Cutaneous melanoma is an aggressive tumor with increasing incidence worldwide. Recent development of promising treatments based on immune checkpoints blockade in cancer immunotherapy or signal transduction inhibitors (B-Raf enzyme inhibitor and MEK inhibitor) requires identification of new biomarkers predictive of either prognosis and/or therapeutic response. Dynamic interaction between melanoma and normal host cells influences tumor progression; proteins regulating connections between melanoma cells and extracellular matrix facilitate tumor invasion and dissemination. We discuss the various functions of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in melanoma and their possible role as prognostic and/or predictive biomarkers. We also studied the correlation with regression of expression of several MMPs and TIMPs in melanoma; regressed and nonregressed components are in fact different tumor subclones; in some cases of melanoma with regression (with a specific morphology), the biologic aggressiveness of the tumor and implicitly the overall prognosis may be more favorable than that of melanoma without regression thus offering the possibility of a supplemental stratification of these patients beyond AJCC staging.
Eosinophilic fasciitis (EF) remains a diagnostic challenge due to its rarity and resemblance to scleroderma. This case report aims to provide a cohesive exploration of EF’s clinical nuances, emphasizing the importance of accurate diagnosis and effective management. A 52-year-old male developed bilateral forearm and calf hardening, along with erythema, pruritus, and pain four months prior to the presentation in our Clinic. The symptoms initially debuted bilaterally in the forearms and progressed to involve the calves, distal arms, and thighs. Clinical examination revealed symmetrical plaques on forearms and calves, featuring erythematous, hyper, and hypopigmented elements extending proximally, a positive “groove sign” and a moderate difficulty in knee joint flexion. Despite these findings, the patient was generally in good condition, without any other notable clinical signs. Initial laboratory findings showed slightly increased percentual eosinophil levels, elevated C-reactive protein (CRP), normal erythrocyte sedimentation rate (ESR), and negative antinuclear and scleroderma specific antibodies. Magnetic resonance imaging (MRI) demonstrated enhanced fascial signal and thickening while the fascia-muscle biopsy revealed marked edema and inflammatory lymphoplasmacytic infiltrate, consistent with the diagnosis of EF. The patient showed a favorable response to systemic corticosteroids. EF predominantly affects males aged 30 to 60 and is characterized by a sudden onset and unclear etiological factors. Differential diagnosis requires careful exclusion of scleroderma and other mimicking conditions. Diagnostic modalities such as skin-muscle biopsy and MRI reveal characteristic findings like inflammatory infiltrate and fascial thickening. Accurate diagnosis and differentiation from scleroderma are crucial, with early intervention involving glucocorticoids and immunosuppressive agents improving long-term outcomes.
Objectives. Congenital myopathies (CM) are a highly heterogeneous group of disorders with genetic cause, characterized by motor deficit and weakness usually manifesting in the neonatal period, with slowly progressive or non-progressive course and affecting both sexes. MC classification has undergone many changes over time, and in recent years molecular genetic studies have enabled identification of novel genes and mutations, thus increasing the diagnostic complexity. We wanted to study the incidence and morphological features of the CM cases diagnosed by muscle biopsy in the Pathology Department of Colentina University Hospital over a period of 10 years (09.2005- 09.2015). Materials and methods. We retrospectively reviewed all the muscle biopsies diagnosed with different types of CM. Muscle biopsies were performed and specifically processed using routine and special stains on cryosections, semithin and ultrathin sections for ultrastructural examination. In all the cases we reassessed the clinical and laboratory data. Results. From a number of 1,530 peripheral nerve and muscle biopsies performed and analyzed in the 10 years period we diagnosed CM in 15 cases, representing 1.03% of the total. Of these, five were “central core myopathies”, five centronuclear/myotubular myopathies, one case of nemaline myopathy, one case of “reducing body myopathy” and three cases with congenital fiber type disproportion. Reassessment of morphological data in the clinical context allowed us to identify numerous overlaps between subtypes both in the clinical and pathological picture. Conclusions. The reduced number of MC identified in our country suggests that these diseases are probably underdiagnosed or diagnosed late, requiring a better understanding of the various clinical and pathological particularities. In the accurate diagnostic algorithm, muscle biopsy remains essential to establish the type of CM and thus to direct genetic tests.
It is suggested that different neuropeptides are actively involved in the pathogenesis of Helicobacter pylori (H. pylori)-induced gastritis acting as important effectors of the neuroimmune complex interactions, but the available data is limited and contradictory. The aim of this study was to determine whether the chronic infection generates changes in substance P (SP) and vasoactive intestinal peptide (VIP) gastric level and to evaluate the dependence of these potential effects on the degree of bacterial colonization or the severity of the inflammatory infiltrate. Therefore, immunohistochemical tests were performed to examine SP and VIP expression in mucosal nerve endings and myenteric neurons. Both SP and VIP levels were significantly higher in gastric samples of patients infected with H. pylori compared to uninfected individuals, confirming that these neuropeptides are neuroimmune modulators involved in the pathogenesis of H. pylori infection. Although their expression did not correlate with the intensity of mucosal inflammation nor with the bacterial density, we observed a strong association between SP neuronal level and the degree of myenteric ganglionitis, which in turn correlated with the severity of mucosal T-cell infiltration. These findings suggest that the mechanisms of neuroimmune cross-talk depend on some other factors that remain to be determined.
Chronic inflammation induced by Helicobacter pylori ( H. pylori ) infection plays a major role in development of gastric cancer. However, recent findings suggested that progression of inflammation and neoplastic transformation in H. pylori infection are more complex than previously believed and could involve different factors that modulate gastric microenvironment and influence host-pathogen interaction. Among these factors, gastric myenteric plexus and its potential adaptive changes in H. pylori infection received little attention. This study is aimed at identifying the impact of H. pylori -associated gastritis on number and morphology of nerve cells in the stomach. The distribution of density, inflammation, and programmed cell death in neurons was immunohistochemically assessed in full-thickness archival tissue samples obtained from 40 patients with H. pylori infection who underwent surgery for gastric cancer and were compared with findings on samples collected from 40 age- and sex-matched subjects without bacteria. Overall, significant differences were noted between H. pylori -positive and H. pylori -negative patients. The analysis of tissue specimens obtained from those with infection revealed higher density and larger surface of the myenteric nervous plexus, as well as a significant increase in the number of gastric neuronal cell bodies and glial cells compared to controls. A predominant CD3-immunoreactive T cell infiltrate confined to the myenteric plexus was observed in infected subjects. The presence of mature B lymphocytes, plasma cells, and eosinophils was also noted, but to a lesser extent, within the ganglia. Myenteric ganglionitis was associated with degeneration and neuronal loss. Our results represent the first histopathological evidence supporting the hypothesis that H. pylori -induced gastric inflammation may induce morphological changes in myenteric gastric ganglia. These findings could help gain understanding of some still unclear aspects of pathogenesis of H. pylori infection, with the possibility of having broader implications for gastric cancer progression.
Autopsies represent medical procedures through which the causes of patients' deaths are determined or, through tissue sampling and microscopic examination of slides in usual stains or special tests, one can offer the basis for understanding the physiopathological mechanisms that contribute to the patients' death Histological findings of tissue samples from patients who have died of COVID-19 have been mainly orientated to lung, heart, liver, kidney damage with a small percent of them following other organs, but none has, to our knowledge, studied skeletal muscle.
Brain metastases arising from cervical cancer are exceedingly rare.We report the case of a 62-year-old woman with a history of cervical cancer who was admitted in our department and was diagnosed with a solitary symptomatic brain metastasis.Treatment included aggressive tumor resection, followed by radiotherapy, but overall, with a poor prognosis.Histopathologic examination confirmed the metastatic origin from a primary cervical squamous cell carcinoma.
The mitochondrial myopathy consists of a heterogeneous group of conditions characterized by primary disfunction of mitochondrial respiratory chain causing muscle disease.Chronic progressive external ophthalmoplegia is a frequent mitochondrial disorder that shares clinical, enzymatic and genetic features with other mitochondrial diseases.We present a case of a patient who was initially diagnosed with myasthenia gravis, did not respond to specific therapy and was subsequently diagnosed by clinical, biochemical and histopathological criteria with a mitochondrial myopathy.A 37 years old woman, suspected and treated for myasthenia gravis presented with ptosis, marked fatigue, muscle weakness and myalgia, symptoms that progressively got worse despite the anticholinesterase therapy.Knowledge of this entity allows us to avoid unnecessary treatment and deferral of the real diagnosis.