Morphological aspects and therapeutic options in melanoma: a narrative review of the past decade.

Melanoma is a malignant cancer of the skin, the incidence of which has been increasing year by year. This neoplasm has high aggressivity as well as the potential for invasion and metastases. Multiple factors related to the proliferation of this type of tumor have been identified, such as exposure to ultraviolet (UV) radiation and specific genetic backgrounds. From a histological and cytological point of view, the most common cells that are found in melanoma are epithelioid or spindle cells. To confirm the diagnosis and the melanocytic origin of the tumor, specific and sensitive markers are used. Also, observation of the behavior of this cancer, including its proliferative properties, has led to the development of multiple therapies, each of which is characteristic of the pathological stage at the time of diagnosis. While surgery is the most important therapeutic and curative option in cases of melanoma in situ, chemotherapy has been the main treatment for advanced stages of melanoma for many years. However, recently, targeted therapy and immunotherapy have changed the approach to treatment. At present, multiple studies are attempting to obtain further data about the tumor microenvironment and investigating how targeting particular molecules can change the prognosis of patients.

S100A8∕A9 is a valuable biomarker and treatment target to detect and modulate neutrophil involvement in myocardial infarction.

Myocardial infarction (MI) leads to irreversible ischemic damage of the heart muscle and is the leading cause of heart failure. The ischemic cardiac injury triggers a potent local and systemic immune response. In the acute phase post-MI, neutrophils infiltrate the myocardium in large numbers and induce further cardiomyocyte death, expanding the infarcted area. The alarmin S100A8∕A9 is a proinflammatory mediator primarily produced by myeloid cells, with an emerging role in MI. We previously demonstrated that short-term inhibition of S100A8∕A9 during the inflammatory phase of the immune response to MI improves long-term cardiac function. In the present study, we investigated the effects of S100A8∕A9 blockade on myocardial inflammation and post-ischemic myocardial injury in a mouse model of coronary artery ligation. Immunohistochemical (IHC) staining revealed that the presence of S100A9 is strongly correlated with neutrophil infiltration in the myocardium on days 1 and 3 post-MI. A 3-day treatment with the S100A8∕A9 blocker ABR-238901 starting immediately after MI decreased the number of neutrophils and S100A9 presence in the myocardium and had a positive impact on cardiac damage, reducing infarction size. These findings promote S100A9 as an IHC biomarker of neutrophil infiltration and a promising immunomodulatory target to regulate neutrophil recruitment, reduce ischemic injury and promote long-term beneficial cardiac recovery after MI.

CK 8∕18: the key to differentiating intracutaneous lesions with pagetoid features.

INTRODUCTION: Neoplasms with pagetoid features are a category of rare lesions defined by the presence of atypical cells at different levels of the epidermis. The most important diseases within this category are mammary Paget disease (MPD), extramammary Paget disease (EMPD), Bowen's disease, in situ melanoma, and pagetoid reticulosis. AIM: The aim of this analysis was to describe the importance of the cytokeratin 8∕18 (CK 8∕18) immunostaining in diagnosing MPD and EMPD and differentiating them from other lesions. MATERIALS AND METHODS: A retrospective study was employed, based on the histopathological and immunohistochemical (IHC) characteristics of 30 cases that presented pagetoid features. The cases were processed and analyzed at the Department of Pathology, Mures Clinical County Hospital, Târgu Mures, Romania, from 2017 to 2020. RESULTS: Five MPD cases, one EMPD case, one pagetoid reticulosis case, 10 Bowen's disease cases, and 13 in situ melanoma cases were collected. Under Hematoxylin-Eosin staining, cells presented pale cytoplasm in MPD, EMPD, and in 25% of the melanoma cases. Hyperchromasia with nuclear enlargement was seen in all cases. Immunostaining with CK 8∕18 was positive in all MPD and EMPD cases. Tests for CK7, p63, and CK AE1∕AE3 were positive in MPD, EMPD, and Bowen's cases. Tests for S100, SRY-box transcription factor 10 (SOX10), human melanoma black 45 (HMB45), and Melan A were positive in melanoma cases, while cluster of differentiation (CD)3, CD4, and CD8 tests were positive in the pagetoid reticulosis case. CONCLUSIONS: CK 8∕18 is an IHC marker that can help establish the diagnosis of MPD and EMPD and differentiate them from other pagetoid neoplasms, ensuring the proper diagnosis and prognosis are provided.

Neuroendocrine tumors (NETs) - experience of a single Center.

INTRODUCTION: Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors arising from cells that are part of the diffuse neuroendocrine system. PATIENTS, MATERIALS AND METHODS: We conducted a retrospective study in which we included a number of 91 cases diagnosed with neuroendocrine tumors (NETs). Descriptive statistics was performed: number of cases based on location, distribution by gender (male∕female), distribution by age, and we also performed a morphological and immunohistochemical (IHC) study. RESULTS: The highest number of cases was found in lungs (60 cases). Tumors located on the skin, breast or bladder have been discovered, locations considered rare for this type of tumor. Of all cases diagnosed in the lungs, 59 were diagnosed as small cell carcinomas (SCCs) and only one case as NET. All surgical specimens were positive for chromogranin A (CgA), with a different expression for the other immunomarkers. For the lung biopsies, the most frequently IHC staining was CgA and cluster of differentiation 56 (CD56), with an increased positivity for the latter. CONCLUSIONS: CgA remains the most sensitive immunomarker in the diagnosis of NETs. CD56 is the most widely used immunomarker for diagnosing small cell lung tumors. Positive expression of thyroid transcription factor 1 (TTF1) immunomarker does not confirm pulmonary origin of SCCs.