Advances in Diagnostic Cytopathology

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (31 August 2022) | Viewed by 30966

Special Issue Editors


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Guest Editor
Servicio de Anatomía Patológica, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria Princesa (IP), 28006 Madrid, Spain
Interests: fine-needle aspiration cytology; immunocytochemistry; cell biology; epithelial-to-mesenchymal transition; mesothelial cells; carcinoma-associated fibroblasts; thyroid cytopathology; brain tumors
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Guest Editor
1. Department of Surgical Pathology, Hospital Clínico San Carlos, Madrid, Spain
2. Health Research Institute of the Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
Interests: tumors; histopathology; immunohistochemistry; histology; cancer diagnostics; surgical pathology; prognostic markers; cancer biomarkers; cancer biology; tumor markers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cytopathology is a well-established discipline within diagnostic pathology. Its main advantage is that it involves minimally invasive procedures that permit easy, safe, and rapid sampling of tumors and other lesions, as well as access to locations where a tissue biopsy is exceedingly difficult or impossible to perform. Its principal limitation is the small amount of material retrieved, which requires optimal management in order to respond to the increasing demand for ancillary studies in our clinical practice. Its reduced invasiveness has led to the development of new diagnostic techniques, such as endoscopic ultrasound-guided fine needle aspiration (FNA) of mediastinal, pancreatic, and other abdominal lesions, greatly contributing to the diagnosis, staging, and treatment of tumors of these locations. Another significant achievement has been the publication of cytologic reporting systems for organs beyond the uterine cervix and thyroid, improving the quality of communication between pathologists and clinicians. Other aspects of diagnostic cytology such as effusion cytology, cervical cytology, and intraoperative cytology also play a key role in offering a minimally invasive pathologic diagnosis.

The latest advances in molecular biology and artificial intelligence are certainly going to revolutionize the diagnosis of neoplasms. What will be the role of conventional diagnostic pathology in this new context, however? In the era of molecular medicine, cytology establishes an ideal link between diagnostic morphology and molecular studies. Due to their low invasiveness, cytological procedures are ideal for obtaining material for molecular studies. This Special Issue will highlight recent advances in basic morphologic aspects of clinical cytopathology, new reporting systems, as well as the bridging role of cytology between diagnostic morphology and molecular studies. Studies revealing negative results are also welcome. This Special Issue will consider original research articles, short clinical series, case reports, as well as reviews on all aspects of diagnostic cytopathology.

Prof. Dr. José A. Jiménez-Heffernan
Dr. Cristina Díaz del Arco
Guest Editors

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Published Papers (8 papers)

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Research

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11 pages, 1644 KiB  
Article
Analysis of Argyrophilic Nucleolar Organizer Regions (AgNORs) in Acute Leukemia in Adults
by Małgorzata Gajewska, Elżbieta Rutkowska, Iwona Kwiecień, Piotr Rzepecki and Kazimierz Sułek
Diagnostics 2022, 12(4), 832; https://doi.org/10.3390/diagnostics12040832 - 28 Mar 2022
Cited by 2 | Viewed by 2766
Abstract
The evaluation of argyrophilic nucleolar organizer regions (AgNORs) uses a simple method used in research into neoplasm. Bone marrow aspirates from 70 patients with acute leukemia underwent morphological, immunophenotypic, and genetic assessment and were stained with silver nitrate. In leukemic cells, the mean [...] Read more.
The evaluation of argyrophilic nucleolar organizer regions (AgNORs) uses a simple method used in research into neoplasm. Bone marrow aspirates from 70 patients with acute leukemia underwent morphological, immunophenotypic, and genetic assessment and were stained with silver nitrate. In leukemic cells, the mean AgNORs number, mean AgNORs area, and mean AgNOR-area-to-nucleus-area ratio were calculated in patients with acute myeloid leukemia (AML), patients with acute lymphoblastic leukemia (ALL), and selected risk groups. A higher value of all measured AgNOR parameters was observed in patients with AML compared to the ALL group. In AML patients, a higher mean AgNOR area was found in the ELN3 cytogenetic group compared to the ELN2 cytogenetic group. A higher value of the mean AgNOR count was observed in patients with white blood cells (WBCs) > 12 × 109/L than in the group with WBCs ≤ 12 × 109/L, as well as in patients with >20% blasts in peripheral blood (PB) than in patients with ≤20% blasts in PB. In the ALL group, a higher mean AgNOR-area-to-nucleus-area ratio was found in group with the presence of Philadelphia chromosome Ph(+) than without the Philadelphia chromosome Ph(−). AgNOR parameter analysis is a valuable method for differentiation of AML and ALL in adults. Full article
(This article belongs to the Special Issue Advances in Diagnostic Cytopathology)
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9 pages, 954 KiB  
Article
Efficacy and Safety of Pancreatic Juice Cytology with Synthetic Secretin in Diagnosing Malignant Intraductal Papillary Mucinous Neoplasms of the Pancreas
by Yohei Takeda, Kazuya Matsumoto, Takumi Onoyama, Taro Yamashita, Hiroki Koda, Wataru Hamamoto, Yuri Sakamoto, Takuya Shimosaka, Shiho Kawahara, Yasushi Horie and Hajime Isomoto
Diagnostics 2022, 12(3), 744; https://doi.org/10.3390/diagnostics12030744 - 18 Mar 2022
Cited by 2 | Viewed by 1890
Abstract
The risk of malignant transformation of intraductal papillary mucinous neoplasm (IPMN) is presently assessed using imaging, which remains unsatisfactory. Given the high viscosity of pancreatic juice, pancreatic juice cytology (PJC) is considered an investigational procedure. We previously demonstrated that the diagnostic performance of [...] Read more.
The risk of malignant transformation of intraductal papillary mucinous neoplasm (IPMN) is presently assessed using imaging, which remains unsatisfactory. Given the high viscosity of pancreatic juice, pancreatic juice cytology (PJC) is considered an investigational procedure. We previously demonstrated that the diagnostic performance of PJC was improved via synthetic secretin loading in pancreatic ductal carcinoma. This study aimed to evaluate the efficacy of synthetic secretin-loaded PJC (S-PJC) for IPMN. The usefulness and safety of S-PJC were prospectively evaluated in 133 patients with IPMN. Overall, 92, 12, and 26 patients had branch duct, main duct, and mixed-type lesions, respectively. The risk classifications based on the 2017 international consensus guidelines were high-risk stigmata, worrisome features, and no risk in 29, 59, and 45 patients, respectively. Synthetic secretin loading improved the sensitivity of PJC from 50.0% to 70.8%. Complications included 13 (9.8%) cases of mild pancreatitis, 1 (0.8%) case of acute cholangitis, and 1 (0.8%) case of Mallory–Weiss syndrome, all of which resolved with conservative treatment. In conclusion, synthetic secretin-loaded PJC improved the diagnostic performance of cytology for malignant IPMN. We recommend using synthetic secretin-loaded PJC for the preoperative pathological diagnosis of malignant IPMN in clinical settings. Full article
(This article belongs to the Special Issue Advances in Diagnostic Cytopathology)
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9 pages, 1083 KiB  
Article
PRAME Immunocytochemistry for the Diagnosis of Melanoma Metastases in Cytological Samples
by Andrea Ronchi, Federica Zito Marino, Elvira Moscarella, Gabriella Brancaccio, Giuseppe Argenziano, Teresa Troiani, Stefania Napolitano, Renato Franco and Immacolata Cozzolino
Diagnostics 2022, 12(3), 646; https://doi.org/10.3390/diagnostics12030646 - 6 Mar 2022
Cited by 7 | Viewed by 2649
Abstract
(1) Background: Fine-needle aspiration cytology is often used for the pre-operative diagnosis of melanoma metastases. The diagnosis may not be confidently established based on morphology alone, and immunocytochemistry is mandatory. The choice of the most advantageous immunocytochemical antibodies is critical, as the sample [...] Read more.
(1) Background: Fine-needle aspiration cytology is often used for the pre-operative diagnosis of melanoma metastases. The diagnosis may not be confidently established based on morphology alone, and immunocytochemistry is mandatory. The choice of the most advantageous immunocytochemical antibodies is critical, as the sample may be scant, and the presence of pigmented histiocytes may be confounding. However, the diagnostic performance of melanocytic markers in this setting is poorly investigated. Moreover, PRAME (preferentially expressed antigen in melanoma) recently emerged as a novel marker for the diagnosis of melanoma. The current work aimed to evaluate the sensitivity and specificity of PRAME for the diagnosis of melanoma metastases in cytological samples, compared to other melanocytic markers. (2) Methods: PRAME, S100, Melan-A, HMB45 and SOX10 were tested on cell block sections of 48 cases of melanoma metastases diagnosed from cytological samples, and 20 cases of reactive lymphadenopathy. (3) Results: S100 and SOX10 showed the highest sensitivity (100%), while the sensitivity of PRAME was 85.4%. PRAME, Melan-A, SOX10 and HMB45 showed a specificity of 100%, while the specificity of S100 was lower (85%), as it marked some histiocytes. (4) Conclusion: PRAME immunocytochemistry is highly specific for the diagnosis of melanoma metastasis from a cytological sample, but is less sensitive compared with other melanocytic markers. Full article
(This article belongs to the Special Issue Advances in Diagnostic Cytopathology)
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16 pages, 6584 KiB  
Article
Cytological Diagnosis of Pancreatic Solid-Pseudopapillary Neoplasm: A Single-Institution Community Practice Experience
by Brant G. Wang, Haresh Mani, Zoe Q. Wang and Wenping Li
Diagnostics 2022, 12(2), 449; https://doi.org/10.3390/diagnostics12020449 - 9 Feb 2022
Cited by 6 | Viewed by 2679
Abstract
Introduction. Pancreatic solid-pseudopapillary neoplasm (SPN) is a rare tumor that typically occurs in young females. Although a cytological diagnosis may be easily made in this age group when there are typical features, atypical clinical presentations and unusual cytological features may make this a [...] Read more.
Introduction. Pancreatic solid-pseudopapillary neoplasm (SPN) is a rare tumor that typically occurs in young females. Although a cytological diagnosis may be easily made in this age group when there are typical features, atypical clinical presentations and unusual cytological features may make this a challenging diagnosis. We present our single-institution experience in a cohort of these tumors, outlining both typical and atypical features. Awareness of unusual clinical and cytological features can help to avoid pitfalls during diagnosis. Methods. We performed a review of all cases of pancreatic SPNs diagnosed over a 15-year period (January 2007 to December 2021). Detailed cytological, clinical, and follow-up histological features were presented and analyzed. Results. Twenty-two cases of SPN were diagnosed at our institution during this 15-year period. Patients ranged from 12 to 73 years of age (mean 33 y, median 26 y) and included 19 females and 3 males. Seventeen patients had cytological material, and fourteen were diagnosed by EUS-FNA. Typical cytological features included papillary clusters with central capillaries, myxoid stroma, monomorphism, cercariform cells, and hyaline globules. Atypical or unusual cytological features that were seen in a few cases were multinucleated giant cells, clear cells, and/or foamy macrophages. A few cases showed features that were similar to pancreatic neuroendocrine tumors (PanNETs). Tumor cells were always positive for β-catenin, CD10, CD56, cyclin-D1, progesterone receptor (PR), and vimentin by immunohistochemistry. They were always negative for chromogranin. Pancytokeratin and synaptophysin stains were positive in 9% and 46% of cases evaluated, respectively. All cases had histological confirmation on resection. The median follow-up duration was 69 months (a range of 2–177 months), with only three cases lost to follow-up. No recurrence or metastasis was identified. Conclusions. We present our experience with cytological diagnoses of SPN in a well-characterized cohort of 22 patients with histological correlation and follow-up data. These tumors occur over a wide range and show varied cytological features. SPNs can be confidently diagnosed on limited cytological material, with limited panel immunohistochemistry aiding diagnosis in atypical cases. Recognizing the associated degenerative changes is crucial in avoiding a misdiagnosis. Full article
(This article belongs to the Special Issue Advances in Diagnostic Cytopathology)
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Review

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15 pages, 3785 KiB  
Review
The Diagnostic Dilemma of Urothelial Tissue Fragments in Urinary Tract Cytology Specimens
by Derek B. Allison, M. Lisa Zhang, Poonam Vohra and Christopher J. VandenBussche
Diagnostics 2022, 12(4), 931; https://doi.org/10.3390/diagnostics12040931 - 8 Apr 2022
Cited by 8 | Viewed by 7225
Abstract
Since the release of The Paris System for Reporting Urinary Cytology (TPS), the assessment of urine cytology specimens has primarily focused on the detection of high-grade urothelial carcinoma (HGUC) and carcinoma in situ (CIS). Fortunately, the malignant cells in these lesions tend to [...] Read more.
Since the release of The Paris System for Reporting Urinary Cytology (TPS), the assessment of urine cytology specimens has primarily focused on the detection of high-grade urothelial carcinoma (HGUC) and carcinoma in situ (CIS). Fortunately, the malignant cells in these lesions tend to be loosely cohesive, resulting in the natural exfoliation of individual malignant cells into the urine. However, HGUC/CIS lesions occasionally exfoliate larger fragments which can be difficult to assess due to cellular overlap and fragment three-dimensionality. Furthermore, reactive benign urothelial fragments and fragments from low-grade urothelial neoplasms (LGUN) may also be seen in urine specimens and contain atypical cytomorphologic features. As a result, the significance of urothelial tissue fragments (UTFs) is often unclear. Herein, we discuss the literature on UTFs before and after the implementation of TPS, as well as strategies to help overcome this diagnostic challenge. Full article
(This article belongs to the Special Issue Advances in Diagnostic Cytopathology)
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13 pages, 1314 KiB  
Review
A Cytological Review of Follicular Dendritic Cell-Derived Tumors with Emphasis on Follicular Dendritic Cell Sarcoma and Unicentric Castleman Disease
by José A. Jiménez-Heffernan, Cristina Díaz del Arco and Magdalena Adrados
Diagnostics 2022, 12(2), 406; https://doi.org/10.3390/diagnostics12020406 - 4 Feb 2022
Cited by 7 | Viewed by 5713
Abstract
Follicular dendritic cells (FDCs) are antigen-presenting cells located in the germinal centers of the lymph nodes. Among the few tumors showing FDC differentiation are follicular dendritic cell sarcoma (FDCS) and Castleman disease (CD), more precisely the unicentric hyaline vascular (HV) variant. Both are [...] Read more.
Follicular dendritic cells (FDCs) are antigen-presenting cells located in the germinal centers of the lymph nodes. Among the few tumors showing FDC differentiation are follicular dendritic cell sarcoma (FDCS) and Castleman disease (CD), more precisely the unicentric hyaline vascular (HV) variant. Both are relatively rare tumors, and the diagnostic cytological experience is limited to descriptions of isolated cases or small series. The purpose of this review is to bring together all the available cytological published information, and our personal experience, in order to obtain a global idea of the cytological features of these peculiar FDC-derived tumors. The different descriptions of FDCS are very similar, reflecting a tumor that shows repetitive and characteristic cytological features. It shows a dimorphic population of mature lymphocytes and large tumoral cells with partial spindle morphology. Most cases of HV variant of CD can be recognized as benign upon cytology, however a precise diagnosis seems more difficult. It is characterized by reactive lymphocytes mixed with vessels and FDCs, either single or forming syncytial aggregates. Both, FDCS and CD are challenging for cytological diagnosis in which a high index of suspicion is necessary for a correct preoperative assessment. Cytology is very useful for follow-up of recurrences and metastases. Full article
(This article belongs to the Special Issue Advances in Diagnostic Cytopathology)
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14 pages, 1116 KiB  
Review
The Value of Cytology in the Evaluation of Malignant Pericardial Effusions: A Systematic Review
by Ranim Shartouni, Roy Shartouni, Maryam Mahmoodi and Ilias P. Nikas
Diagnostics 2022, 12(2), 367; https://doi.org/10.3390/diagnostics12020367 - 1 Feb 2022
Cited by 8 | Viewed by 2793
Abstract
Pericardial effusions can be caused by diverse etiologies, including heart-related conditions, kidney failure, trauma, infections, autoimmune diseases, and cancer. This systematic review aimed to assess the role of cytology in identifying the most prevalent cancers related to malignant pericardial effusions (MPEs), the ability [...] Read more.
Pericardial effusions can be caused by diverse etiologies, including heart-related conditions, kidney failure, trauma, infections, autoimmune diseases, and cancer. This systematic review aimed to assess the role of cytology in identifying the most prevalent cancers related to malignant pericardial effusions (MPEs), the ability of cytology, compared to histology, to detect cancer while evaluating pericardial effusions, and the prognostic impact of MPEs. Four electronic databases were investigated using a predefined algorithm, and specific inclusion and exclusion criteria. We found that the most prevalent primaries associated with MPEs were lung (especially NSCLCs), breast, hematolymphoid, and gastrointestinal cancers. MPEs tended to be hemorrhagic rather than serous or serosanguinous and to occupy larger volumes compared to non-neoplastic effusions. In addition, cytology was shown to exhibit an enhanced ability to detect cancer compared to biopsy in most of the included studies. Lastly, the presence of an MPE was associated with poor prognosis, while survival depended on the specific cancer type detected. Particularly, prognosis was found to be worse when MPEs were caused by lung or gastric cancer, rather than breast or hematolymphoid malignancies. In conclusion, evidence suggests that cytologic evaluation has a significant diagnostic and prognostic impact in patients with MPEs. Full article
(This article belongs to the Special Issue Advances in Diagnostic Cytopathology)
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Other

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6 pages, 4151 KiB  
Case Report
Synchronous Thyrolipoma and Papillary Thyroid Carcinoma: A Rare but Significant Event
by Mariya Kuk, Chu-Jen Kuo, Van-Hung Nguyen and Chien-Chin Chen
Diagnostics 2021, 11(8), 1334; https://doi.org/10.3390/diagnostics11081334 - 26 Jul 2021
Cited by 1 | Viewed by 2437
Abstract
The presence of adipocytes within thyroid glands is a rare finding seen in thyrolipoma, diffuse lipomatosis, or thyroid teratoma. Although some cases present with multinodular goiter or autoimmune thyroiditis, the exact cause has not yet been elucidated. Among reported cases, thyrolipomas mainly occur [...] Read more.
The presence of adipocytes within thyroid glands is a rare finding seen in thyrolipoma, diffuse lipomatosis, or thyroid teratoma. Although some cases present with multinodular goiter or autoimmune thyroiditis, the exact cause has not yet been elucidated. Among reported cases, thyrolipomas mainly occur in females and usually present as a solitary lesion. However, a few reported cases had coexisting papillary thyroid carcinomas. Herein, we present a 51-year-old female with synchronous thyrolipoma (2.0 × 1.5 × 1.3 cm) and papillary thyroid carcinoma (0.7 × 0.6 × 0.6 cm) within the same thyroid lobe. She had diabetes mellitus and hypertension and complained of anterior neck enlargement and discomfort for three months. Thyroid sonography showed multiple hypoechoic nodules, one of which was heterogeneous and ill-defined. Fine needle aspirate cytology for the ill-defined nodule was suspicious for papillary thyroid carcinoma. She subsequently received radical thyroidectomy and neck lymph node dissection. Histopathologically, one thyrolipoma and one papillary thyroid carcinoma were identified in the right lobe of the thyroid gland without metastases of lymph nodes, while other nodules were multinodular goiter. Notably, thyrolipoma may not be simply an incidental finding but might coexist with thyroid carcinomas. A brief review of the pertinent literature of prior reports is also provided. Full article
(This article belongs to the Special Issue Advances in Diagnostic Cytopathology)
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