Recurrent USP6 rearrangement in a subset of atypical myofibroblastic tumours of the soft tissues: low-grade myofibroblastic sarcoma or atypical/malignant nodular fasciitis?

Aims: Low-grade myofibroblastic sarcoma (LGMS) is a rarely metastasizing myofibroblastic tumour mostly affecting extremities and the head and neck of adults. Histologically, it shows long infiltrative fascicles of spindle cells with moderate nuclear atypia. By immunohistochemistry, it stains positive for smooth muscle actin (SMA) and sometimes for desmin.

Sinonasal nodular fasciitis: report of a case with USP6 rearrangement.

Nodular fasciitis (NF) is a benign myofibroblastic proliferation characterized by rapid growth, a self-limiting course, and USP6 gene rearrangement. Although it can arise in the head and neck region, very few cases of NF involving the sinonasal tract have been reported to date. Herein we report a case of NF involving the nasal cavity presenting as a polypoid well-defined mass causing obstructive symptoms in a male with a history of multiple local surgeries.

The Histological Background of Recurrence in Laryngeal Squamous Cell Carcinoma: An Insight into the Modifications of Tumor Microenvironment.

Recurrent laryngeal carcinoma presents differences from the primary tumor that largely depend on the treatment. In this article, we review the histologic and molecular treatment-induced changes that may affect the diagnosis of recurrent laryngeal carcinoma, the assessment of predictive markers, and the response to treatment with immune checkpoint inhibitors. Radiotherapy induces profound modifications that are strictly related to necrosis of different tissue components, fibrosis, and damage of the tumor vessels.

Low levels of miR-34c in nasal washings as a candidate marker of aggressive disease in wood and leather exposed workers with sinonasal intestinal-type adenocarcinomas (ITACs).

Introduction: Sinonasal intestinal-type adenocarcinomas (ITACs) are rare and aggressive tumors, closely related to professional exposure to wood dusts or leather. Here we explored the role of non-coding RNAs controlling MUC2 in liquid biopsies and tumors from ITAC patients with the aim of identifying biomarkers and molecular mechanisms to improve early diagnosis, prognosis, and therapeutic approaches for this rare cancer.

Methods: MiR-34c-3p, lncRNA AF147447 and MUC2 were measured in tumors and normal mucosa, in nasal washings (NW) from the affected and non-affected nostril and in plasma from 17 ITAC patients.

Alteration of the Nucleotide Excision Repair (NER) Pathway in Soft Tissue Sarcoma.

Clinical responses to anticancer therapies in advanced soft tissue sarcoma (STS) are unluckily restricted to a small subgroup of patients. Much of the inter-individual variability in treatment efficacy is as result of polymorphisms in genes encoding proteins involved in drug pharmacokinetics and pharmacodynamics. The nucleotide excision repair (NER) system is the main defense mechanism for repairing DNA damage caused by carcinogens and chemotherapy drugs.

Estimating survival after salvage surgery for recurrent salivary gland cancers: Systematic review.

Recurrent salivary gland carcinomas (RSCs) are poorly characterized and their clinical features and treatment options have not yet been fully described. The goal of this study was to analyze the therapeutic strategies and oncological outcomes of RSC patients through a literature review analysis. This systematic review was performed according to the PRISMA statements.

Durvalumab with cetuximab and radiotherapy for locally advanced squamous cell carcinoma of the head and neck: A phase 1/2 trial.

Background And Purpose: To report on the anti-tumor activity of a novel combination in high-risk locally advanced head and neck squamous cell carcinoma.

Materials And Methods: At a fixed dose of 1500 mg every 28 days, anti PD-L1 Durvalumab was given concomitantly to Radiotherapy and Cetuximab starting from the first week of combined treatment, followed by adjuvant Durvalumab to a maximum of 6 months after completion of radiation. The primary endpoint of the study was 2-year progression-free survival (PFS).

Stereotactic Body Radiotherapy in Oligomestatic/Oligoprogressive Sarcoma: Safety and Effectiveness Beyond Intrinsic Radiosensitivity.

Background: Metastatic soft tissue sarcoma (STS) patients may benefit from local ablative treatments due to modest efficacy of systemic chemotherapy. However, use of stereotactic body radiotherapy (SBRT) is controversial because of presumed radioresistance of STS.

Methods: Patients treated with SBRT for oligometastatic and oligoprogressive metastatic STS were retrospectively reviewed to assess results in terms of local control (LC), disease-free survival (DFS), and overall survival (OS).

Ewing family tumors of the appendicular skeleton: a retrospective analysis of prognostic factors.

Purpose: Authors retrospectively analyzed possible prognostic factors in a series of patients affected by Ewing sarcoma of extremities (eEWS) and treated over a 20-year period at a single institution.

Methods: Between 1997 and 2017, 88 bone eEWS were treated at our institution. Staging, age, gender, tumoral volume, local treatment, surgical margins, post-ChT necrosis were investigated for prognostic correlation with overall survival (OS) and event-free survival (EFS).

TRPA1 Expression in Synovial Sarcoma May Support Neural Origin.

Synovial sarcoma (SS) is a malignant mesenchymal soft tissue neoplasm. Despite its name, the cells of origin are not synovial cells, but rather neural, myogenic, or multipotent mesenchymal stem cells have been proposed as possible cells originators. Unlike other sarcomas, an unusual presentation of long-term pain at the tumor site has been documented, but the exact mechanisms have not been fully clarified yet.

MUC4 is a valuable marker for distinguishing secretory carcinoma of the salivary glands from its mimics.

Aims: Secretory carcinoma (SC) (synonym: mammary analogue secretory carcinoma) is a low-grade salivary gland tumour that occurs in both major and minor salivary glands. SC is known for its wide morphological, architectural and immunohistochemical spectrum, which overlaps with those of several salivary gland neoplasms, including acinic cell carcinoma (AciCC) and intercalated duct-type intraductal carcinoma (IDC) in major salivary glands, and polymorphous adenocarcinoma (PAC) in minor salivary glands. These tumours share with SC some morphological features and SOX10 immunoreactivity; also, with the exception of AciCC, they all coexpress S100 and mammaglobin.

Re-irradiation for oligoprogression under Nivolumab in recurrent head and neck squamous cell carcinoma: A case report.

Immune checkpoint inhibitors (ICIs) represent a recently introduced class of agents active in head and neck squamous cell carcinoma (HNSCC). For a subgroup of patients with recurrent or metastatic disease, long-term benefit can be achieved: maintaining a sustained response to immunotherapy is therefore a critical factor for its efficacy at an individual level. In analogy to targeted agents, a limited pattern of progression, or "oligoprogression", can occur.

The natural history of epithelioid sarcoma. A retrospective multicentre case-series within the Italian Sarcoma Group.

Introduction: This case-series is aimed to describe the natural history of epithelioid sarcoma (ES) and to provide insights into the differential clinical behaviour of its two variants ("classic-type" and "proximal-type"). The value of a subtype-adapted grading system based on pathological features is explored.

Methods: Data from consecutive, primary, localised, INI1-deleted ES operated at three Italian sarcoma reference centres (1995-2015) were included.

Intestinal metaplasia of the sinonasal mucosa adjacent to intestinal-type adenocarcinoma. A morphologic, immunohistochemical, and molecular study.

It has been hypothesized that the development of sinonasal intestinal-type adenocarcinoma (ITAC) occurs through intestinal metaplasia (IM) of the respiratory and/or glandular epithelium. The aim of this study was to characterize the histological, immunohistochemical, and molecular features of sinonasal IM. Histologic slides from 29 consecutive surgical specimens of ITAC were retrieved.

Low prevalence of K-RAS, EGF-R and BRAF mutations in sinonasal adenocarcinomas. Implications for anti-EGFR treatments.

We have previously shown that a subset of sinonasal intestinal-type adenocarcinomas (ITAC) shows activation of the epidermal growth factor-receptor (EGFR) pathway. In this study we examine the status of the EGFR, KRAS and BRAF genes in a series of sinonasal intestinal (ITAC) and non-intestinal type adenocarcinomas (non-ITAC). Eighteen ITACs and 12 non-ITACs were studied immunohistochemically for EGFR expression.

Primary combined neuroendocrine and squamous cell carcinoma of the maxillary sinus: report of a case with immunohistochemical and molecular characterization.

Neuroendocrine neoplasms represent a rare subset of tumors in the sinonasal tract. Combined tumors, with an endocrine and a non-neuroendocrine component, are exceedingly rare, and mainly consist of a combination of neuroendocrine carcinoma with adenocarcinomas. We present the clinico-pathologic and immunohistochemical features of a neuroendocrine carcinoma combined with squamous cell carcinoma, arising in the maxillary sinus.

Diagnostic utility of PLAG1 immunohistochemical determination in salivary gland tumors.

PLAG1 (pleomorphic adenoma gene 1) is a proto-oncogene whose overexpression is a crucial oncogenic event in salivary gland pleomorphic adenomas (PA), and in carcinoma ex-PA. The aim of the present study is to evaluate the sensitivity and the specificity of PLAG1 as a marker in the differential diagnosis of salivary gland benign and malignant tumors. We examined 101 cases, including 36 PAs, 8 myoepitheliomas, 3 basal cell adenomas, and 1 canalicular adenoma among benign tumors; 16 mucoepidermoid carcinomas, 10 adenoid cystic carcinomas, 8 acinic cell carcinomas, 8 polymorphous low-grade adenocarcinomas, 7 salivary duct carcinoma, and 4 epithelial-myoepithelial carcinoma among malignant tumors.

Primary juxtacortical myoepithelioma/mixed tumor of the bone: a report of 3 cases with clinicopathologic, immunohistochemical, ultrastructural, and molecular characterization.

We describe the clinicopathological, immunohistochemical, and molecular features of 3 primary juxtacortical myoepithelioma/mixed tumor of bone. The patients were 2 males (13 and 23 years of age) and a 15-year-old female. The juxtacortical lesions were all located in the femur, and were surgically removed, 2 with wide margins and one with marginal margins.

Immunohistochemical investigation of tumorigenic pathways in sinonasal intestinal-type adenocarcinoma. A tissue microarray analysis of 62 cases.

Aims: Sinonasal intestinal-type adenocarcinoma (ITAC) is an uncommon neoplasm morphologically similar to colorectal adenocarcinoma, with a well-recognized association with occupational exposure to wood or leather dusts. Here, we analyse several gene products with pivotal roles in tumorigenesis, including p53, p16, deleted in colon cancer (DCC), retinoblastoma, adenomatous polyposis coli, β-catenin, E-cadherin and CD10, and discuss their relation to clinical behaviour and to similar pathways in colorectal adenocarcinomas.

Methods And Results: Immunohistochemical analysis of 62 ITACs was conducted on a tissue microarray.

Current diagnostic strategies for undifferentiated tumours of the nasal cavities and paranasal sinuses.

Several malignant tumours occurring in the sinonasal tract may present with an undifferentiated morphology. Overall, these lesions pose significant diagnostic difficulties for the surgical pathologist, especially in limited biopsy material, but their correct classification is becoming increasingly important for an appropriate treatment strategy. This review deals with the criteria for differential diagnosis of these neoplasms, with emphasis on recent advances in immunohistochemistry and molecular biology, as well as with previous progress in electron microscopy.

Sinonasal carcinomas: recent advances in molecular and phenotypic characterization and their clinical implications.

Sinonasal carcinomas are rare tumors with an aggressive clinical behaviour which frequently pose a number of problems regarding the interpretation of diagnostic findings and the treatment. In addition, in comparison with other malignancies of the head and neck region, an elevated fraction of sinonasal carcinomas can be attributed to occupational exposure. This review is focused on the recent advances in the molecular and phenotypic characterization of sinonasal carcinomas, and their possible implications for the interpretation of epidemiological data, as well as for the diagnosis and treatment of these rare malignancies.

Evaluation of lymphangiogenesis in premalignant conditions of the head and neck mucosa.

Background: Our aim was to determine whether lymphangiogenesis occurs in the early steps of cancerogenesis of the upper aerodigestive tract.

Methods: We assessed the number of lymphatics per unit area (lymphatic vascular density [LVD]) and the percent area occupied by the lymphatic vessels (lymphatic vascular area [LVA]) by computer-assisted morphometric analysis in 56 samples immunohistochemically stained with the lymphatic marker D2-40. The results were compared to those obtained in 63 invasive squamous cell carcinomas.

A morphologic and immunohistochemical study of nasal mucosa in leatherworkers.

Background: The association between intestinal-type sinonasal adenocarcinoma and the occupational exposure to leather dusts has been widely documented, but the identification of precursor lesions in exposed workers has remained controversial. The purpose of this study was to investigate the histological changes and modifications in the phenotype of epithelial cells in nasal mucosa of leather workers.

Methods: Biopsy specimens of the mucosa of the middle turbinate were obtained from 139 subjects who had been employed in leather factories for 10-48 years (median, 29 years).