Can tumour budding change the future of pulmonary adenocarcinoma?

BACKGROUND: Pulmonary adenocarcinoma shows different prognosis even in the same pathological subtype and stage. In this study, it is aimed to investigate the relationship between tumour budding and known prognostic values and clinicopathological features in pulmonary adenocarcinoma. METHODS: In this study, there have been 77 patients diagnosed with primary pulmonary adenocarcinoma. In the evaluation process, the number of budding between 0 and 4 is accepted as low budding (Bd1), the number of budding between 5 and 9 is considered as medium budding (Bd2), and the number of budding above 10 is considered as high budding (Bd3). RESULTS: According to the findings of the study, it can be seen that there is a statistical difference between tumour budding and stromal fibrosis (p < 0.001). The presence of pleural invasion, lymph vascular invasion and perineural invasion in patients with Bd3 is found to be statistically higher than the patients with Bd1 (p = 0.048) (p = 0.041) (p = 0.029). CONCLUSIONS: Tumour budding has been associated with pleural invasion, lymph vascular invasion, perineural invasion, and stromal fibrosis. This study is the first to show the relationship between tumour budding and stromal fibrosis in pulmonary adenocarcinomas. The role of tumour budding in lung cancers remains to be clarified.

A novel homozygous mutation in the USP53 gene as the cause of benign recurrent intrahepatic cholestasis in children: a case report.

BACKGROUND: Benign recurrent intrahepatic cholestasis (BRIC) is a rare cause of cholestasis with recurrent episodes of jaundice and pruritus without extrahepatic bile duct obstruction. A mutation in the USP53 gene is known to cause BRIC-like cholestasis with normal serum gamma-glutamyltransferase (GGT) levels. CASE: We report a 16-year-old boy with recurrent episodes of cholestasis since 6 months of age with normal serum GGT levels. The liver biopsy showed ballooning degeneration of hepatocytes which is typical for BRIC, and intrahepatic and canalicular cholestasis with bilirubinostasis. We performed whole exome sequencing (WES) and identified a novel homozygous variant (NM_001371399.1:c.1558C > T) of the USP53 gene at exon 14 as the cause of BRIC. CONCLUSION: This is the first case of USP53 disease from Türkiye with a novel mutation in the USP53 gene. This novel identification of the mutation of c.1558C > T at exon 14 can provide elucidative data for those who work in the field of intrahepatic cholestasis. Our case suggests that USP53 disease must be kept in mind in patients with recurrent intrahepatic cholestasis with normal serum GGT levels.

Celiac crisis with thrombocytopenia and coagulopathy in a child.

BACKGROUND: Celiac disease rarely presents with edema, hypoalbuminemia, acute metabolic deterioration, and electrolyte imbalances. This life-threatening condition is defined as a celiac crisis and may mimic disorders with metabolic derangement and sepsis. The crisis may present at onset or develop in celiac disease patients with poor compliance to a gluten-free diet. The fluid resuscitation and replacement of electrolyte deficits are life-saving modalities. CASE: A 14-month-old girl was admitted with fever, lethargy, severe dehydration, edema, hypotension, and commenced sepsis therapy. However, the patient had a growth delay and loss of weight with diarrhea and delayed motor skills. On admission, laboratory evaluation showed anemia, coagulopathy, hypoalbuminemia, electrolyte disturbances, and metabolic acidosis and developed thrombocytopenia during follow-up. The celiac serological tests and upper gastrointestinal endoscopic duodenal mucosa appearance, and duodenum histopathology findings suggested celiac disease. CONCLUSIONS: This case highlights that a celiac patient may present with a severe illness like sepsis and may be associated with cytopenia and coagulopathy in the celiac crisis.

Lysyl Oxidase Like-4 (LOXL4) as a tumor marker and prognosticator in advanced stage laryngeal cancer / Proteína tipo-lisil oxidase-4 (LOXL4) como marcador tumoral e prognóstico no câncer de laringe em estágio avançado

Abstract Introduction: Lysyl oxidase-like 4 is an amine oxidase from the lysyl oxidase family that was previously shown to be overexpressed in head and neck cancer and upregulated in response to hypoxia. The possible role of lysyl oxidase-like 4 as a tumor marker in advanced stage larynx cancer was investigated. Objective: To investigate the expression of lysyl Oxidase-Like 4 protein in advanced stage laryngeal cancer and elucidate its possible role as a tumor marker, predictor of treatment response and prognosticator. Methods: Diagnostic specimens of 72 patients treated for stage III-IV laryngeal squamous cell carcinoma were evaluated for lysyl oxidase-like 4 expression by immunohistochemistry. Results: Lysyl oxidase-like 4 expression was correlated with advanced tumor stage (p = 0.041) and better differentiation (p = 0.025) but was independent of tumor diameter (p = 0.456). Response to induction chemotherapy or the need for salvage laryngectomy were not affected by lysyl oxidase-like 4 expression (p = 0.999, p = 0.070 respectively). Increased lysyl oxidase-like 4 expression was associated with better 2 year overall survival in both univariate (p = 0.036) and multivariate analyses (p = 0.014). Conclusion: Lysyl oxidase-like 4 expression emerges with advancing stages, is lost with worsening differentiation, and may have tumor suppressive properties in larynx cancer.

Resumo Introdução: A proteína tipo-lisil oxidase-4 é uma amina oxidase da família lisil oxidase cuja superexpressão em câncer de cabeça e pescoço e up-regulação em resposta à hipóxia foram previamente demonstradas. O possível papel da proteína tipo-lisil oxidase-4 como um marcador tumoral no câncer de laringe em estágio avançado foi investigado. Objetivos: Investigar a expressão da proteína tipo-lisil oxidase-4 no câncer de laringe em estágio avançado e elucidar seu possível papel como marcador tumoral, preditor da resposta ao tratamento e do prognóstico. Método: Amostras diagnósticas de 72 pacientes tratados para carcinoma espinocelular da laringe em estágio III-IV foram avaliadas quanto à expressão da proteína tipo-lisil oxidase-4 por imuno-histoquímica. Resultados: A expressão de proteína tipo-lisil oxidase-4 foi correlacionada com o estágio avançado do tumor (p = 0,041) e melhor diferenciação (p = 0,025), mas foi independente do diâmetro do tumor (p = 0,456). A resposta à quimioterapia de indução ou a necessidade de laringectomia de resgate não foram afetadas pela expressão da proteína tipo-lisil oxidase-4 (p = 0,999, p = 0,070 respectivamente). O aumento da expressão da proteína tipo-lisil oxidase-4 foi associado a melhor sobrevida global de 2 anos nas análises univariada (p = 0,036) e multivariada (p = 0,014). Conclusão: A expressão da proteína tipo-lisil oxidase-4 surge com o avanço dos estágios e desaparece com pioria da diferenciação e pode ter propriedades supressoras de tumor no câncer de laringe.

Lysyl Oxidase Like-4 (LOXL4) as a tumor marker and prognosticator in advanced stage laryngeal cancer.

INTRODUCTION: Lysyl oxidase-like 4 is an amine oxidase from the lysyl oxidase family that was previously shown to be overexpressed in head and neck cancer and upregulated in response to hypoxia. The possible role of lysyl oxidase-like 4 as a tumor marker in advanced stage larynx cancer was investigated. OBJECTIVE: To investigate the expression of lysyl Oxidase-Like 4 protein in advanced stage laryngeal cancer and elucidate its possible role as a tumor marker, predictor of treatment response and prognosticator. METHODS: Diagnostic specimens of 72 patients treated for stage III-IV laryngeal squamous cell carcinoma were evaluated for lysyl oxidase-like 4 expression by immunohistochemistry. RESULTS: Lysyl oxidase-like 4 expression was correlated with advanced tumor stage (p = 0.041) and better differentiation (p = 0.025) but was independent of tumor diameter (p = 0.456). Response to induction chemotherapy or the need for salvage laryngectomy were not affected by lysyl oxidase-like 4 expression (p = 0.999, p = 0.070 respectively). Increased lysyl oxidase-like 4 expression was associated with better 2 year overall survival in both univariate (p = 0.036) and multivariate analyses (p = 0.014). CONCLUSION: Lysyl oxidase-like 4 expression emerges with advancing stages, is lost with worsening differentiation, and may have tumor suppressive properties in larynx cancer.

Targeting lysyl oxidase (LOX) overcomes chemotherapy resistance in triple negative breast cancer.

Chemoresistance is a major obstacle in triple negative breast cancer (TNBC), the most aggressive breast cancer subtype. Here we identify hypoxia-induced ECM re-modeler, lysyl oxidase (LOX) as a key inducer of chemoresistance by developing chemoresistant TNBC tumors in vivo and characterizing their transcriptomes by RNA-sequencing. Inhibiting LOX reduces collagen cross-linking and fibronectin assembly, increases drug penetration, and downregulates ITGA5/FN1 expression, resulting in inhibition of FAK/Src signaling, induction of apoptosis and re-sensitization to chemotherapy. Similarly, inhibiting FAK/Src results in chemosensitization. These effects are observed in 3D-cultured cell lines, tumor organoids, chemoresistant xenografts, syngeneic tumors and PDX models. Re-expressing the hypoxia-repressed miR-142-3p, which targets HIF1A, LOX and ITGA5, causes further suppression of the HIF-1α/LOX/ITGA5/FN1 axis. Notably, higher LOX, ITGA5, or FN1, or lower miR-142-3p levels are associated with shorter survival in chemotherapy-treated TNBC patients. These results provide strong pre-clinical rationale for developing and testing LOX inhibitors to overcome chemoresistance in TNBC patients.

Comparison of clinicopathological features and treatments between pre- and postmenopausal female breast cancer patients - a retrospective study.

INTRODUCTION: To find out if there are clinical and biological differences in breast cancer characteristics of premenopausal and postmenopausal women. For this reason, we investigated the differences in terms of the clinicopathological features and treatment methods of premenopausal and postmenopausal breast cancer patients in our study. MATERIAL AND METHODS: In this study, the files of 428 patients who were operated due to breast cancer between 1 January 2007 and 31 December 2017 in Ankara Atatürk Training and Research Hospital were examined retrospectively. The age, tumour size, tumour grade, oestrogen receptor, progesterone receptor, HER2 score, Ki-67 proliferation index, perineural invasion, and lymphovascular invasion were investigated. RESULTS: In patients with premenopausal breast cancer, the tumour diameter was larger (p = 0.047) and the lymph node metastasis was higher (p < 0.001). Oestrogen receptor (OR) expression (p = 0.002), progesterone receptor (PR) expression (p = 0.014), negative human epidermal growth factor receptor 2 (HER2) expression (p = 0.038), and Ki-67 expression (p = 0.017) were higher in the premenopausal group. In the premenopausal group, breast conserving surgery (p = 0.004), chemotherapy (p = 0.007), radiotherapy (p = 0.008), and endocrine therapy (p = 0.025) were higher than in the postmenopausal group. CONCLUSIONS: Premenopausal and postmenopausal female breast cancer patients have significant differences in tumour size, tumour grade, axillary lymph node metastasis, hormone receptor status, HER2 expression, and treatment modalities.

Evaluation of malignancy with thyroid imaging reporting and data system (TI-RADS) in thyroid nodules with persistent nondiagnostic cytology

Background/aim: We aimed to evaluate the utility of thyroid imaging reporting and data system (TI-RADS) in prediction of malignancy in thyroid nodules with persistent nondiagnostic (ND) cytology. Materials and methods: A total of 246 thyroid nodules which were surgically removed and had at least two fine-needle aspirations (FNAs) with ND cytology were included in this study. Ultrasonography features and TI-RADS scores were recorded. Results: Of 246 nodules, 218 (88.6%) had benign and 28 (11.4%) had malignant final histopathology. Frequencies of taller than wide shape, solidity, hypoechogenicity, microcalcifications, and presence of irregular borders were similar between benign and malignant nodules (P > 0.05). The number of nodules categorized as TI-RADS 3, 4a, 4b, and 4c were 12 (4.9%), 53 (21.5%), 104 (42.3%), and 77 (31.3%), respectively. There was not any nodule in TI-RADS 5 category. Malignancy rates of categories 3, 4a, 4b, and 4c were 0%, 13.2%, 9.6%, 14.3%, respectively. No significant differences were detected in TI-RADS categories between benign and malignant nodules (P > 0.05). Conclusion: In this study, we did not demonstrate any suspicious ultrasound (US) finding predictive for malignancy in thyroid nodules with persistent ND cytology and did not determine any difference between malignant and benign nodules regarding TI-RADS scores. Whereas, we found that thyroid nodules in 4a, 4b, and 4c TI-RADS categories had higher malignancy rates than those previously reported in ND cytology. We think that TI-RADS categories in thyroid nodules with persistent ND cytology can be helpful in treatment decision.

Expression of Immunomodulatory Molecules PD-1, PD-L1, and PD-L2, and their Relationship With Clinicopathologic Characteristics in Endometrial Cancer.

Chemotherapeutic agents are not very effective in treating advanced endometrial cancers (ECs). Recent studies have demonstrated the immune evasion mechanism of tumors and possible remedies. Programmed cell death protein 1 (PD-1), programmed death ligand 1 (PD-L1), and programmed death ligand 2 (PD-L2) are immunomodulator molecules that have been the focus of research in lung cancer, melanoma, and renal cell cancer. However, there are few studies concerning EC. This retrospective study aimed to determine PD-1, PD-L1, and PD-L2 expression immunohistochemically in EC, and to study their correlation with clinicopathologic tumor characteristics. This study comprised 127 patients with EC. Anti PD-1, PD-L1, and PD-L2 antibodies were examined immunohistochemically on sections obtained from tissue microarray paraffin blocks. No staining with PD-1 in tumor cells was seen; however, we found positive staining in tumor cells at 36.2% with PD-L1 and 64.4% with PD-L2, and at 61.6% with PD-1, 36.2% with PD-L1, and 93.2% with PD-L2 in immune cells. When comparing staining and clinicopathologic findings, most of the PD-L1 negative tumors (both in tumor and immune cells) were FIGO Stage I, which was significantly higher than stage II-III-IV tumors (P<0.05). There was a statistically significant association between the FIGO grade and the PD-L1 score in immune cells (P=0.009), and between staining of PD-1, PD-L1, and PD-L2 and age (P=0.004, 0.013, and 0.043, respectively). Interaction between PD-1, PD-L1, and PD-L2 may be a potential target for immunotherapy in elderly and advanced stage EC patients.

Investigation of Heme Oxygenase 2 Enzyme Protein Expression in Keratoconus and Normal Human Corneal Epithelium: An Immunohistochemical Study.

PURPOSE: To compare heme oxygenase 2 (HO-2) enzyme levels detected by immunohistochemical staining methods in the cornea epithelium obtained from keratoconus patients and normal subjects. MATERIALS AND METHODS: The keratoconus group included 69 eyes of 69 patients with keratoconus scheduled for cross-linking surgery. The control group included 52 eyes of 52 patients with refractive error scheduled for photorefractive keratectomy surgery. After a detailed ophthalmologic examination, corneal topographic maps of each patient were generated, and then the patients underwent surgery. The corneal epithelium was collected mechanically during the surgery, fixed with formalin, embedded in paraffin blocks, and sectioned by microtomes. HO-2 antibodies were applied to the samples for immunohistochemical evaluation. The intensity of the staining was identified as negative, weak, moderate or strong. The keratoconus group was classified as early (average keratometry (AvrK) ≤ 47 D), moderate (AvrK 47-55 D) and advanced keratoconus (AvrK ≥ 55 D). Finally, intergroup and intragroup comparison analyses were made statistically. RESULTS: In the keratoconus group, 20 (29%) (14 weak and 6 moderate staining) of the 69 corneal epithelial specimens were identified with HO-2 expression. In the control group, 40 (76.9%) (16 moderate and 24 strong staining) of the 52 corneal epithelial specimens were identified with HO-2 expression. HO-2 expression in the corneal epithelial specimens was significantly less in the keratoconus group than in the control group (p < 0.001). There was no substantial difference among the keratoconus subgroups in terms of staining with the HO-2 antibody (p = 0.797). CONCLUSIONS: The HO-2 enzyme staining using immunohistochemical methods was at lower amounts in the keratoconic corneal epithelial cells as compared with normal corneal epithelial cells. The HO-2 enzyme may play a role in the etiopathogenesis of keratoconus.

Is there a difference in the number of interstitial cells, neurons, presence of fibrosis and inflammation in ureteropelvic junction tissues of patients with ureteropelvic junction obstruction with and without crossing vessels?

OBJECTIVE: We compared the number of interstitial cells (ICs), nerves, presence of fibrosis and inflammation at the level of full-thickness human ureteropelvic junction (UPJ) tissues obtained from normal subjects, and patients with UPJ obstruction with and without crossing vessels. MATERIAL AND METHODS: Normal UPJ tissues (n=12) histopathologically confirmed to be without tumor involvement were obtained from subjects who underwent radical nephrectomy for kidney mass. Additional UPJ tissues were obtained from patients who underwent pyeloplasty due to UPJ obstruction. Crossing vessel was identified in 17 patients. In 57 patients, no crossing-vessel was noted. ICs were stained immunohistochemically with anti-human CD117 (c-kit) antibody. Neural tissue was stained with S-100. The numbers of ICs and neurons were compared between the groups: controls with normal UPJ (Group I), Ureteropelvic junction obtruction (UPJO) with crossing vessel (Group II) and UPJ obstruction without crossing vessel (Group III). Groups were also compared in terms of the presence of fibrosis and inflammation. RESULTS: The mean age of total population included in the study was 30.5±18.5 years. No significant differences were detected between the three groups regarding mean and median numbers of ICs at the level of UPJ (lamina propria and muscle layer) and mean and median numbers of neurons at the level of lamina propria (p>0.05). Likewise, no significant differences were detected between the three groups regarding the presence of fibrosis and inflammation (p>0.05). CONCLUSION: Number of ICs, neurons, presence of fibrosis and inflammation seem to be similar in the intact UPJ and UPJ with obstruction with and without crossing vessel. Cellular function rather than the number ICs might play a role that warrants further research.

The diagnostic value of parathyroid hormone washout in primary hyperparathyroidism patients with negative or equivocal 99 m Tc-MIBI results.

BACKGROUND AND OBJECTIVES: The accurate identification of hyper functioning parathyroid gland is needed for definitive surgical treatment in primary hyperparathyroidism. Ultrasonography and 99mTechnetium sestamibi scintigraphy are the two most used methods with varying sensitivities. This study aimed to assess the value of parathyroid hormone (PTH) assay in preoperative ultrasound guided fine needle aspiration (FNA)-PTH washout fluid to verify the correct localisation of lesions with negative or inconclusive scintigraphy results. METHODS: We evaluated data of 28 lesions in 21 patients who underwent US-guided parathyroid fine-needle aspiration (FNA) with PTH washout, retrospectively. The PTH washout results and the reports of parathyroid surgery and imaging studies were reviewed. RESULTS: Of operated 28 lesions 23 had positive and 5 had negative washout results. The median FNA-PTH washout was 2315.5 pg/ ml (min-max: 12.3-6978 pg/ ml). The calculated sensitivity of FNA-PTH washout was 85.7% and the specifity was 28.6%. The positive and negative predictive values were 78.3% and 40.0%, respectively. CONCLUSIONS: FNA-PTH can be used to establish the nature of the lesion, discriminate parathyroid gland from thyroid lesions or cervical lymph nodes, improving the surgical outcomes. It can be used to localise parathyroid lesions preoperatively when negative or discordant ultrasound and scintigraphy findings are obtained.

Association between androgen receptor status and prognosis in triple negative breast cancer.

PURPOSE: Triple negative breast cancer (TNBC) is a heterogeneous disease group with a higher recurrence risk and poorer prognosis. In this study, we aimed to investigate the frequency and prognostic value of androgen receptor (AR) expression in tissues of TNBC patients. METHODS: A total of 84 TNBC patients treated between 2000 - 2015 in Hacettepe University Cancer Institute were included and their medical records were analyzed retrospectively. The available paraffin blocks were assessed immunohistochemically to determine AR expression. Tumors with ≥1% nuclear staining were considered AR-positive, while the ones with <1% staining were considered AR-negative. We analyzed the association between AR expression, and clinical-pathologic characteristics and prognosis in TNBC. RESULTS: Of the 84 TNBC patients, 25 (29.8%) were AR-positive. The frequency of grade 3 tumors was lower among AR-positive TNBC tumors compared to AR-negative tumors (40 vs 86.4%, p<0.001). In the AR-positive group, invasive ductal carcinoma (IDC) was less prevalent compared to AR-negative group (56 vs 86.4%, p<0.002). However, there were not statistically significant differences between AR positive and negative groups in terms of overall survival (OS) and disease free survival (DFS) (p=0.449, p=0.733, respectively). We found that grade 3 tumors were less frequent in AR-positive TNBC in our study. Nonetheless, we did not detect statistically significant difference in terms of overall survival and disease free survival between AR positive and negative TNBC. CONCLUSION: Routine evaluation of AR could contribute to further studies that may enlighten the role of AR targeting therapies in TNBC.

Association between Her2/neu status in colorectal carcinoma and clinicopathological features: a retrospective study using whole - tissue sections.

The human epidermal growth factor receptor 2 (Her2/neu) signal pathway plays a significant role in the occurance of various solid tumor types. The rate of Her2/neu in colorectal carcinoma (CRC) is not clearly elucidated. In this study, we discuss the association between Her2/neu overexpression and clinicopathological parameters in CRC. Her2/neu immunohistochemical (IHC) staining was performed on whole sections of formalin fixed paraffin embedded tumor tissues of 100 CRC resections. Cases with score 3+ and score 2+ expressions were further evaluated by silver in-situ hybridization (ISH) for the existence of Her2/neu gene amplification. Her2/neu membranous overexpression was observed in 12 of the 100 cases (6 cases with a score 3+ and 6 cases with a score 2+) and 6 of these were heterogenous. There were 10 cases with Her2/neu amplification (6/6 score 3+, 4/6 score 2+). Strong cytoplasmic staining was observed in 5 cases. Membranous scores were either 3+ or 2+ in 3 of these 5 cases. Moreover, there was Her2/neu amplification in 2 of these 3 cases. Her2/neu amplification status and overexpression was not related to clinicopathological parameters and overall survival. More clear results can be obtained from studies with Her2/neu IHC and ISH test on whole sections.

Prognostic significance of the programmed death ligand 1 expression in clear cell renal cell carcinoma and correlation with the tumor microenvironment and hypoxia-inducible factor expression.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common renal malignancy. Hypoxia-inducible factors, HIF-1α and HIF-2α, are expressed in the majority of ccRCC. Targeting immune checkpoints with the blockade of PD-1 and its ligand PD-L1 reorganizes T-cell activity in tumor microenvironment and provides important antitumor responses. PD-L1 upregulation has been found to be hypoxia-inducible factor (HIF) dependent. Our aim is to demonstrate the association between PD-L1 and HIF expression and to reveal the role of PD-L1 in prognosis and its association with tumor microenvironment. METHODS: Surgical specimens from 145 patients diagnosed with ccRCC, who had undergone radical or partial nephrectomy, were retrospectively analyzed. Immunohistochemistry on tissue microarrays (TMA) was performed to demonstrate expressions of PD-L1, HIF-1α, and HIF-2α in tumor cells and PD-1, CD4, and CD8 in lymphocytes to assess lymphocyte density in tumor microenvironment. RESULTS: PD-L1 tumor cell expression was detected in 20/125 (13.8%) cases, which correlated with higher levels of PD-1, CD4, CD8 and HIF-2α expression. Low or high expression of HIF-1α was similar in PD-L1-positive cases. When PD-L1-positive cases were compared with negative ones, there was no significant difference in terms of prognostic factors. However, the number of WHO/ISUP grade 3-4 tumors was significantly higher in PD-L1-positive cases than in negative ones. CONCLUSION: PD-L1 tumor cell expression is strongly associated with increased HIF-2α expression and presence of dense lymphocytic infiltration in ccRCCs. Our findings confirm that PD-L1 positivity is associated with high ISUP nucleolar grade. The association between PD-L1, HIF, and lymphocyte density in tumor microenvironment must be clarified and especially taken into account in combination treatment.

Evaluation of p53 and Ki67 Expression Profiles in Basal Cell Carcinomas in a Usual and an Unusual Location.

OBJECTIVE: Owing to their importance in cell proliferation in cutaneous malignancies, we aimed to immunohistochemically compare the expression profiles of p53 and Ki67 in basal cell carcinoma (BCC) cases in both a usual and an unusual locations in this study. MATERIAL AND METHOD: In this study we included 12 in an unusual location of BCC cases and 21 BCC cases in a usual location. Immunohistochemical expression of p53 and Ki67 antibodies were studied in 33 paraffin-embedded tissue specimens of basal cell carcinoma. We compared the p53 and Ki67 staining scores with clinicopathologic features. RESULTS: The tumor size was found to be greater in BCC cases in an unusual location than those in a usual location. The relationship between age and tumor size was also evaluated in both groups and it was found that tumor size increased with age. A comparative study between the two groups showed no difference p53 and Ki67 expression percentages. There was a linear correlation between the Ki67 and p53 marker staining rates (ρ=0.420; p=0.015). In the samples taken from cases in a usual region, there was a linear and moderate relationship between the markers (ρ=0.513; p=0.017). Median tumor diameter results were similar to the marker staining score (p > 0.05). CONCLUSION: This is the first study comparing the expression profiles of p53 and Ki67 of BCC cases in an unusual and a usual location. No significant difference was found concerning Ki67 and p53 expression levels between the two groups.

Role of calcium-sensing receptor, Galectin-3, Cyclin D1, and Ki-67 immunohistochemistry to favor in the diagnosis of parathyroid carcinoma.

BACKGROUND: As histopathological findings of parathyroid carcinoma are not certain, the diagnosis of tumors with degenerative changes may be difficult. In these cases, immunohistochemical markers are beneficial. We aimed to research the acceptability of calcium-sensing receptor (CaSR), Galactin-3, Cyclin D1, and Ki-67 as helpful markers in parathyroid tumors in cases which are difficult to diagnose. MATERIALS AND METHODS: Those cases who had been diagnosed with atypical parathyroid adenoma and parathyroid carcinoma between 2010 and 2015 were reevaluated. Immunohistochemical markers were applied to this cases. RESULTS: About 21 cases were parathyroid adenoma, 14 were atypical adenoma, and 10 cases were parathyroid carcinoma. According to the immunohistochemical results, global loss of CaSR staining was seen in 50% (5/10) of the patients with carcinoma while there was no loss of staining in those with parathyroid adenoma (P = 0,001). Global loss of CaSR staining was found in only one out of 14 cases with atypical adenoma. The expression of Galactin-3 was found to be positive in 40% (4/10) of carcinoma cases, 71.4% (10/14) of those with atypical adenoma, and 14.3% (3/21) of those with adenoma (P = 0,002). Cyclin D1 expression was determined to be positive in 70% (7/10) of patients with carcinoma, 71.4% (10/14) of atypical adenoma cases, and 23.8% (5/21) of those with adenoma. The Ki-67 proliferation index was seen to be above 5% in 50% (5/10) of carcinoma cases and 35,7% (5/14) of those with atypical adenoma. CONCLUSION: In these studies, it has been emphasized that the global loss of CaSR staining was used as a negative marker in the diagnosis of carcinoma. In this study, we have also confirmed that the global loss of CaSR staining is a useful marker to determine potential increased malignancy.

Can Cutting-Needle Biopsy Be an Alternative to Excisional Biopsy in Lymph Node Pathologies?

OBJECTIVE: We aimed to compare cutting-needle biopsy (CNB) diagnoses with excisional biopsy diagnoses of enlarging lymph nodes and to determine the diagnostic value of CNB. MATERIAL AND METHOD: Out of the 291 cases that underwent CNB from lymph nodes between 2010 and 2016, 60 were included in the study in which pathological lymph nodes were excised after CNB. Demographic information, pathology and imaging reports, the diameters of the lymph nodes and the length of the CNBs of these cases were obtained from the hospital registry system. Diagnoses of the CNBs and excisional biopsies were then compared. RESULTS: According to the excisional biopsy diagnosis, 7 of the 60 cases (11.7%) were benign and 53 of them (88.3%) were malignant. 28 (53%) of the malignant cases were diagnosed as Hodgkin's lymphoma while the others (47%) got a non-Hodgkin's lymphoma diagnosis. In the 8 non-diagnostic CNBs, 3(37%) of them were found to be benign/reactive, while 5 (63%) were diagnosed as malign lymphoma in excisional biopsy. Similarly, 7(64%) of the 11 cases diagnosed as benign/reactive in CNB, were found to be malignant with excisional biopsy. When CNB and excisional biopsy were compared, sensitivity and specificity were 90% and 100%; positive predictive value (PPV) and negative predictive value (NPV) were 100% and 0%, respectively, and the diagnostic accuracy rate (DV) was 86.5%. The mean diameter of the benign lymph nodes was 26.1 mm and the mean diameter of the malignant ones was 35.6 mm. There was no significant difference between malignant and benign lymph node size (p > 0.05). There was also no statistically significant difference between CNB length and correct diagnosis (p=0.233). CONCLUSION: CNB is a non-invasive procedure. It is an alternative to excisional biopsy because of its low morbidity and low cost. However, the sensitivity of CNB is lower than its specificity, and we recommend the surgical excision of lymph nodes with a clinically strong neoplasm suspicion because of the presence of false negatives in 7 cases.

Is ultrasonographically detected nodule diameter concordant with pathological tumor size?

INTRODUCTION: We aimed to compare preoperative ultrasonographical and postoperative histopathological diameters of differentiated thyroid cancer (DTC) lesions and investigate possible factors that can predict the discordance between two measurements. METHODS: Data of patients with histopathologically confirmed DTC were reviewed retrospectively. Nodules evaluated by preoperative US were matched with histopathologically examined nodules. Incidental tumors and nodules that can not be matched in US and histopathology reports were excluded. Preoperative US diameter and postoperative histopathological size were compared and percentage difference between two measurements was calculated for each lesion. RESULTS: There were 607 DTC foci in 562 patients. Mean US diameter was significantly higher than histopathological diameter (21.0 ± 15.6 mm vs 17.3 ± 13.6, p < 0.001). US diameter was higher than tumor size in 444 (73.1%), equal in 15 (2.5%) and lower in 148 (24.4%) nodules. Marginal irregularity was observed in 253 (57%) lesions with US diameter > tumor size and 108 (73%) lesions with US diameter < tumor size (p = 0.010). Rate of nodules with peripheral halo was higher in lesions with US diameter > tumor size (30.6% vs 20.3%, p = 0.015). In nodules with US diameter > tumor size, percentage difference was lower in nodules with microcalcification (p = 0.020) and higher in cytologically benign nodules (p < 0.001). Among nodules with US diameter < tumor size, <1 cm nodules had significantly higher percentage difference compared to 1-1.9, 2-3.9 and ≥ 4 cm nodules (p = 0.005). CONCLUSION: Ultrasonographically determined diameter is higher than histopathologically determined size in a considerable ratio of DTCs. It might be helpful to consider this discordance while deciding surgical extent in these patients.

What does the Data of 354,725 Patients from Turkey Tell Us About Cervical Smear Epithelial Cell Abnormalities? - The Epithelial Cell Abnormality Rate is Increasing - Quality Control Studies and Corrective Activity are Musts.

OBJECTIVE: There is no other screening program close to the success rate of PAP test. Cervical cytology constitutes a large workload so that quality control in cervical cytology is important for the quality assurance of pathology laboratories. MATERIAL AND METHOD: In this study, we collected the cervical cytology results from all over Turkey and discussed the parameters influencing the quality of the PAP test. The study was conducted with Turkish gynaecopathology working group and 38 centers (totally 45 hospitals) agreed to contribute from 24 different cities. The study was designed to cover the cervical cytology results during 2013. The results were evaluated from the data based on an online questionnaire. RESULTS: The total number of Epithelial Cell Abnormality was 18,020 and the global Epithelial Cell Abnormality rate was 5.08% in the total 354,725 smears and ranging between 0.3% to 16.64% among centers. The Atypical squamous cells /Squamous intraepithelial lesion ratios changed within the range of 0.21-13.94 with an average of 2.61. When the centers were asked whether they performed quality assurance studies, only 14 out of 28 centers, which shared the information, had such a control study and some quality parameters were better in these centers. CONCLUSION: There is an increase in the global Epithelial Cell Abnormality rate and there are great differences among centers. Quality control studies including the Atypical squamous cells/Squamous intraepithelial lesion ratio are important. Corrective and preventive action according to quality control parameters is a must. A cervical cytology subspecialist in every center can be utopic but a dedicated pathologist in the center is certainly needed.