The Impact of Clinical and Histopathological Factors on Disease Progression and Survival in Thick Cutaneous Melanomas.

Thick cutaneous melanomas (Breslow depth > 4 mm) are locally advanced tumors, generally associated with poor prognosis. Nevertheless, these tumors sometimes display unpredictable behavior. This study aims to analyze clinical and histopathological features that can influence the prognosis of thick melanomas. This is a retrospective study on 94 thick primary cutaneous melanomas diagnosed between 2012 and 2018 that were followed-up for at least five years to assess disease progression and survival. We evaluated the age, gender, tumor location, histological subtype, Breslow depth, Clark level, resection margins, mitotic index, the presence/absence of ulceration, necrosis, regression, microsatellites, neurotropism, lymphovascular invasion, and the pattern of tumor-infiltrating lymphocytes, and their association with disease progression and survival. By conducting univariate analysis, we found that progression-free survival (PFS) was significantly associated with female gender, the superficial spreading melanoma (SSM) subtype, mitotic index, necrosis, microsatellites, and perineural invasion. Overall survival (OS) was significantly associated with female gender, Breslow depth, SSM subtype, necrosis, microsatellites, and perineural invasion. Through multivariate Cox proportional hazards regression, we found that the only factors associated with PFS were Breslow depth, necrosis, microsatellites, and perineural invasion, while the factors associated with OS were Breslow depth, necrosis, microsatellites, and perineural invasion. Certain histopathological features such as Breslow depth, necrosis, microsatellites, and perineural invasion could explain differences in disease evolution. This is one of the first studies to demonstrate an association between necrosis and perineural invasion and outcomes in patients with thick melanomas. By identifying high-risk patients, personalized therapy can be provided for improved prognosis.

Unraveling the Intricate Link: Deciphering the Role of the Golgi Apparatus in Breast Cancer Progression.

Breast cancer represents a paramount global health challenge, warranting intensified exploration of the molecular underpinnings influencing its progression to facilitate the development of precise diagnostic instruments and customized therapeutic regimens. Historically, the Golgi apparatus has been acknowledged for its primary role in protein sorting and trafficking within cellular contexts. However, recent findings suggest a potential link between modifications in Golgi apparatus function and organization and the pathogenesis of breast cancer. This review delivers an exhaustive analysis of this correlation. Specifically, we examine the consequences of disrupted protein glycosylation, compromised protein transport, and inappropriate oncoprotein processing on breast cancer cell dynamics. Furthermore, we delve into the impacts of Golgi-mediated secretory routes on the release of pro-tumorigenic factors during the course of breast cancer evolution. Elucidating the nuanced interplay between the Golgi apparatus and breast cancer can pave the way for innovative therapeutic interventions and the discovery of biomarkers, potentially enhancing the diagnostic, prognostic, and therapeutic paradigms for afflicted patients. The advancement of such research could substantially expedite the realization of these objectives.

Gallbladder Pancreatic Heterotopia-The Importance of Diagnostic Imaging in Managing Intraoperative Findings.

Pancreatic heterotopy is a rare entity defined as the presence of abnormally located pancreatic tissue without any anatomical or vascular connection to the normal pancreas. Heterotopic pancreatic tissue can be found in various regions of the digestive system, such as the stomach, duodenum, and upper jejunum, with the less commonly reported location being the gallbladder. Gallbladder pancreatic heterotopia can be either an incidental finding or diagnosed in association with cholecystitis. Pancreatitis of the ectopic tissue has also been described. In this context, we report three cases of heterotopic pancreatic tissue in the gallbladder with different types of pancreatic tissue according to the Heinrich classification. One patient was a 24-year-old male who presented with acute pancreatitis symptoms and an ultrasonographical detected mass in the gallbladder, which proved to be heterotopic pancreatic tissue. The other two cases were female patients aged 24 and 32, respectively, incidentally diagnosed on histopathological examination after cholecystectomy for symptomatic cholelithiasis. Both cases displayed chronic cholecystitis lesions; one of them was also associated with low grade dysplasia of the gallbladder. Although a rare occurrence in general, pancreatic heterotopia should be acknowledged as a possible incidental finding in asymptomatic patients as well as a cause for acute cholecystitis or pancreatitis.

The Polyvalent Role of CD30 for Cancer Diagnosis and Treatment.

CD30, also known as TNFRSF8 (tumor necrosis factor receptor superfamily member 8), is a protein receptor that is heavily glycosylated inside the Golgi apparatus, as well as a tumor marker that is found on the surface of specific cells in the body, including certain immune cells and cancer ones. This review aims to shed light on the critical importance of CD30, from its emergence in the cell to its position in diagnosing various diseases, including Hodgkin lymphoma, where it is expressed on Hodgkin and Reed-Sternberg cells, as well as embryonal carcinoma, anaplastic large cell lymphoma (ALCL), and cutaneous T-cell lymphoma (CTCL). In addition to its role in positive diagnosis, targeting CD30 has been a promising approach treating CD30-positive lymphomas, and there is ongoing research into the potential use of CD30-targeted therapies for autoimmune disorders. We aim to elaborate on CD30's roles as a tumor marker, supporting thus the hypothesis that this receptor might be the aim of cytostatic treatment.

Primary Undifferentiated/Dedifferentiated Cutaneous Melanomas-A Review on Histological, Immunohistochemical, and Molecular Features with Emphasis on Prognosis and Treatment.

Diagnosing cutaneous melanoma is usually straightforward based on these malignancies' histopathological and immunohistochemical features. Nevertheless, melanomas can imitate various other neoplasms, sometimes lacking the expression of conventional melanocytic markers and expressing non-melanocytic ones. Furthermore, divergent differentiation is more often encountered in metastatic melanomas and is still poorly described in primary cutaneous melanomas, and little is known about these patients' prognosis and therapeutic approach. Therefore, we reviewed the literature on undifferentiated/dedifferentiated cutaneous melanomas, and we discuss the histological, immunohistochemical, and molecular profiles of undifferentiated/dedifferentiated cutaneous melanomas to understand these peculiar lesions better and improve their diagnostic algorithm. In addition to this, we also discuss how different genetic mutations may influence prognosis and become potential therapeutic targets.

Management of Capillary Hemangioma of the Sphenoid Sinus.

Background and objectives: Capillary hemangiomas are rare, benign vascular tumors that mainly affect the skin and soft tissue, with scarce appearance within the nasal cavities and paranasal sinuses. Materials and methods: We present a case report of capillary hemangioma of the sphenoid sinus and a review of the literature in the last ten years. Results: Clinical and endoscopic examination of the nose, radiologic assessment and particular histologic features contribute to the correct diagnosis of capillary hemangioma of the nose and paranasal sinuses. Conclusions: Transnasal endoscopic resection of capillary hemangioma located in the nose and paranasal sinuses is a valuable treatment method with good outcomes.

The Conundrum of Dedifferentiation in a Liposarcoma at a Peculiar Location: A Case Report and Literature Review.

Dedifferentiated liposarcoma of the deep soft tissue of the lower extremities is an infrequent finding. Myxoid liposarcoma is considered the most common soft tissue neoplasia arising in this anatomic region. Divergent differentiation usually occurs within well-differentiated liposarcoma and is exceedingly rare in a myxoid liposarcoma. We report a 32-year-old man who developed a dedifferentiated liposarcoma of the thigh on the background of a pre-existing myxoid liposarcoma. The gross examination of the surgical specimen showed a 11/7/2 cm tumour mass with solid tan-grey areas and focal myxoid degeneration. The microscopic examination revealed a malignant lipogenic proliferation, containing round cells with hyperchromatic nuclei and atypical lipoblasts, confined to the basophilic stroma with a myxoid aspect. Abrupt transition towards a hypercellular, non-lipogenic area consisting of highly pleomorphic spindle cells with atypical mitotic figures was also noted. Immunohistochemical staining was performed. Tumour cells in the lipogenic area were intensely positive for S100 and p16, and CD34 staining highlighted an arborizing capillary network. The dedifferentiated tumour areas showed positive MDM2 and CDK4 staining within neoplastic cells, with the Ki 67 proliferation marker expressed in approximately 10% of the cells. Wild-type TP53 protein expression pattern was documented. Thus, the diagnosis of a dedifferentiated liposarcoma was established. This paper aims to provide further knowledge about liposarcomas with divergent differentiation at peculiar locations, emphasizing the importance of histopathologic examination and immunohistochemical analysis for establishing the diagnosis and assessing the therapeutic response and prognosis of this condition.

Comparative Expression Profiling Reveals Molecular Markers Involved in the Progression of Cutaneous Melanoma towards Metastasis.

Cutaneous melanoma is one of the most aggressive types of cancer and often proves fatal in metastatic stages. Few treatment options are available, and its global incidence is quickly increasing. In order to gain an improved understanding of the molecular features regarding melanoma progression, we have compared gene and small non-coding RNA expression profiles from cell lines derived from primary melanoma (MelJuSo), lymph node metastasis (MNT-1) and brain metastasis (VMM1), representing distinct stages of malignant progression. Our preliminary results highlighted the aberrant regulation of molecular markers involved in several processes that aid melanoma progression and metastasis development, including extracellular matrix remodeling, migratory potential and angiogenesis. Moreover, bioinformatic analysis revealed potential targets of the microRNAs of interest. Confocal microscopy and immunohistochemistry analysis were used for validation at the protein level. Exploring the molecular landscape of melanoma may contribute to the achievement of future efficient targeted therapy, as well as better prevention, diagnosis and clinical management.

Super-resolution re-scan second harmonic generation microscopy.

Second harmonic generation microscopy (SHG) is generally acknowledged as a powerful tool for the label-free three-dimensional visualization of tissues and advanced materials, with one of its most popular applications being collagen imaging. Despite the great need, progress in super-resolved SHG imaging lags behind the developments reported over the past years in fluorescence-based optical nanoscopy. In this work, we demonstrate super-resolved re-scan SHG, qualitatively and quantitatively showing on collagenous tissues the available resolution advantage over the diffraction limit. We introduce as well super-resolved re-scan two-photon excited fluorescence microscopy, an imaging modality not explored to date.

Focus on PD-1/PD-L1 as a Therapeutic Target in Ovarian Cancer.

Ovarian cancer is considered one of the most aggressive and deadliest gynecological malignancies worldwide. Unfortunately, the therapeutic methods that are considered the gold standard at this moment are associated with frequent recurrences. Survival in ovarian cancer is associated with the presence of a high number of intra tumor infiltrating lymphocytes (TILs). Therefore, immunomodulation is considered to have an important role in cancer treatment, and immune checkpoint inhibitors may be useful for restoring T cell-mediated antitumor immunity. However, the data presented in the literature until now are not sufficient to allow for the identification and selection of patients who really respond to immunotherapy among those with ovarian cancer. Although there are some studies with favorable results, more prospective trials are needed in this sense. This review focuses on the current and future perspectives of PD-1/L1 blockade in ovarian cancer and analyzes the most important immune checkpoint inhibitors used, with the aim of achieving optimal clinical outcomes. Future studies and trials are needed to maximize the efficacy of immune checkpoint blockade therapy in ovarian cancer, as well as in all cancers, in general.

PSHG-TISS: A collection of polarization-resolved second harmonic generation microscopy images of fixed tissues.

Second harmonic generation (SHG) microscopy is acknowledged as an established imaging technique capable to provide information on the collagen architecture in tissues that is highly valuable for the diagnostics of various pathologies. The polarization-resolved extension of SHG (PSHG) microscopy, together with associated image processing methods, retrieves extensive image sets under different input polarization settings, which are not fully exploited in clinical settings. To facilitate this, we introduce PSHG-TISS, a collection of PSHG images, accompanied by additional computationally generated images which can be used to complement the subjective qualitative analysis of SHG images. These latter have been calculated using the single-axis molecule model for collagen and provide 2D representations of different specific PSHG parameters known to account for the collagen structure and distribution. PSHG-TISS can aid refining existing PSHG image analysis methods, while also supporting the development of novel image processing and analysis methods capable to extract meaningful quantitative data from the raw PSHG image sets. PSHG-TISS can facilitate the breadth and widespread of PSHG applications in tissue analysis and diagnostics.

A Systematic Approach of the Intrauterine Morphogenesis of the Human Palpebral Apparatus.

The human eyelid embodies a vast diversity of functions. Acting as a protective shield for the ocular apparatus and as a light regulator in the sight process, eyelids stand a fascinating - yet omitted - role in facial aesthetics, serving as a racial trait by which humankind succeeded to manifest heterogeneity as a species. These assumptions are precisely forecasted right from in-utero life through intricate processes of growth and cell differentiation. In the Department of Anatomy of "Carol Davila" University of Medicine and Pharmacy, we performed morphological assessments on 41 embryos and fetuses with gestational ages ranging from 6 to 29 weeks. This study aims to illustrate the morphogenesis of eyelids in human embryos and fetuses and highlight macroscopic features which could potentially have significant clinical implications in ophthalmic pathology.

Primary Bone Lesions in Rosai-Dorfman Disease, a Rare Case and Diagnostic Challenge-Case Report and Literature Review.

Rosai-Dorfman Disease (RDD), also known as sinus histiocytosis, is included in the group of rare diseases, characterized by proliferation and accumulation of histiocytes in the lymph nodes (lymphadenopathy), most often involving the cervical ganglion chains (nodal form). RDD bone involvement is rare, estimated at 10% of cases, but primary bone involvement (extranodal form), is very rare-2-8%. Usually they are solitary lesions, with multifocal primary bone manifestations being extremely rare. Histopathological analysis is of high value for a correct diagnosis. We present the case of a Caucasian woman, 42 years old, initially treated in another clinic, for an osteolytic tumor formation in the right tibial shaft. An excisional biopsy with bone trepanation was performed, the histopathological diagnosis being the chronic inflammatory tissue. The evolution was atypical, with tumor growth, extraosseous, subcutaneous. A needle biopsy was repeated in our clinic, the result being similar to the original one. Evolution of the tumor, and the radiological and imaging aspect (periosteal reaction, eroded and thin bone cortex) suggested a more aggressive disease, these being in inconsistency with the result obtained. The biopsy was repeated, as an excision type this time. The histopathological result and immunohistochemistry indicated an RDD primary bone lesion. Based on this result, and corroborated with the data from the literature, we initiated the surgical treatment, curettage and grafting with bone substitute plus safety osteosynthesis with locked plaque, the patient registering a favorable evolution. RDD primary bone lesions are in fact an atypical manifestation of a rare disease. The correct diagnosis is very difficult due to the non-specific imaging aspect. Histopathological examination errors, especially in the case of needle biopsies can lead to errors in diagnosis and treatment with negative results for the patient.

Ultrasound Pitfalls in a Complex Fetal Cardiac Malformation-Case Report of a New Arteriovenous Central Communication.

Cardiac and cardiovascular malformations are of real interest in terms of definition, epidemiology, and means of early diagnosis by imaging. Although ultrasound examination reaches exceptional performance nowadays, unusual pathologies are still exposed to the risk of either incorrect acquired image or misinterpretation by the specialist in a routine scan. Herein, we present a case of a 20-week-old fetus (from an apparently low-risk pregnancy) with complex cardiac and vascular abnormalities, including an arteriovenous malformation along with ventricular septal defect, ductal coarctation of the aorta, aneurysm of a brachiocephalic vein, and dilation of the entire neck and upper mediastinum venous system, and the limitations that were encountered in the process of diagnosis and management of the case.

Influence of hematoxylin and eosin staining on the quantitative analysis of second harmonic generation imaging of fixed tissue sections.

Second harmonic generation (SHG) microscopy has emerged over the past two decades as a powerful tool for tissue characterization and diagnostics. Its main applications in medicine are related to mapping the collagen architecture of in-vivo, ex-vivo and fixed tissues based on endogenous contrast. In this work we present how H&E staining of excised and fixed tissues influences the extraction and use of image parameters specific to polarization-resolved SHG (PSHG) microscopy, which are known to provide quantitative information on the collagen structure and organization. We employ a theoretical collagen model for fitting the experimental PSHG datasets to obtain the second order susceptibility tensor elements ratios and the fitting efficiency. Furthermore, the second harmonic intensity acquired under circular polarization is investigated. The evolution of these parameters in both forward- and backward-collected SHG are computed for both H&E-stained and unstained tissue sections. Consistent modifications are observed between the two cases in terms of the fitting efficiency and the second harmonic intensity. This suggests that similar quantitative analysis workflows applied to PSHG images collected on stained and unstained tissues could yield different results, and hence affect the diagnostic accuracy.

Attitude of the surgical approach in hyperparathyroidism: A retrospective study.

The present study constitutes a retrospective study for patients with hyperparathyroidism surgically operated on at the Department of Thoracic Surgery of the Central Military Emergency University Hospital 'Dr. Carol Davila', Bucharest, Romania (SUUMC), over a period of 6 years. The study aimed to elucidate the diagnostic and surgical attitude for an effective treatment, practiced at SUUMC, Romania. The study group included 55 patients: 41 women and 14 men, diagnosed at the endocrinology department, who underwent various personalized surgeries (Kocher modified incision) for typical and ectopic locations of parathyroid pseudotumor formations (hyperplasia and parathyroid adenoma), to cure the disease. The recommended protocol was followed by immediate and 30-day postoperative evaluation which showed normalization of the blood tests, and improved clinical and imaging anomalies. In conclusion, the thoracic surgeon has the necessary knowledge to perform surgery at the cervical, thoracic-cervical and mediastinal levels. Postoperative, the results of laboratory tests for calcium (Ca) and parathyroid hormone (PTH) gradually returned to normal, as can be seen from the statistical study.

Assessment of clinical and pathological complete response after neoadjuvant chemoradiotherapy in rectal adenocarcinoma and its therapeutic implications.

Because almost one fourth of patients with rectal adenocarcinoma (RC) achieve pathological complete response (pCR) after neoadjuvant chemoradiation therapy (CRT), having significantly higher survival rates than those without pCR, the assessment of pCR represents a highly important challenge nowadays. Moreover, recent studies revealed that organ-sparing approaches could represent a reasonable alternative to radical surgery (RS) in patients with pCR, achieving similar long-term outcomes with lower morbidity rates and improved quality of life. Unfortunately, the decision of a rectum-sparing approach should be based only on clinical, endoscopic (with or without biopsy) and radiological methods, that must accurately predict the pCR after neoadjuvant CRT, in the absence of the pathological examination of the RS specimen. Thus, a surrogate parameter called clinical complete response (cCR) emerged, to assess the results of neoadjuvant CRT. The evolving accuracy of recent endoscopic and imaging methods in assessment of cCR and their predictive value for estimation of pCR achievement are presented. The usefulness of combining the results of these evaluation methods (resulting in the development of few nomograms) for a more accurate estimation of pCR, as well as the predictive factors for pCR achievement are also debated. Moreover, the changing landscape of therapeutic approaches based on cCR assessment is discussed, emphasizing the advantages and pitfalls of rectum-sparing approaches, compared to RS. Because there are no reliable methods to estimate with 100% accuracy the pCR, the only way to decrease as much as possible the risk of misleading treatment choices is the multidisciplinary team-based decision.

A rare case of placental mesenchymal dysplasia - case report and literature review.

Described as a rare anomaly of the placenta, with a reported incidence of 0.02%, mesenchymal dysplasia is a benign condition characterized by placentomegaly, grape-like vesicles and by microscopic features resembling those of a molar pregnancy, such as hydropic villi, cistern formation and dysplastic blood vessels. We report a rare case of placental mesenchymal dysplasia diagnosed in a pregnancy with early symmetric fetal intrauterine growth restriction and a normal karyotype. Based on this case report, we discuss the particularities of this condition, emphasizing the ultrasonography and histopathological findings.

Squamous metaplasia within a sigmoid adenoma. A rare feature.

Squamous metaplasia occurring within a colorectal polyp is a rare finding, having a reported incidence of approximately 0.44%. The origin of the squamous cells in this type of setting is uncertain (mechanical irritation and chronic inflammation are potential predisposing factors). It has been implied that the significance of squamous metaplasia in colorectal adenomas is that of a preneoplastic lesion for squamous cell and adenosquamous carcinoma, however the evidence to support this statement is scarce. We present a case of a large tubulovillous adenoma located in the sigmoid, with low-grade dysplasia and multiple foci of p16-positive immunoexpression squamous metaplasia in a 54-year-old Caucasian male, presenting with rectal bleeding.

HISTOBREAST, a collection of brightfield microscopy images of Haematoxylin and Eosin stained breast tissue.

Modern histopathology workflows rely on the digitization of histology slides. The quality of the resulting digital representations, in the form of histology slide image mosaics, depends on various specific acquisition conditions and on the image processing steps that underlie the generation of the final mosaic, e.g. registration and blending of the contained image tiles. We introduce HISTOBREAST, an extensive collection of brightfield microscopy images that we collected in a principled manner under different acquisition conditions on Haematoxylin - Eosin (H&E) stained breast tissue. HISTOBREAST is comprised of neighbour image tiles and ensemble of mosaics composed from different combinations of the available image tiles, exhibiting progressively degraded quality levels. HISTOBREAST can be used to benchmark image processing and computer vision techniques with respect to their robustness to image modifications specific to brightfield microscopy of H&E stained tissues. Furthermore, HISTOBREAST can serve in the development of new image processing methods, with the purpose of ensuring robustness to typical image artefacts that raise interpretation problems for expert histopathologists and affect the results of computerized image analysis.