Clinicopathologic characterization of cervical metastasis from an unknown primary tumor: a multicenter study in Korea

Background@#Research regarding cervical metastasis from an unknown primary tumor (CUP) according to human papillomavirus (HPV) and Epstein-Barr virus (EBV) status in Korea has been sporadic and small-scale. This study aims to analyze and understand the characteristics of CUP in Korea according to viral and p16 and p53 status through a multicenter study. @*Methods@#Ninety-five cases of CUP retrieved from six hospitals in Korea between January 2006 and December 2016 were subjected to high-risk HPV detection (DNA in situ hybridization [ISH] or real-time polymerase chain reaction), EBV detection (ISH), and immunohistochemistry for p16 and p53. @*Results@#CUP was HPV-related in 37 cases (38.9%), EBV-related in five cases (5.3%), and unrelated to HPV or EBV in 46 cases (48.4%). HPV-related CUP cases had the best overall survival (OS) (p = .004). According to the multivariate analysis, virus-unrelated disease (p = .023) and longer smoking duration (p < .005) were prognostic factors for poor OS. Cystic change (p = .016) and basaloid pattern (p < .001) were more frequent in HPV-related cases, and lymphoepithelial lesion was frequent in EBV-related cases (p = .010). There was no significant association between viral status and p53 positivity (p = .341), smoking status (p = .728), or smoking duration (p = .187). Korean data differ from Western data in the absence of an association among HPV, p53 positivity, and smoking history. @*Conclusions@#Virus-unrelated CUP in Korea had the highest frequency among all CUP cases. HPV-related CUP is similar to HPV-mediated oropharyngeal cancer and EBVrelated CUP is similar to nasopharyngeal cancer in terms of characteristics, respectively.

Comprehensive Analysis of Clinicopathologic Factors Predictive of an Unfavorable Prognosis in Patients With Acinic Cell Carcinoma of the Parotid Gland

Objectives@#. In subset of patients, acinic cell carcinoma (AcCC) exhibits aggressive features such as recurrence, distant metastasis, and mortality. This study aimed to investigate clinicopathologic factors influencing patients’ prognosis and to identify adverse features predictive of an unfavorable prognosis. @*Methods@#. Between January 2000 and December 2016, 59 patients with AcCC were enrolled in this study. @*Results@#. The patients’ 5-year overall survival rate was 93.3%, and their 5-year recurrence-free survival rate was 80.5%. During the study period, recurrence occurred in 10 patients. The mean time to recurrence after surgery was 26 months (range, 5–60 months). During the study period, three patients died from the disease. Univariate analysis showed that sex, surgical extent, extranodal extension, T classification, and TNM stage were significantly associated with disease recurrence. Multivariate analysis showed that, among the clinicopathologic factors included in the analysis, only TNM stage displayed a statistically significant correlation with disease recurrence. @*Conclusion@#. Surgical treatment alone yielded good results for AcCC, and additional treatment did not affect the recurrence-free survival rate or the overall survival rate, even when the resection margin was less than 1 mm. Other pathologic factors did not show prognostic significance for disease recurrence or death.

Descriptive Analysis of Histiocytic and Dendritic Cell Neoplasms: A Single-Institution Experience

Purpose@#Histiocytic and dendritic cell neoplasms are rare hematologic tumors.This study aimed to describe the epidemiologic features of the entire spectrum of histiocytic and dendritic cell neoplasms, including clinicopathological variables and patient outcomes. @*Materials and Methods@#We comprehensively reviewed 274 patients who were diagnosed with histiocytic and dendritic neoplasms at Severance Hospital, Seoul, South Korea between 1995 and 2018. @*Results@#The most common neoplasm was Langerhans cell histiocytosis (LCH), followed by dermal xanthogranuloma. Among non-LCH sarcomas, histiocytic sarcoma (HS) showed a relatively high prevalence, followed by follicular dendritic cell sarcoma (FDCS). Disseminated juvenile xanthogranuloma (DJG), Erdheim-Chester disease (ECD), indeterminate dendritic cell tumor (IDCT), and interdigitating dendritic cell sarcoma (IDCS) rarely occurred. Generally, these tumors presented in childhood, although the non-LCH sarcoma (HS/FDCS/IDCS/IDCT) group of tumors and ECD occurred in late adulthood. Multiorgan involvement and advanced Ann-Arbor stage, as well as recurrence and death of disease, were not uncommon. The non-LCH sarcoma group had the worst overall survival, compared to the DJG, ECD, and LCH groups. @*Conclusion@#Our findings indicate that histiocytic and dendritic cell neoplasms exhibit heterogeneous epidemiologic characteristics and that some patients may have unfavorable outcomes, especially those with non-LCH sarcoma.

Forkhead Box C1 (FOXC1) Expression in Stromal Cells within the Microenvironment of T and NK Cell Lymphomas: Association with Tumor Dormancy and Activation / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Forkhead box C1 (FOXC1) is critical for maintaining bone marrow microenvironments during hematopoiesis, but its role in hematological malignancies remains obscure. Here, we investigated whether FOXC1 regulates tumor dormancy and activation in the microenvironments of T and natural killer (NK) cell lymphomas. @*Materials and Methods@#One hundred and twenty cases of T and NK cell lymphomas were included; the immunohistochemical expression of FOXC1 was investigated in stromal cells, and numbers of FOXC1+ stromal cells were counted. Furthermore, the expression of phosphorylated p38 (p-p38) and phosphorylated ERK1/2 (p-ERK1/2) in tumor cells was investigated using immunohistochemistry. @*Results@#FOXC1 was variably expressed in C-X-C motif chemokine 12–associated reticular stromal cells, histiocytes, (myo)fibroblasts, and endothelial cells. The phenotypes of cases were categorized as dormant (high p-p38/low p-ERK1/2; n=30, 25.0%), active (high p-ERK1/2/low p-p38; n=25, 20.8%), or intermediate (others; n=65, 54.2%). Lower FOXC1+ stromal cell infiltration was associated with the dormant phenotype, the precursor T lymphoblastic leukemia/lymphoma subtype, and inferior overall survival rates, whereas higher FOXC1+ stromal cell infiltration was associated with the active phenotype and favorable patient prognosis (p < 0.05 for all). @*Conclusion@#These results suggested that FOXC1+ stromal cells within the microenvironments of T and NK cell lymphomas might be related to tumor phenotypes.

Analysis of PD-L1 expression in salivary duct carcinoma with its efficacy as a tumor marker / 대한두경부종양학회지

BACKGROUND/OBJECTIVES: Despite multiple approaches of treatments for salivary duct carcinoma, there has been a need for more successful treatment methods because of its poor prognosis. Treatment options like immunotherapy using new technologies have been attempted. Based on recent study results indicating that targeting programmed death receptors are effective in treating various cancers, this study aimed to identify the frequency of PD-L1 expression and its impact on survival rate in salivary duct carcinoma.MATERIALS #SPCHAR_X0026; METHODS: We studied 33 patients with salivary gland cancer who were available for histologic specimens. We examined the expression of PD-L1 in the tissues and analyzed the association with the survival rate and the association with various clinical parameters.RESULTS: According to this study and review of similar studies, we discovered that the expression of PD-L1 in salivary duct carcinoma was lower than other types of cancers. The impact of PD-L1 on survival rate also showed inconsistency in salivary duct carcinoma.CONCLUSION: Immunotherapy by PD-1/PD-L1 checkpoint blockade in salivary duct carcinoma needs further evaluation for clinical application.

Investigating Trk Protein Expression between Oropharyngeal and Non-oropharyngeal Squamous Cell Carcinoma: Clinical Implications and Possible Roles of Human Papillomavirus Infection / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The relationship between head and neck squamous cell carcinoma (HNSCC) and subtypes of tropomyosin-related kinase (Trk) has not been studied in-depth. In this study, we evaluated the expression patterns of TrkA, TrkB, and panTrk and their clinicopathological significance as well as association with p16 expression and human papilloma virus (HPV) status. MATERIALS AND METHODS: Total of 396 radically resected oropharyngeal (n=121) and non-oropharyngeal (n=275) HNSCCs were included. Immunohistochemistry for TrkA, TrkB, and panTrk was performed. In addition, p16 immunohistochemistry was performed to assess the HPV status. Using HPV-negative HNSCC cell lines, FaDu and CAL27, HPV type 16 E6/E7 gene was transfected, and then changes of TrkA and TrkB expression were analyzed. RESULTS: In the clinical samples of HNSCC, high expression of TrkA and panTrk were more associated with oropharyngeal and p16 positive squamous cell carcinoma (SCC). In patients with completely resected (R0-resected) oropharyngeal SCC, high TrkA expression was related to superior overall survival and recurrence-free survival (RFS). In patients with R0-resected oral cavity SCC, high panTrk was related to poor RFS. In HPV type E6/E7 gene-transfected FaDu and CAL27 cell lines, increase of TrkA expression was observed. CONCLUSION: It seems that expression pattern of panTrk and TrkA differed according to anatomical sites of HNSCC and was closely related to p16 expression and patient prognosis. Trk expression should be considered in the context of anatomical site, p16 expression or HPV status and Trk subtypes.

Molecular Testing of Lymphoproliferative Disorders: Current Status and Perspectives

Molecular pathologic testing plays an important role for the diagnosis, prognostication and decision of treatment strategy in lymphoproliferative disease. Here, we briefly review the molecular tests currently used for lymphoproliferative disease and those which will be implicated in clinical practice in the near future. Specifically, this guideline addresses the clonality test for B- and T-cell proliferative lesions, molecular cytogenetic tests for malignant lymphoma, determination of cell-of-origin in diffuse large B-cell lymphoma, and molecular genetic alterations incorporated in the 2016 revision of the World Health Organization classification of lymphoid neoplasms. Finally, a new perspective on the next-generation sequencing for diagnostic, prognostic, and therapeutic purpose in malignant lymphoma will be summarized.

Clinical Utility of Bone Marrow Study in Gaucher Disease: A Case Report of Gaucher Disease Type 3 With Intractable Myoclonic Seizures

No abstract available.

Long Non-coding RNA HOTAIR Expression in Diffuse Large B-Cell Lymphoma: In Relation to Polycomb Repressive Complex Pathway Proteins and H3K27 Trimethylation

BACKGROUND: A long non-coding RNA hox transcript antisense intergenic RNA (HOTAIR) is involved in epigenetic regulation through chromatin remodeling by recruiting polycomb repressive complex 2 (PRC2) proteins (EZH2, SUZ12, and EED) that induce histone H3 trimethylation at lysine 27 (H3K27me3). Deregulation of c-MYC and interaction between c-MYC and EZH2 are well known in lymphomagenesis; however, little is known about the expression status of HOTAIR in diffuse large B-cell lymphomas (DLBCLs). METHODS: The expression status of PRC2 (EZH2, SUZ12, and EED), H3K27me3, c-MYC, and BCL2 was analyzed using immunohistochemistry (n = 231), and HOTAIR was investigated by a quantification real-time polymerase chain reaction method (n = 164) in DLBCLs. RESULTS: The present study confirmed the positive correlation among PRC2 proteins, H3K27me3, and c-MYC in DLBCLs. Expression level of HOTAIR was also positively correlated to EZH2 (p < .05, respectively). Between c-MYC and HOTAIR, and between c- MYC/BCL2 co-expression and HOTAIR, however, negative correlation was observed in DLBCLs (p < .05, respectively). High level of H3K27me3 was determined as an independent prognostic marker in poor overall survival (hazard ratio, 2.0; p = .023) of DLBCL patients. High expression of HOTAIR, however, was associated with favorable overall survival (p = .004) in the univariate analysis, but the impact was not significant in the multivariate analysis. The favorable outcome of DLBCL with HOTAIR high expression levels may be related to the negative correlation with c- MYC expression or c-MYC/BCL2 co-expression. CONCLUSIONS: HOTAIR expression could be one of possible mechanisms for inducing H3K27me3 via EZH2-related PRC2 activation, and induced H3K27me3 may be strongly related to aggressive DLBCLs which show poor patient outcome.

Overexpression of Endoplasmic Reticulum Oxidoreductin 1-α (ERO1L) Is Associated with Poor Prognosis of Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Gastric cancer is the second leading cause of cancer-related death worldwide. Although surgery is the standard curative treatment for gastric cancer, relapse occurs in a large number of patients, except in the case of early diagnosed gastric cancer. Following previous studies that identified endoplasmic reticulum oxidoreductin 1-α (ERO1L) as a potential marker for gastric cancer, we investigated the functional role of ERO1L in gastric cancer. MATERIALS AND METHODS: For validation of microarray data, the mRNA expression level of ERO1L was measured by quantitative real-time reverse transcription polymerase chain reaction in 56 independent stage III gastric cancer patients. Immunohistochemical staining was performed to examine the protein expression level of ERO1L in 231 gastric cancer patients. Correlation between gene expression and cancer prognosis was evaluated. RESULTS: Patients with high ERO1L expression had poorer survival than those with low expression (p < 0.01). Functional assays demonstrated that ERO1L knockdown inhibited cell proliferation, migration, invasion, and chemoresistance. In addition, involvement of inactivation of Akt and JNK signaling in molecular mechanisms of ERO1L inhibition was demonstrated. CONCLUSION: High expression of ERO1L is associated with poor prognosis of patients with gastric cancer. These results indicate that ERO1L expression may be a clinically promising therapeutic target for prevention of gastric cancer.

Upregulated Neuro-oncological Ventral Antigen 1 (NOVA1) Expression Is Specific to Mature and Immature T- and NK-Cell Lymphomas

BACKGROUND: Recent studies have revealed that the splicing factor neuro-oncological ventral antigen 1 (NOVA1) is enriched in fibroblasts and accumulated T cells of tertiary lymphoid structures. In the present study, we investigated NOVA1 expression in various subtypes of mature and immature T- and natural killer (NK)-cell lymphomas as well as in various B-cell lymphoma subtypes. METHODS: NOVA1 immunoexpression was evaluated in hyperplastic palatine tonsils (n = 20), T- and NK-cell lymphomas (n = 177), diffuse large B-cell lymphomas (n = 151), and other types of B cell lymphomas (n = 31). Nuclear staining intensity and percentage of positive tumor cells were graded. NOVA1 mRNA expression was analyzed in various lymphoma cell lines. RESULTS: Tumor cells of T- and NK-cell lymphomas showed higher expression levels of NOVA1 than did normal paracortical T cells, and 56.5% of T- and NK-cell lymphoma cases showed diffuse and strong expression. The NOVA1 expression level varied according to the subtype; it was higher in angioimmunoblastic T-cell lymphoma, anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL), and T lymphoblastic leukemia/lymphoma (T-LBL), but it was lower in ALK-positive ALCL. In almost all B-cell lymphomas, NOVA1 expression was very low or negative. NOVA1 mRNA was also expressed in Jurkat, a T-LBL cell line. CONCLUSIONS: The present findings suggest that NOVA1 upregulation may be involved in certain subtypes of T- and NK-cell lymphomas, but not in B-cell lymphomas. Upregulated NOVA1 expression seems to be a specific biological feature of activated T cells such as T- and NK-cell lymphomas.

Prognostic Significance of Defining L-Cell Type on the Biologic Behavior of Rectal Neuroendocrine Tumors in Relation with Pathological Parameters / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: In 2010, the World Health Organization categorized L-cell type neuroendocrine tumors (NETs) as tumors of uncertain malignancy, while all others were classified as malignant. However, the diagnostic necessity of L-cell immunophenotyping is unclear, as are tumor stage and grade that may guide diagnosis and management. To clarify the predictive markers of rectal neuroendocrine neoplasms (NENs), 5- and 10-year overall survival (OS) was analyzed by pathological parameters including L-cell phenotype. MATERIALS AND METHODS: A total of 2,385 rectal NENs were analyzed from our previous multicenter study and a subset of 170 rectal NENs was immunophenotyped. RESULTS: In univariate survival analysis, tumor grade (p 10, is useful in defining L-Cell type. In this study, an L-cell immunophenotype was found in 83.5% of all rectal NENs and most, but not all L-cell type tumors were NET G1, small (< 10 mm) and confined to the mucosa/submucosa. CONCLUSION: From these results, the biological behavior of rectal NENs does not appear to be determined by L-cell type alone but instead by a combination of pathological parameters.

Proposal of an Appropriate Decalcification Method of Bone Marrow Biopsy Specimens in the Era of Expanding Genetic Molecular Study

BACKGROUND: The conventional method for decalcification of bone specimens uses hydrochloric acid (HCl) and is notorious for damaging cellular RNA, DNA, and proteins, thus complicating molecular and immunohistochemical analyses. A method that can effectively decalcify while preserving genetic material is necessary. METHODS: Pairs of bilateral bone marrow biopsies sampled from 53 patients were decalcified according to protocols of two comparison groups: EDTA versus HCl and RDO GOLD (RDO) versus HCl. Pairs of right and left bone marrow biopsy samples harvested from 28 cases were allocated into the EDTA versus HCl comparison group, and 25 cases to the RDO versus HCl comparison group. The decalcification protocols were compared with regards to histomorphology, immunohistochemistry, and molecular analysis. For molecular analysis, we randomly selected 5 cases from the EDTA versus HCl and RDO versus HCl groups. RESULTS: The decalcification time for appropriate histomorphologic analysis was the longest in the EDTA method and the shortest in the RDO method. EDTA was superior to RDO or HCl in DNA yield and integrity, assessed via DNA extraction, polymerase chain reaction, and silver in situ hybridization using DNA probes. The EDTA method maintained intact nuclear protein staining on immunohistochemistry, while the HCl method produced poor quality images. Staining after the RDO method had equivocal results. RNA in situ hybridization using kappa and lambda RNA probes measured RNA integrity; the EDTA and RDO method had the best quality, followed by HCl. CONCLUSIONS: The EDTA protocol would be the best in preserving genetic material. RDO may be an acceptable alternative when rapid decalcification is necessary.

Usefulness of Nuclear Protein in Testis (NUT) Immunohistochemistry in the Cytodiagnosis of NUT Midline Carcinoma: A Brief Case Report

No abstract available.

The Limitations of Endoscopic Ultrasound-Guided Fine Needle Aspiration Cytology in the Diagnosis of Pancreatic Serous Cystadenoma: A Brief Case Report

No abstract available.

An Extragastrointestinal Stromal Tumor in the Omentum With Peritoneal Seeding Mimicking an Appendiceal Mucinous Cancer With Carcinomatosis

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. These tumors tend to present most frequently in the stomach, followed by the small intestine. GISTs can also arise from the omentum, retroperitoneum, mesentery, or pleura and are termed extragastrointestinal stromal tumors (EGISTs) when they do so. EGISTs arising from the omentum are very rare. Due to the limited incidence of EGISTs in the omentum, the diagnostic criteria are not well established, and making a correct diagnosis may be difficult. In this report, we present a case of an EGIST of the omentum with peritoneal metastasis that was initially suspected to be an appendiceal mucinous carcinoma with carcinomatosis on positron emission tomography/computed tomography imaging.

Incidence and Malignancy Rates of Diagnoses in the Bethesda System for Reporting Thyroid Aspiration Cytology: An Institutional Experience

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) uses six diagnostic categories to standardize communication of thyroid fine-needle aspiration (FNA) interpretations between clinicians and cytopathologists. Since several studies have questioned the diagnostic accuracy of this system, we examined its accuracy in our hospital. METHODS: We calculated the incidences and malignancy rates of each diagnostic category in the BSRTC for 1,730 FNAs that were interpreted by four cytopathologists in Gangnam Severance Hospital between October 1, 2011, and December 31, 2011. RESULTS: The diagnostic incidences of categories I-VI were as follows: 13.3%, 40.6%, 9.1%, 0.4%, 19.3%, and 17.3%, respectively. Similarly, the malignancy rates of these categories were as follows: 35.3%, 5.6%, 69.0%, 50.0%, 98.7%, and 98.9%, respectively. In categories II, V, and VI, there were no statistically significant differences in the ranges of the malignancy rates among the four cytopathologists. However, there were significant differences in the ranges for categories I and III. CONCLUSIONS: Our findings suggest that institutions that use the BSRTC should regularly update their diagnostic criteria. We also propose that institutions issue an annual report of incidences and malignancy rates to help other clinicians improve the case management of patients with thyroid nodules.

A Case of Double Primary Neuroendocrine Tumor from Duodenum and Pancreas / 대한소화기학회지

Gastrointestinal neuroendocrine tumors arise from cells of the diffuse neuroendocrine system and can take place almost anywhere within the gastrointestinal tract. A 40-year-old man admitted to evaluate a duodenal subepithelial lesion which was incidentally found at health check-up. The polypoid duodenal subepithelial lesion, measuring about 7 mm, was removed by the endoscopic mucosal resection and the pathology confirmed a neuroendocrine tumor. Abdominopelvic computed tomography, done for staging work up, revealed a mass in the pancreatic head and the patient received pylorus preserving pancreaticoduodenectomy. Mass at the pancreas also found out to be neuroendocrine tumor but showed different histopathologic traits under immunohistochemical staining. The patient was also diagnosed as hyperparathyroidism and pituitary microadenoma. Finally, multiple endocrine neoplasia type 1 was confirmed, which was accompanied by duodenal neuroendocrine tumor.

A Case of Double Primary Neuroendocrine Tumor from Duodenum and Pancreas / 대한소화기학회지

Gastrointestinal neuroendocrine tumors arise from cells of the diffuse neuroendocrine system and can take place almost anywhere within the gastrointestinal tract. A 40-year-old man admitted to evaluate a duodenal subepithelial lesion which was incidentally found at health check-up. The polypoid duodenal subepithelial lesion, measuring about 7 mm, was removed by the endoscopic mucosal resection and the pathology confirmed a neuroendocrine tumor. Abdominopelvic computed tomography, done for staging work up, revealed a mass in the pancreatic head and the patient received pylorus preserving pancreaticoduodenectomy. Mass at the pancreas also found out to be neuroendocrine tumor but showed different histopathologic traits under immunohistochemical staining. The patient was also diagnosed as hyperparathyroidism and pituitary microadenoma. Finally, multiple endocrine neoplasia type 1 was confirmed, which was accompanied by duodenal neuroendocrine tumor.

Cytologic Features of Giant Cell Ependymoma: A Case Report and Review of the Literature

Here, we present a case of anaplastic giant cell ependymoma (GCE) occurring in a 15-year-old woman. Squash smear slides for intraoperative frozen section diagnosis revealed oval to round cell clusters with a papillary structure in a fibrillary background. This was occasionally accompanied by the presence of bizarre pleomorphic giant cells with hyperchromatic nuclei and prominent intranuclear inclusions. These intranuclear inclusions were a key clue to diagnosis of ependymoma. Histologic analysis revealed features of a high-grade tumor with perivascular pseudorosettes and bizarre pleomorphic giant cells, which established the diagnosis of GCE. We performed a review of literatures about the cytologic features of GCE, including our case, thus proposing that intraoperative frozen diagnosis of GCE would be established by squash smear preparations featuring the mitosis and necrosis, as well as the high cellularity, and the presence of giant cells showing hyperchromatic nuclei with eosinophilic cytoplasm and intranuclear inclusions/pseudoinclusions.