Anti-TNF-α induced mucous membrane pemphigoid-like disease.

Mucous membrane pemphigoid (MMP) is an autoimmune blistering disease affecting various mucous membranes, with rare skin involvement. We present a case of a 40-year-old woman with recurring desquamative gingivitis, implicating etanercept, an anti-TNF-α agent, in MMP-like lesions confined to the oral mucosa. Suspicion arose due to temporal correlation between drug administration and lesion onset, confirmed by recurrence upon resumption and resolution upon suspension. Laboratory findings supported MMP diagnosis. Notably, the patient had a history of autoimmune urticaria and axial spondylarthritis. A probable adverse drug reaction was established using the Naranjo scale. Possible mechanisms involve the role of TNF-α in MMP pathophysiology and its interaction with viral triggers, exemplified by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. This case underscores the intricate relationship among autoimmune conditions, medications, and external factors in mucocutaneous disorders, advocating for comprehensive patient assessment and interdisciplinary collaboration for optimal management. (Oral Surg Oral Med Oral Pathol Oral Radiol YEAR;VOL:page range).

High charge of cerebroid nests in nodular melanomas predicts tumor aggressiveness and high mutational tumoral burden: a pilot study.

Purpose: Even today, melanoma is a highly aggressive neoplasm with a high mortality rate. The nodular type is very aggressive and has cerebroid nests of melanocytes (CNMs) at the growth edge, morphologically similar to the poorly differentiated neoplastic epithelial cell clusters described in colorectal, breast, and endometrioid endometrial cancers. Patients and methods: We selected 25 nodular melanomas (NMs) with known molecular profiles, of which the entire paraffin-embedded lesion was available. We counted CNMs under a microscopic at a magnification of 20x (i.e., a microscopic field with a major axis of 1 mm). Based on the number of CNMs in the area, melanomas were classified into three groups: G1 (CNMs ranging from 0 to 4), G2 (CNMs ranging from 5 to 9), and G3 (CNMs ≥ 10). The presence of CNMs and their counts were compared with molecular and histopathological data. Results: Seventeen (NMs) were grouped as G1 (68%), 5 as G2 (20%), and 3 as G3 (12%) based on CNMs count. The presence of CNMs correlated with epithelioid cell morphology (p < 0.05), Clark IV and V levels (p < 0.05), vascular invasion (p < 0.05), and biological mutants (p < 0.05). Melanomas with ≥ 10 CNMs more frequently show ulceration (p < 0.02) and the BRAF V600E mutation (p < 0.02). Conclusion: CNMs count has a predictive role regardless of tumor size; their association with the BRAF V600E mutation suggests their predictive significance in response to biologics. However, further investigations are needed to strengthen this hypothesis.

Revolutionizing Cancer Research: The Impact of Artificial Intelligence in Digital Biobanking.

BACKGROUND: Biobanks are vital research infrastructures aiming to collect, process, store, and distribute biological specimens along with associated data in an organized and governed manner. Exploiting diverse datasets produced by the biobanks and the downstream research from various sources and integrating bioinformatics and "omics" data has proven instrumental in advancing research such as cancer research. Biobanks offer different types of biological samples matched with rich datasets comprising clinicopathologic information. As digital pathology and artificial intelligence (AI) have entered the precision medicine arena, biobanks are progressively transitioning from mere biorepositories to integrated computational databanks. Consequently, the application of AI and machine learning on these biobank datasets holds huge potential to profoundly impact cancer research. METHODS: In this paper, we explore how AI and machine learning can respond to the digital evolution of biobanks with flexibility, solutions, and effective services. We look at the different data that ranges from specimen-related data, including digital images, patient health records and downstream genetic/genomic data and resulting "Big Data" and the analytic approaches used for analysis. RESULTS: These cutting-edge technologies can address the challenges faced by translational and clinical research, enhancing their capabilities in data management, analysis, and interpretation. By leveraging AI, biobanks can unlock valuable insights from their vast repositories, enabling the identification of novel biomarkers, prediction of treatment responses, and ultimately facilitating the development of personalized cancer therapies. CONCLUSIONS: The integration of biobanking with AI has the potential not only to expand the current understanding of cancer biology but also to pave the way for more precise, patient-centric healthcare strategies.

Research of Prostate Cancer Urinary Diagnostic Biomarkers by Proteomics: The Noteworthy Influence of Inflammation.

Nowadays, in the case of suspected prostate cancer (PCa), tissue needle biopsy remains the benchmark for diagnosis despite its invasiveness and poor tolerability, as serum prostate-specific antigen (PSA) is limited by low specificity. The aim of this proteomic study was to identify new diagnostic biomarkers in urine, an easily and non-invasively available sample, able to selectively discriminate cancer from benign prostatic hyperplasia (BPH), evaluating whether the presence of inflammation may be a confounding parameter. The analysis was performed by two-dimensional gel electrophoresis (2-DE), mass spectrometry (LC-MS/MS) and Enzyme-Linked Immunosorbent Assay (ELISA) on urine samples from PCa and BPH patients, divided into subgroups based on the presence or absence of inflammation. Significant quantitative and qualitative differences were found in the urinary proteomic profile of PCa and BPH groups. Of the nine differentially expressed proteins, only five can properly be considered potential biomarkers of PCa able to discriminate the two diseases, as they were not affected by the inflammatory process. Therefore, the proteomic research of novel and reliable urinary biomarkers of PCa should be conducted considering the presence of inflammation as a realistic interfering element, as it could hinder the detection of important protein targets.

Development and Multicentre Validation of the Modena Score to Predict Survival in Advanced Biliary Cancers Undergoing Second-Line Chemotherapy.

Background: The role of second-line chemotherapy in advanced biliary cancers (ABCs) has only recently been established in phase III randomized trial and the optimal selection of patients most likely to benefit from it remains challenging. Methods: A cohort of 98 ABC treated second-line chemotherapy was used as a developmental dataset to identify covariates independently associated with overall survival (OS). Kaplan-Meier analysis was used to investigate the association between variables and OS and those retaining statistically significance were combined in a multiplexed score. Results: The following pretreatment variables were independently associated with OS: ECOG PS > 0, peritoneal disease, LDH > 430 UI/L, albumin <3.5 gr/dL, gamma-GT >100 UI/L, sodium <140 mEq/L, absolute lymphocyte count <1000/mmc, and PFS to first-line <6 months. Based on these results, a scoring system was developed that identified three subgroups with statistically different OS: low-risk (mOS 18 months), intermediate-risk (mOS 9.4 months) and high-risk (mOS 2.9 months) (p < 0.001). The prognostic model was both internally and externally validated in a multicentre cohort of 120 ABCs. Conclusion: The Modena score is a multiplexed scoring system capable of accurately risk-stratified ABCs treated with second-line chemotherapy. Based on its reproducibility, usability and generalizability, it has the potential for assisting therapeutic decision-making in the clinic and risk-stratification in future trials.

The Evolving Role of FGFR2 Inhibitors in Intrahepatic Cholangiocarcinoma: From Molecular Biology to Clinical Targeting.

Intrahepatic cholangiocarcinoma (iCCA) is an anatomically and biologically distinct entity with a rising incidence and a poor prognosis on conventional treatments. Surgery followed by adjuvant chemotherapy is a potentially curative option in resectable cases, while palliative-intent chemotherapy is the standard-of-care in the advanced setting. Technological advances through massive parallel sequencing have enabled a deeper understanding of disease biology with the identification of several druggable molecular vulnerabilities in nearly 50% of cases. Among them, gene fusions involving the fibroblast growth factor receptor 2 (FGFR2) are the most therapeutically exploited so far with a number of Phase II clinical trials investigating FGFR2 inhibitors showing unprecedented efficacy results in this molecular subgroup. Over the last year, these efforts have culminated in the US FDA-approval of pemigatinib and infigratinib, the first two oral selective FGFR2 targeted agents for previously treated, locally advanced or metastatic iCCA driven by FGFR2 fusion or rearrangements. While first-line Phase III trials are currently underway to test these targeted approach against standard-of-care chemotherapy, translational studies are trying to better understand primary and secondary resistance mechanisms in order to optimize FGFR2 blockade in iCCA. In this article, we extensively reviewed the current evidence on the biological rationale, as well as preclinical and clinical development of FGFR inhibitors in iCCA.

Cutaneous Metastasis from Colorectal Cancer: Making Light on an Unusual and Misdiagnosed Event.

Cutaneous metastasis from solid tumors is a rare event and usually represents a late occurrence in the natural history of an advanced visceral malignancy. Rarely, cutaneous metastasis has been described in colorectal cancer patients. The most frequent cutaneous site of colorectal metastasis is the surgical scar in the abdomen following the removal of the primary malignancy, followed by the extremities, perineum, head, neck, and penis. Metastases to the thigh and back of the trunk are anecdotical. Dermatological diagnosis of cutaneous metastasis can be quite complex, especially in unusual sites, such as in the facial skin or thorax and in cases of single cutaneous lesions since metastasis from colorectal cancer is not usually the first clinical hypothesis, leading to misdiagnosis. To date, due to the rarity of cutaneous metastasis from colorectal cancer, little evidence, most of which is based on case reports and very small case series, is currently available. Therefore, a better understanding of the clinic-pathological characteristics of this unusual metastatic site represents an unmet clinical need. We present a large series of 29 cutaneous metastases from colorectal cancer with particular concerns regarding anatomic localization and the time of onset with respect to primitive colorectal cancer and visceral metastases.

Cytoproliferative activity in colorectal poorly differentiated clusters: Biological significance in tumor setting.

BACKGROUND: Poorly differentiated clusters (PDCs) have gained a significant prognostic role in colorectal carcinomas (CRCs) being associated to high risk of lymph node metastasis, shorter survival time and poor prognosis. The knowledge in PDC biology is not completely clear. MATERIALS AND METHODS: We assessed Ki-67 LI in 45 CRCs showing ≥10 PDCs. We distinguished PDCs at the periphery of the tumor masses (pPDCs) from those within the tumor masses (cPDCs). We chose 3 cut-offs of Ki-67 labeling index (Ki-67 LI): <10%, 10-50%, and >50% of the labeled cells. RESULTS: Ki-67 LI in pPDCs was<10% in 37 cases (82%), 10-50% in 6 cases (13%) and >50%in 2 cases (5%); Ki-67 LI in cPDCs was<10% in 4 cases (23.5%), 10-50% in 4 (23.5%) and >50% in 9 (54%). Ki-67 LI in tumor budding foci (TBs) was <10% in 8 cases (32%), 10-50% in 8 (32%) and >50% in 9 (36%). The difference of Ki-67 LI reaches the statistical significance (p < 0.005). Ki-67 LI <10% in the pPDCs was associated with nodal metastases (pN+) (p < 0.0001), pTNM stage III and IV(p < 0.0001) and TB (p < 0.001). Ki-67 LI > 50% in cPDC was significantly associated withpT3-pT4 and advanced pTNM stages (p < 0.0001), N+ (p = 0.0001) and LVI (p < 0.05). CONCLUSION: Different Ki-67 LI detected between cPDCs and pPDCs suggesting a biological difference in PDCs. An actively proliferating central tumor areas can be distinguished from the peripheral portion of the tumors in which the cells interact with the stroma acquiring invasive and metastatic potential.

Histopathological findings and clinicopathologic correlation in COVID-19: a systematic review.

The severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) pandemic has had devastating effects on global health and worldwide economy. Despite an initial reluctance to perform autopsies due to concerns for aerosolization of viral particles, a large number of autopsy studies published since May 2020 have shed light on the pathophysiology of Coronavirus disease 2019 (COVID-19). This review summarizes the histopathologic findings and clinicopathologic correlations from autopsies and biopsies performed in patients with COVID-19. PubMed and Medline (EBSCO and Ovid) were queried from June 4, 2020 to September 30, 2020 and histopathologic data from autopsy and biopsy studies were collected based on 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 58 studies reporting 662 patients were included. Demographic data, comorbidities at presentation, histopathologic findings, and virus detection strategies by organ system were collected. Diffuse alveolar damage, thromboembolism, and nonspecific shock injury in multiple organs were the main findings in this review. The pathologic findings emerging from autopsy and biopsy studies reviewed herein suggest that in addition to a direct viral effect in some organs, a unifying pathogenic mechanism for COVID-19 is ARDS with its known and characteristic inflammatory response, cytokine release, fever, inflammation, and generalized endothelial disturbance. This study supports the notion that autopsy studies are of utmost importance to our understanding of disease features and treatment effect to increase our knowledge of COVID-19 pathophysiology and contribute to more effective treatment strategies.

Idiopathic chylous peritonitis mimicking acute appendicitis A case report.

We report an uncommon case of idiopathic acute chylous peritonitis mimicking an acute appendicitis in a 30-year-old female patient with a 2-day history of abdominal pain, nausea and vomiting. Chylous ascites is a rare form of ascites characterized by the presence of a milky fluid rich in triglycerides. It occurs as a result of a damage to the lymphatic system due to trauma or other benign and malignant pathologies. Although the most common clinical presentation is progressive painless abdominal distension, less frequently it can cause acute abdomen symptoms. The management is based on identifying and treating the underlying pathology. Aspiration of the fluid and drainage are the only therapy required if a clinically diagnosis cannot be made. Surgical laparoscopic exploration is necessary to make a diagnosis and to treat effectively acute abdomen cases.In the absence of a significant determining pathology, we talk about idiopathic chylous peritonitis. KEY WORDS: Chylous ascites, peritonitis, laparoscopy.

Urinary proteomic profiles of prostate cancer with different risk of progression and correlation with histopathological features.

Prostate cancer (PCa) is the most common tumor in men with extremely variable outcome, varying from latent or indolent form to very aggressive behavior. High grade tumors, expansions exceeding the prostatic capsule into the surrounding soft tissues and spreading through lymph vascular channels, represent the most consistent unfavorable prognostic factors. However, accuracy in the prediction of the disease progression is sometimes difficult. Along with new molecular diagnostic techniques and more accurate histopathological approaches, proteomic studies challenge to identify potential biomarkers predictive of PCa progression. In our study we analyzed the urinary proteomes of 42 patients affected by PCa through two-dimensional electrophoresis associated with mass spectrometry. Proteomic profiles were correlated to histopathological features including pTNM stage and tumor differentiation in order to provide new promising markers able to define more accurately the PCa aggressiveness and driving new therapeutic approaches.

Laparoscopic treatment of Meckel's diverticulum perforation caused by a chicken bone. A case report.

We describe an uncommon case of a Meckel's diverticulum perforation by a chicken bone in a patient with symptoms of acute appendicitis. Meckel's diverticulum is the most common congenital abnormality of the gastrointestinal tract. The incidence is approximately 2% of the population. Most patients are asymptomatic, only 4-16% presenting complications, including bleeding, obstruction, and diverticulitis. The perforation due to a foreign body is a very infrequent complication and may have a bad prognosis in case of a delayed diagnosis. Only in a few cases, a careful evaluation of the CT scan leads to correct preoperative diagnosis. Definitive treatment is surgical intervention and should not be delayed in patients with peritonitis. Laparoscopy is a safe diagnostic and therapeutic tool to treat complicated Meckel's diverticulum. In our case, a stapled laparoscopic diverticulectomy has been performed with an excellent outcome. KEY WORDS: Laparoscopy, Meckel's diverticulum, Perforation.

Primary laparoscopic approach to repair perforated peptic ulcer. A retrospective cohort study.

BACKGROUND: Perforated peptic ulcer is a serious complication of peptic ulcer disease and carries high risk for morbidity and mortality. Although the incidence of peptic ulcer disease has decreased in recent decades, the percentage of patients with perforated peptic ulcer requiring emergency surgery remains constant. The use of laparoscopic management as a first choice for the treatment of the perforation is growing but is not routine in many centers. METHODS: Clinical and surgical data on 42 patients underwent surgical treatment for perforated peptic ulcer from January 2012 to December 2016 were collected. Laparoscopic repair of the perforation with a three-port technique was made in all cases. The Boey scoring system was used to predict the prognosis. RESULTS: All patients underwent suture-closure of the ulcer, and omental patch through laparoscopy without conversion to open surgery. Duodenal leakages occurred in 3 patients (7.1%), then treated with a conservative approach and resolved on the 10th postoperative day. Two patients (4.7%) had deep space infections in the first week after surgery, therefore subdiaphragmatic and pelvic abscess were drained by ultrasound guidance. Four patients (9.5%) died up to 30-day post-surgery due to progression of multisystem organ failure in absence of leakages or infections. All these patients were American Society of Anesthesiologists Classification >III and Boey Score 3. CONCLUSIONS: Our data show that a primary laparoscopic approach in patients with peptic ulcer perforation is associated with postoperative advantages and acceptable rates of morbidity and mortality, essentially related to high Boey Score. Therefore, we suggest that the surgical repair of PPU could be always started laparoscopically.

Pancreatic ductal adenocarcinoma in colonic wall: metastatic disease or cancerized pancreatic ectopic tissue?

We describe two unusual cases of cancerized ectopic pancreatic parenchyma within the wall of the left colon. Although the morphology of the neoplastic cells and their immunoprofile were consistent with pancreatic ductal adenocarcinoma, the detection of small foci of regular ectopic pancreatic tissue close to dysplastic glands at the periphery of the cancerized mass represented the key diagnostic features. A careful histological examination of surgical samples represents the correct approach to the diagnosis of this rare disease, mostly when total-body CT scan evaluation confirms the lack of bilio-pancreatic masses.

An unusual case of large endometrioma within the rectus abdominis muscle misdiagnosed as desmoid tumour.

We describe an unusual case of giant intramuscular abdominal endometrioma clinically misdiagnosed as desmoid tumour in a 36-year-old female patient with a one-year history of lower abdominal pain. Endometriosis is defined by the presence of endometrial tissue outside the uterine cavity, associated with fibrosis and inflammatory reaction. Although the abdominal wall is one of the most frequent sites of extra pelvic endometriosis, the localization in the anterior rectus abdominis muscle is unusual and associated with previous cesarean section. In most cases, the preoperative diagnosis is erroneous because the different imaging modalities are nonspecific but only useful in determining the extent of disease and in the planning of operative resection. A better acquaintance with the imaging presentation of abdominal wall endometriosis holds the potential of positively impact disease confirmation and may play a crucial role in the face of innovation in treatment. KEY WORDS: Desmoid tumour, Endometrioma, Surgery.