression to CKD in patients with LN (hazard ratio=2.437; p=0.020).Our findings suggest that hyperuricaemia at LN onset is an independent risk factor that predicts the development of CKD in patients with LN.

The risk factors affecting acral melanoma metastasis and prognosis remain unclear. The study included 168 patients with invasive acral melanoma who were followed for ≥3 years. We evaluated patient demographics, stages, clinicopathological features, anatomic site of melanoma including nail versus volar surface, and degree of melanoma pigmentations, sentinel lymph node biopsy results, and the first metastasis sites. Of the 168 patients (mean age 64.5 years; 52.4% male), 43 (25.6%) had invasive melanoma without metastasis, 113 (67.3%) had invasive melanoma with a first lymph node metastasis, and 12 (7.1%) had invasive melanoma with invasive melanoma with a first distant metastasis. Advanced T stage, high mitotic rate, ulceration, and the degree of pigmentation were significant risk factors for metastasis. Amelanotic and mild pigmentation of acral melanoma was associated with first distant metastasis, whereas heavy pigmentation was associated with first lymph node metastasis. Advanced TNM stages, high mitotic rate, volar location (hazard ratio = 2.24, 95% confidence interval 1.18-4.26), and low-pigmentation (hazard ratio = 2.02, 95% confidence interval 1.17-3.49) were associated with melanoma-specific mortality.

To provide the clinical characteristics, prognostic factors, and 5-year relative survival rates of lung cancer diagnosed in 2015.The demographic risk factors of lung cancer were calculated using the KALC-R (Korean Association of Lung cancer Registry) cohort in 2015, with survival follow-up until December 31, 2020. The 5-year relative survival rates were estimated using Ederer II methods, and the general population data used the death rate adjusted for sex and age published by the Korea Statistical Information Service from 2015 to 2020.We enrolled 2,657 patients with lung cancer who were diagnosed in South Korea in 2015. Of all patients, 2,098 (79.0%) were diagnosed with NSCLC and 345 (13.0%) were diagnosed with SCLC, respectively. Old age, poor performance status, and advanced clinical stage were independent risk factors for both NSCLC and SCLC. In addition, the 5-year relative survival rate declined with advanced stage in both NSCLC (82%, 59%, 16%, 10% as the stage progressed) and SCLC (16%, 4% as the stage progressed). In patients with stage IV adenocarcinoma, the 5-year relative survival rate was higher in the presence of EGFR mutation (19% vs 11%) or ALK translocation (38% vs 11%).In this Korean nationwide survey, the 5-year relative survival rates of NSCLC were 82% at stage I, 59% at stage II, 16% at stage III, and 10% at stage IV, and the 5-year relative survival rates of SCLC were 16% in cases with limited disease, and 4% in cases with extensive disease.

BACKGROUND Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor that exhibits an epithelioid and spindle cell morphology. The tumor is characterized by immunoreactivity for melanocytic and myogenic markers but can be misdiagnosed as more common tumors with similar characteristics, including gastrointestinal stroma tumors or leiomyosarcomas. Recently, a subset of PEComas has been reported to harbor a transcription factor binding to TFE3 fusion. Herein, we report a rare case of TFE3-expressing malignant PEComa arising from the mesentery. CASE SUMMARY A 50-year-old woman presented with abdominal discomfort for 3 months. Results of laboratory tests were all within the normal ranges, and the patient had no notable medical history. Magnetic resonance imaging revealed a large tumor on the right side of the pelvic floor, which was originally suspected to be a primary ovarian tumor. However, during surgery, the tumor was revealed to have originated from the mesentery. Histologically, the tumor was composed of bundles of spindle cells and sheets of epithelioid cells. Extensive coagulative necrosis and numerous mitotic figures were observed. Immunohistochemistry revealed that the tumor cells were positive for smooth muscle actin, HMB-45, and TFE3 expression. Tumor involvement of the rectal serosa was identified, leading to a final diagnosis of malignant PEComa of the mesentery. Surgical resection was followed by adjuvant chemotherapy. No recurrence or metastasis was observed over a 6-month follow-up period. CONCLUSION Malignant PEComa of the mesentery is extremely rare and should be distinguished from morphological mimics through differential diagnosis and immunohistochemistry.

Background Extraosseous Ewing sarcoma (EES) usually has a pseudocapsule and high vascularity, making it well circumscribed and focally dense with contrast enhancement on magnetic resonance imaging (MRI). Consequently, it is difficult to diagnose and distinguish from other spinal tumors, based on pretreatment radiologic findings alone. Here, we present a case of EES involving the thoracic spinal column, which was suspected to be spinal schwannoma through pretreatment radiologic findings. Case Description A 54-year-old woman was admitted to our hospital with upper back and left-sided chest pain. Contrast-enhanced MRI of the thoracolumbar spine showed a 17- × 12-mm-sized mass in the epidural region and left neural foramen at the T6-7 level. Our preliminary diagnosis was spinal schwannoma. The patient underwent T6 hemilaminectomy. Intraoperatively, the lesion appeared as gray-colored soft mass with high vascularity, which seemed to have originated from the left T6 nerve root. The tumor was excised with en bloc resection. Histopathologic examination of the lesion revealed classical Ewing sarcoma with high cellularity of small round cells. Immunohistochemistry revealed strong positivity for cluster of differentiation 99 and FLI-1. Intensity-modulated radiation therapy was performed. The patient did not receive chemotherapy. Five years after surgery, follow-up spinal MRI and positron emission tomography computed tomography scan revealed no recurrence of the tumor or new lesions. Conclusions Clinicians should consider EES in the differential diagnosis of other neural foraminal spinal tumors, such as schwannoma. If clinicians are confident that EES has been removed completely and there are no other lesions, radiotherapy is sufficient and additional chemotherapy may not be necessary.

Sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) is a rare malignant neoplasm with epidermoid and glandular differentiation, accompanied by prominent sclerosis along with eosinophilic infiltration. SMECE was first described in 1991 (1) as a distinctive low-grade carcinoma of the thyroid. SMECE shows a female predilection and is associated with Hashimoto's thyroiditis (HT). (2) Cytologic descriptions of SMECE are scant and only five case reports (six cases) with cytologic findings from aspiration specimens have been described. (3-7) Because of the rarity of SMECE, no definitive cytologic criteria have been established. We describe one case of SMECE with an emphasis on the cytomorphologic features. The findings could help inform the cytologic diagnosis of SMECE.

Immune checkpoint inhibitors (ICIs) targeting programmed death-1 (PD-1) pathway have significantly improved outcomes for patients with a variety of malignancies, including non-small cell lung cancer (NSCLC). In contrast, the incidence of immune-related cutaneous adverse events such as vitiligo have been on the rise because of the increasing use of ICIs. Vitiligo-like depigmentation has been reported in only 2.0% to 8.3% of patients with melanoma and is considered a favorable prognostic factor. However, it has been rarely reported in patients with non-melanoma malignancies. We describe a case of vitiligo-like skin depigmentation after pembrolizumab use in a patient with stage IV NSCLC. Multiple ill-defined painless and non-pruritic depigmented patches appeared on the patient’s hands, scrotum, and lower lip after five months of pembrolizumab. We continued treatment with pembrolizumab 2 mg/kg for 14 months with close monitoring of vitiligo lesions until the progression of brain metastasis, but the vitiligo-like depigmentation did not improve by the combined excimer laser and topical corticosteroid therapy. Clinicians should be aware that immune-related cutaneous adverse events such as vitiligo-like depigmentation are not limited to cases of melanoma but arise as a direct result of anti-PD-1 therapy.

Apocrine carcinoma is a rare malignant sweat gland tumor that has been reported in approximately 200 cases. This tumor usually occurs in the axilla, but in rare cases, it can also develop in the scalp. In the present work, we report 2 cases of cutaneous apocrine carcinoma of the scalp.Two men visited our outpatient clinic with recurrence of tumor after undergoing surgery for scalp tumor at another hospital.Brain magnetic resonance imaging of a 56-year old man showed the presence of a 5.0 × 4.5 × 4.4 cm scalp mass in the right parietal region, invading the skull and dura mater and a 2.2 × 2.0 × 0.7 cm bony mass without any skin lesions right next to the scalp mass. Neck magnetic resonance imaging of a 76-year-old man revealed the presence of a well-defined oval mass in the subcutaneous layer of the left occipital scalp and 2 enlarged lymph nodes in the left neck. Definite diagnoses were made postoperatively. The patients were diagnosed with cutaneous apocrine carcinoma. The diagnosis was confirmed through histopathological and immunohistochemical staining tests.The tumors were removed with a wide safety margin and reconstructive surgery was performed.Additional radiotherapy or chemotherapy was performed. Follow-up more than 6 months revealed no recurrence or metastasis.If accurate diagnosis and treatment had taken place at the initial stages of the primary cutaneous apocrine carcinoma, it would have been possible to prevent recurrence and intracranial invasion. As recurrent primary cutaneous apocrine carcinoma can become aggressive and difficult to treat, even a small mass on the scalp must be evaluated carefully and treated properly.

Bile acids have been linked to pathomechanism and prognosis in various types of cancers. The present study aimed to investigate the effect of bile acids on the molecular change in gastric epithelial cancer cells and to evaluate gastric bile acid concentration in patients with early gastric cancer (EGC). Human gastric cancer cells (AGS and NCI‑N87 cell lines) were treated with several bile acid types to determine their effect on molecular changes in the cells. Gastric levels of individual bile acids were measured (primary unconjugated or conjugated bile acids and secondary bile acids) in 39 participants (20 controls and 19 patients with EGC). Exposing gastric epithelial cancer cells to primary bile acids

Extra-pulmonary neuroendocrine carcinoma is a rare and aggressive cancer. Although several biological and histological markers have been suggested as prognostic factors for this cancer, the prognostic importance of systemic inflammatory markers, including the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio, is unclear. This study aimed to evaluate the association between systemic inflammatory markers and the prognosis of extra-pulmonary neuroendocrine carcinoma. We retrospectively analyzed the clinical data of 85 patients with unresectable or metastatic extra-pulmonary neuroendocrine carcinoma who received platinum-based chemotherapy as first-line chemotherapy from August 2007 to November 2019. We used time-dependent receiver operating characteristic curve analysis to determine the cut-off values. The cut-off values for the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio were 3.0 and 158.5, respectively. There was no significant difference in the Eastern Cooperative Oncology Group performance status score, Ki-67 index, or response to chemotherapy between groups. The high neutrophil-lymphocyte ratio group showed significantly worse overall survival (high vs. low, median 11.1 vs. 21.0 months, log-rank p=0.004) and shorter median progression-free survival, but the latter was not statistically significant. The high platelet-lymphocyte ratio group also showed significantly worse progression-free survival and overall survival than the low platelet-lymphocyte ratio group (high vs. low: median 5.6 vs. 9.8 months, log-rank p=0.047 and median 13.8 vs. 21.0 months, log-rank p=0.013, respectively). In multivariable analysis, a high neutrophil-lymphocyte ratio was an independent prognostic factor for overall survival. The neutrophil-lymphocyte ratio is a potent and readily available prognostic factor for extra-pulmonary neuroendocrine carcinoma.

Myxoid pleomorphic liposarcoma (MPL) is a rare aggressive adipocytic tumor that mainly presents in children and adolescents. It is most frequently observed in the mediastinum and rarely in the head and neck, perineal region, or back. Herein, we report the first published case of MPL of the teres minor muscle.A 24-years-old woman presented with a painless palpable mass in her right shoulder.Magnetic resonance imaging identified a 9.0 × 7.0 × 4.0 cm mass suspected to be a sarcoma in the teres minor muscle. Positron emission tomography/computed tomography revealed no evidence of distant metastasis. Histopathological examination revealed the mass to be an MPL, which was assigned a histologic grade of 3 according to the French Federation of Cancer Centers Sarcoma Group system. No tumor cells were observed along the resected margins.Under general anesthesia, the right teres minor muscle containing the mass was excised en bloc and frozen biopsy confirmed that the tumor cells did not invade the surrounding tissues.The patient underwent radiotherapy and was followed up for 6 months without complications.Although MPL in the teres minor muscle is rare, it should be considered in the differential diagnosis in patients with a mass in the teres minor muscle due to its poor prognosis.

Background We correlated the tumor proportion score (TPS) of programmed cell death ligand 1 (PD‐L1, SP263 or 22C3) expression with the disease control rate (DCR, partial remission and stable disease), and progression free survival (PFS) after nivolumab or pembrolizumab treatment. Methods A total of 70 case records (55 males, 15 females) of patients with non‐small cell lung cancer (NSCLC, 46 adenocarcinoma, 22 squamous cell carcinoma, and two others) were reviewed. The PD‐L1 expressions were divided into High (SP263 ≥ 30%, 22C3 ≥ 80%) and Low groups (SP263

To determine the relative frequency and change of malignant lymphoma in Korea according to the 4th World Health Organization (WHO) classification and compare with previous reports. Between 2015 and 2016, 7737 new patients with malignant lymphoma were enrolled from 31 institutes, with their clinicopathologic information obtained, and evaluated for the relative frequency of lymphoma subtypes. The relative frequency of non-Hodgkin lymphoma (NHL) was 94.8%, and that of Hodgkin lymphoma (HL) was 5.2%. B cell lymphomas accounted for 83.1% of all NHLs; T/natural killer (NK) cell lymphomas, 16.4%; and immunodeficiency-associated lymphoproliferative disorders, 0.5%. The most common NHL subtypes were diffuse large B cell (41.5%), extranodal marginal zone (MALT, 19.8%), follicular (7.5%), NK/ T cell (4.2%), and peripheral T cell lymphomas, not otherwise specific (PTCL, NOS, 3.4%). Nodular sclerosis was the predominant HL subtype (48.5%), followed by mixed cellularity (28.7%), lymphocyte-rich (6.8%), lymphocyte-depleted (1.5%), lymphocyte-predominant (2.8%), and unclassified HL (11.8%). Compared with a previous report, increased B cell lymphomas (77.6–83.1%) and slightly decreased NK/T cell lymphomas and PTCL were observed. The incidence of follicular lymphoma increased by more than 2.5-fold (2.9–7.5%). Incidence rates of newly diagnosed lymphomas were lower for HL and higher for extranodal NHL, MALT, and nasal type NK/T cell lymphomas in Korea than those in Western countries. A slight increase in the relative frequency of B cell lymphoma and a prominent increase in follicular lymphoma may be attributed to refined diagnostic criteria and Westernized disease patterns.

Purpose Fluorescence in situ hybridization (FISH) using tumor tissue is the gold standard for detection of anaplastic lymphoma kinase (ALK) rearrangement in non-small cell lung cancer (NSCLC). However, this method often is not repeatable due to difficulties in the acquisition of tumor tissues. Blood-based liquid biopsy using reverse transcription polymerase chain reaction (RT-PCR) is expected to be useful to overcome this limitation. Here, we investigated the feasibility of liquid biopsy using plasma and platelets for detection of ALK rearrangement and prediction of ALK inhibitor treatment outcomes. Methods ALK-FISH assays were performed in 1128 tumor specimens of NSCLC between January 2015 and June 2018. We retrospectively analyzed formalin-fixed paraffin-embedded (FFPE) tissues from previously confirmed FISH-positive (n = 199) and -negative (n = 920) cases. We recruited patients who had available tissue specimens and agreed to venous sampling. RNA was extracted from FFPE blocks, plasma, and platelets. Fusion RNA of echinoderm microtubule-associated protein-like 4 (EML4)-ALK was detected by quantitative PCR. Results Thirty-three FISH-positive and 28 FISH-negative patients were enrolled. In validation, data compared with FISH, RT-PCR using FFPE tissues showed 54.5% sensitivity, 78.6% specificity, and 75.5% accuracy. Liquid biopsy had higher sensitivity (78.8%), specificity (89.3%) and accuracy (83.6%). Higher positivity for liquid biopsy was shown in subgroups with delayed (≥ 6 months from diagnosis) blood sampling (plasma, 85.7%; platelets, 87.0%). In 26 patients treated with crizotinib, the platelet-positive subgroup showed longer median duration of treatment (7.2 versus 1.5 months), longer median progression-free survival (5.7 months versus 1.7 months), a higher overall response rate (70.6% versus 11.1%), and a higher disease control rate (88.2% versus 44.4%) than the platelet-negative subgroup. Conclusion Liquid biopsy could have applications in the diagnosis of ALK-positive NSCLC, even when using RT-PCR, and platelets can be useful for predicting treatment outcomes of ALK inhibitors.

Aim The aim of this study was to define clinical, histopathologic, and prognostic differences according to the presence of anti-ribosomal P antibody (anti-P) in Korean patients with biopsy-proven lupus nephritis (LN). Methods We studied 79 patients who underwent kidney biopsies prior to the start of induction treatment, and who were subsequently treated with immunosuppressive drugs for at least 6 months and followed-up for more than 6 months. Anti-P was measured by immunoblot analysis at the time of renal biopsy. Results Of all patients, 35.4% were anti-P-positive. Such patients exhibited earlier LN onset, a higher Systemic Lupus Erythematosus Disease Activity Index 2000 score, and a higher estimated glomerular filtration rate at the time of renal biopsy, than did those without antibodies. Upon renal histopathological analysis, patients with anti-P exhibited less interstitial inflammation in terms of the activity index, less glomerular sclerosis, less tubular atrophy, and less interstitial fibrosis in terms of the chronicity index. Furthermore, anti-P was associated with lower chronicity scores. At a median follow-up time of 47 months, renal function was preserved in 27 of 28 patients who had anti-P, but only 38 of 51 patients without such antibodies did not progress to chronic renal disease. After multivariate logistic regression, we found that anti-P positivity was associated with a reduced rate of progression to chronic kidney disease after adjusting for gender, baseline creatinine, activity and chronicity score, and treatment response (odds ratio = 0.196, 95% CI: 0.039-0.989, P = 0.048). Conclusion Anti-P was associated with better histological findings, and anti-P-positive patients had better renal outcomes than those without anti-P.

Adventitial cystic disease (ACD) of the veins is a rare vascular disease. Most cases of venous ACD are located adjacent to the joint area, such as the common femoral, external iliac, and popliteal veins. To the best of our knowledge, 67 cases of venous ACD have been reported, and ACD of the superficial femoral vein (SFV) has never been reported. Herein, we report the case of a 57-year-old male who presented with swelling and discomfort in the left leg. Computed tomography venography revealed multiple cystic lesions in the left distal SFV. The patient underwent cyst excision, which relieved the compression in the vein, although mild stenosis prevailed in the SFV. After a week, thrombosis developed in the popliteal vein. The thrombosis resolved after three months of anticoagulant therapy, and the patient showed no recurrence of ACD during three years of follow-up.

BACKGROUNDS: The present study evaluated Korean women with lung cancer and compared the clinical characteristics of ever-smoker and never-smoker groups using the National Lung Cancer Registry. METHODS: In affiliation with the Korean Central Cancer Registry, the Korean Association for Lung Cancer constructed a registry into which 10% of the lung cancer cases in Korea were registered. Female lung cancer patients with valid smoking history were evaluated. RESULTS: Among 735 female lung cancer patients, 643 (87.5%) were never-smokers and 92 (12.5%) were smokers. The median survival was significantly longer in the never-smoker group (28 vs. 14 months; P

BACKGROUND: IBM Watson for Oncology (WFO) is a cognitive computing system helping physicians quickly identify key information in a patient’s medical record, surface relevant evidence, and explore treatment options. This study assessed the possibility of using WFO for clinical treatment in lung cancer patients. METHODS: We evaluated the level of agreement between WFO and multidisciplinary team (MDT) for lung cancer. From January to December 2018, newly diagnosed lung cancer cases in Chonnam National University Hwasun Hospital were retrospectively examined using WFO version 18.4 according to four treatment categories (surgery, radiotherapy, chemoradiotherapy, and palliative care). Treatment recommendations were considered concordant if the MDT recommendations were designated ‘recommended’ by WFO. Concordance between MDT and WFO was analyzed by Cohen’s kappa value. RESULTS: In total, 405 (male 340, female 65) cases with different histology (adenocarcinoma 157, squamous cell carcinoma 132, small cell carcinoma 94, others 22 cases) were enrolled. Concordance between MDT and WFO occurred in 92.4% (k=0.881, P

Background: Traumatic events are thought to be a cause of acral melanoma. However, little is known about the role of mechanical trauma or physical stress in the development of acral melanoma. Objective: In our study, we evaluated the frequency of trauma, physical stress, and occupation in patients with acral melanoma and aimed to identify any pathological correlates of these factors. Methods: We conducted a retrospective study of 313 acral melanoma patients from Chonnam National University Hospital. We mapped melanoma- developed anatomical sites of acral areas and assessed patients’ history of trauma, physical stress, and occupation. Results: Among the 313 acral melanoma patients, many reported a traumatic event (84 of 313; 26.8%) or physical stress (91 of 313; 29.1%) before the melanoma developed. The most common anatomical sites in these patients were on the borders of the foot (136 of 313; 43.5%). Trauma was more commonly associated with the fingernails and toenails than other sites. The frequency of each type of physical stress depended on the site of the lesion. Farmer and fisherman were the most common occupations (130 of 313; 41.5%) of the acral melanoma patients. Conclusion: Our results demonstrate that traumatic events, physical stress, and certain occupations are common in acral melanomas. Further studies are needed to establish whether these are risk factors for acral melanomas. (Ann Dermatol 33(3) 228∼236, 2021)

Purpose Osimertinib is a potent, irreversible third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor for both EGFR-activating and T790M resistant mutation. The treatment efficacy of osimertinib was assessed in previously untreated patients with metastatic non–small cell lung carcinoma (NSCLC) harboring activating EGFR mutations in circulating tumor DNA (ctDNA) as well as tumor DNA.Materials and Methods Patients with activating EGFR mutations in their tumor DNA underwent screening with ctDNA analysis using Mutyper and Cobas v2 assays. Enrolled subjects received osimertinib 80 mg, once daily. Primary endpoint was objective response rate (ORR) and secondary endpoints were ctDNA test sensitivity, progression-free survival (PFS), duration of response (DoR), and safety.Results Among 39 screened patients, 29 were ctDNA positive for activating EGFR mutations and 19 were enrolled (ex19del, n=11; L858R/L861Q, n=7; G719A, n=1). Median age was 70 and most patients had brain metastases (15/19, 79%). ctDNA test sensitivity for activating EGFR mutations was 74% using both methods and 62% (Mutyper) or 64% (Cobas v2) for individual methods. ORR was 68% (13/19), median PFS was 11.1 months (95% confidence interval [CI], 0.0 to 26.7), and median DoR was 17.6 months (95% CI, 3.5 to 31.7). ORR and median PFS were significantly superior with ex19del (91%; 21.9 months; 95% CI, 5.5 to 38.3) than with L858R/L861Q (43%; 5.1 months; 95% CI, 2.3 to 7.9). One patient discontinued the drug because of drug-related interstitial pneumonitis.Conclusion Osimertinib had favorable efficacy in the first-line treatment of metastatic NSCLC harboring activating EGFR mutations in ctDNA as well as tumor DNA.

Chronic pneumonitis of infancy (CPI) is a rare interstitial lung disease (ILD) that can be fatal in some cases. It occurs in infants who initially appear well and then develop respiratory symptoms with hypoxemia and diffuse interstitial infiltrates (1). Recently, the development of molecular genetic techniques has been rapidly increasing the understanding of the cause of CPI, and mutations in related genes encoding proteins such as surfactant protein (SP)-B, SP-C and ATP-binding cassette protein family A3 (ABCA3) have been identified as a representative cause (2).

BACKGROUND In cases of EGFR-tyrosine kinase inhibitor (TKI) failure, re-biopsy may be useful to understand resistance mechanisms and guide further treatment decisions. However, performing re-biopsy is challenging because of several hurdles. We assessed the feasibility of re-biopsy in advanced non-small cell lung cancer (NSCLC) patients in real-world clinical practice. METHODS We retrospectively reviewed the clinical and pathologic data of advanced NSCLC patients who experienced disease progression after previous treatment with EGFR-TKIs at a single tertiary hospital in Korea between January 2014 and December 2016. Re-biopsy specimens included small biopsy, surgical tissue, or liquid-based cytology. EGFR mutation was tested using peptide nucleic acid-mediated clamping PCR. RESULTS Of the 230 NSCLC patients that experienced progression after EGFR-TKI therapy, 105 (45.7%) underwent re-biopsy. Re-biopsy was successfully performed in 94 (89.5%) patients, and 11 patients were diagnosed with no malignancy. The complication rate was 8.6%, including seven cases of pneumothorax. EGFR mutation testing was performed on 75 patients using re-biopsy specimens. Of the 57 patients who had sensitizing mutations at diagnosis, T790M mutations were found in 19 (33.3%), while 38 (66.7%) had no T790M mutation. Multivariate analysis showed that the re-biopsy group was younger (P = 0.002) and exhibited a previous response to EGFR-TKIs (P

Acral melanoma occurring on the palms, soles, and nails is the most common subtype of cutaneous melanoma in Asians. Genetic alterations in acral melanoma and acral melanocytic nevus are not well known. We performed next-generation sequencing and evaluated the correlations between genetic information and the clinicopathologic characteristics from 85 Korean patients with acral melanocytic neoplasms. Of the 64 patients with acral melanoma, most had lesions at the T2 stage or higher, and the heel was the most common anatomical site of melanoma (n = 34 [53.1%]). The five most common mutations were BRAF (22 [34.4%]), NRAS (14, [21.9%]), NF1 (11, [17.2%]), GNAQ (12, [17.2%]), and KIT (7, [10.9%]). In the 21 acral melanocytic nevi, those five gene mutations were also common. Copy number variations were also frequently detected in 75% of acral melanomas and 47.6% of acral melanocytic nevi, and amplification was more common than deletion in both lesions. BRAF mutation was associated with round epithelioid cells and NRAS and NF1 mutations with bizarre cells. NF1 and GNAQ mutations showed elongated and spindle cells with prominent dendrites in acral melanomas. KIT mutations were common in amelanotic acral melanoma. This study suggests that common mutated genes are associated with distinct cytomorphological features in acral melanocytic lesions.

AIM Renal responses to immunosuppressive agents in patients with lupus nephritis (LN) differ depending on ethnicity, follow-up duration, disease severity and treatment. Thus, we evaluated predictors of complete remission during the first year following immunosuppressive treatment in patients with LN. METHODS We retrospectively reviewed 79 patients who underwent kidney biopsy prior to the start of induction treatment and who were subsequently treated with immunosuppressive drugs for at least 6 months and followed-up for more than a year. Complete remission (CR) was defined as inactive urinary sediment, a decrease in urinary protein to a creatinine ratio

Objectives: We aimed to evaluate the prevalence and predictive role of c-MET expression and EGFR mutation in the efficacy of erlotinib in non-small-cell lung cancer (NSCLC). Methods: We prospectively recruited 196 patients with stage IV or recurrent NSCLC treated with erlotinib after failure of first-line chemotherapy. Immunohistochemistry was used to evaluate c-MET overexpression, silver in situ hybridization (SISH) to assess gene copy number, and real-time polymerase chain reaction to detect EGFR mutations, respectively, in tumor tissue. Results: The major histologic type was adenocarcinoma (66.8%). c-MET was overexpressed in 55.8% (87/156) and dominant in females as well as non-squamous histology. Although c-MET gene amplification and high polysomy were observed in 2.0% (3/152) and 11.2% (17/152), they did not correlate with any characteristics. EGFR mutation was detected in 13.1% (20/153). The objective response rate of erlotinib was higher (61.1 vs. 3.7%, p < 0.001) and the median progression-free survival (PFS) was longer (10.2 vs. 1.9 months, p < 0.001) in EGFR-sensitizing mutations. However, c-MET positivity did not show a significant correlation with response to erlotinib or PFS. Conclusion: We reconfirmed EGFR mutation as a strong predictive marker of NSCLC. However, c-MET positivity was not associated with response or PFS, although c-MET overexpression correlated with some clinical characteristics.

An inflammatory myofibroblastic tumor originating from the aorta is extremely rare. Here, we report a case involving a 41-year-old female patient with an aortic inflammatory myofibroblastic tumor. Although preoperative imaging showed a mediastinal mass indicative of invasive thymoma, surgical findings revealed that this mass originated from the aorta. The patient underwent partial resection of the aorta, including the mass with patch angioplasty. Based on the postoperative histological findings, the patient was diagnosed with an aortic inflammatory myofibroblastic tumor and is currently under outpatient follow-up.

A mediastinal germ cell tumor with a sarcomatous component is extremely rare and is accompanied by a poor prognosis. Clinical and radiologic diagnosis is very difficult. Herein, we report a rare case of anterior mediastinal malignant teratoma containing a growing liposarcomatous component and detail the diagnostic process. The case was diagnosed by repeated transthoracic needle biopsy and correlated with changes in follow-up chest computed tomography and serum tumor markers. We also provide a review of the literature.

Summary Background CT radiation is arguably carcinogenic. Results from single-centre studies, mostly retrospective, have advocated lowering the CT radiation dose for the diagnosis of appendicitis. However, adoption of low-dose CT has been slow. We aimed to assess the effectiveness of low-dose CT compared with standard-dose CT in the diagnosis of appendicitis in adolescents and young adults. Methods We did this pragmatic, multicentre, randomi s ed controlled non-inferiority trial at 20 South Korean teaching hospitals with little experience with low-dose CT. Patients aged 15–44 years with suspected appendicitis were randomly assigned (1:1), via computer-generated random assignments (permuted block sizes of two, four, six, and eight) concealed in sequentially numbered envelopes, to receive low-dose CT (2 mSv) or standard-dose CT (≤8 mSv). Randomisation was stratified by site. Group allocation was concealed from patients, outcome assessors, and adverse event adjudicators; care providers, site pathologists, and data collectors were aware of allocation. The primary endpoint was the negative (unnecessary) appendectomy rate among all appendectomies, with a non-interiority margin of 4·5% for low-dose versus standard-dose CT. Primary analy s is was by modified intention to treat, which included all patients who received an appendectomy in the group to which they were assigned. This trial is registered with ClinicalTrials.gov, number NCT01925014. Findings Between Dec 4, 2013, and Aug 18, 2016, we assigned 1535 patients to the low-dose CT group and 1539 patients to the standard-dose CT group. 22 (3·9%) of 559 patients had a negative appendectomy in the low-dose group versus 16 (2·7%) of 601 patients in the standard-dose group (difference 1·3%, 95% CI −0·8 to 3·3; p=0·0022 for the non-inferiority test). We recorded 43 adverse events in 43 (2·8%) of 1535 patients in the low-dose group and 41 adverse events in 40 (2·6%) of 1539 patients in the standard-dose group. One life-threatening adverse event of anaphylaxis caused by an iodinated contrast material occurred in the low-dose group. Interpretation Radiation dose of appendiceal CT for adolescents and young adults can be reduced to 2 mSv without impairing clinical outcomes. In view of the vast number of appendiceal CT examinations done worldwide, use of low-dose CT could prevent a sizeable number of radiation-associated cancers in the future. Funding Korea Health Industry Development Institute, Seoul National University Bundang Hospital, Dasol Life Science, and Bracco Imaging Korea.

Primary pulmonary myxoid sarcoma (PPMS), classified as low to intermediate grade malignant myxoid endobronchial tumor, is rarely reported. Most reported cases occurred in lung parenchyme with an endobronchial component. Herein, we report a case of PPMS in a 29-year-old woman that developed in a major fissure of the left lung without parenchymal invasion. Histopathologically, the diagnosis was compatible to PPMS with EWSR1-CREB1 translocation.

Epstein-Barr virus (human herpesvirus-4) is very common virus that can be detected in more than 95% of the human population. Most people are asymptomatic and live their entire lives in a chronically infected state (IgG positive). However, in some populations, the Epstein-Barr virus (EBV) has been involved in the occurrence of a wide range of B-cell lymphoproliferative disorders (LPDs), including Burkitt lymphoma, classic Hodgkin’s lymphoma, and immune–deficiency associated LPDs (post-transplant and human immunodeficiency virus–associated LPDs). T-cell LPDs have been reported to be associated with EBV with a subset of peripheral T-cell lymphomas, angioimmunoblastic T-cell lymphomas, extranodal nasal natural killer/T-cell lymphomas, and other rare histotypes. This article reviews the current evidence covering EBV-associated LPDs based on the 2016 classification of the World Health Organization. These LPD entities often pose diagnostic challenges, both clinically and pathologically, so it is important to understand their unique pathophysiology for correct diagnoses and optimal management.

Introduction To date, no prospective phase III trials have directly compared the efficacy of pemetrexed plus cisplatin (Pem-Cis) with docetaxel plus cisplatin (Doc-Cis) in patients with nonsquamous non–small-cell lung cancer. Materials and Methods A total of 148 chemotherapy-naive patients lacking driver mutations were randomized into 21-day regimens of cisplatin 70 mg/m 2 with either docetaxel 60 mg/m 2 (n = 71) or pemetrexed 500 mg/m 2 (n = 77) for ≤ 4 cycles. The primary objective was to assess the noninferiority of progression-free survival (PFS) for patients receiving the Doc-Cis regimen. The secondary endpoints were the response rates, overall survival, and toxicity profiles. Results Partial remission was observed in 24 (31.2%) and 24 (33.8%) patients in the Pem-Cis and Doc-Cis groups, respectively. The median PFS was 4.7 months (95% confidence interval [CI], 4.4-5.0) in the Pem-Cis arm and 4.4 months (95% CI, 3.7-5.1) in the Doc-Cis arm ( P > .05). The median overall survival was longer in the Doc-Cis arm (13.3 months; 95% CI, 8.1-18.5) than in the Pem-Cis arm (11.7 months; 95% CI, 8.6-14.8; P > .05). Between the 2 arms, no significant difference was found in the subsequent treatments after failure of first-line treatment. The rate of grade 3 or 4 neutropenia and febrile neutropenia was greater in the Doc-Cis arm than in the Pem-Cis arm. Conclusion In nonsquamous non–small-cell lung cancer patients lacking driver mutations, the PFS and response rates were similar between the 2 arms, and toxicity was tolerable, although adverse events and more severe toxicities were observed more frequently in the Doc-Cis arm.

We investigated whether lupus nephritis (LN) patients could be distinguished based on the time of disease onset and, if so, whether the groups differed in their clinical and laboratory features and long-term prognosis in ethnically homogeneous Korean patients. We enrolled 117 systemic lupus erythematosus patients with available clinical data at the time of renal biopsy of LN. Sociodemographic, clinical, and laboratory data and concomitant diseases were evaluated at the time of renal biopsy. We divided LN patients, according to age at LN diagnosis, into three groups: juvenile-onset LN (JLN, diagnosed at ≤18 years), adult-onset LN (ALN, diagnosed at 18–50 years), and late-onset LN (LLN, diagnosed at >50 years) and compared demographic, clinical, histological, and laboratory findings. We also compared treatment and long-term prognosis of LN. Of the 117 LN patients, 20 (17.8%), 84 (71.3%), and 13 (10.9%) were JLN, ALN, and LLN patients, respectively. LLN patients showed higher white blood cell counts and lower estimated glomerular filtration rate than ALN or LLN patients. LLN patients had higher chronicity indices and scores. Anti-Ro antibodies were found more frequently in ALN patients, and lower complement levels were more common in JLN patients. During a mean follow-up of 76.5 months, development of chronic kidney disease and death were higher in LLN patients than in JLN and ALN patients. LLN patients showed higher chronicity indices and deterioration of kidney function and death in long-term follow-up compared with JLN and ALN patients. Therefore, LLN patients should be carefully monitored to avoid poor outcomes.

ObjectivesWe analyzed the clinical follow-up results of 88 lupus nephritis patients to find prognostic factors for the development of chronic kidney disease in ethnically homogeneous Korean patients with biopsy-proven lupus nephritis.MethodsSociodemographic, clinical, laboratory, and treatment-related data at the time of kidney biopsy and during follow-up were obtained. Renal biopsy specimens were reclassified according to the International Society of Pathology/Renal Pathology Society classification, separately, by two renal pathologists blinded to the previous classification. Univariate and multivariate analyses were performed using the Cox proportional hazard regression model to identify independent risk factors for chronic kidney disease in lupus nephritis patients.ResultsEighteen of 88 patients (20.5%) developed chronic kidney disease during a mean follow-up of 47.6 months (range: 12–96 months). Patients who developed chronic kidney disease were older at onset of lupus nephritis, had less education, and were more likely to have hypertension; they had lower serum albumin levels, lower platelet levels, higher serum creatinine levels, lower estimated glomerular filtration rate, higher chronicity index, and lower frequency of anti-ribosomal P antibodies, and they were less likely to be in complete remission in the first year. In stepwise multivariable analyses, hypertension, lower glomerular filtration rate, and failure to achieve complete remission in the first year of treatment were significant predictors of the development of chronic kidney disease in lupus nephritis patients.ConclusionsThese findings suggest that patients with hypertension and decreased kidney function at the onset of lupus nephritis and showing a poor response to immunosuppressive drugs in the first year should be monitored carefully and managed aggressively to avoid deterioration of kidney function.

Hypocalcemia is relatively uncommon paraneoplastic syndrome. Only one case of hypocalcemia has been reported in a patient with chondrosarcoma. We herein report a case of a 32-year-old woman with metastatic chondrosarcoma with tetany. Her imaging findings revealed multiple calcific metastatic lesions in the lungs, pancreas, left atrium, and pulmonary vein. A laboratory examination showed hypocalcemia with no evidence of any other disease that could induce hypocalcemia. On the basis of the laboratory and clinical findings, we concluded the etiology of her severe hypocalcemia to be excessive calcium consumption by the tumor itself.

Objectives: Bronchial brushing (BB) is often used to obtain supplementary samples for diagnosing lung cancer. We examined the possibility of epidermal growth factor receptor (EGFR) testing on BB samples and compared them with bronchial biopsy samples. Material and Methods: We used 150 BB samples with non-small cell carcinoma submitted to our department within 2 years. Biopsy samples were concurrently submitted for histologic diagnosis. We used the peptide nucleic acid clamping method for EFGR mutation test. Histologic diagnosis identified 137 cases of adenocarcinomas and 13 cases of non-small cell lung carcinoma, not otherwise specified. Each sample was assessed for adequacy and DNA content for EGFR mutation test. Results: Among BB samples, 28 had exon 19 deletion, 21 had mutations in exon 21, 99 were wild type, and analysis of two failed. The EGFR mutation rate in BB samples was 33.1% (49/148). Among bronchial biopsy samples, 26 had exon 19 deletion, 20 had mutations in exon 21, 92 were wild type, and analysis of 12 failed. The EGFR mutation rate using biopsy sample was 33.8% (46/136). The mutation detection results were nearly identical in both groups of samples (131/138, 94.9%). However, in two cases, an exon 21 mZutation was detected in biopsy samples but not in BB samples. In five cases, exon 19 deletion (two cases) and exon 21 mutation (three cases) were detected in BB but not in biopsy samples. The median DNA content was 58.83 ng for BB samples and 48.47 ng for biopsy samples. The failure rate for BB samples was lower than for biopsy samples. Overall, the BB samples were comparable to bronchial biopsy samples in terms of DNA quantity and mutation detection results. Conclusion: We conclude that in case of inadequate biopsy samples, BB samples can be used as a substitute material for EGFR mutation test.

Diaschisis has been described as functional depression distant to the lesion. A variety of neuroscientific approaches have been used to investigate the mechanisms underlying diaschisis. However, few studies have examined the pathological changes in diaschisis at ultrastructural level. Here, we used a rat model of capsular infarct that consistently produces diaschisis in ipsilesional and contralesional motor and sensory cortices. To verify the occurrence of diaschisis and monitor time-dependent changes in diaschisis, we performed longitudinal 2-deoxy-2-[18F]-fluoro-d-glucose microPET (FDG-microPET) study. We also used light and electron microscopy to identify the microscopic and ultrastructural changes at the diaschisis site at 7, 14, and 21 days after capsular infarct modeling (CIM). FDG-microPET showed the occurrence of diaschisis after CIM. Light microscopic examinations revealed no significant histopathological changes at the diaschisis site except a mild degree of reactive astrogliosis. However, electron microscopy revealed swollen, hydropic degeneration of axial dendrites and axodendritic synapses, although the neuronal soma (including nuclear chromatin and cytoplasmic organelles) and myelinated axons were relatively well preserved up to 21 days after injury. Furthermore, number of axodendritic synapses was significantly decreased after CIM. These data indicate that a circumscribed subcortical white-matter lesion produces ultrastructural pathological changes related to the pathogenesis of diaschisis.

Rationale: Current guidelines for advanced non-small cell lung cancer (NSCLC) recommend the use of targeted agents for specific driver genes after confirming genetic alterations. Although epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement are usually mutually exclusive, EGFR and ALK co-alterations have been reported increasingly in cases of NSCLC. However, the optimal treatment for these cases has not been established. Patient concerns: This case series describes three patients diagnosed with advanced non-squamous NSCLC who harbored EGFR and ALK co-alterations. The complaints for each case are as follows: 57-year-old woman with coughing and dyspnea in case 1, 32-year-old man with diplopia in case 2 and 77-year-old woman with chest discomfort in case 3. Diagnoses: Three never-smokers were diagnosed pathologically with stage IV adenocarcinoma of the lung. Subsequent molecular studies revealed the EGFR L858R mutation gene and ALK rearrangement, which were proven by real-time polymerase chain reaction and fluorescence in situ hybridization, respectively. Interventions: All 3 patients received first-line therapy with EGFR-tyrosine kinase inhibitors (TKIs). Cases 1 and 2 were treated with ALK-TKIs as second-line therapy and received additional EGFR-TKIs as third- and fourth-line regimens. Outcomes: The patients achieved partial responses to EGFR-TKIs according to radiologic findings. However, second-line ALK-TKI therapy was ineffective in cases 1 and 2. Lessons: Cases of NSCLC with concomitant EGFR mutation and ALK rearrangement are rare, and the selection of an optimal targeted therapy is challenging. Here, EGFR-TKI appeared to yield better outcomes than ALK-TKI in patients with NSCLC who harbored EGFR/ALK co-alterations.

Rationale: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an uncommon and aggressive hematologic malignancy that arises from plasmacytoid dendritic cells. BPDCN typically presents with skin lesions with or without involvement of lymph nodes, peripheral blood, or bone marrow. However, breast involvement of BPDCN is rare and there has been no report describing the radiologic features of BPDCN within breast parenchyma. Patient concerns: We report a case of a 47-year-old woman who presented with an incidentally detected hypermetabolic breast lesion on PET/CT with concurrent right cheek plaque. Diagnoses: Skin biopsy was performed for the right cheek plaque. Mammography and breast ultrasonography were performed to evaluate the breast lesion. The lesion was depicted as a 2.5 cm sized focal asymmetry on mammogram and an irregular heterogeneous echoic mass within the mammary zone of the right upper outer breast. Core needle biopsy was performed for the breast lesion. Histologic diagnosis of the two lesions was BPDCN. Interventions: The patient was treated with induction and consolidation chemotherapy and received allogenic peripheral blood stem cell transplantation. Outcomes: The patient remains in complete remission state without relapse at 34 months since initial diagnosis. Lessons: This is the first case of BPDCN manifested as a breast parenchymal mass and assessed by diagnostic breast imaging tools (mammography and ultrasonography). This case report is significant for BPDCN within the breast parenchyma and presenting rare radiologic description of BPDCN.

Solitary fibrous tumors (SFTs) are rare benign mesenchymal tumors that occur mainly in the pleura. We herein report the first case of a cellular SFT located in the mental region of the head and neck in a 46-year-old woman. Facial computed tomography revealed a mass measuring 0.8 cm with clear boundaries in the right mental region. After excision of the mass, expert pathologists diagnosed a cellular SFT. To our knowledge, this is the first case of a cellular SFT identified in the subcutaneous tissue of the mental region of the head and neck. Because the postsurgical prognosis of SFTs is unpredictable, long-term follow-up and further studies are necessary to determine the characteristics of cellular SFTs in the head and neck region.

Recent progress in chemotherapy has significantly increased its efficacy, yet the development of chemoresistance remains a major drawback. In this study, we show that GFRA1/GFRα1 (GDNF family receptor α 1), contributes to cisplatin-induced chemoresistance by regulating autophagy in osteosarcoma. We demonstrate that cisplatin treatment induced GFRA1 expression in human osteosarcoma cells. Induction of GFRA1 expression reduced cisplatin-induced apoptotic cell death and it significantly increased osteosarcoma cell survival via autophagy. GFRA1 regulates AMPK-dependent autophagy by promoting SRC phosphorylation independent of proto-oncogene RET kinase. Cisplatin-resistant osteosarcoma cells showed NFKB1/NFκB-mediated GFRA1 expression. GFRA1 expression promoted tumor formation and growth in mouse xenograft models and inhibition of autophagy in a GFRA1-expressing xenograft mouse model during cisplatin treatment effectively reduced tumor growth and increased survival. In cisplatin-treated patients, treatment period and metastatic status were associated with GFRA1-mediated autophagy. These findings suggest that GFRA1-mediated autophagy is a promising novel target for overcoming cisplatin resistance in osteosarcoma.