Endoscopic Ultrasound-guided Fine-needle Biopsy With or Without Rapid On-site Evaluation for Diagnosis of Solid Pancreatic Lesions: A Randomized Controlled Non-Inferiority Trial.

BACKGROUND AND AIMS: The benefit of rapid on-site evaluation (ROSE) on the diagnostic accuracy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) has never been evaluated in a randomized study. This trial aimed to test the hypothesis that in solid pancreatic lesions (SPLs), diagnostic accuracy of EUS-FNB without ROSE was not inferior to that of EUS-FNB with ROSE. METHODS: A noninferiority study (noninferiority margin, 5%) was conducted at 14 centers in 8 countries. Patients with SPLs requiring tissue sampling were randomly assigned (1:1) to undergo EUS-FNB with or without ROSE using new-generation FNB needles. The touch-imprint cytology technique was used to perform ROSE. The primary endpoint was diagnostic accuracy, and secondary endpoints were safety, tissue core procurement, specimen quality, and sampling procedural time. RESULTS: Eight hundred patients were randomized over an 18-month period, and 771 were analyzed (385 with ROSE and 386 without). Comparable diagnostic accuracies were obtained in both arms (96.4% with ROSE and 97.4% without ROSE, P = .396). Noninferiority of EUS-FNB without ROSE was confirmed with an absolute risk difference of 1.0% (1-sided 90% confidence interval, -1.1% to 3.1%; noninferiority P < .001). Safety and sample quality of histologic specimens were similar in both groups. A significantly higher tissue core rate was obtained by EUS-FNB without ROSE (70.7% vs. 78.0%, P = .021), with a significantly shorter mean sampling procedural time (17.9 ± 8.8 vs 11.7 ± 6.0 minutes, P < .0001). CONCLUSIONS: EUS-FNB demonstrated high diagnostic accuracy in evaluating SPLs independently on execution of ROSE. When new-generation FNB needles are used, ROSE should not be routinely recommended. (ClinicalTrial.gov number NCT03322592.).

HER2 in gastric cancer: a digital image analysis in pre-neoplastic, primary and metastatic lesions.

The assessment of human epidermal growth factor receptor 2 (HER2) status in gastric cancer is crucial in selecting patients who may benefit from targeted therapy, yet heterogeneous expression could represent an important drawback for HER2 testing. We aimed to analyze (i) HER2 heterogeneity in primary gastric cancers, pre-neoplastic and metastatic lesions and (ii) HER2 prognostic role. We studied 292 surgically resected primary gastric carcinomas and constructed 21 tissue microarrays including tumor tissue cores, invasive front, paired lymph node metastasis, low- and high-grade dysplasia. Microarrays were immunohistochemically stained with HER2 antibody and digitally scanned. Novel digital analysis algorithms were developed to score HER2 expression. Fluorescence in situ hybridization was performed on equivocal cases. HER2-positive cases were 13% and heterogeneous HER2 expression was observed in 71% of positive samples. Analysis of HER2 status in tumor and tumor invasive front demonstrate concordance in 177 cases (88%). Comparison of HER2 expression in primary cancer and synchronous lymph node metastasis exhibited discordant status in 14% of cases. Dysplastic epithelium surrounding the tumor showed immunohistochemical score 2 or 3 in 19% of high-grade and in 9% of low-grade dysplastic samples. HER2 status was significantly associated with intestinal-type carcinomas (P=0.018) and prognosis since patients with primary HER2-positive tumor showed decreased overall survival (P=0.006). Intratumoral HER2 expression heterogeneity and variable lymph node metastases status strongly suggest evaluating more than one sample and, if available, metastatic foci for routinely HER2 testing.

Schwann cell hamartoma: case report.

BACKGROUND: Colorectal polyps of mesenchymal origin represent a small percentage of gastrointestinal (GI) lesions. Nevertheless, they are encountered with increasing frequency since the widespread adoption of colonoscopy screening. CASE PRESENTATION: We report a case of a small colonic polyp that presented as intramucosal diffuse spindle cell proliferation with a benign cytological appearance, strong and diffuse immunoreactivity for S-100 protein, and pure Schwann cell phenotype. Careful morphological, immunohistochemical and clinical evaluation emphasize the differences from other stromal colonic lesions and distinguish it from schwannoma, a circumscribed benign nerve sheath tumor that rarely arises in the GI tract. CONCLUSION: As recently proposed, this lesion was finally described as mucosal Schwann cell hamartoma.

Original Observation of Primary Bladder Histiocytic Sarcoma: First Case Report.

Histiocytic sarcoma (HS) is a rare malignant lymphohematopoietic neoplasm; it has been cited in the recent World Health Organization (WHO) classification as a malignant proliferation of cells exhibiting morphological and immunophenotypic features of mature histiocytes. To our knowledge, the present case is the first to be described in the bladder of a patient without a history of lymphoma. Only one case has been reported so far regarding a secondary bladder presentation in the setting of a previous diffuse large B-cell lymphoma. We discuss the case of a 68-year-old male who presented with hematuria and dysuria. CT scan revealed a 4-cm intravesical mass that histological examination defined as HS. Our objective was to describe the clinical, histological, immunophenotypical, molecular characteristics and discuss the differential diagnoses of this first case of primary bladder HS. Our research was based on a review of selected articles obtained via the PubMed database. This extremely rare experience provided us with the opportunity to depict an interesting case, highlight its uniqueness, and build up new pathological evidence.

Fine Needle Aspiration versus Fine Needle Biopsy of Biliopancreatic Lesions: Are They Really Opposing Techniques or Can They Be Complementary? Our Experience in a Large Cohort of Cases from a Single Institution.

INTRODUCTION: Nowadays, endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA), and fine needle biopsy (FNB) are considered the best procedures for the diagnosis of biliopancreatic lesions. These methods represent a milestone since they proved to be both safe for the patient and useful to achieve diagnostic material useful to plan the best treatment strategy. OBJECTIVE: Since in the literature, a debate between cytology and histology supporters is still ongoing and the trend is changing in favor of FNB, we would like to present our experience about the diagnostic yield of FNA and FNB. The aim of our study is to highlight FNA versus FNB diagnostic role of biliopancreatic lesions, highlight advantages, and drawbacks of these procedures, and our view on these 2 procedures and whether they should still be considered complementary or opposing techniques. METHODS: We retrospectively reviewed our hospital series of 469 EUS diagnostics procedures of biliopancreatic lesions performed in 419 patients, between 2015 and 2019. RESULTS: The overall adequacy rates of FNA and FNB were, respectively, 98.9 and 100%. Stratifying cases according to anatomic location of the mass (pancreas vs. biliary system), we detected 168 malignancies out of 349 pancreatic lesions (168/349; 48.1%), while biliary system cases positive for malignancy represented 33.8% (23/68 cases) (p value = 0.045, χ2 test). As for concomitant FNB, our series displayed a high rate of diagnostic concordance (88.8%). CONCLUSIONS: Despite numerous data published, it is still unclear which is the most feasible method to use; therefore, we compared FNA, FNB, or their combination to understand the best applicable technique. Our experience confirmed that FNA is extremely efficient in the diagnosis of biliopancreatic lesions, especially in the hands of expert endoscopists and pathologists. Considering anatomic location, EUS-FNA is more accurate for mass-forming neoplasms in the pancreatic parenchyma rather than for lesions of the biliary system. Moreover, concomitant FNB usually confirmed the cytological diagnosis, allowing a deeper immunohistochemical characterization of the neoplasia. This proves that a "pure" cytology and "pure" histology approach should be looked differently since these are complementary techniques especially if we can obtain a cellblock from FNA.

Iron Overload in Gastric Mucosa: Underdiagnosed Condition Rarely Documented in Clinical and Pathology Reports.

The iron-deficiency anemia is a common disorder worldwide. It is widely treated with oral iron supplements as ferrous sulfate compound in pill or tablet form, and continuous therapy can induce gastric diseases. The diagnosis of this unusual drug-induced disease is based on the endoscopic findings and the histopathological biopsy examination, because the clinical symptoms are vague and non-specific. Herein we report five cases of iron pill-induced gastritis after oral ferrous sulfate administration. The aim of this report is to underline that iron pill-induced gastritis is an under-diagnosed entity that must be kept in mind when patients undergo chronic iron-pill therapy because it can carry severe upper digestive tract complications. Moreover, we would speculate about the potential tumorigenic role of iron intake in iron-induced gastric inflammation.

Endoscopic ultrasound-guided radiofrequency ablation of pancreatic neuroendocrine tumors: a case series.

Background and study aims Surgery is the considered the therapeutic cornerstone for pancreatic neuroendocrine tumors (P-NETs), although burdened by high risk of significant adverse events. Recently, endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has been described for P-NETs. We aimed to evaluate the effectiveness and safety of EUS-RFA for treatment of P-NETs. Patients and methods We prospectively included all consecutive patients with P-NET ≤ 20 mm who were treated with EUS-RFA and were followed-up for at least 12 months. Results Ten patients (5 males, mean age 78.6 years, mean body mass index 28.2) with 11 P-NETs (mean size 14.5 mm; range 9 - 20 mm) localized in the pancreatic head (3 lesions), pancreatic body (5 lesions), and tail (3 lesions) underwent complete EUS ablation with one session of RFA. Complete ablation of P-NET was reached using a single-session RFA with a mean of 2.3 treatment applications per session. At both 6 - and 12-months computed tomography scans, all the patients had complete disappearance of lesions with radiological normalization. Regarding safety, only two cases of mild abdominal pain were recorded in two subjects with pancreatic head lesion, which were effectively treated with analgesics. The mean duration of hospital stay was 4 days (range 3 - 7 days). Conclusions EUS-RFA is effective and safe in treating P-NETs. It may be considered an effective therapeutic option in the treatment of small P-NETs independently from their functional status.

Keratinizing squamous metaplasia of the bladder: Our experience and current approaches.

INTRODUCTION: Bladder mucosa is anatomically covered by urothelial epithelium. The replacement of the urothelium with stratified squamous cells is defined as squamous metaplasia which can be keratinizing or non-keratinizing. Clinically, it is also known as leukoplakia or keratinizing cystitis of the bladder. Although several etiologic factors have been proposed such as chronic inflammation, irritative stimuli and infection, its pathogenesis is not clearly understood. The natural history of squamous metaplasia and clinical treatment are controversial. Many authors consider squamous metaplasia as a premalignant lesion, so it is fundamental to find an effective treatment to reduce the risk of developing bladder squamous carcinoma. CASE DESCRIPTION: We report our management of a 58-year-old man with histological evidence of keratinizing squamous metaplasia and severe lower urinary tract symptoms. After repeated transurethral resections, the patient was treated with intravesical instillation of hyaluronic acid showing the regression of the lesion with an improvement of macroscopic appearance followed by the resolution of clinical symptoms. CONCLUSION: The therapeutic management of keratinizing squamous metaplasia is controversial, and currently no effective medical therapy is available for its treatment. Actually, patients undergo transurethral resections and a multidisciplinary approach is required to avoid cystectomy. Annual cystoscopy with multiple biopsies should be performed to determine the presence of dysplasia. Moreover, the therapeutic treatment with hyaluronic acid instillations could be the starting point and the gold standard in the follow-up of our patient. However, at present, further studies are required to formulate an adequate policy for therapeutic management of this unusual lesion of the bladder mucosa.

Potential Difficulties in Cytological Approach of Basal Cell Adenoma of Salivary Glands: The Experience of a Single Institution.

OBJECTIVE: Basal cell adenoma (BCA) is an uncommon benign epithelial neoplasm of salivary glands, which was first described by Kleinsasser and Klein in 1967 and which derives its name from the monomorphic basaloid appearance of tumor cells. This tumor represents 1-2% of all salivary gland epithelial tumors; the most common site of occurrence is the parotid gland. It usually arises in adults over 50 years of age with slight female prevalence. STUDY DESIGN: We analyzed 5 cases of parotid lesions investigated by fine needle aspiration cytology at a single institution between 2002 and 2018. RESULTS: Our series was composed by 3 women and 2 men with a mean age of 62 years. The most important cytological criteria we observed were cohesive sharp-angled clusters of regular basaloid cells, palisaded by p63-positive myoepi-thelial cells, and bordered by basement membrane-like hyaline membrane in the absence of a myxochondroid stroma. Overall features were consistent with the diagnosis of BCA. CONCLUSIONS: Our aim is to highlight the cytological features of these rare lesions improving the awareness of cytological pitfalls of salivary gland basaloid neoplasms. Moreover, the goal of this paper is to add to the literature 5 additional cases of these unusual tumors.

[An uncommon cause of gynecomastia: testicular Leydig cell tumor. Hormonal profile before and after orchiectomy]. / Una causa infrequente di ginecomastia: il leydigioma del testicolo. Profilo ormonale prima e dopo l'orchiectomia.

Leydig cell tumors (LTC) are uncommon neoplasms arising from gonadal stroma that account for 1-3% of all testicular tumors. We report a case of LCT in a 36 years old man who had been suffering from painful bilateral gynecomastia for one year. Endocrine function tests showed decreased gonadotropin concentrations, and reduction of testosterone/estradiol ratio. Ultrasonography revealed a 10-12 mm hypoechoic area in the right testis, not evident on physical examination. Right orchiectomy was performed and histological examination confirmed the supposed existence of a LCT. After surgery, the gynecomastia has completely disappeared and hormonal alterations returned to normal.

Pitfalls and Key Features of a Case of Sclerosing Pneumocytoma: A Cytological Challenge?

BACKGROUND: The aim of the current case report is to re-evaluate the key features and pitfalls of fine-needle aspiration cytology (FNAC) in the diagnosis of sclerosing pneumocytoma (previously named sclerosing hemangioma) and to establish the importance of FNAC in addressing a proper surgical strategy. CASE: Herein we documented a case of a 70- year-old man with a lung nodule which showed a hypermetabolic uptake on positron emission tomography. He therefore underwent FNAC under computed tomography scan guidance with a 22-gauge needle. The cytopathological examination allowed a diagnosis of sclerosing pneumocytoma. A wedge surgical excision was performed and the histological examination confirmed the cytological diagnosis. CONCLUSION: FNAC is a fundamental tool for distinguishing sclerosing pneumocytoma from a malignant lung tumour and together with clinical, radiological and pathological multidisciplinary assessment is indispensable in planning appropriate surgical management. Cytopathologists should be aware of the pitfalls and key features of the cytopathological diagnosis of sclerosing pneumocytoma, which can significantly change the surgical approach to the patient and protect him from aggressive overtreatment.

Primary Effusion Lymphoma: Cytological Diagnosis of a Rare Entity--Report of Two Cases in HIV-Uninfected Patients from a Single Institution.

BACKGROUND: Primary effusion lymphoma (PEL) is a Kaposi's sarcoma-associated herpesvirus (KSHV)-related large B-cell lymphoma often affecting immunocompromised adults. However, several cases in nonimmunocompromised elderly patients have been reported. It usually occurs as a massive, serosal effusion without tumoral masses and lymphadenopathies. The most frequent diagnostic materials are cytological smears, displaying large lymphocytes with variable morphological aspects but with a specific 'null-cell' phenotype associated with the expression of KSHV-related latency-associated nuclear antigen. CASES: We report 2 cases of PEL that occurred in elderly, HIV-uninfected patients. In the first case, an 83-year-old man presented with severe dyspnea of 1 week duration. Radiological images documented pericardial effusion causing cardiac tamponade, without lymphadenopathies and solid masses. In the second case, an HIV-uninfected 94-year-old man was affected by anorexia, fatigue, shortness of breath and nonproductive cough. Radiological studies revealed bilateral pleural effusion, without evidence of abnormal lymphadenopathies and lung and/or pleural masses. Thoracentesis was immediately performed. Cytological evaluations of pericardial (first case) and pleural (second case) fluid effusion showed anaplastic and immunoblastic lymphocytes, respectively, expressing LCA/CD45, CD30 and KSHV. CONCLUSION: Albeit rare, PEL should be kept in mind in the diagnostic algorithm of serosal cytological evaluation in elderly HIV-uninfected patients.

Expression of Translationally Controlled Tumor Protein in Human Kidney and in Renal Cell Carcinoma.

Translationally controlled tumor protein is a multifaceted protein involved in several physiological and biological functions. Its expression in normal kidney and in renal carcinomas, once corroborated by functional data, may add elements to elucidate renal physiology and carcinogenesis. In this study, translationally controlled tumor protein expression was evaluated by quantitative real time polymerase chain reaction and western blotting, and its localization was examined by immunohistochemistry on 84 nephrectomies for cancer. In normal kidney protein expression was found in the cytoplasm of proximal and distal tubular cells, in cells of the thick segment of the loop of Henle, and in urothelial cells of the pelvis. It was also detectable in cells of renal carcinoma with different pattern of localization (membranous and cytoplasmic) depending on tumor histotype. Our data may suggest an involvement of translationally controlled tumor protein in normal physiology and carcinogenesis. However, functional in vitro and in vivo studies are needed to verify this hypothesis.

Unusual presentation of primary T-cell lymphoblastic lymphoma: description of two cases.

BACKGROUND: T-cell lymphoblastic lymphoma comprises approximately 85-90% of all lymphoblastic lymphomas. It often arises as a mediastinal mass, and with bone marrow involvement. Presentation at other sites without nodal or mediastinal localization is uncommon. CASE REPORT: We describe clinical, histologic, immunohistochemical, and molecular features of two cases of primary T-cell lymphoblastic lymphoma arising respectively in uterine corpus and testis. The tumors were composed by medium to large cells, exhibiting a diffuse pattern of growth but sometimes forming indian files or pseudo-rosettes. The neoplastic cells strongly expressed TdT and T-cell markers in both uterine corpus and testis. However, the testis case also showed aberrant expression of B-cell markers, thus molecular biology was necessary to achieve a final diagnosis. T-cell receptor gene rearrangement analysis identified a T-cell origin. CONCLUSIONS: To the best of our knowledge, only one doubtful previous case of primary uterine T-cell lymphoblastic lymphoma and no previous cases of primary testicular T-cell lymphoblastic lymphoma have been reported. Due to the morphology of neoplastic cells, a challenging differential diagnosis with all the tumors belonging to the so-called small round blue cell tumor category is mandatory. In ambiguous lineage cases, molecular biology may represent an adequate tool to confirm diagnosis. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1559880973128230.

Helicobacter pylori-negative Russell body gastritis: case report.

Russell body gastritis is an unusual form of chronic gastritis characterized by the permeation of lamina propria by numerous plasma cells with eosinophilic cytoplasmic inclusions. Very few cases have been reported in the literature; the majority of which have shown Helicobacter Pylori (H. pylori) infection, thus suggesting a correlation between plasma cell presence and antigenic stimulation by H. pylori. We present a case of Russell body gastritis in a 78-year-old woman who was undergoing esophagogastroduodenoscopy for epigastric pain. Gastric biopsy of the gastroesophageal junction showed the presence of cells with periodic acid-Schiff-positive hyaline pink bodies. Giemsa staining for H. pylori infection was negative, as well as immunohistochemical detection. The cells with eosinophilic inclusions stained positive for CD138, CD79a, and κ and lambda light chains, which confirmed plasma cell origin. In particular, κ and lambda light chains showed a polyclonal origin and the patient was negative for immunological dyscrasia. The histological observations were confirmed by ultrastructural examination. The cases reported in the literature associated with H. pylori infection have shown regression of plasma cells after eradication of H. pylori. Nothing is known about the progression of H. pylori-negative cases. The unusual morphological appearance of this type of chronic gastritis should not be misinterpreted during routine examination, and it should be distinguished from other common forms of chronic gastritis. It is mandatory to exclude neoplastic diseases such as gastric carcinoma, lymphoma and plasmocytoma by immunohistochemistry and electron microscopy, which can help with differential diagnosis. The long-term effects of plasma cells hyperactivation are still unknown, because cases of gastric tumor that originated in patients affected by Russell body gastritis have not been described in the literature. We are of the opinion that these patients should be scheduled for endoscopic surveillance.

True prostatic blue nevus associated with melanosis: case report, histogenesis and review of the literature.

We describe a case of true blue nevus of the prostate associated with prostatic melanosis, occurring in a 66-year-old man, who underwent multiple echo-guided prostatic fine-needle biopsies for a suspect prostatic adenocarcinoma. The histological features observed in the bioptic samples were chronic and acute inflammation, together with the presence of polygonal or elongated dendritic elements, scattered within the fibromuscular stroma and containing in their cytoplasm a brown pigment, staining black with the Fontana Masson stain, negative for the Perls stain, bleaching with potassium permanganate treatment and imunoreactive for S-100 protein. The presence of melanin pigment in the prostate is an extremely rare occurence, which may be due to melanosis, blue nevus and malignant melanoma, the latter showing distinctive cytological atypia. The recognition of each entity is fundamental for clinical and prognostic implications.