Pathway from Acute Kidney Injury to Chronic Kidney Disease: Molecules Involved in Renal Fibrosis.

Acute kidney injury (AKI) is one of the main conditions responsible for chronic kidney disease (CKD), including end-stage renal disease (ESRD) as a long-term complication. Besides short-term complications, such as electrolyte and acid-base disorders, fluid overload, bleeding complications or immune dysfunctions, AKI can develop chronic injuries and subsequent CKD through renal fibrosis pathways. Kidney fibrosis is a pathological process defined by excessive extracellular matrix (ECM) deposition, evidenced in chronic kidney injuries with maladaptive architecture restoration. So far, cited maladaptive kidney processes responsible for AKI to CKD transition were epithelial, endothelial, pericyte, macrophage and fibroblast transition to myofibroblasts. These are responsible for smooth muscle actin (SMA) synthesis and abnormal renal architecture. Recently, AKI progress to CKD or ESRD gained a lot of interest, with impressive progression in discovering the mechanisms involved in renal fibrosis, including cellular and molecular pathways. Risk factors mentioned in AKI progression to CKD are frequency and severity of kidney injury, chronic diseases such as uncontrolled hypertension, diabetes mellitus, obesity and unmodifiable risk factors (i.e., genetics, older age or gender). To provide a better understanding of AKI transition to CKD, we have selected relevant and updated information regarding the risk factors responsible for AKIs unfavorable long-term evolution and mechanisms incriminated in the progression to a chronic state, along with possible therapeutic approaches in preventing or delaying CKD from AKI.

Toxic Epidermal Necrolysis, A Serious Side Effect of Tenoxicam Use: A Case Report.

Tenoxicam, a selective cyclooxygenase (COX)-2 inhibitor, has potent analgesic and anti-inflammatory effects and is frequently used for out-of-hospital pain control. Even though other non-steroidal anti-inflammatory drugs were incriminated in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) appearance, the literature is scarce regarding this agent. We report a case of tenoxicam-induced toxic epidermal necrolysis, detailing the multidisciplinary approach in a patient presenting skin detachment of 90% of the total body surface area, with concomitant ocular, oral, nasal, and vaginal mucosae involvement. A skin biopsy confirmed the diagnosis. The immediate cessation of the incriminated drug and rapid initiation of systemic steroids, along with topical therapies, and isolation into a specific environmental condition to limit skin infection were the cornerstones of therapeutic management. The patient was discharged with skin hyperpigmentation area and mild anxiety as long-term sequels. This report emphasized that severe or complicated cases should be transferred to a specialized burn center to reduce mortality risk and long-term morbidity.

Overcoming Drug Resistance in a Clinical C. albicans Strain Using Photoactivated Curcumin as an Adjuvant.

The limited antifungal drugs available and the rise of multidrug-resistant Candida species have made the efforts to improve antifungal therapies paramount. To this end, our research focused on the effect of a combined treatment between chemical and photodynamic therapy (PDT) towards a fluconazole-resistant clinical Candida albicans strain. The co-treatment of PDT and curcumin in various doses with fluconazole (FLC) had an inhibitory effect on the growth of the FLC-resistant hospital strain of C. albicans in both difusimetric and broth microdilution methods. The proliferation of the cells was inhibited in the presence of curcumin at 3.125 µM and FLC at 41 µM concentrations. The possible involvement of oxidative stress was analyzed by adding menadione and glutathione as a prooxidant and antioxidant, respectively. In addition, we examined the photoactivated curcumin effect on efflux pumps, a mechanism often linked to drug resistance. Nile Red accumulation assays were used to evaluate efflux pumps activity through fluorescence microscopy and spectrofluorometry. The results showed that photoactivated curcumin at 3.125 µM inhibited the transport of the fluorescent substrate that cells usually expel, indicating its potential in combating drug resistance. Overall, the findings suggest that curcumin, particularly when combined with PDT, can effectively inhibit the growth of FLC-resistant C. albicans, addressing the challenge of yeast resistance to azole antifungals through upregulating multidrug transporters.

Multidisciplinary Therapeutic Management in Complex Cervical Trauma.

Background and Objectives: In the current literature, mandatory surgical exploration is a controversial topic, with some advocating for it and others against it, proposing a selective conservative management. This multidisciplinary therapeutic approach is based on clinical examination and serial paraclinical explorations associated with supportive drug treatment. Materials and Methods: The study group consisted of 103 patients with complex cervical trauma pathology produced by various mechanisms such as car or domestic accidents, aggression, ballistic trauma, self-inflicted attempts, hanging or strangulation hospitalized in the Ear, Nose and Throat (E.N.T.) Clinic, at "St. Spiridon" Iași Hospital, between 2012 and 2016. Results: The universal clinical indication for urgent surgical exploration of the patient with complex cervical trauma is the presence of the following symptoms: unstable vital signs, significant pulsatile bleeding, hematoma with a substantial increase in size, shock, airway obstruction, open airway wound, hematemesis, or hemoptysis. In this context, we considered it worthwhile to research the management of complex cervical trauma in a reference university medical center, alongside the analysis of the patient's characteristics under different aspects (demographic, pathological aspects, therapeutic). Conclusions: Complex cervical trauma has a variety of clinical aspects, with a variable evolution, which involves multidisciplinary therapeutic management. The increasing trauma rate is one of the main public health problems, requiring epidemiological studies, and the implementation of control strategies.

Emergency Care for Burn Patients-A Single-Center Report.

Burns, one of the main public health problems, lead to significant mortality and morbidity. Epidemiological studies regarding burn patients in Romania are scarce. The aim of this study is to identify the burn etiology, demographics, clinical characteristics, and outcomes in patients requiring treatment in a regional burn unit. DESIGN: We performed a retrospective observational study of 2021. PATIENTS: All patients admitted to our six-bed intensive care unit (ICU) were included. INTERVENTIONS: The following data were collected for further analysis: demographics, burn pattern (etiology, size, depth, affected body region), type of ventilation, ABSI (Abbreviated Burn Severity Index) score, comorbidities, bioumoral parameters, and hospitalization days. RESULTS: There were 93 burned patients included in our study that were divided into two groups: alive patients' group (63.4%) and deceased patients' group (36.6%). The mean age was 55.80 ± 17.16 (SD). There were 65.6% male patients, and 39.8% of the patients were admitted by transfer from another hospital. Further, 59 patients presented third-degree burns, from which 32.3% died. Burns affecting >37% of the total body surface area (TBSA) were noticed in 30 patients. The most vulnerable regions of the body were the trunk (p = 0.003), the legs (p = 0.004), the neck (p = 0.011), and the arms (p = 0.020). Inhalation injury was found in 60.2% of the patients. The risk of death in a patient with an ABSI score > 9 points was 72 times higher. Comorbidities were present in 44.1% of the patients. We observed a median LOS (length of stay) of 23 days and an ICU-LOS of 11 days. Logistic regression analysis showed that admission protein, creatinkinase, and leukocytes were independent risk factors for mortality. The general mortality rate was 36.6%. CONCLUSION: A thermal factor was responsible for the vast majority of burns, 94.6% of cases being accidents. Extensive and full-thickness burns, burns affecting the arms, inhalation injuries, the need for mechanical ventilation, and a high ABSI score represent important risk factors for mortality. Considering the results, it appears that prompt correction of protein, creatinkinase, and leukocytes levels may contribute to improvement in severe burn patients' outcomes.

Cervical intranodal schwannoma - a rare diagnosis.

Intranodal schwannoma is a rare benign tumor, which originates from the peripheral nerve sheath (Schwann cells), fewer cases being reported with lymphatic involvement. We present the case of a middle-aged female patient, with one-year growing mass in the lateral-cervical area, in intimate relation with the vascular package of the neck. Preoperative cervical computed tomography examination showed the tumor features. There was no intraoperative complication, with the piece being completely removed. The morphological examination revealed the structure of a lymph node, and after Hematoxylin-Eosin staining, there were eosinophilic cytoplasm, euchromatic nuclei, with round, elongated or slightly wavy form and reduced pleomorphism, rare degenerative nuclear atypia, and no mitotic activity nor necrosis. The expression of S100 protein on immunohistochemistry, along with negative results for smooth muscle actin and desmin sustained the diagnosis of intranodal schwannoma of the neck. With a low index of cellular proliferation (Ki67), this case is in line with the reported features of schwannoma having extremely rare malignant transformation.

Burn-Induced Acute Kidney Injury-Two-Lane Road: From Molecular to Clinical Aspects.

Severe burn injuries lead to acute kidney injury (AKI) development, increasing the mortality risk up to 28-100%. In addition, there is an increase in hospitalization days and complications appearance. Various factors are responsible for acute or late AKI debut, like hypovolemia, important inflammatory response, excessive load of denatured proteins, sepsis, and severe organic dysfunction. The main measure to improve the prognosis of these patients is rapidly recognizing this condition and reversing the underlying events. For this reason, different renal biomarkers have been studied over the years for early identification of burn-induced AKI, like neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase-2 (TIMP-2), interleukin-18 (IL-18), and insulin-like growth factor-binding protein 7 (IGFBP7). The fundamental purpose of these studies is to find a way to recognize and prevent acute renal injury progression early in order to decrease the risk of mortality and chronic kidney disease (CKD) onset.

Epidemiological Characteristics and Mortality Risk Factors Comparison in Dialysis and Non-Dialysis CKD Patients with COVID-19-A Single Center Experience.

(1) Background: Despite some controversies between studies, chronic kidney disease (CKD) has a negative impact on COVID-19 outcomes, with patients presenting a higher mortality risk than in the general population. Studies have shown an association between COVID-19 severe cases and different inflammatory biomarkers. The aim of this study was to emphasize the epidemiological characteristics of CKD patients diagnosed with COVID-19 and to determine if the risk of mortality, and the severity of this infection might be influenced by different parameters. (2) Methods: Our retrospective study included CKD patients with COVID-19­362 in the non-dialysis group and 132 in the dialysis group. (3) Results: There were significant statistical differences between our groups regarding age (p < 0.001), hemoglobin (p < 0.001), interleukin-6 (p < 0.001), serum albumin (p = 0.016), procalcitonin (p = 0.002), ferritin (p < 0.001), and of course serum creatinine (p < 0.001). Even if the risk of death was higher in the dialysis group (Exp(b) = 1.839), the survival proportions were similar in both groups. (4) Conclusions: High values of hemoglobin, serum creatinine, and LDH at admission, age, length of hospital stay ≤ 10 days, and a pulmonary impairment > 25% are responsible for an adverse outcome in non-dialysis and dialysis patients diagnosed with COVID-19.

Magnesium-A More Important Role in CKD-MBD than We Thought.

Chronic kidney disease (CKD) is associated with different complications, including chronic kidney disease-mineral and bone disorder (CKD-MBD), which represents a systemic disorder that involves the presence of different mineral or bone structure abnormalities (i.e., modification of bone turnover, strength, volume, etc.), including even vascular calcification development. Even if, over the years, different pathophysiological theories have been developed to explain the onset and progression of CKD-MBD, the influence and importance of serum magnesium level on the evolution of CKD have only recently been highlighted. So far, data are inconclusive and conflicting; therefore, further studies are necessary to validate these findings, which could be useful in developing a better, more adequate, and personalized management of CKD patients.

Uric Acid and Oxidative Stress-Relationship with Cardiovascular, Metabolic, and Renal Impairment.

BACKGROUND: The connection between uric acid (UA) and renal impairment is well known due to the urate capacity to precipitate within the tubules or extra-renal system. Emerging studies allege a new hypothesis concerning UA and renal impairment involving a pro-inflammatory status, endothelial dysfunction, and excessive activation of renin-angiotensin-aldosterone system (RAAS). Additionally, hyperuricemia associated with oxidative stress is incriminated in DNA damage, oxidations, inflammatory cytokine production, and even cell apoptosis. There is also increasing evidence regarding the association of hyperuricemia with chronic kidney disease (CKD), cardiovascular disease, and metabolic syndrome or diabetes mellitus. CONCLUSIONS: Important aspects need to be clarified regarding hyperuricemia predisposition to oxidative stress and its effects in order to initiate the proper treatment to determine the optimal maintenance of UA level, improving patients' long-term prognosis and their quality of life.

Overview of Renal Replacement Therapy Use in a General Intensive Care Unit.

OBJECTIVES: Population-based studies regarding renal replacement therapy (RRT) used in critical care populations are useful to understand the trend and impact of medical care interventions. We describe the use of RRT and associated outcomes (mortality and length of intensive care stay) in a level 1 hospital. DESIGN: A retrospective descriptive observational study. PATIENTS: Critically ill patients admitted to the ICU from 1 January to 31 December 2018. INTERVENTIONS: Age, gender, ward of admission, primary organ dysfunction at admission, length of hospital stay (LOS), mechanical ventilation, APACHE, SOFA and ISS scores, the use of vasopressors, transfusion, RRT and the number of RRT sessions were extracted. RESULTS: 1703 critically ill patients were divided into two groups: the RRT-group (238 patients) and the non-RRT group (1465 patients). The mean age was 63.58 ± 17.52 (SD) in the final ICU studied patients (64.72 ± 16.64 SD in the RRT-group), 60.5% being male. Patients admitted from general surgery ward needing RRT were 41.4%. The specific scores, the use of vasopressors, transfusions and mortality were higher in the RRT-group. The ICU LOS was superior in the RRT-group, regardless of the primary organ dysfunction. CONCLUSIONS: RRT was practiced in 13.9% of patients (especially after age of 61), with mortality being the outcome for 66.8% of the RRT-group patients. All analyzed data were higher in the RRT group, especially for multiple trauma and surgical patients, or patients presenting cardiac or renal dysfunctions at admission. We found significant increased ISS scores in the RRT-group, a significant association between the need of vasopressors or transfusion requirement and RRT use, and an association in the number of RRT sessions and LOS (p < 0.001).

The Importance of Iron Administration in Correcting Anaemia After Major Surgery.

INTRODUCTION: Postoperative anaemia can affect more than 90% of patients undergoing major surgeries. Patients develop an absolute iron deficiency in the face of significant blood loss or preoperative anaemia and major surgery. Studies have shown the negative impact of these factors on transfusion requirements, infections, increased hospitalisation and long-term morbidities. AIM OF THE STUDY: The research was performed to determine the correlation between intravenous iron administration in the postoperative period and improved haemoglobin correction trend. MATERIAL AND METHODS: A prospective study was conducted to screen and treat iron deficiency in patients undergoing major surgery associated with significant bleeding. For iron deficiency anaemia screening, in the postoperative period, the following bioumoral parameters were assessed: haemoglobin, serum iron, transferrin saturation (TSAT), and ferritin, direct serum total iron-binding capacity (dTIBC), mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH). In addition, serum glucose, fibrinogen, urea, creatinine and lactate values were also collected. RESULTS: Twenty-one patients undergoing major surgeries (52,38% were emergency and 47,61% elective interventions) were included in the study. Iron deficiency, as defined by ferritin 100-300 µg/L along with transferrin saturation (TSAT) < 20 %, mean corpuscular volume (MVC) < 92 fL, mean corpuscular haemoglobin (MCH) < 33 g/dL, serum iron < 10 µmol/L and direct serum total iron-binding capacity (dTIBC) > 36 µmol/L, was identified in all cases. To correct the deficit and optimise the haematological status, all patients received intravenous ferric carboxymaltose (500-1000 mg, single dose). Using Quadratic statistical analysis, the trend of haemoglobin correction was found to be a favourable one. CONCLUSION: The administration of intravenous ferric carboxymaltose in the postoperative period showed the beneficial effect of this type of intervention on the haemoglobin correction trend in these groups of patients.

The Ideal Time for Iron Administration in Anemia Secondary to Blood Loss-An Experimental Animal Model.

BACKGROUND: Anemia and iron deficiency are two of the main public health problems worldwide, associated with negative outcomes in surgical patients. This experimental study aimed to create a model of acute iron deficiency with anemia through blood loss and extensive surgery. Afterwards, intravenous iron was administered to correct the iron deficiency and to improve the hematological parameters in distinct moments regarding the surgical time. To assess the optimum time for therapeutic intervention, experimental subjects were compared, performing clinical, paraclinical, and histological examinations, as well. METHODS: Male rats (n = 35), aged 11-13 months, were randomly designated into six groups. Anemia and iron deficiency were obtained through a 15% blood volume loss, followed by major surgical intervention (femur fracture and osteosynthesis using Kirschner wire). Therapeutic intervention was obtained with an intravenous ferric carboxymaltose infusion, as follows: group II: intraoperative (n = 7), group III: 48 h after surgery (n = 7), group IV: 48 h before surgery (n = 5), and group V: seven days before surgery (n = 6). Group I (n = 5) was left anemic, while group 0 (n = 5) was nonanemic without therapeutic intervention. RESULTS AND DISCUSSION: In group I, serum iron lower than in group 0 (27.04 ± 6.92 µg/dL versus 60.5 ± 2.34 µg/dL), as well as hemoglobin (10.4 ± 0.54 g/dL versus 14.32 ± 2.01 g/dL) and ferritin values (22.52 ± 0.53 ng/mL versus 29.86 ± 3.97 ng/mL), validated the experimental model. Regarding wound healing after surgical trauma, we observed that neovascularization was more significant in group III, followed by group V, with fewer neutrophils, a well-represented and rich in lymphomonocytes inflammatory infiltrate associated with the biggest collagen fiber dimensions. The periosteal reaction and callus area presented thicker trabeculae in groups II and III compared to the anemic group. CONCLUSIONS: This original experimental study assessed the effect of perioperative intravenous iron administration at a specific time by comparing the weight, hematological, and iron status-defining parameters, as well as histological characteristics of the included subjects. The present findings highlight that correcting the iron deficiency in emergency settings through intravenous iron administration intraoperatively or 48 h postoperatively could determine the improved bioumoral parameters, as well as a better evolution of the postoperative wound and bone healing compared to the anemic group or subjects that received therapeutic intervention 48 h before surgery.

The Impact of Monitoring Depth of Anesthesia and Nociception on Postoperative Cognitive Function in Adult Multiple Trauma Patients.

Background and Objectives: Patients with traumatic injuries have often been excluded from studies that have attempted to pinpoint modifiable factors to predict the transient disturbance of the cognitive function in the postoperative settings. Anesthetists must be aware of the high risk of developing postoperative delirium and cognitive dysfunction (POCD) in patients undergoing emergency surgery. Monitoring the depth of anesthesia in order to tailor anesthetic delivery may reduce this risk. The primary aim of this study was to improve the prevention strategies for the immediate POCD by assessing anesthetic depth and nociception during emergency surgery. Material and Methods: Of 107 trauma ASA physical status II-IV patients aged over 18 years undergoing emergency noncardiac surgery, 95 patients were included in a prospective randomized study. Exclusion criteria were neurotrauma, chronic use of psychoactive substances or alcohol, impaired preoperative cognitive function, pre-existing psychopathological symptoms, or expected surgery time less than 2 h. Entropy and Surgical Pleth Index (SPI) values were constantly recorded for one group during anesthesia. POCD was assessed 24 h, 48 h, and 72 h after surgery using the Neelon and Champagne (NEECHAM) Confusion Scale. Results: Although in the intervention group, fewer patients experienced POCD episodes in comparison to the control group, the results were not statistically significant (p < 0.08). The study showed a statistically significant inverse correlation between fentanyl and the NEECHAM Confusion Scale at 24 h (r = -0.32, p = 0.0005) and 48 h (r = -0.46, p = 0.0002), sevoflurane and the NEECHAM Confusion Scale at 24 h (r = -0.38, p = 0.0014) and 48 h (r = -0.52, p = 0.0002), and noradrenaline and POCD events in the first 48 h (r = -0.46, p = 0.0013 for the first 24 h, respectively, and r = -0.46, p = 0.0002 for the next 24 h). Conclusions: Entropy and SPI monitoring during anesthesia may play an important role in diminishing the risk of developing immediate POCD after emergency surgery.

Rhabdomyolysis-Induced Acute Renal Injury in a Schizophrenic Patient.

Nowadays, schizophrenia is treated with atypical antipsychotics that can determine neuroleptic malignant syndrome or rhabdomyolysis appearance. In addition to trauma and muscular hypoxia, there are some drugs and toxins associated with rhabdomyolysis development, among which olanzapine. A case of severe rhabdomyolysis syndrome, with extremely high levels of serum creatine kinase (CK), followed by acute kidney failure, secondary to olanzapine overdose and prolonged immobilization is outlined. Continuous renal replacement therapy was performed, with a slow clearance of serum CK levels. Under supportive therapy, systemic alkalinisation with volume resuscitation and corticotherapy, patient's general condition was improved, as well as his lower limb paresis. He followed frequent psychiatric evaluations and psychotherapies, before and after being transferred to a medical service. Rhabdomyolysis diagnosis is difficult in mild cases due to non-specific signs and symptoms, but it also has some typical manifestation, generically called "the rhabdomyolysis syndrome triad". The treatment is usually supportive; renal replacement therapy is required in the presence of acute kidney injury unresponsive to aggressive volume resuscitation. The systemic myoglobin release is responsible for renal injury. Olanzapine muscle toxicity can lead to severe rhabdomyolysis syndrome complicated with acute kidney injury and multiple organ dysfunction syndrome. Rapid identification and aggressive therapeutic management are essential for improving patients' outcome and prevent the occurrence of irreversible injuries.

Clinical, histological and therapeutic modern approach of Ledderhose disease.

Ledderhose disease or plantar fibromatosis is a rare hyperproliferative disorder of the plantar aponeurosis, clinically characterized by nodules situated especially on the medial border of the foot. It is histopathologically associated with Dupuytren's disease. This disease has some risk factors, like old age, alcohol or nicotine abuse, liver dysfunction, trauma or exposure to vibrations and autoimmune disorders, but the exact etiology is still unknown. Even though it is benign, the local manifestations can be aggressive, leading to debilitating deformities and contractures of the toes. Ultrasound and magnetic resonance imaging are used to confirm the diagnosis and to eliminate other disorders. Whenever is possible, the conservative therapies are recommended. Having a high recurrence, Ledderhose disease can be hard to treat, needing multiple surgical interventions. This paper aims to cover all the important aspects of this disease for daily medical practice, from history to clinical manifestations, diagnostic methods and histopathological features, to conservative and surgical treatment modalities.

Non-Hodgkin's lymphoma, rare localization at the base of the tongue - case presentation.

The extranodal malignant lymphomas occur mainly in the region of the head and neck, after the gastrointestinal tract. The most common site of the head and neck lymphoma is at the lymphatics ring of Waldeyer, followed by the nasosinusal region. Localization at the base of the tongue is extremely rare. The authors reported a case of a 50-year-old male with a non-Hodgkin's lymphoma, which developed at the base of tongue. An unusual sensation described as a foreign body at the hypopharyngeal region associated with progressive dysphagia were the main symptoms for which the patient was referred to our Hospital. The fibroscopic exam has revealed an oval tumor of the base of tongue, with large dimensions, sessile emergent base and smooth superficial mucosa. The tumor was removed using an endoscopic transoral approach, followed by the histopathological and immunohistochemical examination, which have been suggestive for non-Hodgkin's lymphoma with small B-cells. The treatment continued with chemotherapy, while radiotherapy was not necessary due to the fact that the tumor was completely removed.

Metastatic high-grade myxofibrosarcoma: review of a clinical case.

We present the particular clinical and histological features of a metastatic high-grade myxofibrosarcoma (MFS) of the left buttock in a 77-year-old male patient. The tumor was biopsied and surgically removed in order to increase the patient's comfort, due to its increased size and aggressive clinical behavior. Computed tomography (CT) revealed metastases in the pleura and mediastinal lymph nodes, so limb-sparing tumor excision followed by palliative care was the best practice for the patient until the fatal outcome. The histological assessment revealed a tumor composed partly of solid sheets of spindled and pleomorphic cells, partly of areas with prominent myxoid matrix and numerous elongated capillaries. Mitotic figures are frequent, often atypical, followed by numerous giant cells with abundant eosinophilic elongated cytoplasm, resembling myoid cells often multinucleated. A panel of immunohistochemical stainings, including muscle-specific actin (MSA), S-100, CD34, desmin and myogenin were performed with a negative result, which aided excluding other soft tissue tumors like rhabdomyosarcoma and leiomyosarcomas, while Ki-67 was highly expressed in more than 70% of the tumor cells. This tumor received 6 points in accordance with the Fédération Nationale des Centres de Lutte Contre le Cancer (modified FNCLCC) and was defined as a high-grade MFS [stage IV, G3 pT2bN0M1, according to the 8th edition of TNM Classification of Malignant Tumors, ICD-O 8811÷3 in World Health Organization (WHO) Classification 2013]. Due to the clinical findings combined with the histological profile, the fatal prognosis was expected, though the time period was shorter than predicted, confirming the aggressive nature of the tumor. Even if traditionally was considered MFS as a non-metastatic lesion, recent case reports and studies, including our case revealed that this tumors in fact have the potential to be fatal due to metastatic disease.

Clinical, histological and therapeutic features of Bowen's disease.

Squamous cell carcinoma (SCC) in situ or Bowen's disease (BD) is a slowly progressive malignancy. However, cases of regression have been reported. Recent reviews cover only certain aspects of this disease; therefore, this paper's aim is to cover all the relevant aspects for medical practice, such as clinical, histological and therapeutic details. BD may affect all regions of the skin and mucosa, but in accordance with the region and etiologic factor, it may embrace different clinical forms, some of them very similar with other skin lesions. Dermoscopy may prove useful for establishing a clinical diagnosis. Several patterns have been encountered and may help distinguishing from other diseases. When in doubt, puncture biopsy or complete excision may be performed in order to obtain histological data that could define BD. Different morphological aspects of the involved components are described in order to reduce the risk of misdiagnose. In order for the approach to be complete, relevant information about treatment has been presented, underlining the pros and cons of each available therapy.