Combined fine needle aspiration cytology and core needle biopsy in the same setting: A two-years' experience.

INTRODUCTION: Fine needle aspiration cytology (FNAC) combined with rapid on-site evaluation (ROSE) and ancillary techniques is an accurate diagnostic tool for many pathologies. However, in some cases, it may not be sufficient for actionable diagnoses or molecular testing, especially for cases that require large immunohistochemical panels or cases in which histological features are mandatory for the diagnosis. Core needle biopsy (CNB), on the contrary, provides samples that are suitable for histological features and sufficient for all ancillary studies. However, CNB is often performed by radiologists or clinicians without the direct participation of cytopathologists, which can lead to missed or delayed diagnoses. This study reports on the experience of combining FNAC and CNB performed in one setting by cytopathologists. The aim was to evaluate the impact of CNB on FNAC and the diagnostic efficiency of the combined procedures. MATERIALS AND METHODS: One hundred forty-two FNAC and CNB procedures performed in the same setting over a period of 2 years were analysed. The FNAC diagnoses were compared and integrated with the subsequent CNB diagnoses. The impact of CNB was categorized as follows: non-contributory, in cases of inadequate samples; confirmed, when the CNB and FNAC diagnoses were the same; improved, when the CNB diagnosis was consistent with the FNAC diagnosis and further specified the corresponding entity; allowed, when CNB produced a diagnosis that could not be reached by FNAC; changed, when the CNB changed the previous FNAC diagnosis. RESULTS: CNB confirmed the FNAC diagnosis in 40.1% of cases (n = 57/142). CNB improved the FNAC diagnosis in 47.2% of cases (n = 67/142). CNB allowed a diagnosis that could not be performed on FNAC in 2.1% of cases (n = 3/142). CNB changed a previous FNAC diagnosis in 2.1% of cases (n = 3/142). CNB was non-contributory in 8.4% of cases (n = 12/142). CNB produced a positive impact on the whole diagnostic procedure in 51.4% of total cases (n = 73/142). The combined FNAC and CNB resulted in actionable diagnoses in 91.5% of all cases (n = 130/142). A complete molecular assessment was successfully performed in 14.7% of cases (n = 21/142) utilizing either FNAC or CNB material. CONCLUSIONS: The combined use of FNAC and CNB in one setting improves the diagnostic accuracy of both procedures. This approach exploits the advantages of each procedure, enhancing the accuracy of the final diagnosis.

Changes in mucosal IgG4+- and IL-10+-cell frequencies in adults with eosinophilic esophagitis on a two-food elimination diet.

Eosinophilic esophagitis (EoE) is increasingly diagnosed in patients with dysphagia. Type-2 immunity can induce EoE histopathology via non-IgE-dependent mechanisms, possibly involving IgG4 and IL-10. To elucidate the contribution of this response to EoE pathogenesis, we examined its association with clinical and histologic endpoints in adult EoE patients given a two-food elimination diet. IgG4- and IL-10-expressing cells were counted in esophageal biopsies and serum food-specific IgG4 measured at baseline and follow-up. Variables were correlated with histologic measures of disease activity. Patients exhibited significant reduction in esophageal eosinophilia and overall histology. A significant decrease in IL-10+-cell frequencies correlated with histologic changes. In contrast, a decline in serum and esophageal IgG4, while substantial, did not correlate with IL-10+-cell frequencies or histologic parameters. These results suggest a critical role of IL-10 in EoE pathogenesis. Conversely, IgG4 expression, while reflecting exposure to food antigens, is not obviously related to EoE histopathology or IL-10 expression.

Real-world experience with the Sydney System on 1458 cases of lymph node fine needle aspiration cytology.

INTRODUCTION: Lymph node (LN) fine needle aspiration cytology (FNAC) is a safe, quick, inexpensive, reliable, and minimally invasive technique for the diagnosis of lymphadenopathies. Recently, an international committee of experts proposed guidelines for the performance, classification, and reporting of LN-FNAC: the Sydney System. We set out to analyse the diagnostic performance of the Sydney System in a retrospective study. METHODS: We retrieved 1458 LN-FNACs, reformulated the diagnoses according to the Sydney System, and compared them to the histological control where available (n = 551, 37.8%). RESULTS: The risk of malignancy for each of the five categories was 66.7% for inadequate/insufficient, 9.38% for benign (overall: 0.84%), 28.6% for atypical, 100% for suspicious and 99.8% for malignant. LN-FNAC showed a sensitivity of 97.94%, a specificity of 96.92%, a positive predictive value of 99.58%, and a negative predictive value of 86.30%. CONCLUSIONS: These data support the usage of LN-FNAC as an agile first-level technique in the diagnosis of lymphadenopathies. The Sydney System supports and enhances this role of LN-FNAC, and its adoption is encouraged. In negative cases, coupled with ancillary techniques, LN-FNAC can reassure the clinician regarding the benignity of a lymphadenopathy and indicate the need for clinical follow-up, which will catch possible false negatives. In positive cases, LN-FNAC can provide sufficient information, including predictive biomarkers, to initiate management and obviate the need for subsequent, more invasive procedures. Given its speed, minimal invasiveness, and low cost, LN-FNAC can be performed in most cases, even when more invasive techniques are not feasible.

Hematuria in breast cancer: don't forget bladder metastases!

The bladder is a rare site for breast cancer metastases, and only occasional reports are present in the literature. Most cases coexist with synchronous metastases elsewhere, but isolated cases of a single metastatic localization in the urinary bladder have been reported. The most common symptoms of a metastatic localization of breast cancer to the urinary bladder are hematuria and voiding dysfunction. Herein we present three cases of urinary bladder metastasis from breast carcinoma, all presenting with gross hematuria as the only symptom. After a review of the relevant literature, we discuss the clinical and histological characteristics unique to our cases, highlighting potential clinical and pathological diagnostic pitfalls and differential diagnoses.

A Rare Case of Castleman Disease Presenting as an Ovarian Tumor.

Castleman disease (CD) is a rare lymphoproliferative disorder of unknown etiology. Its most common location is the mediastinum, but many other sites have been reported. We report a case of primary CD of the ovary, a rare localization with only 2 cases including the present case described in the world literature to date. A 58-yr-old woman who initially presented with abdominal pain underwent computed tomography scan which showed bilateral well-circumscribed solid adnexal masses. Because an ovarian bilateral tumor was suspected the patient was treated with a hysterectomy and bilateral salpingo-oophorectomy and the histopathologic examination confirmed the diagnosis of CD hyaline-vascular type of the right ovary associated with a contralateral fibroma. Three years after surgery the patient is alive and well and shows no signs of recurrent disease. The occurrence of this rare presentation of CD is the subject of this report. The problems of differential diagnosis with the most frequent lesions of the female pelvis are also discussed.

Nervous Nipple: Pseudopolythelia Caused by a Neurofibroma of the Areola.

ABSTRACT: The presence of a supernumerary nipple inside the original areola is a rare condition termed intra-areolar polythelia. Rarely, a lesion can macroscopically resemble a nipple. We report a case of a solitary neurofibroma (by itself rare in the areola) mimicking a second, twin nipple. In this case, these 2 rare conditions merge resulting in pseudopolythelia. The relevant literature on polythelia and neurofibromas of the breast is briefly reviewed.

Testing EGFR with Idylla on Cytological Specimens of Lung Cancer: A Review.

The current standard of care for advanced non-small-cell lung cancer is based on detecting actionable mutations that can benefit from targeted therapy. Comprehensive genetic tests can have long turn-around times, and because EGFR mutations are the most prevalent actionable mutation, a quick detection would enable a prompt initiation of targeted therapy. Furthermore, the scarcity of diagnostic material means that sometimes only cytologic material is available. The Idylla™ EGFR assay is a real-time PCR-based method able to detect 51 EGFR mutations in 2.5 h. Idylla is validated for use only on FFPE sections, but some researchers described their experiences with cytological material. We reviewed the relevant literature, finding four articles describing 471 cases and many types of cytological input material: smears, cell-block sections, suspensions, and extracted DNA. The sensitivity, specificity, and limit of detection appear comparable to those obtained with histological input material, with one exception: the usage of scraped stained smears as input may reduce the accuracy of the test. In conclusion, usage of cytological material as input to the Idylla EGFR test is possible. A workflow where common mutations are tested first and fast, leaving rarer mutations for subsequent comprehensive profiling, seems the most effective approach.

BAG3 expression correlates with the grade of dysplasia in squamous intraepithelial lesions of the uterine cervix.

INTRODUCTION: Bcl-2-associated athanogene 3 (BAG3) is a protein involved in apoptosis and stress response, which is overexpressed in invasive cervical cancer. However, nothing is known about BAG3 expression in precancerous lesions of the uterine cervix. We aimed to evaluate the expression of BAG3 in cervical intraepithelial neoplasia/squamous intraepithelial lesions (CIN/SIL). MATERIAL AND METHODS: Forty patients (16 CIN1/L-SIL, 11 CIN2/H-SIL and 13 CIN3/H-SIL) were assessed by immunohistochemistry for BAG3. The intensity of BAG3 expression was categorized as null, minimal, weak, moderate or strong. The association of BAG2 intensity of expression with the grade of dysplasia was assessed using Chi-square test (significant P value <0.05). RESULTS: In all normal controls, BAG3 expression was negative. In L-SIL specimens, BAG3 expression was confined to the basal third of the epithelium, with an intensity minimal in nine cases (56.3%), weak in six (37.5%) and strong in one (6.3%). In H-SIL specimens, BAG3 expression involved also the two upper thirds of the epithelium, with an intensity moderate in 13 cases (54.2%; 8 CIN2 and 5 CIN3) and strong in 11 cases (45.8%; 3 CIN2 and 8 CIN3). The distribution of BAG3 expression correlated perfectly with the grade of dysplasia (P = 0.0); a moderate/strong expression of BAG3 was significantly associated with H-SIL (P < 0.0001), with no significant difference between CIN2 and CIN3 (P = 0.1228). CONCLUSIONS: In CIN/SIL, both distribution and intensity of BAG3 expression correlate directly with the grade of dysplasia, supporting the involvement of BAG3 in all phases of cervical carcinogenesis and its possible diagnostic and prognostic role in cervical premalignant lesions.

Development of an Artificial-Intelligence-Based Tool for Automated Assessment of Cellularity in Bone Marrow Biopsies in Ph-Negative Myeloproliferative Neoplasms.

The cellularity assessment in bone marrow biopsies (BMBs) for the diagnosis of Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs) is a key diagnostic feature and is usually performed by the human eyes through an optical microscope with consequent inter-observer and intra-observer variability. Thus, the use of an automated tool may reduce variability, improving the uniformity of the evaluation. The aim of this work is to develop an accurate AI-based tool for the automated quantification of cellularity in BMB histology. A total of 55 BMB histological slides, diagnosed as Ph- MPN between January 2018 and June 2023 from the archives of the Pathology Unit of University "Luigi Vanvitelli" in Naples (Italy), were scanned on Ventana DP200 or Epredia P1000 and exported as whole-slide images (WSIs). Fifteen BMBs were randomly selected to obtain a training set of AI-based tools. An expert pathologist and a trained resident performed annotations of hematopoietic tissue and adipose tissue, and annotations were exported as .tiff images and .png labels with two colors (black for hematopoietic tissue and yellow for adipose tissue). Subsequently, we developed a semantic segmentation model for hematopoietic tissue and adipose tissue. The remaining 40 BMBs were used for model verification. The performance of our model was compared with an evaluation of the cellularity of five expert hematopathologists and three trainees; we obtained an optimal concordance between our model and the expert pathologists' evaluation, with poorer concordance for trainees. There were no significant differences in cellularity assessments between two different scanners.

Prostatic stromal sarcoma: Report of a rare case in a young male and review of the literature.

INTRODUCTION AND IMPORTANCE: Common prostatic neoplasms are diagnosed frequently, whereas rare entities require particular awareness and special clinical management. CASE PRESENTATION: A 31-year-old man presented with dysuria, hematuria and urinary retention. Histomorphological analysis of material obtained by transurethral resection of the prostate initially favored a sarcomatoid carcinoma, but immunohistochemistry allowed the correct diagnosis of sarcoma of the specialized stroma of the prostate. CLINICAL DISCUSSION: The patient refused surgical treatment and, despite chemotherapy, he died 8 months after the diagnosis. Herein, we will highlight the diagnostic and therapeutic challenge of prostatic stromal sarcoma by illustrating this case and reviewing the relevant literature. CONCLUSION: Although rare and shadowed by more common neoplasms that may mimic it, prostatic stromal sarcoma should be considered in the differential diagnosis of bladder and prostate neoplasms because of its dismal prognosis.

Upper Esophageal Sphincter Metrics across Eosinophilic Esophagitis, Gastroesophageal Reflux Disease and Functional Dysphagia: A Pilot Study.

BACKGROUND: Recent studies have evaluated the upper esophageal sphincter (UES) with high-resolution manometry (HRM) in some esophageal diseases, but not eosinophilic esophagitis (EoE). The aim of our study was to evaluate the function of the UES across EoE, gastroesophageal reflux disease (GERD), functional dysphagia (FD), and the relationship with esophageal symptoms, esophageal body contraction, and esophagogastric junction (EGJ) metrics. METHODS: HRM was performed on 30 EoE, 18 GERD, and 29 FD patients according to the Chicago Classification 3.0. The study data were exported to the online analysis platform Swallow Gateway. The UES was assessed in terms of UES Resting Pressure (UES-RP), UES Basal Pressure (UES-BP), UES Integrated Relaxation Pressure (UES-IRP), UES Relaxation Time (UES-RT), Basal UES Contractile Integral (Basal UES-CI), Post-Deglutitive UES Contractile Integral (Post-Deglutitive UES-CI), and Proximal Contractile Integral (PCI). RESULTS: ANOVA analysis showed significantly higher values of Post-Deglutitive UES-CI in EoE patients compared with FD patients (p = 0.001). Basal UES-CI and UES-RP showed significantly higher values in EoE (p = 0.002, p = 0.038) and GERD (p < 0.001, p = 0.001) patients compared with FD patients. Correlations between LES-CI and Post-Deglutitive UES-CI, Basal UES-CI, and UES-RP (p ≤ 0.001, p = 0.027, p = 0.017, respectively), and between LES-BP and Post-Deglutitive UES-CI (p = 0.019), independent of diagnosis, were shown. No correlations have been demonstrated between the UES, EGJ metrics, and esophageal symptoms. CONCLUSIONS: Some differences in UES metrics in the three different diseases were found. Further studies are needed to confirm the results of our pilot study and possible applications in clinical practice.

Digital Examination of LYmph node CYtopathology Using the Sydney system (DELYCYUS): An international, multi-institutional study.

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.

Rapidly growing intraparotid mass in a young child.

Nodular fasciitis (NF) is a pseudosarcomatous lesion typically involving the subcutaneous tissue and fascia; rarely, it has been observed within a parotid gland. We report a case of NF in an 8-year-old boy who presented with a rapidly growing nodule in the right parotid gland. A preoperative fine-needle aspiration suggested a diagnosis of nodular (pseudosarcomatous) fasciitis. After fine-needle aspiration, the surgical excision of nodule with a conservative approach was made. Intraparotid NF was diagnosed by histopathologic examination confirming the former cytologic diagnosis. This case demonstrates that NF, although rarely may occur in unusual site as parotid gland, in cases of rapidly growing tumor masses in the parotid, a correct cytologic diagnosis in the fine-needle aspirate might spare unnecessary aggressive surgical treatment.

Cytological Diagnosis of Aggressive Small-Cell Lymphomas.

BACKGROUND: Despite their sometimes deceivingly bland appearance, some small-cell lymphomas are very aggressive and the prognosis of patients depends on a prompt diagnosis that allows the initiation of appropriate therapy. SUMMARY: The present review discusses the salient cytological features of the most common aggressive small-cell lymphomas and then proceeds to analyze their main diagnostic criteria, including the usage of ancillary techniques. KEY MESSAGES: Lymph node fine-needle aspiration cytology is a fast, safe, cheap, minimally invasive, and accurate procedure that can be used for a prompt and accurate diagnosis of lymphomas.

Non-urothelial lesions of the urinary bladder A 14.5-year, single-institution review.

CONTEXT: In contrast to urothelial cancers, non-urothelial neoplasms involving the bladder are uncommon and often diagnostically challenging. These lesions include a variety of benign and malignant tumors often presenting with a combination of hematuria and the presence of a polypoid lesion at cystoscopy that may lead to an erroneous diagnosis of urothelial cancer. OBJECTIVE: We set out to quantify and classify the spectrum of non-urothelial lesions diagnosed in our institution, and briefly review the relevant literature on each lesion, with a focus on differential diagnosis and potential pitfalls. DESIGN: We performed a retrospective review (Jan 2008 - Jun 2022) of the cases diagnosed on TURB material at our institution. RESULTS: Out of 4071 TURB specimens, a total of 66 (1.62 %) non-urothelial lesions were identified. Most of these lesions were malignant (n = 51, 77 %), with metastases being the most common (n = 40, 60.6 %), followed by non-Hodgkin lymphoma (n = 8, 12 %). The remaining cases were benign lesions (n = 15, 22.7 %), with the most common being inflammatory myofibroblastic tumor (n = 4, 6.1 %) and endometriosis (n = 3, 4.5 %). CONCLUSIONS: In this retrospective case series, we identified various malignant and benign entities, some of which have been rarely reported in the bladder, such as paragangliomas, inflammatory myofibroblastic tumor, and leiomyosarcoma. These lesions may macroscopically and histologically mimic urothelial carcinoma. Because of their relative rarity and diagnostic overlap with conventional urothelial tumors, the pathologist should always keep in the mind the possibility of non-urothelial lesions.

The best prostate biopsy sampling system-fusion and systematic biopsy: A single center experience.

BACKGROUND: Prostate cancer is the second most commonly diagnosed cancer in men. The diagnostic accuracy in prostate cancer can be increased by employing a preliminary multiparametric MRI followed by a fusion-targeted biopsy. METHODS: To compare the diagnostic accuracy of fusion-targeted biopsy with the standard systematic biopsy in prostate cancer patients, we enrolled 139 patients on which we performed 139 prostate biopsies consisting of three targeted samples followed by 12 regular systematic samples. Based on histology, we analyzed the diagnostic performance of the two methods. RESULTS: Both methods were equally good at detecting clinically significant cancer (83.3%, 50/60), while systematic biopsy detected more clinically insignificant cancers. However, the best diagnostic performance is obtained by combining the two methods. CONCLUSION: The two methods are best seen as synergistic, and the addition of fusion biopsy can be used to detect more clinically significant prostate cancers than systematic biopsy alone.