Salivary Gland Fine-Needle Aspiration: The Current and Future Landscape.

Fine-needle aspiration represents a valid tool for the diagnosis/management of salivary gland lesions. The past years assessed the lack of uniform diagnostic reports for salivary cytopathology leading to interpretative issues. In 2015, an international group of cytopathologists developed an evidence-based tiered classification system for reporting salivary gland fine-needle aspiration (FNA) specimens, the "Milan System for Reporting Salivary Gland Cytopathology" (MSRSGC). The present landscape of salivary cytology is represented by the growing adoption of the MSRSGC and the assessment of its diagnostic role. The future landscape is characterized by the increasing role of ancillary techniques for diagnostic and prognostic purposes.

Neuroendocrine neoplasms of the breast: a review of literature.

Primary neuroendocrine neoplasms (NENs) of the breast are characterized by neuroendocrine architectural and cytological features, which must be supported by immunohistochemical positivity for neuroendocrine markers (such as Chromogranin and Synaptophysin). According to the literature, making a diagnosis of primary neuroendocrine breast cancer always needs to rule out a possible primary neuroendocrine neoplasm from another site. Currently, the latest 2022 version of the WHO of endocrine and neuroendocrine neoplasms has classified breast NENs as well-differentiated neuroendocrine tumours (NETs) and aggressive neuroendocrine carcinomas (NECs), differentiating them from invasive breast cancers of no special type (IBCs-NST). with neuroendocrine features. The current review article describes six cases from our series and a comprehensive review of the literature in the field of NENs of the breast.

Are we ready to bridge classification systems? A comprehensive review of different reporting systems in thyroid cytology.

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.

Seven years of Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP): Rate of Acceptance and Variation of Diagnostic Approaches Across Different Continents.

CONTEXT: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced as a new entity replacing the diagnosis of noninvasive encapsulated follicular variant of papillary thyroid carcinoma (PTC). Significant variability in the incidence of NIFTP diagnosed in different world regions has been reported. OBJECTIVE: To investigate the rate of adoption of NIFTP, change in practice patterns, and uniformity in applying diagnostic criteria among pathologists practicing in different regions. METHODS: Two surveys distributed to pathologists of the International Endocrine Pathology Discussion Group with multiple-choice questions on NIFTP adoption into pathology practice and whole slide images of 5 tumors to collect information on nuclear score and diagnosis. Forty-eight endocrine pathologists, including 24 from North America, 8 from Europe, and 16 from Asia/Oceania completed the first survey and 38 the second survey. RESULTS: A 94% adoption rate of NIFTP by the pathologists was found. Yet, the frequency of rendering NIFTP diagnosis was significantly higher in North America than in other regions (P = .009). While the highest concordance was found in diagnosing lesions with mildly or well-developed PTC-like nuclei, there was significant variability in nuclear scoring and diagnosing NIFTP for tumors with moderate nuclear changes (nuclear score 2) (case 2, P < .05). Pathologists practicing in North America and Europe showed a tendency for lower thresholds for PTC-like nuclei and NIFTP than those practicing in Asia/Oceania. CONCLUSION: Despite a high adoption rate of NIFTP across geographic regions, NIFTP is diagnosed more often by pathologists in North America. Significant differences remain in diagnosing intermediate PTC-like nuclei and respectively NIFTP, with more conservative nuclear scoring in Asia/Oceania, which may explain the geographic differences in NIFTP incidence.

Metastases to the parotid glands: An institutional experience.

BACKGROUND: Metastatic lesions to the salivary gland are rare and mostly affect the parotids. Metastases represent 8% of all malignant lesions of the parotid gland. Around 80% originate from squamous cell carcinomas (SCC) of the head and neck region. Fine needle aspiration (FNA) plays a crucial role in distinguishing primary salivary gland lesions from metastases. Herein we describe our series of metastases to the parotid glands. MATERIALS AND METHODS: We analysed 630 parotid gland FNAs over a decade including conventional and liquid-based cytology specimens. Ancillary techniques such as immunocytochemistry (ICC) were conducted on cell blocks. RESULTS: Eighty (12.4%) cases were malignant lesions, of which 53 (63.75%) were metastases including 24% melanoma, 22.6% SCC, 19% renal carcinomas, 7.5% breast carcinomas, 11.3% lung, 9% intestinal and 1.8% testicular, malignant solitary fibrous tumour and Merkel cell carcinoma. The 53 cases, classified according to the Milan system for salivary cytopathology, belonged to 5 Suspicious for malignancy (SFM) and 48 malignant (M) categories. Forty had a known history of primary malignancy (75.4%), while 13 were suspicious to be a metastatic localisation (24.5%), distributed as 5SFM (2SCC and 3Melanoma) and 8 M. A combination of clinical history, cytomorphology and ICC identified 100% of them. CONCLUSIONS: Fine needle aspiration plays a central role in the diagnostic workup of patients with metastatic lesions to their parotid glands, thereby defining the correct management. Diagnostic accuracy may be enhanced by applying ICC. Although melanoma and SCC are the most common histological types, several other malignancies may also metastasize to the parotid glands and should be kept into consideration.

Single Institution Experience in the Management of Locally Advanced (pT4) Differentiated Thyroid Carcinomas.

BACKGROUND: Locally infiltrating (T4) differentiated thyroid carcinomas (DTC) represent a challenge. Surgical strategy and adjuvant therapy should be planned balancing morbidity and oncologic outcome. A series of patients with T4 DTC who underwent multidisciplinary evaluation and treatment is reported. The main study endpoints were the oncologic outcome, complication rates, and risk factors for tumor recurrence. PATIENTS AND METHODS: All DTC cases operated between 2009 and 2021 were reviewed and T4 DTC cases were identified. En bloc resection of inferior laryngeal nerve (ILN), tracheal, and/or internal jugular vein (IJV) was performed in cases of massive infiltration. In cases of pharyngoesophageal junction (PEJ) invasion, the shaving technique was always applied. RESULTS: Among 4775 DTC cases, 60 were T4. ILN infiltration was documented in 45 cases (en bloc resection in 9), tracheal infiltration in 14 (tracheal resection in 2), PEJ invasion in 11 (R0 resection in 7 cases and < 1 cm residual tissue in 4 cases), IJV resection in 6, and laryngeal in 2. In total, 11 postoperative ILN palsy, 23 transient hypoparathyroidisms, and 2 hematomas requiring reoperation were registered. Final histology showed 7 pN0, 22 pN1a, and 31 pN1b tumors. Aggressive variants were observed in 47 patients. All but 1 patient underwent radioiodine treatment, 12 underwent adjuvant external beam radiation therapy (EBRT), and 2 underwent chemotherapy. At a median follow-up of 58 months, no tumor-related death was registered, and seven patients required reoperation for recurrence. Tracheal invasion was the only significant factor negatively impacting recurrence (p = 0.045). CONCLUSIONS: A multidisciplinary approach is essential for the management of T4 DTC. Individualized and balanced surgical strategy and adjuvant treatments, in particular EBRT, ensure control of locally advanced disease with acceptable morbidity.

Preoperative Direct Puncture Embolization of Castleman Disease of the Parotid Gland: A Case Report.

BACKGROUND: Castleman disease (CD) is an uncommon benign lymphoproliferative disease characterized by hypervascular lymphoid hyperplasia. We present a unique case of unicentric CD of the parotid gland treated by preoperative direct puncture embolization. CASE PRESENTATION: A 27-year-old female patient was admitted for a right neck mass. Ultrasound examination and MRI scan documented a hypervascular mass within the right parotid gland. Preoperative embolization was performed by direct puncture technique: a needle was inserted into the core of the mass under both ultrasound and fluoroscopic guidance and SQUID 12 was injected into the mass under fluoroscopic control, achieving a total devascularization. CONCLUSION: Preoperative direct puncture embolization was safe and effective and provides excellent hemostatic control during the surgical operation, limiting the amount of intraoperative bleeding.

Atypical glandular cells and predictive features of malignancy in Pap smears: A retrospective monocentric study.

OBJECTIVE: The introduction of cytological screening with the Papanicolau smear significantly reduced cervical cancer mortality. However, Pap smear examination can be challenging, being based on the observer ability to decode different cytological and architectural features. This study aims to evaluate the malignancy rate of AGC (atypical glandular cells) category, investigating the relationships between cytological and histological diagnosis. METHODS: Eighty-nine patients, diagnosed as AGC at cytological evaluation and followed up with biopsy or surgical procedure at Policlinico Gemelli Hospital, Rome, Italy, were included in the study. The cytopathological architectural (feathering, rosette formation, overlapping, loss of polarity, papillary formation, three-dimensional formation) and nuclear (N/C ratio, nuclear enlargement and hyperchromasia, mitoses, nuclei irregularity, evident nucleoli) features of AGC were evaluated. Statistical analyses were performed to assess cyto-histological correlation and determine the relevance of architectural and nuclear features in the diagnosis of malignancy. RESULTS: Of the 89 AGC patients, 48 cases (53.93%) were diagnosed as AGC-NOS and 41 (46.07%) were diagnosed as AGC-FN, according to the Bethesda classification system. The follow-up biopsies or surgical resections revealed malignancy in 46 patients (51.69%). The rates of malignancy for AGC-NOS and AGC-FN were 35.41% and 70.73% respectively. Furthermore, analysing cytopathological features, we found that both architectural and nuclear criteria were statistically significant (p < 0.05). Only overlapping, nuclear irregularity and increased N/C ratio were not found to be statistically significant for detecting malignancy. CONCLUSIONS: Cytological diagnosis of glandular lesions remains a valid tool, when appropriate clinical correlation and expert evaluation are available.

Impact of COVID-19 pandemic on thyroidectomy for malignant diseases in high-volume referral centers.

INTRODUCTION: The COVID-19 pandemic has limited the availability of healthcare resources for non-COVID patients and decreased elective surgeries, including thyroidectomy. Despite the prioritization of surgical procedures, it has been reported that thyroidectomy for thyroid cancer (TCa) was adversely impacted. We assessed the impact of the pandemic on the surgical activities of two high-volume referral centers. MATERIALS AND METHODS: Patients operated at two National Referral Centers for Thyroid Surgery between 03/01/2020 and 02/28/2021 (COVID-19 period) were included (P-Group). The cohort was compared with patients operated at the same Centers between 03/01/2019 and 02/29/2020 (pre-COVID-19 pandemic) (C-Group). RESULTS: Overall, 7017 patients were included: 2782 in the P-Group and 4235 in the C-Group. The absolute number of patients with TCa was not significantly different between the two groups, while the rate of malignant disease was significantly higher in the P-Group (1103/2782 vs 1190/4235) (P < 0.0001). Significantly more patients in the P-Group had central (237/1103 vs 232/1190) and lateral (167/1103 vs 140/1190) neck node metastases (P = 0.001). Overall, the complications rate was significantly lower (11.9% vs 15.1%) and hospital stay was significantly shorter (1.7 ± 1.5 vs 1.9 ± 2.2 days) in the P-Group (P < 0.05). CONCLUSION: The COVID-19 pandemic significantly decreased the overall number of thyroidectomies but did not affect the number of operations for TCa. Optimization of management protocols, due to limited resource availability for non-COVID patients, positively impacted the complication rate and hospital stay.

Second edition of the Milan System for Reporting Salivary Gland Cytopathology: Refining the role of salivary gland FNA.

The use of standardized reporting systems for nongynecologic cytopathology has made enormous gains in popularity during the past decade, including for thyroid fine-needle aspiration, urine cytology, serous effusions, pancreas, lymph nodes, lung, and more. In February 2018, the first edition Atlas of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was published. The MSRSGC defines six diagnostic fine-needle aspiration categories encompassing the spectrum of Non-Neoplastic, benign, and malignant lesions of the salivary glands. The goal of the MSRSGC is to combine each diagnostic category with a defined risk of malignancy and a specific clinical and/or surgical management algorithm. Since its initial publication in 2018, more than 200 studies and commentaries have been published confirming the role of the MSRSGC. The second edition of the MSRSGC, published in July 2023, includes refined risks of malignancy based on systematic reviews and meta-analyses, a new chapter summarizing the use of salivary gland imaging, new advances in ancillary testing, and updates in nomenclature. CONCISE SENTENCE: The second edition of the Milan System for Reporting Salivary Gland Cytopathology, published in July 2023, includes refined risks of malignancy based on systematic reviews and meta-analyses, a new chapter summarizing the use of salivary gland imaging, new advances in ancillary testing, updates in nomenclature, and a guide to the practical application of the latest ancillary markers for the diagnosis of selected salivary gland fine-needle aspiration cases.

Second edition of the Milan System for Reporting Salivary Gland Cytopathology: Refining the role of salivary gland FNA.

The use of standardized reporting systems for non-gynecologic cytopathology has made enormous gains in popularity during the past decade, including for thyroid fine-needle aspiration, urine cytology, serous effusions, pancreas, lymph nodes, lung, and more. In February 2018, the first edition Atlas of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was published. The MSRSGC defines six diagnostic fine-needle aspiration categories encompassing the spectrum of non-neoplastic, benign, and malignant lesions of the salivary glands. The goal of the MSRSGC is to combine each diagnostic category with a defined risk of malignancy and a specific clinical and/or surgical management algorithm. Since its initial publication in 2018, more than 200 studies and commentaries have been published confirming the role of the MSRSGC. The second edition of the MSRSGC, published in July 2023, includes refined risks of malignancy based on systematic reviews and meta-analyses, a new chapter summarizing the use of salivary gland imaging, new advances in ancillary testing, and updates in nomenclature.

Second edition of the Milan System for Reporting Salivary Gland Cytopathology: Refining the role of salivary gland FNA.

The use of standardised reporting systems for non-gynaecologic cytopathology has made enormous gains in popularity during the past decade, including for thyroid fine-needle aspiration, urine cytology, serous effusions, pancreas, lymph nodes, lung and more. In February 2018, the first edition of the Atlas of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) was published. The MSRSGC defines six diagnostic fine-needle aspiration categories encompassing the spectrum of non-neoplastic, benign and malignant lesions of the salivary glands. The goal of the MSRSGC is to combine each diagnostic category with a defined risk of malignancy and a specific clinical and/or surgical management algorithm. Since its initial publication in 2018, more than 200 studies and commentaries have been published, confirming the role of the MSRSGC. The second edition of the MSRSGC, published in July 2023, includes refined risks of malignancy based on systematic reviews and meta-analyses, a new chapter summarising the use of salivary gland imaging, new advances in ancillary testing and updates in nomenclature.

Some uncommon cystic lesions in the anterior head and neck region: Pitfalls to be avoided on cytology.

Cystic lesions of the anterior head and neck region are a challenging and frequent finding on cytological smears. The scant amount of cellular material in cystic slides poses the greatest difficulty to interpretation, so that frequently they are diagnosed as inadequate or with minimal cellular component. Despite the majority of cystic lesions being benign, a minor portion consist of malignant cystic entities. In these latter cases, the evidence of very scant malignant cells can be misdiagnosed and/or underestimated, leading to a false negative diagnosis. Many papers have already described and detailed the range of possible benign and malignant cystic lesions in head and neck. In the current review we have focused on the less common entities that often lead to serious misinterpretation.

Bladder Epicheck Test: A Novel Tool to Support Urothelial Carcinoma Diagnosis in Urine Samples.

Bladder cancer and upper urothelial tract carcinoma are common diseases with a high risk of recurrence, thus necessitating follow-up after initial treatment. The management of non-muscle invasive bladder carcinoma (NMIBC) after transurethral resection involves surveillance, intravesical therapy, and cytology with cystoscopy. Urinary cytology, cystoscopy, and radiological evaluation of the upper urinary tract are recommended during follow-up in the international urological guidelines. Cystoscopy is the standard examination for the first assessment and follow-up of NMIBC, and urine cytology is a widely used urinary test with high sensitivity for high-grade urothelial carcinoma (HGUC) and carcinoma in situ (CIS). In recent years, various urinary assays, including DNA methylation markers, have been used to detect bladder tumors. Among these, the Bladder EpiCheck test is one of the most widely used and is based on analysis of the methylation profile of urothelial cells to detect bladder neoplasms. This review assesses the importance of methylation analysis and the Bladder EpiCheck test as urinary biomarkers for diagnosing urothelial carcinomas in patients in follow-up for NMIBC, helping cytology and cystoscopy in doubtful cases. A combined approach of cytology and methylation analysis is suggested not only to diagnose HGUC, but also to predict clinical and histological recurrences.

Delphi expert consensus for whole slide imaging in thyroid cytopathology.

OBJECTIVE: Despite an increase in thyroid fine needle aspiration (FNA) and advances in whole slide imaging (WSI) adoption, digital pathology is still considered inadequate for primary diagnosis of these cases. Herein, we aim to validate the utility of WSI in thyroid FNAs employing the Delphi method strategy. METHODS: A panel of experts from seven reference cytology centres was recruited. The study consisted of two consecutive rounds: (1) an open-ended, free-response questionnaire generating a list of survey items; and (2) a consensus analysis of 80 selected shared WSIs from 80 cases by six investigators answering six morphological questions utilising a 1 to 5 Likert scale. RESULTS: High consensus was achieved for all parameters, with an overall average score of 4.27. The broad majority of items (84%) were ranked either 4 or 5 by each physician. Two badly scanned cases were responsible for more than half of the low-ranked (≤2) values (57%). Good to excellent (≥3) diagnostic confidence was reached in more than 95.2% of cases. For most cases (78%) WSI assessment was not limited by technical issues linked to the image acquisition process. CONCLUSION: This systematic Delphi study indicates broad consensus among participating physicians on the application of DP to thyroid cytopathology, supporting expert opinion that WSI is reliable and safe for primary diagnostic purposes.

Diagnostic role of FNA cytology in the evaluation of cervical lymph nodes in thyroid cancers: Combined evaluation of thyroglobulin in eluate from FNA cytology.

BACKGROUND: The presurgical evaluation of cervical lymph nodes (CLNs) in the management of thyroid malignant lesions is crucial for the extent of surgery or detection of metastases. In these last decades, fine-needle aspiration cytology (FNAC) has been shown to have a central role in the detection of nodal thyroid metastases. It is adopted for the possibility of confirming suspected metastases either in the presurgical phase or in the follow-up of patients after thyroidectomy. However, FNAC from CLNs can be challenging, especially in cystic lesions. In this regard, the combination of FNAC with thyroglobulin measurement in the eluate from FNAC (Tg-FNAC) seems to increase the sensitivity of FNAC in the detection of CLN metastases. The role of FNAC and Tg-FNAC was investigated in this series. METHODS: One hundred fifty-three prospective cytological samples of CLNs were studied along with surgical follow-up in the period between 2020 and 2022. Immunocytochemistry (ICC) was performed on liquid-based cytology-stored material. RESULTS: One hundred fifty-nine enlarged CLNs included 19 central lymph nodes and 140 CLNs. Forty-two thyroidal CLN metastases and 117 reactive lymph nodes were found. Thirty-one CLN dissections were performed in patients with a previous diagnosis of thyroid carcinoma (mostly papillary thyroid carcinoma [PTC]), whereas 128 CLNs with a concomitant suspicious and/or malignant thyroid nodule were found. There was one false-positive case among all the malignant histologically confirmed cases, and two of 117 reactive CLNs (1.7%) had a diagnosis of metastatic PTC. Markedly high Tg-FNAC was found in all metastatic CLNs, including 11 cystic metastatic CLNs detected by Tg-FNAC with a negative FNAC. ICC (including Tg, CK-19, and LCA) recognized nine cases with low Tg-FNAC and scant suspicious thyrocytes. Tg-FNAC plus FNAC diagnosed 94.2% of malignancies. CONCLUSIONS: FNAC represents a valid method for the evaluation of CLNs, especially combined with ICC. Tg-FNAC is an additional method with a useful role in FNAC.