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.

Colonic Perforation After Treatment With Nivolumab in Esophageal Cancer: A Case Report

With the advent of checkpoint inhibitors, it has opened up opportunities for numerous cancer patients. However, as is the case with every treatment, complications need to be weighed. Gastrointestinal adverse effects, such as diarrhea and colitis are well-known complications for checkpoint inhibitors. In severe cases, colitis-induced colonic perforation may occur with an estimation of 1.0% to 1.5% in anti-CTLA-4 antibodies. However, only a handful of cases of such devastating complications have been reported in anti-PD-1 antibodies such as pembrolizumab and nivolumab. We here report a case of intestinal perforation in a patient treated with nivolumab.

Colonic Perforation After Treatment With Nivolumab in Esophageal Cancer: A Case Report

With the advent of checkpoint inhibitors, it has opened up opportunities for numerous cancer patients. However, as is the case with every treatment, complications need to be weighed. Gastrointestinal adverse effects, such as diarrhea and colitis are well-known complications for checkpoint inhibitors. In severe cases, colitis-induced colonic perforation may occur with an estimation of 1.0% to 1.5% in anti-CTLA-4 antibodies. However, only a handful of cases of such devastating complications have been reported in anti-PD-1 antibodies such as pembrolizumab and nivolumab. We here report a case of intestinal perforation in a patient treated with nivolumab.

Clinical Impact of Somatic Variants in Homologous RecombinationRepair-Related Genes in Ovarian High-Grade Serous Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#In this study, we investigated the frequencies of mutations in DNA damage repair genesincluding BRCA1, BRCA2, homologous recombination genes and TP53 gene in ovarian highgradeserous carcinoma, alongside those of germline and somatic BRCA mutations, withthe aim of improving the identification of patients suitable for treatment with poly(ADPribose)polymerase inhibitors. @*Materials and Methods@#Tissue samples from 77 Korean patients with ovarian high-grade serous carcinoma weresubjected to next-generation sequencing. Pathogenic alterations of 38 DNA damage repairgenes and TP53 gene and their relationships with patient survival were examined. Additionally,we analyzed BRCA germline variants in blood samples from 47 of the patients forcomparison. @*Results@#BRCA1, BRCA2, and TP53 mutations were detected in 28.6%, 5.2%, and 80.5% of the 77patients, respectively. Alterations in RAD50, ATR, MSH6, MSH2, and FANCA were also identified.At least one mutation in a DNA damage repair gene was detected in 40.3% of patients(31/77). Germline and somatic BRCA mutations were found in 20 of 47 patients (42.6%),and four patients had only somatic mutations without germline mutations (8.5%, 4/47).Patients with DNA damage repair gene alterations with or without TP53mutation, exhibitedbetter disease-free survival than those with TP53 mutation alone. @*Conclusion@#DNA damage repair genes were mutated in 40.3% of patients with high-grade serous carcinoma,with somatic BRCAmutations in the absence of germline mutation in 8.5%. Somaticvariant examination, along with germline testing of DNA damage repair genes, has potentialto detect additional candidates for PARP inhibitor treatment.

Intrahepatic Cholangiocarcinoma with Ductal Plate Malformation-like Feature Associated with Bile Duct Adenoma

No abstract available.

Desmoid Type Fibromatosis in the Facet Joint of Lumbar Spine: Case Report and Review of Literature

Desmoid type fibromatosis is a benign fibroblastic tumor arising from the fascia or musculoaponeurosis. It may occur in various locations, but most commonly in the shoulder girdle and neck; to our knowledge, there has been no reported case originating from a facet joint of the spine. We report CT and MR imaging findings of a desmoid type fibromatosis, involving the facet joint of the L3-4 spine with bone involvement.

A Case of Ovarian Microinvasive Mucinous Carcinoma and Co-existent Angiosarcoma

Primary ovarian angiosarcoma is very rare with only 27 cases reported so far in the medical literature. We report here on a rare case of ovarian microinvasive mucinous carcinoma that was coexistent with angiosarcoma in a 54-year-old woman. The tumor was a 26x19x10 cm-sized multilocular cystic mass with a 4x3 cm-sized solid hematoma-like nodule in the center. Microscopically, it was composed mostly of mucinous tumor of various grades from borderline to microinvasive carcinoma. The hematoma-like area turned out to be an angiosarcoma, composed of pleomorphic cells that formed slit-like spaces, spindle cells that formed short fascicles and anastomosing vascular channels with atypical endothelial cells. All these cells were positive for CD31, CD34 and factor VIII-related antigen. The patient developed peritoneal and pleural metastases, which were angiosarcoma and mucinous carcinoma, respectively. We believe this case is only the fourth example of an ovarian collision tumor of angiosarcoma and surface epithelial tumor.

The Loss of E-cadherin is Associated with the Epigenetic Alteration of CDH1 in Breast Cancer and it is also Associated with an Abnormal beta-catenin Expression in Lobular Carcinoma

BACKGROUND: APC and E-cadherin are the key molecules in the Wnt/beta-catenin pathway. We attempted to define the epigenetic alteration of APC and CDH1 (the E-cadherin gene) and the expression of Wnt-related molecules in human mammary carcinomas. METHODS: Sixty-four mammary carcinomas, including 52 invasive ductal carcinomas (IDCs) and 12 invasive lobular carcinomas (ILCs), were evaluated using methylation-specific PCR and immunohistochemistry. We performed immunohistochemistry for E-cadherin, beta-catenin, APC, Wnt1, cyclin D1, ER, PR and C-erb B2. RESULTS: Hypermethylation of APC and CDH1 was observed in 38 (59%) and 28 (44%) cases, respectively. CDH1 hypermethylation in ILCs was increased compared to that in IDCs (p=0.002) and it was associated with the loss of E-cadherin (p=0.02) and beta-catenin (p=0.042). APC methylation was positively correlated with the ER expression (p=0.021). Abnormal cytoplasmic localization of beta-catenin was found in 10 cases and any expression was not detected in six cases. In ILCs, the E-cadherin or beta-catenin expression was markedly decreased compared to that in IDCs (p<0.001 in both). CONCLUSIONS: Methylation of APC or CDH1 was relatively frequent in mammary carcinomas. The loss of E-cadherin in mammary carcinoma was associated with CDH1 methylation, and abnormal beta-catenin expression was related to the loss of E-cadherin in ILC.

Gender-specific Association between Polymorphism of Vascular Endothelial Growth Factor (VEGF 936C>T) Gene and Patients with Stomach Cancer

PURPOSE: Angiogenesis plays an important role in the growth, progression, and metastasis of tumors. Vascular endothelial growth factor (VEGF) overexpression has been associated with advanced stage and poor survival in several cancers. We investigated the present case-control study to determine whether there is an association between the VEGF 936C>T polymorphism and stomach cancer. PATIENTS AND METHODS: The association of functional single nucleotide polymorphisms (SNPs) of the VEGF gene with stomach cancer development was evaluated in a case-control study of 154 Korean stomach cancer patients. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: Our results revealed significant association of T allele-bearing genotypes with increased risk for stomach cancer development. Genotype frequencies of the VEGF 936C>T polymorphisms were significantly different between patient and control groups (CT, AOR: 2.007, 95% CI: 1.277-3.156, TT, AOR: 4.790, 95% CI: 1.174-19.539, CT+TT, AOR: 2.147, 95% CI: 1.382-3.337). When stratified by gender and age, genotype frequencies were significantly different for stomach cancer in women and in patients younger than 55 years (in women, CT, OR: 3.049, 95% CI: 1.568-5.930, CT+TT, OR: 3.132, 95% CI: 1.638-5.990; in T polymorphism is a susceptibility factor for stomach cancer, at least in Korean. These observations, however, require further confirmation by a larger multi-ethnic study.

The Safety and Efficiency of the Ultrasound-guided Large Needle Core Biopsy of Axilla Lymph Nodes

PURPOSE: To evaluate the safety and efficiency of the Ultrasound (US)-guided large needle core biopsy of axilla lymph nodes. MATERIALS AND METHODS: From March 2004 to September 2005, 31 patients underwent the US-guided core biopsy for axilla lymph nodes. Twenty five lesions out of 31 were detected during breast US, and 6 of 31 cases were palpable. Lymph nodes were classified based on their shape and cortical morphology. The core biopsy of axilla lymph nodes was performed on suspicious lymph nodes found during breast ultrasonography to find out whether the patients had a history of breast cancer or not. Among the 31 patients, 16 patients were associated with breast cancer. The lesion sizes varied from 0.6cm to 3.3cm (mean = 1.59 +/- 0.76cm). US-guided core biopsies were performed with 14G needles with an automated biopsy gun. Total 3 or 5 specimens were obtained. RESULTS: Among the 31 cases of axilla lymph nodes core biopsies, 11 cases showed malignant pathology. Seven out of 11 cases were metastatic lymph nodes from breast cancer; 2 cases were from primary unknown and 2 cases from lymphomas. On the other hand, 20 histopathologic results of axilla lesions were benign: subacute necrotizing lymphadenitis (n=2), dermatopathic lymphadenitis (n=1), reactive hyperplasia (n=10) and free of carcinoma (n=7). CONCLUSION: The US-guided large needle core biopsy of axilla lesions is safe and effective for the pathological evaluation. The core biopsy is believed to be easy to perform if suspicious lymph nodes or mass lesions are found in the axilla.

The Usefulness of Angiotensin Converting Enzyme in the Differential Diagnosis of Crohn's Disease and Intestinal Tuberculosis

BACKGROUND: Since the pathologic findings of Crohn's disease (CD) and intestinal tuberculosis (IT) overlap to a large degree, the development of other biomarkers will be of great help for making the differential diagnosis of these 2 diseases. The aim of the present study is to examine the clinical efficacy of using the tissue angiotensin converting enzyme (ACE) assay in making the differential diagnosis between CD and IT. METHODS: Tissue specimens were obtained from 36 patients who were diagnosed with CD or IT by the colonoscopic biopsy, as well as by the clinical findings. The expression of tissue ACE was detected by immunohistochemical staining. The optimal cut-off value of the immunoreactive scoring (IRS) system we used to differentiate CD from IT was determined by analysis of the ROC curve and AUROC. RESULTS: Granuloma was present in 15 of 19 patients with CD (78.9%) and in 15 of 17 patients with IT (88.2%). ACE was present in the cytoplasm of the epithelioid cells in the granulomas from 13 of 15 patients with CD and in 14 of 15 patients with IT. The IRS scores of ACE were greater in the patients with CD than that of the patients with IT (8.07+/-4.38 vs. 4.13+/-2.47, respectively, p=0.006). In differentiating CD from IT, the AUROC curve for the IRS of ACE was 0.767 with a sensitivity of 66.7%, a specificity of 93.3% and the cut-off point was 7.5. CONCLUSIONS: The results of our study suggest that the assessment of the tissue ACE expression can be helpful for making the differential diagnosis between CD and IT.

A Case of Combined Hepatocellular-Cholangiocarcinoma with Sarcomatous Transformation and Second Primary Colon Cancer / 대한간학회지

Combined hepatocellular-cholangiocarcinoma is a rare form of primary liver cancer, featuring both hepatocellular and biliary epithelial differentiations. An intrahepatic tumor may be considered as a metastatic lesion. It has been suggested in the literature that the likelihood of metastasis in the cirrhotic liver is lower than that in the non-cirrhotic liver. A rare case of combined hepatocellular-cholangiocarcinoma and second primary colon adenocarcinoma in a 67-year-old male patient with liver cirrhosis is presented. Histologically, the intrahepatic mass was composed of a spindle cell sarcomatous component; a hepatocellular carcinoma component; and a cholangiocarcinoma component. There were focal transitional regions among the different components. Immunohistochemically, the cholangiocarcinoma component of the intrahepatic mass showed positive reactions for CK-7 but negative reactions for CK-20. The adenocarcinoma of the colon showed positive reactions for CK-20 but negative reactions for CK-7.

A Case of Cytomegalovirus Gastric Ulcer Mimicking Gastric Cancer in an Immunocompetent Host / 대한소화기내시경학회지

A 27-year-old woman presented with epigastric pain. Abdominal computed tomography revealed an irregular ulcer with circumferential thickening of the gastric antral wall. An endoscopy suggested advanced gastric cancer or gastric lymphoma. Biopsy of the lesion showed an inclusion body of the cytomegalovirus and positive immunohistochemical staining of the infected cell for cytomegalovirus. A thorough evaluation of her immune system revealed no abnormality. General supportive treatment for gastric ulcer did not relieve her symptoms. Intravenous infusion of ganciclovir improved her symptoms and healed the ulcer. We report a case of cytomegalovirus-associated gastric ulcer mimicking malignancy in an immunocompetent woman.

A Case of Hypersensitivity Myocarditis

Hypersensitivity myocarditis may result from an allergic reaction to a variety of agents such as antibiotics, anticonvulsants and diuretics. A diagnosis of hypersensitivity myocarditis should be considered in any patient with an ongoing allergic reaction to a drug, evidence of peripheral eosinophilia, an appearance of new electrocardiographic changes, mildly elevated cardiac enzyme, mild cardiomegaly on chest X-ray or unexplained tachycardia. This condition is rarely recognized clinically although it is occasionally diagnosed on endomyocardial biopsy. We report a 25 year-old woman with hypersensitivity myocarditis, which was diagnosed by endomyo-cardial biopsy and successfully treated by immunosuppression therapy with corticosteroids.

A case of double primary cancer of hepatocellular carcinoma and mucoepidermoid carcinoma in the liver / 대한내과학회지

Mucoepidermoid carcinoma is a common malignant tumor of the salivary glands, but rare in other sites. Only 10 cases of mucoepidermoid carcinoma of liver have been reported, and there was 1 case of double primary cancer of hepatocellular carcinoma and mucoepidermoid carcinoma. The definite diagnosis and pathogenesis are still controversial. However, hepatocellular carcinoma is the second most common cancer in Korea. Its etiology is better known compared to mucoepidermoid carcinoma. We report a rare case of double primary cancer of mucoepidermoid carcinoma and hepatocellular carcinoma in liver.

beta-Catenin Expression in Gastric Carcinogenesis

BACKGROUND: The molecular pathogenesis of gastric carcinoma is not yet well characterized. The purpose of this study is to assess the role of beta-catenin in gastric carcinogenesis. METHODS: We analyzed beta-catenin expression using immunohistochemistry on 68 gastric adenomas and 34 gastric adenocarcinomas, and compared the result with pathological and molecular types of tumors and E-cadherin expression. RESULTS: Nuclear expression of beta-catenin was noted more frequently in gastric adenomas than in carcinomas (40% vs. 21%, 0.05< or = P<1). There was no significant relationship between nuclear beta-catenin expression and histologic degree of adenoma, histologic type of carcinoma or microsatellite instability. E-cadherin expression showed significantly more frequent decrease in the membrane stainability of carcinomas compared to adenomas (P<0.01). CONCLUSIONS: The frequent nuclear beta-catenin expression in gastric adenomas suggests that the beta-catenin alteration might play an early role in gastric carcinogenesis.