PD-L1 and EBV LMP1 expressions in classic Hodgkin lymphomas and its correlation with clinicopathological parameters and prognosis.

BACKGROUND: Programmed death pathway leads to T cell anergy. Wide range of malignancies take advantage of this pathway by programmed death-ligand 1 (PD-L1) expression either on neoplastic cells or on the nonneoplastic cells of tumour microenvironment. New therapeutic approaches have been directed against this pathway. We studied PD-L1 expression on both neoplastic Hodgkin and Reed-Sternberg (HRS) cells and cells of tumour microenvironment in classic Hodgkin lymphoma (CHL) patients and compared it with Ebstein-Barr virus (EBV) positivity, clinical data, and survival rates. METHODS: Lymph node excision materials of 56 CHL patients diagnosed between 2007 and 2017 were included in this retrospective study. PD-L1 expression of HRS cells and tumour microenvironment cells were evaluated by immunohistochemical assay. Staining intensity and rate of the PD-L1 expressions were estimated. EBV was examined by immunohistochemistry for latent membrane protein 1 (LMP1) antibody. Clinical data of 39 patients and survival data of 34 patients were compared with PD-L1 expressions on tumour cells. RESULTS: PD-L1 expression was present in HRS cells in 89.2% of the cases. There was more than 20% of PD-L1 expression in cells of tumour microenvironment in all the cases. PD-L1 positivity did not show statistically significant difference according to EBV expression, clinical parameters, and prognosis. DISCUSSION: Previous studies showed inconsistent rates for PD-L1 prevalence (20%-95.7%) in CHL patients due to differences in the study methods. Although high prevalence of PD-L1 positivity was found in majority of them, there was no statistically significant difference between PD-L1 positivity on HRS cells and EBV expression, clinical parameters, and prognosis. This high prevalence in patients with various clinical properties makes PD-L1 a potential target for new emerging immunotherapies for CHL.

Percutaneous Biopsy of Metastatic Bone Lesions Invisible on Conventional Computed Tomography.

Early detection and histopathological diagnosis of bone lesions with suspected metastasis are crucial for planning treatment of cancer patients. We present computed tomography (CT) findings of three cases with bone metastases that were diagnosed by CT-guided biopsy. All three bone lesions were highly suspicious for metastasis on magnetic resonance (MR) and fluoro-deoxy-glucose-positron-emission-tomography-CT (FDG-PET-CT); although they were not visible on conventional CT. Hence, all the biopsies were performed with reference to MR and FDG-PET-CT imaging findings. As a result of histopathological examinations, all three lesions were diagnosed as metastases of primary cancers. Bone lesions with positive MR and FDG-PET-CT findings in patients with a primary known cancer may be metastasis although they are invisible on conventional CT. These lesions should be biopsied with reference to MR and PET-CT findings for treatments of cancer patients. Key Words: Bone, Metastasis, Computed tomography, PET scan, Biopsy.

Analysis of Clinical-Radiological-Pathological Factors in FN/SFN Bethesda Category Thyroid Nodules, Contribution of FNAB Repeat, Single Center Experience.

OBJECTIVES: Follicular neoplasm/suspected follicular neoplasm (FN/FNS) Bethesda Category (BC)-4 group cases are known as the gray zone. Nodules diagnosed in cytology are excised. However, very few of these nodules are malignant. Our aim is to investigate the usability of clinical-radiological-pathological parameters to reduce unnecessary surgery. In addition, we questioned the benefit of repeating fine-needle aspiration biopsy (rFNAB) in these nodules, which is not recommended, but performed for clinical or patient-related reasons. METHODS: The files of all thyroid FNAB patients conducted in our institution between January 2014 and September 2020 were scanned in the database. In our study, 185 (5.1%) nodules with cytology results of which were classified as FN/FNS were identified among 3624 nodules that were applied FNAB during this period. Twenty-eight patients were excluded from the study group. 157 nodules belonging to 157 patients between the ages of 21 and 82 years who were operated and met the study criteria were identified from patients with these nodules. The files of all patients were scanned and the results of age, gender, ultrasonographic nodule characteristics, FNAB repeat, type of surgery, and postoperative pathology were recorded. All data were analyzed by comparing them with nodule features. SPSS 15.0 for Windows program was used for statistical analysis. RESULTS: A significant correlation was found between the incidence of malignancy and male gender and hypervascularization (p=0.017 and p=0.002, respectively). Malignancy was less in nodules larger than 2 cm (p=0.014). There was no relationship between other clinical and radiological features and malignancy. In 29 nodules with rFNAB, a significant correlation was found between malignancy and advanced age (52.9-years-old), presence of nodules smaller than 2 cm and hypervascularization (p=0.047, p=0.047, and p=0.030, respectively). CONCLUSION: We recommend careful review of patients with hypervascular, hypoechogenic, and microcalcific BC-4 nodules (male gender and older patients at greater risk). Because of the serious risk of malignancy, patients with these features should be prepared for patient management with total thyroidectomy after examination with frozen section applied to the nodule during the operation.

Diagnostic value of lymph node fine-needle aspiration cytology.

OBJECTIVES: This study aims to assess the diagnostic accuracy of cytology by comparing the results of fine-needle aspiration cytology (FNAC) and histopathologic examination. MATERIAL AND METHODS: A 4-year retrospective study design was conducted on FNAC samples from the lymph nodes of patients in our hospital between January 2015 and December 2018. The cytopathological diagnoses were compared with the histopathological results of the same excised lymph nodes. Diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy rate were calculated. RESULTS: A total of 392 lymph nodes were aspirated during the study period. Cytologic analysis of the lymph nodes revealed the following: Reactive lymphoid hyperplasia, 239 (61%); metastatic, 61 (15.6%); granulomatous lymphadenitis, 24 (6.1%); suspicious, 24 (6.1%); pyogenic abscess, 10 (2.6%); necrosis, 4 (1%); non-Hodgkin lymphoma, 2 (0.5%); and non-diagnostic, 28 (7.1%). Immunohistochemical analysis was performed on 26 (6.6%) cases to the cell block samples. Histopathological correlation was available in 73 (18.7%) cases. The overall diagnostic sensitivity, specificity, PPV, and NPV of FNAC of lymph nodes were 87.9%, 100%, 100%, and 89.7%, respectively. The overall diagnostic accuracy was 94.1%. In case of malignancies, the histopathological correlation was 100%. Of four cases with false negative, three were low-grade non-Hodgkin lymphoma and one was granulocytic sarcoma. CONCLUSION: FNAC of lymph nodes is a safe, easy, cheap, quick diagnostic tool and reduces the need for diagnostic excisional biopsy in many patients. Cytological diagnosis can be supported with immunohistochemical analysis of cell block samples. However, lymphomas, particularly low-grade non-Hodgkin lymphomas, are a diagnostic challenge and additional studies such as flow cytometry are required in cases with suspicious for lymphoma.

Evaluation of Thyroid Fine-Needle Aspiration Biopsies according to Cytological Methods and Comparison with Histopathological Diagnosis.

OBJECTIVES: In this study, we aim to compare the results of aspiration of thyroid nodules evaluated according to the Bethesda category (BC) with tissue diagnoses in the operation materials and to compare the sensitivity, specificity and accuracy rates according to cytology methods. METHODS: The previous fine-needle aspiration biopsy (FNAB) of thyroid nodules of 879 cases diagnosed histopathologically between 2010 and 2017 was examined. The FNAB results determined according to the Bethesda system were matched with tissue diagnoses, sensitivity, specificity, and accuracy rates were investigated according to cytology methods. RESULTS: Sensitivity, specificity, Positive predictive value (PPV), Negative predictive value (NPV) and accuracy rates were found in all FNAB results (in units of %; Sensitivity; 84.7, Specificity; 81.1, PPV; 74.1, NPV; 89.2, Accuracy; 82.5). All of the cytological evaluation methods of thyroid FNABs were found to be reliable and effective (Generally, the results are 80% and above). Specificity and accuracy rates were close to the general average (82.5%) in all methods. However, in cases evaluated with liquid base cytology (LBC) method and in addition to LBC or conventional smear (CS), the sensitivity rates in cases where cell block (CB) were evaluated together were higher than cases in which LBC and CS were used alone (92.6% and 91.0%). When examined statistically, there was no significant difference concerning sensitivity, specificity and accuracy rates of cytological methods (p>0.05, respectively, p=0.576, 0.065, 0.643). CONCLUSION: In cytopathology, when evaluating thyroid aspirations, it is seen that the LBC method is used instead of CS. In our study, we recommend the use of the LBC method, which seems to have the highest sensitivity (taking into account its technical advantages), instead of CS. However, we think that both CS and LBC methods should be evaluated by supporting them with cell block sections.

Relationships between androgen receptor expression and clinicopathological parameters in male breast cancer.

INTRODUCTION: Most patients with male breast cancer (MBC) express the androgen receptor (AR). AR expression in these tumors may have both prognostic and predictive values because its presence indicates the potential benefits of an anti-androgen therapeutic approach. The present study aimed to investigate the relationship between AR expression and clinicopathological parameters in MBC. MATERIAL AND METHODS: The data of 35 patients who received a histological diagnosis of MBC at the pathology department of our hospital between January 2007 and December 2017 were retrospectively reviewed. The patients' demographic data, follow-up records and pathology reports were recorded. AR expression status and its relationship with clinicopathological parameters were evaluated. The chi-square test was used to compare independent groups. Univariate survival analyses were performed using the Kaplan-Meier survival procedure. A p value of ≤0.05 was considered statistically significant. RESULTS: There was no significant relationship between AR expression and AJCC stage (p=0.585), pathologic stage (p=0.696), histologic grade (p=0.685), lymph-node status (p=0.685), survival rate (p=1.000), age(p=1.000), lymphovascular invasion (p=0.700), perineural invasion(p=1.000), skin invasion (p=1.000), nipple involvement(p=1.000), DCIS presence(p=1.000), ER positivity(p=1.000), PR positivity (p=0.218), Her2 expression (p=0.523), Ki67 index (p=0.685), Luminal A group (p=0.700), Luminal B group (p=0.691), triple negative group (p=1.000). CONCLUSION: Further investigation of the relation between AR expression and clinicopathological parameters of patients with MBC might yield important information and lead to the development of additional treatment options. KEY WORDS: Androgen receptor, AR expression, breast cancer, Male Breast cancer, Prognosis, Receptor status.

Mir-129-2-3p Has Tumor Suppressor Role in Ewing Sarcoma Cell Lines and Cancer Tissue Samples

Abstract Deregulation of miRNA expressions was identified as a novel feature of tumor biology in Ewing sarcoma (EWS). The aim was to evaluate the regulatory role of miR-129-2-3p in EWS cell lines and human EWS tissue samples. EWS cell lines TC-71, TC-106, and CHLA-99 were used in the study and real-time PCR was utilized to investigate the functional role of tumor suppressor mir-129-2-3p and miR-129-2-3p levels in the cells. Proliferation, migration, invasion and apoptosis assays were carried out within the scope of functional in vitro studies. Expression levels of CDK6 and SOX4, which are miR-129-2-3p target genes, were examined. Moreover, the change in expression levels of miR-129-2-3p in EWS tumor tissues was also examined. It was determined that miR-129-2-3p expression markedly diminished in all the studied cell lines. In addition, miR-129-3p was found to decrease in proliferation, migration, invasion and apoptosis assays in all EWS cell lines. CDK6 and SOX4 levels were also decreased in miR-129-2-3p transfected cell lines. It was found that miR-129-2-3p levels were significantly decreased in EWS tumor tissue samples compared to the corresponding adjacent normal tissue samples. In line with the results of our current study, where the possible function of miR‐129-2-3p in EWS cell lines was examined, for the first time in the literature miR-129-2-3p was shown to have low expression level in EWS lines and EWS tumor tissue samples, and to provide a tumor suppressor effect.

Radiologic Findings of Scapular Langerhans Cell Histiocytosis Successfully Treated with CT-Guided Corticosteroid Injection.

Although Langerhans cell histiocytosis (LCH) may arise from any bone, flat bones (skull, ribs, scapula, clavicle, and mandible) are more commonly involved.The overall reported incidence of scapular involvement by LCH is nearly 3% in the literature. Intra-lesional corticosteroid injection can be given for lesions that cause pain or postural deformity. We, herein, report a 26-year male with scapular LCH who was suffering from right shoulder pain and right arm weakness. The patient received intra-lesional methylprednisolone under CT-guidance for treatment. On follow-up imaging, almost total regression was observed. We suggest that percutaneous CT-guided intra-lesional steroid injection is an efficient method for the treatment of LCH located in bone. Key Words: Bone, Langerhans cell histiocytosis, Local treatment, Corticosteroid.

Intraoperative Imprint-squash Methods in Central Nervous System Tumors.

OBJECTIVES: Central nervous system (CNS) tumors constitute 1.3% of all cancers in adults and are the seventh leading cause of death in developed countries. CNS tumors are very soft and have a gelatin-like texture. Smear technique is a very simple and fast method for the diagnosis of brain tumors. METHODS: In this study, we evaluated the imprint and squash cytology of 100 cases sent to the pathology clinic. The sections of the paraffin blocks were prepared after the operation in the neurosurgery clinic of the SBU Hamidiye Sisli Efal Training and Research Hospital. The accuracy rate was 90% in the differential diagnosis of malignant tumors from the benign ones. CONCLUSION: Cytological samples were taken from 100 cases of intracranial tumors that were operated in the neurosurgery clinic of Sisli Etfal Hospital, and the paraffin sections prepared from the biopsy materials were examined. The cases with misdiagnosis were usually differentiated from solid-hard tumors, epithelial-grade cystic structures, and medulloblastoma localized in the posterior fossa, medulloblastoma and ependymoma. However, this method has been found to be very convenient in practice due to its ease technically, low cost and equipment savings.

Oncocytic Lesions of Salivary Glands with Morphological and Immunohistochemical Findings.

OBJECTIVES: Salivary gland neoplasms are less than 5% of all head and neck neoplasms (1). Although there are morphological similarities between different neoplasms, there may be catchy morphological differences in a single tumour. According to the World Health Organization (WHO), 4th Head and Neck Tumours Classification oncocytic salivary gland lesions are classified as nodular oncocytic hyperplasia, oncocytoma and oncocytic carcinoma. Oncocytic cells may be a component of other salivary gland neoplasms and metastatic malignities. METHODS: In this study, salivary gland oncocytic lesions diagnosed in 2016-2017 were evaluated with Haematoxylin and Eosin (H&E) sections and PAS, diastase resistance PAS, p63, DOG1, cytokeratin7 (CK7), androgen receptor (AR) and PAX8 stains. RESULTS: Nineteen cases were benign, two cases were malignant. Eighteen of the benign lesions were Warthin tumour (WT), one case was oncocytoma with nodular oncocytic hyperplasia. Acinic cell carcinoma (AciCCA) with oncocytic cells predominant was one of the malignant cases. The other case was high-grade salivary duct carcinoma (SDCA). CONCLUSION: The rarity and heterogeneity of this group of lesions may cause difficulties in diagnosis. We present histochemical and immunohistochemical findings of these lesions in light of the literature.

Correlation between the Expression of PD-L1 and Clinicopathological Parameters in Triple Negative Breast Cancer Patients.

OBJECTIVE: Triple-negative breast cancer (TNBC) is a heterogenous group of tumors with no estrogen receptor (ER), progesterone receptor (PR) and Cerb-B2/HER2 expression. Programmed death ligand-1 (PD-L1) is a transmembrane protein located on both non-tumor and tumor cells and it has been shown to be associated with the escape of tumor cells from the immune system. PD-L1-targeted therapy alone or in combination is now an alternative strategy in several aggressive tumor types. In this respect, TNBC is a potential candidate having limited treatment options and poor outcome. MATERIAL AND METHODS: Sixty-one breast cancers with no expression of ER, PR and Cerb-B2/HER2 were chosen to study PD-L1 immunohistochemistry. PD-L1 staining and its correlation with main clinicopathological parameters were evaluated. RESULTS: The percentage of PD-L1 positivity was 37.7% and 47.5% in tumor and tumor microenvironment, respectively. The positivity rate was higher in breast carcinomas with medullary features (83.3%) and metaplastic carcinoma (66.6%) subgroups. PD-L1 expression of tumors was positively correlated with their Ki-67 score and PD-L1 positivity of the tumor microenvironment. No significant relationship was found between the other variables. CONCLUSION: PD-L1 expression rate was remarkable both in the tumor and the tumor microenvironment of TNBCs. Larger cohorts of TNBC are required to further describe their PD-L1 expression characteristics and help standardize PD-L1 immunohistochemistry assays in these tumors.

Thyroid hemiagenesis: a case report.

Thyroid hemiagenesis is a rare entity in the literature. Developmental hemi-thyroid anomalies can result from either an abnormal descent or an agenesis of one lobe of the thyroid gland. This study aimed at presenting a thyroid hemiagenesis case incidentally diagnosed by neck ultrasonography (USG), who had complaints of pain and swelling in the neck. USG examination revealed lack of left thyroid lobe and multiple nodules in the right lobe. Fine Needle Aspiration Biopsy (FNAB) showed follicular neoplasia, and right subtotal thyroidectomy was performed. We report the rarity of the condition and emphasize the role of imaging techniques in preoperative diagnosis and subsequent management.

Comparison of Monitor-Image and Printout-Image Methods in Ki-67 Scoring of Gastroenteropancreatic Neuroendocrine Tumors.

Gastroenteropancreatic neuroendocrine tumors (GEP-NET) are classified according to tumor grade. Ki-67 and mitotic count are the two determinants of this classification. Therefore, Ki-67 scoring becomes very important in classifying the patients accurately. Eye-balling, counting of cells through the microscope, automated image analysis systems, and manual counting of printed image are the four major scoring methods in use. The aim of this study is to show the agreement between monitor-image method (MIM) and printout-image method (PIM) of Ki-67 scoring. In our study, 120 GEP-NETs from 85 patients diagnosed between January 2005 and July 2017 were evaluated. Thirty-seven cases with either polypectomy or resection material were selected. Seven different scoring methods using either a monitor-image or a printout-image were applied for Ki-67 scoring. They are as follows: whole-PIM, 1/9-PIM, whole-MIM, 1/4-MIM, 1/6-MIM, 1/9-MIM, and 1/12-MIM. In the comparison of Ki-67 scoring methods, intraclass correlation coefficients ranging from 0.951 to 0.999 were found. The Bland-Altman analysis showed near-perfect agreement between whole-MIM and whole-PIM as well as 1/9-MIM and 1/9-PIM. The level of agreements among the other methods were sufficient too, but there was a relative decrease in the level of agreement as the area of counting becomes smaller. The average application time decreased from 373.7 to 41.7 s gradually as the scoring area becomes smaller. Our study shows that there is a remarkable agreement between the MIM and PIM used in Ki-67 scoring.

Nonneoplastic Lesions of the Pancreas: A Retrospective Analysis of 20 Cases.

OBJECTIVES: In the pancreatic lesion cases, surgery is often planned based only on imaging results and without a preoperative histological diagnosis, due to the high risk of malignancy in combination with the difficulty of invasive interventions and limited cytopathological evaluation. In this study, the records of 20 patients who had undergone a pancreatectomy procedure and who were diagnosed with nonneoplastic pancreatic lesions were retrospectively evaluated according to the clinical and histopathological findings. METHODS: A total of 122 cases of patients who underwent a pancreatectomy with suspicious lesions between 2004 and 2016 were retrospectively assessed in detail using the clinical and histopathological findings. RESULTS: Nonneoplastic lesions were observed in 20 (16%) of 122 patients who underwent a pancreatectomy. Histopathological examination revealed 11 cases of chronic pancreatitis, 1 hematoma, 1 instance of hemorrhagic necrosis secondary to trauma, 1 pseudocyst, 1 granulation tissue, 1 retention cyst, 1 bile duct cyst, 1 patient with Castleman disease, and 1 instance of fat necrosis were seen. In 1 patient, no evidence of disease was found. In addition, among the patients with chronic pancreatitis, autoimmune pancreatitis was observed in 1, adenomyoma of the ampulla of Vater was present in 1, and a pseudocyst was found in 1 patient. CONCLUSION: A clinical and histopathological analysis of nonneoplastic lesions found in pancreatectomy patients was performed.

Sarcoidosis with Hepatic Involvement: A Case Report.

Sarcoidosis is a systemic, noncaseating granulomatous disease with an unknown etiology. The liver is one of the most frequently affected organs. This case is presented to emphasize that hepatic granulomatous foci can lead to a determination of etiology in a diagnosis of sarcoidosis. A 53-year-old-female patient with complaints of fatigue and abdominal pain was admitted to the clinic of gastroenterology. The blood levels of alanine transaminase, aspartate transaminase, alkaline phosphatase and gamma-glutamyl transferase were markedly increased. The autoimmune parameters were negative. A Tru-Cut biopsy (Becton, Dickinson and Co., Franklin Lakes, NJ, USA) of the liver was performed based on the initial diagnoses of tuberculosis, lymphoma, and sarcoidosis. Histopathological evaluation revealed noncaseating granulomatous inflammation with Grade 3 macrovesicular steatosis. An investigation for hepatic sarcoidosis was recommended. The angiotensin-converting enzyme levels were 5 times higher than normal. Based on this result, the diagnosis was sarcoidosis with hepatic involvement. The treatment and follow-up of the patient continues.

Primary Pure Uterine Lipoma: A Report of two Cases and Review of the Literature.

Pure uterine lipomas are rare diagnoses despite lipoma being a common entity. The histogenesis of these lesions remains unknown, and its clinical symptoms are similar to those of uterine leiomyomas. In this report, two cases of uterine lipomas were presented with their histopathological and clinical aspects.

A Rare Tumor in Childhood Desmoplastic Infantile Astrocytoma: Two Case Reports.

Desmoplastic infantile astrocytomas (DIAs), are rare supratentorial tumors, usually observed in the first 24 months of life. Despite their aggressive appearance, they tend to follow a favorable clinical course. Total or near total resection of tumor is usually the treatment option. Desmoplastic Infantile Ganglioglioma (DIG) and DIA are WHO grade I tumors that have similar clinical and morphological findings. The only criterion in differential diagnosis is the neural component of DIG. These tumors both have dense fibroblastic stroma and positive staining with glial fibrillar acidic protein (GFAP) and CD34. A rare case of desmoplastic infantile astrocytoma presenting with right side partial seizures presented in a 1-year-old child. A rare case of desmoplastic infantile astrocytoma presenting with focal onset generalized seizures presented in a 1-year-old child. Despite their radiological and histological properties, these tumors have a benign course. After 3-year follow-up for the first case and 1-year follow-up for the second case, there was no recurrence.

Anterior orbital leiomyoma originating from the supraorbital neurovascular bundle.

PURPOSE: To present a young female patient with left anterior orbital leiomyoma that originates from the supraorbital neurovascular bundle. CASE PRESENTATION: A 41-year-old female patient was admitted to our clinic with a complaint of swelling of the left upper eyelid. Based on the ophthalmological and imaging assessments, the excisional biopsy with the preliminary diagnosis of dermoid cyst was planned. The histopathological and immunohistochemical examinations of excised sample revealed surprisingly that the tumour was a leiomyoma. No recurrence was detected in the patient's follow-up. CONCLUSION: Although it is rare, orbital leiomyoma should be considered in the differential diagnosis of patients with orbital tumour.

Surgical Treatment of Confirmed Intraosseous Lipoma of the Calcaneus: A Case Series.

Intraosseous lipoma of the calcaneus is a benign lesion formed by mature adipose tissue. When the lesion is symptomatic, the most frequent presentation is localized pain and soft tissue swelling. Because these lesions can regress spontaneously, conservative treatment methods are recommended. Operative excision is mostly required for painful lesions and pathologic fractures. The data from 14 patients with calcaneal intraosseous lipoma, who had undergone surgery in our clinic, were evaluated retrospectively. Using Milgram's classification system, 9 lesions were classified as stage 1, 4 as stage 2, and 1 as stage 3. All lesions were occupying 100% of intracalcaneal cross-section in the coronal plane and >30% in the sagittal plane of magnetic resonance imaging sections. The mean preoperative visual analog scale score was 5.29 ± 1.14 (range 4 to 7), and the mean postoperative visual analog scale score at the last follow-up visit was 1.14 ± 0.36 (range 1 to 2), which was significantly better (p < .01). The mean Maryland foot score at the last follow-up visit was 97.71 ± 2.02 (range 95 to 100). The mean American Orthopaedic Foot and Ankle Society Ankle-Hindfoot scale score was 97.86 ± 2.11 (range 94 to 100) at the last follow-up visit. The differences between the pre- and postoperative values were statistically significant (p < .01). No recurrence had been detected within a median follow-up period of 84 months. Operative management of symptomatic lesions related to intraosseous lipoma of the calcaneus provides better results compared with the preoperative state.