The Role of Mesothelin Expression in Serous Ovarian Carcinoma: Impacts on Diagnosis, Prognosis, and Therapeutic Targets

Mesothelin (MSLN) is a protein expressed in the mesothelial cell lining of the pleura,peritoneum, and pericardium; its biological functions in normal cells are still unknown. Experimental studies using knockout mice have suggested that this molecule does not play an important role in development and reproduction. In contrast, it has been observed that this molecule is produced in abnormal amounts in several malignant neoplasms, such as mesotheliomas and pancreatic adenocarcinomas. Many molecular studies have also demonstrated that mesothelin is overexpressed in HSOCs. Here, we discuss the current knowledge of mesothelin and focus on its role in clinical and pathological diagnoses, as well as its impact on the prognosis of HSOC. Moreover, regarding the binding of MSLN to the ovarian cancer antigen CA125, which has been demonstrated in many studies, we also report on signal transduction pathways that may play an important role in the spread and neoplasticprogression of this lethal neoplasm. Given that mesothelin is overexpressed in many solid tumours and has antigenic properties, this molecule could be considered an antigenic target for the treatment of many malignancies. Consequently, we also review the literature to report on mesothelin-targeting therapies for HSOC that have been recently investigated in many clinical studies

An unusual mechanism of metastasis in serous carcinoma of the endometrium associated with BRCA1 mutation gene: A case report with clinical and immunohistochemical features

The current case report documented a uterine highgrade serous carcinoma in a 48yearold woman with previous clinical history of breast cancer, BRCA1 gene mutation, and melanoma of the back. Uterine Serous Carcinoma (USC) was minimally invasive with fallopian tubes, ovaries, omentum, peritoneal surface and lymph node biopsy demonstrating no evidence of neoplasm at the time of total abdominal hysterectomy with bilateral salpingooophorectomy. In the peritoneal washing cytology and in the lumen of both fallopian tubes there were neoplastic cells which, on immunohistochemical analysis, showed immunoreactivity for p53 and p16 and negativity for WT1, supporting the endometrial origin of these malignant serous neoplastic cells. One year after surgery, the patient presented with recurrent peritoneal neoplastic nodules and metastases into intestinal lymphnodes. To detect neoplastic USC cells in the fallopian tube lumen and to prove a retrograde transtubal spread into the peritoneal cavity, it is mandatory to examine the fallopian tubes in their entirety according to the SEEFIM (Sectioning and Extensively Examining the Fimbria) protocol. In addition, this case report highlights the importance of the peritoneal cytology and omentectomy during a total abdominal hysterectomy with bilateral salpingooophorectomy to establish adequate staging and future patient management, even in cases of minimally invasive serous endometrial carcinoma

Dedifferentiated Endometrial Carcinoma: A Rare Aggressive Neoplasm-Clinical, Morphological and Immunohistochemical Features

Abstract: Dedifferentiated endometrioid adenocarcinoma is characterised by the coexistence of an undifferentiated carcinoma and a low-grade endometrioid adenocarcinoma. The low-grade component in this subtype of endometrial carcinoma is Grade 1 or 2 according to the Federation of Gynaecology and Obstetrics (FIGO) grading system. The coexistence of low-grade endometrial carcinoma and solid undifferentiated carcinoma can cause diagnostic problems on histological examination. In fact, this combination can often be mistaken for a more common Grade 2 or Grade 3 endometrial carcinoma. Therefore, this subtype of uterine carcinoma can often go under-recognised. An accurate diagnosis of dedifferentiated endometrial carcinoma is mandatory because of its poorer prognosis compared to Grade 3 endometrial carcinoma, with a solid undifferentiated component that can amount to as much as 20% of the entire tumour. The aim of this review is to provide clinical, immunohistochemical, and molecular data to aid with making an accurate histological diagnosis and to establish whether there are any findings which could have an impact on the prognosis or therapeutic implications of this rare and aggressive uterine neoplasm

Immunohistochemical expression of Mesothelin in a series of high grade tubal-ovarian serous carcinoma

Objectives In the current study, the immunohistochemical expression of Mesothelin (MSLN) in a series of high grade tubal-ovarian serous carcinoma (HGSC), was analysed and correlated with BRCA mutation, the stage of development at diagnosis, recurrences, and survival, in order to establish whether the expression of this marker could be useful for predicting the mutational aspects and clinical outcome of this severe malignancy. Material and Methods HGSCs were collected from 73 patients who had been surgically treated at Parma University, from 2001 and 2021. For immunohistochemical study, tissue sections from primary, metastatic and recurrences were incubated with a mouse monoclonal antibody against mesothelin (clone SP74, ready to use, Ventana-Roche). The proportion of mesothelin expression was evaluated according to this percentage of positive cells: 0, 0%, +1<10%, +2, with positivity between 51 and 75%, +3, with positivity between 75% and 95%, +4 with positivity >95%. The scores + 3 and +4 were considered as intense positivity, the scores +2 and +1 instead as weak positivity. A pattern of intense immunoreactivity mixed with weak positivity was defined as heterogeneous. Chi-square test and Fisher’s exact test were performed to investigate the relationship between MSLN expression and clinicopathological data. We compared disease-free survival (DFS), overall survival (OS) and progression-free survival (PFS) differences among groups of MSLN expression and disease stages using the Kaplan–Meier method and log-rank tests. P<0.05 was taken as a level of significance. Results We did not find any significant statistical differences in the MSLN expression between cases with and without BRCA mutation, nor were differences observed between low stages (stage I/II) and higher stages of development (stage III/IV) and metastatic tissue. Some tissue of recurrences and post-chemotherapy showed statistical differences, with a reduction in expression of MSLN compared with the primary neoplasm (respectively p Value: 0.023 and 0.0156). On the contrary, the follow-up revealed that the survival of HGSCs seems to be independent of MSLN expression. Conclusions To summarize, the present study demonstrates that MSLN expression is an independent prognostic factor and it could be used particularly as a potential target for targeting therapy in primary and metastatic neoplasms

Visceral Leishmaniasis Associated with B-Cell Chronic Lymphocytic Leukemia: Report of a Case and Review of the Literature

Infections often complicate the course of hematological diseases and may represent a diagnostic challenge. In particular, visceral leishmaniasis diagnosis may be missed in lymphoma patients, as lymphoma-related immunosuppression can lead to a misleadingly negative Leishmania serology and to atypical clinical manifestations, including the lack of fever, considered a common symptom in leishmaniasis. Herein, we report a case of visceral leishmaniasis in a patient with a long history of B-cell chronic lymphocytic leukemia presenting with increasing fatigue and diarrhea, in the absence of fever. Leishmania serology was negative. Bone marrow biopsy performed with the clinical suspicion of transformation to high-grade lymphoma disclosed intracytoplasmic inclusion bodies resembling Leishmania amastigotes within the cytoplasm of macrophages, and CD1a immunohistochemical expression helped to confirm the diagnosis of leishmaniasis. Liposomal amphotericin B was administered with complete symptom resolution. The correct identification of Leishmania is critical as visceral leishmaniasis represents a severe disease with an often fatal outcome, particularly in frail patients, unless promptly recognized and adequately treated. A review of the literature of visceral leishmaniasis cases occurring in B-cell chronic lymphocytic leukemia patients is performed

Cutaneous Localization of Classic Hodgkin Lymphoma Associated with Mycosis Fungoides: Report of a Rare Event and Review of the Literature

Mycosis fungoides and nodal classic Hodgkin lymphoma (cHL) have been reported to occur concurrently or sequentially in the same patient. A long-lasting mycosis fungoides more often precedes the onset of nodal cHL, although few cases of nodal cHL followed by mycosis fungoides have been observed. Skin involvement is a rare manifestation of cHL that may be observed in the setting of advanced disease. The decrease in skin involvement in cHL is mainly due to the improved therapeutic strategies. The concurrent presence of mycosis fungoides and cutaneous localization of classic Hodgkin lymphoma represents a very uncommon event, with only two cases reported so far. Herein, we describe the case of a 71-year-old man, with a history of recurrent nodal cHL, who developed MF and, subsequently, the cutaneous localization of cHL. The clinicopathological features of the two diseases are described focusing on the main differential diagnoses to be taken into consideration, and a review of the literature is performed