The Immune Response of Cutaneous Basosquamous- and Squamous-Cell Carcinoma Associated with Sun Exposure.

In recent years, there has been an observed increase in the frequency of cutaneous carcinoma, which correlates with sun exposure. This study aims to explore the variances of tumor characteristics and immune response markers among patients diagnosed with cutaneous squamous-cell carcinoma (SCC) and basosquamous-cell carcinoma (BSC) with varying levels of sun exposure. The objective is to elucidate the potential influence of sun exposure on tumor progression and immune response in these types of carcinomas. We conducted a retrospective observational study that included 132 patients diagnosed with SCC and BSC. Participants were separated into high- and low-sun exposure groups. Tumor characteristics and immune response markers, including lymphocyte percentage (LY%), neutrophil-to-lymphocyte ratio (NLR), and lymphocyte-to-monocyte ratio (LMR), were assessed using the Mann-Whitney U test. Our findings revealed the interplay between sun exposure, inflammation, aging, and immune response. In 80% of cases, it was found that individuals had high sun exposure throughout their lifetime. Patients in the high sun exposure category had a significantly higher LY% than those with low sun exposure (24.22 ± 7.64 vs. 20.71 ± 8.10, p = 0.041). Also, the NLR was lower in patients with high sun exposure (3.08 ± 1.47 vs. 3.94 ± 2.43, p = 0.023). Regarding inflammatory markers, the erythrocyte sedimentation rate (ESR), LY%, NLR, and LMR showed significant differences between the two groups. Patients who were diagnosed with SCC had higher ESR values (p = 0.041), higher LY% (p = 0.037), higher NLR (p = 0.041), and lower LMR (p = 0.025). This study provides evidence supporting distinct tumor characteristics and immune response patterns in patients diagnosed with SCC and BSC with a high sun exposure history. These findings imply that sun exposure may contribute to tumor progression and influence the immune response in individuals with SCC and BSC.

System of Implantable Electrodes for Neural Signal Acquisition and Stimulation for Wirelessly Connected Forearm Prosthesis.

There is great interest in the development of prosthetic limbs capable of complex activities that are wirelessly connected to the patient's neural system. Although some progress has been achieved in this area, one of the main problems encountered is the selective acquisition of nerve impulses and the closing of the automation loop through the selective stimulation of the sensitive branches of the patient. Large-scale research and development have achieved so-called "cuff electrodes"; however, they present a big disadvantage: they are not selective. In this article, we present the progress made in the development of an implantable system of plug neural microelectrodes that relate to the biological nerve tissue and can be used for the selective acquisition of neuronal signals and for the stimulation of specific nerve fascicles. The developed plug electrodes are also advantageous due to their small thickness, as they do not trigger nerve inflammation. In addition, the results of the conducted tests on a sous scrofa subject are presented.

Clinical, Dermoscopic and Microscopic Features of a "Collision Tumour" Ultimately Confirmed as a Regressing Melanoma - Lessons Learnt from a Chance Diagnosis.

Spontaneous regression of malignant melanoma was first reported over a century ago. Clinically, areas of blue or grey colouration in lesions may be indicative of regression. Dermoscopy is a very useful tool for diagnosing regression. An important criterion is the blue-white scar. About 10-35% of excised melanomas show features of regression histopathologically. We present a case of regressing melanoma, with clinical and dermoscopic features suggesting a collision tumour, diagnosed histopathologically. This case might improve our knowledge of the potential clinical manifestations, and the biology, of regressing melanoma.

Remote Sensing System for Motor Nerve Impulse.

In this article, we present our research achievements regarding the development of a remote sensing system for motor pulse acquisition, as a first step towards a complete neuroprosthetic arm. We present the fabrication process of an implantable electrode for nerve impulse acquisition, together with an innovative wirelessly controlled system. In our study, these were combined into an implantable device for attachment to peripheral nerves. Mechanical and biocompatibility tests were performed, as well as in vivo testing on pigs using the developed system. This testing and the experimental results are presented in a comprehensive manner, demonstrating that the system is capable of accomplishing the requirements of its designed application. Most significantly, neural electrical signals were acquired and transmitted out of the body during animal experiments, which were conducted according to ethical regulations in the field.

A mesorectal incidentaloma: Rare localization of Castleman disease (Case report).

Incidentalomas are defined as tumors or pseudo-tumoral masses accidentally discovered during clinical and imaging investigations. We present a 51-year-old female patient who presented at the gynecology service for genital bleeding caused by uterine fibromatosis. Computerized pelvic tomography showed an engorged uterus completely deformed by numerous intramural and submucosal nodular structures suggestive of multiple fibroids. Behind the uterus, a well-defined, iodophilic, 49/51 mm diameter, tissue-shaped, nodular mass was identified, with pushing borders into the adjacent fat and showing a mass effect on the rectum against which it retained a demarcation zone. A conclusion of the histopathological examination was made. Histopathological aspects and immunohistochemical tests supported the diagnosis of Castleman disease (CD) variant vascular hyaline variant. The mesorectum is a particularly and extremely rare localization for CD, and preoperative diagnosis is difficult to achieve. The correct surgical attitude in the case of an incidental finding in this localization is the extensive resection that satisfies the presumption of a neoplastic formation.

Primary hyperparathyroidism-related giant parathyroid adenoma (Review).

Primary hyperparathyroidism (PHPT), an endocrine condition caused by a parathyroid adenoma (PTA) in 80-85% of the cases, has shifted in the modern era to a mildly symptomatic phenotype due to the prompt recognition of hypercalcemia and to a minimally invasive surgical approach which has a curative potential. Clinical complications of PHTH are either related to high calcium or parathyroid hormone [also parathormone (PTH)] or both, while the originating tumor typically is small, without local mass effects. A distinct entity is represented by giant PTA (GPTA) which is considered at a weight of more than 3 (3.5) grams. The present article is a review of the literature involving practical points of non-syndromic PHPT-related GPTA. Most authors agree that pre-operatory calcium and PTH are higher in GPTA vs. non-GPTA. However, the clinical presentation of PHPT may be less severe, probably due to local mass effects that bring the patient to an early medical evaluation. Age distribution, sex ratio, rate of successful pre-operatory location do not differ from non-giant PTA. Hypovitaminosis D is more frequent in PTA of higher dimensions. Post-operative hypocalcemia, but not recurrent/persistent PHPT, is expected, even hungry bone disease. A higher rate of atypia is described although the tumor is mostly benign. Unusual presentations such as cystic transformation, initial diagnosis during pregnancy or auto-infarction have been reported. The ectopic localization of PTA presented in almost 15% of all cases may also be found in GPTA. What are the exact cutoffs for defining GPTA is still an open issue.

Adrenal ganglioneuroma: Prognostic factors (Review).

Ganglioneuroma, a rare neural crest-derived tumor, exhibits a benign profile in contrast to other neuroblastic tumors (neuroblastoma/ganglioneuroblastoma). Ganglioneuromas can be found anywhere autonomic ganglia are located, mostly abdominal/pelvic sites followed by the adrenal glands (one-third of cases), mediastinum/thorax and cervical area. Affecting especially children more than 10 years of age, Ganglioneuroma is either asymptomatic or may cause local compressive effects; rarely inducing nonspecific abdominal complains or arterial hypertension related to oversecretion of epinephrine/norepinephrine/dopamine. Despite a good prognosis, adrenalectomy is necessary in order to rule out a malignancy. Open procedure represents the standard therapeutic option; alternatively, centers with large laparoscopic pediatric experience and good stratification protocols have reported successful procedures. High uptake of I123-MIBG is associated with a more severe outcome in cases with increased mitotic index. In neuroblastic tumors, neuron-specific enolase >33 ng/ml, age at diagnosis <49 months, and blood vessel invasion indicate a poor prognosis. Concurrent extra-adrenal/adrenal ganglioneuroma is associated with a more severe prognosis; post-surgical complications are more frequent in non-adrenal vs. adrenal ganglioneuroma. Exceptionally, immune-mediated paraneoplastic neurologic syndromes have been reported: anti-N-methyl-D-aspartate receptor encephalitis and opsoclonus-myoclonus-ataxia syndrome. ROHHAD syndrome is the underlying cause in 40-56% of cases of neuroendocrine tumors including ganglioneuroma; 70% of tumors are diagnosed within the first 24 months after hypothalamic obesity onset, associated with a severe prognosis due to hypoventilation, sleep apnea, and dysautonomia. Recently, the PKB/AKT/mTOR/S6 pathway was identified as a tumorigenic pathway in pediatric ganglioneuroma, not in neuroblastoma; mTOR inhibitors are a potential option for pre-operatory tumor shrinkage. Pediatric adrenal ganglioneuroma has a good prognosis if adequately treated; its recognition requires adrenalectomy. Further development of specific biomarkers is needed. In the present article, we aimed to introduce a review of the literature involving adrenal ganglioneuroma based on a practical, multidisciplinary perspective of prognostic factors.

Neuroendocrine neoplasia and bone (Review).

This is a narrative review focusing on neuroendocrine neoplasia (NEN) and bone status, in terms of metastases and osteoporosis/fractures. One fifth of NEN have skeletal dissemination, this affinity being regulated by intrinsic tumor factors such as the C-X-C chemokine receptor 4 (CXCR4). Bone colonization impairs the patient quality of life, representing a surrogate of reduced survival. Patients with NEN without bone metastases may exhibit low bone mineral density, perhaps carcinoid-related osteoporosis, yet not a standardized cause of osteoporosis. Case-finding strategies to address bone health in NEN with a good prognosis are lacking. Contributors to fractures in NEN subjects may include: menopausal status and advanced age, different drugs, induced hypogonadism, malnutrition, malabsorption (due to intestinal resection, carcinoid syndrome), hypovitaminosis D, impaired glucose profile (due to excessive hormones such as glucagon, somatostatinoma or use of somatostatin analogues), various corticoid regimes, and high risk of fall due to sarcopenia. Pheocromocytoma/paraganglioma involve bone through malignant forms (bone is an elective site) and potential secondary osteoporosis due to excessive hormonal content and increased sympathetic activity which is a key player of bone microarchitecture/quality as reflected by low Trabecular Bone Score. Glucocorticoid osteoporosis is related to NEN-associated ectopic Cushing syndrome. Currently, there are a lack of studies to emphasis that excessive gut-derivate serotonin in NENs with carcinoid syndrome is a specific activator of bone loss thus a contributor to carcinoid-related osteoporosis.

Therapy Delayed is Therapy Denied: A Case Report of Melanoma Misdiagnosed as Diabetic Foot Ulcer.

Malignant melanoma is a deadly form of skin cancer, and prompt diagnosis is a key factor in providing adequate, life-saving therapy. A 75-year-old man, with long-standing type 2 diabetes mellitus, presented with a 2- to 3-year history of right heel ulcer. He had received various therapies for a diagnosis of diabetic foot ulcer, to no avail. Physical examination showed a black, fungating ulcerated lesion on his right heel, with minimal bleeding. No inguinal lymphadenopathy was palpated. A biopsy was done, which revealed BRAF-negative malignant melanoma, with a vertical growth phase, Breslow 3.1 mm, ulceration, 11 mitoses/mm2, Clark level IV, no lymphatic or vascular invasion observed. Right inguinal lymph node sampling suggested no involvement, but PET-CT suggested pulmonary, right inguinal lymph node and bone involvement. The patient was referred to the oncologists. Written informed consent for publication was given by the patient. Diabetic foot ulcers are a frequently encountered, but serious complication of diabetes mellitus. Delayed healing is often seen, despite adequate therapy. The differential diagnosis of diabetic foot ulcers is vast and includes neoplasia. When a foot ulcer fails to heal, other differential diagnoses must be considered, in order for the patient to receive adequate therapy. Here specialist consultations, including dermatology consultations, could improve chances of delivering the right therapy promptly. This is a factor underlying the emphasis on a multidisciplinary approach to foot ulcer therapy. Our presentation - reported according to the CARE guidelines - also illustrates the fact that failure to reach a timely diagnosis may deny the patient the opportunity to receive adequate treatment. In such cases, "delayed therapy becomes denied (or failed) therapy", paraphrasing the old adage "Justice delayed is justice denied".

Cutaneous melanoma arising on pre-existing nevi - case reports.

Skin cancer is a common healthcare issue that affects millions of people worldwide. Only a small part of that population is suffering from melanoma and an even smaller proportion has melanoma developed on a pre-existing nevus. This paper illustrates five such cases, diagnosed over an 18-month period, with their histological particular aspects. Among the total number of patients diagnosed and treated in the Department of Plastic and Reconstructive Surgery, University Emergency Hospital, Bucharest, Romania, over approximately one year, of which half for melanoma in general or for benign nevi, only a small fraction had developed melanoma on a common or dysplastic nevus. These patients, as well as those with de novo developed melanoma, are a reason for concern since most of the lesions were diagnosed in a locally advanced stage of the disease. Though efforts are being made to screen and diagnose early, there are still a lot to be done in order to lower the mortality and morbidity rates for this pathology.

Emerging concepts and latest advances regarding the etiopathogenesis, morphology and immunophenotype of basal cell carcinoma.

Basal cell carcinoma (BCC) represents the most common skin malignancy, which has been linked over time to multifactorial causes. It usually occurs on sun-exposed areas in people with fair skin and with predilection for men. BCC usually affects elderly patients and has an extremely wide range of histological subtypes, which can present clinically under different variants, some with really challenging differentials. Although BCC may occur in familial settings, such as nevoid BCC syndrome, Rombo or Bazex-Dupré-Christol syndromes, nonsyndromic multiple BCCs have also been described in the scientific literature. In this review, we discuss in detail the latest scientific concepts regarding BCC, its etiology, pathogenesis, genetic bases of disease, morphology and immunophenotype, as well as the currently known genetic syndromes, which may lead to development of multiple BCCs, especially in young adults.

Cutaneous microcystic/reticular schwannoma: case report and literature review of an exceedingly rare entity with an unusual presentation.

Conventional schwannoma represents a benign peripheral nerve sheath tumor derived from Schwann cells, which usually arises in the fourth or fifth decade of life, in the subcutaneous tissue of the distal extremities, or in the head and neck region of adult patients, with no gender predilection. In addition to the classic type, at least 11 different histopathological subtypes have been described and unawareness of these uncommon histopathological entities may lead to diagnostic pitfalls and risk of mistreatment. Recently described in the scientific literature, microcystic/reticular schwannoma is still relatively unknown to both surgeons and pathologists. The purpose of this paper is to highlight its existence by describing an additional case that occurred in the retroauricular area, and to further characterize its clinical, histopathological and immunohistochemical features. We reviewed the literature and compared the current case with others that have been documented thus far, discussing all possible differential diagnoses.

Keratoacanthoma centrifugum marginatum: an unusual clinical and histopathological diagnostic pitfall.

Keratoacanthoma centrifugum marginatum (KCM) is a very rare variant of keratoacanthoma characterized by progressive peripheral growth accompanied by central healing. The tumor has the peculiar ability to involute spontaneously. A careful differential diagnostic with other skin carcinomas or hyperkeratotic lesions is required in order to ensure appropriate clinical management. We report a case of KCM in a 62-year-old man presenting with a solitary, large exophytic, sessile tumor located on the ventral side of the right lower leg, which developed over the course of one year from an initial erythematous papule. The patient presented history of local trauma. To our knowledge, this is the second report in the scientific literature supporting a possible traumatic etiology. Due to its rarity and lack of distinctive histopathological features, KCM poses a difficult diagnostic challenge. Therefore, the importance of an accurate histopathological examination and extensive use of ancillary studies for differential diagnosis is emphasized.

Claudin-1 and occludin expression in demyelinating peripheral neuropathies.

In the last years, only few studies focused on the role of tight junctions in human peripheral nerve. This type of junction is found between apposed membranes of myelinating Schwann cells, between perineurial cells and between endothelial cells (of the epi-, peri- and endo-neurium vessels). We investigated the presence of claudin-1 and occludin in peripheral nerve biopsy of patients with demyelinating peripheral neuropathies by immunolabeling (immunohistochemistry and immunofluorescence) and Western blot. Immunolabeling highlighted claudin-1 expression mostly in the tight junctions of the perineurial cells and in the autotypic junctions of the Schwann cells of the patients with demyelinating peripheral neuropathies. Occludin was mostly expressed in the tight junctions of perineurial cells and endothelial cells and only faintly in autotypic junctions of Schwann cells. The Western blot data showed significant differences in claudin-1 and occludin expression levels in patients with demyelinating peripheral neuropathies versus normal unaffected control. Our results show that autotypic tight junctions molecular composition, like claudin-1 and occludin expression could influence the demyelinating process by altering the permeability of the blood-nerve barrier.

Trichilemmal carcinoma - a rare cutaneous malignancy: report of two cases.

The trichilemmal carcinoma is a rare low-grade malignant lesion originating from hair follicle cells that usually occurs on sun-exposed skin of older individuals. A differential diagnostic is required with other skin carcinomas. We report two cases of trichilemmal carcinoma admitted at the Emergency University Hospital of Bucharest, Romania, in 2012, one of these cases being localized in the periocular area and the other one resembling a cutaneous horn. These cases present several unusual aspects that are rarely described in the literature namely the site of the tumor which in the eyelid, development of a cutaneous horn, IHC tests which revealed EMA (epithelial membrane antigen) positivity in tumor cells. Considering that this type of tumor seldom develops metastases or local recurrences, and all the cases had free margins, there was no adjuvant therapy.