Journal of Pathology and Translational Medicine

Case Studies

A Rare Case of Adenosquamous Carcinoma Arising in the Background of IgG4-Related Lung Disease: Sangjoon Choi, Sujin Park, Man Pyo Chung, Tae Sung Kim, Jong Ho Cho, Joungho Han; J Pathol Transl Med. 2019;53(3):188-191. Published online March 11, 2019; DOI: https://doi.org/10.4132/jptm.2019.02.21

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IgG4-related disease is a systemic inflammatory disease and is known as IgG4-related lung disease (IgG4-RLD) when it involves the respiratory system. Primary lung cancer arising from a background of IgG4-RLD is very rare. Herein, we report a case of adenosquamous carcinoma arising from the background of IgG4-RLD and presenting as an interstitial lung disease pattern. A 66-year-old man underwent lobectomy under the impression of primary lung cancer. Grossly, the mass was ill-defined and gray-tan colored, and the background lung was fibrotic. Microscopically, tumor cells showed both squamous and glandular differentiation. Dense lymphoplasmacytic infiltration with fibrosis and obliterative phlebitis were seen in the background lung. IgG4 immunohistochemical stain showed diffuse positivity in infiltrating plasma cells. Primary lung adenosquamous carcinoma has not been reported in a background of IgG4-RLD. Due to the rarity of IgG4-RLD, physicians must follow patients with IgG4-RLD over long periods of time to accurately predict the risk of lung cancer.

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Endometrioid Carcinomas of the Ovaries and Endometrium Involving Endocervical Polyps: Comprehensive Clinicopathological Analyses
Jihee Sohn, Yurimi Lee, Hyun-Soo Kim
Diagnostics.2022; 12(10): 2339. CrossRef
A Case of IgG4-related Disease Composed of a Paravertebral Tumor Alone with Multiple Lung Cancers
Mutsumi Ozasa, Toyomitsu Sawai, Yosuke Harada, Sumako Yoshioka, Nobuko Matsuo, Hiroshi Mukae
Haigan.2021; 61(3): 213. CrossRef
Serous Carcinoma of the Endometrium with Mesonephric-Like Differentiation Initially Misdiagnosed as Uterine Mesonephric-Like Adenocarcinoma: A Case Report with Emphasis on the Immunostaining and the Identification of Splice Site TP53 Mutation
Sangjoon Choi, Yoon Yang Jung, Hyun-Soo Kim
Diagnostics.2021; 11(4): 717. CrossRef
A Case of IgG4-related Thyroiditis Diagnosed by Total Thyroidectomy
Daiki Sakamoto, Masao Yagi, Hiroshi Iwai
Practica Oto-Rhino-Laryngologica.2021; 114(7): 547. 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
Not Cancer After All: Two Rare Cases of IgG4-Related Lung Disease
Josué Pinto, Carla Damas, António Morais
Archivos de Bronconeumología.2020; 56(1): 53. CrossRef
Not Cancer After All: Two Rare Cases of IgG4-Related Lung Disease
Josuèc) Pinto, Carla Damas, António Morais
Archivos de Bronconeumología (English Edition).2020; 56(1): 52. CrossRef
Axillary lymphadenopathy with IgG4 positive plasma cell infiltration as differential diagnosis of metastatic lung adenocarcinoma
Yutaro Ito, Masanori Harada, Namio Kagoo, Tsutomu Kubota, Koshiro Ichijyo, Eisuke Mochizuki, Masahiro Uehara, Shun Matsuura, Masaru Tsukui, Naoki Koshimizu
Respiratory Medicine Case Reports.2020; 31: 101196. CrossRef

Abrupt Dyskeratotic and Squamoid Cells in Poorly Differentiated Carcinoma: Case Study of Two Thoracic NUT Midline Carcinomas with Cytohistologic Correlation: Taebum Lee, Sangjoon Choi, Joungho Han, Yoon-La Choi, Kyungjong Lee; J Pathol Transl Med. 2018;52(5):349-353. Published online July 27, 2018; DOI: https://doi.org/10.4132/jptm.2018.07.16

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Abstract PDF

Cytologic diagnosis of nuclear protein in testis (NUT) midline carcinoma (NMC) is important due to its aggressive behavior and miserable prognosis. Early diagnosis of NMC can facilitate proper management, and here we report two rare cases of thoracic NMC with cytohistologic correlation. In aspiration cytology, the tumor presented with mixed cohesive clusters and dispersed single cells, diffuse background necrosis and many neutrophils. Most of the tumor cells had scanty cytoplasm and medium-sized irregular nuclei, which had fine to granular nuclear chromatin. Interestingly, a few dyskeratotic cells or squamoid cell clusters were present in each case. Biopsy specimen histology revealed more frequent squamous differentiation, and additional immunohistochemistry tests showed nuclear expression of NUT. Because this tumor has a notorious progression and has been previously underestimated in terms of its prevalence, awareness of characteristic findings and proper ancillary tests should be considered in all suspicious cases.

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Diagnostic significance and cytological features of NUT carcinoma by EBUS‐FNA, a case report and literature review
Yaping Ju, Miriam Velazquez, Andy Sherrod, Tiannan Wang
Cytopathology.2024; 35(4): 497. CrossRef
Exploring cytologic features and potential diagnostic challenges of metastatic NUT carcinoma to the parotid gland: A case report and a comprehensive literature review
Crystal Y. Li, Salih Salihoglu, Francisco J. Civantos, Jaylou M. Velez Torres
Diagnostic Cytopathology.2024;[Epub] CrossRef
Nuclear Protein in Testis (NUT) Carcinoma: A Comprehensive Immunohistochemical Analysis of 57 Cases With Consideration of Interpretation and Pitfall Recognition
Ayesha Farooq, Allison L. Kerper, Jennifer M. Boland, Ying-Chun Lo
Archives of Pathology & Laboratory Medicine.2024; 148(8): 898. CrossRef
BRD3‐NUTM1‐expressing NUT carcinoma of lung on endobronchial ultrasound‐guided transbronchial needle aspiration cytology, a diagnostic pitfall
Sameer Chhetri Aryal, Shereen Zia, Shannon Rodgers, Yulei Shen, Kyle Perry, Lisi Yuan
Diagnostic Cytopathology.2022;[Epub] CrossRef
Nuclear protein of the testis midline carcinoma of the thorax
Ayae Saiki, Keita Sakamoto, Yuan Bee, Takehiro Izumo
Japanese Journal of Clinical Oncology.2022; 52(6): 531. CrossRef
Approach to Mediastinal Fine Needle Aspiration Cytology
Zaibo Li, Huihong Xu, Fang Fan
Advances in Anatomic Pathology.2022; 29(6): 337. CrossRef
Diagnosis, Treatment and Prognosis of Primary Pulmonary NUT Carcinoma: A Literature Review
Jiaqian Yuan, Zhili Xu, Yong Guo
Current Oncology.2022; 29(10): 6807. CrossRef
Case report: Immunovirotherapy as a novel add-on treatment in a patient with thoracic NUT carcinoma
Linus D. Kloker, Branko Calukovic, Katrin Benzler, Alexander Golf, Sebastian Böhm, Sven Günther, Marius Horger, Simone Haas, Susanne Berchtold, Julia Beil, Mary E. Carter, Tina Ganzenmueller, Stephan Singer, Abbas Agaimy, Robert Stöhr, Arndt Hartmann, Tho
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Cytomorphology of primary pulmonary NUT carcinoma in different cytology preparations
Rimlee Dutta, Aruna Nambirajan, Saurabh Mittal, Sinchita Roy‐Chowdhuri, Deepali Jain
Cancer Cytopathology.2021; 129(1): 53. CrossRef
Update on genetically defined lung neoplasms: NUT carcinoma and thoracic SMARCA4-deficient undifferentiated tumors
Kyriakos Chatzopoulos, Jennifer M. Boland
Virchows Archiv.2021; 478(1): 21. CrossRef
Immunotherapy and Targeting the Tumor Microenvironment: Current Place and New Insights in Primary Pulmonary NUT Carcinoma
Xiang Li, Hui Shi, Wei Zhang, Chong Bai, Miaoxia He, Na Ta, Haidong Huang, Yunye Ning, Chen Fang, Hao Qin, Yuchao Dong
Frontiers in Oncology.2021;[Epub] CrossRef
Prevalence of NUT carcinoma in head and neck: Analysis of 362 cases with literature review
Taebum Lee, Junhun Cho, Chung‐Hwan Baek, Young‐Ik Son, Han‐Sin Jeong, Man Ki Chung, Sang Duk Hong, Yong Chan Ahn, Dong Ryul Oh, Jae Myoung Noh, Keunchil Park, Myung‐Ju Ahn, Hyung‐Jin Kim, Yi Kyung Kim, Young Hyeh Ko
Head & Neck.2020; 42(5): 924. CrossRef
Lung nuclear protein in testis carcinoma in an elderly Korean woman: A case report with cytohistological analysis
Hwa Jin Cho, Hyun‐Kyung Lee
Thoracic Cancer.2020; 11(6): 1724. CrossRef
Clinicopathological characteristics of primary lung nuclear protein in testis carcinoma: A single‐institute experience of 10 cases
Yoon Ah Cho, Yoon‐La Choi, Inwoo Hwang, Kyungjong Lee, Jong Ho Cho, Joungho Han
Thoracic Cancer.2020; 11(11): 3205. CrossRef

Original Article

Pulmonary Nodular Lymphoid Hyperplasia with Mass-Formation: Clinicopathologic Characteristics of Nine Cases and Review of the Literature: Jongmin Sim, Hyun Hee Koh, Sangjoon Choi, Jinah Chu, Tae Sung Kim, Hojoong Kim, Joungho Han; J Pathol Transl Med. 2018;52(4):211-218. Published online June 15, 2018; DOI: https://doi.org/10.4132/jptm.2018.04.27

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Abstract PDF

Background
Pulmonary nodular lymphoid hyperplasia (PNLH) is a non-neoplastic pulmonary lymphoid disorder that can be mistaken for malignancy on radiography. Herein, we present nine cases of PNLH, emphasizing clinicoradiological findings and histological features.
Methods
We analyzed radiological and clinicopathological features from the electronic medical records of nine patients (eight females and one male) diagnosed with PNLH. IgG and IgG4 immunohistochemical staining was performed in three patients.
Results
Two of the nine patients had experienced tuberculosis 40 and 30 years prior, respectively. Interestingly, none were current smokers, although two were ex-smokers. Three patients complaining of persistent cough underwent computed tomography of the chest. PNLH was incidentally discovered in five patients during examination for other reasons. The remaining patient was diagnosed with the disease following treatment for pneumonia. Imaging studies revealed consolidation or a mass-like lesion in eight patients. First impressions included invasive adenocarcinoma and mucosal-associated lymphoid tissue‒type lymphoma. Aspergillosis was suspected in the remaining patient based on radiological images. Resection was performed in all patients. Microscopically, the lesions consisted of nodular proliferation of reactive germinal centers accompanied by infiltration of neutrophils and macrophages in various degrees and surrounding fibrosis. Ultimately, all nine patients were diagnosed with PNLH and showed no evidence of recurrence on follow-up.
Conclusions
PNLH is an uncommon but distinct entity with a benign nature, and understanding the radiological and clinicopathological characteristics of PNLH is important.

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Clinical and Imaging Features of Pulmonary Nodular Lymphoid Hyperplasia
Dong-Lei Nie, Yan-Hong Shi, Xin-Min Li, Xiao-Jiang Wang, Bao-Li Han, Guo-Fu Zhang
Journal of Thoracic Imaging.2025;[Epub] CrossRef
Utilizing Immunoglobulin G4 Immunohistochemistry for Risk Stratification in Patients with Papillary Thyroid Carcinoma Associated with Hashimoto Thyroiditis
Faridul Haq, Gyeongsin Park, Sora Jeon, Mitsuyoshi Hirokawa, Chan Kwon Jung
Endocrinology and Metabolism.2024; 39(3): 468. CrossRef
Pulmonary Nodular Lymphoid Hyperplasia Evaluated with Bronchoalveolar Lavage Fluid Findings: A Case Report and Review of the Literature on Japanese Patients
Sakiko Moriyama, Takashi Kido, Noriho Sakamoto, Mai Fuchigami, Takatomo Tokito, Daisuke Okuno, Takuto Miyamura, Shota Nakashima, Atsuko Hara, Hiroshi Ishimoto, Yoshitaka Imaizumi, Kazuto Tsuruda, Katsunori Yanagihara, Junya Fukuoka, Hiroshi Mukae
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Jonathan Teow Koon Goh, Issam Al Jajeh, Jessica Han Ying Tan
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Pulmonary nodular lymphoid hyperplasia presenting as cavitating lung mass
Aqeel Alameer, Chary Duraikannu, Avinash Kumar Kanodia, David Dorward
BMJ Case Reports.2023; 16(8): e254121. CrossRef
Clinicopathological Characteristics and Curative Effect of Lymphoma Based on Sampling Theory
Shuxiang Ding, Leipo Liu
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Pulmonary nodular lymphoid hyperplasia presenting as multifocal subsolid nodules: A case report and literature review
Yoon Jin Cha, Duk Hwan Moon, Ji Hyun Park, Sungsoo Lee, Ji Ae Choi, Tae Hoon Kim, Chul Hwan Park
Respiratory Medicine Case Reports.2022; 36: 101581. CrossRef
Pulmonary nodular lymphoid hyperplasia in a 53-year-old man with malignant sign: a case report
Zhen Yang, Lianshuang Wei, Xu Li, Xin Liu
Journal of Cardiothoracic Surgery.2021;[Epub] CrossRef
The diagnostic challenge of adenocarcinoma in pulmonary nodular lymphoid hyperplasia
Anita Savić Vuković, Melita Kukuljan, Morana Dinter, Ksenija Jurinović, Nives Jonjić
SAGE Open Medical Case Reports.2021;[Epub] CrossRef

Case Study

Cytologic Characteristics of Thymic Adenocarcinoma with Enteric Differentiation: A Study of Four Fine-Needle Aspiration Specimens: Ah-Young Kwon, Joungho Han, Hae-yon Cho, Seokhwi Kim, Heejin Bang, Jiyeon Hyeon; J Pathol Transl Med. 2017;51(5):509-512. Published online August 4, 2017; DOI: https://doi.org/10.4132/jptm.2017.03.22

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Abstract PDF

Thymic adenocarcinoma is extremely rare. Although its histologic features have been occasionally reported, a lack of description of the cytologic features has hampered the prompt and accurate diagnosis of this condition. Herein, we describe the cytologic findings and histology of four aspiration cytology specimens of thymic adenocarcinoma. The specimens were obtained from primary tumors, metastatic lymph nodes, and pericardial effusions. All four specimens showed three-dimensional glandular clusters with a loss of polarity and nuclear overlapping. One specimen had extensive extracellular mucinous material. Three specimens contained tumor cells with intracytoplasmic vacuoles. While the specimen with extracellular mucin showed relatively mild cytologic atypia, other specimens exhibited more atypical cytologic changes: irregular nuclear membranes, a coarse chromatin pattern, and prominent nucleoli. The cytologic features were correlated with the histologic features in each case of enteric type thymic adenocarcinoma. The differential diagnosis included other thymic carcinomas, yolk sac tumors, and metastatic adenocarcinoma from the lung or colorectum.

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Case report: Primary adenocarcinoma NOS of the thymus and cytological features
Jonathan Willner, Osvaldo Hernandez, Lea Azour, Andre L. Moreira
Diagnostic Cytopathology.2023;[Epub] CrossRef
Systemic chemotherapy for unresectable or recurrent primary thymic adenocarcinoma of enteric type
Xiaofang Gao
International Cancer Conference Journal.2022; 12(1): 46. CrossRef
Thymic adenocarcinoma accompanied by type A thymoma and pulmonary minimally invasive adenocarcinoma and harboring distinct gene alterations
Yi-Wen Zheng, Lin-Lin Bai, Gui-Yang Jiang, Xu-Yong Lin, Yang Liu, Hong-Tao Xu
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A case report: primary thymic adenocarcinoma with enteric differentiation
Yuuki Kou, Hirokazu Tanaka, Nobuhisa Yamazaki, Hiroyoshi Watanabe, Makoto Sonobe
The Journal of the Japanese Association for Chest Surgery.2020; 34(2): 107. CrossRef
Primary thymic adenocarcinoma with an aggressive clinical course: An autopsy case showing signet ring cell‐like features
Ayako Shiono, Takashi Fujino, Kyoichi Kaira, Tomomi Kato, Masanori Yasuda, Kunihiko Kobayashi, Hiroshi Kagamu
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Primary Thymic Signet Ring Cell Adenocarcinoma: A Currently Unrecognized Variant
Richard Benedict Supan Roxas, Marie Christine Fajatin Bernardo, Araceli Pacis Jacoba, Janet Lim-Dy, Anarose Cariaga Alvarado, Jasna Metovic, Laura Annaratone, Mauro Papotti
International Journal of Surgical Pathology.2019; 27(3): 315. CrossRef
Disseminated and massive tumor burden in a case of primary thymic mucinous adenocarcinoma
Hui-Wen Liu, Chih-Yi Liu, Yi-Chen Yeh
Journal of Cancer Research and Practice.2019; 6(3): 151. CrossRef

Brief Case Report

Metastatic Squamous Cell Carcinoma from Lung Adenocarcinoma after Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy: Hyung Kyu Park, Youjeong Seo, Yoon-La Choi, Myung-Ju Ahn, Joungho Han; J Pathol Transl Med. 2017;51(4):441-443. Published online April 4, 2017; DOI: https://doi.org/10.4132/jptm.2016.10.18

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PDF

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Spontaneous histological transformation of lung squamous-cell carcinoma to large cell neuroendocrine carcinoma and small cell lung cancer
Jin-Dong Li, Cheng-Yan Jin, Yan Zhang, Hang Guo, Guang-Lei Zhang, Chun-Guang Wang
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Morphologic-Molecular Transformation of Oncogene Addicted Non-Small Cell Lung Cancer
Fiorella Calabrese, Federica Pezzuto, Francesca Lunardi, Francesco Fortarezza, Sofia-Eleni Tzorakoleftheraki, Maria Vittoria Resi, Mariaenrica Tiné, Giulia Pasello, Paul Hofman
International Journal of Molecular Sciences.2022; 23(8): 4164. CrossRef
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Jiatao Liao, Yuan Li, Chang Liu, Qianqian Long, Jialei Wang
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Squamous cell carcinoma transformation of lung adenocarcinoma after tyrosine kinase inhibitor therapy: Cytological approach
Alexandra Grosse, Claudia Grosse
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Outcome of EGFR-mutated adenocarcinoma NSCLC patients with changed phenotype to squamous cell carcinoma after tyrosine kinase inhibitors: A pooled analysis with an additional case
Elisa Roca, Marta Pozzari, William Vermi, Valeria Tovazzi, Alice Baggi, Vito Amoroso, Daniela Nonnis, Salvatore Intagliata, Alfredo Berruti
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Jay Gong, Jeffrey P. Gregg, Weijie Ma, Ken Yoneda, Elizabeth H. Moore, Megan E. Daly, Yanhong Zhang, Melissa J. Williams, Tianhong Li
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Original Articles

Size of Non-lepidic Invasive Pattern Predicts Recurrence in Pulmonary Mucinous Adenocarcinoma: Morphologic Analysis of 188 Resected Cases with Reappraisal of Invasion Criteria: Soohyun Hwang, Joungho Han, Misun Choi, Myung-Ju Ahn, Yong Soo Choi; J Pathol Transl Med. 2017;51(1):56-68. Published online October 16, 2016; DOI: https://doi.org/10.4132/jptm.2016.09.17

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Abstract PDF

Background
We reviewed a series of 188 resected pulmonary mucinous adenocarcinomas (MAs) to clarify the prognostic significance of lepidic and non-lepidic patterns.
Methods
Non-lepidic patterns were divided into bland, non-distorted acini with uncertain invasiveness (pattern 1), unequivocal invasion into stroma (pattern 2), or invasion into alveolar spaces (pattern 3).
Results
The mean proportion of invasive patterns (patterns 2 and 3) was lowest in small (≤ 3 cm) tumors, and gradually increased in intermediate (> 3 cm and ≤ 7 cm) and large (> 7 cm) tumors (8.4%, 34.3%, and 50.1%, respectively). Adjusted T (aT) stage, as determined by the size of invasive patterns, was positively correlated with adverse histologic and clinical features including older age, male sex, and ever smokers. aTis tumors, which were exclusively composed of lepidic pattern (n = 9), or a mixture of lepidic and pattern 1 (n = 40) without any invasive patterns, showed 100% disease- free survival (DFS). The aT1mi tumors, with minimal (≤ 5 mm) invasive patterns (n = 63), showed a 95.2% 5-year DFS, with recurrences (n = 2) limited to tumors greater than 3 cm in total size (n = 23). Both T and aT stage were significantly associated with DFS; however, survival within the separate T-stage subgroups was stratified according to the aT stage, most notably in the intermediatestage subgroups. In multivariate analysis, the size of invasive patterns (p = .020), pleural invasion (p < .001), and vascular invasion (p = .048) were independent predictors of recurrence, whereas total size failed to achieve statistical significance (p = .121).
Conclusions
This study provides a rationale for histologic risk stratification in pulmonary MA based on the extent of invasive growth patterns with refined criteria for invasion.

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Distinct Recurrence Pattern and Survival Outcomes of Invasive Mucinous Adenocarcinoma of the Lung: The Potential Role of Local Therapy in Intrapulmonary Spread
Dong Woog Yoon, Soohyun Hwang, Tae Hee Hong, Yoon-La Choi, Hong Kwan Kim, Yong Soo Choi, Jhingook Kim, Young Mog Shim, Jong Ho Cho
Annals of Surgical Oncology.2024; 31(1): 201. CrossRef
Pulmonary invasive mucinous adenocarcinoma
Wei‐Chin Chang, Yu Zhi Zhang, Andrew G Nicholson
Histopathology.2024; 84(1): 18. CrossRef
Micropapillary Pattern in Invasive Mucinous Adenocarcinoma of the Lung: Comparison With Invasive Non-Mucinous Adenocarcinoma
Hui He, Lue Li, Yuan-yuan Wen, Li-yong Qian, Zhi-qiang Yang
International Journal of Surgical Pathology.2024; 32(5): 926. CrossRef
Radiological and clinical features of screening-detected pulmonary invasive mucinous adenocarcinoma
Dae Hyeon Kim, So Young Bae, Kwon Joong Na, Samina Park, In Kyu Park, Chang Hyun Kang, Young Tae Kim
Interactive CardioVascular and Thoracic Surgery.2022; 34(2): 229. CrossRef
Micropapillary Pattern in Invasive Mucinous Adenocarcinoma of the Lung: Comparison with Invasive Non-Mucinous Adenocarcinoma
Hui He, Yuanyuan Wen, Liyong Qian, Zhiqiang Yang
SSRN Electronic Journal .2022;[Epub] CrossRef
Optimal method for measuring invasive size that predicts survival in invasive mucinous adenocarcinoma of the lung
Tomonari Oki, Keiju Aokage, Shogo Nomura, Kenta Tane, Tomohiro Miyoshi, Norihiko Shiiya, Kazuhito Funai, Masahiro Tsuboi, Genichiro Ishii
Journal of Cancer Research and Clinical Oncology.2020; 146(5): 1291. CrossRef
Prognostic Impact of Histopathologic Features in Pulmonary Invasive Mucinous Adenocarcinomas
Wei-Chin Chang, Yu Zhi Zhang, Eric Lim, Andrew G Nicholson
American Journal of Clinical Pathology.2020; 154(1): 88. CrossRef

Transformation to Small Cell Lung Cancer of Pulmonary Adenocarcinoma: Clinicopathologic Analysis of Six Cases: Soomin Ahn, Soo Hyun Hwang, Joungho Han, Yoon-La Choi, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn, Woong-Yang Park; J Pathol Transl Med. 2016;50(4):258-263. Published online May 10, 2016; DOI: https://doi.org/10.4132/jptm.2016.04.19

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Abstract PDF

Background
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are considered the first line treatment for a subset of EGFR-mutated non-small cell lung cancer (NSCLC) patients. Although transformation to small cell lung cancer (SCLC) is one of the known mechanisms of resistance to EGFR TKIs, it is not certain whether transformation to SCLC is exclusively found as a mechanism of TKI resistance in EGFR-mutant tumors.
Methods
We identified six patients with primary lung adenocarcinoma that showed transformation to SCLC on second biopsy (n = 401) during a 6-year period. Clinicopathologic information was analyzed and EGFR mutation results were compared between initial and second biopsy samples.
Results
Six patients showed transformation from adenocarcinoma to SCLC, of which four were pure SCLCs and two were combined adenocarcinoma and SCLCs. Clinically, four cases were EGFR-mutant tumors from non-smoking females who underwent TKI treatment, and the EGFR mutation was retained in the transformed SCLC tumors. The remaining two adenocarcinomas were EGFR wild-type, and one of these patients received EGFR TKI treatment.
Conclusions
NSCLC can acquire a neuroendocrine phenotype with or without EGFR TKI treatment.

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Case Study

Pulmonary Arteriovenous Fistula: Clinical and Histologic Spectrum of Four Cases: Soomin Ahn, Joungho Han, Hong Kwan Kim, Tae Sung Kim; J Pathol Transl Med. 2016;50(5):390-393. Published online May 9, 2016; DOI: https://doi.org/10.4132/jptm.2016.04.18

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Abstract PDF

Pulmonary arteriovenous fistula (PAVF) is abnormally dilated vessels that provide a right-to-left shunt between pulmonary artery and pulmonary vein and is clinically divided into simple and complex type. Here, we report four cases of surgically resected sporadic PAVFs presenting various clinical and histologic spectrums. Cases 1 (a 57-old-female) and 2 (a 54-old-female) presented as incidentally identified single aneurysmal fistulas and the lesions were surgically removed without complication. On the other hand, case 3 (an 11-old-male) showed diffuse dilated vascular sacs involving both lungs and caused severe hemodynamic and pulmonary dysfunction. Embolization and surgical resection of the main lesion failed to relieve the symptoms. Case 4 (a 36-old-male) had a localized multiloculated cyst clinically mimicking congenital cystic adenomatoid malformation. Microscopically, the lesion consisted of dilated thick vessels, consistent with the diagnosis of fistulous arteriovenous malformation/hemangioma.

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Original Article

Non-small Cell Lung Cancer with Concomitant EGFR, KRAS, and ALK Mutation: Clinicopathologic Features of 12 Cases: Taebum Lee, Boram Lee, Yoon-La Choi, Joungho Han, Myung-Ju Ahn, Sang-Won Um; J Pathol Transl Med. 2016;50(3):197-203. Published online April 18, 2016; DOI: https://doi.org/10.4132/jptm.2016.03.09

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Abstract PDF

Background
Although epidermal growth factor receptor (EGFR), v-Ki-ras2 Kirsten rat sarcoma viral oncogene (KRAS), and anaplastic lymphoma kinase (ALK) mutations in non-small cell lung cancer (NSCLC) were thought to be mutually exclusive, some tumors harbor concomitant mutations. Discovering a driver mutation on the basis of morphologic features and therapeutic responses with mutation analysis can be used to understand pathogenesis and predict resistance in targeted therapy.
Methods
In 6,637 patients with NSCLC, 12 patients who had concomitant mutations were selected and clinicopathologic features were reviewed. Clinical characteristics included sex, age, smoking history, previous treatment, and targeted therapy with response and disease-free survival. Histologic features included dominant patterns, nuclear and cytoplasmic features.
Results
All patients were diagnosed with adenocarcinoma and had an EGFR mutation. Six patients had concomitant KRAS mutations and the other six had ALK mutations. Five of six EGFR-KRAS mutation patients showed papillary and acinar histologic patterns with hobnail cells. Three of six received EGFR tyrosine kinase inhibitor (TKI) and showed partial response for 7–29 months. All six EGFR-ALK mutation patients showed solid or cribriform patterns and three had signet ring cells. Five of six EGFR-ALK mutation patients received EGFR TKI and/or ALK inhibitor and four showed partial response or stable disease, except for one patient who had acquired an EGFR mutation.
Conclusions
EGFR and ALK mutations play an important role as driver mutations in double mutated NSCLC, and morphologic analysis can be used to predict treatment response.

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Brief Case Report

A Rare Case of Pulmonary Arteriovenous Hemangioma Presenting as a Peribronchial Mass: Soomin Ahn, Sejin Jung, Jong Ho Cho, Tae Sung Kim, Joungho Han; J Pathol Transl Med. 2016;50(3):243-245. Published online November 17, 2015; DOI: https://doi.org/10.4132/jptm.2015.10.15

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Incidental discovery of a large complicated arteriovenous haemangioma
Alberto Anthony Goizueta, Peter Libbey, Anthony Moulton, Rabih El-Bizri
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Original Article

Comprehensive Cytomorphologic Analysis of Pulmonary Adenoid Cystic Carcinoma: Comparison to Small Cell Carcinoma and Non-pulmonary Adenoid Cystic Carcinoma: Seokhwi Kim, Jinah Chu, Hojoong Kim, Joungho Han; J Pathol Transl Med. 2015;49(6):511-519. Published online October 19, 2015; DOI: https://doi.org/10.4132/jptm.2015.09.07

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Background
Cytologic diagnosis of pulmonary adenoid cystic carcinoma (AdCC) is frequently challenging and differential diagnosis with small cell carcinoma is often difficult. Methods: Eleven cytologically diagnosed cases of pulmonary AdCC were collected and reviewed according to fifteen cytomorphologic characteristics: small cell size, cellular uniformity, coarse chromatin, hyperchromasia, distinct nucleolus, frequent nuclear molding, granular cytoplasm, organoid cluster, sheet formation, irregular border of cluster, hyaline globule, hyaline basement membrane material, individual cell necrosis or apoptotic body, and necrotic background. Twenty cases of small cell carcinoma and fifteen cases of non-pulmonary AdCC were also reviewed for the comparison. Results: Statistically significant differences were identified between pulmonary AdCC and small cell carcinoma in fourteen of the fifteen cytomorphologic criteria (differences in sheet formation were not statistically significant). Cellular uniformity, distinct nucleolus, granular cytoplasm, distinct cell border, organoid cluster, hyaline globule, and hyaline basement membrane material were characteristic features of AdCC. Frequent nuclear molding, individual cell necrosis, and necrotic background were almost exclusively identified in small cell carcinoma. Although coarse chromatin and irregular cluster border were observed in both, they favored the diagnosis of small cell carcinoma. Hyaline globules were more frequently seen in non-pulmonary AdCC cases. Conclusions: Using the fifteen cytomorphologic criteria described by this study, pulmonary AdCC could be successfully distinguished from small cell carcinoma. Such a comprehensive approach to an individual case is recommended for the cytologic diagnosis of pulmonary AdCC.

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Primary pulmonary adenoid cystic carcinoma: A study of clinicopathological features and molecular alterations in twenty-one cases
Zhiyuan Yao, Tong Qiu, Changlei Li, Weimao Kong, Guangqi Li, Peng Song, Guohua Wang, Wenjie Jiao
Lung Cancer.2025; 201: 108414. CrossRef
Recent developments in the pathology of primary pulmonary salivary gland‐type tumours
Julia R Naso, Anja C Roden
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Bronchial cytology of pulmonary adenoid cystic carcinoma – A multi-institute series with emphasis on immunocytochemistry
Joanna K.M. Ng, Ka Pang Chan, Gary M. Tse, Joshua J.X. Li
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Pulmonary adenoid cystic carcinoma: molecular characteristics and literature review
Zhixin Chen, Jiapeng Jiang, Ying Fan, Hongyang Lu
Diagnostic Pathology.2023;[Epub] CrossRef
Recent updates in salivary gland tumors of the lung
Anja C. Roden
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Chiara Saglietti, Marco Volante, Stefano La Rosa, Igor Letovanec, Marc Pusztaszeri, Gaia Gatti, Massimo Bongiovanni
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Brief Case Report

A Rare Case of Thymic Gangliocytic Paraganglioma: Jung Wook Yang, Joungho Han, Hyun Woo Lee, Soo Youn Cho, Hong Kwan Kim; J Pathol Transl Med. 2016;50(2):165-167. Published online October 8, 2015; DOI: https://doi.org/10.4132/jptm.2015.07.15

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Original Article

Analysis of Histologic Features Suspecting Anaplastic Lymphoma Kinase (ALK)-Expressing Pulmonary Adenocarcinoma: In Ho Choi, Dong Won Kim, Sang Yun Ha, Yoon-La Choi, Hee Jeong Lee, Joungho Han; J Pathol Transl Med. 2015;49(4):310-317. Published online June 22, 2015; DOI: https://doi.org/10.4132/jptm.2015.05.13

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Abstract PDF

Background
Since 2007 when anaplastic lymphoma kinase (ALK) rearrangements were discovered in non-small cell lung cancer, the ALK gene has received attention due to ALK-targeted therapy, and a notable treatment advantage has been observed in patients harboring the EML4/ALK translocation. However, using ALK-fluorescence in situ hybridization (FISH) as the standard method has demerits such as high cost, a time-consuming process, dependency on interpretation skill, and tissue preparation. We analyzed the histologic findings which could complement the limitation of ALK-FISH test for pulmonary adenocarcinoma. Methods: Two hundred five cases of ALK-positive and 101 of ALK-negative pulmonary adenocarcinoma from January 2007 to May 2013 were enrolled in this study. The histologic findings and ALK immunohistochemistry results were reviewed and compared with the results of ALK-FISH and EGFR/KRAS mutation status. Results: Acinar, cribriform, and solid growth patterns, extracellular and intracellular mucin production, and presence of signet-ring-cell element, and psammoma body were significantly more often present in ALK-positive cancer. In addition, the presence of goblet cell-like cells and presence of nuclear inclusion and groove resembling papillary thyroid carcinoma were common in the ALK-positive group. Conclusions: The above histologic parameters can be helpful in predicting ALK rearranged pulmonary adenocarcinoma, leading to rapid FISH analysis and timely treatment.

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