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Author(s): Anubhav Narwal [1]; Mohit Mann [2]; Achal K Srivastava [2]; Mehar C Sharma (corresponding author) [1] Key Message: In a clinically unsuspected case of nemaline rod myopathy, reddish granular [...], Sporadic late-onset nemaline rod myopathy is a rare, acquired, sub-acute, adult-onset myopathy characterized by proximal muscle weakness and nemaline rods in the myofibers. In contrast to its congenital form, the prevalence in adult population is comparatively rare. Herein, we report a case of 60-year-old male who presented with insidious onset proximal muscle weakness with myopathic pattern on electromyography. Histopathological examination showed type 1 and 2 muscle fiber atrophy with minimal chronic inflammatory cell infiltrate. Modified Gomori trichrome staining revealed granular deposits in the myofibers. Ultrastructure examination showed numerous nemaline rods in the myofibers; hence, the diagnosis of sporadic late-onset nemaline myopathy was rendered. Its association with monoclonal protein has been reported in the past. One should be aware of this rare entity as without correct diagnosis, there can be treatment failure and unfavorable outcome. Keywords: Monoclonal gammopathy, nemaline rods, sporadic late-onset myopathy

Author(s): Sarvesh Goyal [1]; Het Shah [1]; Shweta Kedia [1]; Rahil Rafiq [2]; Anubhav Narwal [3]; Mehar Sharma [3] Introduction and Background Primary neuroectodermal tumor (PNET) was a term first [...], We present a case report of a 5-year-old child with a primary Primitive Neuroectodermal tumor in the intramedullary region. We have also attempted to identify the positive prognostic factors for primary pediatric intraspinal PNETs using Artificial Neural Network (ANN). After a thorough review of all primary pediatric intraspinal PNETs, ANN analysis was used to identify factors that favorably predict the survival in these cases for more than 6 months. ANN model could predict with 84.6% accuracy the survival period for pediatric primary spinal PNET on 13 tested cases. The most important variables were Treatment (relative significance 100%), followed by the location of the tumor in the axial section (84.6%), involvement of thoracic level (62.7%), and gender (40.3%). We concluded that surgical treatment followed by adjuvant chemoradiotherapy offers a survival advantage as compared to any of the modalities used alone. (P 0.071, with 100% relative importance on ANN). Keywords: Artificial neural network, intramedullary spinal lesions, pediatric neuroepithelial tumors, primary primitive neuroectodermal tumors

Introduction: Current molecular research has shown the several oncogenic pathways that give rise to the peripheral T‐cell lymphoma, not otherwise defined (PTCL, NOS) subtypes, which alter prognosis and might have predictive value. This study was conducted to assess the immunohistochemistry (IHC) algorithm by Amador et al for the subtyping of PTCL, NOS and determine its applicability in relation to the clinicopathological profile. Methods: This study included 43 patients with PTCL, NOS diagnosis. Following the use of IHC for the transcription factors GATA3, TBX21, CCR4, and CXCR3, two pathologists subtyped the samples. Comprehensive clinicopathological correlation was carried out. Results: Applying the algorithm of Amador et al., cases were classified into GATA3 (20), TBX21 (15), and unclassified (8) subtypes. No significant association with clinical parameters of subtypes or CD4/ CD8 positivity was observed. Although a higher proportion of cases in the TBX21 subgroup showed a polymorphic population compared with the GATA3 subgroup, which had a monomorphic population, no significant p‐value (0.111) was observed. Two Lennert lymphomas were classified into the GATA3 subgroup. Multivariate analysis showed no significant difference in overall survival (p‐value = 0.105) and progression‐free survival (p‐value = 0.0509) between IHC‐defined subtypes; trends indicate that overall survival and progression‐free survival are worse in the GATA3 subgroup. Conclusion: Although the algorithm is reproducible, a proportion of cases remains unclassifiable and may require additional investigation and gene expression profiling. The GATA3 subgroup was found to have a monomorphic population with a poor overall prognosis and thus requires a larger sample size for validation. [ABSTRACT FROM AUTHOR]

Introduction: Papillary thyroid carcinoma (PTC) has an excellent prognosis, but few cases are treatment-resistant. To check the applicability of combined BRAF V600E and MEK-targeted therapy, the current study correlated BRAF V600E with the MAPK pathway activation status in a cohort of PTCs. The prognostic relevance of BRAF V600E and the usability of immunohistochemistry (IHC) for detecting the mutation were also assessed. Methods: Randomly selected 50 PTC and 15 non-PTC cases were re-classified according to the 2022 WHO classification. The BRAF mutation status was compared with the IHC of BRAFV600E, pERK1/2, pMEK1/2, and clinicopathological variables, including response to radioactive iodine and disease-free survival. Results: BRAF V600E mutation was present in 38%. Most (87.8%) cases were immunopositive for pMEK1/2 and 40% for pMEK1/2. Although BRAF V600E mutation did not correlate with the MAPK activation status, it had an adverse impact on tumour sensitivity to radioiodine (P < 0.05). Five of the seven radioiodine-resistant tumours were BRAF V600E-mutated. An Allred cut-off score of 7 had a sensitivity of 100% and a specificity of 84% for detecting the mutation by IHC. All the non-PTC cases were BRAF -wild type, but 20% showed weak immunopositivity for mutated protein and were scored 6. Conclusions: BRAF V600E-mutated PTCs are more likely to be RAI-resistant. MAPK pathway activation status did not vary significantly with BRAF mutation. Immunopositivity for pMEK1/2 in most suggests a scope for MEK1-targeted therapy in recalcitrant PTC cases even in the absence of the BRAF mutation. In addition, IHC is a reliable technique for detecting BRAF V600E mutation but needs validation by correlation with molecular studies. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the utility of simple, cost-effective, and non-invasive strategies alternative to BIPSS and peripheral CRH stimulation in differential diagnosis of ACTH-dependent CS. First, we performed ROC analysis to evaluate the performance of various tests for differential diagnosis of ACTH-dependent CS in our cohort (CD, n=76 and EAS, n=23) and derived their optimal cut-offs. Subsequently, combining various demographic (gender), clinical (hypokalemia), biochemical (plasma ACTH, HDDST, peripheral CRH stimulation) and imaging (MRI pituitary) parameters, we derived non-invasive models with 100% PPV for CD. Patients with pituitary macroadenoma (n=14) were excluded from the analysis involving non-invasive models. Relative percent ACTH (AUC: 0.933) and cortisol (AUC: 0.975) increase on peripheral CRH stimulation demonstrated excellent accuracy in discriminating CD from EAS. Best cut-offs for CD were plasma ACTH<97.3 pg/ml, HDDST≥57% cortisol suppression, CRH stimulation≥77% ACTH increase and≥11% cortisol increase. We derived six models that provided 100% PPV for CD and precluded the need for BIPPS in 35/85 (41.2%) patients with ACTH-dependent CS and no macroadenoma (in whom BIPSS would have otherwise been recommended). The first three models included basic parameters and avoided both peripheral CRH stimulation and BIPSS in 19 (22.4%) patients, while the next three models included peripheral CRH stimulation and avoided BIPSS in another 16 (18.8%) patients. Using simple and non-invasive alternative strategies, BIPSS can be avoided in 41% and peripheral CRH stimulation in 22% of patients with ACTH-dependent CS and no macroadenoma; such patients can be directly referred for a pituitary surgery. [ABSTRACT FROM AUTHOR]