Evaluation of the Involvement of Heme Oxygenase-1 Expression in Discoid Lupus Erythematosus Lesions.

Discoid lupus erythematosus (DLE) is a chronic autoimmune disease that primarily affects the skin, causing red, scaly patches that may be disfiguring and can cause permanent scarring. This study aimed to investigate the potential clinical and therapeutic applications of heme oxygenase-1 (HMOX1) in the context of DLE. Immunohistochemical staining and bioinformatics analysis were performed on skin biopsy samples from DLE patients to examine the levels of HMOX1 and to correlate with markers of inflammation. Our study revealed a negative correlation between HMOX1 levels and the inflammatory status of DLE lesions, as well as an inverse correlation between HMOX1 levels and the infiltration of M1 macrophages and activated mastocytes. These findings suggest that HMOX1 plays a crucial role in the regulation of inflammation in DLE and could be a potential therapeutic target and biomarker for DLE.

Nodal frozen section + elective neck dissection as an alternative to sentinel lymph node biopsy for the management of cT1-2N0 oral squamous cell carcinoma patients: a viability and accuracy study.

PURPOSE: Oral Squamous Cell Carcinoma (OSCC) is characterized by a high aggressiveness and a tendency to metastasize. The management of the neck in cT1-2N0 patients c follows three strategies: watchful waiting, elective neck dissection (END) or sentinel lymph node biopsy (SLNB). The aim was to assess the viability of intraoperative frozen sections of the nodes of cT1-2N0 to spot occult metastases as an alternative to SLNB, performing a modified radical neck dissection (MRND) in intraoperatively positive patients. METHODS: The patients were treated at the Maxillo-Facial Surgery Unit of Policlinico San Marco of Catania between 2020 and 2022. END was performed in all patients, including frozen section examination of at least one clinically suspicious node per level. In case of positivity after frozen section examination, neck dissection was extended to levels IV and V. RESULTS: All frozen sections were compared with a definitive test after paraffin inclusion. During surgery, 70 END were performed, and 210 nodes were analyzed with frozen sections. Among the 70 END, 52 were negative after frozen Sects. (156 negative nodes), and surgery was ended. Five of the 52 negative ENDs resulted in pN + after paraffin inclusion (9.6%), which underwent postoperative adjuvant treatment. The sensibility of our END + frozen section method was 75%, while the specificity of our test was 94%. The negative predictive value was 90,4%. CONCLUSIONS: Elective neck dissection + intraoperative frozen section could be an alternative to SLNB to spot occult nodal metastases in cT1-2N0 OSCC due to the opportunity to perform a one-step diagnostic/therapeutic procedure.

Is There a Role of Warburg Effect in Prostate Cancer Aggressiveness? Analysis of Expression of Enzymes of Lipidic Metabolism by Immunohistochemistry in Prostate Cancer Patients (DIAMOND Study).

Prostate Cancer (PCa) is still ranked as the first cancer in the male population and evidences have suggested an alteration of glycemic and lipidic metabolism that are related to its progression and prognosis. The aim of the study is to investigate associations between enzymes' expression, especially involved in the lipidic pathway, and PCa aggressiveness. We retrospectively analyzed data from 390 patients with PCa or benign prostatic hyperplasia (BPH) at the Department of Urology, University of Catania. Immunohistochemical slides were evaluated for the expression of proteins related to glucose and lipidic metabolism. A total of 286 were affected by PCa while 104 by BPH. We demonstrated that ATP-lyase (odds ratio [OR]: 1.71; p < 0.01), fatty acid synthase (OR: 4.82; p < 0.01), carnitine palmitoyl transferase-1a (OR: 2.27; p < 0.05) were associated with androgen receptor (AR) expression. We found that steaoryl Co-A desaturase expression in PCa patients with total cholesterol ≥ 200 mg/dL was independently associated with ISUP ≥4 (OR: 4.22; p = 0.049). We found that CPT-1a+ was associated with biochemical recurrence (hazard ratio: 1.94; p = 0.03]). Our results support the evidence that the manipulation of lipidic metabolism could serve in the future to contrast PCa progression.

Mechanistic Translation of Melanoma Genetic Landscape in Enriched Pathways and Oncogenic Protein-Protein Interactions.

BACKGROUND/AIM: Malignant melanoma is a skin cancer originating from the oncogenic transformation of melanocytes located in the epidermal layers. Usually, the patient's prognosis depends on timing of disease detection and molecular and genetic profiling, which may all significantly influence mortality rates. Genetic analyses often detect somatic BRAF, NRAS and cKIT mutations, germline substitutions in CDKN2A, and alterations of the PI3K-AKT-PTEN pathway. A peculiar molecular future of melanoma is its high immunogenicity, making this tumor targetable by programmed cell death protein 1-specific antibodies. MATERIALS AND METHODS: Ten formalin-fixed paraffin embedded samples derived from melanoma patients were subjected to next-generation sequencing (NGS) analysis using the FDA-approved FoundationOne CDx™ test. The molecular features of each case were then analyzed employing several in silico prediction tools. RESULTS: We analyzed the mutational landscape of patients with metastatic or relapsed cutaneous melanoma to define enriched pathways and protein-protein interactions. The analysis showed that both known genetic alterations and variants of unknown significance rely on redundant signaling converging on similar gene ontology biological processes. Complex informatics analyses of NGS-based genetic results identified pivotal signaling pathways that could provide additional targets for cancer treatment. CONCLUSION: Our data suggest an additional role for NGS in melanoma, as analysis of comprehensive genetic findings using innovative informatic tools may lengthen the list of druggable molecular targets that impact patient outcome.

A Case of Non-Irradiated Balloon Cell Melanoma of the Choroid: Expanding the Morphological Spectrum of Primary Uveal Melanomas.

Uveal melanoma (UM) is the most common primary intraocular tumor in adults and usually has a very poor prognosis. Histologically, UMs have been classified in epithelioid cell type, spindle cell type, and mixed cell type. Balloon cells are large pale cells that contain small, hyperchromatic, central nuclei with vesiculated, clear, and lipid-rich cytoplasm. A balloon cell morphology is infrequently observed in naevi and even less frequently in malignant melanomas of the skin, conjunctiva, ciliary body and choroid. In this regard, UMs that exhibit balloon cell features are generally those previously treated with proton beam irradiation and then enucleated, rather than those that directly underwent primary surgery. To the best of our knowledge, very few cases of primary UM showing extensive balloon cell morphology have been reported in scientific literature to date. We herein present an unusual case of primary UM with diffuse balloon cell changes in a 69-year-old woman.

Glioblastoma, IDH-Wild Type With FGFR3-TACC3 Fusion: When Morphology May Reliably Predict the Molecular Profile of a Tumor. A Case Report and Literature Review.

It has been reported that in-frame FGFR3-TACC3 fusions confer to glioblastomas, IDH-wild type (GBMs, IDHwt) some unusual morphologic features, including monomorphous rounded cells with ovoid nuclei, nuclear palisading, endocrinoid network of "chicken-wire" vessels, microcalcifications and desmoplastic stroma, whose observation may predict the molecular profile of the tumor. We herein present a case of recurrent GBMs, IDHwt, exhibiting some of the above-mentioned morphological features and a molecularly-proven FGFR3-TACC3 fusion. A 56-year-old man presented to our hospital for a recurrent GBM, IDHwt, surgically treated at another center. Histologically, the tumor, in addition to the conventional GBM morphology, exhibited the following peculiar morphologic features: (1) monomorphous neoplastic cells with rounded nuclei and scant pale cytoplasm; (2) thin capillary-like vessels with "chicken-wire" pattern; (3) nuclear palisading; (4) formation of vague perivascular pseudorosettes; (5) spindled tumor cells embedded in a loose, myxoid background. Based on this unusual morphology, molecular analyses were performed and an FGFR3 exon17-TACC3 exon 10 fusion was found. The present case contributes to widening the morphologic spectrum of FGFR3-TACC3-fused GBM, IDHwt and emphasizes that pathologists, in the presence of a GBM, IDHwt with unconventional morphology, should promptly search for this fusion gene.

Vocal Cord Hemangioma: A Common Tumor in an Unusual Localization. A Case Report with Short Review of Literature.

Laryngeal adult-type hemangiomas are very rare lesions, more frequent in men, whose optimal treatment consists of microlaryngoscopical excision. We herein report a case of larynx cavernous hemangioma in a 64-year-old woman with hoarseness for about six months. Histologically, the tumor was composed of multiple vessels embedded in an edematous stroma.

Medullary Carcinoma of the Gastrointestinal Tract: Report on Two Cases with Immunohistochemical and Molecular Features.

Medullary carcinoma of the colon is a rare histological variant characterized by a poorly differentiated morphology, an aberrant immunophenotype, and microsatellite instability. Despite the lack of glandular differentiation, medullary carcinoma is reported to have a good prognosis. It is typically located in the right colon and frequently affects older women. Due to its clinical, histological, biological, and genetic peculiarity, medullary carcinoma requires an accurate diagnosis and the awareness of this diagnostic possibility. We describe the morphological, immunohistochemical, and molecular findings of two interesting cases, the first one in the right colon of a patient and the second one in the terminal ileum of a patient with Crohn's disease. Deeper knowledge of all the biological and clinical features will allow appropriate and specific treatment of this tumor in the future.

Sclerosing Mesenteritis, a Rare Cause of Mesenteric Mass in a Young Adult: A Case Report.

Sclerosing mesenteritis (SM) is a rare fibroinflammatory disorder that involves mesenteric adipose tissue, more frequently localized in the small intestine, with an insidious clinical presentation having symptoms related to mass effect, usually resulting in bowel obstruction, mesenteric ischemia, as well as rapid weight loss. We report a case of a 23-year-old male presenting with palpable abdominal mass, mesogastric pain, and a history of rapid weight loss, who underwent exploratory laparoscopy. A hemorrhagic and gelatinous nodular tumor mass of the mesentery was identified and the surgical procedure was converted to a laparotomic approach. Histologically, the mass was composed of a proliferation of bland-looking spindle cells with slightly eosinophilic cytoplasm and elongated normochromatic nuclei with mild nuclear atypia, haphazardly set in a collagenized stroma; fat necrosis and inflammatory cells (lymphocytes, plasma-cells, and histiocytes) were also evident. The diagnosis of sclerosing mesenteritis was made. Our case emphasizes that histology remains pre-eminent for a correct diagnosis of SM, as pre-operative radiological-based diagnosis is non-specific.

SRSF-1 and microvessel density immunohistochemical analysis by semi-automated tissue microarray in prostate cancer patients with diabetes (DIAMOND study).

OBJECTIVE: To study the association between insulin receptors (isoforms α and ß), insulin growth factor-1 (IGF1) and serine/arginine splicing factor 1 (SRSF-1) in patients with prostate cancer (PC) and diabetes. MATERIALS AND METHODS: We retrospectively analyzed data from 368 patients who underwent surgery for PC or benign prostatic hyperplasia (BPH) between 2010 and 2020 at the Department of Urology, University of Catania. Tissue microarray slides were constructed and they were stained for androgen receptor (AR), insulin receptor-α and -ß, IGF1 (IGF1-R), Ki-67, and prostate specific membrane antigen (PSMA) expression using validated score. RESULTS: The final cohort was represented by 100 patients with BPH and 268 with PC, with a median age of 68 years. We found that SRSF-1 expression was associated with AR (odds ratio [OR]: 1.66), PSMA (OR: 2.13), Ki-67 (OR: 5.99), insulin receptor (IR)-α (OR: 2.38), IR-ß (OR: 3.48), IGF1-R (OR: 1.53), and microvascular density (MVD) was associated with PSMA (OR: 3.44), Ki-67 (OR: 2.23), IR-α (OR: 2.91), IR-ß (OR: 3.02), IGF1-R (OR: 2.95), and SRSF-1 (OR: 2.21). In the sub cohort of PC patients, we found that SRSF-1 expression was associated with AR (OR: 2.34), Ki-67 (OR: 6.77), IR-α (OR: 2.7), and MVD (OR: 1.98). At the Kaplan-Meier analysis, SRSF-1+ patients had worse 5- and 9-year biochemical recurrence (36% and 6%) respect to SRSF-1- (67% and 7%; p < .01) and similarly MVD+ patients (44% and 7%) respect to MVD- (64% and 8%; p < .01). Restricting the analysis only in patients with PC and diabetes, we found that SRSF-1+ was associated with Ki-67+ (OR: 8.75; p < .05) and MVD+ (OR: 7.5; p < .05). CONCLUSIONS: PC exhibits widespread heterogeneity in protein expression. In particular, the expressions of the SRSF-1 protein and of the MVD are associated with a worse prognosis and in particular with a greater cell proliferation. These results, although preliminary, may offer new future scientific insights with the aim of highlighting possible genetic alterations linked to a greater expression of SRSF-1 and associated with a worse prognosis.

Insulin signaling, androgen receptor and PSMA immunohistochemical analysis by semi-automated tissue microarray in prostate cancer with diabetes (DIAMOND study).

In the last years, many studies have highlighted the hypothesis that diabetes and hyperglycemia could be relevant for prostate cancer (PC) development and progression. We aimed to identify the prognostic value of tissue expression of androgen receptor (AR), Prostate-Specific Membrane Antigen (PSMA), Ki-67, insulin receptors (IR)  α and ß, insulin growth factor-1 (IGF-1) receptor, in patients with PC and to evaluate their association with diabetes. We retrospectively collected data from 360 patients who underwent radical prostatectomy for PC or surgery for benign prostatic hyperplasia (BPH), between 2010 and 2020. We constructed tissue microarray for immunohistochemistry (IHC) analysis. In the final cohort (76 BPH and 284 PC), 57 (15.8%) patients had diabetes, 17 (22.37%) in BPH and 40 (14.08%) in PC (P = 0.08). IR-α was more expressed in patients with PC compared to the BPH Group (95.96% vs 4.04%; P <0.01). We found that AR was associated with increased risk of International Society of Urological Pathology (ISUP) score ≥4 (OR: 2.2; P <0.05), higher association with Ki-67 (OR: 2.2; P <0.05) and IR-α (OR: 5.7; P <0.05); IGF-1 receptor was associated with PSMA (OR: 2.8; P <0.05), Ki-67 (OR: 3.5; P <0.05) and IR-ß (OR: 5.1; P <0.05). Finally, IGF-1 receptor was predictive of ISUP ≥ 4 (OR: 16.5; P =0.017) in patients with PC and diabetes. In the present study we highlighted how prostate cancer patients have a different protein expression in the tissue. This expression, and in particular that relating to IGF-1R, is associated with greater tumor aggressiveness in those patients with diabetes. We suppose that these results are attributable to an alteration of the insulin signal which therefore determines a greater mitogenic activity that can influence tumor progression.

Endomyometriosis of the Rectum With Disseminated Peritoneal Leiomyomatosis 8 Years After Laparoscopic Myomectomy: A Case Report.

Endomyometriosis is a rare finding and it can be challenging to diagnose and to treat. It can arise in the uterus, in the ovary, in the broad ligament, in the peritoneal surface and in other pelvic structures. Usually patients with endomyometriosis are asymptomatic, but symptoms could occur due to large dimensions or site of the mass. We present a case of a 49-year-old woman with a symptomatic pelvic mass in the rectal wall, with no history of endometriosis, who underwent laparoscopic myomectomy 8 years earlier.

Wilms' Tumor 1 (WT1): A Novel Immunomarker of Dermatofibrosarcoma Protuberans-An Immunohistochemical Study on a Series of 114 Cases of Bland-Looking Mesenchymal Spindle Cell Lesions of the Dermis/Subcutaneous Tissues.

PURPOSE: to investigate the immunohistochemical expression and distribution of Wilms' tumor 1 (WT1) (transcription factor produced by the tumor suppressor gene of the same name) in a series of 114 cases of bland-looking mesenchymal spindle cell lesions of the dermis/subcutaneous tissues to establish whether this immunomarker is differentially expressed in dermatofibrosarcoma protuberans (DFSP) versus its potential morphological mimickers. METHODS: This retrospective multi-centric immunohistochemical study included 57 DFSP cases, 15 dermatofibromas, 5 deep fibrous histiocytomas, 8 neurofibromas, 5 spindle cell lipomas, 8 dermal scars, 6 nodular fasciitis, 5 cutaneous leiomyomas and 5 solitary fibrous tumors. Among the 57 DFSP cases, 11 were recurrent lesions; 2 non-recurrent cases exhibited an additional "fibrosarcomatous" overgrowth and 1 recurrent and 2 primary tumors contained a minority of "giant cell fibroblastoma" components. RESULTS: Most DFSP (95% of cases) exhibited cytoplasmic staining for WT1; 11/11 residual/recurrent tumors showed diffuse and strong WT1 cytoplasmic immunoreactivity; apart from neurofibromas, WT1 expression was lacking in all the other cases studied. CONCLUSIONS: The cytoplasmic expression of WT1 may be exploitable as a complementary diagnostic immunomarker to CD34 in confirming the diagnosis of DFSP and to better evaluate the residual/recurrent tumor component.

Macrophage Migration Inhibitory Factor (MIF) and Its Homologue d-Dopachrome Tautomerase (DDT) Inversely Correlate with Inflammation in Discoid Lupus Erythematosus.

Discoid Lupus Erythematosus (DLE) is a chronic cutaneous disease of unknown etiology and of immunoinflammatory origin that is characterized by inflammatory plaques and may lead to disfiguring scarring and skin atrophy. Current treatments are limited, with a large proportion of patients either poorly or not responsive, which makes DLE an unmet medical need. Macrophage migration inhibitory factor (MIF) is the prototype of a pleiotropic family of cytokine that also includes the recently discovered homologue D-dopachrome tautomerase (DDT) or MIF2. MIF and DDT/MIF-2 exert several biological properties, primarily, but not exclusively of a proinflammatory nature. MIF and DDT have been suggested to play a key role in the pathogenesis of several autoimmune diseases, such as multiple sclerosis and type 1 diabetes, as well as in the development and progression of certain forms of cancers. In the present study, we have performed an immunohistochemistry analysis for the evaluation of MIF in DLE lesions and normal skin. We found high levels of MIF in the basal layer of the epidermis as well as in the cutaneous appendage (eccrine glands and sebocytes) of normal skin. In DLE lesions, we observed a significant negative correlation between the expression of MIF and the severity of inflammation. In addition, we performed an analysis of MIF and DDT expression levels in the skin of DLE patients in a publicly available microarray dataset. Interestingly, while these in silico data only evidenced a trend toward reduced levels of MIF, they demonstrated a significant pattern of expression and correlation of DDT with inflammatory infiltrates in DLE skins. Overall, our data support a protective role for endogenous MIF and possibly DDT in the regulation of homeostasis and inflammation in the skin and open up novel avenues for the treatment of DLE.

Solitary fibrous tumor with atypical features of the paravesical space: benign clinical course at the 10-years follow-up. Report of a case and review of the literature.

Extra-pleural solitary fibrous tumor (SFT) is a relatively rare soft tissue neoplasm, with only rare cases reported in the pelvic cavity. Most SFTs are histologically benign, with only a few malignant cases reported in the literature so far. We report a rare case of SFT arising in the paravesical space of a 79-year-old man. Histologically the tumor corresponds to an "intermediate risk tumor" according to a risk stratification scheme for metastatic potential, which incorporates patient age, tumor size, mitotic activity and necrosis. Notably tumor showed a benign clinical course without evidence of local recurrence after a 10-years follow-up. Tumor was composed of both spindle and epithelioid cells variably set in a fibro-myxoid stroma, with focal pleomorphic, necrotic and highly mitotic (> 4 mitoses/10HPF) areas. Immunohistochemistry, showing a diffuse CD34 and STAT6 immunoreactivity, supported the diagnosis of SFT. The present case emphasizes that the clinical course of the pelvic SFTs with atypical morphological features is unpredictable on the basis of morphology alone, and thus the term "SFT with atypical features, including the risk stratification class" should be preferred to "malignant SFT".

Benign multicystic mesothelioma and peritoneal inclusion cysts: are they the same clinical and histopathological entities? A systematic review to find an evidence-based management.

PURPOSE: Peritoneal mesothelial cysts (PMC) are a clinical dilemma because of their true pathogenic nature. Many definitions have been associated with PMC, including "benign multicystic mesothelioma", "cystic mesothelioma", "multilocular peritoneal inclusion cysts", ''inflammatory cysts of the peritoneum" or "postoperative peritoneal cyst". METHODS: We herein performed a systematic review of the literature focusing on clinical and histopathological aspects of PMC, diagnosis, and therapies. Moreover, we described our experience with a case of PMC in a young female. RESULTS: Since there is often a history of prior surgery or inflammatory disease, most authors consider PMC of reactive origin. However, in some cases they occur without any documentable signs of disease or injury. A variety of clinical findings can complicate the preoperative assessment and a multitude of histological pictures may potentially lead to a misdiagnosis. The absence of a uniform treatment strategy and lack of long-term follow-up often hinder the accurate definition leading to unnecessary or unnecessarily aggressive therapy. CONCLUSIONS: PMC are more common than had previously been thought. Most authors consider them non-neoplastic; thus the designation of "peritoneal inclusion cyst" is preferable. The term "mesothelioma" should be used only in cases of histological evidences of atypia. The high rates of recurrence suggest that the goal of treatment should not be necessarily complete eradication, but symptomatic relief through individualized treatment. This is a topic of particular importance, especially in young female where recurrence rates could be lower than those reported in adults and where an improperly aggressive treatment could have repercussions on fertility.