Comparison of four histological scoring systems for autoimmune hepatitis to improve diagnostic sensitivity

Background/Aims@#The histological criteria in the 1999 and 2008 scoring systems proposed by the International Autoimmune Hepatitis Group (IAIHG) have their inherent limitations in diagnosing autoimmune hepatitis (AIH). In this study, we evaluated the histology components of four scoring systems (1. revised original scoring system [“1999 IAIHG”], 2. simplified scoring system [“2008 IAIHG”], 3. modified histologic criteria [“2017 UCSF”], and 4. a new histologic criteria proposed by the International AIH Pathology Group [“2022 IAHPG”]) in AIH patients. @*Methods@#Medical records and liver biopsies were retrospectively reviewed for 68 patients from two independent medical institutions, diagnosed with AIH based on the 1999 IAIHG system between 2006 and 2016. The histological features were reviewed in detail, and the four histological scoring systems were compared. @*Results@#Out of the 68 patients, 56 (82.4%) patients met the “probable” or “definite” AIH criteria of the 2008 IAIHG system, and the proportion of histologic score 2 (maximum) was 40/68 (58.8%). By applying the 2017 UCSF criteria, the number of histology score 2 increased to 60/68 (88.2%), and “probable” or “definite” AIH cases increased to 61/68 (89.7%). Finally, applying the 2022 IAHPG histology score resulted in the highest number of cases with histologic score 2 (64/68; 94.1%) and with a diagnosis of “probable” or “definite” AIH (62/68; 91.2%). @*Conclusions@#The recently proposed UCSF/IAHPG histological criteria increased the histology score of AIH. Substituting the histology component of the 2008 IAIHG system with the 2022 IAHPG criteria increased the sensitivity for diagnosing AIH (≥“Probable AIH”) from 82.4% to 91.2%.

Interpretation of PD-L1 expression in gastric cancer: summary of a consensus meeting of Korean gastrointestinal pathologists

Nivolumab plus chemotherapy in the first-line setting has demonstrated clinical efficacy in patients with human epidermal growth factor receptor 2–negative advanced or metastatic gastric cancer, and is currently indicated as a standard treatment. Programmed death-ligand 1 (PD-L1) expression is an important biomarker for predicting response to anti–programmed death 1/PD-L1 agents in several solid tumors, including gastric cancer. In the CheckMate-649 trial, significant clinical improvements were observed in patients with PD-L1 combined positive score (CPS) ≥ 5, determined using the 28-8 pharmDx assay. Accordingly, an accurate interpretation of PD-L1 CPS, especially at a cutoff of 5, is important. The CPS method evaluates both immune and tumor cells and provides a comprehensive assessment of PD-L1 expression in the tumor microenvironment of gastric cancer. However, CPS evaluation has several limitations, one of which is poor interobserver concordance among pathologists. Despite these limitations, clinical indications relying on PD-L1 CPS are increasing. In response, Korean gastrointestinal pathologists held a consensus meeting for the interpretation of PD-L1 CPS in gastric cancer. Eleven pathologists reviewed 20 PD-L1 slides with a CPS cutoff close to 5, stained with the 28-8 pharmDx assay, and determined the consensus scores. The issues observed in discrepant cases were discussed. In this review, we present cases of gastric cancer with consensus PD-L1 CPS. In addition, we briefly touch upon current practices and clinical issues associated with assays used for the assessment of PD-L1 expression in gastric cancer.

Clinical Characteristics and Outcomes in Patients With Localized Gastric Langerhans Cell Histiocytosis: A Case Series / 대한Helicobacter연구학회지

Objectives@#Localized gastric Langerhans cell histiocytosis (LCH) characterized by abnormal proliferation of Langerhans cells in the stomach without systemic involvement, is rare; therefore, the clinical characteristics and outcomes of LCH remain unclear. We investigated the clinical characteristics and outcomes in patients diagnosed with localized gastric LCH and have also discussed treatment strategies for this rare disease. @*Methods@#The study included seven patients diagnosed with localized gastric LCH at our hospital between September 1997 and December 2023. We retrospectively reviewed medical records and analyzed the clinicopathological characteristics and patient outcomes. @*Results@#Endoscopically, localized gastric LCH appeared as a small erosion in the distal part of the stomach. Positron emission tomography-computed tomography revealed normal findings in 100.0% (4/4) of patients during pre-treatment workup. Immunohistochemical analysis using S-100 and CD1a showed immunopositive cells in all tested patients. Of the six patients who underwent follow-up, two (33.3%) showed metachronous recurrence at a location distinct from the initial site. However, all patients eventually showed spontaneous regression of the disease, and no gastric LCH-induced mortality was observed during follow-up. @*Conclusions@#Careful and regular surveillance may be sufficient for patients with localized gastric LCH without systemic involvement.

The First Korean Adult Case of Progressive Familial Intrahepatic Cholestasis Type 7 with Novel USP53 Splicing Variants by Next Generation Sequencing

Progressive familial intrahepatic cholestasis (PFIC) is a group of rare genetic disorders caused by defects in biliary epithelial transporters. It mostly presents as low γ-glutamyltransferase cholestasis. Recently, USP53 has been identified as one of the novel genes associated with PFIC. Herein, we report a 21-year-old Korean male patient with a late-onset PFIC. Initial work-up, including whole genome sequencing, did not find any associated gene. However, reviewing sequencing data identified novel compound heterozygous variants in splicing site of USP53 (NM_001371395.1:c.972+3_972+6del, and c.973-1G>A). The patient’s bilirubin level fluctuated during the disease course. At 4.5 years after the initial presentation, the patient’s symptom and high bilirubin level were normalized after administration of high-dose ursodeoxycholic acid. Recognition of this disease entity is important for prompt diagnosis and management. USP53 is recommended for the work-up of low γ-glutamyltransferase cholestasis.

A Standardized Pathology Report for Gastric Cancer: 2nd Edition

The first edition of ‘A Standardized Pathology Report for Gastric Cancer’ was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements.The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.

A standardized pathology report for gastric cancer: 2nd edition

The first edition of ‘A Standardized Pathology Report for Gastric Cancer’ was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.

Dual Biological Therapy for Ulcerative Colitis with Intractable Pyoderma Gangrenosum

Pyoderma gangrenosum is one of the dermatological extra-intestinal manifestations of ulcerative colitis (UC). We report a case of a 26-year-old male patient suffering from relapsed UC with a newly developed pyoderma gangrenosum. His skin and intestinal symptoms were intractable to treatment with steroids, immunosuppressants, or a single biological agent such as infliximab, golimumab, or vedolizumab. For the first time in Korea, we report a successful treatment experience of pyoderma gangrenosum in UC using dual biological agents, vedolizumab and infliximab. We strategically targeted each of the intestinal and skin symptoms, with a specific biological agent based on the drug’s mechanism of action.

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.

Four-Tier Pathologic Tumor Regression Grading System Predicts the Clinical Outcome in Patients Who Undergo Surgical Resection for Locally Advanced Pancreatic Cancer after Neoadjuvant Chemotherapy

Background/Aims@#Neoadjuvant chemotherapy is increasingly utilized in patients with borderline or locally advanced pancreatic cancer (LAPC). However, the pathologic evaluation of tumor regression is not routinely performed or well established. We aimed to evaluate the prognostic value of three tumor regression grading systems frequently used in LAPC and to determine the correlation between pathologic and clinical response. @*Methods@#We included a total of 38 patients with LAPC who were treated with neoadjuvant chemotherapy and subsequent resection. Pathologic tumor regression was graded based on the College of American Pathologists (CAP), Evans, and MD Anderson grading systems. @*Results@#One out of 38 patients (2.6%) achieved a pathologic complete response. Unlike other grading systems (Evans, p=0.063; MD Anderson, p=0.110), the CAP grading system was a significant prognostic factor for overall survival (p=0.043). Pathologic N stage (p=0.023), margin status (p=0.044), and radiologic response (p=0.016) correlated with overall survival. In the multivariate analysis, CAP 3 was an independent predictor of shorter overall survival (p=0.026). The CAP grading system correlated with the radiologic response (p=0.007) but not the carbohydrate antigen 19-9 level (p=0.333). @*Conclusions@#The four-tier CAP pathologic tumor regression grading system predicted the clinical outcome in LAPC patients who underwent resection after neoadjuvant chemotherapy. Therefore, a more comprehensive pathologic evaluation is warranted in these patients.

Eosinophil and Mast Cell Counts in the Stomach and Duodenum of Patients with Functional Dyspepsia without a Helicobacter pylori infection / 대한소화기학회지

Background/Aims@#Symptom-based subtyping of functional dyspepsia (FD) is used to segregate patients into groups with homogenous pathophysiological mechanisms. This study examined whether subtyping could reflect the duodenal and gastric microinflammation in FD patients. @*Methods@#Twenty-one FD patients without Helicobacter pylori infection were recruited. An endoscopic biopsy was performed in the duodenum 2nd portion, stomach antrum, and body. The eosinophil and mast cell counts per high-power field (×40) were investigated by H&E and c-kit staining, respectively. The degree of inflammatory cell infiltration, atrophy, and intestinal metaplasia was also determined by H&E staining in the stomach. The baseline characteristics and eosinophil and mast cell infiltrations were compared among the three groups (epigastric pain syndrome, postprandial distress syndrome, and overlap). @*Results@#According to the symptom assessment, seven subjects were classified into the epigastric pain syndrome group, 10 into the postprandial syndrome group, and four into the overlap group. The baseline variables were similar in the three groups. Eosinophil infiltration was more prominent in the duodenum than in the stomach. In contrast, mast cell infiltration was similar in the duodenum and stomach. The eosinophil counts in the duodenum were similar in the three groups. The eosinophil counts in the stomach and mast cell counts in the duodenum and stomach were also similar in the three groups. @*Conclusions@#Duodenal eosinophil infiltration was prominent in FD patients, but the eosinophil counts were similar regardless of the symptom-based subtypes of FD. Hence, the current symptom-based subtyping of FD does not reflect duodenal eosinophil and mast cell infiltration.

Pancreatic High-Grade Neuroendocrine Neoplasms in the Korean Population: A Multicenter Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The most recent 2017 World Health Organization (WHO) classification of pancreatic neuroendocrine neoplasms (PanNENs) has refined the three-tiered 2010 scheme by separating grade 3 pancreatic neuroendocrine tumors (G3 PanNETs) from poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs). However, differentiating between G3 Pan- NETs and PanNECs is difficult in clinical practice. @*Materials and Methods@#Eighty-two surgically resected PanNENs were collected from 16 institutions and reclassified according to the 2017 WHO classification based on the histological features and proliferation index (mitosis and Ki-67). Immunohistochemical stains for ATRX, DAXX, retinoblastoma, p53, Smad4, p16, and MUC1 were performed for 15 high-grade PanNENs. @*Results@#Re-classification resulted in 20 G1 PanNETs (24%), 47 G2 PanNETs (57%), eight G3 well-differentiated PanNETs (10%), and seven poorly differentiated PanNECs (9%). PanNECs showed more frequent diffuse nuclear atypia, solid growth patterns and apoptosis, less frequent organoid growth and regular vascular patterns, and absence of low-grade PanNET components than PanNETs. The Ki-67 index was significantly higher in PanNEC (58.2%± 15.1%) compared to G3 PanNET (22.6%±6.1%, p < 0.001). Abnormal expression of any two of p53, p16, MUC1, and Smad4 could discriminate PanNECs from G3 PanNETs with 100% specificity and 87.5% sensitivity. @*Conclusion@#Histological features supporting the diagnosis of PanNECs over G3 PanNETs were the absence of a low-grade PanNET component in the tumor, the presence of diffuse marked nuclear atypia, solid growth pattern, frequent apoptosis and markedly increased proliferative activity with homogeneous Ki-67 labeling. Immunohistochemical stains for p53, p16, MUC1, and Smad4 may be helpful in distinguishing PanNECs from G3 PanNETs in histologically ambiguous cases, especially in diagnostic practice when only small biopsied tissues are available.

A Case of Autoimmune Hepatitis after Occupational Exposure to N,N-Dimethylformamide

N,N-dimethylformamide (DMF), a widely used solvent in the chemical industry, is known to induce toxic hepatitis. However, there have been no reported cases of DMF-associated autoimmune hepatitis. A 31-year-old healthy man working at a glove factory since July 2015 had intermittently put his bare hands into a diluted DMF solution for his first 15 days at work. After 2 months, he felt nausea, fatigue, and hand cramping, and a jaundice followed. His laboratory findings showed positive autoantibodies and elevated immunoglobulin G (IgG), and his liver biopsy pathology was typical of autoimmune hepatitis (AIH). Prednisolone and azathioprine therapy began, and he recovered rapidly without adverse events. Though his liver chemistry was normalized, the IgG level remained persistently upper normal range. His 2nd liver biopsy performed in April 2019 showed mild portal activity, and he was well under a low dose immunosuppressive therapy up to April 2020. This case warns of the hazard of occupational exposure to DMF, and clinicians should be aware of DMF-related AIH for timely initiation of immunosuppressive therapy.

Higher Tumor Cellularity in Resected Pancreatic Ductal Adenocarcinoma Is a Negative Prognostic Indicator

Background/Aims@#Desmoplasia is a prominent feature of pancreatic ductal adenocarcinoma (PDA). Stromal desmoplasia reflects the low cellularity that is characteristic of PDA, and it may play a role in PDA chemoresistance. In this retrospective study, we evaluated the relationship between tumor cellularity in resected PDA specimens and long-term patient outcomes. @*Methods@#We retrospectively reviewed the data from 175 patients who underwent PDA resection between January 2010 and December 2015 at Seoul National University Bundang Hospital, and analyzed their clinicopathological features and the relationship between tumor cellularity (high vs low based on a cutoff of 30% cellularity) and patient outcomes. @*Results@#The high-cellularity group had significantly shorter overall survival (OS) (18.7 months vs 26.6 months, p=0.006) and disease-free survival (11.0 months vs 16.9 months, p=0.031) than the low-cellularity group. Multivariate analysis revealed that high tumor cellularity was an independent risk factor for poor OS (hazard ratio, 2.008; 95% confidence interval, 1.361 to 2.962; p<0.001). Adjuvant therapy improved OS in the low-cellularity group (16.3 months vs 41.3 months, p=0.001) but not in the high-cellularity group (15.9 months vs 24.4 months, p=0.107). @*Conclusions@#Tumor cellularity in PDA specimens may be a prognostic and predictive biomarker that could aid in identifying patients who would benefit from adjuvant therapy for PDA.

HER2 status in breast cancer: changes in guidelines and complicating factors for interpretation

Human epidermal growth factor receptor 2 (HER2) protein overexpression and/or HER2 gene amplification is found in about 20% of invasive breast cancers. It is a sole predictive marker for treatment benefits from HER2 targeted therapy and thus, HER2 testing is a routine practice for newly diagnosed breast cancer in pathology. Currently, HER2 immunohistochemistry (IHC) is used for a screening test, and in situ hybridization is used as a confirmation test for HER2 IHC equivocal cases. Since the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines on HER2 testing was first released in 2007, it has been updated to provide clear instructions for HER2 testing and accurate determination of HER2 status in breast cancer. During HER2 interpretation, some pitfalls such as intratumoral HER2 heterogeneity and increase in chromosome enumeration probe 17 signals may lead to inaccurate assessment of HER2 status. Moreover, HER2 status can be altered after neoadjuvant chemotherapy or during metastatic progression, due to biologic or methodologic issues. This review addresses recent updates of ASCO/CAP guidelines and factors complicating in the interpretation of HER2 status in breast cancers.

Changes in Biomarker Status in Metastatic Breast Cancer and Their Prognostic Value / 한국유방암학회지

PURPOSE: There is cumulative evidence that changes in biomarker status occur frequently during the metastatic progression of breast cancer and affect treatment response. The purpose of this study was to evaluate the frequency of biomarker changes in metastatic breast cancer (MBC) and its impact on prognosis. METHODS: A total of 152 patients diagnosed with MBC at the time of initial diagnosis or during post-surgical follow-up were included. Changes in biomarker status in MBCs, their frequency according to various metastatic sites, tumor characteristics, and their association with patient survival were analyzed. RESULTS: Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 status changed in 9 (6.0%), 40 (26.3%), 12 (7.9%), and 29 (19.1%) patients, respectively. ER, PR, and HER2 mainly showed positive to negative conversion, whereas Ki-67 changed mostly from a low to high index. There were no differences in the frequencies of biomarker changes according to the metastatic sites. As for ER and HER2, cases with negative conversion showed low expression levels in the primary tumor. Survival analyses indicated that a positive to negative conversion of ER was an independent poor prognostic factor in patients with primary ER-positive breast cancer. CONCLUSION: Changes in biomarker status are not rare, and usually occur in an unfavorable direction in breast cancer metastases. Negative conversion of ER status is a predictor of poor prognosis. Thus, it is beneficial to evaluate changes in biomarker status in MBC not only for the purpose of determining treatment options but also for prognostication of patients.

Evaluation of Modified Core-Needle Biopsy in the Diagnosis of Thyroid Nodules

OBJECTIVE: Core needle biopsy (CNB) of the thyroid is an additional diagnostic method for non-diagnostic or indeterminate cytology samples. We sought to evaluate a new modified core biopsy technique and compare the concordance of its diagnosis with the final diagnosis of the surgically resected specimen. MATERIALS AND METHODS: A retrospective analysis was conducted on 842 patients who had a thyroid CNB with or without a previous fine-needle aspiration from August 2002 to March 2015; 38% of patients ultimately underwent thyroidectomy. We divided the patients into two groups for comparison: conventional group (n = 329) and new modified technique group (n = 513) that enabled sampling of not only the lesion but also the margin and surrounding parenchyma. The diagnostic conclusiveness of CNB and concordant rate with thyroidectomy was compared between the two groups. RESULTS: The overall diagnostic conclusiveness did not exhibit a significant increase (77% in the conventional technique group and 75% in the modified technique group, p = 0.408). In terms of the diagnostic concordance rate between CNB and thyroidectomy, no overall significant increase was observed (83% in the conventional technique group and 88% in the modified technique group, p = 0.194). However, only in follicular-patterned lesions (nodular hyperplasia, follicular neoplasm, and follicular variant of papillary thyroid carcinoma), a significant increase in the diagnostic concordance rate was observed (83% in the conventional group and 94% in the modified technique group, p = 0.033). CONCLUSION: Modified CNB technique can be beneficial for the accurate diagnosis of follicular-patterned thyroid lesions.

The Clinicopathological and Prognostic Significance of the Gross Classification of Hepatocellular Carcinoma

BACKGROUND: We aimed to determine the clinicopathological significance of the gross classification of hepatocellular carcinoma (HCC) according to the Korean Liver Cancer Association (KLCA) guidelines. METHODS: A retrospective analysis was performed on 242 cases of consecutively resected solitary primary HCC between 2003 and 2012 at Seoul National University Bundang Hospital. The gross classification (vaguely nodular [VN], expanding nodular [EN], multinodular confluent [MC], nodular with perinodular extension [NP], and infiltrative [INF]) was reviewed for all cases, and were correlated with various clinicopathological features and the expression status of “stemness”-related (cytokeratin 19 [CK19], epithelial cell adhesion molecule [EpCAM]), and epithelial-mesenchymal transition (EMT)–related (urokinase plasminogen activator receptor [uPAR] and Ezrin) markers. RESULTS: Significant differences were seen in overall survival (p=.015) and disease-free survival (p = .034) according to the gross classification; INF type showed the worst prognosis while VN and EN types were more favorable. When the gross types were simplified into two groups, type 2 HCCs (MC/NP/INF) were more frequently larger and poorly differentiated, and showed more frequent microvascular and portal venous invasion, intratumoral fibrous stroma and higher pT stages compared to type 1 HCCs (EN/VN) (p < .05, all). CK19, EpCAM, uPAR, and ezrin expression was more frequently seen in type 2 HCCs (p < .05, all). Gross classification was an independent predictor of both overall and disease-free survival by multivariate analysis (overall survival: p=.030; hazard ratio, 4.118; 95% confidence interval, 1.142 to 14.844; disease-free survival: p=.016; hazard ratio, 1.617; 95% confidence interval, 1.092 to 2.394). CONCLUSIONS: The gross classification of HCC had significant prognostic value and type 2 HCCs were associated with clinicopathological features of aggressive behavior, increased expression of “stemness”- and EMT-related markers, and decreased survival.

Combined Hepatocellular Carcinoma and Neuroendocrine Carcinoma with Ectopic Secretion of Parathyroid Hormone: A Case Report and Review of the Literature

Primary combined hepatocellular carcinoma (HCC) and neuroendocrine carcinoma is a rare entity, and so is hypercalcemia due to ectopic parathyroid hormone (PTH) secretion by tumor. A 44-year-old man with hepatitis B virus associated chronic liver disease presented with a hepatic mass. Hemihepatectomy discovered the mass as combined HCC and poorly differentiated cholangiocarcinoma. During adjuvant chemoradiation therapy, he presented with nausea, and multiple systemic metastases were found. Laboratory tests revealed hypercalcemia with markedly elevated PTH and neuron specific enolase. Parathyroid scan showed normal uptake in parathyroid glands, suggestive of ectopic PTH secretion. Subsequently, immunohistochemistry of neuroendocrine marker was performed on the primary lesion, and confirmed the neuroendocrine differentiation in non-HCC component. The patient died 71 days after surgery. This report may suggest the possibility of ectopic PTH secretion by neuroendocrine carcinoma of hepatic origin causing hypercalcemia. Caution for neuroendocrine differentiation should be exercised when diagnosing poorly differentiated HCC.

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.

Donor Specific Antibody Negative Antibody-Mediated Rejection after ABO Incompatible Liver Transplantation / 대한이식학회지

Antibody-mediated rejection (AMR) is a major complication after ABO-incompatible liver transplantation. According to the 2016 Banff Working Group on Liver Allograft Criteria for the diagnosis of acute AMR, a positive serum donor specific antibody (DSA) is needed. On the other hand, the clinical significance of the histological findings of AMR in the absence of DSA is unclear. This paper describes a 57-year-old man (blood type, O+) who suffered from hepatitis B virus cirrhosis with hepatocellular carcinoma. Pre-operative DSA and cross-matching were negative. After transplantation, despite the improvement of the liver function, acute AMR was observed in the protocol biopsy on postoperative day 7; the cluster of differentiation 19+ (CD19+) count was 0% and anti-ABO antibody titers were 1:2. This paper presents the allograft injury like AMR in the absence of DSA after ABOi living donor liver transplantation with low titers of anti-ABO antibody and depleted serum CD19+ B cells.