Cortical Tumors Research Articles

FOXR2 targets LHX6+/DLX+ neural lineages to drive CNS neuroblastoma.

Central nervous system neuroblastoma with FOXR2 activation (NB-FOXR2) is a high-grade tumor of the brain hemispheres and a newly identified molecular entity. Tumors express dual neuronal and glial markers, leading to frequent misdiagnoses, and limited information exists on the role of FOXR2 in their genesis. To identify their cellular origins, we profiled the transcriptomes of NB-FOXR2 tumors at the bulk and single-cell levels and integrated these profiles with large single-cell references of the normal brain. NB-FOXR2 tumors mapped to LHX6+/DLX+ lineages derived from the medial ganglionic eminence, a progenitor domain in the ventral telencephalon. In vivo prenatal Foxr2 targeting to the ganglionic eminences in mice induced postnatal cortical tumors recapitulating human NB-FOXR2 specific molecular signatures. Profiling of FOXR2 binding on chromatin in murine models revealed an association with ETS transcriptional networks, as well as direct binding of FOXR2 at key transcription factors that coordinate initiation of gliogenesis. These data indicate that NB-FOXR2 originate from LHX6+/DLX+ interneuron lineages, a lineage-of-origin distinct from that of other FOXR2-driven brain tumors, highlight the susceptibility of ventral telencephalon-derived interneurons to FOXR2-driven oncogenesis, and suggest that FOXR2-induced activation of glial programs may explain the mixed neuronal and oligodendroglial features in these tumors. More broadly, this work underscores systematic profiling of brain development as an efficient approach to orient oncogenic targeting for in vivo modeling, critical for the study of rare tumors and development of therapeutics.

Changes in WHO classification of adrenal tumors and new ideas for multi-dimensional diagnosis and treatment

In 2022, WHO updated the classification and concept of adrenal cortical and medullary tumors. In terms of adrenal cortical tumors, the WHO classification further standardizes the nomenclature of nodular adrenal cortical disease and refines the pathological classification of primary aldosteronism. In terms of adrenal medullary tumors, the WHO classification unifies the concepts of pheochromocytoma and paraganglioma, and reclassifies various concepts, including paraganglioma-like neuroendocrine tumors. The new standards not only cover the clinical manifestations of the disease, but also include other multiple aspects such as the histological origin of the disease, immunohistochemical manifestations, physiological mechanisms of the disease, hereditary susceptibility and prognostic factors. This article intends to explore how to improve the diagnostic and therapeutic level of adrenal tumors.

The Role of Decreased Expression of Glucocorticoid Receptors in the Development of Itsenko-Cushing Syndrome

Background: Itsenko-Cushing syndrome is caused by unregulated excessive cortisol incretion by the adrenal cortex. The causes of increased stimulation of cortisol incretion by the adrenal cortex, leading to hyperplasia and tumors (adenoma and cancer) of the adrenal cortex, as well as to adenoma of the pituitary gland itself, remain unclear to date. Materials and Methods: 6 patients with adrenal Itsenko-Cushing syndrome with adrenal cortex adenoma were under observation. The age of the patients ranged from 24 to 87 years. The patients underwent removal of the adrenal gland on the affected side. The control group consisted of 6 individuals who underwent surgical treatment of varicocele and hernias of various localization. In patients of the main group and control group, with their consent, a small fragment of skin from the edge of the surgical wound was taken for examination, which were fixed in a 10% formalin solution. Results: The presence of adrenal Itsenko-Cushing syndrome in patients of the main group was confirmed by laboratory and instrumental studies, as well as characteristic clinical manifestations. The average Histochemical score of the expression of glucocorticoid receptors (GR) of the skin in patients of the main group with Itsenko-Cushing adrenal syndrome was 2.7 times less than the same value in the control group. Conclusions: A decrease in the formation or absence of glucocorticoid receptors (congenital or acquired) blocks the negative feedback of cortisol suppression of corticoliberin production by the hypothalamus and ACTH-pituitary gland. The resulting excessive incretion of corticoliberin becomes the main link in pathogenesis of pituitary adenoma formation, and an excessive incretion of ACTH leads to the formation of cortical hyperplasia and tumors (adenomas, cancers) of the adrenal cortex. Unregulated excessive cortisol production by hyperplastic adrenal tissues or benign/malignant adrenal tumors leads to overcoming resistance to glucocorticoids and, according to the principle of negative feedback, suppresses the production of corticoliberin by the hypothalamus and ACTH-pituitary gland. As a result, the pituitary form of Itsenko-Cushing syndrome turns into an adrenal form with an unregulated increase in cortisol levels and a decrease in ACTH levels. Transfusion of the mononuclear fraction of peripheral blood obtained from healthy donors, which allows the pluripotent stem cells contained in it to partially replace the altered cells of all tissues of patients, is a promising method of treating patients with Itsenko-Cushing syndrome due to a hereditary decrease in the expression of glucocorticoid receptors.

Unusual location of pleomorphic xanthoastrocytoma: a case report

BackgroundPleomorphic xanthoastrocytoma is a rare astrocytic tumor often diagnosed at a young age. Typically, they appear as supratentorial cortical tumors, frequently involving the temporal lobe with few reported rare locations. The prognosis is favorable following surgical excision; however, recurrence, dissemination, and anaplastic transformation occurred in some cases.Case presentationA 50-year-old female presented with convulsions and an altered consciousness. Imaging showed a periventricular mixed solid and cystic lesion. Histopathological examination revealed features of pleomorphic xanthoastrocytoma WHO grade 2 without necrosis or mitotic activity.ConclusionsThis report highlights the classic imaging findings of pleomorphic xanthoastrocytoma but in an atypical periventricular location. Although rare, pleomorphic xanthoastrocytoma should be considered in the differential diagnosis of mixed solid and cystic periventricular lesions.

Association of Elevated C-Reactive Protein with Worsened Outcomes in Different Histologies of Renal Cortical Tumors: Analysis of the INMARC Registry

BackgroundTo evaluate relationship between histological subtypes of renal cell carcinoma (RCC) and preoperative c-reactive protein (CRP). Patients and MethodsWe queried the International Marker Consortium for Renal Cancer database for patients affected by RCC. Patients were classified according to their histology: benign tumors, clear cell (cc) RCC, chromophobe (ch) RCC, papillary (p) RCC, and variant histology (vh) RCC; and according to CRP (mg/L): low CRP ≤5 and high CRP >5. Primary outcome was all-cause mortality (ACM). Secondary outcomes were cancer-specific mortality (CSM), recurrence and association between CRP and histology. Multivariable analysis (MVA) via Cox regression and multivariable logistic regression were fitted to elucidate predictors of outcomes. ResultsTotal 3902 patients (high CRP n = 1266) were analyzed; median follow up 51 (IQR 20-91) months. On MVA elevated CRP was an independent risk factor associated with increased risk of ACM in benign tumors (HR 5.98, P < .001), ccRCC (HR 2.69, P < .001), chRCC (HR 3.99, P < .001), pRCC (HR 1.76, P = .009) and vhRCC (HR 2.97, P =.007). MVA for CSM showed CRP as risk factor in ccRCC (HR 2.77, P < .001), chRCC (HR 6.16, P = .003) and pRCC (HR 2.29, P = .011), while in vhRCC was not (P = .27). MVA for recurrence reported CRP as risk factor for ccRCC (HR 1.30, P = .013), while in chRCC (P = .33), pRCC (P = .34) and vhRCC (P = .52) was not. On multivariable logistic regression CRP was a predictor of pRCC (OR 1.003, P = .002), while decreasing CRP was associated with benign tumors (OR 0.994, P = .048). ConclusionElevated CRP was a robust predictor of worsened ACM in all renal cortical neoplasms. While most frequently observed in pRCC patients, elevated CRP was independently associated with worsened CSM in non-vhRCC. Conversely, elevated CRP was least likely to be noted in benign tumors, and elevation in this subgroup of patients should prompt further consideration for surveillance given increased risk of ACM. Further investigation is requisite.

International consensus on mitotane treatment in pediatric patients with adrenal cortical tumors: indications, therapy, and management of adverse effects.

Mitotane is an important cornerstone in the treatment of pediatric adrenal cortical tumors (pACC), but experience with the drug in the pediatric age group is still limited and current practice is not guided by robust evidence. Therefore, we have compiled international consensus statements from pACC experts on mitotane indications, therapy, and management of adverse effects. A Delphi method with 3 rounds of questionnaires within the pACC expert consortium of the international network groups European Network for the Study of Adrenal Tumors pediatric working group (ENSAT-PACT) and International Consortium of pediatric adrenocortical tumors (ICPACT) was used to create 21 final consensus statements. We divided the statements into 4 groups: environment, indications, therapy, and adverse effects. We reached a clear consensus for mitotane treatment for advanced pACC with stages III and IV and with incomplete resection/tumor spillage. For stage II patients, mitotane is not generally indicated. The timing of initiating mitotane therapy depends on the clinical condition of the patient and the setting of the planned therapy. We recommend a starting dose of 50 mg/kg/d (1500 mg/m²/d) which can be increased up to 4000 mg/m2/d. Blood levels should range between 14 and 20 mg/L. Duration of mitotane treatment depends on the clinical risk profile and tolerability. Mitotane treatment causes adrenal insufficiency in virtually all patients requiring glucocorticoid replacement shortly after beginning. As the spectrum of adverse effects of mitotane is wide-ranging and can be life-threatening, frequent clinical and neurological examinations (every 2-4 weeks), along with evaluation and assessment of laboratory values, are required. The Delphi method enabled us to propose an expert consensus statement, which may guide clinicians, further adapted by local norms and the individual patient setting. In order to generate evidence, well-constructed studies should be the focus of future efforts.

Optimization of direct cortical stimulation using tibial versus median nerve sensory mapping during midline brain tumor resection: illustrative case.

During brain tumor resection, neurophysiological mapping and monitoring help surgeons locate, characterize, and functionally assess eloquent brain areas in real time. The selection of mapping and monitoring targets has implications for successful surgery. Here, the authors compare direct cortical stimulation (DCS) as suggested by median nerve (MN) with posterior tibial nerve (PTN) cortical sensory mapping (SM) during mesial lesion resection. Recordings from a 6-contact cortical strip served to generate an MN and a PTN sensory map, which indicated the strip was anterior to the central sulcus. Responses exhibited an amplitude gradient with no phase reversal (PR). DCS, elicited through a stimulus probe or contact(s) of the strip, yielded larger responses from the corresponding sensory mapped limb; that is, PTN SM resulted in larger lower limb muscle responses than those suggested by MN SM. SM of the MN and PTN is effective for localizing eloquent cortical areas wherein the PTN is favored in surgery for mesial cortical tumors. The recorded amplitude of the cortical somatosensory evoked potential is a valuable criterion for defining the optimal location for DCS, despite an absent PR. The pathway at risk dictates the specifics of SM, which subsequently defines the optimal location for DCS.

Hand2 Immunohistochemistry in the Diagnosis of Paragangliomas and Other Neuroendocrine Neoplasms.

Hand2 is a core transcription factor responsible for chromaffin cell differentiation. However, its potential utility in surgical pathology has not been studied. Thus, we aimed to investigate its expression in paragangliomas, other neuroendocrine neoplasms (NENs), and additional non-neuroendocrine tumors. We calibrated Hand2 immunohistochemistry on adrenal medulla cells and analyzed H-scores in 46 paragangliomas (PGs), 9 metastatic PGs, 21 cauda equina neuroendocrine tumors (CENETs), 48 neuroendocrine carcinomas (NECs), 8 olfactory neuroblastomas (ONBs), 110 well-differentiated NETs (WDNETs), 10 adrenal cortical carcinomas, 29 adrenal cortical adenomas, 8 melanomas, 41 different carcinomas, and 10 gastrointestinal stromal tumors (GISTs). Both tissue microarrays (TMAs) and whole sections (WSs) were studied. In 171 NENs, previously published data on Phox2B and GATA3 were correlated with Hand2. Hand2 was positive in 98.1% (54/55) PGs, but only rarely in WDNETs (9.6%, 10/104), CENETs (9.5%, 2/21), NECs (4.2%, 2/48), or ONBs (12.5%, 1/8). Any Hand2 positivity was 98.1% sensitive and 91.7% specific for the diagnosis of PG. The Hand2 H-score was significantly higher in primary PGs compared to Hand2-positive WDNETs (median 166.3 vs. 7.5; p < 0.0001). Metastatic PGs were positive in 88.9% (8/9). No Hand2 positivity was observed in any adrenal cortical neoplasm or other non-neuroendocrine tumors, with exception of 8/10 GISTs. Parasympathetic PGs showed a higher Hand2 H-score compared to sympathetic PGs (median H-scores 280 vs. 104, p < 0.0001). Hand2 positivity in NENs serves as a reliable marker of primary and metastatic PG, since other NENs only rarely exhibit limited Hand2 positivity.

Vascular endothelial growth factor and endocan expression in adrenal cortical tumors and their relationship with histopathological prognostic parameters.

The aim of this study was to determine the tissue expressions of vascular endothelial growth factor (VEGF) and endocan in adrenal cortical tumors and the factors associated with them. The study included 6 subjects with adrenocortical adenoma (ACA), 7 subjects with adrenocortical carcinoma (ACC), and 13 control subjects with a normal adrenal cortex. The status of VEGF and endocan expression was determined by the proportions of cells staining on a scale ranging from negative (not staining at all) to strongly positive. VEGF expression was detected in 1 (16.7%) of 6 subjects in the ACA group and in 6 (85.7%) of 7 subjects in the ACC group. VEGF expression was not detected in any of the subjects in the control group. Endocan expression was detected in 6 (100%) of 6 subjects in the ACA group and in 7 (100%) of 7 subjects in the ACC group, while it was detected in only 4 (30.7%) of 13 subjects in the control group. VEGF was expressed with a high frequency in subjects with ACC and with a low frequency in subjects with ACA, but it was not expressed in subjects with normal adrenal cortex tissue. Although endocan was expressed with a higher frequency in subjects with ACC and ACA, it was also expressed in subjects with normal adrenal cortex tissue. The percentage of cells expressed endocan in subjects with ACC was also significantly higher than in subjects with both ACA and normal adrenal cortex.

The algorithm for morphological assessment of malignant potential of adrenocortical tumors using mathematical modeling method

To develop the mathematical model with high sensitivity and specificity to assess the malignant potential of adrenal cortical tumors, which can be used to diagnose adrenocortical carcinoma (ACC) in adults. Pathomorphological examination of surgical and consultative material of adrenocortical neoplasms was carried out. All cases were verified according to the WHO Classification of adrenal gland tumors (5th ed., 2022), the tumor's histogenesis was confirmed by immunohistochemical examination. Statistical analysis of the histological and immunohistochemical factors in terms of their value in relation to the diagnosis of ACC was carried out on Python 3.1 in the Google Colab environment. ROC analysis was used to identify critical values of predictors. The cut-off point was selected according to the Youden`s index. Logistic regression analysis using l1-regularisation was performed. To validate the model, the initial sample was divided into training and test groups in the ratio of 9:1, respectively. The study included 143 patients divided into training (128 patients) and test (15 patients) samples. A prognostic algorithm was developed, which represent a diagnostically significant set of indicators of the currently used Weiss scale. The diagnosis is carried out in 3 stages. This mathematical model showed 100% accuracy (95% CI: 96-100%) on the training and test samples. The developed algorithm could solve the problem of subjectivity and complexity in the interpretation of some of the criteria of current diagnostic algorithms. The new model is unique in that, unlike others, it allows verification of all morphological variants of ACC.

PATH-30. GLIOMAS WITH FGFR ONCOGENIC ALTERATIONS: CLINICO-PATHOLOGICAL FEATURES, MANAGEMENT AND OUTCOMES IN PEDIATRIC, ADOLESCENT AND YOUNG ADULT PATIENTS.

Abstract INTRODUCTION Fibroblast growth factor receptor (FGFR1-4) pathway alterations are rare in pediatric cancers (1-3%) but are enriched in certain specific subtypes of difficult to treat pediatric and AYA brain tumors. Some of the common oncogenic alterations include structural variants (fusions, duplications), mutations and amplifications. METHODS We describe here the clinico-pathological features and therapeutic outcomes of pediatric and AYA patients (ages 0-39yrs) with FGFR pathway altered gliomas diagnosed in the past 10yrs (2013-2023). Data was collected from review of patient charts. RESULTS We identified 13 patients with gliomas harboring an oncogenic FGFR alteration. Median age at diagnosis was 16yrs (range, 6-30yrs) and was more common in males (M: F-3:1). Seizures were the most common presenting symptom (N=5/13, 38%); all of these patients had cortical tumors, which were resected and seizures were adequately controlled. A biopsy only approach was done in more than half (N=7/13, 54%) of the patients. Pathological diagnosis included low grade glio-neuronal tumors in all but one of the patients, who had a high-grade glioma (Pilocytic astrocytoma N=6, Diffuse astrocytoma N=2, glio-neuronal tumors N=2, PLNTY N=2). FGFR alterations included oncogenic fusions (FGFR1-TACC1=1, FGFR2-TACC1=1, FGFR2-CTNNA3=2, FGFR3-TACC3=1), tandem duplications (FGFR1-TKD-ITD=3) and mutations (FGFR1- N546K=2, K654E=1, K656E=2). Co-occurring mutations were seen in 4 patients (H3.3-K27M=1, PIK3CA-E545K=1, PTPN11-G503V=1, PTPN11-E69K=1). Patients with symptomatic residual tumors (N=6, 46%) were treated with targeted therapies (Erdafitinib=3, Trametinib=1, Ponatinib / Everolimus=1, Dasatinib=1) and two patients received Radiation therapy. Erdafitinib was discontinued in one patient due to intra-tumoral bleed. Rest of the patients are tolerating the targeted therapy well and all of the patients are alive. CONCLUSION In summary, cortical tumors bearing FGFR alterations present with refractory seizures and are eminently treatable with surgical resection. Targeted therapy with FGFR specific inhibitors is tolerated well and updated response assessment of our patients will be presented in the meeting.

FRI214 Adrenal Adenoma With Biochemical Findings Suggestive Of Cushing's Disease

Abstract Disclosure: A. Calimag: None. U. Tarabichi: None. M. Ahmad: None. M. Kazi: None. Introduction: We are presenting a case of a young female with prior history of multiple endocrinopathies presenting with a left adrenal adenoma with biochemical findings suggestive of Cushing's disease. Case Presentation: A 22-year-old female with a history of Type 1 Diabetes Mellitus was found to have a left adrenal adenoma 2.8 cm on CT. Absolute washout of 85 % and a relative washout of 63%, having 12 Hounsfield units (HU) on the non-contrast phase, findings suggestive of a benign adenoma. Further work up including 1 mg Dexamethasone suppression test (DST) showed unsuppressed plasma ACTH 17 pg/ml and total cortisol 9.4 mcg/dL. 8 mg DST showed ACTH 12 pg/ml, AM cortisol 8.8 mcg/dL, and Dexamethasone 991 ng/dl. Late night salivary cortisol 0.07 ug/dl, and 0.09 ug/dl, 24 hr urine cortisol 40.7. Other labs showed Aldosterone level was normal at 6.7, Renin level was also normal at 1.1. 24 hr urine catecholamines were Norepinephrine 35 mcg/24 hr, Epinephrine 3.9 mcg/24 hr, while urine Metanephrine level was &amp;lt;0.24, and normetanephrine level at 0.34. TSH 1.2mcU/ml. One day prior to surgery ACTH level was suppressed at 2.1 pg/ml drawn from a different lab. MRI of the Pituitary showed a slightly enlarged pituitary gland with uniform contrast enhancement and no definite lesion. The patient underwent a laparoscopic left adrenalectomy. Pathology showed an adrenal cortical neoplasm consistent with adrenal cortical adenoma, with no significant cytologic atypia, mitotic activity, or necrosis. Immunoperoxidase stain, the tumor is positive for inhibin and negative for PAX8. Post-op she developed adrenal insufficiency which was treated with hydrocortisone. The follow-up cortisol level was 11.3 mcg/dL when the patient was off hydrocortisone. Discussion: In this case, the biochemical exam showed elevated cortisol with ACTH not fully suppressed at both 1 mg and 8 mg DST which was done twice, and normal 24-hour urine cortisol. Determining whether this is adrenal vs pituitary mediated was one of the clinical dilemmas of this case. Initially, the patient’s ACTH was unsuppressed however the day before surgery ACTH was suppressed and the patient’s cortisol level normalized after the left adrenalectomy. Immunoassays for ACTH levels may occasionally be susceptible to analytical errors. (1-2) There are several case series and studies mentioning assay interference when using Immulite Assay versus Cobas ACTH assay. (1-2) Therefore, it is important to analyze clinical findings and biochemical testing and if lab tests are discordant, recheck using a different analytical platform in a different lab or an alternate ACTH assay to confirm ACTH levels. (1-2)

THU602 A Comprehensive Review Of Incidence, Demographics, Laterality And Survival Analysis Of Adrenal Malignancies.

Abstract Disclosure: K. Desai: None. K. Pereira: None. S. Iqbal: None. B. Baralo: None. M. Vidhi: None. M. Renzu: None. M. Rather: None. R. Thirumaran: None. Background: Adrenal malignancy is extremely rare in the United States with only ∼200 new cases/per year. Adrenocortical carcinoma is the most common histologic subtype, followed by pheochromocytoma and neuroblastoma. In this study, our aim is to evaluate the incidence rate and compare the survival analysis based on race, laterality, and histologic tissue involvement. Method: The data were collected from Surveillance, Epidemiology, and End Result database 17 Registries, Nov 2021 Sub (2000-2019). We included patients above 20 years with a primary diagnosis of an adrenal malignant tumor. Neuroblastomas were excluded due to low incidence in the adult population. We analyzed incidence rates using linear regression with t-test and compared overall survival (OS) curves using the Log-rank test (GraphPad Prism). Result: 3323 cases were identified with the majority being female (54.68%). 50.29% were adrenal cortical tumors, followed by pheochromocytoma (14.44%) &amp; neuroblastoma (0.51%). 48.03% were left-sided, 39.54% were right-sided, 3.64% were bilateral &amp; the rest were unspecified. The incidence rate for adrenal tumors is 2.77 per 1 million. The highest incidence was among Caucasians (2.98), followed by African American (2.63, p=0.09), which is higher than Asians (2.03, p&amp;lt;0.0001) and Hispanics (2.42, p=0.0002). A review of the incidence trends showed that only African-American patients had rising incidence rates from 1.46 in 2000 to 2.48 in 2019 (p=0.02). Patients with adrenal cortical tumors had worse survival compared to patients with pheochromocytoma (19 vs 98 months) HR 2.236 [1.988-2.232]. No significant statistical difference was noticed in the survival of left vs. right-sided tumors or racial groups when subdivided based on histology. However, there was a difference in the median survival of the women with pheochromocytoma (123m), compared to men (75m) HR 1.397 [1.064 - 1.834]. Conclusion: The incidence rate of adrenal malignancies remained stable and is higher among Caucasians compared to Hispanics and Asians. We noticed concerning rising incidence among African American patients. Patients with adrenocortical tumors had worse survival compared to patients with pheochromocytoma. Laterality of the tumor and race of the patients plays no role in survival in adrenal malignancies, unlike the colon and kidneys. However, there is a noticeably lower survival of the male population with pheochromocytoma. Presentation: Thursday, June 15, 2023

Expression of EMP 1, 2, and 3 in Adrenal Cortical Neoplasm and Pheochromocytoma.

The purpose of this study is to investigate the expression of the epithelial membrane proteins (EMP) 1, 2, and 3 in adrenal gland neoplasm and to explore the broader implications of this. Tissue microarrays were constructed for 132 cases of adrenal cortical neoplasms (ACN) (adrenal cortical adenoma (115 cases), and carcinoma (17 cases)) and 189 cases of pheochromocytoma. Immunohistochemical staining was performed to identify EMP 1, 2, and 3, and was compared with clinicopathological parameters. The H-score of EMP 3 (p < 0.001) was higher in pheochromocytoma when compared to that of ACN, and the H-score of EMP 1 (p < 0.001) and EMP 3 (p < 0.001) was higher in adrenal cortical carcinomas when compared to that of adrenal cortical adenomas. A higher EMP 1 H-score was observed in pheochromocytomas with a GAPP score ≥3 (p = 0.018). In univariate analysis, high levels of EMP 1 and EMP 3 expression in ACN were associated with shorter overall survival (p = 0.001). Differences were observed in the expression of EMPs between ACN and pheochromocytoma. EMPs are associated with malignant tumor biology in adrenal cortical neoplasm and pheochromocytoma, suggesting the role of a prognostic and/or predictive factor for EMPs in adrenal tumor.

PEComa of the Adrenal Gland: A Clinicopathologic Series of 7 Cases.

PEComas are a family of mesenchymal neoplasms composed of histologically distinctive perivascular epithelioid cells which demonstrate myomelanocytic differentiation. PEComas of the adrenal gland are very rare and can represent a considerable diagnostic challenge given their morphologic overlap with more common adrenal cortical neoplasms. We present the clinicopathologic features of 7 primary adrenal PEComas. The cohort comprised 5 male and 2 female patients with a median age of 63 years (range: 31 to 71y). One patient had Birt-Hogg-Dubé syndrome and another had Lynch syndrome; however, none had a history of tuberous sclerosis complex. Histologically, tumors showed nested and/or sheet-like growth and epithelioid cytomorphology with pale-to-eosinophilic granular cytoplasm. Two tumors had an admixed spindle cell component. There was a median of 4 mitoses per 10HPFs (range: 0 to 8). Necrosis was present in 4 tumors and lymphovascular invasion in 1. Four tumors were classified as malignant. By immunohistochemistry, tumors were positive for HMB-45 (3/7), MITF (3/3), Melan-A (3/7), smooth muscle actin (5/7), desmin (5/7), and caldesmon (1/1). Two tumors were positive for TFE3 (2/4). Inhibin and SF1 were negative in all tumors assessed (0/6). Of 3 patients with available clinical follow-up information, 1 patient developed locally recurrent and metastatic disease (at 18mo) and was alive with persistent disease at the last follow-up. Two patients had no recurrent or metastatic disease at the last follow-up (60 and 25mo). Although PEComas of the adrenal gland are rare, pathologists need to be alert to this entity in the differential diagnosis of primary adrenocortical neoplasms. In suspected cases, the judicious use of melanocytic and smooth muscle markers, in addition to TFE3 and markers of adrenocortical differentiation (such as SF1 and inhibin) can assist in diagnosis. As in PEComas arising at other visceral sites, an association with tuberous sclerosis complex seems to be uncommon.

Expression of Amine Oxidase Proteins in Adrenal Cortical Neoplasm and Pheochromocytoma.

We delved into the expression of amine oxidase family proteins and their potential significance in adrenal gland neoplasm. Tissue microarrays were prepared for 132 cases of adrenal cortical neoplasm (ACN) consisting of 115 cases of adrenal cortical adenoma (ACA), 17 cases of adrenal cortical carcinoma (ACC), and 163 cases of pheochromocytoma (PCC). Immunohistochemical stainings for MAOA, MAOB, LOX, and AOC3 were performed to evaluate the H-scores and compare them with clinicopathological parameters. The H-scores of MAOA (T; p = 0.005) and MAOB (T; p = 0.006) in tumor cells (T) were high in ACN, whereas LOX (T, S; p < 0.001) in tumor and stromal cells (S) and AOC3 (T; p < 0.001) were higher in PCC. In stromal cells, MAOA (S; p < 0.001) and AOC3 (S; p = 0.010) were more expressed in ACA than in ACC. MAOB (S) in PCC showed higher H-scores when the grading of adrenal pheochromocytoma and paraganglioma (GAPP) score was 3 or higher (p = 0.027). In the univariate analysis, low MAOA expression in stromal cells of ACN was associated with shorter overall survival (p = 0.008). In conclusion, monoamine oxidase proteins revealed differences in expression between ACN and PCC and also between benign and malignant cells.

The Function of Magnetic Resonance Imaging in Chronic Epilepsy Prospective Study

Background: Magnetic resonance imaging (MRI) has revolutionised the treatment of intractable epilepsy. ninety nine patients were sent to the KTH Peshawar Radiology Department for an evaluation of the function of MRI in the diagnosis, treatment, and prognosis of their alleged intractable epilepsy. Using a 1.5 Tesla Philips MRI scanner, the patients were examined, and twenty one aberrant findings were found in them, including vascular malformations, tumours, cortical dysplasia, gliosis, and white matter disorders. The ability to diagnose these disorders with MRI has proved to be helpful. The results of the research demonstrate the value of MRI in the diagnosis and management of intractable epilepsy. Using MRI may help with both determining the source of seizures and providing recommendations for possible treatments. Additionally, in epilepsy patients, MRI surveillance can forecast prognosis and illness progression. Aim: Using MRI, it is possible to identify the diagnosis, course of treatment, and prognosis for intractable epilepsy. This makes it possible to identify the underlying cause, direct treatment choices, track the development of the condition, and forecast the prognosis of the patient. Furthermore, it is critical to assess MRI's precision in this field. Methods: The Radiology Department of KTH Peshawar studied possible epilepsy patients between April 2015 and April 2016. The research included ninety-nine patients, each of whom had a thorough medical history, neurological examination, and standard radiographic evaluation. The patients' MRI scans were carried out and examined for any anomalies using a 1.5 Tesla Philips MRI equipment. In order to compare the results of the MRI scans with the clinical data and therapeutic outcomes of the patients. Results: twenty-one of the ninety-nine individuals that were assessed had abnormal MRI scan findings. Cortical dysplasia, gliosis, vascular malformations, tumours, and white matter disorders were among the illnesses that were found. The MRI scans were shown to be a useful tool for detecting and treating instances of untreatable epilepsy. Finding the origin of the seizures helped with the diagnosis and provided the best alternatives for therapy. Additional crucial MRI scan tasks included monitoring the progression of diseases and predicting the prognosis. Keywords: Diagnosis, Management, Prognosis, MRI, Intractable Epilepsy, KTH Peshawar

Adrenocortical tumors in children: Sri Lankan experience from a single center, and a mini review

BackgroundPediatric adrenocortical tumors include both benign adenomas and highly virulent malignant tumors. However, they are very rare among children. The aim of this study is to evaluate the clinicopathological data of children presenting with adrenocortical tumors and assess their survival in a South Asian population.Case presentationThis is a retrospective cohort study that includes patients diagnosed with adrenocortical tumors from August 2020 to August 2022 followed-up at Lady Ridgeway Hospital. Seven children were diagnosed with adrenal cortical tumors. Their ages ranged from 10 months to 6.5 years. Five of them were boys. All displayed signs of peripheral precocious puberty. One boy phenotypically had features of Beckwith–Wiedemann syndrome. The median time for diagnosis after the onset of symptoms was 4.4 months. The preoperative diagnosis was based on clinical manifestations, elevated dehydroepiandrosterone sulfate levels, and suprarenal masses on computed tomography. All five boys had right-sided suprarenal masses, while the two girls had them on the left side. All underwent surgery for tumor resection. The diagnosis was confirmed based on the histopathology of the adrenal specimens. Four children had a Wieneke score of 4 or more, suggesting the possibility of adrenocortical carcinoma; however, only two of them behaved as malignant tumors. To date, two children have developed local recurrences within a very short period.ConclusionAdrenocortical tumors are uncommon in children, and treatment options are limited. To identify early recurrences, routine clinical, radiological, and biochemical examinations at least once every 6–8 weeks is important.

Surgical Pathological Features of Epileptogenic Brain Lesions: Cortical Dysplasia and Tumors

Cortical dysplasia and tumors are representative brain lesions associated with intractable epilepsy. Focal cortical dysplasia type II is characterized by cortical cytoarchitectural abnormalities, dysmorphic neurons, and balloon cells, and is associated with somatic mutations of mTOR pathway molecules. Glioneuronal and neuronal tumors, including dysembryoplastic neuroepithelial tumor and ganglioglioma, are the major tumor types for the clinical phenotype. Recently, various subtypes and characterizing molecular profiles have been recognized.

Prognostic Value of Microscopic Tumor Necrosis in Adrenal Cortical Carcinoma

Adrenal cortical carcinoma (ACC) is an uncommon neoplasm with variable prognosis. Several histologic criteria have been identified as predictors of malignancy in adrenal cortical tumors. The Weiss score is the system most widely employed for diagnostic purposes, but also possesses prognostic value. We aim to determine the relative impact of each Weiss parameter on ACC patient survival. A multicenter retrospective analysis was conducted on a series of 79 conventional ACCs surgically treated at the Florence and Utrecht centers of the European Network for the Study of Adrenal Tumors (ENSAT). Weiss classification was recapitulated using principal component analysis (PCA). The Kaplan–Meier and Cox multivariate regression analyses were applied in order to estimate the prognostic power of Weiss versus other clinical parameters. PCA reduced the nine Weiss parameters to the best fitting 4-component model, each parameter clustering with a single component. Necrosis and venous invasion clustered together with the highest scores, thus establishing the most relevant component (Component 1) to explain Weiss distribution variability. Only Component 1 significantly predicted overall survival (OS, log-rank = 0.008) and disease-free survival (DFS, log-rank < 0.001). When considering the prognostic power of Weiss parameters, necrosis alone could independently assess OS (log-rank = 0.004) and DFS (log-rank < 0.001) at both the Kaplan–Meier and multivariate Cox regression analyses [hazard ratio (HR) = 7.8, 95% confidence interval [CI] = 1.0–63.5, p = 0.05, and HR = 12.2, 95% CI = 1.6–95.0, p = 0.017, respectively]. The presence of necrosis significantly shortened time to survival (TtS) and time to recurrence (TtR), 57.5 [31.5–103.5] vs 34 [12–78] months (p = 0.05) and 57.5 [31.5–103.5] vs 7 [1.0–31.5] months (p < 0.001), respectively. Our study suggests that, of the Weiss parameters, necrosis is the most powerful adverse factor and the best predictor of OS and DFS in ACC patients.