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Background Non-invasive biomarkers for early chemotherapeutic response in Ewing sarcoma family of tumors (ESFT) are useful for optimizing existing treatment protocol. Purpose To assess the role of diffusion-weighted magnetic resonance imaging (MRI) in the early evaluation of chemotherapeutic response in ESFT. Material and Methods A total of 28 patients (mean age = 17.2 ± 5.6 years) with biopsy proven ESFT were analyzed prospectively. Patients underwent MRI acquisition on a 1.5-T scanner at three time points: before starting neoadjuvant chemotherapy (baseline), after first cycle chemotherapy (early time point), and after completion of chemotherapy (last time point). RECIST 1.1 criteria was used to evaluate the response to chemotherapy and patients were categorized as responders (complete and partial response) and non-responders (stable and progressive disease). Tumor diameter, absolute apparent diffusion coefficient (ADC), and normalized ADC (nADC) values in the tumor were measured. Baseline parameters and relative percentage change of parameters after first cycle chemotherapy were assessed for early detection of chemotherapy response. Results The responder:non-responder ratio was 21:7. At baseline, ADC ([0.864 ± 0.266 vs. 0.977 ± 0.246]) × 10−3mm2/s; P = 0.205) and nADC ([0.740 ± 0.254 vs. 0.925 ± 0.262] × 10−3mm2/s; P = 0.033) among responders was lower than the non-responders and predicted response to chemotherapy with AUCs of 0.6 and 0.735, respectively. At the early time point, tumor diameter (27% ± 14% vs. 4.6% ± 10%; P = 0.002) showed a higher reduction and ADC (75% ± 44% vs. 52% ± 72%; P = 0.039) and nADC (81% ± 44% vs. 48% ± 67%; P = 0.008) showed a higher increase in mean values among responders than the non-responders and identified chemotherapy response with AUC of 0.890, 0.723, and 0.756, respectively. Conclusion Baseline nADC and its change after the first cycle of chemotherapy can be used as non-invasive surrogate markers of early chemotherapeutic response in patients with ESFT.

Subependymal giant cell astrocytoma (SEGA) is a World Health Organization grade 1 neoplasm, which, due to its dubious morphologic features, may be misdiagnosed as a high-grade tumor at times. This tumor shows binary immunoexpression including both glial and neural markers, leading to a state of diagnostic quandary. Recent evidences have surmised the diagnostic utility of thyroid transcription factor 1 (TTF-1), spurring us to study the practicality of this marker in distinguishing SEGAs from its mimics.In this study, TTF-1 immunohistochemistry using clone 8G7G3/1 (1:50) was performed in 38 cases of SEGA, 30 cases of central neurocytoma, 10 cases each of intraventricular glioblastoma and ependymoma, and 5 cases of cortical tubers. Additionally, serine/threonine-protein kinase B-Raf (BRAFV600E) mutation, a common genetic alteration in pediatric low-grade-glial tumors with neuronal-differentiation, was analyzed using Ventana immunohistochemistry platform.TTF-1 immunopositivity was seen in all 38 cases (100%) of SEGAs, with 20 cases (52.6%) showing diffuse (50% of tumor area) expression while focal (50%) immunopositivity was seen in 18 cases (47.3%). None of the cases demonstrated serine/threonine-protein kinase B-Raf immunolabeling. Barring 2 cases of neurocytoma (6.6%), all other cases including ependymoma, glioblastoma, and cortical tubers were immunonegative for TTF-1.The congruous finding of TTF-1 expression in SEGA and cells of the developing neuroepithelium in the medial ganglionic eminence hint toward a primogenitor cell with neoplastic potential in the presence of impelling factors.

Background and aims The pathophysiology of sarcopenia in cirrhosis is poorly understood. We aimed to evaluate the histological alterations in the muscle tissue of patients with cirrhosis and sarcopenia, and identify the regulators of muscle homeostasis. Methods Computed tomography images at third lumbar vertebral level were used to assess skeletal muscle index (SMI) in 180 patients. Sarcopenia was diagnosed based on the SMI cut-offs from a population of similar ethnicity. Muscle biopsy was obtained from the vastus lateralis in 10 sarcopenic patients with cirrhosis, and the external oblique in five controls (voluntary kidney donors during nephrectomy). Histological changes were assessed by hematoxylin and eosin staining and immunohistochemistry for phospho-FOXO3, phospho-AKT, phospho-mTOR, and apoptosis markers (annexin V and caspase 3). The messenger ribonucleic acid (mRNA) expressions for MSTN, FoxO3, markers of ubiquitin-proteasome pathway (FBXO32, TRIM63), and markers of autophagy (Beclin-1 and LC3) were also quantified. Results The prevalence of sarcopenia was 14.4%. Muscle histology in sarcopenics showed atrophic angulated fibers (p = 0.002) compared to controls. Immunohistochemistry showed a significant loss of expression of phospho-mTOR (p = 0.026) and an unaltered phospho-AKT (p = 0.089) in sarcopenic patients. There were no differences in the immunostaining for annexin-V, caspase-3, and phospho-FoxO3 between the two groups. The mRNA expressions of MSTN and Beclin-1 were higher in sarcopenics (p = 0.04 and p = 0.04, respectively). The two groups did not differ in the mRNA levels for TRIM63, FBXO32, and LC3. Conclusions Significant muscle atrophy, increase in autophagy, MSTN gene expression, and an impaired mTOR signaling were seen in patients with sarcopenia and cirrhosis.

Atrophic kidney-like lesion (AKLL) is a provisional renal entity with distinct morphological and immunohistochemical features. It characteristically resembles thyroid-like follicular renal cell carcinoma (RCC) of kidney, an emerging renal entity. Very few patients of AKLL have been reported in the literature. We are hereby describing the clinicopathological features of AKLL in a 38-year-old man. The patient was incidentally found to have a renal mass and underwent radical nephrectomy. The morphological and immunohistochemical findings revealed features of AKLL. The patient on 24 months’ post-operative period follow-up is alive without recurrence or metastasis.

Spinal cord injury (SCI) is one of the most devastating injuries which causes either complete or partial loss of movement, balance, muscular coordination and endurance. Electromagnetic field (EMF) stimulation has been shown to reduce muscle atrophy and fiber-type switching and improves muscle function in a hindlimb suspension model. The present study aims to elucidate the therapeutic potential of EMF stimulation on motor neuron excitability, soleus muscle morphology and function in complete SCI rats. Thirty-six adult male Wistar rats were randomly divided into Sham, SCI and SCI+EMF groups. Complete transection was done at the T13 spinal level, followed by whole-body EMF exposure for 7 or 14 days. Hyper-reflexia, muscle atrophy, reduction in twitch and tetanic force with earlier onset of fatigue was evident in the SCI group. EMF stimulation showed significant improvement in H and M wave parameters, H/M ratio, muscle twitch and tetanic force, fusion frequency and fatigability. A significant increase in regenerating myofibers and reduction in muscle degeneration following EMF was evident on histopathological examination. Further, EMF significantly increased myogenic protein levels responsible for muscle regeneration. Our study demonstrates for the first time the potential of EMF to modulate motor neuron excitability and muscle contractile function in SCI rats through activity-dependent mechanisms.

Ependymoma is a relatively rare glial tumor of the central nervous system that arise from the cells lining the ventricles and central canal of the spinal cord. Ependymosarcoma (ES) is a newly introduced tumor entity of uncertain prognosis characterized by a rare phenomenon of a malignant mesenchymal transition arising within an ependymoma. ESs are surgically challenging tumors for diagnosis and therapy with a high incidence of morbidity and mortality. Here, we report two diagnostically challenging cases of primary ES in a 25-year-old female and a 17-year-old male. Both the cases presented with progressive and sequential neurological deficits over a period of five to eight months, and histological examination revealed a biphasic gliomesenchymal architecture comprised of anaplastic ependymomatous and sarcomatous components. Molecular genetic analysis revealed the presence of type 1 C11orf95:RELA fusion transcript. To date, 22 cases of ES have been reported in the literature, and only one case harbored type 1 C11orf95:RELA fusion transcript.

Calcium sensing receptor (CaSR), on the surface of normal parathyroid cells, is essential for maintaining serum calcium levels. The normal pattern of CaSR immunostaining remains undefined and is presumptively circumferential. Given the physiological variation in serum calcium, we postulated that CaSR expression could not be uniformly circumferential. Also, cytoplasmic expression has not been evaluated either in normal or pathological tissues. We studied normal parathyroid tissues derived from forensic autopsies and those rimming parathyroid adenomas for membranous and cytoplasmic CaSR immunoexpression. Results were compared with primary hyperparathyroidism (PHPT) to look for any pathogenetic implications. We evaluated 34 normal parathyroid tissues from 11 autopsies, 30 normal rims, 45 parathyroid adenoma, 10 hyperplasia, and 7 carcinoma cases. Membranous expression was categorized complete/incomplete and weak/moderate/strong; scored using Her2/Neu and Histo-scores; predominant pattern noted. Cytoplasmic expression was categorized negative/weak/moderate/strong; predominant intensity noted. Normal autopsy-derived parathyroid tissues were Her2/Neu 3 + , but incomplete membranous staining predominated in 85%. Their immune-scores were significantly more than the cases (p

Primary liposarcoma at vallecula is an extremely rare tumor in hypopharyngeal region. Vallecular liposarcoma shares both clinical and imaging features with other common lesions at this site such as benign lipoma, mucus retention cysts, fibrovascular/ inflammatory polyp and epithelial malignancies extending from adjacent anatomical structures. The two closest mimickers in laryngeal region, atypial lipoma and well differentiated liposarcoma are very difficult to differentiate on laryngoscopic examination and radiological investigations. Dedifferentiation; a poor prognostic histological feature can rarely occur after multiple recurrences but liposarcoma with de novo de-differentiation in larynx is very rare. Herein, we describe a case of liposarcoma with de novo de-differentiation originating from vallecula in a 66 years old male with review of literatures.

A 42-year-old businessman had a 27-year history of multiple complaints. He had been born of a non-consanguineous marriage, but his siblings had young-onset hypertension. When aged 15 years, he developed an ulcerated skin lesion on the medial right thigh with right foot drop. This was presumptively treated as tuberculosis with corticosteroids and antituberculous therapy; the skin lesion resolved in 1–2 weeks and the foot drop recovered within 6–8 weeks. He stopped antituberculous therapy after 1 month. When aged 24 years, he developed a left foot drop that improved with oral corticosteroids in 3–4 weeks. However, on corticosteroid withdrawal he developed fever, left foot ulceration and abdominal pain. Biopsy of the skin ulcer was reported as ‘systemic lupus erythematosus-like’. His symptoms resolved with tapering corticosteroids over 4–6 months. He was also diagnosed and treated for hypertension at this time. When aged 30 years, he developed similar complaints. A rheumatologist prescribed monthly cyclophosphamide for 6 months with symptom resolution. He was then lost to follow-up for 6 years. When aged 36 years he presented with fever, abdominal and testicular pain, with skin ulcerations in the lower limbs. His viral markers for HIV, hepatitis B, hepatitis C were negative and a CT aortogram was normal. His condition responded well to pulsed corticosteroids and mycophenolate mofetil. He had further recurrent relapses every 1–2 years and tried a combination of multiple immunosuppressants: mycophenolate, azathioprine and cyclophosphamide. When aged 40 years, he had another relapse (fever, abdominal pain, left foot drop and weight loss) with significant (22 kg) unintentional weight loss over 2 months. CT scan of abdomen showed a left perirenal haematoma, with splenic and bilateral renal cortical infarcts. CT aortic angiogram showed multiple aneurysms in medium-sized abdominal aortic visceral branches. Chest X-ray and two-dimensional echocardiography were unremarkable. Upper gastrointestinal endoscopy identified oesophageal candidiasis, whereas colonoscopy showed multiple …

Amphicrine phenotype in medullary thyroid carcinoma (MTC) is a rare phenomenon characterized by tumor cells that show both endocrine differentiation (calcitonin secretion) and exocrine differentiation (mucin production and secretion). Not much is known about the pathobiology of amphicrine MTCs. This report undertook a case-based review approach by discussing the cytological, histopathological, and ultrastructural features of this rare enigmatic entity, expanding on the radiological and novel MUC immunohistochemistry findings from a 28-year-old MEN2B syndrome patient with C cell hyperplasia and multifocal MTC with amphicrine features. The patient had widespread hematogenous metastases at presentation. MUC immunoexpression analysis revealed evidence of micro-lumina formation, and unique to-date unreported expression patterns of MUC1, MUC5AC, and MUC6 in an amphicrine subtype of MTC. Review of the literature identified five other MTC cases with well-documented amphicrine features. Of these six cases, two were associated with MEN2B syndrome, and four had metastatic disease. Follow-up was available in three patients, and two died of disease. Recognition of this rare subtype of MTC may be of clinical interest given their frequent link to MEN2B syndrome and biological aggressiveness.

Introduction: Spinal atypical teratoid/rhabdoid tumour (AT/RT) is exquisitely rare and constitutes 2% of all AT/RTs. Case Presentation: A 6-year-old boy presented with low backache for the last 5 months. MRI of the spine showed a 1.5 × 1.5 × 4.7 cm intradural extramedullary mass extending from D10 to D12, causing compression of the conus medullaris. With a preoperative diagnosis of ependymoma, a gross total resection (GTR) of tumour was performed. Post-operative histopathology showed AT/RT. The tumour cells were immunopositive for cytokeratin, epithelial membrane antigen, smooth muscle actin, and p53 and immunonegative for MIC2, desmin, glial fibrillary acidic protein, and INI1. Post-operative neuraxis MRI revealed post-operative changes (D10–D12) with a 9 mm enhancing lesion at L5-S1 junction suggesting drop metastasis. There was no lesion in brain. Cerebrospinal fluid cytology did not show any malignant cell. The metastatic work-up was normal. He received 3 cycles of chemotherapy with ICE regimen (ifosfamide, carboplatin, and etoposide). Subsequently, he received craniospinal irradiation (CSI)-36 Gy/20 fractions/4 weeks followed by focal boost to primary tumour bed and spinal drop metastasis-14.4 Gy/8 fractions/1.5 weeks. Thereafter, he received 3 more cycles of ICE regimen. End-of-treatment MRI spine showed post-op changes (D10–D12) and 38.9% reduction of the L5-S1 lesion suggesting partial response. Six monthly spinal MRI showed serial reduction of the metastatic lesion leading to complete response (CR) 1 year after completion of treatment. On last follow-up (30 months from the initial diagnosis), he was neurologically intact and in CR. Conclusion: Multimodality management comprising GTR of tumour, CSI followed by focal boost, and multiagent chemotherapy (ICE) can lead to successful outcome in patients with this rare and aggressive spinal tumour.

Background: Limb girdle muscular dystrophy recessive type 1 (LGMDR1, Previously LGMD2A) is characterized by inactivating mutations in CAPN3. Despite the significant burden of muscular dystrophy in India, and particularly of LGMDR1, its genetic characterization and possible phenotypic manifestations are yet unidentified. Material and Methods: We performed bidirectional CAPN3 sequencing in 95 LGMDR1 patient samples characterized by calpain-3 protein analysis, and these findings were correlated with clinical, biochemical and histopathological features. Results: We identified 84 (88.4%) cases of LGMDR1 harboring 103 CAPN3 mutations (71 novel and 32 known). At least two mutant alleles were identified in 79 (94.2%) of patients. Notably, 76% exonic variations were enriched in nine CAPN3 exons and overall, 41 variations (40%) correspond to only eight exonic and intronic mutations. Patients with two nonsense/out of frame/splice-site mutations showed significant loss of calpain-3 protein as compared to those with two missense/inframe mutations (P = 0.04). We observed a slow progression of disease and less severity in our patients compared to European population. Rarely, presenting clinical features were atypical, and mimicked other muscle diseases like FSHMD, distal myopathy and metabolic myopathies. Conclusion: This is first systematic study to characterize the genetic framework of LGMDR1 in the Indian population. Preliminary calpain-3 immunoblot screening serves well to direct genetic testing. Our findings prioritized nine CAPN3 exons for LGMDR1 diagnosis in our population; therefore, a targeted-sequencing panel of nine exons could serve well for genetic diagnosis, carrier testing, counseling and clinical trial feasibility study in LGMDR1 patients in India.

Background Granular cell astrocytoma (GCA) is an aggressive variant of astrocytoma characterized by predominantly round-to-polygonal cells with abundant eosinophilic granular cytoplasm. This tumor usually lack the morphological signatures of conventional astrocytoma and are devoid of typical features which define a malignant neoplasm, leading to potential misdiagnosis. Case Description We report GCA in a 50-year-old man presenting with severe headache along with vertiginous sensation and sensory seizures of left upper limb for past two months. Imaging showed multiple intra-axial, hyperintense space-occupying lesions in bilateral anterior temporal lobe, left parietal lobe, left thalamus and cerebellum, raising possibility of lymphoma/metastases. Histopathologic examination revealed sheets of large polygonal cells with distinct cellular outline, ample amount of eosinophilic PAS-positive granular cytoplasm, eccentrically placed irregular, round-to-ovoid nuclei with occasional prominent nucleoli. On immunohistochemistry, tumor cells were diffusely immunopositive for Olig2, S100, EMA, lysozyme and CD68, and they were immunonegative for GFAP, LCA, pan-CK, TTF-1, TFE-3, PAX-8, SOX10, MAP2, MBP, NF, H3K27M, H3K27me3, p53, IDH1 (R132H), CD1a, langerin and BRAFV600E. Numerous scattered macrophages were highlighted by CD163. MIB 1-labelling-index was approximately 5%–6%. Overall features were congruous with final diagnosis of GCA. Conclusions GCAs behave in a belligerent manner irrespective of their morphologic grade as they are seen to exhibit genetic alterations similar to glioblastoma. Thereby, they warrant early diagnosis for conducive patient management.

The authors report a case of extremely uncommon malignancy of lacrimal gland epithelial-myoepithelial carcinoma. This carcinoma is more commonly encountered in salivary glands and comprises 1% of all salivary gland tumors. Its occurrence in the orbit is very rare with only 6 cases reported in the literature, most of which arose in a pleomorphic adenoma. Epithelial-myoepithelial carcinoma is primarily a tumor of older adults, with a peak incidence in the sixth and seventh decades of life. The present case is the youngest patient reported to date and had no history of preexisting neoplasm in the lacrimal gland. Histological diagnosis of epithelial-myoepithelial carcinoma is challenging because of the similarity with other lacrimal gland epithelial tumors like malignant adenoid cystic carcinoma and benign pleomorphic adenomas.

Atrial myxomas are the most common primary benign cardiac tumors. The embolization of tumor particles is not infrequent, and in nearly half of them, the cerebral arteries are affected, usually leading to embolic ischemic stroke. Formation of intracranial aneurysms, development of parenchymal brain metastasis, and intracerebral hemorrhage due to ruptured aneurysms are rarer. Diagnosis of such lesions in a previously undiagnosed case of myxoma may be challenging for a pathologist. Herein, we present two patients of cardiac myxoma with varied neurological manifestations and their pathological findings.

Histopathological examination (HPE) is the current gold standard for assessing chemotherapy response to tumor, but it is possible only after surgery. The purpose of the study was to develop a noninvasive, imaging-based robust method to delineate, visualize, and quantify the proportions of necrosis and viable tissue present within the tumor along with peritumoral edema before and after neoadjuvant chemotherapy (NACT) and to evaluate treatment response with correlation to HPE necrosis after surgery. The MRI dataset of 30 patients (N = 30; male:female = 24:6; age = 17.6 ± 2.7 years) with osteosarcoma was acquired using 1.5 T Philips Achieva MRI scanner before (baseline) and after 3 cycles of NACT (follow-up). After NACT, all patients underwent surgical resection followed by HPE. Simple linear iterative clustering supervoxels and Otsu multithresholding were combined to develop the proposed method—SLICs+MTh—to subsegment and quantify viable and nonviable regions within tumor using multiparametric MRI. Manually drawn ground-truth ROIs and SLICs+MTh-based segmentation of tumor, edema, and necrosis were compared using Jacquard index (JI), Dice coefficient (DC), precision (P), and recall (R). Postcontrast T1W images (PC-T1W) were used to validate the SLICs+MTh-based necrosis. SLICs+MTh-based necrosis volume at follow-up was compared with HPE necrosis using paired t test (p ≤ 0.05). Active tumor, necrosis, and edema were segmented with moderate to satisfactory accuracy (JI = 62–78%; DC = 72–87%; P = 67–87%; R = 63–88%). Qualitatively and quantitatively (DC = 74 ± 9%), the SLICs+MTh-based necrosis area correlated well with the hypointense necrosis areas in PC-T1W. No significant difference (paired t test, p = 0.26; Bland–Altman plot, bias = 2.47) between SLICs+MTh-based necrosis at follow-up and HPE necrosis was observed. The proposed multiparametric MRI-based SLICs+MTh method performs noninvasive assessment of NACT response in osteosarcoma that may improve cancer treatment monitoring, planning, and overall prognosis. • The simple linear iterative clustering supervoxels and Otsu multithresholding-based technique (SLICs+MTh) successfully estimates the proportion of necrosis, viable tumor, and edema in osteosarcoma in the course of chemotherapy. • The proposed technique is noninvasive and uses multiparametric MRI to measure necrosis as an indication of anticancer treatment response. • SLICs+MTh-based necrosis was in satisfactory agreement with histological necrosis after surgery.

Cushing's disease (CD) is a spectrum of clinical manifestations due to adrenocorticotropic hormone-secreting pituitary adenoma. Transsphenoidal adenomectomy remains the standard treatment. There has been a paradigm shift from microscopic to endoscopic transsphenoidal surgery in recent years. However, the efficacy of endoscopic transsphenoidal surgery has not been established. Therefore, it is of interest to determine the superiority of endoscopic transsphenoidal surgery, if any, over microscopic surgery.To assess the efficacy of endoscopic endonasal transsphenoidal surgery for the treatment of CD and to determine the factors affecting remission.Patients undergoing surgery for CD from 2009 to 2017 were analyzed retrospectively. Transsphenoidal resection was the preferred treatment, with recent trends in favor of the endonasal endoscopic skull base approach. Postoperative cortisol level of2 μg/dL was taken as remission and value between 2 and 5 μg/dL as possible remission.In total, 104 patients operated primarily for CD were included for analysis; 47 patients underwent microscopic surgery, 55 endoscopic surgery, and 2 were operated transcranially. Remission was achieved in 76.47% of patients. In univariate analysis, factors significantly associated with remission were 1) type of surgery (P = 0.01); remission in endoscopy surgery (88.23%) is better than microscopy (56.6%); 2) postoperative day 1 morning cortisol (P = 0.004); and 3) postoperative day 1 morning ACTH (P = 0.015). In multivariate analysis, only postoperative day 1 cortisol was found to be significant predictor of remission (P = 0.02).Postoperative plasma cortisol level is a strong independent predictor of remission. Remission provided by endoscopy is significantly better than the microscopic approach.

Prothymosin-α (PTMA), a nuclear protein, is strikingly associated with unfavorable clinical outcomes in many cancers. However, no information about its clinical relevance in glioma was available. Therefore in the present study, we evaluated the prognostic utility of this protein in a cohort of 81 glioma patients. The PTMA expression was assessed by immunohistochemical analysis, quantitative PCR, and Western blotting. Furthermore, the association of PTMA with clinicopathological features and molecular alterations were assessed in the patient cohort and validated in multiomics datasets, The Cancer Genome Atlas (TCGA; n=667) and Chinese Glioma Genome Atlas (CGGA; n=1013). We observed an increase in PTMA expression with increasing histological grades of this malignancy. PTMA immunostaining also displayed a strong positive association with the MIB-1 index. Univariate analysis revealed a superior prognostic value of PTMA to predict overall survival (OS) as compared with the routinely used markers (p53, isocitrate dehydrogenase (IDH) 1 (IDH1), α-thalassemia/intellectual disability syndrome X-linked (ATRX), and Ki-67). Interestingly, in Cox regression analysis it emerged as an independent predictor of OS (hazard ratio (HR) = 13.71, 95% CI = 5.96–31.52, P

Systemic inflammatory markers have been found to be of value in predicting the prognosis in renal cell and gastrointestinal cancers. Recent studies in gliomas correlating with Systemic inflammatory markers (SIMS) have shown promise in predicting survival.Meningiomas are the commonest intracranial primary brain tumors in adults. There is a need to distinguish low and high grade meningiomas preoperatively as they have crucial implications for the radicality of surgical excision and prognostication.A retrospective search was conducted, and the newly diagnosed meningioma cases were studied. The preoperative hematological parameters of the patients and pathological tumor grades were noted. The grade 1 meningioma was defined as low-grade meningioma while grade 2 and 3 meningiomas were defined as high-grade meningioma. Statistical analysis was performed to determine the association between the hematological parameters and tumor grade.Seven hundred and eighty meningioma cases with a mean age of 43.5 years were included. The ANC, NLR, and dNLR were found to be significantly elevated in high-grade meningioma (P = 0.03). Other inflammatory parameters including TLC failed to show a statistically significant difference when compared between the grades of meningioma. ROC analysis further showed limited value of these markers in predicting meningioma grade. However, an elevated ANC (OR = 1.08, 95% CI = 1.02-1.14), male sex (OR = 1.71, 95% CI = 1.13-2.58), and tumor origin from sites other than the skull base or thecal sac (OR = 3.33, 95% CI = 1.93-6.12) were predictive of high-grade meningioma in regression analysis.Preoperative hematological inflammatory parameters have limited value in predicting the grade of tumor in meningiomas. An elevated preoperative ANC, NLR, and dNLR were found to be more frequently associated with high grade of meningiomas.

Primary cutaneous anaplastic large-cell lymphoma (C-ALCL) is a cutaneous CD30-positive lymphoproliferative disorder. The patients usually present with single or multiple cutaneous nodules or papules and about 10% cases present with extracutaneous manifestations, which are predominantly in the form of regional lymph nodal involvement. Visceral involvement especially pulmonary or hepatic involvement in C-ALCL is only rarely described in the scientific literature. Approximately 20%-42% cases show spontaneous regression, about 50% cases may recur; however, C-ALCL generally carries a good prognosis. We present a rare case of primary C-ALCL in a 66-year-old man with regional lymph nodal and hepatic involvement. Differential diagnostic entities are discussed in this report with the review of the literature.

Osteosarcoma is the heterogeneous primary malignancy of bone which is most commonly found among children and adolescents. Recent data related to treatment of osteosarcoma indicates the lack information about the progression of the disease. Osteosarcoma has been a challenge for the oncologist because even after surgical removal of primary tumors many patients go on to develop pulmonary metastasis. Protein deubiquitination controls many intracellular processes, including cell cycle progression, transcriptional activation, and signal transduction. Ubiquitin specific peptidases (USPs) remove ubiquitin tags from target proteins to alter protein configuration and function. Recent studies have revealed that Ubiquitin specific peptidase 37 (UPS37) regulates replication stress by regulating important protein involved in several important cellular functions. Analysis of TCGA data indicated that overexpression of USP37 correlated with reduced progression free survival (PFS) in osteosarcoma patients. Next generation sequencing (NGS) analysis of osteosarcoma cells indicated that distinct set of genes were altered on overexpression or knockdown of USP37. Our data indicate that USP37 overexpression confers survival advantage while its depletion enhances sensitivity for cell killing in osteosarcoma cells due to replication stress. USP37 overexpressing cells were able to resolve DNA damage foci much more rapidly than the control cells or cells in which USP37 was depleted in response to genotoxic stress. USP37 depletion results in reduced resolution of γ H2AX and 53BP1 DNA damage foci and increase in number of collapsed replication fork which indicates the reduced ability of cells to carry out constitutive DNA replication. USP37 was found to interact with PCNA (Proliferative cell nuclear antigen). Interestingly docking studies indicated that USP37 and PCNA interacted with stronger affinity in presence of double stranded DNA through different residues. We further correlated our data with archived tissue blocks of osteosarcoma patients by analyzing if USP37 and PCNA expression colocalized. Present data suggests that USP37 is required for tolerance of replication stress as it interacts with PCNA which is required to dock additional replication factors and stabilize DNA replication fork. The current data provides new mechanistic details for the regulation of replication stress by USP37 which merits the development of targeting strategies to explore its therapeutic potential in osteosarcoma by inducing synthetic lethality. Citation Format: Ravi Chauhan, Lakshay Malhotra, Ashna Gupta, Ajaz Bhat, Gunjan Dagar, Tariq Masoodi, Muzafar A. Macha, Ethayathulla Abdul Samath, Atul Batra, Mehar Chand Sharma, Mohammad Haris, Ammira Al-Shabeeb Akil, Tej K. Pandita, Shahab Uddin, Mayank Singh. Ubiquitin Specific Peptidase 37promotes Osteosarcoma oncogenesis by interacting with PCNA and impacting constitutive replication fork movement. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 335.

Background Pilocytic astrocytomas (PAs) are the primary tumors most frequently found in children and adolescents, accounting for 5.4% of all gliomas. The overall prognosis of PAs is good, yet a substantial no of cases have a poor outcome, with recurrence, and ultimately death. The KIAA1549-BRAF fusion is a useful putative diagnostic marker for PAs and BRAF also is an important therapeutic marker. Aim and Objectives To study the frequency of KIAA1549-BRAF fusion (16-9, 15-9 and 16-11) in different locations of PAs using qRT-PCR technique in FFPE samples. Methodology Three different exon rearrangements of KIAA1549-BRAF (16-9, 15-9 and 16-11) fusions were assessed in 50 cases of PAs by using qRT-PCR (gold standard). FISH assay was also performed in all the cases. Results Out of 50 PAs, 32 were localised in midline structures such as the cerebellum, optic pathway, hypothalamus, and brain stem while 18 in non-midline regions like the cerebral hemispheres. Majority of the cases (35/50); 70% were positive for KIAA1549-BRAF fusion by RT-PCR. Of these, (16/35); 45.7% harboured 15-9 fusion, (15/35); 42.8% harboured 16-9 fusion, and only (4/35); 11.4% had 16-11 fusion. Only (24/30); 48% KIAA1549-BRAF showed fusion by FISH assay. There was 54.2% concordance between FISH and RT-PCR results. KIAA1549-BRAF fusion was observed in 78% of midline and 55.5% of non-midline cases. The frequency of KIAA1549-BRAF fusion decreased with increasing age, 77% in the age group 40. Conclusion 15-9 and 16-9 KIAA1549-BRAF were the most frequently occurring fusions dominantly seen in the midline. The presence of fusion is inversely proportional to the age of patients. qRT-PCR is the gold standard technique and FISH assay has moderate concordance with qRT-PCR platform.