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.

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.

Ampullary Adenocarcinoma with Incidental Pancreatic Neuroendocrine Tumor: Report of an Extremely Rare Case and Review of Literature.

Periampullary neoplasms are a heterogeneous group of tumors arising within 2 cm of the ampulla of Vater. Neuroendocrine tumors can originate throughout the entire body, from neuroendocrine cells. These neoplasms exhibit deep differences, according to their origin and biological behavior. We describe a case of a 79-year-old man who underwent pancreaticoduodenectomy for adenocarcinoma of the ampulla of Vater after proper staging. At gross histology, an incidental pancreatic neuroendocrine tumor was also documented. Despite two synchronous neoplasms, the patient survived 34 months with no evidence of recurrence at follow-up. The synchronous presence of a second primitive tumor in patients affected by a neuroendocrine tumor is reported in the literature; incidence is variable and the most common site is the gastrointestinal tract. Diagnostic workup for ampullary neoplasms includes abdominal computed tomography (CT) scan, magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS). These investigations infrequently may detect subcentimetric lesions. We believe this case is currently extremely rare. Preoperative diagnosis of synchronous PanNET would not have changed our approach since surgical therapy represents the gold standard in resectable ampullary neoplasms, and it has a primary role in the prognosis of the present patient.

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.

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.

The alteration of lipid metabolism in Burkitt lymphoma identifies a novel marker: adipophilin.

BACKGROUND: Recent evidence suggests that lipid pathway is altered in many human tumours. In Burkitt lymphoma this is reflected by the presence of lipid droplets which are visible in the cytoplasm of neoplastic cells in cytological preparations. These vacuoles are not identifiable in biopsy section as lipids are "lost" during tissue processing. METHODS AND RESULTS: In this study we investigated the expression of genes involved in lipid metabolism, at both RNA and protein level in Burkitt lymphoma and in other B-cell aggressive lymphoma cases. Gene expression profile indicated a significant over-expression of the adipophilin gene and marked up-regulation of other genes involved in lipid metabolism in Burkitt lymphoma. These findings were confirmed by immunohistochemistry on a series od additional histological samples: 45 out of 47 BL cases showed strong adipophilin expression, while only 3 cases of the 33 of the not-Burkitt lymphoma category showed weak adipophilin expression (p<0.05). CONCLUSIONS: Our preliminary results suggest that lipid metabolism is altered in BL, and this leads to the accumulation of lipid vacuoles. These vacuoles may be specifically recognized by a monoclonal antibody against adipophilin, which may therefore be a useful marker for Burkitt lymphoma because of its peculiar expression pattern. Moreover this peptide might represent an interesting candidate for interventional strategies.

Renal infarction due to polyarteritis nodosa in a patient with angioimmunoblastic T-cell lymphoma: a case report and a brief review of the literature.

Angioimmunoblastic T-cell lymphoma is one of the most common subtypes of peripheral T-cell lymphoma (15-20% of all cases), accounting for approximately 1-2% of all non-Hodgkin lymphomas. It often presents autoimmune phenomena including hemolytic anemia, thrombocytopenia, glomerulonephrities and circulating immune complexes. Polyarteritis nodosa is an autoimmune disease characterized by necrotizing vasculitis of medium vessels, which rarely develops in association with hematological malignant disorders. Herein we report the case of a 40-year-old man who underwent lymph node biopsy in the suspicious of sarcoidosis. On the basis of histological and immunohistochemical findings, the diagnosis of angioimmunoblastic T-cell lymphoma was performed. The patient was successfully treated with cytarabine-based regimen for 6 cycles. Three months after the initial diagnosis of angioimmunoblastic T-cell lymphoma, a whole body computed tomography showed a lesion in the lower pole of the left kidney. Renal cell carcinoma was suspected, thus a nephrectomy was carried out. The histological findings were compatible with polyarteritis nodosa. To the best of our knowledge, the association between polyarteritis nodosa and angioimmunoblastic T-cell lymphoma has been described only once. This relation may be secondary to the induction of an autoimmune phenomenon by the lymphoma with the formation of circulating immune complexes, leading to vessels walls injury. A careful evaluation is needed in the management of angioimmunoblastic T-cell lymphoma patients with signs of renal failure in order to avoid delay of treatment and organ damage.

Diagnosis of Burkitt lymphoma using an algorithmic approach--applicable in both resource-poor and resource-rich countries.

Distinguishing Burkitt lymphoma (BL) from B cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma (DLBCL) and BL (DLBCL/BL), and DLBCL is challenging. We propose an immunohistochemistry and fluorescent in situ hybridization (FISH) based scoring system that is employed in three phases - Phase 1 (morphology with CD10 and BCL2 immunostains), Phase 2 (CD38, CD44 and Ki-67 immunostains) and Phase 3 (FISH on paraffin sections for MYC, BCL2, BCL6 and immunoglobulin family genes). The system was evaluated on 252 aggressive B-cell lymphomas from Europe and from sub-Saharan Africa. Using the algorithm, we determined a specific diagnosis of BL or not-BL in 82%, 92% and 95% cases at Phases 1, 2 and 3, respectively. In 3·4% cases, the algorithm was not completely applicable due to technical reasons. Overall, this approach led to a specific diagnosis of BL in 122 cases and to a specific diagnosis of either DLBCL or DLBCL/BL in 94% of cases that were not diagnosed as BL. We also evaluated the scoring system on 27 cases of BL confirmed on gene expression/microRNA expression profiling. Phase 1 of our scoring system led to a diagnosis of BL in 100% of these cases.

Rheumatoid nodule and combined pulmonary carcinoma: topographic correlations; a case report and review of the literature.

An association between rheumatoid arthritis (RA) and malignancies has been ascertained and patients with RA appear to be at higher risk of lymphoma and lung cancer. The higher risk of the latter malignancy may be related to rheumatoid interstitial lung disease and immunosuppressive therapies. Herein we illustrate the case of a 59-year-old male smoker affected by RA and treated with cortisone, methotrexate and TNF-α antagonists, who underwent right lower lobectomy for a nodular lesion. On microscopic examination, the lesion consisted of two distinct areas: a central area of fibrinoid necrosis, bordered by histiocytes in a palisaded arrangement, lymphocytes and a 0.4 cm thick peripheral area constituted by a combined small cell anaplastic carcinoma, adenocarcinoma and squamous cell carcinoma. The combination of three histotypes is very rare in such a small tumour. In our case, it may be hypothesized that synchronous, heterogeneous mutations occurred in different type of committed cells or in stem cells, due to the production of cytokines by RA nodule histiocytes and lymphocytes, which are contiguous to the carcinomatous area. Since few studies have evaluated the topographic correlation between tumors and rheumatoid lung lesions, further morphological and molecular studies are needed to clarify this association and the pathogenetic relationship between RA and cancer of the lung.

Analysis of the IgVH genes in T cell-mediated and antibody-mediated rejection of the kidney graft.

AIMS: Grafts have been shown to be sites where the alloimmune response develops in a direct interaction between the targeted tissue and the immune effectors. An important issue in renal rejection is B cell infiltrate that may contribute to the development or persistence of rejection. Analysis of gene-expression patterns also provides a window on the biology and pathogenesis of renal allograft rejection. METHODS: To better understand the role exerted by B cells in a renal acute rejection, the authors analysed the IgVH gene repertoire in six cases of transplanted kidneys with acute T cell-mediated rejection (TCMR), three of which were associated with antibody-mediated rejection (ABMR). RESULTS: The authors found mutated and unmutated sequences, without any evidence of clonal relationships, in all patients with TCMR alone and in two of the three cases with both acute TCMR and ABMR. The remaining patient showed glomerular inflammation and thrombosis, with diffuse C4d glomerular and peritubular capillary deposition, and hypermutated V region genes. CONCLUSIONS: These results suggest that there is more than one pathway to the onset and perpetuation of CD20 (+) B cells infiltration in acute rejection; furthermore, the CD20 (+) B cells' clonal expansion may be responsible for a more severe pattern of ABMR, through immune-mediated tissue damage.

Lymphoepithelioma-like carcinoma of the ovary.

Only one case of lymphoepithelioma-like carcinoma of the ovary has been reported so far. A new case is herein illustrated in a 69-year-old woman: an ovarian mass adherent to urinary bladder dome with peritoneal carcinomatosis. Histologically, undifferentiated carcinomatous areas were intermingled with abundant lymphoid tissue. Epstein-Barr virus has not been detected either in neoplastic or in lymphoid cells.

Alteration of microRNAs regulated by c-Myc in Burkitt lymphoma.

BACKGROUND: Burkitt lymphoma (BL) is an aggressive B-cell lymphoma, with a characteristic clinical presentation, morphology and immunophenotype. Over the past years, the typical translocation t(8;14) and its variants have been considered the molecular hallmark of this tumor. However, BL cases with no detectable MYC rearrangement have been identified. Intriguingly, these cases express MYC at levels comparable with cases carrying the translocation. In normal cells c-Myc expression is tightly regulated through a complex feedback loop mechanism. In cancer, MYC is often dysregulated, commonly due to genomic abnormalities. It has recently emerged that this phenomenon may rely on an alteration of post-transcriptional regulation mediated by microRNAs (miRNAs), whose functional alterations are associated with neoplastic transformation. It is also emerging that c-Myc modulates miRNA expression, revealing an intriguing crosstalk between c-Myc and miRNAs. PRINCIPAL FINDINGS: Here, we investigated the expression of miRNAs possibly regulated by c-Myc in BL cases positive or negative for the translocation. A common trend of miRNA expression, with the exception of hsa-miR-9*, was observed in all of the cases. Intriguingly, down-regulation of this miRNA seems to specifically identify a particular subset of BL cases, lacking MYC translocation. Here, we provided evidence that hsa-miR-9-1 gene is heavily methylated in those cases. Finally, we showed that hsa-miR-9* is able to modulate E2F1 and c-Myc expression. CONCLUSIONS: Particularly, this study identifies hsa-miR-9* as potentially relevant for malignant transformation in BL cases with no detectable MYC translocation. Deregulation of hsa-miR-9* may therefore be useful as a diagnostic tool, suggesting it as a promising novel candidate for tumor cell marker.

Possible implication of local immune response in Darier's disease: an immunohistochemical characterization of lesional inflammatory infiltrate.

Cell-mediated immunity is considered to be normal in Darier's Disease (DD), an inherited skin disorder complicated by skin infections. To date, there are no investigations on the local inflammatory infiltrate in DD skin lesions. In this immunohistochemical study we characterized and quantified it, making comparisons with two other inflammatory skin disorders, that is, pemphigus vulgaris (PV) and lichen ruber planus (LRP), and with the normal skin (NSk). We found a significant (P < .05) decrease of CD1a+ Langerhans cells (LCs) in DD, compared to PV, LRP, and NSk, and of CD123+ plasmacytoid dendritic cells (pDCs), compared to PV and LRP. We hypothesize that the genetic damage of keratinocytes might result in a loss of some subsets of dendritic cells and, consequently, in an impaired local immune response, which might worsen the infections that inevitably occur in this disease.

A rare case of primary small bowel adenocarcinoma with intussusception.

Other than in childhood, intussusception is unusual and nearly always caused by a structural and well demonstrable lesion. In contrast with the colon tract, the incidence of primary malignancies in the small bowel is very low. We report the case of a 51-year-old man presenting with jejunal intussusception due to a primary adenocarcinoma. To our knowledge, only a few similar cases have been reported in the literature to date. The patient was referred to our division for bowel obstruction. A CT scan showed a jejunal intussusception and surgical exploration was hence considered. At laparotomy, jejunal intussusception located just after the ligament of Treitz due to a polypoid lesion was confirmed and resection of the first jejunal loop was carried out. Histological examination of the specimen resulted in a diagnosis of a primary adenocarcinoma of the small bowel. In adult intestinal intussusception, resection without reduction is considered the optimal management if an underlying primary malignancy cannot be excluded.

Italy-Japan agreement and discrepancies in diagnosis of superficial gastric lesions.

The agreement between Italian and Japanese endoscopists and pathologists on endoscopic and histopathological diagnoses of superficial gastric lesions is verified with the use of Paris and Vienna classifications. The correlations between Paris endoscopic types and Vienna histopathological categories is high in both the independent Italian and Japanese evaluations. However, the agreement between Italian and Japanese endoscopists is moderate due to the difficult evaluation of the height of the lesions, in particular when they are mixed. The agreement on the size of the lesions is fairly good. The probability of the same allocation to the Vienna categories of a single case is 87 per cent, disagreements remaining in dysplasia grading, between dysplasia, not only high-grade but also low-grade, and in situ carcinoma, and on cancer invasion of the lamina propria. The results indicate that use of the Paris and Vienna classifications has reduced the discrepancies between Western and Japanese endoscopists and pathologists in the diagnosis of these lesions.