The assessment of reactive oxygen species (ROS) offers immense prospects for the diagnosis of chronic diseases. A protocol to assess redox imbalance in exfoliated cells can prove beneficial in our understanding of the role of ROS in the diagnosis of these diseases. Further studies on the development of such protocols are needed.
The risk of malignancy (ROM) remains an area of interest for further evaluation in reporting systems including in International System for reporting serous fluid cytopathology (TIS), which is a standardized system for reporting effusion cytology. Herein, we report our findings in further investigation of ROM in TIS by studying on paired pleural effusion specimens and corresponding pleural biopsies with emphasis on negative for malignancy, and atypia of undetermined significance categories.
The Johns Hopkins Hospital pathology database was retrospectively searched for patients with a pleural biopsy (PBX) and a paired pleural effusion (PF) cytology specimens over a 4-year period. We employed the TIS categories. The following statistical parameters were evaluated: sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and ROM.
A total of 223 patient cases were included. Effusions TIS reclassification and ROM were as follows: 1.8% non-diagnostic (ROM 75%), 75.8% negative for malignancy (ROM 23%), 4.9% atypical cells of undetermined significance (ROM 45%), 2.2% suspicious for malignancy (ROM 80%), and 15.2% malignant (ROM 100%). Overall accuracy, sensitivity, specificity, PPV and NPV were calculated and were 79.4%, 45%, 97.7%, 91.2% and 77%, respectively. Among, discordant cases diagnosed negative for malignancy on PF and positive for malignancy on PBX, there were significant number of lymphomas, mesotheliomas, and sarcomas. Lung cancer was the most common carcinoma; however, rare types of carcinomas were noted. Cells blocks and immunohistochemistry (IHC) studies were utilized to confirm either malignant conditions or rule out malignancy in both cell blocks and histology biopsies.
This study demonstrates the high specificity and ROM for ‘malignant’ and ‘suspicious for malignancy’ categories in the TIS reporting system and highlights the modest negative predictive value for the ‘negative for malignancy’ category. Although Tissue biopsies are usually considered as ‘gold standard’, any definitive diagnosis of malignancy of body fluid should be considered positive for malignancy in further clinical decision-making.
We report the case of a patient with a BRAFV600E mutant mCRC, with evidence of acquired ‘NeoBRAF wild-type’ (wt) state. The patient, longitudinally assessed by liquid biopsy, obtained a remarkable clinical outcome with a multimodal approach including surgery, systemic treatment and targeted therapy.
In patients with newly diagnosed RAS and BRAFV600E mutant mCRC, longitudinal assessment with liquid biopsy is not routinely used in clinical practice. We report the case of a patient with a BRAFV600E mutant mCRC, with evidence of acquired ‘neoBRAF wild-type’ (wt) state. The patient obtained a remarkable clinical outcome and has been longitudinally assessed by liquid biopsy.
Endometrial Gastric-type Carcinoma is a rare disease, especially in cytology. A 65-year-old woman was admitted to the hospital due to intermittent chest tightness with dyspnoea. The chest CT showed a soft tissue shadow of the left lung with bronchial occlusion and pericardial effusion. What was her diagnosis?
The reported risk of malignancies (ROM) remains controversial for fine needle aspiration (FNA) of thyroid nodules in the African American (AA) population. Herein, the ROM along with frequency was assessed for each of the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) diagnostic categories.
The electronic pathology archive of a large academic hospital was retrospectively searched for cytopathology reports of thyroid nodules in AA patients (2010–2019) and Non-African American (NAA) control cases. The patients' demographic, thyroid nodule characteristics, FNA results using TBSRTC and surgical diagnoses were recorded, whenever available.
Three hundred ninety-one cases were identified, 317 females (81.1%) and 74 males (18.9%) with median age 50.0 (SD = 14.4). The mean size of the nodules was 2.1 cm (SD = 1.4). The Bethesda categories were: 5.4% (I), 35.0% (II), 35.3% (III), 7.7% (IV), 3.3% (V) and 13.3% (VI). The overall ROM of thyroid nodules was 43.8% (89/203) on surgical follow-up (203/391). The ROM in each Bethesda categories were: 33.3% (I), 11.6% (II), 35.2% (III), 15.8% (IV), 83.3% (V) and 100% (VI) on surgical follow-up. The frequency of thyroid nodules was higher in AA females; however, the ROM was higher in AA males (48.3%) compared with AA females (41.2%).
The ROM in Categories I, II and III was higher than those reported in the TBSRTC while being similar in Categories IV, V and VI. The overall risk of thyroid malignancy in our AA patient population was higher than those in the literature. The overall ROM of thyroid nodules in AA males was higher than of AA females.
The evaluation of thyroid lesions is common in the daily practice of cytology. While the majority of thyroid nodules are benign, in recent decades, there has been increased detection of small and well-differentiated thyroid cancers. Combining ultrasound evaluation with fine-needle aspiration cytology (FNAC) is extremely useful in the management of thyroid nodules. Furthermore, the adoption of specific terminology, introduced by different thyroid reporting systems, has helped effectively communicate thyroid FNAC diagnoses in a clear and understandable way. In 1996, the Papanicolaou Society thyroid cytological classification was introduced. This was followed in 2005 by the first Japanese and then in 2007 by the Bethesda System for Reporting Thyroid Cytopathology, which subsequently underwent two revisions. Other international thyroid terminology classifications include the British, Italian, Australasian and other Japanese cytology systems. This review covers similarities and differences among these cytology classification systems and highlights key points that unify these varied approaches to reporting thyroid FNAC diagnoses.
Immunocytochemistry (ICC) is essential for enhancing diagnostic accuracy and identifying markers for diagnosis, prognosis and targeted therapies. While cell blocks (CBs) are preferred for standardization and optimized staining, cytological smears are an alternative when CBs are unavailable. However, the literature on ICC protocols for smears is sparse. This review addresses preparation, fixation and protocols for nuclear and cytoplasmic antibodies on smears, drawing from our laboratory's experience.
We reviewed procedures for ICC on cytological smears using existing literature and practical insights from our laboratory.
Commercially available antibodies were found to be reliable for ICC on smears if specimens are properly prepared and fixed. Protocols developed in our laboratory maintained antigenicity and provided clear staining results.
Although ICC on CBs is the gold standard for standardization, cytological smears are a viable alternative when CBs are unavailable. Success in ICC on smears depends on proper preparation and fixation. This review offers practical protocols and insights to help laboratories optimize ICC on cytological smears. Further research and standardization are necessary to enhance reproducibility and reliability of ICC on smears. The practical information provided is based on personal experience in our laboratory.
There are conflicting results on whether the presence of oncocytes modifies the risk of neoplasm (RON) or malignancy (ROM) for thyroid fine-needle aspirates (FNAs): Atypia of undetermined significance AUS and Follicular Neoplasm, FN, or Oncocytic Neoplasm, ON. To our knowledge, the effect of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) has not yet been studied. We compared RON and ROM between follicular type AUS (AUS-FT) and oncocytic type AUS (AUS-OT) and between FN and ON.
We retrospectively analysed all thyroid FNAs with the diagnostic category of AUS-other or Neoplasm (2005–2015). AUS-FT had predominance of microfollicles and AUS-OT had predominance of oncocytes. Histology follow-up was then reviewed and RON, ROM was then calculated and compared (significant at p < 0.05). We repeated the search for 2018 to evaluate for NIFTP effect.
Pre-NIFTP, 859/5063 cases (17%) were AUS-FT, AUS-OT, FN, and ON. Histology follow-up was available for 297 cases (35%). RON was 83/183 (45%) for AUS-FT, 35/76 (46%) for AUS-OT, 15/25 (60%) for FN and 11/13 (85%) for ON. Post-NIFTP, RON was 11/31 (35%) for AUS-FT, 5/8 (63%) for AUS-OT, 1/2 (50%) for FN and 4/5 (80%) for ON. For both periods, RON, ROM of AUS-FT was not significantly different than AUS-OT, and no significant differences were observed comparing FN and ON.
The predominance of oncocytes does not modify the implied RON, ROM for categories of AUS or FNON, even after the adoption of NIFTP.
Fine-needle aspiration cytology (FNAC) is a reliable method for preoperative evaluation of thyroid nodules particularly if ultrasound-guided (USG-FNAC). The main purpose of this study is to evaluate the efficacy of USG-FNAC and its accuracy.
We retrospectively studied 212 thyroidectomy cases with preoperative ultrasonography and FNAC data during the period 2015–2022 using TI-RADS for final ultrasound diagnosis and Bethesda system for cytological diagnosis.
The studied cases were 200 females and 12 males. Thyroid cancer was more prevalent under 20 years old (78.5%). Papillary thyroid carcinoma comprises 84% of all cancer cases. Significant ultrasound features (p-value <0.05) favour malignancy were hypoechogenicity (66%), mixed echogenicity (84%), irregular border (61%), microcalcification (68%) and rim halo (63.6%). Malignancy was found in 21% of TI-RADS-2, 65% of TI-RADS-4 and 100% of TI-RADS-5. There is a significant difference between different categories of Bethesda system. All cases in Cat-VI were malignant (100%). Malignancy was also found in 81% of Cat-V, 20% of Cat-IV, 33% of Cat-III, 16% of Cat-II and 43% of Cat-I. Cytological features consistent with malignancy were as follows: grooving (94%), nuclear irregularities (89%), nuclear pseudoinclusion (89%) and little colloid (82%). In our study, USG-FNAC sensitivity was 83%, specificity 85%, PPV 85%, NPV 83% and accuracy 84%.
Ultrasound features in favour of malignancy in thyroid nodules are hypoechoic or complex echogenicity, irregular border, punctuate calcification and presence of rim halo. Cytological features in favour of malignancy are grooving, nuclear irregularities, nuclear pseudoinclusion and little or absent colloid.
Given its frequent recurrence and the potential for high-grade transformation, accurate diagnosis of low-grade papillary urothelial carcinoma (LGPUC) in urine cytology is clinically important. We attempted to identify cytomorphologic features in urine samples, which could be helpful for the identification of LGPUC.
We conducted a retrospective review of voided urine specimens collected from patients with histopathologic diagnoses of LGPUC. Their cytomorphological features were compared with those from patients with benign conditions and high-grade papillary urothelial carcinoma (HGPUC).
A total of 115 voided urine specimens were evaluated, including 30 benign, 41 LGPUC, and 44 HGPUC cases. In LGPUC, 18 cases (44%) were diagnosed as atypical, a proportion significantly higher than that observed in benign cases (4 cases, 13%), while the remaining 23 cases (56%) were diagnosed as negative. LGPUC urine samples tended to have higher cellularity than benign cases, but the difference was not statistically significant. Three cytological features, namely nuclear enlargement, higher nuclear-to-cytoplasmic (N/C) ratio, and presence of small cell clusters, were statistically more prevalent in LGPUC compared to benign cases, although the changes were relatively subtle. In contrast, cytomorphological distinction between LGPUC and HGPUC was evident, as high cellularity, nuclear enlargement, hyperchromasia, high N/C ratio, irregular nuclear membrane, and apoptosis were significantly more prevalent in HGPUC cases.
Several cytomorphologic features in voided urine samples were more prevalent in cases with LGPUC, albeit not observed in all instances. Since these alterations were relatively subtle, meticulous attention to these cytomorphologic details is crucial to suggest the possibility of LGPUC.
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