Binnur Önal

Objective: To analyse the diagnostic role of trefoil factor‐1 and ‐3 (TFF1, TFF3), forkhead box protein A1 (FOXA1), carbonic anhydrase XII (CA XII) and trichorhinophalangeal syndrome type 1 (TRPS1) in serous effusions. The prognostic role of these markers in breast carcinoma was additionally studied.Methods: Protein expression by immunohistochemistry was analysed in 247 effusions, consisting of 60 breast carcinomas, 54 tubo‐ovarian carcinomas, 47 mesotheliomas, 44 lung carcinomas, 20 uterine corpus and cervical carcinomas, 17 gastrointestinal carcinomas and 5 cancers of other origin.Results: TFF1, TFF3, FOXA1, CA XII and TRPS1 expression was found in 67%, 70%, 88%, 82% and 83% of breast carcinomas, respectively. Expression of all markers was seen in some carcinomas of other origin, most commonly in GI metastases, but was least frequent for TRPS1. CA XII expression was additionally seen in mesotheliomas and reactive mesothelial cells. All 5 markers were significantly overexpressed in breast compared to tubo‐ovarian carcinoma (all p < 0.001) and lung carcinoma (all p < 0.001 except for FOXA1, p = 0.023). TFF1 (p = 0.003), TFF3 (p = 0.008) and FOXA1 (p = 0.017) expression was significantly higher in receptor‐positive compared to receptor‐negative primary breast carcinomas. In survival analysis for 44 breast carcinoma patients with clinical data, TFF1 expression was associated with a trend for longer overall (p = 0.096) and disease‐free (p = 0.06) survival.Conclusion: TFF1, TFF3, FOXA1, CA XII and TRPS1 are sensitive breast carcinoma markers, with FOXA1 performing best in terms of sensitivity and TRPS1 being the most specific. Whether the expression of these markers in breast carcinoma effusions is informative of survival merits further research.

Background: Major diagnostic and therapeutic changes led to the implementation of the ‘lung cancer diagnosis in small biopsies and cytology specimens’ concept in the WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart in 2015. Touch imprints are an established technique in cytology that provides a rapid and minimally invasive method for morphological diagnoses of clinical specimens, accurate subtyping, and molecular characterizations of malignancies. The extended diagnostic requirements from the increasingly limited material provided by minimally invasive biopsy techniques pose major challenges for pathology. Recognizing the relevant features and potential pitfalls is essential for cytologists to avoid misinterpretation. Materials and Methods: A retrospective analysis of endoscopic and surgical biopsy diagnostics was performed on 717 patients (303 women and 414 men; average age of 66.9 years) with clinically suspicious tumor findings at the LungenClinic Grosshansdorf in 2020. A total of 1363 cytological samples were obtained pre-therapeutically from 986 distinct biopsies covering 330 surgically and 656 endoscopically examined pulmonary, mediastinal, and bronchial regions. These samples were then compared with the histological diagnoses that were critical for determining the final therapy. Results: Out of a total of 656 endoscopically examined cases, 322 were classified as malignant, 308 as benign, and 26 as undetermined. While touch imprints and histological analysis separately achieved specificity values of 95.4% and 98.8%, both methods showed sensitivity values of 82.1% and 86.5%, respectively. In contrast, combining the two methods improved the sensitivity by 8 percentage points to 94.6%. Out of 330 cases of surgically examined samples, 137 were malignant, 190 were benign, and 3 were undetermined. The specificity of the morphological examinations for these samples was comparably high at 97.9% and 100%, respectively. In this surgical setting, touch imprints alone achieved a sensitivity of 75.9% (n = 104/137 cases), with a specificity of 97.9% (n = 186/190 cases). The outcome of the histological approach alone and in combination with touch imprints reached a sensitivity of 96.4% (n = 132/137 cases). Conclusions: Cytology and histology achieved comparably high sensitivity and specificity values on small biopsies. Under optimal conditions for morphological analysis in a surgical setting, the sensitivity of cytology for detecting malignant tumors was only 6 percentage points lower compared with the clinical endoscopic setting. A combined approach of cytologic–histologic evaluation for endoscopically examined specimens significantly increased the sensitivity by approximately 8% compared with the surgical setting (p < 0.003).

Background: This prospective study assesses the use of rapid remote online cytological evaluation for diagnosing endoscopical achieved biopsies. It focuses on its effectiveness in identifying benign and malignant conditions using digital image processing. Methods: The study was conducted between April 2021 and September 2022 and involved analyses of 314 Rapid Remote Online Cytological Evaluations in total (154 imprint cytologies, 143 fine needle aspirations and 17 brush cytologies) performed on 239 patients at the LungenClinic Grosshansdorf. During on-site evaluation via telecytology, the time requirement was recorded and the findings were compared with the cyto-/histological and final diagnoses. Results: By means of rapid remote online evaluation, findings of 86 cytological benign, 190 malignant and 38 unclear diagnoses were recorded (Ø assessment time, 100 s; range, 11–370 s). In 27 of the 37 specimens with unclear diagnoses, the final findings were malignant tumours and only 6 were benign changes. The diagnosis of another 4 of these 37 findings remained unclear. Excluding these 37 specimens, rapid remote online evaluation achieved a sensitivity of 90.5% with a specificity of 98.5% and a correct classification rate of 92.4% with regard to the final diagnosis of all cases. As expected, an increase in the sensitivity rate for the cytological detection of malignant tumours (76.1% vs. 92.5%) was found especially in fine-needle aspirations. Conclusions: Rapid remote online analysis allows the fast quantitative and qualitative evaluation of clinically obtained cytological specimens. With a correct classification rate of more than 93%, sampling deficiencies can be corrected promptly and diagnostic and therapeutic approaches can be derived.

Background: This prospective study assesses the use of Rapid Remote Online Cytological Evaluation analysis for diagnosing endoscopical achieved biopsies. It focuses on its effectiveness in identifying benign and malignant conditions using digital image processing. Methods: The study was conducted between April 2021 and September 2022 and involved a total of 314 Rapid Remote Online Cytological Evaluations (17 brush, 143 fine needle aspirations and 154 imprint cytologies) analyses performed on 239 patients at the LungenClinic Grosshansdorf. During on-site evaluation via telecytology, the time requirement was determined and the findings were compared with the cyto-/histological and final diagnoses. Results: By means of Rapid Remote Online Evaluation, 86 cytological benign and 190 malignant and 38 findings of unclear diagnosis were recorded (Ø assessment time 100 sec., range 11 - 370sec.). In 27 of the 38 cases with unclear diagnosis, the final findings were malignant tumours and only 6 were benign changes. The diagnosis of another five of these 38 cases remained unclear. Excluding these 38 findings, the Rapid Remote online cytology achieved a sensitivity of 78.6% with a specificity of 99.5% and a correct classification rate of 93.1% with regard to the final diagnosis of all cases. As expected, an increase in the sensitivity rate for the cytological detection of malignant tumours (76.1% vs. 92.5%) was found especially in fine-needle aspirations. Conclusions: Rapid remote online analysis allows fast quantitative and qualitative evaluation of clinically obtained cytological specimens. With a correct classification rate of more than 93%, sampling deficiencies can be corrected promptly and diagnostic and therapeutic approaches can be derived.

Serous pleural effusions result from increased permeability and changed hydrostatic or colloid osmotic pressure. Laboratory biochemical findings provide conclusions about the effusion compositions. Together with the anamnesis and clinical assessment, they enable the evaluation of the effusion nature. The present study retrospectively analyzed combined biochemical and morphological findings in 2307 effusions of patients from two clinical centers: LungenClinic Grosshansdorf in Germany and Duzce University in Turkey. The effusion cytology results of 1771 and 536 patients from the respective centers were combined with clinical/radiological/biochemical findings and counter compared with the final diagnoses. Cytology verified 738 malignant tumors (643 and 95, respectively). Most effusions were benign (n = 1,569; 77%) and 367 of them were paramalignant (293 and 74, respectively) and 594 were inflammatory (465 and 129, respectively). There was a distinctly lower number of malignant tumors in transudates than exudates (87 vs. 725; p < 0.0001). Squamous cell carcinoma was more frequent in paramalignant pleura effusions (122 cases out of the 367 effusions) than pleural carcinomatosis (32 cases out of the 780 malignant tumors; p < 0.0001). The cell formula was a suitable marker for malignant mesothelioma, predominantly mesothelial, or neutrophilic characterized by elevated LDH (>500 U/L) in the early stage of empyema or its late manifestation. İn conclusion, most effusions are benign. Cytologists, assisted by clinical and biochemical data and microscopic findings, can make significant differential diagnostic contributions beyond the sole detection of malignancy.

Background: Extramedullary plasmacytoma (EMP) of the thyroid is a rare neoplasm that may present either as a solitary plasmacell tumor or involvement of plasma cell myeloma (PCM). In this report, we present a unique case of PCM presented as a thyroid mass without previous history, and initially misinterpreted as medullary carcinoma on fine-needle aspiration cytology (FNAC). Case Presentation: A 77-year-old female presented with shortness of breath and palpitation. Ultrasonography-guided FNAC from the large thyroid mass revealed hypercellular smears composed of monomorphic plasmacytoid cells, focally binucleated, scattered diffusely. Subsequent histopathological examination and immunohistochemistry of thyroidectomy specimen showed infiltration of sheets of plasma cells and diagnosed as EMP. Histology of the bone marrow displayed Lambda positive neoplastic plasma cells. A combination of singly distributed cells and aggregates with plasmacytoid morphology on a proteinous background without clinical suspicion and previous history leads to misinterpretation of FNAC. Conclusion: Clinical correlation, immunocytochemistry, and complementary cytological approach including various preparation techniques of staining are crucial for avoiding diagnostic pitfalls and the patients’ proper treatment.

Background/aim: The management of nodules with indeterminate cytology [atypia of undetermined significance (AUS), follicular lesion of undetermined significance (FLUS), follicular neoplasm (FN), suspicious for a follicular neoplasm (SFN), and suspicious for malignancy (SM)] results is controversial. To assess the role of the elastography technique in the diagnosis of malignancy in the subtypes of indeterminate thyroid nodules. Materials and methods: We included 132 patients with indeterminate cytology who underwent thyroid surgery. Sensitivity, specificity, area under the curve, and optimal cut-off points were calculated with receiver operating characteristic (ROC) analysis for elastography score (ES) and strain index (SI). Results: Malignancy was observed in 27/95 (28.4%) of the AUS-FLUS cytology and 12/24 (50%) of FN, SFN cytology. All of the 13 patients (100 %) with SM are found to be malignant on histology. In the FLUS group, nodules with ES greater or equal to 3, the presence of malignancy was higher 17/41 (41.5%) when compared with nodules with ES smaller than 39/46 (19.6 %) (p = 0.023). In the SFN group, 2 of 2 nodules with an ES score of 4 and 1 of 1 nodule with an ES score of 5 were malignant. In the FLUS group, 4 of 10 nodules with an ES score of 4 and 2 of 2 nodules with an ES score of 5 were malignant. Conclusion: Thyroid elastography may reduce unnecessary surgery for both patients with AUS/FLUS and selected SFN cytology. Elastography appears to be helpful in follicular variants and other types of papillary thyroid cancer, however, not in follicular thyroid cancer.

Objective: The study aims to evaluate the usefulness of non-invasive diagnostic methods, shear wave elastography (SWE), and diffusion-weighted magnetic resonance imaging (DWI) to differentiate benign and malignant lesions in the thoracic pleural based masses by comparing them with histopathological findings.Materials and Methods: Sixty-three patients having a pleural-based peripheral mass on CT, admitted to the interventional radiology department for transthoracic biopsy, were included in the study. All patients underwent DWI, and ADC values of the groups were measured. Transthoracic biopsy was performed with the guidance of US from the area where the highest shear wave velocity (SWV) value was calculated. ADC and SWV values of histopathologically proven benign and malignant lesions were statistically compared.Results: Fifty-six patients were male, and seven were female. The mean age was 64.68±10.13 years (41-85 years). Fourty-four patients were malignant, and 19 were benign. The maximum SWV was found to be 4.13±0.59 m/s in malignant cases and 3.55±0.71 m/s in benign cases, and the difference was significant (p = 0.001). Mean ADC value was measured as 1.04±0.30 x 10-3 mm2/s in malignant cases and 1.32±0.33 x 10-3 mm2/s in benign cases on DWI and the difference was significant (p = 0.002). In malignant cases, the minimum ADC was 0.73±0.29 x 10-3 mm2/s, and 0.99±0.44 x 10-3 mm2/s in benign cases, the difference was significant (p = 0.024). ROC analysis revealed a cut-off value of ≥4.08 m/s for SWVmax, ≤1.01x10-3 mm2/s for mean ADC, and ≤0.8x10-3 mm2/s for minimum ADC showed a significant performance in distinguishing malignant and benign lesions. Conclusions: Transthoracic US elastography and DWI are useful in differentiating malignant and benign lesions in appropriate cases. Both SWE and DWI are useful in routine use because they are non-invasive and do not contain radiation. In particular, SWE is suitable for biopsy guidance and may prevent the possibility of insufficient material.