Immunoexpression of Ki67, P16 and Beta-catenin in precursor lesions of cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (CSCC) is the second most common type of skin cancer, after basal cell carcinoma, representing about 10-20% of all malignant skin tumors. The mortality rates of CSCC approach those of renal and oropharyngeal carcinomas, as well as melanoma, with the increasing of the risk once metastases and perineural invasion occur. Both actinic keratosis (AK) and Bowen's disease (BD) are direct precursors with the potential for progression to CSCC. In this study, we analyzed the expression of Ki67, P16 and Beta-catenin in the precursor lesions of CSCC in relation to histological prognostic parameters, respectively between them, with the aim of identifying possible correlations with a role in prognosis. Ki67 and P16 presented higher scores in advanced precancerous lesions, such as keratinocyte intraepithelial neoplasia (KIN) III and BD and low scores in seborrheic keratosis (SK). The immunoreactivity to the investigated markers confirms the multistage skin carcinogenesis, and their involvement starting from the initiation phase of the cancer process. The importance of the studied markers in the evolution and prognosis of precancerous lesions of CSCC is also supported by the linear correlations revealed between the immunoexpressions of P16, Ki67 and the membranous immunoexpression of Beta-catenin in AK.

Cutaneous Malignant Melanoma Metastatic to the Larynx and Trachea: A Case Report and Review of the Literature.

Malignant melanoma rarely develops in mucous membranes. Statistical data show that approximately 0.6-9.3% of patients with cutaneous malignant melanoma will develop metastases in the upper aerodigestive tract mucosa, and within these metastatic sites, the least common are the laryngeal and tracheobronchial ones. This exceedingly rare clinical entity has no clear treatment recommendations; radical surgery does not seem to benefit the patient in term of life expectancy. We present the case of a 56-year-old male patient diagnosed with laryngeal and tracheobronchial melanoma metastases. Prior to admission to our clinic the patient had a personal history of malignant melanoma of the nuchal region operated on 7 years ago, malignant melanoma of the gallbladder and metastatic left axillary polyadenopathy for which he underwent surgical treatment 3 months prior. Histopathological and immunohistochemical reports established the diagnosis of laryngeal metastasis of malignant melanoma. Genetic molecular analysis was positive for B-Raf (BRAF) gene and hence Vemurafenib was administered, with a favorable outcome at the one-year follow-up. Nevertheless, there are currently no clear universally accepted guidelines for the treatment of laryngeal melanoma, mainly due to the rarity of this clinical entity. We conducted a review of similar cases reported in the literature. Interestingly, reviewing the cases reported in the literature, it appears that laryngeal metastases of a primary cutaneous melanoma are more common in men, with an average time to metastasis of 4.3 years.

Entheseal involvement in a group of psoriatic arthritis patients: An ultrasonographic study.

Psoriatic arthritis (PsA) is an inflammatory potentially destructive disease that requires early diagnosis and therapeutic approach. Its main pathogenic event and the condition's hallmark is considered to be enthesitis. Clinical examination of the enthesis can be a challenge in the clinical practice; thus, ultrasonography (US) has emerged as an indispensable imaging tool for evaluating both structural and inflammatory changes of this structure. In the present study, we aimed to analyze the type and frequency of entheseal involvement in PsA patients by US examination, performing a retrospective study on 41 patients diagnosed with PsA. Ultrasonographically confirmed enthesitis, identified according to Outcome Measures in Rheumatology group (OMERACT, initially Outcome Measures in Rheumatoid Arthritis Clinical Trials) definitions, was present in 26 of the included patients, Achilles enthesis being the most common site involved. The prevalence of tendon structure abnormalities and the presence of entesophytes underlines the importance of chronic inflammation on entheseal sites. US examination has proven to be a reliable imaging method, with significant and continuous improvement, which is clearly a requisite part for current understanding and diagnosis of enthesitis and more than this, for the patient follow-up algorithm.

Vulvar Verrucous Carcinoma and Genital Condylomatosis.

Verrucous carcinoma is a histopathological type of well-differentiated squamous cell carcinoma, clinically characterized by slow and continuous growth, having a local destructive character, but low metastasis potential. Condyloma acuminatum is a sexually transmitted infection caused mainly by subtypes 6 and 11 of HPV, with subtypes 16, 18 being involved in malignant transformation. We present the case of a 70-year-old woman, hospitalized for a vulvar and perineal vegetative, ulcerated, bleeding tumor, with onset 20 years ago. The therapeutic option was surgical excision of the lesions and long-term oncological monitoring.

The perioperative effect of anesthetic drugs on the immune response in total intravenous anesthesia in patients undergoing minimally invasive gynecological surgery.

BACKGROUND: The specific mechanism of action of each anesthetic drug on the immune system is still incompletely known. It is important to know how the various anesthetics used in minimally invasive surgery (MIS) act on the inflammatory response because the choice of the anesthetic agent can influence the patient's immune system. AIM: Evaluation of the effect of anesthetic drugs used for total intravenous anesthesia (Propofol and Midazolam) on the inflammatory response after minimally invasive gynecological surgery. PATIENTS, MATERIALS AND METHODS: The inflammatory response in 20 female patients who underwent minimally invasive gynecological surgery under which intravenous anesthesia was performed. Depending on the combination of anesthetics used, we subdivided the study group into two groups, Group 1 consisting of the patients (n=10) who were given for total intravenous anesthesia, the combination with Midazolam+Fentanyl, and Group 2 (n=10) the patients who received the combination of Propofol+Fentanyl, respectively. Surgical interventional procedures included day surgery: diagnostic and operative hysteroscopy, endometrial ablation, surgical treatment of vulvar disorders. Serological profiling of patients was performed by dosing the serum concentration of nucleotide-binding domain (NOD) and leucine-rich repeat protein 3 (NLRP3) inflammasomes, interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), IL-10 before and two hours after the surgical procedure. RESULTS: In our study, we found that in both groups of patients (Midazolam+Fentanyl - Group 1, Propofol+Fentanyl - Group 2), NLRP3 and cytokines concentrations in the serum were higher after MIS than those before MIS. CONCLUSIONS: It appears that both Midazolam and Fentanyl and Propofol and Fentanyl have an immunomodulatory action due to the anti-inflammatory effect of both anesthetics. Therefore, anesthesiologists must choose an anesthetic method that uses individualized anesthetic agents, depending on the patient's immune status and disease.

E-cadherin, fibronectin and Slug immunoexpression in non-melanoma skin cancers.

Epithelial-mesenchymal transition (EMT) is an essential biological process involved in the initiation and progression of cancer by which epithelial tumor cells lose their differentiated characteristics, such as cell-cell adhesion and apical-basal polarity and acquire a more invasive and∕or metastatic mesenchymal phenotype. The present study investigated the expression of immunomarkers with a role in EMT of non-melanoma skin cancers (NMSCs), such as E-cadherin, fibronectin and Slug, for a number of 50 NMSCs, represented by 30 cases of basal cell carcinomas (BCCs) and 20 cases of squamous cell carcinomas (SCCs). For BCC, the statistical analysis of the investigated immunomarkers indicated significantly differences in relation to the depth of invasion, and for E-cadherin and fibronectin with the degree of risk. In the case of SCC, the statistical analysis indicated significant differences of E-cadherin and Slug with the degree of tumor differentiation, and for fibronectin and Slug with the depth of invasion. The analysis of the distribution for the percentage values of the investigated immunomarkers in the case of BCC indicated a significant negative linear relation between E-cadherin/fibronectin and E-cadherin/Slug, and in SCC a significant negative linear relation between E-cadherin∕fibronectin, E-cadherin∕Slug and a positive linear one in the case of fibronectin∕Slug. The study indicates through the statistically significant relation between E-cadherin∕fibronectin and E-cadherin∕Slug, the EMT intervention in carcinogenesis of NMSC.

Clinical, histopathological and immunohistochemical study of keratoacanthoma.

Keratoacanthoma (KA) is an epithelial tumor of the skin, classically considered as having a malignant transformation risk of 15%; however, many authors and the new World Health Organization (WHO) Classification of skin tumors consider KA as an incipient variant of the cutaneous squamous cell carcinoma (SCC). The aims of the study were to assess the clinical, histopathological (HP) and immunohistochemical (IHC) aspects of the KA and the role of these factors in malignancy occurrence. The studied group comprises 194 patients diagnosed with KA or malignant KA, hospitalized in the Clinic of Dermatology, Emergency County Hospital, Craiova, Romania, between 2006 and 2019. There were 83 males and 111 females, aged 34 to 90 years, 57.21% of the patients being from the rural environment. The histopathology diagnosed 51 KAs and 143 malignant KAs (SCCs). Clinical diagnosis had a limited value in detecting the absence or presence of malignancy in the KA lesion, due to a low accuracy (36.08% and 29.89%, respectively) and specificity (23.07% and 27.02%, respectively); therefore, the HP exam of the surgical excision specimen has a paramount importance in establishing the diagnosis. IHC analysis revealed that the immunostainings for apoptosis-associated proteins and keratinocyte proliferative activity [p53, B-cell lymphoma-2 (Bcl-2), Ki-67 and proliferating cell nuclear antigen (PCNA)] provide some arguments to differentiate between KA and SCC in the studied cases. The correlation of clinical, HP and IHC data lead to an accurate diagnosis of KA; moreover, the clinical, HP and IHC data sustain the idea that KA is a particular form of well-differentiated SCC, which require an active therapeutic attitude.

Involvement of inflammatory cells in chronic rhinosinusitis with nasal polyps.

Inflammation plays an important role in the pathogenesis of nasal polyps. Understanding the biomolecular action mechanisms of inflammatory elements can contribute to improving the prognosis of these lesions. The study analyzed the distribution and immunohistochemically quantified eosinophils [eosinophil major basic protein (BMK-13)], lymphocytes [cluster of differentiation (CD) 4, CD8, CD20] and plasmocytes (CD138) in both the epithelial and stromal compartment in relation to composite scores, which included specific histopathological parameters for 50 sinonasal polyps. Inflammatory elements predominated at stromal level, the high histological composite scores being frequently associated with increased expression of inflammatory elements. Also, the numerical distribution of inflammatory elements indicated positive linear relations within the groups BMK-13∕CD8 and CD4∕CD20∕CD138, and a negative linear relation between the two groups. This aspect can support the existence of alternative or sequential pathogenic mechanisms involved in the pathogenesis of sinonasal polyps, and the results obtained can be used for a better stratification of patients in order to optimize the therapy.

Stage IV duodenal GIST requiring emergency pancreaticoduodenectomy - diagnosis difficulties and therapeutic options.

This paper presents a very rarely encountered case of a 45-year-old female, admitted in our Surgical Clinic for upper digestive bleeding (repeated hematochezia). The upper endoscopy was negative, but the barium meal discovered an apparently extrinsic duodenal (D3) stenosis; abdominal ultrasound diagnosed a left liver mass suggesting a metastatic tumor. The hematochezia relapse, with hemodynamic instability imposed emergency surgery; on laparotomy, a bleeding tumor located on the duodenopancreatic region was discovered, and a pylorus-preserving pancreaticoduodenectomy (Traverso-Longmire) was performed. The histology and immunohistochemistry established the diagnosis of duodenal stromal tumor, CD34 and CD117 positive, with an estimated progression risk of 34%. The postoperative evolution was favorable, the patient being alive, four years after the surgery.

Squamous esophageal carcinoma and mucinous adenocarcinoma of the colon - an unusual association.

The existence of a simultaneous cancer of the esophagus and colon is a rare situation that recognizes an increased incidence in recent years in the world, probably as a result of the improved measures of diagnosis and treatment, as well as the development of screening programs. The aim of this work is to present a case of synchronous esophageal squamous carcinoma with mucinous adenocarcinoma of the hepatic angle of the colon. The patient was hospitalized to our Surgical Clinic with the thoracic squamous esophageal carcinoma diagnosis. On admission, symptoms were dominated by overall dysphagia, patient showing a weight loss of 10 kg for the last 30 days. Preoperative imaging tests did not revealed regional or distant metastatic disease. Preoperative colonoscopy was incomplete (only until the splenic angle of the left colon) due to the insufficient mechanical preparation. On laparotomy, a carcinoma of the hepatic angle of the colon, partially stenosing was discovered. An upper pole esogastrectomy with intrathoracic esogastrostomy and a right colectomy with ileotransversostomy were practiced, at the same operative session. Postoperative evolution was poor and the patient died on the ninth day from the surgery during an alcohol withdrawal crisis.

The sentinel lymph node (SLN) significance in colorectal cancer: methods and results. General report.

Colorectal cancer appears to be one of the most important malignancies in the world, with a survival rate depending on the TNM stage. The presence of lymph nodes metastasis indicates the necessity of adjuvant chemotherapy but exact classification of the N stage requires at least 12 lymph nodes to be pathologically examined. The sentinel lymph node (SLN) is considered to be the closest lymph node to the tumor, bearing the highest risk of malignant cells colonization. The main advantage of the sentinel lymph node mapping in colorectal cancer is identification and separate pathological examination of the nodes carrying the highest risk of metastasis. There are still open questions regarding the best method for sentinel lymph node mapping (in vivo or ex vivo), the factors influencing it, which substance is better for identification and which are the best histological methods and markers to be used. Numerous studies have discussed the quality and applicability of the method, but the importance of the SLN in colorectal carcinoma remains an open issue.

The immunohistochemical analysis of the proliferative activity and the maturity degree of lymphatic vessels in oral squamous cell carcinomas.

Oral cancers still represent a major health problem; regional lymph node metastases occur in 30-40% of head and neck squamous cell carcinomas and are associated with unfavorable prognosis and decreased survival. The study included 35 cases of oral squamous cell carcinomas (OSCC), which were analyzed by double reactions to determine the proliferative activity (anti-human D2-40/Ki67) and the maturity degree (anti-human D2-40/α-SMA) of lymphatic vessels, both intratumoral (IT) and in the advancing edge (AE), and in relation to clinicopathological prognostic parameters. The mean values of D2-40 lymphatic vessel density (LVD) were higher in AE then in IT level. Poorly differentiated carcinomas, T3/T4, presented the highest LVD values, both IT and in the AE. LVD was higher in advanced stages and metastasizing carcinomas. Ki67 was positive in all cases, Ki67 proliferation index (IP) indicated higher values in poorly differentiated carcinoma, T3/T4, metastasizing ones, both IT and in the AE. LVD and IP Ki67 showed a positive linear correlation. D2-40/Ki67-positive vessels were identified only at the AE or close to it. D2-40/Ki67 LVD had highest values in advanced stages carcinoma, with metastases. D2-40/α-SMA-positive vessels were identified only in the neighborhood of the tumor and LVD highest values were present in early-stage carcinomas and without metastases. A negative linear correlation between proliferation and maturity of the lymphatic vessels was found. The study indicated a strong association between lymphatic proliferative activity and lymph node metastases, suggesting the need for targeted antilymphangiogenic therapies in OSCC.

c-abl and YWHAZ gene expression in gastric cancer.

This study aims to determine the gene expression for c-abl and YWHAZ in gastric cancer and the differences between the c-abl and YWHAZ gene expression inside the tumor versus healthy tissue (at the resection edges). This prospective study included 34 patients with gastric neoplasia, 21 men and 13 women, aged between 49 and 79 years (65.5 years median). After the surgical procedure, in these cases, we collected two tissue samples: one sample was obtained from inside the tumoral tissue and another sample from the gastric tissue, which was identified as normal apparently, as far as possible from the tumor (resection edge). For determining the c-abl and YWHAZ gene expression, we used the quantitative real-time polymerase chain reaction. Regarding the c-abl gene expression in gastric cancer, c-abl expression was identified as lower inside tumor cells comparing to the normal gastric tissue (resection limit). This difference of gene expression emphasize the role of the c-abl gene in normal tissue growth and the involvement in apoptosis induction when alteration of DNA occurs, as a result to different agents actions as stress, ionizing radiations. The loss of expression or even the down-regulation of the c-abl is a fundamental event that leads to genesis and progression of tumors. No significant differences of the YWHAZ gene expression between the tumoral and normal gastric tissue probes were recorded in our study.

Extrarenal retroperitoneal angiomyolipoma with unusual evolution.

The aim of this paper is to present the case of an extrarenal retroperitoneal angiomyolipoma with unusual evolution, due to the herniation through the inguinal canal, determining an extraperitoneal hernia. A ureteral duplicity and associated hydronephrosis contributed to the peculiarity of the case. The case was operated (en block tumor and right kidney removal), the postoperative evolution being favorable at seven years after the surgery.

Cutaneous mastocytosis, problems of clinical diagnosis of four cases.

Mastocytosis is a rare disease characterized by a pathological increased of mast cells in one or more tissues, particularly in the skin, bone marrow, liver, spleen, lymph nodes and gastrointestinal tract. Cutaneous mastocytosis represents over 90% of cases found with predilection in children. The aim of the paper was to summarize the authors' clinical, histopathological and immunohistochemical observations on patients with cutaneous mastocytosis. We present four cases of cutaneous mastocytosis, sporadic form, customized by clinical presentation and age of onset: two installed in the neonatal period, a case with onset in infancy and another in adulthood. For the assessment of the severity and the effectiveness of the treatment, we used SCORMA Index. We performed in each patient histopathological examination of the skin (Hematoxylin-Eosin and Giemsa stains), the dosage of mediators (serum tryptase level, serum histamine levels, urinary histamine metabolites) and the balance of expansion (complete blood cell count, liver biological investigations, abdominal ultrasound, skeletal radiography, chest radiography). For the adult with mastocytosis, we performed abdominal scanner and cytological study of the bone marrow. Following investigations carried out in each case, we mentioned the diagnosis of cutaneous mastocytosis, and also excluded several diseases confounded by clinically and histologically aspect. Considering the fact that the balance expansion was negative, we excluded the diagnosis of systemic mastocytosis. The presence of anemia and protein energetic malnutrition in children with mastocytosis involves carrying out balance extension for the exclusion of a systemic form of the disease. Histopathological examination of the skin using special stains, the dosage of mediators (serum tryptase level, serum histamine levels, urinary histamine metabolites) and balance expansion establish the diagnosis of cutaneous mastocytosis and also exclude many confusions because of the clinical presentation.

Histopathologic features of Spitzoid lesions in different age groups.

Spitz nevus is one of the most difficult melanocytic lesions to diagnose in regard of malignancy, even for experienced dermatopathologists. We analyzed 28 tumors with Spitzoid morphology from 15 children (three little children 2-4-year-old, 12 peripubertary children 9-17-year-old) and 13 adults; there were 21 Spitz nevi, five atypical Spitz tumors and two Spitzoid melanomas in order to establish the diagnostic value of several morphologic parameters in different age groups. No significant differences in respect of age and/or tumor type occurred for gender, location, dimension, symmetry, sharp lateral demarcation, junctional nests orientation, adipose tissue extension, side-to-side cytologic symmetry, uniform melanin deposits, nuclear pleomorphism, presence of mitoses, inflammation and epidermal alterations. Pagetoid growth and/or melanin deposits in the keratin layer were significantly higher in little children. In adults, presence of isolated cells within the lateral margins allows differentiating Spitz nevus from atypical Spitz tumor and Spitzoid melanoma. Deep located mitoses were statistically associated with Spitzoid melanoma in adults. Ulceration was statistically more frequent in peripubertary patients than in adults, probably due to trauma. In conclusion, presence of worrisome morphologic features (pagetoid growth, isolated cells within the lateral margins or ulceration) is correlated to patient's age and less to tumor type; there is no unique morphologic feature to relay on when evaluating a Spitzoid tumor, the final diagnosis being the results of interpretation of multiple clinical, morphologic, immunohistochemical and molecular data and not least dermatopathologist's personal experience.

The prognostic value of the immunohistochemical aspects of tumor suppressor genes p53, bcl-2, PTEN and nuclear proliferative antigen Ki-67 in resected colorectal carcinoma.

UNLABELLED: This study aim was to identify the relations between tumor suppressor genes (p53, bcl-2, PTEN), nuclear proliferative antigen Ki-67 and epidemiologic, morphologic and histologic patient related factors, in colorectal cancer. MATERIALS AND METHODS: Twenty-two prospectively collected colorectal cancer resection specimens were histologically prepared, using standard paraffin-embedded and Hematoxylin-Eosin staining method; for immunohistochemical study, the Streptavidin-Biotin (sABC)/Horseradish Peroxidase (HRP) method was used. RESULTS: P53 was positive in 86.36% of cases, more intense (>50%) in rectal cancer and in women 59.16 ± 9.49-year-old; the G1/2 adenocarcinoma was dominant. Bcl-2 was positive in 18.18% of the cases, in distal colorectal cancer, only in men, 63.5 ± 13.2-year-old. PTEN was positive in 95.45% of the cases; intense positivity was recorded in 12 men and six women, 61.47 ± 11.67-year-old, in rectal topography. Ki-67 was positive in 86.36% of the cases, more intense in four men and four women, 63.45 ± 12.22-year-old, in proximal and advanced colorectal cancers (pT3N1/2 - 62.5%). CONCLUSIONS: Tumor suppressor genes mutations are often present in colorectal cancer; the intensity of the expression of these mutations varies, which could explain the different prognosis for these patients.

The value of the histopathologic examination in the diagnosis and management of the actinic keratosis.

Actinic keratosis, considered lately as an intraepithelial squamous cell carcinoma in evolution, are powerful predictors of the risk for developing a cutaneous carcinoma and melanoma. The aims of the study were to establish the value of the histopathologic examination as a confirmation method for the actinic keratosis diagnosis, to assess the percentage of these lesions that suffer a malignant transformation, and also the frequency of the association between actinic keratosis and cutaneous carcinomas. This is a retrospective study, performed on 208 patients diagnosed with different types of cutaneous precancers, hospitalized in Dermatology Clinic of Craiova, Romania, between 2006 and 2010. Actinic keratosis represented 37.93% (79 cases) of all cutaneous precancers (the most frequent cutaneous precancer). Patient's age ranged from 17 to 85 years, 54.8% of the patients being from rural environment; 86.07% of the lesions were located on the solar exposed skin (head and face). 72.16% of the actinic keratosis was clinical subdiagnosed. The most frequent form was hypertrophic actinic keratosis (89.06%); in 18.98% of cases, malignant transformation in squamous cell carcinoma was noticed. Actinic keratosis represent 86% of the precancers that associate a carcinoma, basal cell carcinoma being diagnosed the most frequent. In conclusion, actinic keratosis are the most frequent cutaneous precancer, diagnosed in chronic sun-exposed patients, and manifest a tendency to progress into a squamous cell carcinoma without a proper treatment. Pathologic evaluation is mandatory to an accurate assessment of the actinic keratosis prevalence, and for the right management of these lesions.