Clinico-radio-pathological predictors of outcomes in patients with acromegaly undergoing endoscopic transsphenoidal surgery.

Background: Acromegaly is a rare chronic endocrine disorder with variable biochemical remission rates from 40% to 85%. Hence, understanding the factors predicting biochemical cures helps in planning targeted and personalized treatment. We aimed to study the various clinico-radio-pathological predictors of outcomes in patients with pituitary neuroendocrine tumor (PitNET) who underwent transsphenoidal surgery (TSS) at 3 months follow-up. Methods: Our cohort included 61 consecutive patients with acromegaly treated at an institute in northwest India between January 2019 and June 2021. The outcomes of TSS were assessed at the end of 3 months postoperatively as defined by Endocrine Society Guidelines 2014. Results: The mean age at diagnosis was 38 ± 12 years, with the majority being females (67.2%). The median tumor volume was 2376 mm3 with high insulin-like growth factor-1 levels (3.12 ± 1.76 times the upper reference limit). Forty-two patients (68.8%) had radiological evidence of cavernous sinus invasion. Overall, the biochemical remission rate at 3 months was 34.4%. Unlike preoperative Knosp grading, T2-hypointensity was not predictive of biochemical remission. The granularity of PitNET, as well as immunohistochemical (IHC) markers such as Ki-67 index somatostatin receptor subtype (SSTR2/5) and low-molecular-weight cytokeratin (CAM5.2) expression, failed to show any significant correlation with remission. Conclusion: Overall, bulky tumors, higher hormone burden, and advanced Knosp grades translated to lower rates of biochemical remission in the present study cohort. Contrary to earlier studies, conventional IHC markers such as Ki-67, SSTR2/5, and CAM5.2 were not useful for predicting biochemical remission at 3 months.

Patient satisfaction and value based purchasing in hospitals, Odisha, India.

Objective: To examine how a general inpatient satisfaction survey functions as a hospital performance measure. Methods: We conducted a mixed-methods pilot study of the Hospital Consumer Assessment of Health Providers and Systems survey in Odisha, India. We divided the study into three steps: cognitive testing of the survey, item testing with exploratory factor analysis and content validity indexing. Cognitive testing involved 50 participants discussing their interpretation of survey items. The survey was then administered to 507 inpatients across five public hospitals in Odisha, followed by exploratory factor analysis. Finally, we interviewed 15 individuals to evaluate the content validity of the survey items. Findings: Cognitive testing revealed that six out of 18 survey questions were not consistently understood within the Odisha inpatient setting, highlighting issues around responsibilities for care. Exploratory factor analysis identified a six-factor structure explaining 66.7% of the variance. Regression models showed that interpersonal care from doctors and nurses had the strongest association with overall satisfaction. An assessment of differential item functioning revealed that patients with a socially marginalized caste reported higher disrespectful care, though this did not translate into differences in reported satisfaction. Content validity indexing suggested that discordance between experiences of disrespectful care and satisfaction ratings might be due to low patient expectations. Conclusion: Using satisfaction ratings without nuanced approaches in value-based purchasing programmes may mask poor-quality interpersonal services, particularly for historically marginalized patients. Surveys should be designed to accurately capture true levels of dissatisfaction, ensuring that patient concerns are not hidden.

Idiopathic hypereosinophilic syndrome presenting with stroke.

Hypereosinophilic syndrome (HES) is characterized by eosinophilia associated with organ damage. The disorder has substantial clinical heterogeneity and a highly variable prognosis. This report describes an interesting autopsy case of a 62-year-old lady presenting with itching and stroke-like symptoms. She was diagnosed with an "idiopathic" variant of HES after a thorough exclusion of all known causes. Despite adequate measures, she deteriorated rapidly. At autopsy, acute cerebral infarcts were identified in multiple vascular territories including infarcts in watershed areas. Additionally, her heart showed classic pathological features of eosinophilic myocarditis spanning all three stages.

Isolated cavernous venous malformation of the eyelid.

Cavernous hemangioma, currently known as "cavernous venous malformation," is a common, benign, non-infiltrative, slowly progressive vascular malformation of the orbit presenting in adults. We report the case of a 9-year-old girl who presented with a painless palpable mass over the right upper eyelid of 7 years' duration. A computed tomography scan of the orbits revealed a heterogeneously enhancing, well-circumscribed mass in the right upper eyelid with no orbital extension. A transcutaneous excisional biopsy with histopathology disclosed cavernous venous malformation. The majority of cavernous venous malformations are intraconal and present in the fourth to fifth decade of life.

Prostate-Specific Membrane Antigen-Avid Neurofibroma Mimicking Cutaneous Metastasis in Metastatic Castration-Resistant Prostate Cancer on 18 F-PSMA-1007 PET/CT.

ABSTRACT: The occurrence of cutaneous metastases in prostate cancer is exceedingly rare. Many benign lesions and nonprostatic cancers can express the prostate-specific membrane antigen (PSMA). They can potentially mimic metastasis of prostate cancer and lead to misinterpretation of PSMA PET/CT findings. Additionally, it has significant management and prognostic implications. We present a rare case of an 88-year-old man with metastatic castration-resistant prostate cancer who showed a PSMA-expressing subcutaneous nodule in the scalp on 18 F-PSMA-1007 PET/CT, raising the suspicion of cutaneous metastasis. However, its biopsy revealed a neurofibroma, altering the disease prognosis and management.

Rat Model of Isoproterenol-Induced Myocardial Injury.

Isoproterenol (ISO) administration produces significant biochemical and histological changes including oxidative stress, reactive oxygen species (ROS) overproduction, and inflammation that leads to aggravation of myocardial injury. Subcutaneous or intraperitoneal ISO injection into rats can replicate several features of human heart disease, making it a useful tool for comprehending the underlying mechanisms and evaluating potential therapeutic strategies. In the present chapter, we elaborate on how depending on the precise experimental goals and the intended level of severity, different dosages and regimens are employed to induce myocardial injury.

Suprasellar masquerader: Chordoid glioma.

BACKGROUND: Chordoid glioma is a rare well-circumscribed glial neoplasm arising in adults and predominantly affects females. Tanycytes of the third ventricle have been proposed as the cell of origin owing to its location. It is characterized by chordoid features with myxoid and inflammatory stroma and recurrent PRKCA p.D463H missense mutation. CASE REPORT: We present two cases (30-year-old female and 45-year-old male) with similar complaints of behavioral change and headache. Midline suprasellar homogeneously enhancing mass was seen on contrast-enhanced magnetic resonance imaging. Histopathology and immunohistochemistry was characteristic of chordoid glioma with cords and clusters of epithelioid cells arranged in a solid pattern. There were variable amounts of myxoid stroma and lymphoplasmacytic infiltrate. No mitosis, necrosis, or brain invasion was noted. The cells expressed strong diffuse positivity for glial fibrillary acid protein (GFAP) and weak nuclear thyroid transcription factor (TTF-1). Epithelial membrane antigen (EMA)and brachyury were negative. Subsequently, the lady underwent gross total excision and died soon after the operation. The male patient received radiotherapy and is currently doing well after 6 months of follow-up. CONCLUSION: The rare occurrence as well as the radiological and morphological overlaps in chordoid gliomas make them a true masquerader. Combination of GFAP and TTF-1 in the immunohistochemical panel can be useful in differential diagnosis. Mainstay of treatment is complete surgical excision, with adjuvant radiotherapy becoming increasingly important.

Cytomorphologic and immunocytochemical characterization of pediatric pleuropulmonary blastoma with a comprehensive review of the literature.

INTRODUCTION: Pleuropulmonary blastoma (PPB) is a rare, aggressive, primary intrathoracic malignancy typically seen in infancy and early childhood. Accurate distinction from congenital cystic lung lesions is crucial due to significant prognostic and therapeutic differences. Cytologic features have rarely been described. Establishing a cytodiagnosis is challenging owing to its rarity, lack of awareness, and multiple morphologic mimics. MATERIALS AND METHODS: This was a retrospective study conducted over 8 years. The histopathology and cytopathology databases were searched for all pediatric PPB cases. The corresponding cytologic samples were reviewed to identify characteristic features that can help distinguish PPB from its mimics. RESULTS: There was a total of six cases of pediatric PPB reported during the study period. Of these, four (66.7%) presented as intrathoracic, and two (33.3%) as pleural-based masses. Cytology smears showed discretely scattered and perivascular arrangements of round-oval tumor cells with background eosinophilic stromal material. The tumor cells were mildly pleomorphic (n = 3) with round nuclei, fine chromatin, inconspicuous nucleoli, and scanty cytoplasm; however, three cases showed marked anaplasia, and one each showed necrosis and rhabdoid differentiation. On immunocytochemistry (4/6), these were positive for vimentin and desmin and negative for WT1, chromogranin, SALL4, cytokeratin, CD45, and CD99. FISH (1/6) did not show N-Myc amplification. CONCLUSIONS: Knowledge of the characteristic cytomorphological and immunocytochemical features of PPB is vital to establish a prompt and accurate cytodiagnosis with appropriate clinicoradiologic correlation.

Clinical, immunological and molecular profiles of DOCK8 deficiency in six patients from a tertiary care centre in North India.

BACKGROUND: Dedicator of cytokinesis protein 8 (DOCK8) deficiency is an autosomal recessive form of combined immunodeficiency. This rare disorder is characterized by an increased predisposition to allergy, autoimmunity and malignancies. OBJECTIVES: To analyse clinical, immunological and molecular profiles of patients with DOCK8 deficiency. METHODS: Clinic records of all patients attending the primary immunodeficiency clinic from 2018 to 2021 were reviewed. Six patients from five families were found to have DOCK8 deficiency. RESULTS: Median age at diagnosis was 7.5 years (range 2-13), with a male/female ratio of 5 : 1. Among the six patients, recurrent eczematous skin lesions were the predominant cutaneous manifestation, present in five patients (83%). Warts and molluscum contagiosum were evident in two patients (33%) and one patient (16%), respectively. Two patients had recalcitrant prurigo nodularis lesions and two had epidermodysplasia verruciformis-like lesions. Food allergies and asthma were reported by one patient each. Of the six patients, recurrent sinopulmonary infections were detected in five (83%). Epstein-Barr virus-driven non-Hodgkin lymphoma with liver metastases was the only case of malignancy, in a 4-year-old boy. IgE was elevated in all patients. Lymphopenia and eosinophilia were observed in three patients (50%) and five patients (83.3%), respectively. Genetic analysis showed DOCK8 pathogenic variants in all patients: homozygous deletion mutations in two patients, compound heterozygous deletion mutations in one, and homozygous nonsense mutations in two. A novel pathogenic homozygous missense variant in the DOCK8 gene was identified in one patient. CONCLUSIONS: DOCK8 deficiency should be considered as a possibility in any patient with early onset eczema, cutaneous viral infections and increased predisposition to allergy, autoimmunity and malignancy.

Isolated embryonal rhabdomyosarcoma of the anterior petrous bone in a young child: Focusing on the intra-operative diagnosis and differentials.

OBJECTIVE: Rhabdomyosarcoma is a common soft tissue tumor, but isolated involvement of anterior portion of petrous bone is exceedingly rare. Here, we present a case of embryonal rhabdomyosarcoma involving the anterior petrous without involvement of the mastoid and middle ear. PATIENT: A 6-year-old boy presented with a progressive right side lower motor neuron facial paresis for 1-month duration along with headache and recurrent vomiting episodes. Radiology showed a contrast-enhancing lesion involving the right petrous apex. He underwent craniotomy and excision of the lesion. Based on the frozen section, a diagnosis of rhabdomyosarcoma was rendered, and gross total resection could be achieved. Postoperative course was uneventful. CONCLUSION: Isolated petrous bone involvement of embryonal rhabdomyosarcoma is a rare presentation. Intra-operative frozen section plays a key role in decision making regarding the extent of excision. Hence, a prompt and accurate diagnosis is essential in managing these cases.

MYCN amplification, TERT rearrangements and ATRX mutations in neuroblastoma: clinicopathological correlates- an Indian perspective.

BACKGROUND: Neuroblastoma (NB) is the most common extracranial solid tumour in childhood with a diverse clinical presentation and course. The early age of onset, high frequency of metastatic disease at diagnosis and tendency for spontaneous regression in infancy sets it apart from other childhood tumors. This heterogeneity is largely attributed to underlying genetic aberrations which are distinct in low-risk and high-risk NB. To this end, we sought to analyse our NB cases for the molecular alterations and find its correlation with clinical behaviour. METHODS: NB cases (n = 50) diagnosed over last 7 years were retrospectively analysed for MYCN amplification (fluorescent-in-situ hybridization), TERT rearrangements (qRT-PCR), ATRX mutations (immunohistochemistry). These findings were correlated with demographic profiles, histologic features and clinical outcome. RESULTS: Age ranged from 1 month to 30 years (mean 2.8 years) with male preponderance. Poorly differentiated subtype constituted the majority (64%), followed by differentiating (28%) and undifferentiated subtype (8%) which were equally distributed across all age groups. MYCN amplification, TERT-mRNA upregulation and ATRX mutations was observed in 30%, 42% and 24%, respectively. Cases with TERT-mRNA upregulation were distributed equally across all histological subtypes while those with ATRX mutations and MYCN amplification were frequent in poorly differentiated NB. ATRX mutation was mutually exclusive of TERT-mRNA upregulation and MYCN amplification. Kaplan-Meier analysis revealed significantly shorter overall and progression-free survival for tumors harboring MYCN amplification and TERT-mRNA upregulation, while that for ATRX mutant tumors was not significant. CONCLUSIONS: Our results provide data indicating poor clinical outcome in NB carrying MYCN amplification and TERT-mRNA upregulation.

Association between intraoperative anatomical variation and histopathological parameters in cases of ureteropelvic junction obstruction in children: A cross-sectional study.

Introduction: The intraoperative anatomical findings (IOAF) of all ureteropelvic junction obstruction (UPJO) cases are not identical. Moreover, there is also controversy in the literature regarding histopathological (HP) findings in cases of UPJO. In the present study, we evaluated different IOAF and assessed their association with specific HP parameters. Materials and Methods: This was a cross-sectional study set-up, which was carried out in a tertiary care centre. Children with UPJO who underwent surgery between 2017 and 2020 were enrolled. The following IOAF were noted: Type of pelvis (extrarenal or intrarenal), insertion of the ureter (high or normal), presence of lower pole crossing vessel (CV), negotiation of UPJ segment with double J stent (3 Fr) and length of internal narrowing (LIN) at UPJ. The resected segment of UPJ was assessed at three levels (pelvis, UPJ and ureter) for various HP parameters including fibrosis, oedema, inflammation and smooth muscle hypertrophy (SMH). Results: Thirty-nine children were included in the study with a mean age of 31 months. The summary statistics of IOAF were intrarenal pelvis in 5 cases, high insertion of the ureter (HIU) in 9, CV in 6, negotiable UPJ in 23, and 16 cases showed LIN >1 cm. All cases showed SMH at the pelvis region and SMH with fibrosis at the UPJ region. At the pelvis region, there was an association between (1) HIU with oedema and chronic inflammation (CIF), (2) CV with CIF and (3) LIN with CIF and SMH. At the UPJ region, there was an association between (1) CV and negotiable UPJ with less fibrosis and (2) LIN with SMH. At the ureteric end, CV showed an association with less fibrosis and more CIF. Conclusion: All UPJO cases have some common HP findings. Although, some particular IOAF, i.e., presence of CV, negotiable UPJ, HIU and LIN showed association with specific HP parameters.

Immunohistochemical Surrogates for Molecular Stratification in Medulloblastoma.

BACKGROUND: The WHO classification of central nervous system neoplasms (2016) recognized 4 histologic variants and genetically defined molecular subgroups within medulloblastoma (MB). Further, in the 2021 classification, new subtypes have been provisionally added within the existing subgroups reflecting the biological diversity. YAP1, GAB1, and ß-catenin were conventionally accepted as surrogate markers to identify these genetic subgroups. OBJECTIVES: We aimed to stratify MB into molecular subgroups using 3 immunohistochemical markers. TP53 mutation was also assessed in Wingless (WNT), and Sonic Hedgehog (SHH) subgroups. Demographic profiles, imaging details, and survival outcomes were compared within these molecular subgroups. PATIENTS AND METHODS: Our cohort included 164 MB cases diagnosed over the last 10 years. The histologic variants were identified on histology, and tumors were molecularly stratified using YAP1, GAB1, and ß-catenin. Further, TP53 mutation was assessed using immunohistochemical in WNT and SHH subgroups. The clinical details and survival outcomes were retrieved from the records, and the mentioned correlates were evaluated statistically. RESULTS: The age ranged from 1 to 52 years with M:F ratio of 2:1. Group 3/group 4 constituted the majority (48.4%), followed by SHH (45.9%) and WNT subgroups (5.7%). Desmoplastic/nodular and MB with extensive nodularity had the best survival, whereas large cell/anaplastic had the worst. The follow-up period ranged from 1 to 129 months. The best outcome was observed for the WNT subgroup, followed by the SHH subgroup; group 3/group 4 had the worst. Among the SHH subgroup, TP53 mutant tumors had a significantly poorer outcome compared with SHH-TP53 wildtype. CONCLUSIONS: Molecular stratification significantly contributes to prognostication, and a panel of 3 antibodies is helpful in stratifying MB into its subgroups in centers where access to advanced molecular testing is limited. Our study reinforces the efficacy of incorporating this cost-effective, minimal panel into routine practice for stratification. Further, we propose a 3-risk stratification grouping, incorporating morphology and molecular markers.

Protease-activated receptors in kidney diseases: A comprehensive review of pathological roles, therapeutic outcomes and challenges.

Studies have demonstrated that protease-activated receptors (PARs) with four subtypes (PAR1-4) are mainly expressed in the renal epithelial, endothelial, and podocyte cells. Some endogenous and urinary proteases, namely thrombin, trypsin, urokinase, and kallikrein released during diseased conditions, are responsible for activating different subtypes of PARs. Each PAR receptor subtype is involved in kidney disease of distinct aetiology. PAR1 and PAR2 have shown differential therapeutic outcomes in rodent models of type-1 and type-2 diabetic kidney diseases due to the distinct etiological basis of each disease type, however such findings need to be confirmed in other diabetic renal injury models. PAR1 and PAR2 blockers have been observed to abolish drug-induced nephrotoxicity in rodents by suppressing tubular inflammation and fibrosis and preventing mitochondrial dysfunction. Notably, PAR2 inhibition improved autophagy and prevented fibrosis, inflammation, and remodeling in the urethral obstruction model. Only the PAR1/4 subtypes have emerged as a therapeutic target for treating experimentally induced nephrotic syndrome, where their respective antibodies attenuated the podocyte apoptosis induced upon thrombin activation. Strikingly PAR2 and PAR4 subtypes involvement has been tested in sepsis-induced acute kidney injury (AKI) and renal ischemia-reperfusion injury models. Thus, more studies are required to delineate the role of other subtypes in the sepsis-AKI model. Evidence suggests that PARs regulate oxidative, inflammatory stress, immune cell activation, fibrosis, autophagic flux, and apoptosis during kidney diseases.