Every patient with advanced non–small cell lung cancer (NSCLC) should be tested for targetable driver mutations and gene arrangements that may open avenues for targeted therapy. As most patients with NSCLC in the advanced stage of the disease are not candidates for surgery, these tests have to be performed on small biopsies or cytology samples. A growing number of other genetic changes with targetable mutations may be treatable in the near future. To identify patients who might benefit from novel targeted therapy, relevant markers should be tested in an appropriate context. In addition, immunotherapy of lung cancer is guided by the status of programmed death-ligand 1 expression in tumor cells. The variety and versatility of cytological specimen preparations offer significant advantages for molecular testing; however, they frequently remain underused. Therefore, evaluating the utility and adequacy of cytologic specimens is important, not only from a lung cancer diagnosis, but also for the large number of ancillary studies that are necessary to provide appropriate clinical management. A large proportion of lung cancers is diagnosed by aspiration or exfoliative cytology specimens; thus, optimizing strategies to triage and best use the tissue for diagnosis and biomarker studies forms a critical component of lung cancer management. In this review, we discuss the opportunities and challenges of using cytologic specimens for biomarker testing of lung cancer and the role of cytopathology in the molecular era.
Due to the extremely indolent behavior, a subset of noninvasive encapsulated follicular variant papillary thyroid carcinomas has been classified as “noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)” since 2016 and is no longer considered carcinoma. Since the introduction of this new terminology, changes and refinements have been made in diagnostic criteria. Initially, the incidence of NIFTP was estimated substantial. However, the reported incidence of NIFTP varies greatly among studies and regions, with higher incidence in North American and European countries than in Asian countries. Thus, the changes in the risk of malignancy (ROM) in the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) differ inevitably among regions. Because more conservative surgery is recommended for NIFTPs, distinguishing NIFTPs from papillary thyroid carcinomas in preoperative fine-needle aspiration cytology became one of the major concerns. This review will provide comprehensive overview of updates on diagnostic criteria, actual incidence and preoperative cytologic diagnoses of NIFTP, and its impact on the ROM in TBSRTC.
High-throughput genomics and transcriptomics are often applied in routine pathology practice to facilitate cancer diagnosis, assess prognosis, and predict response to therapy. However, the proteins rather than nucleic acids are the functional molecules defining the cellular phenotype in health and disease, whereas genomic profiling cannot evaluate processes such as the RNA splicing or posttranslational modifications and gene expression does not necessarily correlate with protein expression. Proteomic applications have recently advanced, overcoming the issue of low depth, inconsistency, and suboptimal accuracy, also enabling the use of minimal patient-derived specimens. This review aims to present the recent evidence regarding the use of high-throughput proteomics in both exfoliative and fine-needle aspiration cytology. Most studies used mass spectrometry, as this is associated with high depth, sensitivity, and specificity, and aimed to complement the traditional cytomorphologic diagnosis, in addition to identify novel cancer biomarkers. Examples of diagnostic dilemmas subjected to proteomic analysis included the evaluation of indeterminate thyroid nodules or prediction of lymph node metastasis from thyroid cancer, also the differentiation between benign and malignant serous effusions, pancreatic cancer from autoimmune pancreatitis, non-neoplastic from malignant biliary strictures, and benign from malignant salivary gland tumors. A few cancer biomarkers—related to diverse cancers involving the breast, thyroid, bladder, lung, serous cavities, salivary glands, and bone marrow—were also discovered. Notably, residual liquid-based cytology samples were suitable for satisfactory and reproducible proteomic analysis. Proteomics could become another routine pathology platform in the near future, potentially by using validated multi-omics protocols.
Background The Continuous Quality Improvement program for cytopathology in 2020 was completed during the coronavirus pandemic. In this study, we report the result of the quality improvement program.
Methods Data related to cytopathology practice from each institute were collected and processed at the web-based portal. The proficiency test was conducted using glass slides and whole-slide images (WSIs). Evaluation of the adequacy of gynecology (GYN) slides from each institution and submission of case glass slides and WSIs for the next quality improvement program were performed.
Results A total of 214 institutions participated in the annual cytopathology survey in 2020. The number of entire cytopathology specimens was 8,220,650, a reduction of 19.0% from the 10,111,755 specimens evaluated in 2019. Notably, the number of respiratory cytopathology specimens, including sputum and bronchial washing/ brushing significantly decreased by 86.9% from 2019, which could be attributed to the global pandemic of coronavirus disease. The ratio of cases with atypical squamous cells to squamous intraepithelial lesions was 4.10. All participating institutions passed the proficiency test and the evaluation of adequacy of GYN slides.
Conclusions Through the Continuous Quality Improvement program, the effect of coronavirus disease 2019 pandemic, manifesting with a reduction in the number of cytologic examinations, especially in respiratory-related specimen has been identified. The Continuous Quality Improvement Program of the Korean Society for Cytopathology can serve as the gold standard to evaluate the current status of cytopathology practice in Korea.
Because different types of thyroid malignancies have distinct embryological origins, coexisting tumors are rarely observed. We describe a coexisting papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC) first suspected by fine-needle aspiration cytology (FNAC). A 57-year-old female presented with an irregular mass in the right thyroid lobe. The cytopathologic findings of fine-needle aspiration showed two components: a papillary-like arrangement consisting of cells with pale enlarged nuclei indicative of PTC and loose clusters comprised of oval cells with granular chromatin indicative of MTC. The diagnosis of a coexisting PTC and MTC was initially confirmed by calcitonin immunocytochemistry and later after total thyroidectomy. Although some surgical case reports of PTC and MTC coexisting in either the same or different lobes have been documented, a case suspected by FNAC before the surgery has rarely been reported. Because appropriate treatment and prognosis of PTC and MTC are different, cytopathologists should be aware of this rare entity.
Background Gastric-type endocervical adenocarcinoma (GEA) is unrelated to human papillomavirus (HPV) infection and is clinically aggressive compared with HPV-associated usual-type endocervical adenocarcinoma (UEA). The cytological diagnosis falls short of a definitive diagnosis of GEA and is often categorized as atypical glandular cells (AGCs). To improve cytologic recognition, cytological findings of HPV-independent GEA were analyzed and the results compared with HPV-associated UEA.
Methods Cervical Papanicolaou (Pap) smears from eight patients with a histopathologic diagnosis of GEA and 12 control cases of UEA were reviewed. All slides were conventionally prepared and/or liquid-based prepared (ThinPrep) and stained following the Pap method. A mucinous background, architectural, nuclear, and cytoplasmic features were analyzed and compared with UEA.
Results Preoperative cytologic diagnoses of the eight GEA cases were AGCs, favor neoplastic in three cases, adenocarcinoma in situ in one case, and adenocarcinoma in four cases. Cytologically, monolayered honeycomb-like sheets (p = .002) of atypical endocervical cells with vacuolar granular cytoplasm (p = .001) were extensive in GEA, and three-dimensional clusters (p = .010) were extensive in UEA. Although the differences were not statistically significant, background mucin (p = .058), vesicular nuclei (p = .057), and golden-brown intracytoplasmic mucin (p = .089) were also discriminatory findings for GEA versus UEA.
Conclusions Although GEA is difficult to diagnose on cytologic screening, GEA can be recognized based on cytologic features of monolayered honeycomb sheets of atypical endocervical cells with abundant vacuolar cytoplasm and some golden-brown intracytoplasmic mucin. UEA cases are characterized by three-dimensional clusters.
Lymphocyte-rich effusions represent benign reactive process or neoplastic condition. Involvement of lymphoproliferative disease in body cavity is not uncommon, and it often causes diagnostic challenge. In this review, we suggest a practical diagnostic approach toward lymphocyte-rich effusions, share representative cases, and discuss the utility of ancillary tests. Cytomorphologic features favoring neoplastic condition include high cellularity, cellular atypia/pleomorphism, monomorphic cell population, and frequent apoptosis, whereas lack of atypia, polymorphic cell population, and predominance of small T cells usually represent benign reactive process. Involvement of non-hematolymphoid malignant cells in body fluid should be ruled out first, followed by categorization of the samples into either small/medium-sized cell dominant or large-sized cell dominant fluid. Small/medium-sized cell dominant effusions require ancillary tests when either cellular atypia or history/clinical suspicion of lymphoproliferative disease is present. Large-sized cell dominant effusions usually suggest neoplastic condition, however, in the settings of initial presentation or low overall cellularity, ancillary studies are helpful for more clarification. Ancillary tests including immunocytochemistry, in situ hybridization, clonality test, and next-generation sequencing can be performed using cytologic preparations. Throughout the diagnostic process, proper review of clinical history, cytomorphologic examination, and application of adequate ancillary tests are key elements for successful diagnosis.
Metastatic leiomyosarcoma to the thyroid is an extremely rare occurrence, and only 18 cases have been reported. Here, we report a case of a 37-year-old woman who presented with multiple masses on the scalp. Excisional biopsy was done and the mass revealed fascicles of smooth muscle fibers which showed positive staining for smooth muscle actin, thus confirming the diagnosis of leiomyosarcoma. The patient was also found to have a 0.9 cm mass within the left thyroid. Fine-needle aspiration was done and the cytological smear showed hypercellular spindle cell clusters with hyperchromatic and large nuclei. Normal thyroid follicular cells were found within or around tumor cells. In this report, we present the cytologic findings of metastatic leiomyosarcoma to the thyroid and offer differential diagnoses of the aspirated spindle cells.
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In Taiwan, thyroid fine-needle aspiration cytology is easily accessible and reliable for evaluating thyroid nodules. The sonographic pattern plays a major role and is the deciding factor for aspiration. We conducted a nationwide survey in 2017 and it revealed that 31% of laboratories had adopted The Bethesda System for Reporting Thyroid Cytopathology. There was a relatively high unsatisfactory rate (24.04%) and low rates of indeterminate diagnoses, including atypia of undetermined significance/follicular lesions of undetermined significance: 4.87%, and follicular neoplasm/suspicious for a follicular neoplasm: 0.35%. Moreover, the risks of malignancy in benign, atypia of undetermined significance, and suspicious for a follicular neoplasm were relatively high. These may reflect strict diagnostic criteria for indeterminate categories and better patient selection for surgery. Improvements in specimen sampling and continuing education programs are crucial. Newly-developed thyroid cytology technologies, such as immunocytochemistry, molecular testing, and computerized cytomorphometry, may further facilitate cytology diagnoses.
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Background The Korean Society for Cytopathology has conducted the Continuous Quality Improvement program for cytopathology laboratories in Korea since 1995. In 2018 as part of the program, an annual survey of cytologic data was administered to determine the current status of cytopathology practices in Korea. Methods: A questionnaire was administered to 211 cytopathology laboratories. Individual laboratories submitted their annual statistics regarding cytopathology practices, diagnoses of gynecologic samples, inadequacy rates, and gynecologic cytology-histology correlation review (CHCR) data for 2018. In addition, proficiency tests and sample adequacy assessments were conducted using five consequent gynecologic slides. Results: Over 10 million cytologic exams were performed in 2018, and this number has almost tripled since this survey was first conducted in 2004 (compounded annual growth rate of 7.2%). The number of non-gynecologic samples has increased gradually over time and comprised 24% of all exams. The overall unsatisfactory rate was 0.14%. The ratio of the cases with atypical squamous cells to squamous intraepithelial lesions accounted for up to 4.24. The major discrepancy rate of the CHCR in gynecologic samples was 0.52%. In the proficiency test, the major discrepancy rate was approximately 1%. In the sample adequacy assessment, a discrepancy was observed in 0.1% of cases. Conclusions: This study represents the current status of cytopathology practices in Korea, illustrating the importance of the Continuous Quality Improvement program for increasing the accuracy and credibility of cytopathologic exams as well as developing national cancer exam guidelines and government projects on the prevention and treatment of cancer.
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Current status of cytopathology practice in Korea: impact of the coronavirus pandemic on cytopathology practice Soon Auck Hong, Haeyoen Jung, Sung Sun Kim, Min-Sun Jin, Jung-Soo Pyo, Ji Yun Jeong, Younghee Choi, Gyungyub Gong, Yosep Chong Journal of Pathology and Translational Medicine.2022; 56(6): 361. CrossRef
Background Since 1995, the Korean Society for Cytopathology has overseen the Continuous Quality Improvement program for cytopathology laboratories. The Committee of Quality Improvement has carried out an annual survey of cytology data for each laboratory and set standards for proficiency tests. Methods: Evaluations were conducted four times per year from 2008 to 2018 and comprised statistics regarding cytology diagnoses of previous years, proficiency tests using cytology slides provided by the committee, assessment of adequacy of gynecology (GYN) cytology slides, and submission of cytology slides for proficiency tests. Results: A total of 206 institutes participated in 2017, and the results were as follows. The number of cytology tests increased from year to year. The ratio of liquid-based cytology in GYN gradually decreased, as most of the GYN cytology had been performed at commercial laboratories. The distribution of GYN diagnoses demonstrated nearly 3.0% as atypical squamous cells. The rate for squamous cell carcinoma was less than 0.02%. The atypical squamous cell/squamous intraepithelial lesion ratio was about 3:1 and showed an upward trend. The major discordant rate of cytology-histology in GYN cytology was less than 1%. The proficiency test maintained a major discordant rate less than 2%. The rate of inappropriate specimens for GYN cytology slides gradually decreased. Conclusions: The Continuous Quality Improvement program should be included in quality assurance programs. Moreover, these data can contribute to development of national cancer examination guidelines and facilitate cancer prevention and treatment.
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Background The cytologic diagnosis of poorly differentiated thyroid carcinoma (PDTC) is difficult because it lacks salient cytologic findings and shares cytologic features with more commonly encountered neoplasms. Due to diverse cytologic findings and paucicellularity of PDTC, standardization of cytologic diagnostic criteria is limited. The purpose of this study is to investigate and recognize diverse thyroid findings of fine needle aspiration (FNA) cytology and frozen smear cytology in diagnosis of this rare but aggressive carcinoma.
Methods The present study included six cases of FNA cytology and frozen smears of histologically diagnosed PDTCs.
Results PDTC showed cytologic overlap with well-differentiated thyroid carcinomas (WDTCs). Five of six cases showed dedifferentiation arising from well differentiated thyroid carcinomas. Only one de novo PDTC showed highly cellular smears composed of discohesive small cells, high nuclear/cytoplasmic (N/C) ratio, prominent micronucleoli, and irregular nuclei. Retrospectively reviewed, these findings are highly suspicious for PDTC. Cytologic findings of nuclear atypia, pleomorphism, and irregularity were frequently found, whereas scattered small cells were seen only in the de novo case.
Conclusions Heterogeneous cytologic findings of PDTCs are shared with those of WDTCs and contribute to difficult preoperative cytologic diagnoses. Most PDTCs show dedifferentiation from WDTCs. Albeit rare, de novo PDTC should be considered with cytology showing discohesive small cells with high N/C ratio. This will enable precise diagnosis and prompt treatment of this aggressive malignancy
Background Hyperchromatic crowed groups (HCGs) are defined as three-dimensional aggregates of crowded cells with hyperchromatic nuclei, and are frequently encountered in cervicovaginal liquid-based cytology (LBC). Here, we aimed to examine the prevalence of HCGs in cervicovaginal LBC and the cytomorphological characteristics of various epithelial cell clusters presenting as HCGs.
Methods We first examined the prevalence of HCGs in a “routine cohort” of LBC cytology (n=331), consisting of all cervicovaginal LBCs accessioned over 3 days from outpatient clinics (n=179) and the screening population (n=152). Then we examined a second “high-grade epithelial cell abnormalities (H-ECA) cohort” (n=69) of LBCs diagnosed as high-grade squamous intraepithelial lesion (HSIL), squamous cell carcinoma (SCC), or adenocarcinoma during 1 year.
Results HCGs was observed in 34.4% of the routine cohort and were significantly more frequent in the epithelial cell abnormality category compared to the non-neoplastic category (p=.003). The majority of HCGs represented atrophy (70%). Of the 69 histologically confirmed H-ECA cases, all contained HCGs. The majority of cases were HSIL (62%), followed by SCC (16%). Individually scattered neoplastic cells outside the HCGs were significantly more frequent in SCCs compared to glandular neoplasia (p=.002). Despite the obscuring thick nature of the HCGs, examining the edges and the different focal planes of the HCGs and the background were helpful in defining the nature of the HCGs.
Conclusions HCGs were frequently observed in cervicovaginal LBC and were mostly non-neoplastic; however, neoplastic HCGs were mostly high-grade lesions. Being aware of the cytomorphological features of different HCGs is important in order to avoid potential false-negative cytology interpretation.
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A 51-year-old woman presented with severe dizziness. The brain magnetic resonance image revealed a 5.5 cm multiloculated mass with a thick rim in the left temporal lobe. Cytological examination of frozen diagnosis of the mass showed hypercellular sheets of round and rhabdoid cells in a hemorrhagic background, and two mitotic figures were observed. Histologically, the excised dura-based mass consisted of predominantly round cells with small foci of rhabdoid tumor cells in a pseudoalveolar pattern in a hemorrhagic background, and the cells showed nuclear positivity for signal transducer and activator of transcription 6 as well as frequent mitosis. The mass was diagnosed as a grade 3 solitary fibrous tumor (SFT)/hemangiopericytoma (HPC). The cytological diagnosis of SFT/HPC is challenging because of the heterogeneous cytological findings, such as histological heterogeneity, and because there are no standardized cytological criteria for malignant SFT/HPC. Cytological findings, such as singly scattered small cells, hypercellularity, rare ropy collagen, and round and rhabdoid cells with pseudoalveolar pattern, may assist in the diagnosis of malignant SFT/HPC.
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Intraoperative frozen cytology of intraosseous cystic meningioma in the sphenoid bone Na Rae Kim, Gie-Taek Yie Journal of Pathology and Translational Medicine.2020; 54(6): 508. CrossRef
Myunghee Kang, Dong Hae Chung, Na Rae Kim, Hyun Yee Cho, Seung Yeon Ha, Sangho Lee, Jungsuk An, Jae Yeon Seok, Gie-Taek Yie, Chan Jong Yoo, Sang Gu Lee, Eun Young Kim, Woo Kyung Kim, Seong Son, Sun Jin Sym, Dong Bok Shin, Hee Young Hwang, Eung Yeop Kim, Kyu Chan Lee
J Pathol Transl Med. 2019;53(2):104-111. Published online January 14, 2019
Background Pathologic diagnosis of central nervous system (CNS) neoplasms is made by comparing light microscopic, immunohistochemical, and molecular cytogenetic findings with clinicoradiologic observations. Intraoperative frozen cytology smears can improve the diagnostic accuracy for CNS neoplasms. Here, we evaluate the diagnostic value of cytology in frozen diagnoses of CNS neoplasms.
Methods Cases were selected from patients undergoing both frozen cytology and frozen sections. Diagnostic accuracy was evaluated.
Results Four hundred and fifty-four cases were included in this retrospective single-center review study covering a span of 10 years. Five discrepant cases (1.1%) were found after excluding 53 deferred cases (31 cases of tentative diagnosis, 22 cases of inadequate frozen sampling). A total of 346 cases of complete concordance and 50 cases of partial concordance were classified as not discordant cases in the present study. Diagnostic accuracy of intraoperative frozen diagnosis was 87.2%, and the accuracy was 98.8% after excluding deferred cases. Discrepancies between frozen and permanent diagnoses (n = 5, 1.1%) were found in cases of nonrepresentative sampling (n = 2) and misinterpretation (n = 3). High concordance was observed more frequently in meningeal tumors (97/98, 99%), metastatic brain tumors (51/52, 98.1%), pituitary adenomas (86/89, 96.6%), schwannomas (45/47, 95.8%), high-grade astrocytic tumors (47/58, 81%), low grade astrocytic tumors (10/13, 76.9%), non-neoplastic lesions (23/36, 63.9%), in decreasing frequency.
Conclusions Using intraoperative cytology and frozen sections of CNS tumors is a highly accurate diagnostic ancillary method, providing subtyping of CNS neoplasms, especially in frequently encountered entities.
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