Journal of Pathology and Translational Medicine

Review

Welcoming the new, revisiting the old: a brief glance at cytopathology reporting systems for lung, pancreas, and thyroid: Rita Luis, Balamurugan Thirunavukkarasu, Deepali Jain, Sule Canberk; J Pathol Transl Med. 2024;58(4):165-173. Published online July 15, 2024; DOI: https://doi.org/10.4132/jptm.2024.06.11

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Abstract PDF: This review addresses new reporting systems for lung and pancreatobiliary cytopathology as well as the most recent edition of The Bethesda Reporting System for Thyroid Cytopathology. The review spans past, present, and future aspects within the context of the intricate interplay between traditional morphological assessments and cutting-edge molecular diagnostics. For lung and pancreas, the authors discuss the evolution of reporting systems, emphasizing the bridge between past directives and more recent collaborative efforts of the International Academy of Cytology and the World Health Organization in shaping universal reporting systems. The review offers a brief overview of the structure of these novel systems, highlighting their strengths and pinpointing areas that require further refinement. For thyroid, the authors primarily focus on the third edition of The Bethesda System for Reporting Thyroid Cytopathology, also considering the two preceding editions. This review serves as an invaluable resource for cytopathologists, offering a panoramic view of the evolving landscape of cytopathology reporting and pointing out the integrative role of the cytopathologist in an era of rapid diagnostic and therapeutic advancements.

Case Study

Primary pulmonary epithelioid inflammatory myofibroblastic sarcoma: a rare entity and a literature review: Priyanka Singh, Aruna Nambirajan, Manish Kumar Gaur, Rahul Raj, Sunil Kumar, Prabhat Singh Malik, Deepali Jain; J Pathol Transl Med. 2022;56(4):231-237. Published online July 7, 2022; DOI: https://doi.org/10.4132/jptm.2022.05.08

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Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is an aggressive subtype of inflammatory myofibroblastic tumor (IMT) harboring anaplastic lymphoma kinase (ALK) gene fusions and is associated with high risk of local recurrence and poor prognosis. Herein, we present a young, non-smoking male who presented with complaints of cough and dyspnoea and was found to harbor a large right lower lobe lung mass. Biopsy showed a high-grade epithelioid to rhabdoid tumor with ALK and desmin protein expression. The patient initially received 5 cycles of crizotinib and remained stable for 1 year; however, he then developed multiple bony metastases, for which complete surgical resection was performed. Histopathology confirmed the diagnosis of EIMS, with ALK gene rearrangement demonstrated by fluorescence in situ hybridization. Postoperatively, the patient is asymptomatic with stable metastatic disease on crizotinib and has been started on palliative radiotherapy. EIMS is a very rare subtype of IMT that needs to be included in the differential diagnosis of ALKexpressing lung malignancies in young adults.

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Mediastinal epithelioid inflammatory myofibroblastic sarcoma with the EML4‐ALK fusion: A case report and literature review
Tingyu Pan, Xinyu Sun, Xiao Wu, Futing Tang, Xianmei Zhou, Qian Wang, Shi Chen
Respirology Case Reports.2024;[Epub] CrossRef
Primary epithelioid inflammatory myofibroblastic sarcoma of the brain with EML4::ALK fusion mimicking intra-axial glioma: a case report and brief literature review
Eric Eunshik Kim, Chul-Kee Park, Koung Mi Kang, Yoonjin Kwak, Sung-Hye Park, Jae-Kyung Won
Journal of Pathology and Translational Medicine.2024; 58(3): 141. CrossRef
Epithelioid Inflammatory Myofibroblastic Sarcoma: A Report of a Rare Case
Varun Ronanki, Vaddatti Tejeswini, Inuganti Venkata Renuka, Shaik Raheema, Bakkamanthala S K Kanth
Cureus.2024;[Epub] CrossRef
Thoracic epithelioid inflammatory myofibroblastic sarcoma: a rare and aggressive disease with case report and literature review
Linke Yang, Pei Li, Runze Liu, Baomin Feng, Huiqing Mao, Xiaoyong Tang, Guangjian Yang
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Epithelioid inflammatory myofibroblastic sarcoma with exceptionally long response to lorlatinib—a case report
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Case report: Epithelioid inflammatory myofibroblastic sarcoma treated with an ALK TKI ensartinib
Mengmeng Li, Ruyue Xing, Jiuyan Huang, Chao Shi, Chunhua Wei, Huijuan Wang
Frontiers in Oncology.2023;[Epub] CrossRef
Epithelioid Inflammatory Myofibroblastic Sarcoma With Poor Response to Crizotinib: A Case Report
Soheila Aminimoghaddam, Roghayeh Pourali
Clinical Medicine Insights: Case Reports.2023;[Epub] CrossRef
Epithelioid inflammatory myofibroblastic sarcoma: a case report and brief literature review
Weidong Dou, Yu Guan, Tao Liu, Hang Zheng, Shuo Feng, Yingchao Wu, Xin Wang, Zhanbing Liu
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Original Articles

Correlation of TTF-1 immunoexpression and EGFR mutation spectrum in non–small cell lung carcinoma: Tripti Nakra, Varsha Singh, Aruna Nambirajan, Prabhat Singh Malik, Anant Mohan, Deepali Jain; J Pathol Transl Med. 2021;55(4):279-288. Published online July 8, 2021; DOI: https://doi.org/10.4132/jptm.2021.05.10

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Abstract PDF

Background
Thyroid transcription factor (TTF-1) is a diagnostic marker expressed in 75%–85% of primary lung adenocarcinomas (ACs). Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene is the most common targetable driver alteration in lung AC. Previous studies have shown a positive correlation between TTF-1 and EGFR mutation status. We aimed to determine the predictive value of TTF-1 immunoexpression for underlying EGFR mutation status in a large Indian cohort.
Methods
This retrospective designed study was conducted with medical record data from 2011 to 2020. All cases of primary lung AC and non–small cell lung carcinoma not otherwise specified (NSCLC, NOS) with known TTF-1 expression diagnosed by immunohistochemistry using 8G7G3/1 antibodies and EGFR mutation status diagnosed by quantitative polymerase chain reaction were retrieved, reviewed, and the
results
were analyzed. Results: Among 909 patient samples diagnosed as lung AC and NSCLC, NOS, TTF-1 was positive in 76.8% cases (698/909) and EGFR mutations were detected in 29.6% (269/909). A strong positive correlation was present between TTF-1 positivity and EGFR mutation status (odds ratio, 3.61; p < .001), with TTF-1 positivity showing high sensitivity (90%) and negative predictive value (87%) for EGFR mutation. TTF-1 immunoexpression did not show significant correlation with uncommon/dual EGFR mutations (odds ratio, 1.69; p = .098). EGFR–tyrosine kinase inhibitor therapy was significantly superior to chemotherapy among EGFR mutant cases irrespective of TTF-1 status; however, no significant differences among survival outcomes were observed.
Conclusions
Our study confirms a strong positive correlation between TTF-1 expression and common EGFR mutations (exon 19 deletion and exon 21 L858R) in advanced lung AC with significantly high negative predictive value of TTF-1 for EGFR mutations.

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Mutation profile and programmed death ligand 1 status of patients with non‐small cell lung cancer diagnosed with “adenocarcinoma” and “non‐small cell carcinoma favor adenocarcinoma”
Naoko Shigeta, Tomoyuki Yokose, Shuji Murakami, Tetsuya Isaka, Kanako Shinada, Emi Yoshioka, Atsuya Narita, Kengo Katakura, Tetsuro Kondo, Terufumi Kato, Takuya Nagashima, Haruhiro Saito, Hiroyuki Ito
Thoracic Cancer.2024; 15(6): 458. CrossRef
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Huiyue Lin, Juyong Wang, Qing Shi, Minmin Wu
PeerJ.2024; 12: e17338. CrossRef
TTF-1 is a highly sensitive but not fully specific marker for pulmonary and thyroidal cancer: a tissue microarray study evaluating more than 17,000 tumors from 152 different tumor entities
Katharina Möller, Tayyaba Gulzar, Maximilian Lennartz, Florian Viehweger, Martina Kluth, Claudia Hube-Magg, Christian Bernreuther, Ahmed Abdulwahab Bawahab, Ronald Simon, Till S. Clauditz, Guido Sauter, Ria Schlichter, Andrea Hinsch, Simon Kind, Frank Jac
Virchows Archiv.2024; 485(5): 815. CrossRef
Identifying immunohistochemical biomarkers panel for non-small cell lung cancer in optimizing treatment and forecasting efficacy
Xiaoya Zhang, Junhong Meng, Mingyue Gao, Cheng Gong, Cong Peng, Duxian Liu
BMC Cancer.2024;[Epub] CrossRef
Expression landscapes in non-small cell lung cancer shaped by the thyroid transcription factor 1
Herdee Gloriane C. Luna, Marcelo Severino Imasa, Necy Juat, Katherine V. Hernandez, Treah May Sayo, Gloria Cristal-Luna, Sheena Marie Asur-Galang, Mirasol Bellengan, Kent John Duga, Bien Brian Buenaobra, Marvin I. De los Santos, Daniel Medina, Jamirah Sam
Lung Cancer.2023; 176: 121. CrossRef
Malignant pleural effusion cell blocks are reliable resources for PD-L1 analysis in advanced lung adenocarcinomas: a concordance study with matched histologic samples
Swati Mahajan, Aruna Nambirajan, Ishan Gupta, Nalini Gupta, Parikshaa Gupta, Deepali Jain
Journal of the American Society of Cytopathology.2022; 11(5): 253. CrossRef
Clinicopathologic Features and Molecular Biomarkers as Predictors of Epidermal Growth Factor Receptor Gene Mutation in Non-Small Cell Lung Cancer Patients
Lanlan Liu, Xianzhi Xiong
Current Oncology.2021; 29(1): 77. CrossRef

Endobronchial Smooth Muscle Tumors: A Series of Five Cases Highlighting Pitfalls in Diagnosis: Tripti Nakra, Aanchal Kakkar, Shipra Agarwal, Karan Madan, Suresh C Sharma, Deepali Jain; J Pathol Transl Med. 2018;52(4):219-225. Published online July 11, 2018; DOI: https://doi.org/10.4132/jptm.2018.05.16

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Abstract PDF

Background
Primary endobronchial smooth muscle tumors (SMTs), which are extremely rare, include endobronchial leiomyomas and leiomyosarcomas. Clinically, SMTs present with signs and symptoms of bronchial obstruction, and lack specific radiological findings. Thus, histopathological examination is required for accurate diagnosis as well as for tumor grading. We examined the histomorphological and immunohistochemical features of endobronchial SMTs and highlighted pitfalls in diagnosis, particularly when using small biopsies.
Methods
Cases of primary endobronchial SMTs diagnosed at our Institute over the last 6 years (2012–2017) were retrieved from the departmental archives. Histopathological features and immunohistochemistry performed for establishing the diagnosis were reviewed.
Results
Five cases of SMTs occurring in endobronchial locations were identified. These included three cases of leiomyoma, and two cases of leiomyosarcoma. The age distribution of patients ranged from 13 to 65 years. Leiomyomas showed more consistent staining with smooth muscle markers (smooth muscle actin, desmin, and smooth muscle myosin heavy chain), while tumors of higher grade showed variable, focal staining, leading to erroneous diagnosis, especially on small biopsies.
Conclusions
The diagnosis of endobronchial SMTs relies on histopathological examination, for both confirmation of smooth muscle lineage and determination of the malignant potential of the lesion. Appropriate immunohistochemical panels including more than one marker of smooth muscle differentiation are extremely valuable for differential diagnosis from morphological mimics, which is necessary for instituting appropriate management.

Citations

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Case report: Successful bronchoscopic interventional treatment of endobronchial leiomyomas
Yinfeng Wang, Yixiang Zhang, Ruirui Tong
Open Life Sciences.2024;[Epub] CrossRef
Pediatric endobronchial tumors with a mimicker: A case series
Kulwiwat Promsawasdi, Teerasak Phewplung
Pediatric Pulmonology.2024; 59(10): 2669. CrossRef
Smooth Muscle Conditions of the Chest
Matthew R. McCann, Lucas R. Massoth, Carlos A. Rojas, Yin P. Hung, John P. Lichtenberger, Gerald F. Abbott, Justin T. Stowell
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A Well-Defined Endobronchial Tumor in a 26-Year-Old Man
Christina Triantafyllidou, Petros Effraimidis, Mirjam Schimanke, Simone Ignatova, Anders Ringman, Susann Skoog, Farkas Vánky, Miklós Boros, Karin Cederquist
Chest.2021; 159(5): e313. CrossRef
Primary Pulmonary Leiomyoma
Mohammad Abu-Hishmeh, Gowthami Kobbari, Fouzia Shakil, Oleg Epelbaum
Journal of Bronchology & Interventional Pulmonology.2020; 27(4): e54. CrossRef

Review

Thyroid Cytology in India: Contemporary Review and Meta-analysis: Shipra Agarwal, Deepali Jain; J Pathol Transl Med. 2017;51(6):533-547. Published online October 5, 2017; DOI: https://doi.org/10.4132/jptm.2017.08.04

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Abstract PDF

Fine-needle aspiration cytology (FNAC) is a screening test for triaging thyroid nodules, aiding in subsequent clinical management. However, the advantages have been overshadowed by the multiplicity of reporting systems and a wide range of nomenclature used. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) was formulated in 2007, to give the world a uniform thyroid cytology reporting system, facilitating easy interpretation by the clinicians. Here, we review the status of thyroid FNAC in India in terms of various reporting systems used including a meta-analysis of the previously published data. An extensive literature search was performed using internet search engines. The reports with detailed classification system used in thyroid cytology were included. The meta-analysis of published data was compared with the implied risk of malignancy by TBSRTC. More than 50 studies were retrieved and evaluated. TBSRTC is currently the most widely used reporting system with different studies showing good efficacy and interobserver concordance. Ancillary techniques have, as of now, limited applicability and acceptability in thyroid cytology in India. Twenty-eight published articles met the criteria for inclusion in the meta-analysis. When compared with TBSRTC recommendations, the meta-analysis showed a higher risk of malignancy for categories I and III. Thyroid FNAC is practiced all over India. TBSRTC has found widespread acceptance, with most institutions using this system for routine thyroid cytology reporting. However, reasons for a high malignancy risk for categories I and III need to be looked into. Various possible contributing factors are discussed in the review.

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Thermal imaging based pre-diagnostics tool for Graves’ disease
Vaishali Sharma, Vandana K Dhingra, Snehlata Shakya, Ashok Kumar, Mayank Goswami
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High Malignancy Risk and Its Predictors in South Indian Patients With Bethesda II Thyroid Nodules
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DIAGNOSTIC EFFICACY OF FNAC IN THYROID LESIONS, CLASSIFIED ACCORDING TO BETHESDA SYSTEM WITH CYTOHISTOLOGICAL CORRELATION
KIRAN KUMARI MEENA, SANDHYA BORDIA, POOJA KANWAT, SEEMA MEENA, PRAGYA JAKHAR
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Evaluation of Thyroid Lesions by the Bethesda System for Reporting Thyroid Cytopathology
Syed Asif Hashmi, Monika Aggrawal, Rahul Pandey, Deepika Gulati, Inam Danish Khan
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Incidence and Malignancy Rates in Thyroid Nodules in North-East Indian Population by Bethesda System: A Single Institutional Experience of 3 Years
Suvamoy Chakraborty, Manu C. Balakrishnan, Vandana Raphael, Prachurya Tamuli, Anuradha Deka
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Evaluation of Concordance of Ultrasound, Cytology, and Histopathology in Solitary Thyroid Nodules
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Cytomorphological Categorization of Thyroid Lesions according to The Bethesda System for Reporting Thyroid Cytology and Correlation with their Histological Outcome
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Original Article

Acid-Fastness of Histoplasma in Surgical Pathology Practice: Madhu Rajeshwari, Immaculata Xess, Mehar Chand Sharma, Deepali Jain; J Pathol Transl Med. 2017;51(5):482-487. Published online September 14, 2017; DOI: https://doi.org/10.4132/jptm.2017.07.11

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Abstract PDF

Background
Histoplasmosis (HP) is diagnosed by visualizing intracellular microorganisms in biopsy and/or culture. Periodic-acid Schiff (PAS) and Gomori methenamine silver (GMS) staining methods are routinely used for identification. The acid-fast property of Histoplasma was identified decades ago, but acid-fast staining has not been practiced in current surgical pathology. Awareness of the acid-fast property of Histoplasma, which is due to mycolic acid in the cell wall, is important in distinguishing Histoplasma from other infective microorganisms. Here, we examined acid-fastness in previously diagnosed cases of Histoplasma using the Ziehl-Neelsen (ZN) stain and correlated those findings with other known fungal stains. Methods: All cases diagnosed as HP were retrieved and reviewed along with ZN staining and other fungal stains. We also stained cases diagnosed with Cryptococcus and Leishmania as controls for comparison. Results: A total of 54 patients ranging in age from 11 to 69 years were examined. The most common sites of infection were the skin, adrenal tissue, and respiratory tract. Of the total 43 tissue samples, 20 (46.5%) stained positive with the ZN stain. In viable cases, a significant proportion of microorganisms were positive while necrotic cases showed only rare ZN-positive yeasts. In comparison to PAS and GMS stains, there was a low burden of ZN-positive yeasts. Cryptococcus showed characteristic ZN staining and all cases of Leishmania were negative. Conclusions: Although the morphology of fungal organisms is the foundation of identification, surgical pathologists should be aware of the acid-fast property of fungi, particularly when there is the potential for confusion with other infective organisms.

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