[Causes of mediastinal/hilar granulomatous lymphadenitis]. / Mediastinal/hiler granülomatöz lenfadenit etyolojisi.

INTRODUCTION: Granulomatous lung disease (GLD) is caused by a wide range of conditions and it is challenge for pulmonologist. A detailed history of exposures is fundamental in GDL and has been found pivotal to reach a precise diagnosis. MATERIALS AND METHODS: Between September 2014 and December 2016, the distribution of patients diagnosed with granulomatous lymphadenitis in the mediastinal/hilar lymph nodes by endobronchial ultrasound (EBUS) or mediastinoscopy was analyzed. To be listed as 'confident', a diagnosis of sarcoidosis required compatible histological, radiological and clinical findings in conjunction with negative cultures. Infectious entities listed as 'confident' had either microorganisms in tissue section, positive culture, positive serology or positive antigen detection in a consistent clinical pathological setting. RESULT: Granulomatous lymphadenitis was detected in 110 patients. The included 110 cases consisted of 70.9% women and median age of 53 (range 44-61) years. The final diagnosis of the patients was accepted to be sarcoidosis in 79 (71.8%), sarcoid like granulomas in 7 (6.4%), tuberculosis in 4 (3.6%), silicosis in 4 (3.6%), drug-associated granuloma in 2 (1.8%), hypersensitivity pneumonitis in 1 (0.9%), Chron disease in 1 (0.9%), unspecified in 12 (10.9%). Three patients were classified as tuberculosis based on culture. CONCLUSIONS: In this study, we found that the most common cause of granulomatous lymphadenitis was sarcoidosis. Contrary to expectations, the number of patients diagnosed with tuberculosis was very low.

Nuclear morphometric findings in undetermined cytology: A possible clue for prediction of BRAF mutation in papillary thyroid carcinomas.

PURPOSE: To investigate the possible relationship between the nuclear morphometric characteristics (nuclear perimeter, roundness, nuclear area, and nuclear shape) and BRAF mutation status in papillary thyroid carcinoma cases with a prior diagnosis of undetermined cytology. MATERIALS AND METHODS: Total thyroidectomy specimens obtained from 48 patients with papillary thyroid carcinoma with a prior diagnosis of undetermined cytology were included. Morphometric analysis under light microscopy included measurements of the perimeter, shape factor, nuclear area, and roundness of thyrocyte nuclei from the cytological smear preparations. Mutational analysis, including immunohistochemistry and polymerase chain reaction, was performed in formalin fixed paraffin embedded tissue blocks. RESULTS: BRAF V600E mutation was detected in 7 of 48 cases (14.5%). The nuclear perimeter and nuclear area in mutated cases were significantly higher than the wild type (p = 0.005). Shape factor (p = 0.681) and roundness (p = 0.752) values did not significantly differ between the wild-type and mutant groups. No significant relationship was evident between BRAF expression and BRAF point mutation. CONCLUSION: In cases with positivity for BRAF mutation, the nuclear perimeter and nuclear area were significantly increased. These findings suggest that morphometric variables are predictive markers for papillary thyroid carcinoma cases with positivity for BRAF mutation. However, further trials on larger series are warranted to understand the significance and predictive value of nuclear morphometric analysis in these circumstances.

[Bilateral total lung lavage in a patient with pulmonary alveolar proteinosis]. / Pulmoner alveoler proteinozisli hastada iki tarafli total akciger lavaji.

Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disease characterised by alveolar accumulation of surfactant composed of proteins and lipids. Three main categories of PAP have been defined depending on the aetiology: primer/idiopathic, neonatal/congenital, secondary and exogenous/environmental exposure. Radiologically diffuse ground glass opacities, interlobular and intralobular septal thickening is seen. Although open lung biopsy is accepted as the gold standard in diagnosis, it can be diagnosed by showing bronchoalveolar lavage (BAL) fluid with a milky appearance and periodic acid-schiff (PAS) positive globules in biopsy with clinical and radiological findings. Theraphy for PAP are supportive care (oxygen), total lung lavage, inhale/subcutaneous granulocyte macrophage colony stimulating factor (GM-CSF), rituximab, plasmapheresis, lung transplantation. We report a case of PAP presented with cough and shortness of breath, diagnosed with BAL and transbronchial lung biopsy, treated by total lung lavage by reviewing literature.

Comparison of Microsatellite Instability With Clinicopathologic Data in Patients With Colon Adenocarcinoma.

Background Microsatellite instability (MSI) is a genetic condition caused by errors in DNA repair genes that cause colorectal cancer (CRC). The literature contradicts the frequency of MSI in sporadic CRCs and its effect on prognosis. This study investigated the distribution of clinicopathologic features and the relationship between MSI and survival outcomes. Methodology This is a retrospective study of 101 consecutive cases of CRC and immunohistochemical studies. All cases were retrospectively reviewed and reevaluated by histological grade, lymphovascular invasion, perineural invasion, tumor borders, dirty necrosis, tumor-infiltrating lymphocytes (TILs), Crohn's-like lymphoid reaction, mucinous and medullary differentiation, and tumoral budding from pathological slides. An immunohistochemical study was performed in appropriate blocks for using MLH-1, MSH-2, MSH-6, and PMS-2. We collected the clinical stage, pathological tumor stage, lymph node metastasis, age, sex, tumor diameter, distant metastasis, localization, and survival information from patients' clinical data. Results There was no statistically significant difference between the two groups regarding age, gender, tumor diameter, histological grade, tumor border, dirty necrosis, TILs, N and M stage, perineural and lymphovascular invasion, mucinous differentiation, medullary differentiation, and tumor budding characteristics of the patients. The MSI-H group was more frequently located in the right colon and transverse colon (p < 0.001), and the T stage was higher among them than in the MSI-L group (p = 0.014). Upon multivariate regression analysis, MSI status had no significant effect on survival time. Age and stage N and M were independent prognostic factors for colon cancer prognosis. Conclusions Our study presented the distribution of clinicopathological features and their relationship with MSI for 101 regional CRC patients. MSI status was detected by immunohistochemistry. Identifying MSI in CRCs may help personalize therapy planning. As the distribution of the features may vary from population to population, further investigations are needed on this topic.

Is there any way to protect from tacrolimus-induced renal and pancreas injury?

BACKGROUND: The aim of this study was to explore effects of erythropoietin and pentoxifylline in tacrolimus-induced pancreatic beta cell and renal injury in rats. METHODS: Rats in group I were given saline; rats in group II were injected with tacrolimus; rats in group III were received erythropoietin (Epo) and tacrolimus; while rats in group IV were injected pentoxifylline (Ptx) plus tacrolimus for nine d. On 10th day, blood and tissue samples were taken for biochemical and pathological evaluations. RESULTS: Tacrolimus-injected animals exhibited significant elevation in blood urea nitrogen (BUN), and serum BUN levels were improved in rats pretreated with Ptx. Significantly more apoptotic nuclei were observed in kidneys of tacrolimus group. In rats subjected to tacrolimus and pretreated with Epo, there was significant decrease in apoptotic nuclei staining than those in tacrolimus group. Blood trough levels of tacrolimus were significantly higher in erythropoietin-pretreated group, although same amount of tacrolimus was injected with other groups. CONCLUSION: Results of our study demonstrated significant antiapoptotic effects of erythropoietin on renal tubules, increasing effect of erythropoietin on tacrolimus blood levels, and insignificant antioxidant effects of both erythropoietin and pentoxifylline on renal and pancreas tissues. Study with clinically greater tacrolimus levels may be useful to confirm these findings.

Protective effect of the grape seed proanthocyanidin extract in a rat model of contrast-induced nephropathy.

AIM: Contrast-induced nephropathy (CIN) is a common cause of hospital-acquired acute renal failure. Although it is so common, there has been no approved therapy yet. We aimed to investigate the effect of grape seed proanthocyanidin extract (GSPE) on preventing CIN. MATERIALS AND METHODS: 24 rats were divided into four groups as control group, GSPE group, contrast medium (CM) group, and CM+GSPE group. The experiment was discontinued on the ninth day. Blood samples were obtained for the measurement of renal function parameters. Renal tissues of the rats were removed for the analysis of oxidative system parameters. In addition to renal histopathology, transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) was performed to determine apoptosis. RESULTS: There was a significant increase in BUN, creatinine, malondialdehyde (MDA) levels, apoptotic index (AI) and histopathological alteration in the CM group as compared to the control group. Furthermore, BUN, creatinine, MDA, total oxidant system and oxidative stress index levels, AI as well as renal histopathological alteration were significantly decreased in the CM+GSPE group. CONCLUSION: For the first time in the literature, we showed that GSPE provided biochemical and histopathological improvement in CIN. Our findings revealed that this improvement was associated with the decrease in oxidative damage and apoptosis.

Anti-apoptotic and anti-oxidant effects of grape seed proanthocyanidin extract in preventing cyclosporine A-induced nephropathy.

AIM: Although the pathogenesis of cyclosporine (CsA) nephropathy is not completely understood, it is attributed to oxidative damage and apoptosis. Grape seed proanthocyanidin extract (GSPE) is a molecule with anti-oxidant and anti-apoptotic properties. Our aim was to demonstrate the effects of GSPE in preventing CsA nephropathy. METHODS: Twenty-four Sprague-Dawley rats were divided into four groups. The control, GSPE, CsA and CsA+GSPE groups were given 1 mL olive oil, 100 mg/kg GSPE, 25 mg/kg CsA and 100 mg/kg GSPE+25 mg/kg CsA, respectively. On day 21, blood samples were taken for blood urea nitrogen (BUN), creatinine and CsA levels, and renal tissue was used for total oxidant system (TOS), total anti-oxidant system (TAS), oxidative stress index (OSI) and malondialdehyde (MDA) measurements. In addition to renal histopathology, apoptosis staining was performed on renal tissue. RESULTS: The BUN, creatinine, TOS, OSI, MDA, histopathological score, and apoptotic index exhibited increases in the CsA group. In the CsA+GSPE group, however, BUN, creatinine, OSI, MDA, renal histopathological score and apoptotic index (AI) decreased and TAS levels increased. In addition, there was no difference between the CsA and CsA+GSPE groups with regard to CsA levels. CONCLUSION: We demonstrated that GSPE prevents CsA nephropathy and that this effect is achieved by anti-apoptotic and anti-oxidant activity. We also achieved a significant recovery in kidney functions without affecting CsA plasma levels.

The effect of grape seed proanthocyanidin extract in preventing amikacin-induced nephropathy.

BACKGROUND/AIMS: Nephrotoxicity induced by aminoglycosides (AGs) limits their clinical use. As yet, no molecules have been approved to prevent AG nephropathy. We aim to investigate the effectiveness of grape seed proanthocyanidin extract (GSPE) in the prevention of amikacin (AK)-induced nephrotoxicity. METHODS: A total of 24 rats were allocated into control, GSPE, AK, and AK + GSPE groups. While 1 mL saline was administered for 6 days in control and AK groups, 100 mg/kg GSPE was administered in GSPE and AK + GSPE groups. On day 7, intraperitoneal (i.p.) saline was administered in control and GSPE groups, while 1.2 g/kg i.p. AK was administered in AK and AK + GSPE groups. The experiment was terminated on day 9. Blood samples were taken for the measurement of renal functions. Renal tissues of the rats were removed for the analysis of malondialdehyde (MDA), total oxidant system (TOS), total antioxidant system, oxidative stress index (OSI), and for histopathological examination. RESULTS: MDA level was found to be lower in GSPE group compared with other study groups. There was significantly more renal histopathological damage and higher blood urea nitrogen, creatinine, TOS, OSI, and MDA levels in the AK group compared with the control and AK + GSPE groups. The same parameters showed significant improvement in AK + GSPE group compared with AK group. CONCLUSION: Our findings demonstrate for the first time that GSPE reduces oxidative damage in AK nephropathy and provides biochemical and renal histopathological improvements.

Antiapoptotic and antioxidant effects of GSPE in preventing cyclosporine A-induced cardiotoxicity.

OBJECTIVES: Cyclosporine A (CsA) is an immunosuppressive drug, but cardiotoxicity is one of its side effects. Free oxygen radical damage and apoptosis are considered to be responsible for CsA-induced cardiotoxicity. Grape seed proanthocyanidin extract (GSPE) displays antioxidant and antiapoptotic activities. Therefore, we aimed to evaluate the effect of GSPE on CsA-induced cardiotoxicity. MATERIALS AND METHODS: Twenty-four rats were divided into four groups, with six rats in each group. CsA-induced nephropathy was induced by administration of 25 mg/kg CsA. The experiment was discontinued on day 21, and total oxidant system (TOS), total antioxidant system (TAS), oxidative stress index (OSI), and malondialdehyde (MDA) were measured in order to evaluate oxidative damage to the heart tissue. In addition to cardiac histopathology, transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) was performed to determine apoptosis. RESULTS: The CsA group showed a significant increase in TOS, OSI, MDA, cardiac histopathological score, and apoptotic index (AI); in the CsA + GSPE group, OSI, MDA, cardiac histopathological score, and AI decreased significantly, and TAS levels showed a significant increase. CONCLUSION: In this study, we demonstrated for the first time in the literature that GSPE prevents CsA cardiotoxicity and that this effect can be achieved by antiapoptotic and antioxidant activities.

Effects of lidocaine plus epinephrine and prilocaine on autologous fat graft survival.

Although fat grafting is frequently used in plastic surgery practice, debate about the viability of the graft still persists owing to its questionable long-term success. The ultimate aim is to obtain long-term graft viability. Vascularization of the graft is essential for this purpose. The effects of 2 different local anesthetic preparations frequently used during harvesting of fat grafts on long-term graft survival were compared with angiogenesis and volumetric measurements. Twenty-four male Wistar rats were divided into 3 groups. The inguinal region was selected as the fat graft donor site. The first group was injected with isotonic saline, the second was injected with lidocaine plus epinephrine, and the third was injected with prilocaine. Fat grafts were implanted into the dorsal regions of rats, and volumetric measurements were performed initially and on days 30 and 180 at which microvascular angiogenesis were also analyzed. Microvascular angiogenesis was assessed both with the reverse transcription-polymerase chain reaction and immunohistochemistry through determination of vessels stained with factor VIII. No significant difference was obtained between the 3 groups in graft volume or microvascular angiogenesis at any stage of the study. Results from this experimental study indicate that there is no negative effect of lidocaine plus epinephrine or prilocaine on microangiogenesis and the survival of fat grafts.

A rare localization of a common disease: Primary uterine Non-Hodgkin lymphoma mimicking leiomyosarcoma.

Genitourinary system lymphomas comprise a small part of extra-nodal lymphomas (ENLs). ENLs of uterine origin are extremely rare and are often confused with gynecological malignancies. We present an 80-year-old female patient diagnosed with diffuse large B-cell lymphoma (DLBCL) with a single focus of the uterus. The patient's only complaint was abnormal uterine bleeding. Magnetic resonance imaging revealed an intramural-subserous-submucous multiple mass lesion with minimal contrast enhancement mimicking leiomyosarcoma. Diffuse pathological 18F-fluorodeoxyglucose uptake was detected in the entire uterus corpus and cervix on positron emission tomography/computed tomography (PET/CT) scanning. The pathology of the endocervical and endometrial curettage material obtained was DLBCL; the patient was diagnosed with ENL, and a single focus was the uterus. ENLs should be considered in the differential diagnosis of gynecological malignancies in patients with abnormal uterine bleeding. PET/CT is crucial in showing metabolically active spread areas in these patients.

PD-L1 expression in invasive solid papillary breast carcinomas.

Background: Invasive solid papillary carcinomas (ISPC) are rare malignant neoplasms in the classification of WHO 2019 breast tumors. Aims: We aimed to investigate the correlations between programmed cell death ligand-1 (PD-L1) expression status of tumor and immune cells and clinicopathological parameters by molecular classification of this rare morphological subtype. This study will contribute to the literature about the PD-L1 expression state of ISPCs for the first time. Material and Methods: The study included 19 invasive solid papillary carcinoma cases diagnosed between 2009 and 2019 in Pathology Department. Molecular subtyping was performed in 19 cases by immunohistochemical studies (ER/PR, Her-2/neu, Ki-67), and PD-L1 expression was evaluated in neoplastic and immune cells. Results: PD-L1 expression was detected in 4 (21%) cases, 3 (75%) of them were in luminal B and 1 (25%) were in the luminal A group. The correlation between molecular subtypes and PD-L1 expression was statistically significant (P = 0.016). Patients with PD-L1 expression had a higher Ki-67 index than patients without PD-L1 expression (P = 0.037). In addition, there was a statistically significant correlation between PD-L1 expressions of intratumoral lymphocytes and PD-L1 expressions of neoplastic cells (P = 0.004). Conclusions: While predicting the group that will benefit more from immunotherapy in solid papillary carcinoma cases, not only PD-L1 expression of tumor cells but also PD-L1 expression in tumor infiltrating lymphocyte (TIL) can help. In addition, PD-L1 staining rates of tumor cells as well as clinicopathological parameters (molecular subtype, high Ki-67 index, presence of TIL) can be predictive about immunotherapy.

Ectopic Cushing's Syndrome due to Thymic Neuroendocrine Tumor Treated with Surgery and Radiotherapy.

The most common cause of ectopic Cushing's syndrome is small cell lung cancer; less common causes include pancreatic and thymic neuroendocrine tumors. A 35-year male was investigated after detecting low potassium in the tests performed for weakness. The patient was admitted for exclusion of Cushing's syndrome because of high cortisol (108 µg/dl) and ACTH (827ng/L) levels. There was no suppression in the high-dose dexamethasone test, and the patient was thought to have ectopic Cushing's syndrome. A mass in the thymus was detected in thorax tomography. Postoperative ACTH and cortisol levels decreased rapidly. Postoperatively, ACTH did not drop to normal, suggesting the possibility of residual tumor. Radiotherapy was given to the patient because the surgical margin was positive in the pathology report. No functional focus was detected in Ga 68 DOTATATE PET CT after radiotherapy. This case is presented because of the rare association of a thymic neuroendocrine tumor with ectopic Cushing's syndrome, which was revealed during the investigation of the etiology of hypokalemia. Key Words: Hypokalemia, Cushing syndrome, Thymic neuroendocrine tumor.

Frequency of skin cancer and evaluation of risk factors: A hospital-based study from Turkey.

OBJECTIVES: Skin cancers are the most common type of cancer with a significantly increasing incidence. The purpose of the study was to uncover the one-year frequency of melanoma and non-melanoma skin cancers (NMSC) and to determine the risk factors in the development of skin cancer. METHODS: The study included 7396 people from all age groups admitted to the dermatology clinic between October 2020 and 2021. The sociodemographic characteristics, sun protection habits, chronic diseases, and drug and vitamin use were evaluated. Lesions with clinical suspicion of skin cancer were excised. RESULTS: The frequency of skin cancer was found to be 2.7%, basal cell cancer (BCC) 1.2%, squamous cell cancer (SCC) 1.1%, malignant melanoma (MM) was 0.4%. Daily black tea consumption was found to be a risk factor for three type of skin cancer, BCC (p = 0.021), SCC (p = 0.006), and MM (p = 0.002), respectively. Obesity was observed as a risk factor for BCC (p = 0.005) and MM (p = 0.008). We found that having a history of alcohol use were an independent risk factor for all skin cancer types and BMI <30 for SCC. Vitamin D and supplemental drugs intake were observed as protective factors for BCC (p = 0.035, p = 0.007, respectively). Daily coffee consumption was determined as a protective factor for SCC (p < 0.001) and MM (p = 0.049). CONCLUSION: This study estimates the frequency of NMSC and melanoma. Also provides evidence to determine the risk factors and probably protective factors for the development of skin cancers.

Neurocytoma arising in an adrenal gland mature teratoma.

Mature teratoma of adrenal gland is a rare entity. Neurocytoma is a low grade neuronal tumor even rarely seen among central nervous system tumors. Nervous system tumors arising in teratomas are frequently originated from glial or primitive neuroectodermal cells. Here we report a neurocytoma arising in mature cystic teratoma in the right adrenal gland of an 8 years old boy. Histological examination revealed a tumor composed of solid sheets in fibrillar basis with small uniform cells in the neuroglial tissue in teratoma. This is only the second case demonstrating a neurocytoma arising in a mature cystic teratoma in the literature.

Ossifying fibroma of the lumbar spine: case report.

Ossifying fibroma of the vertebra is a very rare condition. We report a 16-year-old boy with ossifying fibroma of the third lumbar vertebra. Neurological and laboratory examinations demonstrated normal findings. Low-back pain, in the absence of radicular pain, was the presenting symptom. Plain radiography and computerized tomography scanning revealed an osteolytic lesion. The tumor in the third lumbar vertebra was curetted and filled with bone allograft. The histopathological diagnosis was consistent with ossifying fibroma. There was no postoperative complication. The case is the second to be reported. The clinical and radiological aspects of this rare tumor are discussed with the pertinent literature.

Mixed endocervical adenocarcinoma and high-grade neuroendocrine carcinoma of the cervix: A case report.

Adenocarcinoma admixed with neuroendocrine carcinoma of the uterine cervix is a rare malignancy with a poor prognosis. In the literature, there are few reported cases. Herein, we report a case of a 56-year-old Turkish woman with cervical adenocarcinoma admixed with small cell neuroendocrine carcinoma. Histological examination of endocervical curettage specimens revealed a tumor composed of almost equal areas of small cell neuroendocrine carcinoma and adenocarcinoma. Neuroendocrine differentiation was confirmed by immunohistochemistry for chromogranin-A, synaptophysin, and CD 56. After the adenocarcinoma and small cell neuroendocrine carcinoma association was detected in the curettage material, both cervicovaginal smear and then total abdominal hysterectomy and bilateral salpingo-oophorectomy resection material of the patient were submitted to our pathology department. Histological features of both curettage and resection material were determined by immunohistochemical studies.

The expression of MCM-2 in invasive breast carcinoma: a stereologic approach.

OBJECTIVES: The aim of this study is to examine the expression of MCM-2 and conventional proliferation marker Ki-67 in breast carcinoma by stereologic technique and to compare it with various clinicopathologic parameters. METHODS: The expression of MCM-2 and Ki-67 on paraffin-embedded tumor tissue sections of patients with invasive breast carcinoma was analyzed immunohistochemically. Stereologic method was used for evaluation of the percentage of positively stained tumor cells. RESULTS: Significant positive correlation was found between the expression of MCM-2 and that of Ki-67 (r = 0.74, p < 0.001). MCM-2 and Ki-67 expression was significantly associated with histologic grade (p < 0.05), and negative correlation was observed between MCM-2 or Ki-67 expression and estrogen status (p < 0.05). No significant association was observed between MCM-2 or Ki-67 expression and patient age, tumor size, lymph node status, clinical stage and menopausal status. CONCLUSION: Our results suggest that MCM-2 expression is significantly associated with histologic grade of breast carcinoma and with cell proliferation capacity (Ki-67 labelling index). Additional studies are required using the stereologic method to compare and understand the utility of Ki-67 and MCM-2 expression in invasive breast carcinoma (Tab. 1, Fig. 4, Ref. 34). Full Text (Free, PDF) www.bmj.sk.