Are micro-RNA 21 and 143 indicative as prognostic biomarkers in dedifferentiated endometrial adenocarcinoma?

AIM: Dedifferentiated endometrial adenocarcinoma (DEAC) is a rare, aggressive subtype, accounting for 2% of all endometrial cancers. Poor survival in DEAC prompts the need for effective treatment modalities through better prognostic classification. MicroRNAs (miRNA) have essential roles in tumor angiogenesis, which might enable their use as novel biomarkers. In this study, we aimed to reveal the relationship between the expression of miRNA-21 and miRNA-143, which are associated with angiogenesis, and the prognosis of DEAC. METHOD: The study included six cases diagnosed with DEAC. The expression levels of miRNA-21 and miRNA-143 were detected by quantitative real-time PCR. Microvascular density (MVD) was measured by CD34 staining. All data and effects on survival were compared for statistical significance. RESULTS: Six cases diagnosed with DEAC were included in the study. The percentage of undifferentiated components ranged from 50 to 90%. The second component of differentiated carcinoma was detected as endometrioid (3/5 grade I, 1/5 grade II, 1/5 grade III) in five cases and serous in one case. The mean MVD was 27 (range 17-44, SD 9.4). In three cases, miRNA-21 expression was down-regulated in neoplastic areas compared to non-neoplastic areas. On the contrary, it was found to be up-regulated in the remaining three cases. MiRNA-143 expression decreased in four cases and increased in two cases. CONCLUSIONS: Based on these findings, we found a significant irregular expression of miRNA-21 in DEACs. As in other cancers, angiogenesis is significantly associated with survival in DEACs. This study provides initial data for revealing possible implications of miRNAs as prognostic indicators in DEAC.

Prognostic evaluation of breast cancer patients with evident bone marrow metastasis.

In this study, we aimed to evaluate the clinicopathologic characteristics and prognosis of breast cancer (BC) patients with symptomatic bone marrow metastasis (BMM). Fifty-four BC patients, including patients with and without BMM, were evaluated retrospectively. In particular, the clinicopathologic features and survival of the patients with BMM (n = 27) were assessed and compared with the patients without BMM. All of the patients with BMM also had osseous metastases, and bone was the first site for distant recurrence in the majority of patients in the study group. Anemia was the most frequent symptom at presentation. The median time to BMM was 36.1 months (range 1.6-70.5 months, 95% CI). HER2(+) patients developed BMM earlier than HER2(-) patients (3.2 versus 38.3 months, 95% CI; p = 0.05). Patients with advanced disease at the time of initial BC diagnosis developed BMM earlier than patients with early disease (p = 0.04). Time to development of BMM was significantly shorter in tumors with perinodal infiltration (p = 0.001) and multicentric focus (p = 0.025). Median survival time after the diagnosis of apparent BMM was 6.43 months. Survival after BMM diagnosis in patients with grade III tumors was significantly shorter than in patients with grade I-II tumors (1.43 versus 5.36 months, 95% CI; p < 0.001). Systemic therapy after BMM diagnosis significantly prolonged survival (17.3 versus 0.93 months, 95% CI; p < 0.001). Hormone receptor-positive, high-grade, advanced-stage tumors at the time of initial BC diagnosis were more common in patients with BMM. Invasive lobular histology was also more frequent in patients with BMM. In conclusion, the presence of hormone receptor-positive, multicentric, grade III, advanced-stage tumors may be important risk factors for the development of evident BMM in BC patients. Systemic single-agent chemotherapy can prolong survival in these patients. However, multicenter analyses are required to verify these findings.

Prognostic significance of bone marrow fibrosis in diffuse large B-cell lymphoma.

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphomas. The aim of this study is to determine the relationship between the increase in the degree of fibrosis in the bone marrow and prognosis and mortality in newly diagnosed DLBCL. METHODS: Bone marrow biopsy of 153 newly diagnosed DLBCL patients was determined by staining with reticulin, Masson's trichrome histochemical stain, and the degree of fibrosis was determined. RESULTS: In the bone marrow biopsy performed at the time of diagnosis, bone marrow fibrosis (BMF) was observed in 70 patients. While BMF-1 was detected in 42 patients (60%), BMF-2 was detected in 25 patients (35%) and BMF-3 was detected in 3 patients (4%). As the degree of BMF increased, the median overall survival and median progression-free survival times were significantly shorter (p: 0.008), (p < 0.001). In patients with an increased degree of BMF, a significant decrease in leukocyte and neutrophil counts was observed after chemotherapy (p: 0.004). According to the results of the multivariate Cox regression model, it was determined that high NCCN-IPI risk (HR: 8.25; %95 CI: 1.09-62.52; p = 0.041) and being BMF ≥ 2 (HR: 3.75; %95 CI: 1.65-8.51; p = 0.002), increased the risk of death (p = 0.002, -2 loglikelihood = 392,553). CONCLUSION: When the literature was reviewed, it was seen that this study was the first to define that bone marrow fibrosis grade 2 and above in DLBCL is a prognostic marker associated with worse survival. In the bone marrow pathology, which is examined to detect advanced disease in DLBCL, besides lymphomatous involvement, the detection of fibrosis grade is very important.

Prognostic Significance of Bcl-2 and p53 Protein Expressions and Ki67 Proliferative Index in Diffuse Large B-cell Lymphoma.

OBJECTIVE: Diffuse large B-cell lymphoma (DLBCL) is a high-grade neoplasm that has heterogeneous properties in clinical, morphological, and immunophenotypic aspects. In the present study the effects of p53, Bcl-2, and Ki67 on prognosis and their relationships with clinical parameters were examined. MATERIALS AND METHODS: Thirty-five patients who had been diagnosed with nodally located DLBCL at Izmir Atatürk Training and Research Hospital between January 1999 and June 2006 were included in the study. The Ann Arbor classification system was used to determine the stage of the patients. The patients were evaluated according to age, sex, stage, B symptoms, extranodal involvement, and lactate dehydrogenase (LDH) level as well as immunohistochemically. P53 protein and Bcl-2 oncoprotein expressions and Ki67 proliferation index were assessed immunohistochemically. RESULTS: High Bcl-2 expression was found in 9 patients (25.7%), high p53 expression was found in 10 patients (28.6%), and high Ki67 was observed in 23 patients (65.7%). There was no significant correlation between p53 expression, Bcl-2 expression, or Ki67 proliferation index and age, sex, stage, B symptoms, extranodal involvement, LDH level, and overall survival (p>0.05). We did not find a relationship among p53 expression, Bcl-2 expression, Ki67 proliferation index, and prognosis (p>0.05). There was no significant relationship between overall survival and age, sex, stage, B symptoms, extranodal involvement, or LDH level (p>0.05). Our results revealed that Bcl-2 and p53 protein expressions and Ki67 proliferation index have no effect on overall survival of patients with DLBCL. CONCLUSION: The prognostic importance of p53 and Bcl-2 protein expressions and Ki67 proliferation index in DLBCL, which has biological and clinical heterogeneity, can be understood in a large series of studies that have subclasses and immunohistochemical markers with optimal cut-off values. CONFLICT OF INTEREST: None declared.

Epithelioid schwannoma of soft tissue: unusual morphological variant causing a diagnostic dilemma.

Epithelioid variant of peripheral nerve sheath tumors is a rare but, at the same time, a well-known entity especially in the malignant counterpart. However, peculiar epithelioid morphology in soft tissue schwannomas is unusual and has been defined recently. These tumors may cause diagnostic errors owing to their increased cellularity and epithelioid morphology. Typical histologic features of classic schwannoma such as Antoni A and B areas, Verocay bodies, and hyalinized vessels are either absent or only present in focal areas. Furthermore, strong and diffuse S-100 protein expression is seen in both benign and malignant counterparts of epithelioid schwannoma. The findings that are suggestive of the benign nature of the lesion are long-term clinical history, small size, superficial localization, encapsulation, bland morphology, lack of mitosis and necrosis, and a benign clinical course after complete excision. Pathologists should be aware of the epithelioid variant of schwannoma to avoid false diagnosis of malignancy. We hereby report 3 cases of unusual benign epithelioid schwannoma of the soft tissue with special regard to problems in differential diagnosis.

BCR-ABL1-Negative Chronic Myeloproliferative Neoplasms and Pulmonary Hypertension: A Prospective Long-Term Follow-up Study of the Impact of Pulmonary Hypertension on Survival.

PURPOSE: To assess the prevalence of PHT in patients with BCR-ABL1-negative CMPN and to evaluate impact of PHT on survival during long-term follow-up. PATIENTS AND METHODS: A total of 122 patients with BCR-ABL1-negative CMPN underwent transthoracic echocardiographic (TTE) evaluation at the beginning of study. Patients undergoing PHT on TTE examination were also evaluated by a pulmonologist. Patients were divided into 3 groups. Group A comprised patients with CMPN-related PHT; group B, patients with no PHT; and group C, patients with PHT due to secondary causes. Patients were evaluated again every 3 to 6 months. RESULTS: PHT was detected in 33 (27%) of 122 patients. Eight (6.5%) had CMPN-related PHT and the remaining 25 (20.5%) had non-CMPN-related PHT. Positivity for JAK2 V617F mutation in the study population was 72.9%. Groups were similar with respect to hematologic parameters and gender. Follow-up times were as follows: median (range) time from diagnosis to TTE and study end were 34 (1-158) months and 107 (16-251) months, respectively, and from TTE to study end was 88 (7-110) months. No significant differences found among the groups in terms of median time from diagnosis to TTE, follow-up, and overall survival. CONCLUSION: BCR-ABL1-negative CMPN patients had a lower prevalence of PHT compared to earlier studies. There was no statistically significant difference in median overall survival between patients with or without PHT. This may be because patients with PHT were asymptomatic and PHT was mild. The impact of PHT on survival was negligible.

Intimal sarcoma of the pulmonary artery with retrograde extension into the pulmonic valve and right ventricle.

We describe the case of a 42-year-old man who presented with dyspnea on exertion and a history of anticoagulation therapy for what was thought to be pulmonary arterial thromboembolism. He underwent surgery for obstruction of the right ventricular outflow tract. This is a very rare case of an intimal sarcoma of the pulmonary artery, which we confirmed by pathologic studies.

Cutaneous Alternariasis in a Patient With Renal Transplant.

INTRODUCTION: Alternaria is a common saprophyte, which is usually not pathogenic in humans. Generally, local wounds infections of Alternaria occur with presence of immunosuppression factors such as HIV infection and renal transplant patients. CASE PRESENTATION: We reported a case of wound infection induced by Alternaria spp. in a renal transplant patients. The main interest in this case was the rareness of the cutaneous alternariasis, its clinical aspects and good response to therapy. Recognition of Alternaria spp. as potential opportunistic pathogens is important for differential diagnosis of dermatological lesions, such as granulomatous or ulcerative lesions in immunocompromised patients. CONCLUSIONS: Alternariasis or similar cases may be increased due to the increased number of immunosuppressed patients. From this point of view, skin lesions in these patients must be planned and microbiologically evaluated considering the molds.

Molecular alterations in malignant blue nevi and related blue lesions.

Malignant blue nevi (MBN) are extremely rare dermal melanocytic tumors that arise in association with atypical cellular blue nevi (ACBN), cellular blue nevi (CBN), common blue nevi (BN), or de novo. The frequency of BRAF, NRAS, and KIT mutations in malignant melanoma varies according to histological subtype and localization. These mutations are rarely observed in blue nevi, which have recently been shown to carry activating mutations in GNAQ/GNA11 genes. Only few small molecular studies of MBN have been published. The aim of the present study was to analyze in MBN and related blue lesions such as ACBN, CBN, and BN the prevalence of BRAF, NRAS, KIT, GNAQ, and GNA11 gene mutations and their association with clinicopathological features. We included in our study 12 MBN, 6 ACBN, 29 CBN, and 35 common BN diagnosed between 1996 and 2014. Sanger sequencing method was used for mutation analysis. Overall, GNAQ exon 5 mutation was the most frequent alteration (46 %), in 2 of 12 (17 %) MBN, 1 of 6 (17 %) ACBN, 22 of 29 (76 %) CBN, and 13 of 35 (37 %) common BN. BRAF V600E and GNA11 exon 5 mutations were respectively detected in 3 of 12 (25 %) and in 2 of 12 (17 %) MBN while none in ACBN, CBN, and common BN. None of the cases harbored NRAS exon 2/3, KIT exon 9/11/13/17/18, or GNAQ/GNA11 exon 4 mutations. GNAQ gene exon 5 mutations are rare in MBN and ACBN but frequent in CBN and common BN. Remarkably, BRAF V600E and GNA11 exon 5 mutations were only detected in MBN, whereas none were found in ACBN, CBN, or common BN. Our data contribute new elements to the limited data on molecular alterations in MBN.

Passive infusion: a simple delivery method for retrograde cardioplegia.

Some damage to the capillaries and increase in myocardial edema have been shown when retrograde cardioplegia perfusion pressure exceeds 40-50 mmHg, or possibly when it falls within this pressure interval. To avoid these complications, we designed a very simple delivery method for retrograde cardioplegia: passive continuous infusion by gravitational force alone. From August 2002 through April 2003, 147 patients undergoing elective coronary artery bypass surgery were randomly allocated into 2 groups. In both groups, isothermic blood cardioplegic solution was infused continuously in a retrograde fashion, after antegrade cardioplegic arrest. Group 1 (n=76) received retrograde infusion passively by gravitational force, while Group 2 (n=71) received retrograde infusion from a manually controlled pressure bag, with the pressure maintained at about 40 mmHg. Myocardial biopsy specimens were taken just before the aorta was declamped, and myocardial edema was scored upon histopathologic examination. Postoperative myocardial damage was evaluated with periodic measurements of CK-MB isoenzyme and cardiac troponin T levels. We recorded cardioplegic infusion pressures and rates, and the total amount of potassium administered. The mean cardioplegic infusion pressures and rates, total potassium levels, and cardioplegic solution amounts were significantly lower in Group 1 than Group 2. Histologic observations revealed significantly less myocardial edema in Group 1. There were no differences between groups in CK-MB isoenzyme or cardiac troponin T levels, mortality, or morbidity. Retrograde continuous infusion of isothermic blood cardioplegic solution by gravitational force alone appears to provide satisfactory myocardial protection and to eliminate the harmful effects of higher pressures upon the myocardium.

Soft tissue giant cell tumor of low malignant potential of the neck: a case report and review of the literature.

Giant cell tumor of soft parts is a rare tumor that is clinically and histologically similar to giant cell tumor of the bone. We present a 53-year-old female with a giant cell tumor of low malignant potential arising from the neck. The clinicopathological features and the importance of immunohistochemistry in the differential diagnosis with other giant cell rich tumors was discussed.

Primary non-Hodgkin follicular lymphoma of the prostate: A case report.

Primary lymphoma of the prostate is a rare condition, representing 0.09% of prostatic malignancies. The clinical presentation of malignant lymphoma of the prostate is difficult to distinguish from other prostatic diseases. Systemic symptoms are rare. Treatments include surgery, chemotherapy and/or radiotherapy. We report a case of primary lymphoma of the prostate in a male patient who presented with lower urinary tract symptoms.

JAK2 V617F mutation status of 232 patients diagnosed with chronic myeloproliferative neoplasms.

INTRODUCTION/BACKGROUND: The aim of this study was to investigate the presence of Janus kinase 2 (JAK2) V617F mutation in patients with break point cluster region-abelson negative chronic myeloproliferative neoplasms (CMPNs) in our center. PATIENTS AND METHODS: We compared patients with and without the mutation, and also patients with the homozygous and heterozygous mutation, in terms of different clinical and laboratory features. RESULTS: The JAK2 V617F mutation was detected in 77 (95%), 88 (68%), and 17 (77%) of polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) patients, respectively. Among JAK2 V617F-positive patients, the homozygous genotype was found in 39 (50.6%) of the 77 PV, 23 (26.1%) of the 88 ET, and 11 (64.7%) of the 17 PMF patients. Bleeding was seen in 14 (6%) of all patients. Upper gastrointestinal bleeds were the most common, seen in 11 patients. Out of 232 CMPN patients, 44 (19%) had thrombosis. The most common thrombotic event was transient ischemic attack (52%). Progression to myelofibrosis was seen in 1 (1.2%) PV and 3 (2.3%) ET patients, and progression to acute leukemia was seen in 2 (2.5%) PV and 3 (2.3%) ET patients. Three patients with PV (3.7%), 3 with ET (2.7%), and 5 with PMF (2.7%) died during follow-up. CONCLUSION: JAK2 V617F mutation frequencies in our PV and ET patients were similar to those reported previously. JAK2 V617F mutation frequency in our PMF patients was greater than in previous reports. All of our PV patients with thrombosis and most of our ET patients with thrombosis (76.1%) were JAK2 V617F mutation-positive. This mutation seems to be correlated with thrombosis risk.

The prognostic significance of bone marrow metastases: evaluation of 58 cases.

BACKGROUND: Bone marrow biopsy is widely used method for diagnosis, follow-up and staging of hemato-oncologic diseases. This procedure is also used for determining the bone marrow metastasis in patients with solid tumors. In this study, clinical, hematological, and pathological features of 58 patients with bone marrow metastases diagnosed by bone marrow biopsies were examined retrospectively MATERIALS AND METHODS: Among 3345 bone marrow biopsies performed in our hospital between January 2006 and August 2013, 58 cases with solid tumor metastasized to bone marrow were included in this study. RESULTS: Among 58 cases with solid organ carcinoma metastasis in bone marrow, mean age was 59.9. Thirty-nine cases were found to have a known primary tumor focus. The most common tumors metastasized to bone marrow were breast carcinomas (23 patients, 59%), gastric carcinomas (6 patients, 15.3%), prostate carcinomas (4 patients, 10,2%), and lung carcinomas (3 patients, 7.7%), respectively. Nineteen patients were firstly diagnosed from bone marrow biopsies as metastatic carcinomas. The median overall survival after bone marrow metastasis was 28 days (95% confidence interval: 7.5-48.4). The median overall survival difference was not statistically significant between patients with primary known and unknown tumor (P = 0.973). Statistically significant difference was observed between the survival of breast cancer and gastric cancer (P = 0.028). The most common hematologic symptom was the coexistence of anemia and thrombocytopenia (31%), thrombocytopenia (27.6%) and anemia (20.7%) alone. The median overall survival difference was statistically significant between patients who have anemia and thrombocytopenia (P < 0.005). CONCLUSION: Bone marrow biopsy is an easily accessible, easily applied, a useful procedure for diagnosing metastatic diseases in patients with hematologic symptoms such as anemia and thrombocytopenia besides being an uncomfortable procedure for patients. Furthermore, it is useful in predicting the prognosis and short survey after diagnosing bone marrow metastasis.

Langerhans Cell Sarcoma of the Axillary Lymph Node: A Case Report and Review of the Literature.

Langerhans cell sarcoma is a rare, high-grade neoplasm with overtly malignant cytological features and the Langerhans phenotype. Herein, we present a rare case of Langerhans cell sarcoma in a 65-year-old female that presented with a painless enlarging mass in her right axillary region, along with the histopathological features and diagnostic characteristics in the light of literature on Langerhans cell sarcoma.

Lymphoma of the cervix: A diagnostic pitfall on cervicovaginal smear.

Malignant lymphoma that secondarily involves the cervix is a rare condition and may be difficult to distinguish from follicular cervicitis and small cell carcinoma. Cervical lymphoma is sometimes misdiagnosed on cervicovaginal cytology due to its rarity. We report a case of a cervical lymphoma in a 65-year-old woman, which was diagnosed as a squamous cell carcinoma on cervicovaginal cytology.