Potential prognostic determinants for FET::CREB fusion-positive intracranial mesenchymal tumor.

Intracranial mesenchymal tumor (IMT), FET::CREB fusion-positive is a provisional tumor type in the 2021 WHO classification of central nervous system tumors with limited information available. Herein, we describe five new IMT cases from four females and one male with three harboring an EWSR1::CREM fusion and two featuring an EWSR1::ATF1 fusion. Uniform manifold approximation and projection of DNA methylation array data placed two cases to the methylation class "IMT, subclass B", one to "meningioma-benign" and one to "meningioma-intermediate". A literature review identified 74 cases of IMTs (current five cases included) with a median age of 23 years (range 4-79 years) and a slight female predominance (female/male ratio = 1.55). Among the confirmed fusions, 25 (33.8%) featured an EWSR1::ATF1 fusion, 24 (32.4%) EWSR1::CREB1, 23 (31.1%) EWSR1::CREM, one (1.4%) FUS::CREM, and one (1.4%) EWSR1::CREB3L3. Among 66 patients with follow-up information available (median: 17 months; range: 1-158 months), 26 (39.4%) experienced progression/recurrences (median 10.5 months; range 0-120 months). Ultimately, three patients died of disease, all of whom underwent a subtotal resection for an EWSR1::ATF1 fusion-positive tumor. Outcome analysis revealed subtotal resection as an independent factor associated with a significantly shorter progression free survival (PFS; median: 12 months) compared with gross total resection (median: 60 months; p < 0.001). A younger age (< 14 years) was associated with a shorter PFS (median: 9 months) compared with an older age (median: 49 months; p < 0.05). Infratentorial location was associated with a shorter overall survival compared with supratentorial (p < 0.05). In addition, the EWSR1::ATF1 fusion appeared to be associated with a shorter overall survival compared with the other fusions (p < 0.05). In conclusion, IMT is a locally aggressive tumor with a high recurrence rate. Potential risk factors include subtotal resection, younger age, infratentorial location, and possibly EWSR1::ATF1 fusion. Larger case series are needed to better define prognostic determinants in these tumors.

Predicting Isocitrate Dehydrogenase Mutation Status of Grade 2-4 Gliomas with Diffusion Tensor Imaging (DTI) Parameters Derived from Model-Based DTI and Model-Free Q-Sampling Imaging Reconstructions.

OBJECTIVE: To determine whether diffusion tensor imaging (DTI) parameters acquired with model-based DTI and model-free generalized Q-sampling imaging (GQI) reconstructions may noninvasively predict isocitrate dehydrogenase (IDH) mutational status in patients with grade 2-4 gliomas. METHODS: Forty patients with known IDH genotype (28 IDH wild-type; 12 IDH mutant) who underwent preoperative DTI evaluation on a 3-Tesla magnetic resonance imaging scanner were analyzed retrospectively. Absolute values obtained from model-based and model-free reconstructions were compared. Using the intraclass correlation coefficient, interobserver agreement was assessed for various sampling techniques. Variables having statistically significant distributions between IDH groups were subjected to a receiver operating characteristic (ROC) analysis. Using multivariable logistic regression analysis, independent predictors, if present, were identified and a model was developed. RESULTS: Six imaging parameters (3 from model-based DTI and 3 from model-free GQI reconstructions) showed statistically significant differences between groups (P < 0.001, power >0.97), with very high correlation to each other (P < 0.001). Age difference between the groups was statistically significant (P < 0.001). The optimal logistic regression model comprised a GQI-based parameter and age, which were independent predictors as well, producing an area under the ROC curve, accuracy, sensitivity, and specificity of 0.926, 85%, 75%, and 89.3%, respectively. Using the GQI reconstruction feature alone with a cut-off of 1.60, an 85% of accuracy was also achieved with ROC analysis. CONCLUSIONS: The imaging parameters acquired from model-based DTI and model-free GQI reconstructions, combined with the clinical variable age, may have the ability to noninvasively predict the IDH genotype in gliomas, either alone or in particular combinations.

The time from injury to surgery is an important factor affecting the mechanoreceptors at stump of torn anterior cruciate ligament.

INTRODUCTION: Restoration of proprioceptive function after anterior cruciate ligament (ACL) reconstruction is as important as mechanical stability. For this purpose, remnant of the torn ACL is the only source of nerve endings. Our aim in this study is to investigate the quantity of mechanoreceptors in the remnants ACL stumps in injured knees and to correlate that with the quantity in intact ACL in control cases. MATERIALS AND METHODS: 48 patients that underwent ACL reconstruction between January 2016 and December 2018 as study group and 20 knees of 10 fresh frozen cadavers that as control group included in the study. Remaining stumps from study group and native ACL from control group were collected and investigated with S100 immunostaining. The type and number of mechanoreceptors in standardized areas was determined. The correlation of number of mechanoreceptors and time to surgery after ACL rupture were evaluated. RESULTS: The free nerve endings (FNE) and total number of mechanoreceptors were significantly lower in the study group as compared to the control group (p < 0.001 and p = 0.004, respectively). The number of Golgi-Mazzoni corpuscle decreased significantly with time (p = 0.041 CC: - 0.438). CONCLUSION: The time from injury to surgery is an important factor affecting the mechanoreceptors at stump of torn ACL. The surgeon and patient should be aware of the fact that delay in surgery could lead to the loss of mechanoreceptors.

Greater presence of receptors for relaxin in the ligamentum teres of female infants who undergo open reduction for developmental dysplasia of the hip.

BACKGROUND: While many factors involved in the etiology of developmental dysplasia of the hip (DDH), one of which is the hormone relaxin. Relaxin concentrations in patients with DDH may lead to pathodynamic changes during hip development by altering the physiological nature of the ligament, as well as by long-term exposure to relaxin during pregnancy. Our objective in this study was to determine the number of relaxin receptors in the ligamentum teres and their role in causing DDH. METHODS: We identified 26 infants between birth and 3 years of age who had undergone open reduction for DDH between 2010 and 2012. 12 hips of 12 miss abortus fetus between 20 to 35 weeks of gestation were used as control group. Specimens obtained from two groups were stained with Relaxin-2 antibody, and the amount of staining for relaxin receptors was determined using an ordinal H score. RESULTS: The mean (SD) H scores of infants with DDH were significantly higher than those of controls: 215 (59) versus 52 (48); P = 0.00; 95% CI. Statistically significant difference between the two groups in terms of gender was not found. CONCLUSION: As a result, increased number of relaxin receptors in the ligamentum teres could be a risk factor for DDH. LEVEL OF EVIDENCE: Level 2, Prospective comparative study.

Necrotizing Skin Findings in Coronavirus Disease 2019: A Case Report.

Coronavirus is a single-stranded RNA virus that causes acute respiratory syndrome and various skin lesions. In addition, ischemic acral lesions have been reported in patients with severe coronavirus disease 2019 (COVID-19) due to coagulation disorders. We here present a case with ischemic acral lesions caused by COVID-19. The patient was 51-year old male who was hospitalized with COVID-19 pneumonia. After 28 days in the Intensive Care Unit, patient developed acroischemic lesions in the fingers and toes. In the histopathologic examination, vasculitis was observed as the infiltration of mixed-type inflammatory cells in the mid-sized muscular arteries wall. Moreover, microthrombosis was detected in small capillaries. It is clear that thrombotic lesions have occurred as a result of COVID-19 or administered treatment. Further studies are required to confirm and better characterize the skin reactions in COVID-19.

The prognostic relationship between histopathological and immunohistochemical features of hepatocellular carcinoma, intrahepatic cholangiocarcinoma and mixed type.

Hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and combined hepatocellular and cholangiocarcinoma are the most common cancers of the liver. In this study, our first aim is to evaluate the relationship between prognosis and clinicopathological parameters. The second aim involves investigating the need for immunohistochemical staining and patterns of tumours to differentiate between them. Sixty-one cases were included in this study. For IHC, we used Hep par-1, CK7, CK19, CD56 and p53 staining, and the patterns of tumours were evaluated in haematoyxylin-eosin sections. No significant differences were found in Kaplan-Meier life analysis between the tumour types and OS and DFS values, but these values were greater in HCC than in ICC. There were no relationships between clinicopathologic parameters and OS and DFS. Although the multifocality, stage and grade of tumour were higher in HCC than in ICC, the perineural invasion and lymph node metastasis were more common in ICC than in HCC. The diagnosis was changed in 4 cases, from HCC to ICC in one case and to combined type in 3 cases after IHC. Pathologist should be alert to mixed patterns in terms of diagnosis and IHC, because it helps differential diagnosis in these cases.

Interobserver reproducibility of tumor-infiltrating lymphocyte evaluations in breast cancer.

AIM: Tumor-infiltrating lymphocytes (TILs) have a prognostic value in breast cancer (BC); however, because of the lack of standard evaluation methods, we aimed to assess the interobserver agreement of stromal TILs (sTILs) and intratumoral TILs (iTILs) as well as the effect of hot spot areas and molecular subtyping on the overall agreement. METHODS: The study consisted of 121 haematoxylin and eosin (H and E)-stained slides of invasive BC samples obtained from the pathology archives. The TIL assessment was based on the International TIL Working Group recommendations for the percentage of sTILs and was conducted by four pathologists. The percentage of iTILs, the number of lymphocytes in hot spot areas (iTILs-HS), and the overall interobserver agreement for the molecular subtypes were evaluated. The interclass correlation coefficient (ICC) was used to assess interobserver agreement among the four pathologists. RESULTS:: The ICC score among the observers for the sTIL percentages was 0.74, and the individual ICC values for each molecular subtype were 0.55, 0.88, and 0.79 for luminal, HER2-positive, and triple-negative tumors, respectively. The compliance value for the iTILs was 0.29 (95% confidence interval (CI) = 0.06-0.48], whereas the compliance value for the iTILs-HS was 0.63 (95% CI = 0.49-0.71). The compliance values for the iTILs-HS subtypes were 0.72, 0.43, and 0.55 for luminal, HER2-positive, and triple-negative tumors, respectively. CONCLUSION: The IWTILG recommendations are reproducible and reliable. The interobserver agreement of the sTIL percentages was considerably higher for the triple-negative and HER2-positive cases than the luminal cases, whereas the interobserver agreement for the assessment of iTILs-HS in tumors was higher for the luminal subtype.

Lower numbers of mechanoreceptors in the posterior cruciate ligament and anterior capsule of the osteoarthritic knees.

PURPOSE: Impaired proprioception accuracy of the knee has been proposed as a local factor in the onset and progression of knee osteoarthritis. Patients with decreased numbers of mechanoreceptors could be more likely to develop arthrosis due to a loss in proprioception of the joint. We aimed to identify and quantify the mechanoreceptors of the posterior cruciate ligament (PCL), the anterior capsule (AC) and the medial meniscocapsular junction (MCJ) in knee arthrosis. METHODS: PCLs, ACs and MCJs were harvested from 30 patients with Kellgren and Lawrence grades 3 and 4 osteoarthritis (OA), and ten knees taken from five cadavers without OA were used as a control group. PCL degeneration was evaluated with haematoxylin & eosin, and the types and numbers of mechanoreceptors were evaluated using S100 immunostaining. RESULTS: The patient ages in the OA and control groups (n.s.) did not differ. PCL degeneration was more severe in the gonarthrosis group than in the control group (p = 0.04). The numbers of Golgi corpuscles, Ruffini corpuscles, free nerve endings, total nerve endings and small vessels of the PCL were low in the OA group, as were the numbers of Golgi corpuscles, free nerve endings and total nerve endings of the AC. No significant correlation was found regarding the mechanoreceptors of the MCJ between the two groups. CONCLUSION: The numbers of mechanoreceptors in patients with OA were low in the PCLs and ACs. A loss in proprioception could be a local risk factor in OA. The proprioceptive impact of preserving PCL while performing total knee arthroplasty may not be exaggerated as its thought. LEVEL OF EVIDENCE: Prognostic study, Level I.

Mechanoreceptors of the ligaments and tendons around the knee.

Proprioceptive inputs from the joints and limbs arise from mechanoreceptors in the muscles, ligaments and tendons. The knee joint has a wide range of movements, and proper neuroanatomical organization is critical for knee stability. Four ligaments (the anterior (ACL) and posterior (PCL) cruciate ligaments and the medial (MCL) and lateral (LCL) collateral ligaments) and four tendons (the semitendinosus (STT), gracilis (GT), popliteal (PoT), and patellar (PaT) tendons) from eight fresh frozen cadavers were harvested. Each harvested tissue was divided into its bone insertion side and its tendinous part for immunohistochemical examination using S100 staining. Freeman-Wyke's classification was used to identify the mechanoreceptors. The mechanoreceptors were usually located close to the bone insertion. Free nerve endings followed by Ruffini endings were the most common mechanoreceptors overall. No Pacini corpuscles were observed; free nerve endings and Golgi-like endings were most frequent in the PCL (PCL-PaT: P = 0.0.1, PCL-STT: P = 0.00), and Ruffini endings in the popliteal tendon (PoT-PaT: P = 0.00, Pot-STT: P = 0.00, PoT-LCL: P = 0.00, PoT-GT: P = 0.00, PoT-ACL: P = 0.09). The cruciate ligaments had more mechanoreceptors than the medial structures (MS) or the patellar tendon (CR-Pat: P = 0.000, CR-MS: P = 0.01). The differences in mechanoreceptor distributions between the ligaments and tendons could reflect the different roles of these structures in the dynamic coordination of knee motion. Clin. Anat. 29:789-795, 2016. © 2016 Wiley Periodicals, Inc.

PET-MRI Findings of Two Patients with Breast Carcinoma before Treatment.

Integrated positron-emission tomography-magnetic resonance imaging (PET-MRI) is a new hybrid simultaneous imaging modality with higher soft tissue contrast and lower radiation doses compared with PET-CT. Two patients who were referred to our hospital with left breast masses that were pathologically diagnosed as invasive ductal carcinoma. The women were then scanned using the first PET-MRI system in Turkey, which was established in our department. In this case report, we aimed to determine the advantages of PET-MRI in staging, follow-up, neoadjuvant chemotherapy response, and to compare the usefulness of this modality with PET-CT and dynamic contrast-enhanced breast MRI.

A Rare Tumor that Mimicked Metastasis in a Patient with Breast Cancer: Epithelioid Hemangioendothelioma.

A woman aged 50 years was diagnosed as having an invasive ductal carcinoma in the right breast and ductal carcinoma in situ in the left breast and underwent bilateral mastectomy eight years ago. A mass was identified during follow-up in positron-emission tomography (PET) image in the left infraclavicular region, indicating metastasis. Histopathologic examination showed a mass of 1.9 × 1 × 0.7 cm in dimensions characterized by spindle or round nuclei cells that formed island or cords in hyaline and myxoid ground and intracytoplasmic vacuoles containing erythrocytes. In the immunohistochemical analysis, tumor cells were widespread with diffuse positivity with CD34 and vimentin. These findings redirected us from a diagnosis of metastatic carcinoma to epithelioid hemangioendothelioma, a rare tumor of intermediate vascular tumor groups. In this respect, confirmation through biopsy from considered cases of metastasis is important in making a definite pathologic differential diagnosis.

The Relationship between Bone Mineral Density and Estrogen Receptor Positivity in Patients with Breast Cancer.

OBJECTIVE: The effect of estrogen on bone mineral density (BMD) and breast cancer has been known for a long time. The aim of this study was to compare of the BMD of patients with breast cancer and healthy individuals, and to investigate the degree of correlation of estrogen receptor (ER) with BMD. MATERIALS AND METHODS: Seventy-one patients with postmenopausal breast cancer and 79 healthy dividuals were included in the study. The patient demographics (age, menopause age, body mass index, number of children, BMD, Z scores, and estrogen status for breast cancer patients) were taken from hospital records. RESULTS: No significant difference was detected between the case and control groups in lumbar region Z scores (p=0.074). At the femur neck, the control group Z scores was higher than patient group (p=0.002). BMI was higher in the patients with breast cancer (p=0.001). There was no statistically significant correlation between ER positivity, BMD, and BMI in ER-positive patients (p=0.495, p=0.8, p=0.846, respectively). There was no difference between the Z scores when the patients were divided into two groups as ER positive and negative (p=0.156, p=0.335, respectively). CONCLUSION: This study revealed that there is no difference in lumbar region Z scores between patients with breast cancer and heathy controls; however, the Z scores were higher in the femur neck in the control group, and the BMI was lower in the patient group. Tumor ER positivity does not positively affect BMD.

The effect of diclofenac on matrix metalloproteinase levels in the rotator cuff.

INTRODUCTION: Matrix metalloproteinases (MMPs) are involved in physiological events such as restructuring of the tissue, morphogenesis, wound healing and normal developmental process. Use of diclofenac sodium following rotator cuff repair can disrupt healing of tendon through acting on MMPs. MATERIALS AND METHODS: Supraspinatus tendons of rats (n = 84) were detached from their insertion on humerus, and repaired to anatomic footprint. Rats were divided into study group (n = 42) and control group (n = 42). Study group received a dose of 1 mg/kg daily diclofenac sodium subcutaneously. The rats were killed at weeks 1, 3 and 6, and seven rats from each groups were included in biomechanical and immunohistological examinations. Immunohistological staining of MMP-2, MMP-3 and MMP13 were used. RESULTS: Maximum load was reduced in the study group at the end of week 1 (8.76 vs. 5.28 N) (p = 0.01). MMP-3 level was statistically significantly lower in the study group at the end of week 1. MMP-13 level and stiffness decreased towards week 6 in the study group while in the control group the level of MMP-2 decreased towards week 6. CONCLUSION: Diclofenac has an impact on the levels of MMP-2, MMP-3 and MMP-13, which are needed for normal healing process, and it can also lead to disruption of tendon healing.

Schwannoma of the submandibular gland: a case report.

INTRODUCTION: Schwannoma is a benign, solitary, and slowly progressive encapsulated tumor originating from the sheath of myelinated nerve fibers. Schwannoma of the salivary gland is a particularly rare form of an extracranial neurogenic tumor. Here, we present an unusual case of a schwannoma of the submandibular gland in a 19-year-old man. Total excision of the submandibular gland resulted in complete resolution of symptoms with no cranial nerve deficits. The details of the histopathologic and immunohistochemical features are presented. CASE PRESENTATION: A 19-year-old Caucasian man was admitted to our clinic with a painless mass on the right side of his neck that he had had for the past four months. A neck examination revealed a smooth-surfaced, mobile, firm, and painless mass, 6cm in its greatest diameter, on the right side of the submandibular region. Fine-needle aspiration cytology was suggestive of a submandibular gland schwannoma. After the initial evaluation, our patient was prepared for surgical evaluation and resection with a presumptive diagnosis of a neurogenic tumor of the submandibular gland. The final diagnosis of schwannoma was verified by microscopic and immunohistochemical studies. At one-year follow-up of the case, there was no evidence of recurrence. CONCLUSIONS: Schwannoma of the salivary gland is a particularly rare form of an extracranial neurogenic tumor. Our findings indicate good prognosis in an unusual case of a submandibular gland schwannoma in a 19-year-old man treated by surgical excision with no recurrence within 12 months of follow-up.

Correlation of survivin and MMP9 expressions with prognosis and clinicopathological parameters in surface epithelial ovarian carcinomas.

OBJECTIVE: Pathological stage is the most important prognostic factor in ovarian carcinomas, and many studies have been carried out to predict prognosis. In our study, we searched the expression of survivin, which prevents apoptosis and matrix metalloproteinase-9 (MMP-9), which promotes the metastasis of the tumour by splitting up the basal membrane in primary epithelial ovarian carcinomas. We aimed to observe their effects on prognosis by comparing clinicopathological parameters. MATERIAL AND METHOD: 60 cases diagnosed with epithelial ovarian carcinoma between 2003 and 2008 and treated and followed up at the oncology clinic were included in the study. 42 patients were serous, 11 endometrioid, 5 mixed type, 1 was clear cell and 1 was undifferentiated adenocarcinoma. Survivin and MMP-9 expression was evaluated in each tumour and assosication with clinicopathological parameters (age, tumour diameter, localisation, histological type of tumour, grade, stage, recurrence and metastasis) were searched and also overall survival and disease free of survival were evaluated. RESULTS: Survivin was statistically insignificant within the clinicopathological parameters. The correlation between the tumour grade and the staining density of MMP-9 in epithelial cells (p=0.028) and the correlation between disease free of survival and MMP-9 expression in stromal cells (p=0.0326) was significant. When the stage was compered with clinocopathologic parameters; recurrence (p=0.005) and death rates (p < 0.001) were significantly increased but overall survival (p=0.0269) was significantly decreased in advanced-stage patients. CONCLUSION: In the present study, the stage was found to be an important prognostic parameter in surface epithelial ovarian carcinomas and an association was found between MMP-9 stromal staining and survival.