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Background and Aims: EUS-guided through-the-needle microforceps biopsy (EUS-TTNB) was introduced as a new diagnostic tool to establish pancreatic cyst histotype and help to better risk stratify the patients. The aim of this study was to describe the technical success, diagnostic yield, and adverse events of through-the-needle biopsy and discuss the technique variations, focusing on future procedure standardization. Methods: We performed a prospective single-center study including patients with presumed mucinous cysts harboring worrisome features or indeterminate cyst type on imaging, submitted to EUS-TTNB using Moray® microforceps between March 2018 and September 2021. Specimens were processed as a cell-block. Results: We included 40 patients. Technical success was 97.5%. The diagnostic yield was 72.5% for TTNB whereas for cyst fluid cytology/analysis it was 27.5%. Moreover, without TTNB 5 mucinous lesions would not have been diagnosed. TTNB had a sensitivity of 76% and a specificity of 91%, while FNA cytology had a sensitivity and specificity of 35% and 91%, respectively. Moreover for IPMN lesions, subtyping was possible in 63% of cases. TTNB resulted in change in clinical management in 20% of patients. We registered three adverse events: 2 self-limited intracystic bleeding and 1 patient with abdominal pain not associated with pancreatitis. Conclusion: TTNB proved superior to cyst fluid analysis and cytology for the definition of cyst histotype and mucinous cyst diagnosis with acceptable risk profile. Further studies should explore the best steps for procedure standardization.

Individuals within specific risk groups for pancreatic ductal adenocarcinoma (PDAC) [mucinous cystic lesions (MCLs), hereditary risk (HR), and new-late onset diabetes mellitus (NLOD)] represent an opportunity for early cancer detection. Endoscopic ultrasound (EUS) is a premium image modality for PDAC screening and precursor lesion characterization. While no specific biomarker is currently clinically available for this purpose, glypican-1 (GPC1) is overexpressed in the circulating exosomes (crExos) of patients with PDAC compared with healthy subjects or those harboring benign pancreatic diseases.To evaluate the capacity of GPC1This cross-sectional study with a prospective unicentric cohort included 88 subjects: 40 patients with MCL, 20 individuals with HR, and 20 patients with NLOD. A control group (CG) was submitted to EUS for other reasons than pancreatic pathology, with normal pancreas and absence of hereditary risk factors (Half of MCLs harbored worrisome features (WF) or high-risk stigmata (HRS). Pancreatic abnormalities were detected by EUS in 10.0% and 35.0% in HR and NLOD individuals, respectively, all considered non-malignant and "harmless." Median levels of GPC1GPC1

The clinical management of patients with pancreatic cystic lesions is of utmost importance to identify those at high risk for pathological progression. Current recommendations are guided by clinical presentation and radiologic criteria, but the results fall short for a disease that the only curative option is surgical resection. There is an urgent need for the introduction of biomarkers that can help in risk assessment of such lesions. We report a case of a pancreatic cystic lesion without imagiological findings suggestive of advanced disease, and high levels of a circulating biomarker, glypican-1 (GPC-1), which parallel those of patients with pancreatic cancer. One year after, the patient revealed malignant progression at follow-up. Our report is unprecedented in the literature. It describes a clinical case in which a biomarker was positive for a patient that only showed progression one year after its detection. This clinical information goes beyond the current knowledge in the field because it shows that the introduction of liquid biopsy and biomarkers is a highly promising clinical tool for the non-invasive assessment of pancreatic cancer precursor lesions, ultimately increasing the rate of patients eligible for surgical resection.

Background: The evaluation of lymph nodes (LN) by fine-needle aspiration cytology (FNAC) is routinely used in many institutions but it is not uniformly accepted mainly because of the lack of guidelines and a cytopathological diagnostic classification. A committee of cytopathologists has developed a system of performance, classification, and reporting for LN-FNAC. Methods: The committee members prepared a document that has circulated among them five times; the final text has been approved by all the participants. It is based on a review of the international literature and on the expertise of the members. The system integrates clinical and imaging data with cytopathological features and ancillary techniques. The project has received the endorsement and patronage of the International Academy of Cytology and the European Federation of the Cytology Societies. Results: Clinical, imaging, and serological data of lymphadenopathies, indications for LN-FNAC, technical procedures, and ancillary techniques are evaluated with specific recommendations. The reporting system includes two diagnostic levels. The first should provide basic diagnostic information and includes five categories: inadequate/insufficient, benign, atypical lymphoid cells of undetermined/uncertain significance, suspicious, and malignant. For each category, specific recommendations are provided. The second diagnostic level, when achievable, should produce the identification of specific benign or malignant entities and additional information by utilizing ancillary testing. Conclusion: The authors believe that the introduction of this system for performing and reporting LN-FNAC may improve the quality of the procedure, the report, and the communication between cytopathologists and the clinicians. This system may lead to a greater acceptance and utilization of LN-FNAC and to a better interdisciplinary understanding of the results of this procedure.

Pediatric-type follicular lymphomas are rare lymphomas, affecting mostly children and young adults. These are characterized by an excellent prognosis, despite their conservative therapeutic approach. Recognized as an entity in the most recent 2016 WHO classification of tumors of hematopoietic and lymphoid tissues, its diagnosis is based on the recognition of an exclusively nodular architecture, thus conditioning the possibility of a cytological diagnosis. It is thus not odd, the scant literature found on the cytological approach to these lesions. Herein we describe a case of a pediatric-type follicular lymphoma, first approached through fine needle biopsy. The case is thoroughly discussed from a cytologic, immunophenotypic, and molecular point of view. Differential diagnoses are discussed. The final diagnosis was performed on histology.

Background: Small round blue cell tumors or more commonly called small round cell tumors (SRCTs) are undifferentiated neoplasms, sharing an overlapping morphological pattern of small round blue cells. Diagnosing these tumors represents a complex challenge for cytopathologists and for general surgical pathologist alike. This stems from the fact that these tumors share not only similar morphological features, but also some immunophenotypic characteristics, thus requiring a broad panel of antibodies, which might not be included in the most basic immunohistochemistry panels, used in the routine work of most pathology laboratories. Furthermore, one should note that the diagnosis, prognosis, and/or therapeutic decision are often dependent on the knowledge of the existence of specific molecular alterations, which requires access to sophisticated molecular ancillary techniques. Cytological diagnosis of SRCT should be systematized. A thorough understanding of the morphological pattern of these tumors, the small details they entail, the background and cellular patterns, and the nuclear and cytoplasmic peculiarities, may hint to the most probable diagnosis. Minor clues, such as the presence of a fibrillar background, the presence of rosettes or a specific “salt and pepper” chromatin, are important clues toward a probable diagnosis of a neuroblastoma, or the presence of a tigroid background is a characteristic of rhabdomyosarcoma and the Ewing family tumors. However, in poorly differentiated tumors, morphology alone will not suffice, making it essential for the access to complementary diagnostic techniques in order to reach the final diagnosis. Summary and Key Messages: The cytological diagnosis and treatment of SRCTs require an experienced, well-articulated, proficient teamwork, and sophisticated complementary diagnostic techniques, only available in centers of reference.

Background and study aims The utility of suction during endoscopic ultrasound (EUS) fine-needle biopsy (FNB) using Franseen-tip needle remains unclear and has not been evaluated in randomized trials. We designed a randomized crossover trial to compare the diagnostic yield during EUS-FNB using a 22G Franseen-tip needle, with and without standard suction. Patients and methods Consecutive patients undergoing EUS-guided sampling of solid pancreatic lesions were recruited. A minimum of two passes were performed for each case: one with 20-mL syringe suction (S+) and another without (S–). The order of passes was randomized and the pathologist blinded. The endpoints were the diagnostic yield and the impact of blood contamination in the diagnosis. Results Fifty consecutive patients were enrolled. The overall diagnostic accuracy was 84 %. A diagnosis of malignancy was obtained in 70 samples: 36 in the S+group and 34 in the S–group. A statistically significant difference was seen in the diagnostic accuracy (S+: 78 % vs. S–: 72 %, P Conclusions We found a higher diagnostic yield with the use of suction. It was associated with a higher degree of sample blood contamination that did not affect the diagnostic performance.

Fine needle aspiration biopsy cytopathology (FNAC) of lymph nodes is a very common, inexpensive, and rapid diagnostic procedure and can lead to the accurate and timely diagnosis of one of the wide range of pathological processes that involve lymph nodes. These diagnoses include specific reactive processes, specific infections such as tuberculosis, metastatic carcinomas and melanomas, and some lymphomas. The FNAC effectively triages the lymph node material, but the initial diagnosis often requires ancillary testing as a second diagnostic step to make a specific diagnosis, such as the particular infectious agent, the type of lymphoma or Hodgkin lymphoma, or the specific type of metastatic malignancy. An international group of cytopathologists have begun the process of developing a system for the standardized reporting of lymph node FNAC. The group is addressing the pre-analytical issues related to the FNAC, including the role of clinical information and the use of ultrasound, and developing a structure of reporting categories based on the cytopathological findings linked to management recommendations. The basis of the system is the integration of the FNAC with the clinical setting, imaging, and ancillary tests that utilize the FNAC material, to produce a final report that will enhance patient care.

Case Report. A four-year-old girl presented with fever and a painful limp in the left hip. Pain characteristics and anemia detected in the blood analyses were the first warning signs that the hip process was not standard. Although the primary suspicion was of septic arthritis, a CT scan of the abdomen revealed an adrenal neuroblastoma.Conclusion.The presenting signs of neuroblastoma are commonly atypical. About 25% of presentations are orthopedic and mimic a variety of severe orthopedic conditions. The most important clinical dilemma is distinguishing benign and self-limiting disorders from septic or malignant processes.

Objectives Multinodular goiter (MNG) and well-differentiated thyroid carcinoma (WDTC) are emerging phenotypes of DICER1 syndrome. Methods Histologic and molecular findings of botryoid-type embryonal rhabdomyosarcoma (bERMS) and thyroid nodules from a 12-year-old DICER1 mutation carrier (p.Arg1060Ilefs*7) were investigated, providing interesting clues for understanding thyroid carcinogenesis. Results The patient had bERMS at age 7 years. The thyroid was enlarged and multinodular (61 g). Histologically, some nodules were classified as adenomatous and others as tumors with "intermediate" nuclei. One displayed vascular invasion and was classified as WDTC not otherwise specified (NOS). Somatic DICER1 mutations were identified in bERMS, two tumors with "intermediate" nuclei and WDTC. No somatic DICER1 mutations were found in adenomatous nodules. No molecular alterations were detected in BRAF600, NRAS61, HRAS12/61, KRAS12/61, TERT promoter, RET/PTC1, RET/PTC3, and PAX8/PPARγ. Conclusions The findings obtained from this single case support the assumption that DICER1 syndrome-related WDTC NOS may develop on a background of MNG, via a stepwise process, involving DICER1 somatic mutations and additional molecular events, distinct from the classic pathways of papillary/follicular carcinoma.

Background: Anal squamous intraepithelial lesions (ASIL) are precancerous lesions of anal squamous cell carcinoma, with a higher prevalence in immunosuppressed patients. There are some studies in kidney transplant recipients, but there is no information regarding prevalence in liver transplantation. Our aim was to evaluate the prevalence of ASIL in this setting. Methods: Prospective case–control study involving liver transplant recipients without any other known risk factor for ASIL (n=59), which were compared with a healthy control group (n=57). All were submitted to anal cytology and high-resolution anoscopy was performed in those with abnormal results. Results: Ten (17%) of liver transplant recipients had abnormal cytological results, seven patients had atypical squamous cells of undetermined significance (ASC-US), one patient had atypical squamous cells that cannot exclude high-grade (ASC-H) and two patients had high-grade squamous intraepithelial lesions (HSIL). In the control group, one patient (2%) had an ASC-US result (P=0.005). Anal squamous intraepithelial lesions were confirmed in 7 out of 10 of liver transplant patients and 0 out of 1 in the controls (P=0.013) by high-resolution anoscopy with biopsies. Current smoking was the only risk factor for abnormal cytology (odds ratio=5.87, 95% confidence intervals=1.22–28.12, P=0.027). Conclusions: Liver transplant patients have a higher risk of ASIL. Screening should be considered, especially in smokers.

Multinodular goiter (MNG) and well-differentiated thyroid carcinoma (WDTC) are emerging phenotypes of DICER1 syndrome.Histologic and molecular findings of botryoid-type embryonal rhabdomyosarcoma (bERMS) and thyroid nodules from a 12-year-old DICER1 mutation carrier (p.Arg1060Ilefs*7) were investigated, providing interesting clues for understanding thyroid carcinogenesis.The patient had bERMS at age 7 years. The thyroid was enlarged and multinodular (61 g). Histologically, some nodules were classified as adenomatous and others as tumors with "intermediate" nuclei. One displayed vascular invasion and was classified as WDTC not otherwise specified (NOS). Somatic DICER1 mutations were identified in bERMS, two tumors with "intermediate" nuclei and WDTC. No somatic DICER1 mutations were found in adenomatous nodules. No molecular alterations were detected in BRAF600, NRAS61, HRAS12/61, KRAS12/61, TERT promoter, RET/PTC1, RET/PTC3, and PAX8/PPARγ.The findings obtained from this single case support the assumption that DICER1 syndrome-related WDTC NOS may develop on a background of MNG, via a stepwise process, involving DICER1 somatic mutations and additional molecular events, distinct from the classic pathways of papillary/follicular carcinoma.

Large-cell neuroendocrine tumors (NETs) are poorly differentiated malignancies of rare incidence and aggressive nature. NETs mostly arise in the lung followed by the gastrointestinal tract, although they are potentially ubiquitous throughout the body. Primary unknown NET has a worse prognosis and shorter survival comparing with other NETs, with limited available data in the literature concerning this subgroup. The authors report the case of large-cell NET with supraclavicular lymph node presentation. Total excisional biopsy revealed an enlarged adenopathy 18 × 15 × 10 mm, which was extensively infiltrated by a solid malignant neoplasm composed of large cells with granular chromatin, nuclear pseudo-inclusions, high mitotic index, and focal necrosis, with a Ki 67 index 25-30% and positive immunohistochemical study for the expression of cytokeratin 8/18, chromogranin, synaptophysin, and thyroid transcriptional factor-1 (TTF-1). There was no evidence of primary location apart from two infracentimetric lung lesions that could not be accessed for biopsy and were negative at both somatostatin receptor scintigraphy and positron emission tomography. The NET relapsed with three mediastinal masses, so the patient was started on chemotherapy with carboplatin and etoposide with initial total response. Early progression showed no response to further chemotherapy regimens (temozolomide, oral etoposide); therefore, the patient was treated with local radiotherapy. This patient has an atypical long survival (54 months) compared to the literature data. In fact, there are few long-term survivors of large-cell NET and they are all related to complete surgical resection.

The range of pathologies that lymph node (LN) fine needle cytology (FNC) may encounter is extremely wide and ancillary techniques, in addition to traditional smears, are generally required to reach reliable cytologic diagnoses. Storing part of the cytologic material may be useful or necessary for molecular testing. The main difficulties concern the generally small size of the sample and the different methods of acquisition of LN-FNC. Therefore, the preanalytic phase is extremely important for LN-FNC. This article outlines the management of LN-FNC material, vials, technical devices (e.g.: additional smears, cytospin slides, LBC slides, cards, resins, etc.) and main ancillary techniques to assess their optimal application, taking into account the different diagnostic needs and cell storage.

Background: Rapid on-site evaluation (ROSE) has the potential to increase endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) accuracy in the diagnosis of mediastinal lesions and lung cancer staging. However, studies have reported controversial results.The purpose of our study was to evaluate the influence of ROSE on sample adequacy and diagnostic accuracy of EBUS-TBNA. Methods: Prospective observational study that enrolled 81 patients who underwent EBUS-TBNA for investigation of hilo-mediastinal lesions or lung cancer staging. The first 41 patients underwent EBUS-TBNA with ROSE (ROSE group) and the last 40 patients without ROSE (non-ROSE group). Sample adequacy and diagnostic accuracy of EBUS-TBNA in both groups were compared. Results: Adequate samples were obtained in 93% of the patients in the ROSE group and 80% in non-ROSE group (p = 0.10). The diagnostic accuracy of EBUS-TBNA was 91% in ROSE group and 83% in non-ROSE group (p = 0.08). Analyzing the EBUS-TBNA purpose, in the subgroup of patients who underwent EBUS-TBNA for investigation of hilo-mediastinal lesions, these differences between ROSE and non-ROSE group were higher compared to lung cancer staging, 93% of patients with adequate samples in the ROSE group vs. 75% in the non-ROSE group (p = 0.06) and 87% of diagnostic accuracy in ROSE group vs. 77% in non-ROSE group (p = 0.10). Conclusions: Despite the lack of statistical significance, ROSE appears to be particularly useful in the diagnostic work-up of hilo-mediastinal lesions, increasing the diagnostic yield of EBUS-TBNA. Keywords: EBUS-TBNA, ROSE, Sample adequacy, Diagnostic accuracy

Cytology features of childhood jaw tumors are infrequently reported in the literature. Fine-needle aspiration cytology (FNAC) has been used with good results in the differential diagnosis of bone lesions, being an excellent tool for the diagnosis of metastases and in the frontline approach to primary lesions. We report 3 cases of young children aged 3 years (case 1), 5 months (case 2), and 15 years (case 3) with jaw tumors diagnosed by FNAC. In the first two cases the diagnosis was prognoma, and in the third case cementifying fibroma. Despite the clinical and imaging similarity of the 3 cases – large maxillary/mandibular tumors – their characteristic cytological features allowed a confident diagnosis, excluding other differential alternatives. In both case 1 and case 2 a dual cell population of neuroepithelial and melanocytic cells was identified, consistent with a melanotic neuroectodermal tumor. In case 3 the presence of a bland spindle cell population as well as of several nodular dense eosinophilic, osteoid-like (cement) matrices, indicated a cementifying fibroma. All cases were resected and confirmed by histological examination. A review of the literature, including differential diagnosis, addresses the utility of FNAC in childhood jaw tumors.

The routine use of ancillary studies is reshaping the practice of cytopathology. Currently, most cytopathologists recognize the importance of immunocytochemistry and molecular techniques as adjuncts to morphology to achieve a precise diagnosis. Cytopathologists also are expected to include specific prognostic and predictive information in their reports. The objective of this review was to address the use of immunocytochemistry and molecular techniques to refine the preoperative diagnosis and classification of lung cancer, thyroid cancer, kidney cancer, gastrointestinal cancer, and soft tissue tumors. Fine-needle aspiration also offers a suitable alternative to biopsy in a variety of clinical settings, in particular, when it may be useful to obtain material to study prognostic and predictive markers. This is particularly relevant to obtain material from metastatic sites. The study of KRAS in colon cancer, CKIT in gastrointestinal stromal tumors, and epidermal growth factor receptor mutational status in lung cancer also are addressed particularly in this report. Cancer (Cancer Cytopathol) 2012;. © 2012 American Cancer Society.

Fine-needle aspiration cytology (FNAC) is a recognized ancillary tool in the diagnosis of tumours and infectious diseases. Throughout decades cytopathologists did tremendous marvels with pure morphologic criteria, diagnosing in shrinking amounts of material. The recent understanding of complex cancer biology reshapes the practice of FNAC. The scientific advance of image techniques gave cytopathologists the possibility to go to deep locations and collecting material from previous unlikely locations. This conjunction of knowledge's and techniques has increased the role of FNAC in the diagnosis, prognosis and in the establishment of new therapeutic targets. Lately, core needle biopsy is gaining popularity and advantage regarding FNAC. The sample limitation of FNAC regarding immunocytochemical staining with proper controls, as well as the limitation in appreciating invasiveness has lead, in some fields, like soft tissue tumours, breast, lymph node, and prostate, to diminish the use of FNAC. However FNAC still is a less invasive, effective, and cost efficient technique. In this review we demonstrate the application of basic molecular techniques to FNAC as a crucial tool in the diagnosis, prognosis and planning of alternative molecular therapeutics of tumours.

Nephroblastoma is a success of paediatric oncologic therapy, yet, there are still some cases where favourable response to preoperative chemotherapy is not achieved. Fine needle biopsy has the role of diagnostic confirmation and, idyllically of predicting a response to preoperative chemotherapy. To advance in this aim, we retrieved a total of 14 nephroblastomas, (seven male patients and seven female with a mean age of 44.4 months), diagnosed in our department by fine needle biopsy and submitted afterward to chemotherapy and nephrectomy, in the last 10 years. Correlation between cytologic features, (morphology, cell death, and proliferation (Ki-67 labelling index), and post chemotherapy tumour evaluation was done. Cytologic pattern per se was not predictive of histologic tumour classification (P = 0.6061). We did not find any correlation between the percentage of necrosis and apoptosis (P = 0.682) in cytologic smears and histologic regressive changes but when both these two criteria coexisted in cytologic blastemal component of nephroblastomas, this fact seemed to lead to a favourable response of the tumour to chemotherapy. When evaluation of Ki-67 labelling index was done in the blastematous component present in the smears, divergent results were obtained. The small number of cases prevented any firm conclusions. By summing up, our results support the idea that there are probably two types of blastema in nephroblastoma with different “suicide” potential and chemotherapeutic response. Further studies should be performed to stratify the influence of necrosis, apoptosis, and proliferation in chemosensivity of nephroblastomas. Diagn. Cytopathol. 2010. © 2009 Wiley-Liss, Inc.