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We describe a case of a 17-year-old girl with a mediastinal large B-cell lymphoma with IRF4 rearrangement (LBCL-IRF4r) with an atypical clinical presentation in an unusual location, diagnosed by fine needle biopsy, flow cytometry and FISH. We review the literature and discuss the differential diagnosis, clinical presentation, cytological and immunophenotypical characteristics of this unique case that raises very interesting questions regarding this new entity.
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BACKGROUND: After a series of standardized reporting systems in cytopathology, the Sydney system was recently introduced to address the need for reproducibility and standardization in lymph node cytopathology. Since then, the risk of malignancy for the categories of the Sydney system has been explored by several studies, but no studies have yet examined the interobserver reproducibility of the Sydney system. METHODS: The authors assessed interobserver reproducibility of the Sydney system on 85 lymph node fine-needle aspiration cytology cases reviewed by 15 cytopathologists from 12 institutions in eight different countries, resulting in 1275 diagnoses. In total, 186 slides stained with Diff-Quik, Papanicolaou, and immunocytochemistry were scanned. A subset of the cases included clinical data and results from ultrasound examinations, flow cytometry immunophenotyping, and fluorescence in situ hybridization analysis. The study participants assessed the cases digitally using whole-slide images. RESULTS: Overall, the authors observed an almost perfect agreement of cytopathologists with the ground truth (median weighted Cohen κ = 0.887; interquartile range, κ = 0.210) and moderate overall interobserver concordance (Fleiss κ = 0.476). There was substantial agreement for the inadequate and malignant categories (κ = 0.794 and κ = 0.729, respectively), moderate agreement for the benign category (κ = 0.490), and very slight agreement for the suspicious (κ = 0.104) and atypical (κ = 0.075) categories. CONCLUSIONS: The Sydney system for reporting lymph node cytopathology shows adequate interobserver concordance. Digital microscopy is an adequate means to assess lymph node cytopathology specimens.
Subject(s)
Neoplasms , Humans , Reproducibility of Results , In Situ Hybridization, Fluorescence , Neoplasms/pathology , Cytodiagnosis/methods , Lymph Nodes/diagnostic imaging , Lymph Nodes/pathologyABSTRACT
Kaposiform lymphangiomatosis (KLA) is a rare and aggressive generalized lymphatic anomaly (GLA), with distinctive clinical, radiology, morphologic, and genetic features. It does not have a current standard treatment and presents poor overall prognosis. Somatic mutations in the RAS pathway were reported as the likely driver for the majority of patients. We report a case of a 17-year-old male adolescent who was referred to the emergency department due to a severe anemia. Laboratory workup confirmed the anemia and revealed coagulation factor consumption and fibrinolysis. Chest-abdomen-pelvis computed tomography revealed an extensive cervical, mediastinal, abdominal and retroperitoneal "hematoma." During admission, progressive pancytopenia, and disseminated intravascular coagulation were observed, and the hypothesis of a tumor/neoplastic etiology was considered. A thoracoscopy revealed a moderate hemorrhagic pleural effusion and a mediastinal mass resembling a "hemolymphangiomatosis" malformation, which was biopsied. Histology displayed a lymphatic-venous malformation. The patient was presented at the multidisciplinary Vascular Anomalies Center and, due to the complex vascular anomaly diagnosis, oral sirolimus monotherapy was initiated. Four years later, the patient remains clinically stable, with stability of the lesion's dimensions and characteristics. A p.Q61R variant in the NRAS gene [NM_002524.4: c.182A>G, p.(Gln61Arg)], with 5% allelic fraction and 1993x coverage was detected. In conjunction with clinical and pathological findings, it allowed KLA final diagnosis. This case reinforces the importance of a high index of clinical suspicion and highlights the need of referring these cases to referral to Vascular Anomalies Centers.
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Pleural Effusion , Sirolimus , Humans , Male , Adolescent , Tomography, X-Ray ComputedABSTRACT
Infantile myofibromatosis is an uncommon soft tissue neoplasm that may present at birth or in early infancy. Although rare, this neoplasm is one of the most common benign fibrous tumors of infancy. Even though these tumors do not spread, they can compress or damage nearby organs. There is not an established management protocol, but it is advisable to maintain periodic clinical and imagological control until stability. Watchful waiting is an option to consider in the absence of problematic symptoms and visceral involvement. We report a case of solitary infantile myofibromatosis, without visceral involvement. It showed an initial rapid growth, raising concern among medical doctors and motivating soft tissue biopsy, always recommended as the clinical picture deviates from the classic presentation. Histology interpretation is often challenging, making genetics and clinical evaluation essential to exclude and prevent the misdiagnosing of more aggressive lesions.
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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.
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Pancreatic Cyst , Pancreatic Neoplasms , Humans , Prospective Studies , Pancreatic Neoplasms/diagnosis , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Pancreatic Cyst/diagnosis , Pancreatic Cyst/pathology , EndosonographyABSTRACT
BACKGROUND: 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. AIM: To evaluate the capacity of GPC1+ crExos to identify individuals at higher risk within these specific groups, all characterized by EUS. METHODS: This 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 (n = 8). The inclusion period was between October 2016 and January 2019, and the study was approved by the Ethics Committee of Centro Hospitalar Universitário de São João, Porto, Portugal. All patients provided written informed consent. EUS and blood tests for quantification of GPC1+ crExos by flow cytometry and carbohydrate antigen 19-9 (CA 19-9) levels by ELISA were performed in all subjects. EUS-guided tissue acquisition was done whenever necessary. For statistical analysis, SPSS® 27.0 (IBM Corp., Armonk, NY, United States) version was used. All graphs were created using GraphPad Prism 7.00 (GraphPad Software, San Diego, CA, United States). RESULTS: 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 GPC1+ crExos were statistically different: MCL [99.4%, interquartile range (IQR): 94.9%-99.8%], HR (82.0%, IQR: 28.9%-98.2%), NLOD (12.6%, IQR: 5.2%-63.4%), and CG (16.2%, IQR: 6.6%-20.1%) (P < 0.0001). Median levels of CA 19-9 were within the normal range in all groups (standard clinical cut-off of 37 U/mL). Within HR, individuals with a positive history of cancer had higher median levels of GPC1+ crExos (97.9%; IQR: 61.7%-99.5%), compared to those without (59.7%; IQR: 26.3%-96.4%), despite no statistical significance (P = 0.21). Pancreatic cysts with WF/HRS were statistically associated with higher median levels of GPC1+ crExos (99.6%; IQR: 97.6%-99.8%) compared to those without (96.5%; IQR: 81.3%-99.5%) (P = 0.011), presenting an area under the receiver operating characteristic curve value of 0.723 (sensitivity 75.0% and specificity 67.7%, using a cut-off of 98.5%; P = 0.012). CONCLUSION: GPC1+ crExos may act as biomarker to support the diagnosis and stratification of PDAC precursor lesions, and in signaling individuals with genetic predisposition in the absence of EUS abnormalities.
Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , CA-19-9 Antigen , Carbohydrates , Carcinoma, Pancreatic Ductal/diagnostic imaging , Carcinoma, Pancreatic Ductal/genetics , Cross-Sectional Studies , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Genetic Predisposition to Disease , Glypicans/genetics , Humans , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/genetics , Prospective Studies , Pancreatic NeoplasmsABSTRACT
BACKGROUND: To evaluate the performance of TBSRTC through multi-institutional experience in the paediatric population and questioning the management recommendation of ATA Guidelines Task Force on Paediatric Thyroid Cancer; Methods: A retrospective search was conducted in 4 institutions to identify consecutive thyroid FNAC cases in paediatric population between 2000 and 2018. Following the 2nd TBSRTC, the risk of malignancy ratios (ROMs) was given in ranges and calculated by 2 different ways. Sensitivity, specificity, PPV, NPV and DA ratios were calculated using histologic diagnosis as the gold standard; Results: Among a total of 405 specimens, the distribution of cases for each category was, 44 (11%) for ND, 204 (50%) for B category, 40 (10%) for AUS/FLUS, 36 (9%) for FN/SFN, 24 (6%) for SFM and 57 (14%) for M categories. 153 cases have a histological diagnosis. The ratio of surgery was 23% in ND, 16% in the B, 45% for AUS/FLUS, 75% for SFN/FN and 92% for SFM and 75% in M categories; Conclusions: The data underlines the high ROM values in paediatric population which might be clinically meaningful. The high rate of malignancy of the cohort of operated patients (50%) also underlines the need of better preoperative indicators for stratification. Considering that more than half of the nodules in AUS/FLUS category were benign, direct surgery recommendation could be questionable as proposed in ATA 2015 guidelines.
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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.
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Neuroblastoma , Sarcoma, Ewing , Cell Nucleus/pathology , Child , Diagnosis, Differential , Humans , Immunohistochemistry , Immunophenotyping , Neuroblastoma/chemistry , Neuroblastoma/diagnosis , Neuroblastoma/pathology , Sarcoma, Ewing/pathologyABSTRACT
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.
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Flow Cytometry , In Situ Hybridization, Fluorescence , Lymphoma, Follicular/pathology , Adolescent , Biopsy, Fine-Needle , Child , Humans , Lymphoma, Follicular/diagnostic imaging , Male , Positron Emission Tomography Computed TomographySubject(s)
Galactans/chemistry , Mannans/chemistry , Plant Gums/chemistry , Urine/chemistry , Aged , Aged, 80 and over , Carcinoma/diagnosis , Carcinoma/pathology , Cyamopsis/chemistry , Cytological Techniques/methods , Female , Humans , Kidney Neoplasms/diagnosis , Kidney Neoplasms/pathology , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/pathology , Urothelium/pathologyABSTRACT
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 84â%. A diagnosis of malignancy was obtained in 70 samples: 36 in the S+group and 34 in the S-group.âA statistically significant difference was seen in the diagnostic accuracy (S+: 78â% vs. S-: 72â%, P â<â0.01) and blood contamination (S+: 68â%; S-: 44â%, P â<â0.01). The sensitivity, specificity, negative likelihood ratio and positive likelihood ratio for S+vs. S-samples were 76.6â% vs. 73.9â%, 100â% vs. 100â% and 0.23 vs. 0.26, NA vs NA, respectively. A negative impact of blood contamination in the overall diagnostic yield wasn't seen, even in samples where suction was used (OR 0.36, P â=â0.15) 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.
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Histiocytic Necrotizing Lymphadenitis , Mixed Connective Tissue Disease , Diagnosis, Differential , Histiocytic Necrotizing Lymphadenitis/complications , Histiocytic Necrotizing Lymphadenitis/diagnosis , Humans , Lymph Nodes , Mixed Connective Tissue Disease/complications , Mixed Connective Tissue Disease/diagnosisSubject(s)
Biopsy, Fine-Needle , Hodgkin Disease/diagnosis , Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Lymphadenopathy/diagnosis , Cell Transformation, Neoplastic/genetics , Diagnosis, Differential , Hodgkin Disease/genetics , Hodgkin Disease/pathology , Humans , Ki-1 Antigen/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Lewis X Antigen/genetics , Lymphadenopathy/genetics , Lymphadenopathy/pathology , Male , Middle AgedABSTRACT
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.
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Biopsy, Fine-Needle/methods , Cytodiagnosis/methods , Lymph Nodes/pathology , HumansABSTRACT
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.
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Exosomes/metabolism , Glypicans/chemistry , Pancreatic Cyst/diagnosis , Biopsy, Fine-Needle , Diagnosis, Differential , Disease Progression , Female , Humans , Middle Aged , Pancreatectomy , Pancreatic Cyst/diagnostic imaging , Pancreatic Cyst/pathology , Pancreatic Neoplasms/pathology , Risk AssessmentABSTRACT
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.
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Cytodiagnosis , Neoplasms/diagnosis , Specimen Handling/methods , Biological Specimen Banks , Flow Cytometry , Humans , In Situ Hybridization, Fluorescence , Lymph Nodes/pathology , Neoplasms/pathologyABSTRACT
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.
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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.