Journal of Pathology and Translational Medicine

Original Article

Long Non-coding RNA HOTAIR Expression in Diffuse Large B-Cell Lymphoma: In Relation to Polycomb Repressive Complex Pathway Proteins and H3K27 Trimethylation: Eun Ji Oh, Soo Hee Kim, Woo Ick Yang, Young Hyeh Ko, Sun Och Yoon; J Pathol Transl Med. 2016;50(5):369-376. Published online August 22, 2016; DOI: https://doi.org/10.4132/jptm.2016.06.06

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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.

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Brief Case Report

Peritoneal Carcinosarcoma and Ovarian Papillary Serous Carcinoma Are the Same Origin: Analysis of TP53 Mutation and Microsatellite Suggests a Monoclonal Origin: Chang Gok Woo, Dae Shik Suh, Joo Young Kim, Chang Ohk Sung, Jene Choi, Kyu-Rae Kim; Korean J Pathol. 2014;48(6):449-453. Published online December 31, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.6.449

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Original Articles

P2X₇ Receptor Expression in Coexistence of Papillary Thyroid Carcinoma with Hashimoto's Thyroiditis: Ji Hyun Kwon, Eun Sook Nam, Hyung Sik Shin, Seong Jin Cho, Hye Rim Park, Mi Jung Kwon; Korean J Pathol. 2014;48(1):30-35. Published online February 25, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.1.30

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Abstract PDF

Background

This study was aimed at investigating the relation of P2X₇ receptor (P2X₇R) expression with the clinicopathological features of papillary thyroid carcinoma (PTC) coexisting with Hashimoto's thyroiditis (HT).

Methods

We examined 170 patients (84, PTC with HT; 86, PTC without HT). P2X₇R expression was examined by immunohistochemical methods. The staining intensity and patterns were evaluated and scored using a semi-quantitative method.

Results

The PTC with HT group was more likely to contain women and had less extrathyroid extension, lymph node (LN) metastasis, lymphovascular invasion, and recurrence than the PTC without HT group. Patients positive for P2X₇R had significantly higher frequencies of lymphovascular invasion, extrathyroid extension, LN metastasis, and absence of HT. As shown by multivariate analysis, the expression of P2X₇R was significantly higher if HT was absent and extrathyroid extension was present. In the PTC with HT group, the expression of P2X₇R was significantly higher in patients with tumor multifocality, lymphovascular invasion, and extrathyroid extension. In the PTC without HT group, the expression of P2X₇R was significantly higher in women and those having tumor multifocality.

Conclusions

Coexistence of PTC with HT is associated with good prognostic factors, and P2X₇R expression in PTC was correlated with poor prognostic factors and the absence of HT.

Citations

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ERG Immunohistochemistry as an Endothelial Marker for Assessing Lymphovascular Invasion: Sehun Kim, Hyung Kyu Park, Ho Young Jung, So-Young Lee, Kyueng-Whan Min, Wook Youn Kim, Hye Seung Han, Wan Seop Kim, Tae Sook Hwang, So Dug Lim; Korean J Pathol. 2013;47(4):355-364. Published online August 26, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.4.355

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Abstract PDF

Background

ERG, a member of the ETS family of transcription factors, is a highly specific endothelial marker. We investigated whether the use of ERG immunostaining can help pathologists detect lymphovascular invasion (LVI) and decrease interobserver variability in LVI diagnosis.

Methods

Fifteen cases of surgically resected colorectal cancers with hepatic metastasis were selected and the most representative sections for LVI detection were immunostained with ERG, CD31, and D2-40. Eight pathologists independently evaluated LVI status on hematoxylin and eosin (H&E) and the corresponding immunostained sections and then convened for a consensus meeting. The results were analyzed by kappa (κ) statistics.

Results

The average rate of LVI positivity was observed in 43% with H&E only, 10% with CD31, 29% with D2-40, and 16% with ERG. Agreement among pathologists was fair for H&E only (κ=0.27), D2-40 (κ=0.21), ERG (κ=0.23), and was moderate for CD31 (κ=0.55). Consensus revealed that ERG nuclear immunoreactivity showed better visual contrast of LVI detection than the other staining, with improved agreement and LVI detection rate (κ=0.65, LVI positivity rate 80%).

Conclusions

The present study demonstrated a superiority with ERG immunostaining and indicated that ERG is a promising panendothelial marker that might help pathologists increase LVI detection and decrease interobserver variability in LVI diagnosis.

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P2X7Receptor Expression in Coexistence of Papillary Thyroid Carcinoma with Hashimoto's Thyroiditis
Ji Hyun Kwon, Eun Sook Nam, Hyung Sik Shin, Seong Jin Cho, Hye Rim Park, Mi Jung Kwon
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ERG Immunohistochemistry and Clinicopathologic Characteristics in Korean Prostate Adenocarcinoma Patients: Ja Hee Suh, Jeong-Whan Park, Cheol Lee, Kyung Chul Moon; Korean J Pathol. 2012;46(5):423-428. Published online October 25, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.5.423

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Abstract PDF

Background

Transmembrane protease serine 2-ETS related gene (TMPRSS2-ERG) gene fusion, the most common genetic alternation in prostate cancer, is associated with protein expression of the oncogene ERG. Recently, an immunohistochemical staining method using an anti-ERG antibody was shown to have a strong correlation with altered ERG protein expression.

Methods

We analyzed a total of 303 radical prostatectomy specimens (obtained from Korean prostate cancer cases) using a constructed tissue microarray and ERG immunohistochemical staining. Thereafter, we evaluated the association between ERG expression and clinicopathological factors.

Results

The ERG-positive rate was 24.4% (74/303) and significantly higher ERG expression was observed in the subgroup with a lower Gleason score (p=0.004). Analysis of the histologic pattern of prostate adenocarcinomas revealed that tumors with discrete glandular units (Gleason pattern 3) displayed higher frequency of ERG expression (p=0.016). The ERG-positive rate was lower than that found (approximately 50%) in studies involving western populations. Other factors including age, tumor volume, initial protein-specific antigen level, a pathological stage and margin status were not significantly related with the ERG expression.

Conclusions

ERG immunohistochemical staining is significantly higher in tumors with well-formed glands and is associated with a lower Gleason score.

Citations

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The relevance of ERG immunoexpression intensity for prostatic adenocarcinoma in radical prostatectomy of 635 samples
Priscilla Mariana Freitas Aguiar Feitosa, Carlos Gustavo Hirth, Isabelle Joyce De Lima Silva‐Fernandes, Conceição Aparecida Dornelas
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Anan Fathi, Naglaa A. Mostafa, Nabila Hefzi, Khaled A. Mansour
Egyptian Journal of Pathology.2018; 38(1): 162. CrossRef
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Se Un Jeong, Anuja Kashikar Kekatpure, Ja-Min Park, Minkyu Han, Hee Sang Hwang, Hui Jeong Jeong, Heounjeong Go, Yong Mee Cho
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Ji-Youn Sung, Hwang Gyun Jeon, Byong Chang Jeong, Seong Il Seo, Seong Soo Jeon, Hyun Moo Lee, Han Yong Choi, So Young Kang, Yoon-La Choi, Ghee Young Kwon
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Prostate Cancer Prognosis Defined by the Combined Analysis of 8q, PTEN and ERG
Maria P. Silva, João D. Barros-Silva, Elin Ersvær, Wanja Kildal, Tarjei Sveinsgjerd Hveem, Manohar Pradhan, Joana Vieira, Manuel R. Teixeira, Håvard E. Danielsen
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Cytologic findings of Hodgkin's disease with special emphasis on Reed-Sternberg cells and their variants.: Young Hyeh Ko, Chan Pil Park, Jung Dal Lee; Korean J Cytopathol. 1991;2(1):1-7.

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Abstract PDF: Cytologic findings from five cases with variable types of Hodgkin' disease were reviewed with special emphasis on the Reed-Sternberg (R-S) cells and their variants. Typical R-S and Hodgkin's cells were mono- or binucleated, and nuclei had rounded smooth contour. Acidophilic prominent nucleoli with perinucleolar halo were conspicuous. In comparison to typical Reed-Sternberg cells, L & H (lymphocytic and histiocytic) cells in the lymphocyte predominant type tended to show pop-corn like irregular nuclear contour and to lack the prominent nucleoli. Lacunar cells in the nodular sclerosis type had multilobated nuclei with prominent acidophilic nucleoli. There was no prominent perinucleolar halo in L & H and lacunar cells. In conjuction with the number of Reed-Sternberg cells and back ground findings observed on the smears, the characteristic features of R-S cells and their variants allowed to make typing of Hodgkin's disease.

Case Reports

Acute Appendicitis Associated with Aspergillosis in a Leukemia Patient: A Case Report.: Bong Hee Park, Jae Hee Suh, Hye Jeong Choi, Hee Jeong Cha, Chang Woo Nam, Young Min Kim; Korean J Pathol. 2010;44(3):330-332.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.330

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Abstract PDF

Herein we describe a rare case of acute appendicitis associated with localized aspergillosis in an 8-year-old boy with acute lymphoblastic leukemia. During chemotherapy, the patient complained of mild abdominal pain in the peri-umbilical area and displayed an increased C-reactive protein level. Abdominal ultrasonography disclosed appendicitis and consequently an appendectomy was done. Histologically, acute appendicitis and Aspergillus hyphae were identified in the lumen and necrotic mucosa. However, there was no evidence of systemic aspergillosis. While aspergillosis is a common fungal infection in immunocompromised patients treated with chemotherapy, acute appendicitis associated with localized aspergillosis without systemic infection is a very rare occurrence.

Citations

Citations to this article as recorded by

A scoping review on acute gastrointestinal surgical complications in immunocompromised pediatric patients
Tarek Bou Dargham, Mohamad Bahij Moumneh, Christine Atallah, Ahmad Zaghal
Annals of Pediatric Surgery.2022;[Epub] CrossRef
Acute isolated Aspergillus appendicitis in pediatric leukemia
Yutaro Yada, Yuhki Koga, Hiroaki Ono, Yoshitomo Motomura, Genshiro Esumi, Kenichi Kohashi, Yasunori Muraosa, Katsuhiko Kamei, Toshiharu Matsuura, Yoshinao Oda, Shouichi Ohga
Journal of Infection and Chemotherapy.2020; 26(11): 1229. CrossRef
Isolated Acute Appendicitis Caused by Aspergillu s in a Patient Who Underwent Lung Transplantation: A Case Report
H.S. Kim, H.J. Yeo, D.H. Shin, W.H. Cho, D. Kim
Transplantation Proceedings.2018; 50(4): 1199. CrossRef
Fungal Appendicitis in Immunocompromised Children. Indications and Contraindications for Laparoscopic Appendectomy: A Report on 2 Successful Cases
Veronica Carlini, Valeria Calcaterra, Nunzia Decembrino, Laura Rubert, Noemi Pasqua, Mattia Novario, Marco Lucioni, Marco Brunero, Gloria Pelizzo
Journal of Pediatric Hematology/Oncology.2016; 38(7): 581. CrossRef
Characteristic clinical features ofAspergillusappendicitis: Case report and literature review
Mihajlo Gjeorgjievski
World Journal of Gastroenterology.2015; 21(44): 12713. CrossRef

Intra-abdominal Desmoplastic Small Round Cell Tumor Diagnosed by Lymph Node Biopsy: A case report.: Myung Jin Ju, Kwang Min Lee, Hye Kyung Lee, Dong Kyu Chung; Korean J Pathol. 1995;29(5):698-701.

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Abstract: Intra-abdominal desmoplastic small round cell tumor has been described in the literature since 1989. It is characterized by the occurrence in ages less than 40 with male predominance, an intra-abdominal location, and small round to oval shaped tumor cells with divergent differentiation in the background of the desmoplastic stroma. We recently experienced this tumor in an inguinal lymph node of a 36-year-old man. It is suspected that it metastasized from a lower intra-abdominal tumor. Immunohistochemical stains for keratin, epithelial membrane antigen, vimentin, S-100 protein and neuron specific enolase were positive. This is the first documented case in Korea. Herein, we report on this tumor with a review of literature.

Intraabdominal Desmoplastic Small Cell Tumors with Divergent Differentiation: Report of two cases with immunohistochemical and ultrastructural studies.: Young Ha Oh, Nam Hoon Kim, Joo Seob Keum, Moon Hyang Park; Korean J Pathol. 1996;30(1):40-49.

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Abstract PDF: We studied two intraabdominal desmoplastic small cell tumors. The patients were two men, 37 and 23 years old, with jaundice and palpable abdominal masses. On exploratory laparotomy, each patient revealed a huge mass in the greater omentum with disseminated peritoneal seeding, measuring 32 cm and 11 cm in its greatest dimension, respectively. The tumor involved the diaphragm, rectal shelf, and cul de sac in case 1, and it involved the porta hepatis, retroperitoneum, and serosal surface of the ascending and transverse colon in case 2. Omentectomy of the huge mass and satellite masses was performed in each patient. Both tumors showed nearly the same histopathologic features. The histologic pattern was suggestive of a metastatic small cell carcinoma, but there was no specific, single primary site. The tumors consisted of variably sized, discrete islands of epithelial-like small cells in dense desmoplastic stroma. The tumor cells revealed divergent epithelial, mesenchymal, and neural differentiation by histologic, immunohistochemical, and electron microscopic observations. Only one cycle of chemotherapy including cisplatin and VP-16 was given in case 1 because of a subsequent hepatic problem, who, thereafter, showed massive intraabdominal recurrent tumors 6 months after diagnosis. In case 2, the poor condition of the patient had made chemotherapy and radiotherapy impossible. Case 2 died of disseminated intravascular coagulation following progressive cachexia 7 months after diagnosis.

Pulmonary Pseudallescheriasis: A case report and Histopathologic Comparision with Pulmonary Aspergillosis.: Young Sill Kim, Chang Suk Kang, Kyung Ja Han, Kyo Young Lee, Sang In Shim, Young Shin Kim; Korean J Pathol. 1998;32(2):147-149.

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Abstract PDF: Infection by pseudallescheria boydii is an occasional cause of mycetoma, corneal ulcers, endophthalitis, sinusitis, pneumonia, endocarditis, meningitis, arthritis, and osteomyelitis. But, it also causes serious disseminated or localized infection in immunocompromised patients. We report a case of pulmonary pseudallescheriasis developed in a 32-year-old man who has been a sofa manufacturer for several years. He presented with a cystic mass in the lung, 5cm in the largest dimension. Dark green necrotic material was evacuated from the cavity. Microscopically, the cystic wall and adjacent lung parenchyme were infiltrated by histiocytes rather than eosinophils and there was little fibrosis in the wall. The P. boydii was isolated from the cystic contents, which revealed white floccose colonies in Sabouraud dextrose agar and revealed single or multiple-celled oval conidia being produced on short hyalinated hyphae and on the elongated annellides in the slide culture. The differential findings with aspergillosis are discussed.

Tracheobronchial Aspergillosis An autopsy case report.: Tae jung Kwon, Dong Joo Lee, Il Hoon Kwon; Korean J Pathol. 1999;33(8):620-623.

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Abstract: Tracheobronchial aspergillosis is an unusual form of invasive aspergillosis characterized by noninvasive or only superficially invasive tracheobronchitis with a propensity for dissemination. We report a two-year-old male who suddenly died of respiratory failure. Postmortem examination revealed a pseudomembrane covering the mucosa of larynx, trachea and bronchial tree of both lungs. This pseudomembrane was composed predominantly of Aspergillus hyphae. There was transmural necrotizing bronchitis with fungal invasion to the narrow zone of peribronchial tissue, and dissemination to the stomach and kidney. This form of pulmonary aspergillosis had not been reported in this country.

Pulmonary Aspergillus niger Fungus Ball Associated with Calcium Oxalate Crystal: A Case Report.: Eunhee Lee, Heejung Kim, Eundeok Chang, Kyo Young Lee, Byung Kee Kim; Korean J Pathol. 2001;35(2):165-167.

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Abstract PDF: Pulmonary aspergillomas are considered to represent saprophytic growth of hyphae within the preexisting lung cavity. Causative Aspergillus species are mostly composed of A. fumigatus and A. flavus and, occasionally, A. niger. It is difficult to identify these species using histopathologic evaluation without a culture of sputum and bronchoalveolar lavage. We recently experienced a case of pulmonary Aspergillus niger infection associated with characteristic calcium oxalate crystal formation. A large cavity contained hyphae with a typical conidial head, conidiophore, and conidia. Characteristic birefrigent calcium oxalate crystals were demonstrated in the cavity wall.

Disseminated Systemic Candidiasis and Aspergillosis in a Liver Transplant Patient: An Autopsy Report.: Na Rae Kim, Dae Su Kim, Young Hyeh Ko, Sung Joo Kim; Korean J Pathol. 2002;36(5):348-352.

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Abstract PDF: Postoperative complications of liver transplantation include rejection, infection, hepatic vascular thrombus, and primary graft failure, etc. Among them, fungal infection shows nonspecific clinical symptoms and overlapping laboratory findings with variable etiologies causing post-transplant hepatic dysfunction. Therefore, early diagnosis of fungal infection is not easy. Here, we report an autopsy case of disseminated candidiasis and aspergillosis in a liver transplant patient. The case was at first misinterpreted as acute cellular rejection on biopsy because the histology of predominantly cellular infiltration, ductulitis and endothelialitis were similar to those of acute cellular rejection. On autopsy, the liver, lung and kidney showed multifocal hemorrhagic infarcts due to intra-arterial fungal emboli, which were composed mostly of candida species and a minor fraction of aspergillus. Fungal thrombi invading portal vein, intrahepatic arterioles with subsequent coagulation necrosis, venulitis and ductulitis were ascribed to the misdiagnosis on biopsies. It is unusual that systemic candidiasis, unlike aspergillosis, involves large arteries.

Aspergillous Hypophysitis: A Case Report.: Jeana Kim, Leeso Maeng, Je Hoon Lee, Kyoung Mee Kim, Anhi Lee, Chang Suk Kang; Korean J Pathol. 2005;39(3):197-199.

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Abstract PDF: Aspergillous hypophysitis is an unusual cause of sella turcica enlargement, and this malady has a clinical presentation as a pituitary tumor, and especially as a pituitary adenoma. We report here on a case of aspergillous hypophysitis that developed in a 37-year-old healthy woman. She first experienced a blurred vision with amenorrhea and galactorrhea. Three months later, the CT scan revealed an intrasellar mass. The patient underwent a transsphenoidal exploration of the sella turcica for a presumed pituitary tumor. Histologically, the pituitary displayed necrotizing granuloma with the acutely branching fungal hyphae of Aspergillus.

Original Article

A Study of Lectin Histochemistry in Allergic Contact Dermatitis of Guinea Pig.: Joung Ho Han, Eun Sook Nam, Young Chul Kye, Han Kyeom Kim, Seung Yong Paik; Korean J Pathol. 1991;25(4):281-290.

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Abstract PDF: The alterations in the localization of keratinocyte membrane glycoconjugates in allergic contact dermatitis were investigated in guinea pig skin treated with topical application of 2.4-dinitro-chlorobenzene. We employed the avidin-biotin complex(ABC) method for the detection of localization of 10 commercially available lectins labelled with biotin: Con-A, SBA, WGA, DBA, UEA-1, RCA-1, PNA, HP, MPA, and ECA. Staining with WGA showed a remarkably decreased intensity in basal and spinous layers of the allergic skin in comparison to those of the control skin, suggesting loss of terminal sialic acids in cell membrane glycoconjugates. The other lectins showed no remarkable difference in the staining patterns between the normal and the allergic ski. The results suggest that epidermal cell membrane glycoconjugates undergoes selective perturbations in acute allergic contact dermatitis, and that the keratinocytes might be an active part of the cutaneous immune system.

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