Journal of Pathology and Translational Medicine

Original Article

Blocking Toll-like receptor 9 attenuates bleomycin-induced pulmonary injury: Badr Alzahrani, Mohamed M. S. Gaballa, Ahmed A. Tantawy, Maha A. Moussa, Salma A. Shoulah, Said M. Elshafae; J Pathol Transl Med. 2022;56(2):81-91. Published online March 2, 2022; DOI: https://doi.org/10.4132/jptm.2021.12.27

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Background
Acute respiratory distress syndrome (ARDS) is one of the most common complications in coronavirus disease 2019 patients suffering from acute lung injury (ALI). In ARDS, marked distortion of pulmonary architecture has been reported. The pulmonary lesions in ARDS include hemodynamic derangements (such as alveolar edema and hemorrhage), vascular and bronchiolar damage, interstitial inflammatory cellular aggregations, and eventually fibrosis. Bleomycin induces ARDS-representative pulmonary damage in mice and rats; therefore, we used bleomycin model mice in our study. Recently, Toll-like receptor 9 (TLR9) was implicated in the development of ARDS and ALI.
Methods
In this study, we evaluated the efficiency of a TLR9 blocker (ODN2088) on bleomycin-induced pulmonary damage. We measured the apoptosis rate, inflammatory reaction, and fibroplasia in bleomycin- and bleomycin + ODN2088-treated mice.
Results
Our results showed a significant amelioration in bleomycin-induced damage to pulmonary architecture following ODN2088 treatment. A marked decrease in pulmonary epithelial and endothelial apoptosis rate as measured by cleaved caspase-3 expression, inflammatory reaction as indicated by tumor necrosis factor α expression, and pulmonary fibrosis as demonstrated by Van Gieson staining and α-smooth muscle actin immunohistochemistry were observed following ODN2088 treatment.
Conclusions
All these findings indicate that blocking downstream TLR9 signaling could be beneficial in prevention or mitigation of ARDS through hemodynamic derangements, inflammation, apoptosis, and fibrosis.

Citations

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A novel mouse model of myositis-associated interstitial lung disease was established by using TLR9 agonist combined with muscle homogenate
Ling Bai, Jiarui Zhu, Wenlan Ma, Peipei Zhao, Feifei Li, Cen Zhang, Sigong Zhang
Clinical and Experimental Immunology.2025;[Epub] CrossRef
Toll-like Receptor 9 Inhibition Mitigates Fibroproliferative Responses in Translational Models of Pulmonary Fibrosis
Glenda Trujillo, Alicia Regueiro-Ren, Chunjian Liu, Buqu Hu, Ying Sun, Farida Ahangari, Vitoria Fiorini, Genta Ishikawa, Karam Al Jumaily, Johad Khoury, John McGovern, Chris J. Lee, Xue Yan Peng, Taylor Pivarnik, Huanxing Sun, Anjali Walia, Samuel Woo, Sh
American Journal of Respiratory and Critical Care Medicine.2025; 211(1): 91. CrossRef
CD103+ dendritic cell–fibroblast crosstalk via TLR9, TDO2, and AHR signaling drives lung fibrogenesis
Hannah Carter, Rita Medina Costa, Taylor S. Adams, Talon M. Gilchrist, Claire E. Emch, Monica Bame, Justin M. Oldham, Steven K. Huang, Angela L. Linderholm, Imre Noth, Naftali Kaminski, Bethany B. Moore, Stephen J. Gurczynski
JCI Insight.2025;[Epub] CrossRef
Mechanisms underlying dose-limiting toxicities of conventional chemotherapeutic agents
Mohammad Amin Manavi, Mohammad Hosein Fathian Nasab, Razieh Mohammad Jafari, Ahmad Reza Dehpour
Journal of Chemotherapy.2024; 36(8): 623. CrossRef
Innate Immune Response-Mediated Inflammation in Viral Pneumonia
Weiwei Ni, Xin Wei, Rui Wu
Journal of Pediatric Infectious Diseases.2024; 19(03): 140. CrossRef
Combination of losartan with pirfenidone: a protective anti-fibrotic against pulmonary fibrosis induced by bleomycin in rats
Arian Amirkhosravi, Maryamossadat Mirtajaddini Goki, Mahmoud Reza Heidari, Somayyeh Karami-Mohajeri, Maryam Iranpour, Maryam Torshabi, Mitra Mehrabani, Ali Mandegary, Mehrnaz Mehrabani
Scientific Reports.2024;[Epub] CrossRef
Suppression of miR-17 Alleviates Acute Respiratory Distress-associated Lung Fibrosis by Regulating Mfn2
Mei-xia Xu, Tao Xu, Ning An
Current Medical Science.2024; 44(5): 964. CrossRef
Study of Recombinant Interleukin-1 Receptor Antagonist Compositions Biological Activity After Injection and Inhalation in Mouse Model of Pulmonary Inflammation
Alexander M. Ischenko, Ksenia A. Nekrasova, Denis S. Laptev, Dmitry V. Bobkov, Alexander A. Kolobov, Andrey S. Simbirtsev
Cytokines and inflammation.2024; 21(3): 153. CrossRef
TLR9: A friend or a foe
Mona M. Saber, Nada Monir, Azza S. Awad, Marwa E. Elsherbiny, Hala F. Zaki
Life Sciences.2022; 307: 120874. CrossRef

Case Study

Appendiceal actinomycosis mimicking appendiceal tumor, appendicitis or inflammatory bowel disease: You-Na Sung, Jihun Kim; J Pathol Transl Med. 2021;55(5):349-354. Published online June 26, 2020; DOI: https://doi.org/10.4132/jptm.2020.05.17

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Abstract PDF

Appendiceal actinomycosis is very rare and its diagnosis is often difficult even in surgically resected specimens. Here we report two cases of appendiceal actinomycosis confirmed by pathologic examination of surgically resected specimens. Characteristic histologic features included transmural chronic inflammation with Crohn-like lymphoid aggregates and polypoid mucosal protrusion into cecal lumen through fibrous expansion of the submucosa. Chronic active inflammation involved the mucosa of the appendix and cecum around the appendiceal orifice. Crohn’s disease with predominant cecal involvement and inflammatory pseudotumor were considered as differential diagnoses. Careful examination revealed a few actinomycotic colonies in the mucosa, confirming the diagnosis. A high index of suspicion with awareness of the characteristic histologic features might prompt careful inspection for the actinomycotic colonies, leading to the appropriate diagnosis of this rare disease.

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Appendicular actinomycosis: The first reported case of an uncommon finding of a common ailment from Nepal
Sujan Bohara, Manoj Khadka, Pawan Singh Bhat, Prajwal Syangtang, Badal Karki, Bhagawan Shrestha, Shoshan Arja Acharya, Khusbhu Khetan, Jyoti Rayamajhi, Sushil Bahadur Rawal
Clinical Case Reports.2023;[Epub] CrossRef
Abdominopelvic actinomycosis: An unexpected diagnosis in an elderly female with a destructive-appearing soft tissue mass
Elise Hyser, Drashti Antala, Harvey Friedman, Jonathan Stake
IDCases.2022; 28: e01479. CrossRef

Original Article

Does Polymerase Chain Reaction of Tissue Specimens Aid in the Diagnosis of Tuberculosis?: Yoo Jin Lee, Seojin Kim, Youngjin Kang, Jiyoon Jung, Eunjung Lee, Joo-Young Kim, Jeong Hyeon Lee, Youngseok Lee, Yang-seok Chae, Chul Hwan Kim; J Pathol Transl Med. 2016;50(6):451-458. Published online October 10, 2016; DOI: https://doi.org/10.4132/jptm.2016.08.04

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Abstract PDF

Background
Mycobacterial culture is the gold standard test for diagnosing tuberculosis (TB), but it is time-consuming. Polymerase chain reaction (PCR) is a highly sensitive and specific method that can reduce the time required for diagnosis. The diagnostic efficacy of PCR differs, so this study determined the actual sensitivity of TB-PCR in tissue specimens.
Methods
We retrospectively reviewed 574 cases. The results of the nested PCR of the IS6110 gene, mycobacterial culture, TB-specific antigen-induced interferon-γ release assay (IGRA), acid-fast bacilli (AFB) staining, and histological findings were evaluated.
Results
The positivity rates were 17.6% for PCR, 3.3% for the AFB stain, 22.2% for mycobacterial culture, and 55.4% for IGRA. PCR had a low sensitivity (51.1%) and a high specificity (86.3%) based on the culture results of other studies. The sensitivity was higher (65.5%) in cases with necrotizing granuloma but showed the highest sensitivity (66.7%) in those with necrosis only. The concordance rate between the methods indicated that PCR was the best method compared to mycobacterial culture, and the concordance rate increased for the methods using positive result for PCR or histologic features.
Conclusions
PCR of tissue specimens is a good alternative to detect tuberculosis, but it may not be as sensitive as previously suggested. Its reliability may also be influenced by some histological features. Our data showed a higher sensitivity when specimens contained necrosis, which indicated that only specimens with necrosis should be used for PCR to detect tuberculosis.

Citations

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The Need for Persistence in the Diagnosis of Mycobacterium Tuberculosis Mono-arthritis: A Unique Case Presentation
T. Bekoulis, P. Christodoulou, K. Dogramatzis, E. Markopoulou, Emmanouel Antonogiannakis, E. Kokkinakis, Alexandros P. Apostolopoulos, A. Manimanaki
Journal of Long-Term Effects of Medical Implants.2024; 34(1): 35. CrossRef
A Case Report on Scrofuloderma: A Cutaneous Manifestation of Tuberculosis
Soham R Meghe, Adarshlata Singh, Drishti M Bhatt, Shreya N Gupta, Varun Hanumanthaiah, Shree Ramya Talasila
Cureus.2024;[Epub] CrossRef
An overview of infectious disease laboratory methods: an update for the histopathologist
Daniel R. Stevenson
Diagnostic Histopathology.2024; 30(10): 534. CrossRef
Diagnostic Utility of Biplex/Multiplex Polymerase Chain Reaction in Infectious Granulomatous Dermatitis in North Indian Population
Mayur Parkhi, Mukin Kumar S, Dipankar De, Rakesh Yadav, Sunil Sethi, Bishan Dass Radotra, Uma Nahar Saikia
The American Journal of Dermatopathology.2021; 43(8): 567. CrossRef
Reduction of turnaround time for non-tuberculous mycobacteria detection in heater–cooler units by propidium monoazide–real-time polymerase chain reaction
S. Ditommaso, M. Giacomuzzi, G. Memoli, R. Cavallo, A. Curtoni, M. Avolio, C. Silvestre, C.M. Zotti
Journal of Hospital Infection.2020; 104(3): 365. CrossRef
Ergonomic Diagnostic Tool based on Chip Mini RT-PCR for Diagnosis of Pulmonary and Extra Pulmonary Tuberculosis
V Mangayarkarasi, Sneka P, Sujith R, Jayaprakash Jayaprakash
Journal of Pure and Applied Microbiology.2019; 13(2): 1185. CrossRef
Cutaneous Tuberculosis: Clinicopathologic Arrays and Diagnostic Challenges
Priyatam Khadka, Soniya Koirala, Januka Thapaliya
Dermatology Research and Practice.2018; 2018: 1. CrossRef
Utility of Real-Time Quantitative Polymerase Chain Reaction in DetectingMycobacterium tuberculosis
Zhongquan Lv, Mingxin Zhang, Hui Zhang, Xinxin Lu
BioMed Research International.2017; 2017: 1. CrossRef
Primary Appendicular Tuberculosis
Vipul D Yagnik
Gastroenterology & Hepatology: Open Access.2017;[Epub] CrossRef

Case Study

Oncocytic Renal Cell Carcinoma with Tubulopapillary Growth Having a Fat Component: Na Rae Kim, Hyun Yee Cho; J Pathol Transl Med. 2015;49(5):413-417. Published online July 30, 2015; DOI: https://doi.org/10.4132/jptm.2015.07.01

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Abstract PDF

We report a rare case of oncocytic renal cell carcinoma (RCC) with tubulopapillary growth in the background of tuberculous end-stage kidney disease. Histology of the renal mass consisted of oncocytic cells forming solid, thin tubules and rare papillae. The tumor had abundant eosinophilic oncocytic cells containing occasional cytoplasmic Mallory body–like hyaline globules and a tiny focus of clear cells with intervening mature fat. Both the oncocytic cells and clear cells were immunoreactive for a-methylacyl-CoA racemase, vimentin, pancytokeratin, and CD10, and negative for transcription factor E3, CD15, human melanoma black 45, and c-kit. Mallory body–like hyaline globules were positive for CAM 5.2 and periodic acid–Schiff with or without diastase. Ultrastructurally, the tumor cells had abundant cytoplasmic mitochondria. The present case is a rare case of oncocytic RCC with tubulopapillary growth pattern. The case is unique in that the tumor was mixed with fat component, which is not common in RCC and thus can lead to misdiagnosis.

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Oncocytic papillary renal cell carcinoma (OPRCC): 2 case report and literature review
Yanchen Wang, Lihui Guan, Yaming Liu, Yuxuan Liu, Xiaoyan Guo, Yaofei Sun
Frontiers in Oncology.2025;[Epub] CrossRef

Original Article

Prognostic Significance of Amplification of the c-MYC Gene in Surgically Treated Stage IB-IIB Cervical Cancer.: Tae Jung Kim, Ahwon Lee, Sung Jong Lee, Won Chul Lee, Yeong Jin Choi, Kyo Young Lee, Chang Suk Kang; Korean J Pathol. 2011;45(6):596-603.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.596

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Abstract PDF

BACKGROUND
Mutations of c-MYC have been described in cervical cancer. However, association between c-MYC gene status and its prognostic significance have not been clarified.
METHODS
Tissue microarray sections from 144 patients with stage IB-IIB cervical cancer treated by radical hysterectomy were analyzed by fluorescence in situ hybridization using a region-specific probe for c-MYC and a centromere-specific probe for chromosome 8.
RESULTS
Seventy five percent (108/144) of c-MYC gain and 6.9% (10/144) of c-MYC gene amplification were observed. c-MYC gene alteration was more frequently observed in squamous cell carcinoma than adenocarcinoma or adenosquamous carcinoma and were associated with low Ki67 labeling index (p=0.013). c-MYC amplification was not associated with clinicopathologic parameters except absence of bcl2 expression (p=0.048). Survival analysis revealed that patients with c-MYC amplification were significantly associated with higher risk of disease recurrence (p=0.007) and cancer related death (p=0.020). However, c-MYC gain was not associated with unfavorable outcome. Multivariate analysis proved c-MYC amplification as independent prognostic factors of shorter disease free survival and cancer-related death (p=0.028 and p=0.025, respectively).
CONCLUSIONS
c-MYC amplification, not gain, is an independent prognostic marker for shorter disease free and cancer specific survival in cervical cancer treated by radical hysterectomy.

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A Rare Case of Cutaneous Plasmacytosis in a Korean Male
Corey Georgesen, Meenal Kheterpal, Melissa Pulitzer
Case Reports in Pathology.2017; 2017: 1. CrossRef

Case Report

Mycophenolate Mofetil-Related Colitis: A Case Report.: Kyungeun Kim, Jerad M Gardner, Mary Schwartz, Matthew L Tompson, Jae Y Ro; Korean J Pathol. 2010;44(3):333-337.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.333

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Abstract PDF

Mycophenolate mofetil (MMF)-related colitis is one of the common causes of afebrile diarrhea in transplant patients. Pathologic diagnosis of MMF-related colitis is difficult because microscopic findings of MMF effects resemble those of graft-versus-host disease, inflammatory bowel disease and ischemic colitis. However, if diagnosed, MMF-induced colitis can be markedly improved by discontinuing the drug. A 70-year-old man having a history of transplantation presented with a one month history of afebrile diarrhea. Colonoscopy revealed patchy erosions. The colonoscopic biopsy specimen showed not only crypt disarray with degenerated crypts and scattered epithelial cell apoptosis, but also stromal inflammatory cell infiltration. A review of his medical records showed that he had been taking immunosuppressive drugs including MMF since his heart transplantation 6 years prior. The histologic findings of colonic mucosa were consistent with MMF-related colitis. After discontinuing MMF, the diarrhea quickly resolved and has not recurred for 10 months.

Citations

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Colitis eosinofílica inducida por micofenolato: reporte de caso
Mario Alberto Caviedes-Cleves, Ariel Antonio Arteta-Cueto
Iatreia.2023;[Epub] CrossRef
Mycophenolate Mofetil-Induced Colonic Injury Manifesting Endoscopically As Ischemic Colitis
Clive J Miranda, Murad H Ali, Muddasir Ayaz, Raheel M Khan, Mayada Ismail
Cureus.2023;[Epub] CrossRef
Transformation of the Amino Acid Pool in the Rat Brain under Conditions of Experimental Immunodeficiency
N. I. Filina, M. N. Kurbat
Neurochemical Journal.2022; 16(2): 174. CrossRef
A Case Series of De Novo Inflammatory Bowel Disease After Kidney Transplantation
P. Azevedo, C. Freitas, P. Aguiar, H. Silva, T. Santos, P. Farrajota, M. Almeida, S. Pedroso, L.S. Martins, L. Dias, R. Vizcaíno, A. Castro Henriques, A. Cabrita
Transplantation Proceedings.2013; 45(3): 1084. CrossRef

Original Articles

Comparison of Various Detection Methods of Mycobacterium Species in Formalin-Fixed Paraffin-Embedded Tissue with Chronic Granulomatous Inflammation.: Hyun Seung Lee, Hyoungnam Lee, Soyoung Im, Yun Su Lee, Kyo Young Lee, Yeong Jin Choi; Korean J Pathol. 2010;44(3):259-266.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.259

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Abstract PDF

BACKGROUND
To determine the most effective method for detecting mycobacteria in formalin- fixed paraffin-embedded (FFPE) tissue, we compared the results of Ziehl-Neelsen stain (ZNS) and mycobacterial culture with those of polymerase chain reaction (PCR) and real-time quantitative PCR (RQ-PCR).
METHODS
We analyzed 54 cases diagnosed as chronic granulomatous inflammation. In all cases, ZNS and nested PCR using three different primers, IS6110, Mpb64 and IS6110/Rpobeta were done. RQ-PCR with the IS6110/Rpobeta primer was done in 51 cases.
RESULTS
Mycobacteria were identified by ZNS in 15/54 (27.8%) cases. RQ-PCR had the highest sensitivity (80.0%) compared to PCR with IS6110 (73.3%), Mpb64 (60.0%) and IS6110/Rpobeta (73.3%). Specificity was higher in all PCR experiments (79.5-82.1%) than in RQ-PCR (69.4%) experiments. The false negative rate was lowest for RQ-PCR (20.0%) than for PCR with IS6110 (26.7%), Mpb64 (40.0%) and IS6110/Rpobeta (26.7%). The false positive rate was highest for RQ-PCR (30.6%) compared to PCR with IS6110 (20.5%), Mpb64 (17.9%) and IS6110/Rpobeta (20.5%).
CONCLUSIONS
RQ-PCR had the highest sensitivity, and the lowest false negative rate, but it also had a higher false positive rate than PCR for detection of mycobacteria in FFPE tissues.

Citations

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Clinical Usefulness of PCR for Differential Diagnosis of Tuberculosis and Nontuberculous Mycobacterial Infection in Paraffin-Embedded Lung Tissues
Yo Na Kim, Kyoung Min Kim, Ha Na Choi, Ju Hyung Lee, Ho Sung Park, Kyu Yun Jang, Woo Sung Moon, Myoung Jae Kang, Dong Geun Lee, Myoung Ja Chung
The Journal of Molecular Diagnostics.2015; 17(5): 597. CrossRef
Usefulness of PCR to Mycobacterium Tuberculous and Nontuberculous Mycobacteria from Paraffin-embedded Tissues
Yeon-Il Choi, Hye-Young Kim
Korean Journal of Clinical Laboratory Science.2014; 46(2): 47. CrossRef

Pathologic Findings of Surgically Resected Nontuberculous Mycobacterial Pulmonary Infection.: Hye Jong Song, Jung Suk An, Joungho Han, Won Jung Koh, Hong Kwang Kim, Yong Soo Choi; Korean J Pathol. 2010;44(1):56-62.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.1.56

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Abstract PDF: BACKGROUND
Surgical resection of the involved lung for nontuberculous mycobacteria (NTM) has become an important curative therapy. However, there is limited information on the histopathological features of NTM pulmonary disease in Korean patients with NTM infection.
METHODS
We evaluated 51 specimens from 49 patients who were treated at our referral center from 2002 to 2009.
RESULTS
Almost all the cases showed bronchiectasis with lymphocytic infiltration. Variable features of granulomatous inflammation were found; well-defined granulomas in the parenchyma (68.6%), pneumonia-like granulomatous lesions (49.0%) and granulomatous inflammation in the bronchial wall (41.2%) were identified. The microscopic findings of cavitary lesions (37.3%) showed that these lesions were composed of granulomas and necrosis.
CONCLUSIONS
The differentiation of tuberculosis from NTM could not be accurately made based solely on the histological features. However, the airway centered tendency of NTM reflected an airborn etiology, and this could be correlated with the classification according to the radiological findings. In addition, coexisting constitutional lung diseases, and especially bronchiectasis, were suspected to be predisposing conditions for NTM organisms to colonize and progress to true NTM pulmonary disease.

Case Report

Granulomatous Mycosis Fungoides: A case report.: Kyung Sin Lee, Young Oak Kim, Kee Suck Suh, Sang Tae Kim, Man Ha Huh; Korean J Pathol. 1995;29(5):694-697.

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Abstract: Granulomatous mycosis fungoides is an extremely rare and unusual histologic variant of mycosis fungoides. This form is clinically characterized by spontaneous resolution of ulcerated nodular lesions into poikiloderma. Histologically, a strong granulomatous component can obscure the underlying cutaneous lymphoma, which is frequently mistaken for non-neoplastic dermatitides or cutaneous sarcoidosis. We report a case of granulomatous mycosis fungoides occurring on the left cheek of 34-year-old man confirmed histologically with an aid of immunohistochemistry and clinical course (immediate response to PROMACE-CYTOBAM chemotherapy), with emphasis on differential diagnosis, along with a review of literature. This is the first documented report in the Korean literature.

Original Article

Expression of p53, c-myc, Transforming Growth Factor-alpha and -beta in Human Epithelial Ovarian Tumors.: Jae Hwa Lee, Young Ok Lee, Man Ha Huh; Korean J Pathol. 1996;30(1):23-31.

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Abstract PDF: The author examined expression of tumor-related antigens, such as p53 tumor supressor protein, c-myc, TGF-alpha, and TGF-beta proteins in 75 cases of surgically resected epithelial ovarian tumors. Peroxidase immunohistochemistry was used to determine the frequency of expression, the relationship among expression of these antigens and histopathological spectrums, and clinical stage, and their potential prognostic significance. The results are summarized as follows. A positive correlation was found between expression of p53(P=0.02), c-myc(P=0.03), and TGF-alpha(P=0.001) and histological degrees of malignancy(benign, borderline, or malignant) in epithelial ovarian tumors. A significant correlation was found between expression of p53 and histological degrees of malignancy in serous ovarian tumors(P=0.003) and mucinous tumors (P=0.049). A significant correlation was also found between expression of c-myc and the histological grade of serous carcinomas(P=0.02). A correlation between expression of these antigenic proteins and clinical stage of epithelial ovarian tumors was not demonstrated. Expression of p53 and c-myc was closely correlated with expression of TGF-alpha irrespective of the histological degrees of malignancy and type of epithelial ovarian tumors(0.4 < or = K < or = 0.7). The results of this study support the ideas that expression of c-myc and TGF-alpha might be a useful prognostic indicator in human ovarian carcinomas, and expression of p53 could be another indicator of prognosis, as the expression of p53 is characteristic in that the expression is mostly seen in invasive ovarian carcinomas.

Case Report

Chromomycosis of the Nasolacrimal Duct: Report of a case.: So Dug Lim, Ji Eun Kim, Kyu Rae Kim; Korean J Pathol. 1996;30(4):358-360.

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Abstract PDF: Chromomycosis is a chronic cutaneous fungal infection characterized by the presence of dark brown parasitic forms of fungi in biopsied tissues. It is usually resulted from the entry of the causative organism through a minor trauma, and therefore, most lesions are found on the exposed part of the body, such as limbs or face, and occurrence on the nasolacrimal duct is extremely rare. We report a case of chromomycosis of the right nasolacrimal duct, which was presented with clinical symptoms of nasolacrimal duct obstruction. The patient was a 40 year-old male who had had minor injuries on his left eye twice by paper and branches of the tree two months prior to epiphora in right eye. On dacryocystorhinostomy, right nasolacrimal duct was obstructed by pinkish brown mucoid ball. Microscopically, the mucoid ball revealed eosinophilic, amorphous, necrotic materials admixed with brown pigmented fungi. The organism showed characteristic dark brown, round, thick-walled, often septated, sclerotic bodies and brown pigmented long bead-like hyphae. The adjacent mucosa shows marked chronic nonspecific inflammation with fibrosis.

Original Articles

Detection of bcl-2/IgH Gene Rearrangement and Expression of c-myc and p53 Oncoprotein in B-cell Lymphoma.: Ghee Young Kwon, Chul Woo Kim; Korean J Pathol. 1996;30(5):437-446.

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Abstract PDF: Many kinds of genetic changes have been known to be associated with malignant lymphoma and bcl-2, p53 and c-myc are some examples. We investigated the expression of p53 and c-myc protein in follicular and diffuse B cell lymphoma by immunohistochemistry to study the possible role of these proteins in the lymphomagenesis and transformation of the tumor. The rearrangement of bcl-2 oncogene and the immunoglobulin heavy chain gene was searched for in those cases by polymerase chain reaction(PCR). Paraffin-embedded tissues of fifteen follicular lymphomas and 14 diffuse lymphoma cases were used. The results of immunohistochemical staining are summarized as follows: 1) p53 positivity is significantly higher in diffuse lymphoma than in follicular lymphoma(P=0.001); 2) c-myc expression is not increased in diffuse lymphoma compared with follicular lymphoma; 3) PCNA index is significantly higher in diffuse lymphoma than in follicular lymphoma(P=0.03) but there was no statistically significant correlation between PCNA index and p53 positivity(P=0.44); 4) Eight out of 14 cases of follicular lymphoma and 12 of 14 cases of diffuse lymphoma showed rearrangement of the immunogloblulin heavy chain gene; 5) bcl-2 oncogene rearrangement was identified in only one case of follicular lymphoma and all the diffuse type lymphomas were negative in bcl-2/IgH rearrangement. In conclusion, assuming that the follicular pattern of B-cell lymphoma often transforms to diffuse type in later stages, c-myc over-expression might be an earlier event than p53 mutation in the process of tumor progression in B-cell lymphoma. bcl-2/IgH gene rearrangement in follicular lymphoma is a rare finding in Korea compared to that of Western countries.

Expression of bcl-2 and c-myc Proteins in Epidermal and Melanocytic Tumors.: Young Ha Oh, Chan Kum Park, Jung Dal Lee; Korean J Pathol. 1996;30(9):810-818.

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Abstract PDF: bcl-2 and c-myc protein expression were studied in 44 epidermal (8 seborrheic keratoses, 21 squamous cell carcinomas, and 15 basal cell carcinomas), and 26 melanocytic tumors(8 nevi, and malignant melanomas) by immunohistochemistry using the specific anti-bcl-2 and anti-c-myc monoclonal antibodies. 14 out of 15 basal cell carcinomas(BCC) (93.3%) showed expression of bcl-2 protein, 12 of which (85.7%) showed coexpression of c-myc protein. In the melanocytic tumors, 7 out of 8 nevi showed bcl-2 expression (87.5%). Five of these 7 cases (62.5%) also showed c-myc protein expression. Eight of 18 malignant melanomas(MM) (44.4%) showed expression of bcl-2 protein and 7 of these 8 cases (38.9%) also showed c-myc protein expression. All seborrheic keratoses and squamous cell carcinoma(SCC) were negative for bcl-2 proteins. 12 of 15 SCCs(80%) were positive for c-myc protein. In conclusion, bcl-2 and c-myc proteins were coexpressed in BCCs, nevi, and MMs. Coexpression of bcl-2 and c-myc proteins in these tumors was statistically significant(p<0.01), while no considerable differences of bcl-2 and c-myc expression were found between nevi and MMs. These results suggests that bcl-2 may cooperate with c-myc to promote tumorigenesis of BCCs, nevi, and MMs(p<0.01).

The Effects of Cyclosporine A on Minimal Change Nephrosis and Focal Segmental Glomerulosclerosis Induced by Administration of Puromycin Aminonucleoside in Rats.: Sun Hee Sung; Korean J Pathol. 1996;30(11):981-997.

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Abstract PDF: Cyclosporine A(CsA) is known as a potent immunosupressive agent, and recently its supressive effects of proteinuria in minimal change nephrotic syndrome, and other glomerular diseases have been demonstrated. But the mechanism of supression of proteinuria is not clear. This study aimed to investigate the mechanism of supression of proteinuria in puromycin aminonucleoside (PAN) induced minimal change nephrosis(MCN), by a single dose of PAN, and focal segmental glomerulosclerosis(FSG) by long term repeated administration of PAN with unilateral nephrectomy in Sprague-Dawley rats, using transmission electron microscopy. We also analysed the effects of CsA on the histopathologic changes such as glomerular sclerosis, and subtypes of infiltrated mononuclear cells in glomeruli and renal interstitium. The results are as follows: Marked proteinuria was developed in MCN and FSG groups. It was significantly reduced by administration of CsA. BUN and creatinine were significantly increased in FSG with the administration of CsA, compared with FSG without CsA. On ultrastructural examination, MCN group showed effacement of foot processes, and microvillous transformation. Occasional focal detatchment of podocytes from the GBM, vacuolar degeneration, and electron dense droplets in the podocytes were also seen. The latter findings were remarkably reduced by CsA. The Above ultrastructural findings, seen in the MCN group, were more severe in the FSG groups. On comparison of ultrastructural fingings of FSG with or without CsA groups, severe vacuolar degeneration, abundant electron dense granules, and focal detatchment of foot processes were more frequently seen in FSG groups and they were significantly reduced by CsA. But irregularity and thickening of GBM were deepend in FSG with CsA group. There were no significant differences of glomerular sclerosis, adhesion to the Bowman's capsules in both the MCN and the FSG groups by administration of CsA. Foamy degeneration of endothelial and mesangial cells, epithelial proliferation, hyalinosis and mononuclear infiltration were significantly reduced by CsA in FSG groups. Microcalcification was commonly seen in CsA administrated groups. The main sutype of infiltrated mononuclear cells in glomeruli and interstitium were monocytes in FSG groups. The proportion of T cells were higher in interstitium by disease progression and it was significantly decreased by CsA. On conclusion the most important ultrastructural changes, regarded as the main mechanism of supression of proteinuria is that the CsA stabilize the podocytes, by preventing vacuolar degeneration and focal detatchment. But CsA does not influence the progression of glomerular sclerosis in PAN induced nephrosis.

Microsatellite Instability and the Expression of Tumor-associated Genes in Multiple Cancer.: Kyung Soo Kim, Chan Choi, Chang Soo Park, Sang Woo Juhng; Korean J Pathol. 1997;31(7):617-627.

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Abstract PDF: Genetic changes associated with oncogenes or tumor suppressor genes are frequently observed in human cancers. These changes may be more frequent in multiple primary cancers than sporadic cancers. These experiments were designed in order to know the genetic changes using microsatellite PCR technique and the expression of tumor-associated genes by immunohistochemistry for c-myc and p53 in 17 cases of multiple primary carcinomas. The niicrosatellite instability (MSI) were found in 8 of 17 cases (47.1 %); six cases showed MSI in more than two microsatellite loci and two cases revealed MSI in one locus. MSI was found in 2 out of 7.patients (28.6%) of multiple primary carcinomas arising from the unrelated organs, and 6 out of 10 patients (60.0%) arising from the same or related organs. When each case of multiple primary carcinomas was examined, immunohistochemistry for c-myc was positive in 25 cases (71.4%) and p53 was positive in 21 cases (60.0%) out of 35 cases. But there was no correlation between MSI and expression of tumor-associated genes. From the above the results, MSI is more important in carcinogenesis of multiple primary carcinomas arising from the same or related organs than those from unrelated organs.

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