Exploring the Impact of Cytogenetic Abnormalities on Treatment Responses and Survival Outcomes in Multiple Myeloma: A Single-Centre Experience of 13 Years of Follow-Up.

(1) Background: The introduction of novel therapies has led to a considerable evolution in the management of Multiple Myeloma, and chromosomal abnormalities predict the success of treatment. We aimed to characterize cytogenetic abnormalities for risk stratification in the patient population and to evaluate the predictive and prognostic value of the specified abnormalities in distinct treatment modalities. (2) Methods: This study included patients with Multiple Myeloma who applied to the Internal Medicine Clinic of the Cukurova University Faculty of Medicine. Between 2010 and 2023, 98 cases with cytogenetic abnormality data were identified. We analysed the effects of cytogenetic abnormalities on survival and response rates to first chemotherapies. (3) Results: P53 del was the most prevalent abnormality, and t(11;14) was the most common translocation. There was no significant difference in the mean survival and treatment response rates for specific cytogenetic abnormalities. When chemotherapies based on lenalidomide were initiated, patients' life-death statuses differed significantly from those of treatments without lenalidomide. Regardless of the type of chromosomal aberration, lenalidomide-based treatments independently enhanced average survival 14-fold, while there was no significant difference in overall survival among treatments. (4) Conclusions: In individuals with cytogenetic abnormalities, lenalidomide-based treatments should be started regardless of the chemotherapy to be used for the condition.

Effects of enhancer of zeste homolog 2 and mucin 1 expressions on treatment response in breast cancer.

OBJECTIVE: Breast cancer is the most common malignancy in women. In the treatment of these patients, pathological complete response is defined as the absence of invasive cancer in breast or lymph node tissue after the completion of neoadjuvant chemotherapy. In this study, we aimed to investigate the relationship of enhancer of zeste homolog 2 and mucin 1 expressions with pathological complete response in patients with breast cancer receiving neoadjuvant chemotherapy. METHODS: A total of 151 patients were included in the study. Enhancer of zeste homolog 2 and mucin 1 expressions were evaluated in the biopsy materials pre-neoadjuvant chemotherapy and post-neoadjuvant chemotherapy surgical material, and their relationship with pathological complete response was investigated. RESULTS: The pathological complete response rates were significantly higher among the hormone receptor-negative patients, those with a high Ki-67 score, and patients with HER2-positive. Higher pathological complete response rates were obtained from patients with enhancer of zeste homolog 2 expression positivity pre-neoadjuvant chemotherapy. In addition, after neoadjuvant chemotherapy, enhancer of zeste homolog 2 expression was found to be completely negative in materials with pathological complete response; that is, in breast tissues considered to be tumor-free. While there was no significant relationship between mucin 1 expression and pathological complete response pre-neoadjuvant chemotherapy, mucin 1 expression was determined to significantly differ between the tissues with and without pathological complete response among the surgical materials examined. CONCLUSION: In our study investigating the relationship between enhancer of zeste homolog 2 and mucin 1 expression and pathological complete response in patients who received neoadjuvant chemotherapy, we found that enhancer of zeste homolog 2 expression could be used as a predictive marker for pathological complete response. However, mucin 1 expression was not associated with pathological complete response.

Effects of enhancer of zeste homolog 2 and mucin 1 expressions on treatment response in breast cancer

SUMMARY OBJECTIVE: Breast cancer is the most common malignancy in women. In the treatment of these patients, pathological complete response is defined as the absence of invasive cancer in breast or lymph node tissue after the completion of neoadjuvant chemotherapy. In this study, we aimed to investigate the relationship of enhancer of zeste homolog 2 and mucin 1 expressions with pathological complete response in patients with breast cancer receiving neoadjuvant chemotherapy. METHODS: A total of 151 patients were included in the study. Enhancer of zeste homolog 2 and mucin 1 expressions were evaluated in the biopsy materials pre-neoadjuvant chemotherapy and post-neoadjuvant chemotherapy surgical material, and their relationship with pathological complete response was investigated. RESULTS: The pathological complete response rates were significantly higher among the hormone receptor-negative patients, those with a high Ki-67 score, and patients with HER2-positive. Higher pathological complete response rates were obtained from patients with enhancer of zeste homolog 2 expression positivity pre-neoadjuvant chemotherapy. In addition, after neoadjuvant chemotherapy, enhancer of zeste homolog 2 expression was found to be completely negative in materials with pathological complete response; that is, in breast tissues considered to be tumor-free. While there was no significant relationship between mucin 1 expression and pathological complete response pre-neoadjuvant chemotherapy, mucin 1 expression was determined to significantly differ between the tissues with and without pathological complete response among the surgical materials examined. CONCLUSION: In our study investigating the relationship between enhancer of zeste homolog 2 and mucin 1 expression and pathological complete response in patients who received neoadjuvant chemotherapy, we found that enhancer of zeste homolog 2 expression could be used as a predictive marker for pathological complete response. However, mucin 1 expression was not associated with pathological complete response.

Tumor-derived CTF1 (cardiotrophin 1) is a critical mediator of stroma-assisted and autophagy-dependent breast cancer cell migration, invasion and metastasis.

Macroautophagy/autophagy is an evolutionarily conserved cellular stress response mechanism. Autophagy induction in the tumor microenvironment (stroma) has been shown to support tumor metabolism. However, cancer cell-derived secreted factors that initiate communication with surrounding cells and stimulate autophagy in the tumor microenvironment are not fully documented. We identified CTF1/CT-1 (cardiotrophin 1) as an activator of autophagy in fibroblasts and breast cancer-derived carcinoma-associated fibroblasts (CAFs). We showed that CTF1 stimulated phosphorylation and nuclear translocation of STAT3, initiating transcriptional activation of key autophagy proteins. Additionally, following CTF1 treatment, AMPK and ULK1 activation was observed. We provided evidence that autophagy was important for CTF1-dependent ACTA2/α-SMA accumulation, stress fiber formation and fibroblast activation. Moreover, promotion of breast cancer cell migration and invasion by activated fibroblasts depended on CTF1 and autophagy. Analysis of the expression levels of CTF1 in patient-derived breast cancer samples led us to establish a correlation between CTF1 expression and autophagy in the tumor stroma. In line with our in vitro data on cancer migration and invasion, higher levels of CTF1 expression in breast tumors was significantly associated with lymph node metastasis in patients. Therefore, CTF1 is an important mediator of tumor-stroma interactions, fibroblast activation and cancer metastasis, and autophagy plays a key role in all these cancer-related events.Abbreviations: ACTA2/α-SMA: actin, alpha 2, smooth muscle CAFs: cancer- or carcinoma-associated fibroblasts CNT Ab.: control antibody CNTF: ciliary neurotrophic factor CTF1: cardiotrophin 1 CTF1 Neut. Ab.: CTF1-specific neutralizing antibody GFP-LC3 MEF: GFP-fused to MAP1LC3 protein transgenic MEF LIF: leukemia inhibitory factor IL6: interleukin 6 MEFs: mouse embryonic fibroblasts MEF-WT: wild-type MEFs OSM: oncostatin M TGFB/TGFß: transforming growth factor beta.

Modified techniques versus Hadfield's procedure in patients with periductal mastitis.

BACKGROUND: Periductal mastitis (PM) is a rare disease characterized by chronic inflammation of the terminal mammary ducts. Complete removal of terminal lactiferous ducts with Hadfield procedure is a previously defined technique in treatment but carries various complications risks. This study aims to evaluate the effectiveness of modified techniques in the treatment of PM. METHODS: Twenty women who underwent surgery due to PM between January 2012 and December 2019 were retrospectively analyzed. Types of PM were determined. All patients were operated on with three different incisions [Hadfield's operation with periareolar incision (n:11), periareolar combined radial incision (n:7), and round block incision (n:2)]. RESULTS: The mean age was 37.5 ± 6.5 years (range: 24-49). Sixty percent of patients had type 3 PM. In Hadfield's procedure, NAC retraction (n:2), seroma (n:1), and hematoma (n:1) were seen. In the periareolar incision combined radial incision group only one patient had complications (seroma) and none in the round block method. Follow-up was 12 ± 1.5 months and disease relapse occurred in two patients in the Hadfield group. Patients who underwent round block were more satisfied with the appearance of the nipple. CONCLUSIONS: In the treatment of PM, the main principle of surgical treatment is the excision of the affected canal with a clear margin. Apart from the classical Hadfield procedure, the round block method and periareolar combined radial incision techniques can be performed in the treatment of PM.

Prognostic significance of EGFR, MUC1 and PD-L1 expressions in cases with triple negative breast cancer.

PURPOSE: Twenty percent of the breast cancers are triple negative (TNBC). Despite the impressive progression in the biology of this subgroup, data is limited as compared to hormone and/or HER2 positive cases. Thus, the aim of this study was to detect the expression levels and to identify the prognostic values of MUC1, EGFR and PD-L1 in TNBC. METHODS: MUC1, EGFR and PD-L1 expressions were detected by immunohistochemistry in 97 cases with TNBC. Associations between clinical and histopathological parameters with overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method and compared by the log-rank test. Prognostic effects were analyzed by Cox proportional hazard models. RESULTS: During a median follow-up of 93 months (0.6-168.7) the mean PFS was 110.1 and OS was 121.8 months. Tumor diameter (T), involved lymph node status (N) and TNM were found to be prognostic for PFS and OS. PD-L1 in microenvironment (PD-L1 ME) and EGFR expression were found to be associated with longer PFS and OS, but MUC1 and tumor PD-L1 (PD-L1 TM) expressions were not. All combined analyses showed that in the subgroups of MUC1, PD-L1 TM or ME positive, EGFR expression was correlated with longer PFS and OS than those who were not. Older age (≥70 years), T and N status and also EGFR expression were found to be independent prognostic factors for OS in Cox regression analysis. CONCLUSION: EGFR expression was found to be one of the most important prognostic factors in addition to T and N status in cases with TNBC.

Unicentric Castleman Disease Mimicking an Autoinflammatory Disorder: A Diagnostic Challenge in a Pediatric Patient With Recurrent Fever.

Unicentric Castleman disease (CD) is a rare lymphoproliferative disorder that is characterized by the enlargement of lymph nodes on the neck, mediastinum, and retroperitoneum. Herein, we present a 6-year-old female patient, referred to our medical center because of recurrent fever accompanied by cervical lymphadenopathy and elevated inflammatory markers since 3 years of age. Fever episodes lasting 1 day continued irregularly without any accompanying symptom. MEditerranean FeVer (MEFV) gene analysis showed no mutations; however, as inflammatory markers including serum amyloid A remained markedly high during attack-free periods, colchicines was initiated. The patient did not respond to maximally tolerated doses of colchicine; therefore, we added canakinumab and systemic methylprednisolone, subsequently. Unresponsiveness to 3 doses of bimonthly canakinumab and new-onset hepatosplenomegaly led us to investigate large-vessel vasculitis and malignancy; therefore, we performed Position emission tomography, which further revealed a hypermetabolic retroperitoneal solid mass. After performing the excisional biopsy, the patient has been diagnosed as suffering from hyaline vascular variant CD, confirmed by histopathology. In conclusion, we report a pediatric unicentric CD, which resembled autoinflammatory diseases and responded well to surgical resection, with the normalization of inflammatory markers 1 month after the procedure. CD, even the unicentric and hyaline vascular variant, should be considered in the differential diagnosis of the patients with an autoinflammatory phenotype.

Myeloid Neoplasia and Lymphoblastic Lymphoma with Eosinophilia After Radioactive Iodine: A Case Report.

BACKGROUND: Thyroid cancer is the most common endocrine cancer, with an increasing incidence around the world in the last three decades. The increased risk of secondary cancer is associated with a genetic predisposition or radioactive iodine used in the treatment. CASE REPORT: A 65-year old male patient was operated on for thyroid papillary cancer. He received radioactive iodine on two occasions postoperatively. After six years, he presented with malaise and fatigue with leukocytosis and eosinophlilia. The physical examination revealed inguinal lymphadenopathies and splenomegaly, after examining the bone marrow and lymph node biopsies, he was diagnosed with eosinophilic myeloproliferative neoplasia and T-cell lymphoblastic leukaemia/lymphoma. CONCLUSION: Leukaemia and other haematological malignencies may develop after radioactive iodine treatment. Patients with radioactive iodine ablation history should be monitored for a long time.

Prevalence of cytogenetic abnormalities in chronic lymphocytic leukemia in the southern part of Turkey.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia among adults in Western populations. CLL has a wide range of clinical presentations and varied outcomes. For CLL, cytogenetic assessment is essential for estimating prognoses and determining the treatment of choice. The fluorescence in situ hybridization (FISH) technique is widely used for genetic assessment due to its high sensitivity. AIM: This study aimed to evaluate the frequencies of deletions of 13q14.3, 17p13.1, 11q22.3, and 13q34 and of trisomy 12 and to observe their effects on survival in 226 Turkish CLL patients using FISH analysis. RESULT AND CONCLUSION: The frequencies of abnormalities were 65.4% for del 13q14.3, 39.8% for del 17p13.1, 19% for del 11q22.3 (del ATM), and 15.9% for trisomy 12. No patients had a 13q34.3 aberration. Our results are partially consistent with literature findings. However, certain conflicts with prior results were observed, particularly with respect to the high prevalence of 17p13.1 deletions and the enhanced survival of patients with such deletions. These inconsistencies may represent population-based differences in the genetic epidemiology of CLL.

Micro-RNA (miRNA) profile in Hodgkin lymphoma: association between clinical and pathological variables.

miRNAs are small RNAs and control the expression of protein-encoding genes. The aim of this study was to determine the association between miRNA profile and clinical variables including age, stage, B symptom, histopathologic subtype, response to treatment, disease-free survival (DFS) and overall survival (OS) in classical Hodgkin lymphoma (cHL). A total of 377 miRNAs were studied by qPCR in 32 cases with cHL, and results were compared with 60 samples taken from cases with reactive lymphadenopathy. Biogazelle qbasePLUS 2.0 software was used to analyze the results. miR-582-3p, miR-525-3p, miR-448, miR-512-3p, miR-642a-5p, miR-876-5p, miR-532-3p, miR-654-5p, miR-128, miR-145-5p, miR-15b-5p, miR-328 and miR-660-5p were found to be decreased in cHL compared with controls. In contrast, miR-34a-5p (2.626-fold), miR-146a-5p (4.32-fold), miR-93-5p (2.347-fold), miR-20a-5p (4.930-fold), miR-339-3p (4.948-fold), miR-324-3p (4.98-fold), miR-372 (7.038-fold), miR-127-3p (8.234-fold), miR-155-5p (4.947-fold), miR-320a (17.502-fold) and miR-370 (21.479-fold) (p < 0.05) were found to be increased in cHL. There was no difference in miRNA profile according to the age, sex, stage, response to treatment, DFS and OS. However, miR-889 was found to be increased in patients with B symptom and miR-127-3p was found to be increased in nodular sclerosing subtype. Some miRNAs increase and some decrease in cHL. However, there was no clinical association between clinical variables and with the majority of the miRNA profile studied in this study. miR-889 and miR-127-3p were related to B symptom and nodular sclerosis subtype, respectively. We need more studies evaluating miRNA profile and clinical outcome in Hodgkin Lymphoma.

Colchicine therapy in amyloidosis related with plasmacytic Castleman disease presenting with nephrotic syndrome.

Castleman disease (CD) is a neoplasm that presents with single or multiple lymphadenopathy. The disease is characterized by fever, weight loss, anemia, polyclonal hyperglobulinemia, splenomegaly, thrombocytosis and peripheral lymphadenopathy. In this paper, we report a young man with plasmacytic type CD and amyloid A (AA) deposition who presented with intra-abdominal mass and nephrotic syndrome. He was successfully treated with colchicine following surgery.

PRAME Expression and Its Clinical Relevance in Hodgkin's Lymphoma.

OBJECTIVES: Although Hodgkin's lymphoma (HL) is one of the most curable cancers in adult patients, new targets have to be defined in cases resistant to traditional chemotherapy. The preferentially expressed antigen of melanoma (PRAME) is a cancer testis antigen and its expression is very scarce or absent in normal tissues. For this reason PRAME is a promising candidate for tumor immunotherapy. The aim of this study is to understand the correlation of PRAME expression with prognostic factors in HL, to determine the utility of PRAME as a targeted molecule for immunotherapy and to compare real-time polymerase chain reaction (real-time PCR) and immunohistochemistry (IHC) for the detection of PRAME. METHODS: In 82 patients, PRAME was studied using real-time PCR and IHC. Data analyses were performed using statistical methods such as t test, Mann-Whitney U test, χ 2 test, Kaplan-Meier method, log-rank test and Cox regression analysis. RESULTS: PRAME was detected in 15 (18.3%) patients using IHC and in 8 (9.8%) patients using real-time PCR. A correlation was found between PRAME positivity and higher International Prognostic Score (p = 0.039). PRAME positivity detected using real-time PCR was found to be correlated with shorter disease-free survival (DFS) and overall survival (OS, p = 0.0005). DISCUSSION: The demonstration of PRAME especially in histiocytes and Reed-Sternberg cells may provide guidance for immunotherapy. Although PRAME positivity increases the risk for death (3.56), independent risk factors that affected DFS and OS occurred in advanced age and high-risk groups. CONCLUSION: Although real-time PCR is sensitive in the detection of PRAME, IHC can be another useful method. Despite the need for studies conducted on larger patient samples, PRAME expression is considered as a poor prognostic parameter in HL.

Programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), and EBV-encoded RNA (EBER) expression in Hodgkin lymphoma.

Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) are new targets in cancer immunotherapy. PD-1 protein is an immune checkpoint expressed in many tumors. Epstein-Barr virus (EBV) is present in malignant Hodgkin/Reed-Sternberg (HRS) cells in approximately 40-50 % of Hodgkin lymphoma (HL). The aim of this study is to evaluate the clinical and prognostic importance of PD-1 and/or PD-L1 in HL and also to determine the association between EBV-encoded RNA (EBER) and PD-1/PD-L1. Formalin-fixed, paraffin-embedded tissue samples from 87 cases with HL were analyzed in this study. Immunohistochemical staining was performed to detect the PD-1 and PD-L1 expressions. Chromogenic in situ hybridization for EBER was performed using fluorescein-labeled oligonucleotide probes. PD-1 and PD-L1 expressions were found in 20 % of the cases. The EBER positivity was found in 40 cases (45 %). It has been found that co-expression of PD-1 and PD-L1 was associated with shorter survival although PD-1 or PD-L1 expressions were not found to be related with survival. Overall survival (OS) and disease-free survival (DFS) in cases without PD-1 and PD-L1 expressions were 135 and 107 months, respectively. OS and DFS in cases with co-expression for PD-1 and PD-L1 were 24 and 20 months, respectively, and these differences were found to be statistically significant for both OS and DFS (p = 0.002 and p = 0.003, respectively). Cox regression analysis showed that co-expression of PD-1 and PD-L1 was found to be an independent risk factor for prognosis (OR 6.9, 95 % CI 1.9-24.3). Targeting PD-1 and/or PD-L1 is meaningful due to the 20 % expression of each in HL, and we did not find an important association between PD-1 and PD-L1 and EBER expression in HL. Very poor outcome in cases with co-expression of PD-1/PD-L1 suggests new avenues to detect the new prognostic markers and also therapeutic approaches in HL.

DNA repair gene polymorphisms in B cell non-Hodgkin's lymphoma.

Cancer is a group of diseases characterized by DNA injury, and genetic and environmental factors are important in the etiology of the cancers. It is well known that there are association variabilities in DNA repairment and sensitivity against the cancer. The aim of this study is to look for some important gene polymorphisms associated with DNA repair in cases with B cell non-Hodgkin's lymphoma (B-NHL). Ninety-four cases with NHL and 96 healthy controls were included in this study. ERCC2 (Lys751Gln), XPC (Gln939Lys), ERCC5 (Asp1104His), and XRCC3 (Thr241Met) gene polymorphisms were studied by using Tm Shift Real-Time PCR Technology. ERCC5 Asp1104His polymorphism showed a protective effect against the B-NHL in individuals carrying this mutant allele (p = 0.009), and differences were more prominent in males (p = 0.001). When the patient and control groups were divided according to their smoking habit, the mutant allele of the XPC gene showed a protective effect in the nonsmoker group (p = 0.040). The mutant allele G of ERCC5 (CG) polymorphism was found to be protective against lymphoma (p = 0.010). There were no differences among cases with B-NHL and controls for ERCC2 codon 751, XPC codon 939, and XRCC3 codon 241 gene polymorphisms. DNA repair gene polymorphisms can affect the risk of lymphoma, and it will be useful to detect the DNA repair gene polymorphisms in cases with lymphoma in studies covering a higher number of cases.

Extramedullary myeloid tumor involving the pancreas: a case report and review of the literature.

Extramedullary myeloid tumors (EMMTs) are the tumors of myeloid cells. These tumors may occur in all of the organs of the body, but some localizations are rare. Pancreatic involvement of EMMTs is a rare entity. Here we report a case of EMMT of the pancreas 4 years after allogeneic stem cell transplantation and we review the existing data about EMMTs involving the pancreas.

Abdominal actinomycosis with multiple myeloma: A case report.

Actinomycosis is a chronic suppurative infection, for which immune suppression is a predisposing factor. In unusual cases, this disease may present as an abdominal wall involvement simulating a soft tissue tumor as seen in the present case. The presented patient had no signs of trauma or surgical approach and the pathology was considered to be a primary abdominal wall actinomycosis. Preoperative diagnosis is difficult due to the nonspecific nature of clinical presentation, radiographic and laboratory findings. Surgery combined with antibiotic treatment is a curative approach for this relatively rare infection. Surgeons must be aware of this disease in order to ensure correct diagnosis and to prevent performing any unnecessary procedures. The present study describes a case of abdominal actinomycosis with multiple myeloma, together with a review of important points related to this disease.

A new approach to the treatment of metastatic paraganglioma: sorafenib.

Paragangliomas are relatively rare chromaffin cell tumors which may be cured through resection. Patients with paragangliomas may develop metastatic diseases. There is no consensus regarding refractory chemotherapy for treatment of metastatic disease. In this report, we presented a case of a 43-year-old woman who was admitted to the hospital with a history of episodic headaches, diaphoresis, and weakness. Elevated plasma catecholamine levels and a right paraaortic mass were observed on computed tomography. The mass was excised, and a diagnosis of paraganglioma was confirmed. After 20 months of follow-up, local recurrence and metastases were detected in the thorax, abdomen, and skeletal system. Plasma and urinary catecholamine levels were high. Chemotherapy was administered, and no improvement was observed. Therefore, following this palliative conventional chemotherapy, sorafenib was administered for three months, and, finally, positron emission tomography showed that the patient's lesions had completely regressed.

Perinatal autopsy evaluation of 2150 autopsies in the Çukurova region of Turkey.

OBJECTIVE: We aimed to document the reasons of perinatal deaths in a large autopsy series performed in our institute, which is a reference center in the Çukurova region of Turkey. MATERIAL AND METHOD: The study included 2150 autopsies performed between January 2000 and December 2012 at our institute. Diagnoses were categorized according to the detected pathologies; congenital malformations were detailed based on systems. RESULTS: A pathology was detected in 1619 of 2150 (73.3%) autopsies. Congenital malformations were the most common diagnosis with 68.2%. Neural tube defects and central nervous system malformations were the most frequent system malformation in 28.8% of cases, followed by the urogenital system (11.4%) and musculoskeletal system (8.3%), respectively. Malformation syndromes including multisystem anomalies were defined in 109 cases (9.3%). CONCLUSION: Congenital malformations are the most common reason for perinatal deaths, with autopsy having an additive role to prenatal and genetic evaluations and providing foresight for planning a subsequent pregnancy.