Banu Yaman

Expression of matrix metalloproteinase‐9 in predicting prognosis of hepatocellular carcinoma after liver transplantation

Matrix metalloproteinases (MMPs) are known to play an important role in cell migration during cancer invasion by degrading extracellular matrix proteins. This study aimed to determine the role of MMP‐9 in hepatocellular carcinoma (HCC) carcinogenesis. Eighty‐nine cases who underwent liver transplantation for HCC in cirrhotic liver were selected for this study. The tumor characteristics such as nodule number, maximal diameter, portal vein invasion, and the preoperative alpha‐fetoprotein levels were reviewed. The intensity of immunostaining and the percentage of immunoreactive cells with MMP‐9 were evaluated. All patients were evaluated for HCC recurrence and/or death, and cause of death was noted. There was a lower survival and more recurrence risk among participants with 4 or more nodules exceeding 3 cm in diameter, with poorly differentiated tumor, and with large‐vessel involvement. Eleven patients developed recurrent HCC (12.4%). Twelve patients died as a result of HCC (13.5%). Among 89 HCCs, the incidences of a weak (+) and moderate (++) expression of MMP‐9 in carcinoma cells were 30.3% (23/89) and 43.8% (39/89), respectively. Increased expression and intensity of MMP‐9 were found to be inversely associated with poor tumor differentiation (P = 0.016, P = 0.009, respectively). A significant correlation between expression and intensity of MMP‐9 and large vascular invasion (P = 0.01, and P = 0.03) was also observed. As far as prognosis is concerned, increased immunoreactivity and intensity of MMP‐9 were found to exert an unfavorable impact on overall survival rates (P < 0.01, P = 0.01, respectively) and recurrences (P = 0.001, P = 0.02). Multivariate analyses revealed that MMP‐9 staining percentage (P = 0.007) and portal vein invasion (P = 0.002) were independent predictors of survival, whereas the only independent predictor of recurrences was portal vein invasion (P = 0.007). In this study, our results indicate a positive association between MMP‐9 expression and histopathologic parameters that indicate poor prognosis. We conclude that together, MMP‐9 staining percentage and portal vein invasion in HCC may aid to predict poor outcome. Nevertheless MMP‐9 staining percentage is expected to be a potential predictive marker on survival and needs to be studied more in detail. Liver Transpl 16:621‐630, 2010.

Clinicopathological characteristics and mutation profiling in primary cutaneous melanoma.

Background:The incidence of mutations in malignant melanoma varies remarkably according to the subtype of melanoma, and this in itself is affected by racial and geographical factors. Studies screening melanoma case series for different types of mutations are relatively rare. Method:The authors analyzed the frequency of various somatic point mutations of 10 genes in 106 primary cutaneous melanoma cases. The mutations (BRAF, NRAS, KIT, CDKN2A, KRAS, HRAS, PIK3CA, STK11, GNAQ, CTNNB1) were evaluated with real-time PCR-based PCR-Array through allele-specific amplification, and the results were correlated with various clinicopathological characteristics. Results:Mutations were found in 64.2% of the melanomas overall. BRAF (42.5%), NRAS (15.1%), and CDKN2A (13.2%) were the 3 most common mutations. BRAF and NRAS mutations were more frequent in nodular and superficial spreading melanomas (P < 0.001). Associations with BRAF mutation were as follows: male gender [odds ratio (OR) = 2.4], younger age (OR = 2.7), superficial spreading (OR = 15.6) and nodular melanoma (OR = 9.5), trunk localization (OR = 6.3), and intermittent sun exposure (OR = 4.6). A considerable percentage of V600K (44.4%) mutations were found among the BRAF mutations, whereas KIT mutations (3.8%) were less frequent. Multiple mutations were detected in 13.2% of the melanomas. The most common co-occurrences were in the BRAF, NRAS, and CDKN2A genes. Conclusions:The authors analyzed 10 somatic mutations in the main subtypes of primary cutaneous melanomas from the western region of Turkey. Mutations were found in 64.2% of the melanomas overall. The most common mutations were in the BRAF and NRAS genes. In addition to other less common mutations, a notable number of multiple mutations were encountered. The multiplicity and concurrence of mutations in this study may provide further study areas for personalized targeted therapy.

Biliary intraductal papillary mucinous neoplasia: three case reports

Intrahepatic cholangiocarcinoma is subdivided as mass-forming, periductal-infiltrating, and intraductal-growing types. Intraductal-growing type is an entity described in recent years as mucin-producing intrahepatic cholangiocarcinoma or intrahepatic (biliary) intraductal papillary mucinous neoplasia (b-IPMN). b-IPMN is classified as adenoma, borderline tumor, carcinoma in situ, and carcinoma, from benign to malignant. Using a different classification, b-IPMNs are subdivided into intestinal, pancreatobiliary, gastric, or oncocytic based on morphology of the cells forming the lesion and expression of MUC1, MUC2, and MUC5 gene proteins in the mucin family. The clinical and histopathological features of b-IPMN diagnosed in three cases are presented herein. Case 1 was classified as borderline. Case 2 was diagnosed as carcinoma in situ. Case 3 had large invasive areas, and was diagnosed as carcinoma. In all three cases, immunohistochemical investigation revealed MUC1 and MUC5AC to be positive, and MUC2 to be negative. We present herein three cases diagnosed with the clinical and pathological findings of a new entity in the literature, b-IPMN, and we discuss the macroscopic, histological, and immunohistochemical features.

BRAF-V600 Mutation Heterogeneity in Primary and Metastatic Melanoma: A Study With Pyrosequencing and Immunohistochemistry.

Background:The BRAF-V600 mutation is the most common mutation in cutaneous melanomas and is currently considered a target mutation when planning treatment for metastatic melanoma patients. Various techniques are used to determine the mutation status. The aim of this study was to determine the BRAF-V600 mutation status in primary and metastatic foci of melanoma cases and the consistency between the results of immunohistochemical and molecular methods. Methods:A total of 48 primary or metastatic cases were included in the study. Pyrosequencing was used as the molecular method and the VE1 antibody for immunohistochemical evaluation when determining the BRAF-V600 mutation. Results:The BRAF-V600 mutation was found in 75 of the 96 tumors (78.1%) from the 48 cases. V600E and V600K were present in 60 and 10 tumors, respectively, whereas V600R and V600M were present in 2 tumors and V600G in 1 tumor. There was no mutation in 5 metastases (12.8%) of the 39 cases with a V600 mutation in the primary tumor and no mutation in the primary tumor of 2 of the 36 cases (5.6%) with the V600 mutation in the metastasis. Fifty-six tumors were immunohistochemically positive where a V600E mutation was detected with pyrosequencing. Wild-type tumors (n = 20) and tumors with non-V600E mutations (n = 15) on pyrosequencing were immunonegative with VE1. The sensitivity and specificity of immunohistochemistry were 93.3% and 97.2%, respectively. Conclusions:In conclusion, BRAF-V600 mutation inconsistencies of up to 14.5% can be seen between the primary and metastatic foci in melanoma cases. These findings should be taken into account when planning targeted therapy and deciding on treatment responsiveness/unresponsiveness. An immunohistochemical method can be used as the first step to detect a BRAF-V600 mutation but additional molecular methods should be used when immunohistochemistry results are negative.

Long-term Follow-up of Positive Surgical Margins in Basal Cell Carcinoma of the Face.

BACKGROUND Basal cell carcinoma (BCC) in central facial locations and tumors with positive margins are at a higher risk of recurrence. The most effective treatment is total excision, which includes an adequate pathological margin. OBJECTIVE To evaluate the outcome of the patients who underwent surgery for BCCs of the head and neck and of those who had positive surgical margins where Mohs surgery is not available. METHODS This study was conducted at Ege University Medical School between 2004 and 2014. One hundred thirty patients with 154 BCC who underwent surgical excision were included. In the histopathologic report, the existence of positive margin, BCC subtype, localization of the tumor, and distance of margins to the tumor were evaluated. RESULTS Twenty-three lesions (14.9%) of 22 patients revealed positive surgical margins. Six patients (26.1%) had recurrences on the surgical site. The BCC subtypes of recurrent patients were reported to be multifocal superficial in 2 (33.3%), infiltrative (16.7%) in 1, and micronodular (50%) in 3. CONCLUSION Patients with superficial multifocal or micronodular tumors should undergo reoperation because of high recurrence rates.

A rare human‐to‐human transmission of orf

the dose was then tapered gradually. However, polyarthralgia recurred after two years of treatment. Löfgren’s syndrome, an acute form of sarcoidosis, is characterized by erythema nodosum, bilateral hilar lymphadenopathy, and arthralgia. It is a common form of sarcoidosis in Caucasian populations but not in Japanese subjects. It is usually a self-limiting disease, becoming inactive within the first two years. Patients with this syndrome may have arthralgia, requiring NSAIDs, but corticosteroids are rarely required. In addition, the presence of erythema nodosum is a predictor of good prognosis in patients with sarcoidosis. However, some patients with Löfgren’s syndrome are resistant to NSAIDs and show a chronic course. In the present case, symptoms persisted despite treatment with NSAIDs. Histopathological confirmation is important in establishing the diagnosis of sarcoidosis, including Löfgren’s syndrome, particularly if corticosteroid treatment is considered. It is necessary to exclude the possibility of diseases such as lymphoma, tuberculosis, fungal infection, berylliosis, and other conditions associated with hilar lymphadenopathy. Careful physical examination may reveal skin lesions suggestive of granulomatous lesions. More frequently, an asymptomatic myopathy is present in patients with Löfgren’s syndrome and other forms of sarcoidosis. The myopathy is frequently associated with systemic involvement, although the link with specific organ damage is not known. Muscle biopsies in patients with sarcoidosis are useful for histological confirmation of granulomatous inflammation despite the absence of muscle symptoms. It has been recommended to biopsy the gastrocnemius muscle, which has a diagnostic yield of 20–75%. We used high-frequency sonographic imaging for evaluation of myopathy and performed muscle biopsy based on these findings. High-frequency sonography is frequently used for evaluating the thickness of skin tumors in dermatology. As muscle biopsy is an invasive surgical procedure, accurate evaluation of muscle condition before the biopsy is essential to minimize patient discomfort. High-frequency sonography is a useful means of detecting muscle alterations, even in patients with no symptoms, and thus allows us to determine biopsy sites precisely. Atsuko Ohashi, MD Hiroshi Koga, MD Koichi Hayashi, MD, PhD Hisashi Uhara, MD, PhD Ryuhei Okuyama, MD, PhD Department of Dermatology Shinshu University School of Medicine Matsumoto Japan E-mail: rokuyama@shinshu-u.ac.jp

Primary Systemic Al Amyloidosis Presenting as Temporal Arteritis

Temporal arteritis is most common vasculitis in elderly and imitated by miscellaneous disorders. Temporal artery biopsy is the gold standard test in the diagnosis of giant cell arteritis (GCA). Hereby, we describe a case of a 67-year-old man who presented initially with temporal arteritis; however, a lip biopsy then revealed AL amyloidosis. In this respect, temporal artery biopsy should be performed for definitive diagnosis of GCA particularly patients with systemic symptoms and treatment resistant.

Choroidal malignant melanoma with no extraocular extension presenting as orbital cellulitis

ABSTRACT This report describes a patient with choroidal malignant melanoma presenting as orbital cellulitis without extraocular tumor extension. It is an interventional case report with histopathologic correlation. A 68-year-old male presented with a 3-day history of painful hyperemia and swelling in the right eye. The examination showed edematous eyelids, mechanical ptosis and chemosis with conjunctival injection. B-scan ultrasonography showed a mass with medium level echogenicity that filled the vitreous cavity. Magnetic resonance imaging showed a solid choroidal mass with hemorrhagic and inflammatory changes with no obvious extraocular extension. Due to these suggestive findings of choroidal melanoma the right eye was enucleated. A spindle cell choroidal melanoma including intense pigmentation and necrosis was confirmed by histopathological examination. Although rare; choroidal melanoma may present as orbital cellulitis, particularly when the tumor is necrotic.

Expression of p63, TTF-1 and Maspin in Non-Small Cell Lung Carcinoma and Their Effect on the Prognosis and Differential Diagnosis.

Abstract Objective: Lung cancer is still the leading cause of cancer mortality. Antiapoptotic genes and protease inhibitors play an important role in the development of lung cancer. Material and Method: p63, TTF-1 and maspin expression and their role in the differential diagnosis, overall survival, progression-free survival and other clinicopathological characteristics of the patients were investigated in 80 surgically-resected non-small cell lung carcinomas. Results: The maximal tumor diameter range was 1.5-11 cm (mean: 4.06±1.8 cm). Forty-five (56.3%) tumors were adenocarcinoma, 23 (28.8%) squamous cell carcinoma, four (5%) large cell carcinoma, six (7.5%) large cell neuroendocrine carcinoma, one (1.2%) sarcomatoid carcinoma while one was (1.2%) both adenocarcinoma and squamous cell carcinoma. The patients with advanced TNM stage and a tumor diameter more than 3 cm had markedly poor survival. Immunohistochemically, p63 staining was present in 87.5% of squamous cell carcinomas, 4.3% of adenocarcinomas, 25% of large cell carcinomas, and 16.7% of large cell neuroendocrine carcinomas. Similarly, maspin was positive in 66.7% of squamous cell carcinomas and 17.4% of adenocarcinomas. The TTF-1 staining rate was higher in adenocarcinomas (84.8%). There was no immunoreactivity in squamous cell carcinomas (p<0.001). We found that p63 and TTF-1 had no significant effect on survival in either tumor group (p>0.05) while maspin has a negative prognostic effect in adenocarcinoma (p=0.048). Conclusion: This study suggests that p63 and TTF-1 are reliable markers in non-small cell lung carcinoma and can be used in differential diagnosis. Maspin has been identified as a prognostic marker in adenocarcinoma. However, more studies are required to elucidate the significance of maspin. Öz Amaç: Akciğer kanseri, kanser ölümlerinin önde gelen nedenlerindendir. Antiapopitotik genler ve proteaz inhibitörleri akciğer kanseri gelişiminde önemli role sahiptir. Gereç ve Yöntem: Seksen opere küçük hücreli dışı akciğer karsinom olgusunda p63, TTF-1 ve maspin ekspresyonunun ayırıcı tanıya olan katkıları, sağkalım ve hastalıksız sağkalım üzerine etkileri ve diğer klinikopatolojik özellikler değerlendirildi. Bulgular: Ameliyat materyallerinde izlenen tümörlerin çapları 1,5-11 cm arasında (ort. 4,06±1,8) olup, 45 (%56,3) adenokarsinom, 23 (%28,8) skuamöz hücreli karsinom, dört (%5) büyük hücreli karsinom, altı (%7,5) büyük hücreli nöroendokrin karsinom, bir (%1,2) sarkomatoid karsinom ve bir (%1,2) adenokarsinom ve skuamöz hücreli karsinom birlikteliğinden oluşmakta idi. İleri TNM evreli ve üç cm’den daha büyük tümör çapı olan olgular daha kötü prognozlu idi. İmmünohistokimyasal incelemede skuamöz hücreli karsinomların %87,5’i, adenokarsinomların %4,3’ü, büyük hücreli karsinomların %25’i ve büyük hücreli nöroendokrin karsinomların %16,7’si p63 ile pozitif boyandı. Benzer olarak maspin de skuamöz hücreli karsinomlarda %66,7 ve adenokarsinomlarda %27,4 oranında pozitifti. TTF-1 ekspresyonu, adenokarsinomlarda oldukça yüksek oranda idi (%84,8). Skuamöz hücreli karsinomlarda immünreaktivite izlenmedi (p<0.001). p63 ve TTF-1, her iki tümör grubunda sağkalım üzerine etkili değil iken, maspin immünreaktivitesi adenokarsinomlarda kötü prognostik faktör idi (p=0,048). Sonuç: Çalışmamızda, p63 ve TTF-1’in küçük hücreli dışı akciğer karsinomlarında güvenilir belirleyiciler oldukları ve ayırıcı tanıda kullanılabilecekleri gösterildi. Maspinin adenokarsinomlarda prognostik bir belirleyici olduğu saptandı. Ancak maspin ile ilgili tüm çalışmalar henüz net değildir ve daha fazla çalışmaya ihtiyaç duyulmaktadır.

The diagnostic value of cell blocks in Liquid-Based Cytology of bronchial aspiration and bronchial brushing materials

Fibreoptic bronchoscopy is used for the diagnosis and treatment of several pulmonary diseases. Conventional smear and Liquid‐based cytology (LBC) methods are applied to cytology samples of various bronchoscopic techniques. If the cytology sample is sufficient for evaluation, a cell block (CB) can be prepared from the remaining material. The aim of this study is to identify the diagnostic value of conventional smear, LBC and CB methods in bronchial cytological specimens.