Journal of Pathology and Translational Medicine

Case Study

A case of concomitant EGFR/ALK alteration against a mutated EGFR background in early-stage lung adenocarcinoma: Ki-Chang Lee, Jiwon Koh, Doo Hyun Chung, Yoon Kyung Jeon; J Pathol Transl Med. 2021;55(2):139-144. Published online January 22, 2021; DOI: https://doi.org/10.4132/jptm.2020.12.16

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Rare cases of lung adenocarcinoma (LUAD) with concomitant epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) translocation have been reported. However, their clonal and evolutional relationship remains unclear. We report a case of early-stage EGFR-mutated LUAD with a focal concomitant EGFR/ALK alteration. A 63-year-old male underwent lobectomy to remove a 1.9-cm-sized lung nodule, which was diagnosed with EGFR-mutated LUAD. ALK immunohistochemistry (IHC) showed focal positivity within the part of the tumor characterized by lepidic pattern, also confirmed by fluorescence in-situ hybridization (FISH). Targeted next-generation sequencing was performed separately on the ALK IHC/FISH-positive and -negative areas. EGFR L833V/L858R mutations were detected in both areas, whereas EML4 (echinoderm microtubule-associated protein-like 4)-ALK translocations was confirmed only in the ALK IHC/FISH-positive area, suggesting the divergence of an EGFR/ALK co-altered subclone from the original EGFR-mutant clone. Our study suggests that concurrent alterations of EGFR and ALK can arise via divergent tumor evolution, even in the relatively early phases of tumorigenesis.

Citations

Citations to this article as recorded by

Identification and validation of molecular subtype and prognostic signature for lung adenocarcinoma based on neutrophil extracellular traps
Yanhua Zuo, Guangyi Leng, Ping Leng
Pathology and Oncology Research.2023;[Epub] CrossRef
Machine Learning-Based Integration Develops a Macrophage-Related Index for Predicting Prognosis and Immunotherapy Response in Lung Adenocarcinoma
Zuwei Li, Minzhang Guo, Wanli Lin, Peiyuan Huang
Archives of Medical Research.2023; 54(7): 102897. CrossRef
Big data analysis identified a telomere-related signature predicting the prognosis and drug sensitivity in lung adenocarcinoma
Weiyi Zhang
Medicine.2023; 102(46): e35526. CrossRef

Original Articles

Carcinoma in situ of the urinary bladder in bladder washing cytology.: Doo Hyun Chung, In Ae Park, Eui Keun Ham; Korean J Cytopathol. 1991;2(1):51-55.

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Abstract PDF: The diagnosis of carcinoma in situ of urinary bladder is difficult in that the symptoms and cystoscopic findings are nonspecific. The cytology of urine could be helpful for diagnosis of carcinoma in situ of urinary bladder. We present a case of bladder washing cytology of carcinoma in situ. A 54 year old man presented with dysuria for 1 year. Cystoscopic findings revealed multifocal reddish trabeculated lesions. The bladder washing cytology revealed rather uniform tumor cells which were singly scattered or forming syncytium in the clean background. The nuclei were round to oval with inconspicious nucleoli. The cystoscopic biopsy revealed typical histologic features of carcinoma in situ of urinary bladder.

Differential Expression of Glut1 in Pulmonary Neuroendocrine Tumors: Correlation with Histological Grade.: Hyun Ju Lee, Seol Bong Yoo, Won Woo Lee, Doo Hyun Chung, Jeong Wook Seo, Jin Haeng Chung; Korean J Pathol. 2009;43(3):201-205.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.3.201

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Abstract PDF

BACKGROUND
Increased glucose uptake, a process that is mediated by glucose transporter (Glut1) proteins, is an important metabolic feature in a variety of cancer cells. The overexpression of Glut1 in human cancers is known to be related to a variety of histopathological parameters, including histological grade, proliferation rate, and lymphatic invasion. The principal objective of this study was to evaluate Glut1 expression in the spectrum of pulmonary neuroendocrine (NE) tumors including typical carcinoid tumor (TC), atypical carcinoid tumor (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell carcinoma (SCC), and to characterize the relationship between Glut1 expression and the histologic grade of NE tumors.
METHODS
19 TC, 7 AC, 13 LCNEC, and 6 SCC patients were included in this study. The percentages of Glut1-positive tumor cells in these patients were determined. For statistical analysis, Glut1 expression was subdivided into a Glut1-low expression group (0-30%) and a Glut1-high expression group (31-90%).
RESULTS
In our subgroup analyses, the histological grade of pulmonary neuroendocrine (NE) tumors was significantly correlated with Glut1 expression; TC (n=19, 3.6+/-4.2%), AC (n=7, 20.0+/-4.9%), LCNEC (n=13, 60.0+/-21.1%), and SCC (n=6, 74.2+/-16.9%). Glut1-high expression was significantly associated with high-grade NE tumors such as LCNEC and SCC (n=19, 62.6+/-21.0%) (p=0.000).
CONCLUSIONS
The results of this study appear to indicate that Glut1 overexpression is a consistent feature of high-grade NE lung tumors.

Citations

Citations to this article as recorded by

GLUT1: A novel tool reflecting proliferative activity of lung neuroendocrine tumors?
Nazim Benzerdjeb, Pascal Berna, Henri Sevestre
Pathology International.2017; 67(1): 32. CrossRef
Oncocytic carcinoid tumor of the lung with intense F-18 fluorodeoxyglucose (FDG) uptake in positron emission tomography–computed tomography (PET/CT)
Yuki Tanabe, Yoshifumi Sugawara, Rieko Nishimura, Kohei Hosokawa, Makoto Kajihara, Teruhiko Shimizu, Tadaaki Takahashi, Shinya Sakai, Shigeki Sawada, Motohiro Yamashita, Haruhiko Ohtani
Annals of Nuclear Medicine.2013; 27(8): 781. CrossRef

The Increased Expression and Diagnostic Usefulness of CD56 Antigen in Paraffin Embedded Plasma Cell Neoplasm.: Seok Hyung Kim, Chan Sik Park, Eun Young Choi, Hyun Wook Kang, Seong Hoe Park, Doo Hyun Chung; Korean J Pathol. 2001;35(3):201-205.

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Abstract PDF: BACKGROUND
The natural killer cell antigen CD56 (NCAM) is a member of the immunoglobulin superfamily and is expressed on neurons, astrocytes, and Schwann cells. Recently, it has been reported that CD56 expression is detected on plasma cells of multiple myeloma by flow cytometry.
METHOD
In this study, to test the diagnostic usefulness of the anti-CD56 antibody for plasma cell neoplasm on paraffin-embedded materials, we performed immunohistochemical staining of samples from 19 patients with plasma cell neoplasms. These cases included 14 cases of multiple myeloma, 3 cases of solitary plasmacytoma of the bone, and two cases of extramedullary plasmacytoma.
RESULTS
The neoplastic plasma cells from 68 % of the patients with plasma cell neoplasms expressed CD56 highly. CD56 was expressed in all three cases of solitary plasmacytoma of the bone and one of two extramedullary plasmacytoma, and nine out of 14 multiple myeloma cases. In contrast, reactive plasma cells from the 18 patients with miscellaneous lesions were completely negative for CD56.
CONCLUSIONS
CD56 is aberrantly expressed on the neoplastic plasma cells, and it may be used as a useful marker for the diagnosis of plasma cell neoplasms in paraffin-embedded tissues.

Case Report

Bronchoalveolar Lavage (BAL) Cytology and Ultrastructural Findings in a Patient with Amiodarone-Induced Pulmonary Toxicity: A Case Report.: Sun Lee, Min A Kim, Young Soo Shim, Chun Taek Lee, Je G Chi, Doo Hyun Chung; Korean J Pathol. 2002;36(3):175-178.

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Abstract PDF: Amiodarone is a potent antiarrhythmic agent and can cause potentially life-threatening pulmonary fibrosis. Of the numerous side effects associated with amiodarone therapy, lugn toxicity is one of the most serious adverse reactions. Recently, we experienced a case of amiodarone-induced pulmonary toxicity (APT), which induced severe dyspnea and productive coughing, confirmed by cytologic and electron microscopic examination of the bronchoalveolar lavage (BAL). The symptoms and abnormalities in the chest X-ray were improved after the withdrawal of amiodarone. Cytologic examination of the BAL revealed numerous foam cells with cytoplasmic vacuoles or small particles. Ultrastructurally, the foam cells demonstrated characteristic lysosomal inclusions, which were electron-dense multilamellated bodies, crystalloid bodies, and mixed forms with small lipid vacuoles. It is strongly suggested that only cytologic and electron microscopic examination of the BAL without open lung biopsy is enough for diagnosis of APT, when APT is clinically suspected in a patient who has a history or ingestation of amiodarone.

Original Articles

Immunohistochemical Analysis of Insular Carcinoma of the Thyroid Gland.: Hye Sook Min, Jin Ho Paik, Kyoung Bun Lee, Seong Hoe Park, Doo Hyun Chung; Korean J Pathol. 2005;39(5):326-331.

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Abstract PDF: BACKGROUND
Insular thyroid carcinoma (ITC) is a relatively infrequent thyroid carcinoma that has distinctive histologic features. ITC shows an aggressive clinical course and the predominant presence of an insular component, which has been reported to be an independent factor of a poor prognosis. We retrospectively examined clinical details of the nine ITC patients, which represented 9 years of experience with ITC, and investigated the expressions of variable neuroendocrine and other immunohistochemical markers associated with well-differentiated thyroid carcinomas.
METHODS
We adopted an immunohistochemical approach and studied the expressions of synaptophysin, chromogranin A, CD56, NSE, S-100, RET, PPARgamma, calcitonin, galectin-3, and thyroglobulin in formalin-fixed, paraffin embedded tissue array slides of the 9 ITC patients, and investigated clinical features. Seven cases of follicular carcinoma and 4 cases of medullary carcinoma were also included as controls.
RESULTS
ITCs were positive for synaptophysin (44%, 4/9), CD56 (11%, 1/9), NSE (89%, 8/9), S100 (67%, 6/9), calcitonin (22%, 2/9), galectin-3 (78%, 7/9), and thyroglobulin (100%, 9/9), but completely negative for chromogranin A, RET, and PPARgamma.
CONCLUSION
ITCs express neuroendocrine markers in variable proportions and appear not to be associated with the oncoproteins of conventional thyroid carcinomas. Notably, its differential diagnosis from medullary carcinoma is required in cases showing focal calcitonin positivity.

Ovarian mature cystic teratoma with histologic features of chronic thyroiditis: Histologic analysis of 4 cases.: Doo Hyun Chung, Weon Seo Park, Soo Min Kang, Eun Sil Yu, Seong Hoe Park; Korean J Pathol. 1992;26(3):209-214.

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Abstract PDF: We have reviewed ovarian mature cystic teratomas with features of chronic thyroiditis that were diagnosed at the department of pathology, Seoul National University Hospital during 7 years, 1984-1991. Twenty three case(8%) containing thyroid tissue among 285 ovarian mature teratomas were available for histopathologic examination. Among these, 4 cases(1.4%) showed lymphocytic infiltration with lymphoid follicle formation. These four cases were examined according to the strict histologic criteria of autoimmune thyroiditis and reactive non-autoimmune thyroiditis for the purpose of differentiation of pathogenesis. Two cases were similar to autoimmune in nature and the other two cases simply seemed to reflect reactive features to adjacent stimulating elements. In conclusion, thyroid tissue present in ovarian cystic teratoma may have histologic features of chronic thyroiditis of either autoimmune or non-autoimmune origin.

Epithelial-Myoepithelial Carcinoma of Intercalated Duct of Parotid Gland.: Soong Deok Lee, Doo Hyun Chung, Sung Hye Park, Chul Woo Kim, Je G Chi; Korean J Pathol. 1992;26(1):76-81.

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Abstract PDF: Epithelial-myoepithelial carcinoma of intercalated duct(origin) is a recently described tumor characterized by its typical biphasic pattern of central duct like cell and peripheral clear cell. We described a case of epithelial-myoepithelial carcinoma in a 10-year-old boy. Microscopically, the tumor showed typical biphasic pattern, diffuse proliferation of clear cells and linining epithelial cells of tubular structures. Immunohistochemically, the clear cell showed positive reaction to S-100 protein, and the epithelial cells expressed cytokeratin indicating myoepithelial and epithelial differentiation respectively. Biphasic differentiation of the tumor cells could be also proved by electronmicroscopic study.

Case Report

Brain Stem Glioma (An autopsy case).: Doo Hyun Chung, Soong Deok Lee, Hee Jin Yang, Dae Hee Han, Je G Chi; Korean J Pathol. 1991;25(6):607-610.

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Abstract PDF: We report an autopsy case of the brain stem glioma that extended extensively in the brain stem itself and cephalad. This 18-year-old boy first presented with dizziness, vomiting and left side weakness with left facial palsy. Brain MRI revealed a diffusely infiltrative tumor involving whole medulla, pons and lower midbrain. A total of 4000 R was given with some alleviation of respiratory difficulty. He died one year after the onset. Autopsy revealed the tumor involving pons, a portion of medulla oblongata, and cerebellum. The tumor showed diffusely infiltrative pattern and extended along the periventricular area to the thalamus and corpus callosum. The cut surface was grayish white and solid. It also showed areas of myxoid degeneration and necrosis probably related to radiation therapy. Microscopically the tumor was a cellular and pleomorphic glioma that showed some astrocytic differentiation. It was diffuse without geographic necrosis.

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