PRAME Expression in Mucosal Melanoma of the Head and Neck Region

PRAME (PReferentially expressed Antigen in MElanoma), a cancer-testis antigen expressed in normal and neoplastic tissues with several functions, proved to be a useful diagnostic tool in the differential diagnosis between benign and malignant melanocytic lesions. The current study aims to perform PRAME stain on a retrospective case series of mucosal melanocytic tumors of the head and neck region to compare 3 different scores and evaluate the most reliable one in this diagnostic set. Immunohistochemical analysis for PRAME was performed in 54 benign and malignant mucosal melanocytic tumors of the head and neck region collected from 41 patients. The best-performing cutoff of PRAME-positive cells (nuclear stain) to differentiate benign and malignant mucosal melanocytic tumors of the head and neck region is that proposed by Raghavan and colleagues (<60%/≥60% of PRAME-positive cells), with 100% and 77.8% of benign lesions and malignant tumors respectively correctly identified. Applying this score, PRAME stain showed the best results (sensitivity, specificity, accuracy, and positive and negative predictive values) for the diagnosis of head and neck melanocytic tumors. However, a subset of PRAME-negative malignant tumors was identified, especially located in the palatal area (hard and soft palate). Finally, high PRAME expression (≥60%) was associated with specific sites (nasal cavity/nasal septum/turbinates nasopharynx, and the maxillary sinus), nodular histotype, and female sex

\u201cIMMUNOHISTOCHEMICAL CHARACTERIZATION OF A SERIES OF PEDIATRIC MEDULLOBLASTOMAS\u201d - Investigation of JAM molecules expression in pediatric medulloblastoma

Background and aims. Medulloblastoma (MB) is the most frequent embryonal tumor of the CNS and the most common malignat pediatric brain tumor, arising mainly in the fourth ventricle. MB is characterized by four molecularly defined subgroups with distinct clinicopathological features and prognosis: WNT (MBWNT), SHH (MBSHH), group 3 (MBGrp3), and group 4 (MBGrp4). Standard therapy is ineffective in subsets of MB, thus there is a great need to identify novel prognostic markers and treatment targets. Junctional adhesion molecules (JAM)-A, -B, -C may be relevant candidate for this role, based on clinical and preclinical data. The aim of this study was to examine gene and protein expression of JAMs and assess their prognostic value by relying on both open access large datasets and a sample of pediatric MB. Methods. In the gene expression study, founded on two public datasets (n=763 and n=223), combined risk stratification models based on transcript levels of JAM genes (namely F11R, JAM-2 and JAM-3) and clinically relevant features were identified by multivariate Cox proportional hazards analysis. In the experimental study, we sought to examine the immunohistochemical expression of JAM-A,B,C in a sample of pediatric MB (n=65). Nanostring profiling and immunohistochemistry were adopted to obtain molecular classification. Association and survival analyses were conducted to validate trascriptomic findings. Results. Gene expression analyses showed that JAMs were differentially expressed across consensus molecular subgroups of MB (p<0.0001). In particular, JAM-3 was differentially expressed between MBGrp3 and MBGrp4 and its overexpression was significantly associated with large cell/anaplastic (LC/A) pathology (p=0,007) and shorter survival (p=0,002). These findings were only partially supported by immunohistochemical data, since high expression (3+) of JAM-C was strongly associated with a subset of MBGrp3 with LC/A pathology but did not differentiate between MBGrp3 and MBGrp4. Further, survival analyses displayed a trend for a shorter survival in patients with high expression of JAM-C. Thus, JAM-C may be useful to identify a subset of MBGrp3 with LC/A pathology carrying poor clinical outcomes. Conclusions. JAM-C may have a role as subtyping marker and prognostic factor in pediatric MB. Our findings are consistent with recent evidence suggesting that MBGrp3 and MBGrp4 display significant molecular overlap. In particular, JAM-C is useful to identify a subset of MBGrp3 showing LC/A pathology and dismal prognosis which could at least partially correspond to a recently identified high-risk subtype of MBGrp3 showing LC/A pathology and harbouring MYC amplification. Given the lack of reliable immunohistochemical markers for such emerging subgroup, further studies are needed to investigate the role of JAM-C in relation to clinicopathological features, molecular characteristics and overall prognosis

The Value of Large Sections in Surgical Pathology

Large format sections (LS) first have been introduced in breast pathology more than a century ago. Since then, they constituted for longtime a research tool to better understand breast microanatomy and the relationship between radiological images and pathological features. Similarly LS have been used to study neoplastic, inflammatory, and degenerative diseases affecting various organs, as brain, lung, gastrointentinal tract, bone, urinary tract, prostate, and placenta. Currently LS are mostly applied to diagnostic routine to better stage tumours such as prostate and breast carcinomas or to correlate radiologic imaging to gross specimens. The purpose of the present paper is to review the historical background and the basis of the applications of LS in surgical pathology, with special emphasis on breast tumours

Unusual Histological Evidence of Dysplasia in a Case of Oral Pemphigus Vulgaris

This report describes the management of an unusual case of oral pemphigus vulgaris (PV). The patient was referred for a painful single bullous lesion together with a small proliferative area localized in the soft palate. Histology and direct immunofluorescence data were consistent for PV but disclosed unusual signs of high-grade dysplasia in the proliferative area. At surgical removal of the dysplastic area 1 week after the start of cortisone therapy there was no evidence of dysplasia. Histological signs of high-grade dysplasia in oral mucosa are often associated with concurrent or subsequent carcinoma. However, severe inflammation may induce reactive epithelial cell changes and hence mimic histologic dysplasia. Pathologic evaluation of dysplasia in an inflammatory disease like PV may be a diagnostic challenge and a careful pathological evaluation is advisable before choosing between surgical and medical approach

Unexplained Vascular Pulmonary Nodule

Incidental pulmonary nodules are commonly encountered in computed tomography (CT) imaging [...

Diffuse Pulmonary Meningotheliomatosis: Clinic-Pathologic Entity or Indolent Metastasis from Meningioma (or Both)?

Pulmonary minute meningothelial-like nodules (MMNs) are common incidental findings in surgical specimens, consisting of tiny proliferation (usually no larger than 5–6 mm) of bland-looking meningothelial cells showing a perivenular and interstitial distribution, sharing morphologic, ultrastructural, and immunohistochemical profiles with meningiomas. The identification of multiple bilateral MMNs leading to an interstitial lung disease characterized by diffuse and micronodular/miliariform patterns radiologically allows the diagnosis of diffuse pulmonary meningotheliomatosis (DPM). Nevertheless, the lung is the most common site of metastatic primary intracranial meningioma, and differential diagnosis with DPM may be impossible without clinic–radiologic integration. Herein, we report four cases (three females; mean age, 57.5 years) fitting the criteria of DPM, all incidentally discovered and histologically evidenced on transbronchial biopsy (2) and surgical resection (2). All cases showed immunohistochemical expression of epithelial membrane antigen (EMA), progesterone receptor, and CD56. Notably, three of these patients had a proven or radiologically suspected intracranial meningioma; in two cases, it was discovered before, and in one case, after the diagnosis of DPM. An extensive literature review (44 patients with DPM) revealed similar cases with imaging studies excluding intracranial meningioma in only 9% (4 of 44 cases studied). The diagnosis of DPM requires close correlation with the clinic–radiologic data since a subset of cases coexist with or follow a previously diagnosed intracranial meningioma and, thus, may represent incidental and indolent metastatic deposits of meningioma

Genomic Characterization of Rare Primary Cardiac Sarcoma Entities

Primary cardiac sarcomas are considered rare malignant entities associated with poor prognosis. In fact, knowledge regarding their gene signature and possible treatments is still limited. In our study, whole-transcriptome sequencing on formalin-fixed paraffin-embedded (FFPE) samples from one cardiac osteosarcoma and one cardiac leiomyosarcoma was performed, to investigate their mutational profiles and to highlight differences and/or similarities to other cardiac histotypes. Both cases have been deeply detailed from a pathological point of view. The osteosarcoma sample presented mutations involving ATRX, ERCC5, and COL1A1, while the leiomyosarcoma case showed EXT2, DNM2, and PSIP1 alterations. Altered genes, along with the most differentially expressed genes in the leiomyosarcoma or osteosarcoma sample versus the cardiac angiosarcomas and intimal sarcomas (e.g., YAF2, PAK5, and CRABP1), appeared to be associated with cell growth, proliferation, apoptosis, and the repair of DNA damage, which are key mechanisms involved in tumorigenesis. Moreover, a distinct gene expression profile was detected in the osteosarcoma sample when compared to other cardiac sarcomas. For instance, WIF1, a marker of osteoblastic differentiation, was upregulated in our bone tumor. These findings pave the way for further studies on these entities, in order to identify targeted therapies and, therefore, improve patients’ prognoses

New evidence of cutaneous leishmaniasis in north-eastern Italy

Background: Human leishmaniasis is on increase in the Mediterranean Europe. However, the exact prevalence of cutaneous leishmaniasis (CL) is largely unknown as underdiagnosis and under reporting are common. Objective: To evaluate epidemiological, clinicopathological and microbiological aspects of CL cases occurring in the Bologna Province, north-eastern Italy. Methods: We performed a retrospective, observational study on CL cases diagnosed in the Bologna Province between January 2013 and December 2015. Results: During 2013\ue2\u80\u932015, 30 cases of CL were identified in the Bologna Province with an average incidence of 1.00/100 000, with an increase of fourfold to 12-fold as compared to previous years. 16 of 30 (53%) CL cases presented as single, typical lesions. CL diagnosis was carried out by histological and molecular techniques, although in 7 of 29 (24%) PCR-positive cases, amastigotes were not visible on histology. Conclusions: We report new evidence of CL cases in a focal area of north-eastern Italy in 2013\ue2\u80\u932015. Our study highlights the importance of CL surveillance in the Mediterranean basin and emphasizes the need for the molecular laboratory surveillance of CL in endemic areas

Correlations Between Cardiac Magnetic Resonance and Myocardial Histologic Findings in Fabry Disease

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