Mucormycosis due to Apophysomyces species complex- 25 years' experience at a tertiary care hospital in southern India.

Apophysomyces elegans species complex is an important cause of cutaneous mucormycosis in India. However, majority of those cases are reported as case reports only. We desired to analyze our patients with Apophysomyces infection reported over 25 years (1992-2017) to understand the epidemiology, management, and outcome of the disease. During the study period 24 cases were reported, and the majority (95.8%) of them presented with necrotizing fasciitis following accidental/surgical/iatrogenic trauma. One patient presented with continuous ambulatory peritoneal dialysis (CAPD) related peritonitis. Healthcare related Apophysomyces infection was noted in 29.2% patients. In addition to trauma, comorbidities were noted in 37.5% patients (type 2diabetes mellitus-6, chronic alcoholism-2, and chronic kidney disease-1). Of the 24 isolates, 11 isolates starting from year 2014 were identified as Apophysomyces variabilis by molecular methods. Majority (95.8%) of the patients were managed surgically with or without amphotericin B deoxycholate therapy, while one patient was treated with amphotericin B deoxycholate alone. Among 24 patients, seven (29.1%) recovered, six (25%) patients could not afford antifungal management and left the hospital against medical advice, and 11 (45.9%) patients died.The present case series highlights that necrotizing fasciitis caused by A. variabilis is prevalent in India, and the disease may be healthcare related. Although diagnosis is not difficult, awareness among surgeons is still limited about the infection, leading to a delay in sending samples to the mycology laboratory. Apophysomyces infection must be considered in the differential diagnosis in apatient with progressive necrosis of a wound who is not responding to antibacterial therapy.

C4d as a marker of complement activation in dermatomyositis muscle tissue.

AIM: To study C4d expression as a marker of complement activation in the diagnosis of dermatomyositis. MATERIAL AND METHODS: Muscle biopsies from patients diagnosed as definite dermatomyositis (10), nonspecific myositis associated with connective tissue disease (9), necrotizing autoimmune myositis (1), inclusion body myositis (1), and normal muscle (1) according to European Neuromuscular criteria 2004 were studied for C4d expression and capillary loss on CD 34 immunohistochemistry. RESULTS: C4d was expressed in all biopsies of definite dermatomyositis in the perimysial vessels and in 3/10 endomysial capillaries corresponding to capillary loss on CD 34.C4d expression was seen in 2/3 perimysial and endomysial vessels in nonspecific myositis (2/3 overlap myositis), and 1/1 of nectrotizing autoimmune myositis.Necrotic muscle fibers in all biopsies showed positivity irrespective of the diagnosis. CONCLUSION: C4d can be used as a marker of complement activation for the diagnosis of dermatomyositis.

Idiopathic inflammatory myopathies in adults: A comparative study of Bohan and Peter and European Neuromuscular Center 2004 criteria.

BACKGROUND: Bohan and Peter criteria are widely used for the diagnosis of idiopathic inflammatory myopathies (IIMs). Recently, European Neuromuscular Center (ENMC) formulated criteria to identify subgroups of IIMs. AIM: To compare the two diagnostic criteria in adult IIMs. MATERIALS AND METHODS: This was a retrospective review of case records of histologically confirmed IIMs in adults between January 2014 and May 2015. Both the Bohan and Peter, and ENMC 2004 criteria were applied in the same group of patients to subgroup the IIMs. Muscle biopsy was evaluated in all the four domains: muscle fiber, inflammatory, connective tissue, and vascular, with the basic panel of histological stains. Sporadic inclusion body myositis (s-IBM) was diagnosed using ENMC IBM diagnostic research criteria 2011. RESULTS: During the study period, 69 patients fulfilled the ENMC criteria for IIMs including 16 patients with s-IBM. The subgrouping as per the ENMC criteria (53) was: dermatomyositis (DM) in 30; polymyositis (PM) in 2; immune-mediated necrotizing myopathy (IMNM) in 9; and nonspecific myositis (NM) in 12 patients, whereas subgrouping by the Bohan and Peter criteria was DM in 9 and PM with and without connective tissue disease (CTD) in 26 patients only. There was underdiagnosis of DM, as perifascicular atrophy is not recognized as a diagnostic histological feature, and overdiagnosis of PM with and without CTD due to poor characterization of histological features in PM by the Bohan and Peter criteria. CONCLUSIONS: Systematic evaluation of muscle biopsy according to the ENMC criteria with basic panel of histochemical stains improved the diagnostic yield of IIM significantly when compared to the Bohan and Peter criteria.

Meningiomas: Objective assessment of proliferative indices by immunohistochemistry and automated counting method.

BACKGROUND: The most reliable histological correlate of recurrence risk in meningiomas is increased mitotic activity. Proliferative index with Ki-67 immunostaining is a helpful adjunct to manual counting. However, both show considerable inter-observer variability. A new immunohistochemical method for counting mitotic figures, using antibody against the phosphohistone H3 (PHH3) protein was introduced. Similarly, a computer based automated counting for Ki-67 labelling index (LI) is available. AIMS AND OBJECTIVES: To study the use of these new techniques in the objective assessment of proliferation indices in meningiomas. MATERIALS AND METHODS: This was a retrospective study of intracranial meningiomas diagnosed during the year 2013.The hematoxylin and eosin (H and E) sections and immunohistochemistry (IHC) with Ki-67 were reviewed by two pathologists. Photomicrographs of the representative areas were subjected to Ki-67 analysis by Immunoratio (IR) software. Mean Ki-67 LI, both manual and by IR were calculated. IHC with PHH3 was performed. PHH3 positive nuclei were counted and mean values calculated. Data analysis was done using SPSS software. RESULTS: A total of 64 intracranial meningiomas were diagnosed. Evaluation on H and E, PHH3, Ki-67 LI (both manual and IR) were done in 32 cases (22 grade I and 10 grade II meningiomas). Statistically significant correlation was seen between the mitotic count in each grade and PHH3 values and also between the grade of the tumor and values of Ki-67 and PHH3. CONCLUSION: Both the techniques used in the study had advantage over, as well as, correlated well with the existing techniques and hence, can be applied to routine use.

Altered tryptophan metabolism in human meningioma.

Meningiomas are the neoplasms that arise from the arachnoid cells of the meninges. It was reported that cancer cells escape from immune system through the metabolism of an aromatic essential amino acid tryptophan (TRP) via Kynurenine (KYN) pathway. However, the role of TRP metabolites such as, 5-Hydroxy tryptophan (5-HTP), 5-Hydroxy tryptamine (5-HT), N-acetyl serotonin (NAS), Melatonin (MEL), KYN, N-acetyl tryptamine, 5-Hydroxy indole acetic acid (5-HIAA) and 5-Methoxy indole acetic acid is not yet evaluated in human meningioma. Therefore, in the current study we have evaluated the levels of TRP and its metabolites in the progression of human meningioma using tumor biopsy samples and autopsy control meninges with Reverse Phase-HPLC. We here report that TRP metabolism favors towards KYN pathway in human meningioma and it could be due to increased indoleamine 2,3-dioxygenase 2 levels as we found its m-RNA levels to be up regulated in human meningioma. We observed significant increase in KYN and 5HIAA levels and significant decrease in TRP, 5-HTP, 5-HT, NAS and MEL levels in meningioma compared to control meninges. Since TRP metabolites regulate inducible nitric oxide synthase (INOS) gene expression and thereby nitric oxide (NO) production, we have also evaluated the INOS and NO levels. The INOS and NO levels were up regulated in human meningioma. The present data corroborates with existing data on TRP metabolism in tumor progression and may serve to target TRP metabolism as a therapeutic intervention.

Diagnosis of filamentous fungi on tissue sections by immunohistochemistry using anti-aspergillus antibody.

Identification based on histology alone has limitations as Aspergillus species share morphology with other filamentous fungi. Differentiation of Aspergillus species from hyalohyphomycetes and dematiaceous fungi is important as the antifungal susceptibility varies among different species and genera. Given these problems, ancillary techniques are needed to increase specificity. Our aim was to study the utility of immunohistochemistry (IHC) with anti-Aspergillus antibody in the identification of Aspergillus species and to differentiate them from other filamentous fungi. Fifty formalin fixed, paraffin embedded tissue sections including 47 from cases of culture proven filamentous fungi, 3 from colonies of cultures of hyalohyphomycetes, and 11 smears from cultures were subjected to IHC studies using polyclonal rabbit anti-Aspergillus antibody (Abcam, UK) after antigen retrieval. The IHC on tissue sections was positive in 88% cases involving culture proven Aspergillus species. There was no cross reactivity with Mucorales species, Candida species, dematiaceous fungi and hyalohyphomycetes. Hence immunohistochemistry can be used as an ancillary technique for the diagnosis of Aspergillus species.

Series of paraneoplastic vasculitic neuropathy: a rare, potentially treatable neuropathy.

BACKGROUND: Paraneoplastic vasculitic neuropathy (PVN) is a rare paraneoplastic syndrome. It is characterized by non-systemic subacute vasculitic neuropathy. It is most commonly associated with small cell lung cancers (SCLC) and lymphomas. PVN presents as a painful symmetrical or asymmetrical sensorimotor axonal neuropathy. The neurological symptoms may predate the tumor and may be the initial manifestations, or they may develop after a tumor is diagnosed. Recognition of this entity is important because of its potential treatability. AIM: To study the clinical features of PVN and briefly review the literature. MATERIALS AND METHODS: The data was collected retrospectively from the medical records of our hospital. RESULTS: Of the 14 cases of paraneoplastic neuropathies, 4 had a PVN. The age of onset was more than 50 years and there was no sex preponderance. Pain was seen in three patients. Two patients were previously treated for a thymoma. Two patients, following their presentation with PVN, were diagnosed with a colonic carcinoma and lung carcinoma, respectively. CONCLUSIONS: The recognition of PVN is important as this syndrome may respond to immunosuppression and tumor removal.

LC-MS/MS analysis of differentially expressed glioblastoma membrane proteome reveals altered calcium signaling and other protein groups of regulatory functions.

Membrane proteins play key roles in the development and progression of cancer. We have studied differentially expressed membrane proteins in glioblastoma multiforme (GBM), the most common and aggressive type of primary brain tumor, by high resolution LC-MS/MS mass spectrometry and quantitation by iTRAQ. A total of 1834 membrane proteins were identified with high confidence, of which 356 proteins were found to be altered by 2-fold change or more (198 up- and 158 down-regulated); 56% of them are known membrane proteins associated with major cellular processes. Mass spectrometry results were confirmed for representative proteins on individual specimens by immunohistochemistry. On mapping of the differentially expressed proteins to cellular pathways and functional networks, we notably observed many calcium-binding proteins to be altered, implicating deregulation of calcium signaling and homeostasis in GBM, a pathway also found to be enriched in the report (Dong, H., Luo, L., Hong, S., Siu, H., Xiao, Y., Jin, L., Chen, R., and Xiong, M. (2010) Integrated analysis of mutations, miRNA and mRNA expression in glioblastoma. BMC Syst. Biol. 4, 163) based on The Cancer Genome Atlas analysis of GBMs. Annotations of the 356 proteins identified by us with The Cancer Genome Atlas transcriptome data set indicated overlap with 295 corresponding transcripts, which included 49 potential miRNA targets; many transcripts correlated with proteins in their expression status. Nearly 50% of the differentially expressed proteins could be classified as transmembrane domain or signal sequence-containing proteins (159 of 356) with potential of appearance in cerebrospinal fluid or plasma. Interestingly, 75 of them have been already reported in normal cerebrospinal fluid or plasma along with other proteins. This first, in-depth analysis of the differentially expressed membrane proteome of GBM confirms genes/proteins that have been implicated in earlier studies, as well as reveals novel candidates that are being reported for the first time in GBM or any other cancer that could be investigated further for clinical applications.

Grossing to reporting of Wilms tumor with emphasis on proper sampling in treatment-naive and postchemotherapy specimens and their clinicopathological correlation with outcome.

Context: Emphasis on grossing to reporting for the assessment of histopathological parameters predicting outcomes in Wilms tumor. Aims: To analyze various clinicopathological parameters that effect outcomes in treatment naïve and post chemotherapy Wilms tumor specimens. Settings and Design: This was a retrospective observational study. Subjects and Methods: All patients diagnosed with Wilms tumor between 2012 and 2018 at our institute will be included with their clinical findings, laboratory reports, and radiological findings. The patients will be categorized into two groups based on treatment protocol (Society of Pediatric Oncology (SIOP) or the National Wilms Tumor Study Group/Children's Oncology Group (COG) guidelines) used. Details of Grossing and reporting protocols used for the in pre treatment and post treatment specimens will be analyzed. Follow-up till December 2020 will be analyzed. Statistical Analysis Used: Chi-square and Fisher's exact tests were used for statistical analysis. Results: A total of 36 patients with the diagnosis of Wilms tumor were included in the present study. The mean age of presentation was 3.9 ± 0.7 years, and males were more common than females. Most of them presented as abdominal mass and few with isolated hematuria. Twenty-six (72%) patients were treated under SIOP protocol with preoperative neoadjuvant chemotherapy. Ten patients underwent upfront surgery as per COG protocol. In SIOP group patients, the mean tumor size was 9.3cm. Forty percent (n = 10) we mixed histological type followed by blastemal type constituting (32%, n = 8). Regressive and epithelial histological types constituted 16% (n = 4) and 12% (n = 3), respectively. In the SIOP group 72% (n = 19) had no anaplasia and 28% (n = 7) had anaplasia. Fifty seven percent (n = 15) cases were Stage I, followed by 26.9% n = 7) and 11.5% (n = 3) being Stage II and Stage III, respectively. Ten patients underwent upfront surgery as per COG protocol. The mean tumor size among this group was 8 cm ranging from 7 cm to 11 cm. Eight (80%) cases had favorable histology and two cases showed focal anaplasia. Heterologous differentiation is seen in 3 (70%). Out of the 10 cases, one case was Stage I, six were Stage 2, one was Stage III, and two were clinical Stage IV. None of the cases showed either vessel or lymph node metastasis. All the patients received adjuvant chemotherapy postsurgery and were followed up till December 2020 for (at least 3 years). Of 25 patients in the SIOP group, 18 (72%) had complete remission with no radiological evidence of residual disease. Of the 10 patients in the COG group, 6 (70%) had complete remission. Conclusions: Histopathological evaluation of Wilms tumor is a critical aspect in the management of Wilms tumor, as tumor characteristics are different in the tumors treated under SIOP and COG protocols, which will ultimately affect the prognostic risk stratification. This necessitates the knowledge of the important grossing and reporting of these tumors under the two protocols.

Heterogeneous nuclear ribonucleoproteins and their interactors are a major class of deregulated proteins in anaplastic astrocytoma: a grade III malignant glioma.

Anaplastic astrocytoma is a high grade malignant glioma (WHO grade III) of the central nervous system which arises from a low grade II tumor and invariably progresses into lethal glioblastoma (WHO grade IV). We have studied differentially expressed proteins from the microsomal fraction of the clinical specimens of these tumors, using iTRAQ and high-resolution mass spectrometry followed by immunohistochemistry for representative proteins on tissue sections. A total of 2642 proteins were identified, 266 of them with minimum 2 peptide signatures and 2-fold change in expression. The major groups of proteins revealed to be differentially expressed were associated with key cellular processes such as post transcriptional processing, protein translation, and acute phase response signaling. A distinct inclusion among these important proteins is 10 heterogeneous nuclear ribonucleoproteins (hnRNPs) and their interacting partners which have regulatory functions in the cell. hnRNP-mediated post transcriptional events are known to play a major role in mRNA processing, stability, and distribution. Their altered levels have also been observed by us in lower (diffused astrocytoma) and higher (glioblastoma) grades of gliomas, and membrane localization of hnRNPs has also been documented in the literature. hnRNPs may thus be major factors underlying global gene expression changes observed in glial tumors while their differential presence in the microsomal fraction suggests yet additional and unknown roles in tumorigenesis.

Significance of tumor-infiltrating lymphocytes in tumor regression in breast cancer: A study in a tertiary care cancer center in South India.

BACKGROUND: Tumor immunology plays a significant role in predicting tumor biology and how a tumor is going to respond to neoadjuvant chemotherapy (NACT). Tumor-infiltrating lymphocytes (TILs) are the easiest and by far the cheapest method of assessing tumor immunity. Many studies have suggested that TILs play an important role in tumor regression in breast cancer. AIM: The aim of the current study was to determine significance of TILs in tumor regression in breast cancer. MATERIALS AND METHODS: Patients with newly diagnosed and histologically proven breast cancer who were treated with both NACT and surgery in our institute were included in the study. TILs were assessed both before and after NACT, and were correlated with the relative amount of tumor regression and molecular subtypes based on the immunohistochemistry profile. RESULTS: The study included 43 specimens of carcinoma breast in females. 42 cases were diagnosed with invasive carcinoma, no special type (NST), and one with lobular carcinoma. Pathological complete remission (pCR) was noted in 6 cases, partial remission (PRe) in 12 cases, and no response in 25 cases. TILs were noted before and after NACT in all cases and were correlated with other clinicopathological parameters. CONCLUSION: The present study highlights that TILs play a vital role in tumor regression and can be included in routine reporting. It can provide an insight into tumor biology.

Utility of GATA-3 and associated immunohistochemical markers in the differential diagnosis of poorly differentiated urothelial carcinoma.

Aims: The aims are to study the utility of GATA-3 along with panel of immunohistochemical (IHC) markers in the differential diagnosis of primary and metastatic poorly differentiated urothelial carcinoma (UC). Settings and Design: This is a prospective and retrospective observational study. Subjects and Methods: Poorly differentiated carcinomas of urinary tract and metastatic sites from January 2016 to December 2017 were subjected to a panel of four IHC markers including GATA-3, p63, Cytokeratin (CK) 7, and CK20. Additional markers such as p16, an enzyme called alpha-methylacyl-CoA racemase, CDX2, and thyroid transcription factor 1 were also done depending on the morphology and site. Statistical Analysis Used: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of GATA-3 in making the diagnosis of UC were calculated. Results: Forty-five cases were included in the study and after appropriate IHC, the diagnosis was resolved as UC in 24 cases. GATA-3 was positive in 83.33% of UC; all the four markers positive in 33.33% and all negative in 4.17% of UC. However, at least one of the four markers was present in 95.83% of UC, except in sarcomatoid UC. GATA-3 had 100% specificity in differentiating from prostate adenocarcinoma. Conclusion: GATA-3 is a useful marker in the diagnosis of UC in the primary and metastatic sites with a sensitivity of 83.33%. GATA-3 along with other IHC markers in correlation with clinical and imageological features is necessary for making specific diagnosis of poorly differentiated carcinoma.

Increased ß-catenin/Tcf signaling in pilocytic astrocytomas: a comparative study to distinguish pilocytic astrocytomas from low-grade diffuse astrocytomas.

Although pilocytic and diffuse grade II astrocytomas considered as low-grade tumors, the distinction between them is still a major clinical problem. Previously we reported the activation of Wnt/ß-catenin/Tcf signaling pathway in diffuse astrocytomas, however its role in pilocytic astrocytomas is not well understood. In this study, we investigated the Wnt/ß-catenin/Tcf pathway in pilocytic astrocytomas and compared with diffuse astrocytomas. We observed the differential expression of ß-catenin, Tcf4, Lef1 and c-Myc in astrocytomas particularly higher levels were observed in pilocytic astrocytomas and GBM while very little expression was documented in grade II tumors. Further, immunohistochemical analysis revealed the strong positivity of ß-catenin, Tcf4, Lef1 and c-Myc in pilocytic astrocytomas than that of grade II tumors and also exhibited the strong positivity in vascular endothelial cells of pilocytic astrocytomas and GBM. Hence, Wnt/ß-catenin/Tcf signaling pathway is differentially expressed in astrocytomas, activation of this pathway might be helpful in separating pilocytic astrocytomas from low-grade diffuse astrocytomas.

Dual gliomas with syringomyelia in a child: case report and literature review.

BACKGROUND AND IMPORTANCE: The occurrence of multiple tumors of different histopathologies in the central nervous -system is rare. Here, we report a case of a child with dual neuroepithelial tumors of different histological cell types and -review the available literature for analyzing the causal hypo-thesis. CASE REPORT: A 7-year-old girl presented with history of headaches associated with multiple episodes of early morning projectile vomiting and visual blurring. Magnetic resonance imaging (MRI) showed a well-defined lesion in the hypothalamic region. The patient underwent resection of the tumor by the transcallosal transfornicial approach. Histopathology was suggestive of pilocytic astrocytoma. After 3 years, the patient presented with low back pain radiating to the right lower limb followed by sudden onset of weakness in both lower limbs. Recent MRI brain and spine scans showed a small residual lesion at the hypothalamus with D1 to D10 syrinx. A T1 hypointense and T2 hyperintense cystic lesion from D10 to S2 with intensely enhancing solid component at the S1, S2 region was also detected. The patient underwent L4 to S2 laminectomy and the histopathological examination revealed myxopapillary ependymoma. CONCLUSION: The presence of multiple neuroepithelial tumors of different histopathology in the same patient is extremely rare, and we report one such case of dual gliomas with hypothalamic pilocytic astrocytoma and cauda equina myxopapillary ependymoma in a 10-year-old patient. During the course of development, displacement and dedifferentiation of primitive totipotent neuroepithelial germ cells may be a causal factor for the appearance of the different neuroepithelial tumors in neuraxis concomitantly or subsequently, which might be substantiated by common cytogenetic abnormalities in different neuroepithelial tumor histogenesis.

Granulomatous diseases of the central nervous system: Approach to diagnosis.

Diagnosis of central nervous system (CNS) granulomas is challenging. The etiology may be infectious or non-infectious. The infectious causes are due to mycobacteria, fungi, parasites and rarely bacteria. The non-infectious causes include autoimmune diseases, diseases of uncertain etiology like sarcoidosis, those associated with neoplasms and reparative processes. Histologic evaluation of type of granuloma as necrotizing, non-necrotizing, fibrotic/calcific or foreign-body type, site of CNS involvement (leptomeninges/dura, brain/spinal cord) and identification of etiologic agent on histochemistry/culture/molecular methods resolves the diagnosis in a many a patient. Correlation with clinical and imaging features, risk factors and route of spread, geographical location and travel history are important. However, diagnosis may remain unresolved despite the application of all available techniques, highlighting the need for better diagnostic techniques.

Pathogenesis and Pathology of COVID-Associated Mucormycosis: What Is New and Why.

Purpose of Review: There is global increase in the incidence of mucormycosis. However, a sudden increase in the COVID-associated mucormycosis (CAM) was noted, particularly in India, during the second wave of the COVID-19 pandemic. The interplay of factors involved in the pathogenesis is complex. In this review, the influence of pre-existing disease, exaggerated risk factors, altered milieu due to COVID-19 itself and the consequences of its treatment on the host pathogen interactions leading to the disease and morphology of the fungus will be highlighted. Recent Findings: Hyperglycemia, acidosis, available free iron, lowered host defenses, and the fungal virulence factors promote the growth of Mucorales. There is a high background prevalence of diabetes mellitus (DM) in India. Uncontrolled or undiagnosed DM, COVID-19 itself, and inappropriate administration of corticosteroids in high doses and for prolonged periods result in hyperglycemia. Diabetic ketoacidosis (DKA) and metabolic acidosis due to hypoxia or renal failure contribute to acidic pH and dissociate bound iron from serum proteins. The host defenses are lowered due to COVID-19-induced immune dysregulation, hyperglycemia itself, and administration of corticosteroids and immune suppressants for the treatment of COVID-19. The altered metabolic milieu in the local microenvironment of nose and paranasal sinuses (PNS) promotes specific interaction of glucose-regulated protein-78 (GRP-78) on host cells with spore coat protein homologue (CotH 3) on Mucorales resulting in rhino-orbito-cerebral mucormycosis (ROCM) as the predominant clinical form in CAM. The pathology is extensive soft tissue involvement with angioinvasion and perineural invasion. Melanized hyphae and sporangia were seen on histopathology, which is unique to CAM. While many factors favor the growth of Mucorales in CAM, hyperglycemia, hyperferritinemia, and administration of hyperbaric oxygen result in reactive oxygen species (ROS) and inadequate humidification results in dehydration. Melanization is possibly the adaptive and protective mechanism of Mucorales to escape the unfavorable conditions due to the treatment of COVID-19. Summary: High background prevalence of DM, inappropriate administration of corticosteroids and immune dysregulation due to COVID-19 favor the growth of Mucorales in CAM. Melanization of Mucorales hyphae and sporangia on histopathology probably represent adaptive and protective mechanism due to the treatment with hyperbaric oxygen with inadequate humidification as well as the metabolic alterations.

Pituitary blastoma, expanding the spectrum of newly recognized entities. A case report.

Tumors of the pituitary gland and sellar region represent about 15% of all brain tumors, with pituitary adenoma being the commonest and pituitary carcinoma being very rare. Pituitary tumors in children are even rarer. Pituitary blastoma, a pediatric adenohypophysial tumor, is a new entity described in the 2017 WHO classification of pituitary tumors. This is a very rare tumor with only 21 cases reported so far. Hence, we are reporting this unusual case seen in a 7-month-old infant who presented with a large sellar/suprasellar mass with pressure symptoms of short duration. Typically, they present between 7-24 months of age. On histopathology, a cellular tumor was seen with primitive-looking round cells with scanty cytoplasm with few well-defined gland or rosette-like structures. The immunohistochemical stains showed diffuse strong staining for synaptophysin with a very high MIB-1 index. Other markers for common round cell tumors in this age group and hormonal markers of pituitary tumors were negative with INI-1 being intact. The initial cases described by Scheithauer presented with Cushing's disease and at least focally expressed adrenocorticotrophic hormone on immunohistochemistry. However, nonfunctioning tumors are also seen, albeit rarely. These are known to be associated with DICER 1 mutations and have a poor prognosis. Hence, morphologic recognition in the right clinical context and excluding other differential diagnoses in infants help make the correct diagnosis.

Pathogenetic factors fanning the flames of COVID-19 to cause rhino-orbito-cerebral mucormycosis: An observational study.

BACKGROUND AND AIMS: Published studies on coronavirus disease 19 (COVID-19) associated rhino-orbito-cerebral mucormycosis (CAROCM) were primarily descriptive. Therefore, we aimed to identify features of COVID-19 that could predispose to CAROCM and explore the pathogenic pathways. PATIENTS AND METHODS: This retrospective hospital-based study was done during the first (March 2020 - January 2021) and the second (February 2021 - June 2021) waves of the COVID-19 pandemic. Subjects were grouped into four categories: first-wave CAROCM (n-4); second-wave CAROCM (n-27); first-wave non-mucor COVID (n-75), and second-wave non-mucor COVID (n-50). Data elements included age, gender, comorbidities, COVID-19 severity, steroid therapy, peak values of interleukin-6 (IL-6), serum ferritin and D-dimer, nadir values of absolute lymphocyte count (ALC), absolute neutrophil count (ANC) and platelet count (Pl. C). RESULTS: Thirty-one patients of CAROCM were included. The mean (SD) age was 51.26 (11.48) years. 27 (87.1%) were aged ≥ 40 years and males. Severe COVID-19 was seen more often in the second wave than the first wave (P-0.001). CAROCM group was significantly younger (P-0.008) and showed a higher incidence of uncontrolled diabetes (P-0.001) and renal dysfunction (P-0.004) than non-mucor COVID. While IL-6, ferritin and D-dimer were significantly elevated in CAROCM than non-mucor COVID, clinical severity, ANC, ALC and Pl. C showed no significant difference. CONCLUSION: CAROCM is seen often in middle-aged diabetic males with uncontrolled hyperglycaemia, diabetic ketoacidosis, renal dysfunction and those infected by more transmissible delta variants and treated with steroids. IL-6, D-dimer, serum ferritin are more often elevated in CAROCM and might play a pathogenic role.

Acanthamoeba meningoencephalitis in an immunocompetent patient: an autopsy case report.

Chronic granulomatous CNS infections may be caused by tuberculosis, fungi and rarely by free-living amoeba, especially in immunocompromised individuals. We report a rare, fatal case of granulomatous amoebic encephalitis in an immunocompetent patient mimicking CNS tuberculosis, and review the imageological features and diagnostic tests.

Outcome of epilepsy surgery in children after evaluation with non-invasive protocol.

OBJECTIVE: To assess outcome of epilepsy surgery in children with medically refractory partial epilepsy evaluated with non-invasive protocol and to determine the predictors of outcome. PATIENTS AND METHODS: Retrospective analysis of presurgical, surgical, and postsurgical data was performed in 87 children who had at least 1 year post surgery follow-up. Outcome was assessed according to Engel's outcome classification. Stepwise regression followed by logistic regression analysis was employed in data analysis. RESULTS: Mean follow-up was 32 (12-58) months and 44 (50.6%) were males. The age of onset of epilepsy was below the age of 2 years in 24 (30.8%). Resective surgery was done in 78 children. The commonest surgery performed was a temporal resection (88.9%) in adolescents and an extra-temporal resection ( 60.6%) in children. The commonest pathology was hippocampal sclerosis (HS) in adolescents and developmental, tumoral lesions, and gliosis in children. At last follow-up, 50 (64.1%) were seizure free and Engel's favourable outcome was noted in 59 (75.6%). After stepwise regression analysis, variables found to be significant (P < 0.05) and predicting a favourable outcome were lesion on MRI, normal IQ, and partial seizures without secondary generalization. Bilateral spikes on interictal EEG and acute postoperative seizures were predictors of poor outcome. A regression model was developed; the sensitivity, specificity, accuracy, and area under ROC curve were 82%, 91%, 88.5%, and 0.97%, respectively. CONCLUSION: Favourable outcome after epilepsy surgery can be obtained in children with temporal lobe epilepsy with HS and lesion-related epilepsies in developing countries with limited resources, after evaluation with a non-invasive protocol.