Journal of Pathology and Translational Medicine

Original Article

Tumor-infiltrating T lymphocytes evaluated using digital image analysis predict the prognosis of patients with diffuse large B-cell lymphoma: Yunjoo Cho, Jiyeon Lee, Bogyeong Han, Sang Eun Yoon, Seok Jin Kim, Won Seog Kim, Junhun Cho; J Pathol Transl Med. 2024;58(1):12-21. Published online January 10, 2024; DOI: https://doi.org/10.4132/jptm.2023.11.02

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Abstract PDF: Background
The implication of the presence of tumor-infiltrating T lymphocytes (TIL-T) in diffuse large B-cell lymphoma (DLBCL) is yet to be elucidated. We aimed to investigate the effect of TIL-T levels on the prognosis of patients with DLBCL.
Methods
Ninety-six patients with DLBCL were enrolled in the study. The TIL-T ratio was measured using QuPath, a digital pathology software package. The TIL-T ratio was investigated in three foci (highest, intermediate, and lowest) for each case, resulting in TIL-T–Max, TIL-T–Intermediate, and TIL-T–Min. The relationship between the TIL-T ratios and prognosis was investigated.
Results
When 19% was used as the cutoff value for TIL-T–Max, 72 (75.0%) and 24 (25.0%) patients had high and low TIL-T–Max, respectively. A high TIL-T–Max was significantly associated with lower serum lactate dehydrogenase levels (p < .001), with patient group who achieved complete remission after RCHOP therapy (p < .001), and a low-risk revised International Prognostic Index score (p < .001). Univariate analysis showed that patients with a low TIL-T–Max had a significantly worse prognosis in overall survival compared to those with a high TIL-T–Max (p < .001); this difference remained significant in a multivariate analysis with Cox proportional hazards (hazard ratio, 7.55; 95% confidence interval, 2.54 to 22.42; p < .001).
Conclusions
Patients with DLBCL with a high TIL-T–Max showed significantly better prognosis than those with a low TIL-T–Max, and the TIL-T–Max was an independent indicator of overall survival. These results suggest that evaluating TIL-T ratios using a digital pathology system is useful in predicting the prognosis of patients with DLBCL.

Case Studies

Adenocarcinoma of the minor salivary gland with concurrent MAML2 and EWSR1 alterations: Sangjoon Choi, Junhun Cho, Seung Eun Lee, Chung-Hwan Baek, Yi-Kyung Kim, Hyung-Jin Kim, Young Hyeh Ko; J Pathol Transl Med. 2021;55(2):132-138. Published online January 22, 2021; DOI: https://doi.org/10.4132/jptm.2020.12.11

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Salivary gland tumors are histologically diverse, and each entity has distinctive histopathological and molecular features. We report two cases of salivary gland tumors with unique histological and molecular findings, which have not been documented previously. The tumors were located in the base of the tongue in both patients. Most tumor cells were arranged in cords and nests, giving a trabecularlike appearance. Focally, glandular structures with intraluminal mucin and perivascular pseudorosette-like configurations were identified. Tumor cells had eosinophilic to clear cytoplasm, and showed mild nuclear atypia. They were positive for pancytokeratin and negative for S-100, p63, c-KIT, androgen receptor, and neuroendocrine markers. Multiple foci of capsular or lymphovascular invasion were identified, but the Ki-67 labeling index was low (< 5%). Fluorescence in situ hybridization revealed concurrent alterations of MAML2 and EWSR1 gene. Further investigations with a larger number of cases with similar histological and molecular features will accurately classify this tumor.

Citations

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Salivary Gland Neoplasms With a Unique Trabecular Histology and MAML2 Translocation
Bokyung Ahn, Seung-Ho Choi, Doeun Kim, Deokhoon Kim, Kyung-Ja Cho
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Hyun Hee Koh, Eunhyang Park, Hyun-Soo Kim
Diagnostics.2022; 12(2): 326. CrossRef
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Kanwalpreet Kaur, Shailee Mehta, Sangita Vanik, Priti Trivedi, Nirmalya Banerjee, Harsh Dhar, Sourav Datta, Subhadeep Karanjai
European Archives of Oto-Rhino-Laryngology.2022; 279(8): 3769. CrossRef
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Yurimi Lee, Kiyong Na, Ha Young Woo, Hyun-Soo Kim
Diagnostics.2022; 12(5): 1102. CrossRef
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Jihee Sohn, Yurimi Lee, Hyun-Soo Kim
Diagnostics.2022; 12(10): 2339. CrossRef
Mesonephric-like Differentiation of Endometrial Endometrioid Carcinoma: Clinicopathological and Molecular Characteristics Distinct from Those of Uterine Mesonephric-like Adenocarcinoma
Sujin Park, Go Eun Bae, Jiyoung Kim, Hyun-Soo Kim
Diagnostics.2021; 11(8): 1450. CrossRef
Mesonephric-like Adenocarcinoma of the Uterine Corpus: Comprehensive Immunohistochemical Analyses Using Markers for Mesonephric, Endometrioid and Serous Tumors
Hyunjin Kim, Kiyong Na, Go Eun Bae, Hyun-Soo Kim
Diagnostics.2021; 11(11): 2042. CrossRef

Congenital Peribronchial Myofibroblastic Tumor: A Case Study and Literature Review: Yuil Kim, Ha Young Park, Junhun Cho, Joungho Han, Eun Yoon Cho; Korean J Pathol. 2013;47(2):172-176. Published online April 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.172

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Abstract PDF

Congenital peribronchial myofibroblastic tumor (CPMT) is a benign pulmonary spindle cell neoplasm of intrauterine and perinatal period, which is thought to arise from primitive peribronchial mesenchyme. We present a case detected incidentally in a one-month-old infant. The solid and partially necrotic tumor involved the right middle and lower lobes of the lung with extension to the diaphragm. Histologically, the tumor was composed of fasciculated monotonous spindle cells, proliferating peribronchiolar cartilage and round cells with rich vasculature, and high mitotic activity was identified in the round cell area. Immunohistochemical and electron microscopic studies showed that the spindle cells were myofibroblastic in phenotype. Although the tumor showed several malignant pathological features, recurrence was not observed in the two-year follow-up period, consistent with the benign clinical behavior of CPMT.

Citations

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Congenital peribronchial myofibroblastic tumor (CPMT): a case report with long term follow-up and next-generation sequencing (NGS)
Ping Zhou, Shuang Li, Weiya Wang, Yuan Tang, Lili Jiang
BMC Pediatrics.2023;[Epub] CrossRef
Neonatal congenital lung tumors — the importance of mid-second-trimester ultrasound as a diagnostic clue
Stephan L. Waelti, Laurent Garel, Dorothée Dal Soglio, Françoise Rypens, Michael Messerli, Josée Dubois
Pediatric Radiology.2017; 47(13): 1766. CrossRef
Congenital peribronchial myofibroblastic tumor: Case report and review of literature
Jolanta Jedrzkiewicz, Eric Scaife, Bo Hong, Sarah South, Mouied Alashari
Journal of Pediatric Surgery Case Reports.2015; 3(4): 154. CrossRef
Perinatal Thoracic Mass Lesions: Pre- and Postnatal Imaging
Evan J. Zucker, Monica Epelman, Beverley Newman
Seminars in Ultrasound, CT and MRI.2015; 36(6): 501. CrossRef
Prenatal imaging and immunohistochemical analysis of congenital peribronchial myofibroblastic tumor
Y.‐A. Tu, W.‐C. Lin, H.‐J. Chen, J.‐C. Shih
Ultrasound in Obstetrics & Gynecology.2015; 46(2): 247. CrossRef
A Congenital Peribronchial Myofibroblastic Tumor Detected in a Premature Infant at 28 Weeks but That Resolved in the Late Stage of Pregnancy
Bo Xia, Gang Yu, Chun Hong, Lei Zhang, Jing Tang, Cuifen Liu
Medicine.2015; 94(42): e1842. CrossRef
Congenital peribronchial myofibroblastic tumor
Yuka Hotokebuchi, Kenichi Kohashi, Satoshi Toyoshima, Naoko Matsumoto, Toshinori Nakashima, Yoshinao Oda
Pathology International.2014; 64(4): 189. CrossRef

Silent Colonic Malakoplakia in a Living-Donor Kidney Transplant Recipient Diagnosed during Annual Medical Examination: Go Eun Bae, Nara Yoon, Ha Young Park, Sang Yun Ha, Junhun Cho, Yunkyung Lee, Kyoung-Mee Kim, Cheol Keun Park; Korean J Pathol. 2013;47(2):163-166. Published online April 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.163

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Abstract PDF

Malakoplakia is a characteristic inflammatory condition, which is usually seen in the urogenital tract, and less frequently in the gastrointestinal tract. We present a case of colonic malakoplakia in an immunocompromised patient. A 55-year-old female visited the outpatient clinic for routine cancer surveillance. Her past medical history was significant for kidney transplantation 11 years ago, and she had been taking immunosuppressants. A colonoscopy revealed several depressed flat lesions and elevated polyps, which were 0.3 to 0.4 cm in size and accompanied by whitish exudates. A biopsy revealed an infiltration of histiocytes with ample granular eosinophilic cytoplasm, with some lymphocytes and plasma cells. Many histiocytes had the characteristic morphology, described as Michaelis-Gutmann bodies: one or several round basophilic structures of approximately 1 to 10 µm in size with some being laminated, some appearing homogeneous, and others having a dense central core with a targetoid appearance. These Michaelis-Gutmann bodies were positively stained on von Kossa stain, and were diagnostic for malakoplakia.

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Caecal malakoplakia: a rare mimic of malignancy
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John Fredy Nieto‐Ríos, Isabel Ramírez, Mónica Zuluaga‐Quintero, Lina María Serna‐Higuita, Federico Gaviria‐Gil, Alejandro Velez‐Hoyos
Transplant Infectious Disease.2017;[Epub] CrossRef
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Journal of Korean Medical Science.2015; 30(1): 110. CrossRef

Original Articles

Methylation and Immunoexpression of p16^INK4a Tumor Suppressor Gene in Primary Breast Cancer Tissue and Their Quantitative p16^INK4a Hypermethylation in Plasma by Real-Time PCR: Jae Jun Lee, Eunkyung Ko, Junhun Cho, Ha Young Park, Jeong Eon Lee, Seok Jin Nam, Duk-Hwan Kim, Eun Yoon Cho; Korean J Pathol. 2012;46(6):554-561. Published online December 26, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.554

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Abstract PDF

Background

The p16^INK4a gene methylation has been reported to be a major tumorigenic mechanism.

Methods

We evaluated the methylation status of the p16^INK4a genes in 231 invasive breast cancer and 90 intraductal carcinoma specimens using a methylation-specific polymerase chain reaction and p16 protein expression using immunohistochemistry. The quantity of cell-free methylated p16^INK4a DNA in the plasma samples of 200 patients with invasive breast cancer was also examined using a fluorescence-based real-time polymerase chain reaction assay.

Results

The frequencies of p16^INK4a methylation in invasive and intraductal tumors were 52.8% (122/231) and 57.8% (52/90), respectively. The p16 protein was overexpressed in 145 of the 231 invasive carcinomas (62.8%) and 63 of the 90 intraductal carcinomas (70%). High p16 expression in invasive carcinomas correlated significantly with a high histologic grade, a negative estrogen receptor and progesterone receptor status, p53 immunoreactivity and high Ki-67 expression with immunohistochemistry. In addition, the methylation index of p16^INK4a was significantly higher in the cancer patients than the normal controls (p<0.001).

Conclusions

High p16 immunoreactivity correlated with a loss of differentiation in breast carcinomas and high frequency of p16^INK4a promoter methylation in both invasive and intraductal carcinomas, suggesting it may be involved in the pathogenesis of breast cancer.

Citations

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Mechanisms of resistance to estrogen receptor modulators in ER+/HER2− advanced breast cancer
Jin Zhang, Qianying Wang, Qing Wang, Jiangran Cao, Jiafu Sun, Zhengmao Zhu
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Aberrantly Methylated cfDNA in Body Fluids as a Promising Diagnostic Tool for Early Detection of Breast Cancer
Igor Stastny, Pavol Zubor, Karol Kajo, Peter Kubatka, Olga Golubnitschaja, Zuzana Dankova
Clinical Breast Cancer.2020; 20(6): e711. CrossRef
Epigenetic modulation of BRCA‐1 and MGMT genes, and histones H4 and H3 are associated with breast tumors
Parisa Paydar, Gholamreza Asadikaram, Hamid Zeynali Nejad, Hamed Akbari, Moslem Abolhassani, Vahid Moazed, Mohammad Hadi Nematollahi, Ghasem Ebrahimi, Hossein Fallah
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The 9p21 locus: A potential therapeutic target and prognostic marker in breast cancer
Mahdi Rivandi, Mohammad‐Sadegh Khorrami, Hamid Fiuji, Soodabeh Shahidsales, Malihe Hasanzadeh, Mir Hadi Jazayeri, Seyed Mahdi Hassanian, Gordon A. Ferns, Nafiseh Saghafi, Amir Avan
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p16INK4a overexpression as a predictor of survival in ocular surface squamous neoplasia
Sheetal Chauhan, Seema Sen, Anjana Sharma, Seema Kashyap, Radhika Tandon, Mandeep S Bajaj, Neelam Pushker, Murugesan Vanathi, Shyam S Chauhan
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Diagnostic Value of MDM2 and DDIT3 Fluorescence In Situ Hybridization in Liposarcoma Classification: A Single-Institution Experience: Junhun Cho, Seung Eun Lee, Yoon-La Choi; Korean J Pathol. 2012;46(2):115-122. Published online April 25, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.2.115

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Abstract PDF

Background

The amplification of murine double minutes (MDM2) is the primary feature of well-differentiated liposarcomas (WDLPS) and dedifferentiated liposarcomas (DDLPS), while DDIT3 rearrangement is the main one of myxoid liposarcomas (MLPS). Our aim was to evaluate the added value of MDM2 amplification and DDIT3 rearrangement in making a diagnosis and classifying lipogenic tumors.

Methods

Eighty-two cases of liposarcoma and 60 lipomas diagnosed between 1995 and 2010 were analysed for MDM2 amplification and DDIT3 rearrangement using a fluorescence in situ hybridization (FISH). The subtypes of liposarcoma were reclassified according to the molecular results, whose results were reviewed with an analysis of the relevant histologic and immunohistochemical findings.

Results

One case of lipoma (1.67%) was reclassified as a WDLPS. Of the liposarcomas, 13.4% (16/82) were reclassified after the molecular testing. Five cases of MLPS were reclassified as four cases of DDLPS and one case of myxoid lipoma. Two cases of WDLPS were reclassified as one case of spindle cell lipoma and another case of myxofibrosarcoma. Four cases of DDLPS were reclassified as two cases of leiomyosarcoma, one case of angiomyolipoma and another case of fibroinflammatory lesion. Of the six cases of pleomorphic liposarcoma, five were reclassified as DDLPS.

Conclusions

In our series, a critical revision of diagnosis was found at a rate of 3.5% (5/142) after a review of the lipomatous lesions. The uses of molecular testing by MDM2 and DDIT3 FISH were valuable to make an accurate subtyping of liposarcomas as well as to differentiate WDLPS from benign lipomatous tumor.

Citations

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Myxoid liposarcoma with nuclear pleomorphism: a clinicopathological and molecular study
Naoki Kojima, Takashi Kubo, Taisuke Mori, Kaishi Satomi, Yuko Matsushita, Shintaro Iwata, Yasushi Yatabe, Koichi Ichimura, Akira Kawai, Hitoshi Ichikawa, Akihiko Yoshida
Virchows Archiv.2024; 484(1): 71. CrossRef
FISH Diagnostic Assessment of MDM2 Amplification in Liposarcoma: Potential Pitfalls and Troubleshooting Recommendations
Alessandro Gambella, Luca Bertero, Milena Rondón-Lagos, Ludovica Verdun Di Cantogno, Nelson Rangel, Chiara Pitino, Alessia Andrea Ricci, Luca Mangherini, Isabella Castellano, Paola Cassoni
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Expression of CTAG1B clone EPR13780 versus DDIT3 gene rearrangement distinguishes myxoid liposarcoma from its mimics with detection of novel DDIT3 gene copy number variations
Marwa M. Abdelaziz, Hanan Y. Tayel, Amany Abdel-Bary, Omnia M. Badawy
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Min Jeong Song, Kyung-Ja Cho, Jong-Seok Lee, Joon Seon Song
Applied Immunohistochemistry & Molecular Morphology.2017; 25(10): 712. CrossRef
FluorescenceIn SituHybridization forMDM2Amplification as a Routine Ancillary Diagnostic Tool for Suspected Well-Differentiated and Dedifferentiated Liposarcomas: Experience at a Tertiary Center
Khin Thway, Jayson Wang, John Swansbury, Toon Min, Cyril Fisher
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