INTRODUCTION:Histiocytic Myocardial Inflammatory Disease (HMID) is a rare and under-recognized form of myocarditis, characterized by predominant histiocytic infiltration within the myocardial tissue. Unlike more common lymphocytic and eosinophilic forms, HMID remains diagnostically challenging, particularly in children. Here we present a pediatric case, outlining the clinical course and the difficulties encountered, and highlighting the histopathological and immunohistochemical features essential for establishing the diagnosis. CASE DESCRIPTION:A 4-year-old girl accompanied by her parents, who showed up at the hospital with persistent fever, abdominal pain, and vomiting. A cardiac evaluation revealed a mild pericardial effusion with preserved systolic function. Doctors treated her with corticosteroids and broad-spectrum antibiotics, but her condition rapidly deteriorated, resulting in cardiogenic shock and death from cardiac arrest. We performed a forensic autopsy that included histopathological examination and immunohistochemical analysis of the cardiac muscle (in particular in the right ventricle). The CD68 positivity highlighted the presence of a diffuse infiltrate of hystiocites. CD3, CD4, CD8, and CD20 staining showed only scarce lymphocyte representation. The child's history gave no hint of autoimmune or inflammatory disease, underscoring the abrupt and unexpected nature of her illness. DISCUSSION:HMID is rare but can mimic common myocarditis, complicating diagnosis. Its fulminant course requires early recognition and confirmation by histopathology and immunohistochemistry. This case shows the importance of recognizing HMID in pediatric cardiogenic shock or sudden cardiac death of unclear cause.

Background: To search for H. pylori infection and gastric precancerous lesions in cirrhotic patients is worthwhile when considering the high incidence of peptic ulcers and gastric cancer in these patients. We tested if gastric juice analysis allows to avoid unrewarding gastric biopsies. Methods: This prospective study enrolled consecutive patients with liver cirrhosis who underwent upper endoscopy with standard gastric biopsies. Real-time gastric juice analysis was performed with a specific device (EndoFaster®) that test ammonium concentration for H. pylori diagnosis, and pH values to suspect extensive atrophy/metaplasia involving gastric body mucosa. Sensitivity, specificity, positive predictive value, negative predictive value (NPV), the overall accuracy, and the likelihood ratio were calculated for both H. pylori infection and extensive precancerous lesions on gastric mucosa. Results: A total of 78 cirrhotic patients (males: 55; mean age: 66 ± 12 years) were enrolled. When considering as positive EndoFaster® results when at least one of two (ammonium and pH levels) tests were positive, the NPVs were as high as 89% and 86%, respectively, to rule out H. pylori and extensive precancerous lesions on gastric mucosa, with an overall accuracy of 83% and 74%. Conclusions: This study supports the evidence that real-time gastric juice analysis allows to avoid clinically unrewarding and potentially unsafe gastric biopsies in a definite portion of cirrhotic patients, but more data are needed.

Hereditary transthyretin amyloidosis (hATTR) is a multisystemic, rare, inherited, progressive and adult-onset disease, affecting the sensory-motor nerves, heart, autonomic function, and other organs. There are over 130 mutations known in the TTR gene. The His90Asn mutation has been previously reported in several reports, but its pathogenetic role is still debated. We report two sporadic cases of adult women with a heterozygous His90Asn mutation in TTR gene and neurological involvement extensively investigated. A typical Congo red-positive pathologic deposition of amyloid fibrils in the salivary glands was documented in one subject. Patients were successfully treated with patisiran with a good clinical outcome. These data support a pathogenetic role of His90Asn mutation in hATTR, and suggest early treatment in symptomatic carriers of His90Asn mutation.

Splenic rupture and hematoma are significant complications that can occur in patients with non-Hodgkin lymphoma (NHL). Understanding these associated complications is essential for optimal patient management and enhanced patient outcomes. Histopathological and immunohistochemical analyses are crucial in diagnosing NHL and assessing splenic involvement. In this study, a judicial autopsy had been requested by the Prosecutor’s Office for a malpractice claim due to a fall in the hospital. In the Emergency Department, a 72-year-old man fell from a gurney and reported sustaining a wound to his forehead. No other symptoms were reported. A face and brain CT scan showed no abnormalities. Nine days after discharge, the patient presented with abdominal pain. An abdominal CT revealed splenic rupture and hemoperitoneum. The patient underwent open splenectomy but showed signs of hemodynamic shock and subsequently died. The evidence from the autopsy allowed us to diagnose mantle cell non-Hodgkin lymphoma with spleen involvement, previously unknown. Histopathological and immunohistochemical analyses were performed to assess the diagnosis of splenic rupture and estimate its timing. The findings strongly suggest that the splenic rupture was associated with the patient’s fall and the pre-existing malignancy. This case highlights the importance of considering an underlying hematological malignancy when investigating delayed splenic rupture. An immunohistochemical study of spleen samples allowed the timing of splenic hematoma and rupture to be assessed, leading to the establishment of a causal relationship with trauma.

(1) Background: Gangliogliomas are rare tumors accounting for about 0.4% of all central nervous system tumors. They are usually located in the temporal lobes of children and young adults, though such tumors in the infratentorial region and adult-age patients rarely reported. (2) Methods: A systematic review on ganglioglioma with infratentorial location in the adult population was conducted in accordance with the PRISMA guidelines. A total of 275 articles were found, and 23 were included. Demographic data, the location and histology of the lesion, pre-operative neurological status, the type of surgery, recurrence, radiotherapy/chemotherapy adjuvant treatments, neurological outcomes and follow-up information were collected. We also presented an illustrative case. (3) Results: A total of 27 patients were included. In 51%, the location was the cerebellum; in 40%, it was the fourth ventricle; in 11%, it was brainstem; and in 4%, it was the cerebellopontine angle. STR was performed in 44%, GTR in 26% and biopsy in 15% of the cases. Adjuvant radiotherapy was found in 22% of cases. Disease recurrence occurred in 15% of patients between 1 and 12 months after surgery with a diagnosis of high-grade ganglioglioma, while in six cases, no disease recurrence was documented. (4) Conclusions: Infratentorial glioneuronal tumors are rare findings in the adult population. Histopathological characterization does not seem to fully reflect their true behavior. Future studies are warranted for better characterizing histopathological findings and treatment.

Castleman disease is non-clonal lymphoproliferative disorders defined by hypertrophy of lymph nodes. The multicentric form (MCD), in which multiple lymph node stations are involved, is not associated with HHV8 infection, but considered idiopathic, although IL-6 appears to play a central role in its pathogenesis. Here, we report the case of a patient who presented with mixed autoimmune hemolytic anemia (AIHA) and adenopathy that was very challenging to diagnose due to very low values of hemoglobin and refractoriness of obtaining any improvement of AIHA with standard first and second lines of therapy (steroids, rituximab, immunoglobulin, erythropoietin, and cyclosporine). When we safely proceeded to lymph node biopsy, a diagnosis of MCD was established. This permitted the treatment with siltuximab, an anti-IL-6 monoclonal antibody. After only 1 week, hemoglobin raised and he was discharged. After 1 year, he was still in remission. This case underlines the challenges in diagnosis of MCD, and the first case of response to siltuximab after the failure of rituximab to relieve mixed AIHA.

Background: Polymorphous adenocarcinoma (PAC) is the second-most common malignant tumour of the minor salivary glands. Although PAC predominantly affects the palate, it can also involve the buccal mucosa. This systematic review aims to investigate the literature data about PAC. Furthermore, we report two cases of patients affected by PAC in an infrequently considered anatomical site. Methods: According to PRISMA guidelines, a systematic review search was conducted on PubMed, Scopus, and Web of Science. Observational studies conducted on patients with a histological diagnosis of PAC were selected and analysed. Furthermore, two cases of patients with PAC affecting the buccal mucosa were reported. Results: Twenty-nine studies were included, and 143 patients affected by PAC were analysed (62 males, 75 females, and 6 undefined, with a mean age of 57.4 ± 14.5 years). The palate was the most affected site (99/143, 69.2%), followed by the buccal mucosa (12/143, 8.4%). Moreover, we report two cases of patients with PAC affecting the buccal mucosa (one male and one female, with a mean age of 70.5 ± 2.5 years). Conclusions: The present study underscores the importance of considering the buccal mucosa as a possible location of minor salivary gland tumours; although it is a less-considered affliction, it is not uncommon.

BackgroundMerkel cell carcinoma (MCC) is a rare and aggressive skin cancer, associated with a worse prognosis. The Immune Checkpoint Inhibitors (ICIs) avelumab and pembrolizumab have been recently approved as first-line treatment in metastatic MCC (mMCC). The clinical observation of improved outcomes in obese patients following treatment with ICIs, known as the “obesity paradox”, has been studied across many types of tumors. Probably due to the rarity of this tumor, data on mMMC patients are lacking.Patients and methodsThis is an observational, hospital-based, study to investigate the role of Body Mass Index (BMI) as predictive biomarker of ICI response in mMCC patients treated with avelumab as first-line treatment. The study population included the patients treated from February 2019 to October 2022 in an Italian referral center for rare tumors. Clinico-pathological characteristics, BMI, laboratory parameters (NLR and platelet count), and response to avelumab were analyzed from a MCC System database prospectively collected.ResultsThirty-two (32) patients were included. Notably, the presence of pre-treatment BMI ≥ 30 was significantly associated with longer PFS [BMI < 30 Group: median PFS, 4 months (95% CI: 2.5-5.4); BMI ≥ 30 Group: median PFS, not reached; p<0.001)[. Additionally, the median PFS was significantly higher in patients with higher PLT (median PFS: 10 months in the “low PLT” Group (95% CI: 4.9, 16.1) vs 33 months (95% CI: 24.3, 43.2) in the “high PLT” Group (p=0.006). The multivariable Cox regression model confirmed these results.ConclusionTo our knowledge, this is the first study that investigates the predictive role of BMI in MCC patients. Our data were consistent with the clinical observation of improved outcomes in obese patients across other tumor types. Thus, advanced age, a weakened immune system, and the obesity-associated “inflammaging”, are key factors that could impact the cancer immune responses of mMCC patients.

Introduction: Multiple myeloma (MM) is an incurable blood cancer.It is linked to a variety of symptoms, so mastery would allow for early diagnosis and management, particularly in less developed regions, including Sub-Saharan Africa.The aim of this study was to investigate the clinical and radiological symptoms, outcomes, and management characteristics of MM in sub-Saharan African patients.Methods: Four databases (PubMed, Web of Science, Global Index Medicus, and Excerpta Medica Databases) were searched in a systematic database and gray literature search and the design of the study has followed PRISMA standard guidelines.Results: This study included 32 articles in total, corresponding to 21172 cases.The overall prevalence of multiple myeloma in sub-Saharan African patients was 10.34% (95% CI: 6.35-15.15).Patients with blood diseases were the most affected, with a prevalence of 18.49% (95% CI: 8.60-31.02).The main radiological symptoms of MM in sub-Saharan Africa were bone lesions (lytic bone lesions, osteolytic lesions, and bone deficiency, essentially) and fractures (long bone fractures, vertebral compression fractures, and vertebral collapse, essentially).The main clinical symptoms at diagnosis of MM in sub-Saharan Africa were musculoskeletal (bone pain and lumbar pain, essentially), haematological (clinical anemia), and constitutional (asthenia).The majority of patients with MM in sub-Saharan Africa were in Stage III.The prevalence of death was 38% (95% CI: 27.31-49.28),with a 5-year survival rate of 16.54% (95% CI: 11.33-22.47) in patients with MM in sub-Saharan Africa.Palliative care was the most commonly used treatment (analgesic), followed by chemotherapy (Alexanian essentially) and combination chemotherapy (Vincristine /Carmustine/ Adriamycin /Prednisone essentially).Conclusions: This study has a low risk of bias (100% of studies).The findings suggest that multiple myeloma is a serious health condition in sub-Saharan African patients, and the need to educate the community and clinicians on the characteristics of the disease, for early and optimal management.

Background: Vascularized nerve grafts (VNGs) have been proposed as a superior alternative to free nerve grafts (FNGs) for complex nerve defects. A greater regenerative potential has been suggested by clinical and experimental studies, but conclusive evidence is still lacking. Methods: In this experimental study, 10 adult male Wistar rats received a non-vascularized orthotopic sciatic nerve graft on their right side, and a vascularized orthotopic sciatic nerve graft nerve on their left side. Functional outcome following nerve regeneration was evaluated through electrodiagnostic studies, target muscles weight and histomorphology, and data of VNGs and FNGs were compared. Results: The results of this study showed a significant difference in the motor unit number of Gastrocnemius Medialis (GM) estimated by MUNE in the VNG side compared to the FNG side. No other significant differences in axonal regeneration and muscle reinnervation were evident at either electrodiagnostic, histomorphology studies or muscle weight. Conclusions: This experimental model showed slight differences in nerve regeneration between VNGs and FNGs, but cannot support a high clinical advantage for VNGs. The results of this study show that VNGs are not strongly superior to FNGs in the rat model, even in avascular beds. Clinical advantages of VNGs are likely to be limited to extensive and thick nerve defects and can only be assessed on experimental model with bigger animals. Also, we showed that the MUNE technique provided a reliable and reproducible evaluation of functional outcomes in the rat sciatic nerve and defined a reproducible protocol for functional evaluation of muscle reinnervation.

Background: Syphilis is a worldwide sexually transmitted infection caused by Treponema pallidum. In most cases, the oral manifestations of syphilis infection are associated with cutaneous involvement. However, the present case report is noteworthy since the oral lesions are the sole clinical sign in an HIV-positive transgender patient. Case presentations: We reported an uncommon case of secondary syphilis in a 37-year-old seropositive transgender male, whose diagnostic suspect was based only on oral mucosal lesions. The patient was referred to the Oral Medicine Unit for the presence of multiple undiagnosed painful oral lesions. The intraoral examination revealed the presence of white and red plaques on the right and the left buccal mucosa and several painful lesions localized on the upper and lower labial mucosa. No cutaneous lesions were observed. Considering the sexual history of the patient and clinical findings, secondary syphilis infection was suspected. The serologic analysis was conducted, and the diagnosis of syphilis was confirmed. Moreover, to exclude the presence of oral epithelial dysplasia or malignant disease, an incisional biopsy was performed. Discussion: Compared to the literature data, oral lesions as lone signs of secondary syphilis infection are uncommon, especially in HIV-positive patients. Syphilis and HIV coinfection create a concerning situation as they interact synergistically, leading to an increased risk of transmission and faster disease progression. Conclusions: This case report emphasizes the importance of considering syphilis as a diagnostic possibility, even when oral lesions are the only clinical manifestations, especially in HIV-positive patients. Comprehensive evaluation, including a detailed sexual history and careful oral examination, is essential for accurate diagnosis and appropriate management in such cases.

Here, we describe the case of a naïve HIV late presenter female African patient with progressive disseminated histoplasmosis and a severe life-threatening clinical picture in a non-endemic area. She had not visited Africa in the past decade. She developed a reactive hemophagocytic lymphohistiocytosis and an acute psychiatric disorder. Histoplasmosis was diagnosed after two bone marrow biopsies. Therapy with liposomal amphotericin B resulted in rapid and progressive improvements in blood examinations and clinical conditions, including the disappearance of psychiatric disorders. The characteristics of our case were compared with those of all other cases of hemophagocytic syndrome secondary to histoplasmosis in HIV-positive patients reported in PubMed. In conclusion, clinicians outside endemic areas should evaluate histoplasmosis as a cause of severe clinical picture, especially in a patient with a travel history to an endemic area, even after many years, considering the possible reactivation of latent infection.

Jellyfish envenomation is a common problem in coastal areas all over the world; usually symptoms are self-limited with no long-lasting complications. Despite that, some jellyfish species, mainly populating the Indian Ocean, are renown to be potentially lethal and in some cases may cause severe myopathy. We report the first case of rhabdomyolysis following a jellyfish sting in the Mediterranean Sea. A 17-year-old patient was admitted to the intensive care unit of our hospital in life-threatening conditions. He was dyspnoeic and dysphagic with pain and functional impairment of upper and lower limbs. The evidence of a red mark in his face and the clinical presentation, coupled with the diagnostic test performed, allowed the diagnosis of toxidrome from jellyfish venom. Treatment with hydration, ventilatory support and steroids led to a progressive improvement of patient conditions. Our case report stresses the importance of prompt identification and treatment of potential rhabdomyolysis determined by jellyfish and rises awareness on the presence of such venomous species in the Mediterranean Sea.

BackgroundDiffuse large B-cell lymphoma (DLBCL) is a hematological malignancy representing one-third of non-Hodgkin’s lymphoma cases. Notwithstanding immunotherapy in combination with chemotherapy (R-CHOP) is an effective therapeutic approach for DLBCL, a subset of patients encounters treatment resistance, leading to low survival rates. Thus, there is an urgent need to identify predictive biomarkers for DLBCL including the elderly population, which represents the fastest-growing segment of the population in Western countries.MethodsGene expression profiles of n=414 DLBCL biopsies were retrieved from the public dataset GSE10846. Differentially expressed genes (DEGs) (fold change >1.4, p-value <0.05, n=387) have been clustered in responder and non-responder patient cohorts. An enrichment analysis has been performed on the top 30 up-regulated genes of responder and non-responder patients to identify the signatures involved in gene ontology (MSigDB). The more significantly up-regulated DEGs have been validated in our independent collection of formalin-fixed paraffin-embedded (FFPE) biopsy samples of elderly DLBCL patients, treated with R-CHOP as first-line therapy.ResultsFrom the analysis of two independent cohorts of DLBCL patients emerged a gene signature able to predict the response to R-CHOP therapy. In detail, expression levels of EBF1, MYO6, CALR are associated with a significant worse overall survival.ConclusionsThese results pave the way for a novel characterization of DLBCL biomarkers, aiding the stratification of responder versus non-responder patients.

Salivary gland tumors represent a serious medical problem and new tools for differential diagnosis and patient monitoring are needed. Here, we present data and discuss the potential of molecular chaperones as biomarkers and therapeutic targets, focusing on Hsp10 and Hsp90. The salivary glands are key physiological elements but, unfortunately, the information and the means available for the management of their pathologies, including cancer, are scarce. Progress in the study of carcinogenesis has occurred on various fronts lately, one of which has been the identification of the chaperone system (CS) as a physiological system with presence in all cells and tissues (including the salivary glands) that plays a role in tumor-cell biology. The chief components of the CS are the molecular chaperones, some of which belong to families of evolutionarily related molecules named heat shock protein (Hsp). We are quantifying and mapping these molecular chaperones in salivary glands to determine their possible role in the carcinogenetic mechanisms in these glands and to assess their potential as diagnostic biomarkers and therapeutic targets. Here, we report recent findings on Hsp10 and Hsp90 and show that the quantitative and topographic patterns of tissue Hsp90 are distinctive of malignant tumors and differentiate benign from malignant lesions. The Hsp90 results show a correlation between quantity of chaperone and tumor progression, which in turn calls for negative chaperonotherapy, namely, elimination/inhibition of the chaperone to stop the tumor. We found that in vitro, the Hsp90 inhibitor Ganetespib is cytotoxic for the salivary gland UM-HACC-2A cell line. The drug, by interfering with the pro-survival NF-κB pathway, hampers cellular proliferation and migration, and favors apoptosis, and can, therefore, be considered a suitable candidate for future experimentation to develop a treatment for salivary gland tumors.

Background: Dumbbell tumors are typically benign schwannomas, neurofibromas, and meningiomas and only rarely there are malignant variants of these lesions or other malignant histotypes. Here, a 34-year-old male presented with a thoracic spinal dumbbell metastatic neuroendocrine carcinoma of unknown primary origin. Case Description: A 34-year-old male presented with 2 months of thoracic pain and progressive mid thoracic sensory loss. A post contrast thoracic MRI showed a dumbbell tumor localized between the T7 and T9 levels with extension laterally into the T7-T8 and T8-T9 foramina. The patient underwent a laminectomy for tumor resection following which his pain and gait improved. Histopathologically, the tumor demonstrated multiple rounded small cells with a Ki67 level around 30%, suggesting a malignant metastatic neuroendocrine tumor of unknown etiology. Conclusion: We successfully treated a 34-year-old male with a T7-T9 malignant spinal dumbbell neuroendocrine tumor of unknown etiology utilizing a decompressive laminectomy.

BACKGROUND:Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults. Novel treatments are needed to counteract the molecular mechanisms of GBM growth and drug resistance. The chaperone system (CS) members are typically cytoprotective but some, termed Hsp, can become pathogenic and participate in carcinogenesis, along with the vascular endothelial growth factor (VEGF), and we investigated them in GBM biopsies and derived cell lines. The objectives were to identify diagnostic-prognostic biomarkers and gather information for developing chaperonotherapy.METHODS:Cell lines from GBMs were established, characterized (morphology, growth characteristics, and specific markers), and stored. Chaperones and angiogenic factors [Hsp10, Hsp27, Hsp60, Hsp70, Hsp90, FLT-1 (VEGFR-1), FLK1 (KDR, VEGFR-2), and FLT-4 (VEGFR-3)] were observed in cells by immunofluorescence while the chaperones were measured in tumor tissue by immunohistochemistry.RESULTS:Four cell lines were derived from four different GBMs; the cells were spindle shaped or polygonal and grew at high rates as adherent monolayers or clusters without evidence of contact inhibition. The astrocyte-specific glial fibrillary acidic protein (GFAP); and the neuronal NSE, malignancy VIM, and proliferation PCNA, markers were determined. The cells expressed GFAP but no NSE, indicating that they were primary glioblastoma cell lines, with high levels of Hsp10, Hsp27, Hsp60, Hsp90, and Flk1; and low levels of Hsp70, Flt1, and Flt4.CONCLUSIONS:Four cell lines were established derived from four out of ten GBM tumors studied. The cell lines showed intense positivity for chaperones studied and factors connected to malignancy and the tumors showed increased levels of chaperones, making them potential diagnostic-prognostic biomarkers and targets for anti-cancer compounds.