Meningioma Research Articles

CLRM-02 CALCIFIED SPINAL MENINGIOMAS: A SYSTEMATIC REVIEW OF CLINICAL CHARACTERISTICS, TREATMENT STRATEGIES, AND OUTCOMES

Abstract Calcified meningiomas involving the spine are rare but can pose significant surgical challenges. We systematically reviewed the literature on calcified spinal meningiomas. PubMed, EMBASE, Web-of-Science, and Scopus databases were searched to include studies reporting clinical data of patients with calcified spinal meningioma. Included articles were analyzed for symptoms, imaging, spine level of the tumor, tumor location relative to the spinal cord, calcification status, treatment regimen, recurrence, progression-free survival, and outcomes. A total of 35 articles encompassing 94 patients were included. Most patients were female (90.4%), presenting with lower extremity weakness (44%) and/or lower extremity paresthesia (38.1%). Most calcified spinal meningiomas occurred in the thoracic spine (82%) and on the dorsal (33.3%) or ventral (27.2%) side relative to the spinal cord. Most tumors were intradural (87.2%). Histologically, most calcified spinal meningiomas were WHO grade I (97.4%) and psammomatous (50.7%). Most tumors demonstrated macroscopic calcification (48.9%). Most patients underwent gross total resection (91.5%) through a posterior approach (100%). Two patients (2.1%) received adjunctive radiotherapy. The most common treatment related complication was CSF leakage. Post-operatively, most patients demonstrated symptomatic improvement (75.5%) and 2 (2.1%) had local tumor recurrence. Calcified spinal meningiomas are uncommon but benign entities. These neoplasms tend to adhere to surrounding tissues and nerves and, thus, can be surgically challenging to remove. In most patients, safe gross total resection remains the standard of care, but accurate surgical planning is necessary to reduce the risks of postoperative complications.

Automated Detection and Diagnosis of Spinal Schwannomas and Meningiomas Using Deep Learning and Magnetic Resonance Imaging.

Spinal cord tumors are infrequently identified spinal diseases that are often difficult to diagnose even with magnetic resonance imaging (MRI) findings. To minimize the probability of overlooking these tumors and improve diagnostic accuracy, an automatic diagnostic system is needed. We aimed to develop an automated system for detecting and diagnosing spinal schwannomas and meningiomas based on deep learning using You Only Look Once (YOLO) version 4 and MRI. In this retrospective diagnostic accuracy study, the data of 50 patients with spinal schwannomas, 45 patients with meningiomas, and 100 control cases were reviewed, respectively. Sagittal T1-weighted (T1W) and T2-weighted (T2W) images were used for object detection, classification, training, and validation. The object detection and diagnosis system was developed using YOLO version 4. The accuracies of the proposed object detections based on T1W, T2W, and T1W + T2W images were 84.8%, 90.3%, and 93.8%, respectively. The accuracies of the object detection for two spine surgeons were 88.9% and 90.1%, respectively. The accuracies of the proposed diagnoses based on T1W, T2W, and T1W + T2W images were 76.4%, 83.3%, and 84.1%, respectively. The accuracies of the diagnosis for two spine surgeons were 77.4% and 76.1%, respectively. We demonstrated an accurate, automated detection and diagnosis of spinal schwannomas and meningiomas using the developed deep learning-based method based on MRI. This system could be valuable in supporting radiological diagnosis of spinal schwannomas and meningioma, with a potential of reducing the radiologist's overall workload.

Genomic analysis of spinal meningiomas: correlation with histopathological grade.

Spinal meningiomas are one of the most common primary intradural tumors of the adult spine. Spinal meningiomas typically have a benign course with low rates of recurrence. Recent advances in genomic profiling have provided valuable information on meningioma biology and natural history, but these studies have focused primarily on cranial meningiomas. Chromosomal copy number analysis of meningiomas has been shown to be a valuable molecular profiling technique for distinguishing benign from aggressive tumors. The Integrated Grade for Meningioma is a novel grading scheme that uses mitotic index and copy-number profile to identify aggressive tumors at high risk for recurrence. The integrated grade has been shown to be a better predictor of tumor behavior than WHO grade alone. The objective of this study was to evaluate the chromosomal copy-number profile of spinal meningiomas, and to correlate these findings with the assigned WHO grades. The authors evaluated 94 spinal meningiomas treated surgically at their institution between 2002 and 2022. The histopathological results including WHO grade, mitotic index, presence of atypical features, and MIB-1 index were recorded. Chromosomal copy number as determined by institutional whole-genome DNA copy-number profiling was available for 57 tumors. The WHO grades of the cohort consisted of 81 (86%) WHO grade 1 tumors and 13 (14%) WHO grade 2 tumors. In tumors for which copy-number profiling was available, 44 (77%) of 57 demonstrated loss of 22q/NF2. Notably absent were frequent high-risk copy number alterations including loss of 1p, 3p, 4p/q, 6p/q, 10p/q, 14q, 18p/q, 19p/q, and focal loss of CDKN2A on 9p. Of the 9 WHO grade 2 tumors for which copy-number profiling was available, 6 tumors were reclassified to a lower risk profile (integrated grade 1). This analysis suggests that spinal meningiomas exhibit overwhelmingly indolent biology, as supported by their benign integrated grade. These findings have implications in the surgical management of these patients in relation to the need for complete Simpson grade I resection, as well as the potential avoidance of adjuvant therapy following surgery in the setting of otherwise frequently benign pathology.

The Expression of Progesterone Receptor in Meningothelial Meningioma

Background: By elucidating the role of PR expression in meningothelial meningiomas, this study may contribute to our understanding of the underlying molecular mechanisms driving tumor development and progression. Additionally, it may provide insights into the potential utility of hormonal therapies as adjuvant treatment options for PR-positive meningothelial meningiomas. Ultimately, this research has the potential to impact clinical decision-making, leading to more personalized and effective management strategies for patients with meningothelial meningioma. Objective: To assess the expression of progesterone receptor in meningothelial meningioma. Method: This descriptive cross-sectional study was carried out at the Department of Pathology, Dhaka Medical College over a period of two years from January 2018 to December 2019. A total of 60 Patient of any age group with histologically diagnosed meningiomas of the central nervous system were included as a sample population. During the collection of specimens, all relevant information were recorded systematically in a prepared proforma. All the cases were numbered chronologically and the same number was given to H&E as well as in immunohistochemically stained slides. Results: It was observed that 55% cases were meningothelial meningioma, 8 (13.3%) patients had atypical meningioma, 5 (8.3%) patients had transitional meningioma, 4 (6.7%) patients had psammomatous meningioma and 1(1.7%) cases had anaplastic meningioma. According to PR expression, It was observed that 56.7% study patients had positive PR expression and 43.3% had negative PR expression. 68.8% patients with age group 51-60 years were found positive PR expression and 50% male patients had positive PR expression and 50% male patients had negative PR expression. In female 59.5% cases showed positive and 43.3% showed negative PR expression. It was found that in meningothelial subtype 72.7% cases were PR positive and 27.3% cases were PR negative. In atypical ..

Craniofacial malignant tumors, their extensions, and surgical strategy for their treatment

Purpose: To identify extension routes of craniofacial malignancies and formulate a surgical treatment plan based thereupon. Material and Methods: We retrospectively reviewed the medical records of 253 patients with craniofacial malignancies who underwent surgical treatment at the Romodanov Neurosurgery Institute from 2002 through 2022. Of the 253 patients, 112 had a primary tumor, and 141, a secondary tumor. Preoperative Karnofsky performance scores ranged from 50 to 70 points. Patients underwent neurological and ophthalmological status assessment, as per routine protocols. Results: Epithelial malignancies were the most common (53.7%), whereas anaplastic meningioma and embryonal malignancies were rather uncommon (1.2% and 0.4%, respectively) craniofacial malignancies. The presence of certain clinical symptoms was associated primarily with tumor origin and extension. A high rate of general brain and rhinological symptoms in our study sample was caused by a high percentage of intracranial and paranasal sinus tumors. Craniofacial malignancies most commonly originate from the midline (particularly, anterior midline skull base). Ethmoidal labyrinth was the most common site of origin (45.0%), followed by a sphenoid sinus (12.2%), pterygopalatine and infratemporal fossae (9.9%), whereas the cavernous sinus and olfactory fossa were the least common sites of origin (0.4% and 1.2%, respectively). Craniofacial tumors extended most commonly intracranially (transdurally, epidurally, via adhesion to the dura mater, and/or cavernous sinus growth) or intraorbitally. Anterior craniofacial resection (bifrontal craniotomy with combined with either lateral rhinotomy or supraorbital advancement; or a subcranial approach) was the most common surgical treatment. Postoperative cerebrospinal fluid rhinorrhea and infectious complications (meningitis and meningoencephalitis) were the most frequent complications. The overall postoperative mortality rate was 2.0%. Conclusion: First, compared to the transcranial and facial approaches, the craniofacial resection is advantageous in terms of the radicality of tumor excision. Second, the subcranial approach is preferable to the bifrontal approach in the presence of marked extracranial tumor component, whereas the transbasal Derome approach is effective in the presence of marked extracranial and/or intracranial tumor components. Finally, both the orbitozygomatic and infratemporal approaches allow for the radicality of excision of lateral skull base malignancies, but the latter approach is associated with a lower rate of complications.

Episod maniacal indus prin corticoterapie postalblaţie de meningiom spinal. Rolul realităţii virtuale în psihoterapia anxietăţii postoperatorii

Corticosteroids have been linked to various neuropsychiatric adverse effects, including mood disorders. This case study describes a post-surgical manic episode (spinal meningioma ablation D11-D12) in a 57-year-old female patient on corticosteroids. This presentation aims to highlight corticosteroids’ potential psychiatric adverse effects and to emphasize the importance of recognizing and treating such complications. In this case, the management strategy involved discontinuing corticosteroids, initiating mood-stabilizing medications, and closely monitoring the symptoms. A mood stabilizer and a second-generation antipsychotic were administered to the patient to treat transient manic symptoms and prevent relapse. After discontinuing corticosteroids and beginning therapy with mood stabilizers, the patient’s bipolar symptoms improved. Psychoeducation and therapeutic support were provided to aid the patient in managing acute symptoms and encourage adherence to the treatment plan. As anxiety persisted after manic symptoms were controlled, the case management involved a psychotherapy technique facilitated by virtual reality. Relaxation breathing techniques were emulated through a virtual reality Oculus Quest 2 headset, improving patient-physician trust, subjectively relieving correlated anxiety, and ensuring therapeutic compliance during the admission and at home. Healthcare professionals must be vigilant to identify and effectively treat these complications of steroid anti-inflammatory medication. Immediate cessation of corticosteroids, the initiation of mood stabilizers and psychoeducation are essential for managing these cases. By presenting this case report, we hope to increase healthcare professionals’ awareness on the psychiatric consequences of corticosteroid use, the necessity of a multidisciplinary therapeutic approach, and the role of add-on virtual reality as integrated, personalized patient care to alleviate anxiety.

Anaplastic Meningioma of the Orbit

Anaplastic Meningioma of the Orbit

Anaplastic meningioma in an adolescent: Case report and brief literature review

Anaplastic meningioma is an uncommon neoplasm in childhood and adolescence. In contrast to the case in adults, pediatrics have a predominance of males over females. We report a case of a 17 years old with progressive scalp swelling on the right side. Patient underwent subtotal tumor resection at previous hospital three months ago. The operation was stopped due to extensive bleeding. Radiological investigations revealed a dura-based tumor with a cystic component. Following preoperative embolization, a craniotomy was done, and the tumor was almost completely removed. The tumor's histopathological analysis revealed characteristics of an anaplastic meningioma. The aggressive behavior of this tumor necessitates meticulous monitoring of therapeutic measures in such patients.

Spinal meningiomas: Management and outcomes.

Spinal meningiomas are relatively rare, benign, intradural, extramedullary tumours, that are typically slow-growing and well-defined. Surgery is always the first line for treating spinal meningiomas. Here, we have discussed the existing literature on spinal meningiomas and the role of surgery in determining the outcomes.

Detection and Segmentation of Meningioma Brain Tumors in MRI brain Images using Curvelet Transform and ANFIS

The detection of abnormal tumor region brain Magnetic Resonance Images (MRI) is complex task due to its similar structures between tumor and its surrounding regions. In this paper, Adaptive Neuro Fuzzy Inference System (ANFIS) classification method-based meningioma brain tumor detection is proposed. The proposed method consists of the following stages as preprocessing, transformation, feature extraction and classifications. The brain MR images are enhanced in preprocessing stage and this spatial domain image is converted into multi resolution image using Curvelet transform. The texture and statistical features are extracted from the transformed coefficients. These features are trained and classified by ANFIS classifier and further morphological operations are applied on the classified brain image to segment the tumor regions. This proposed meningioma tumor detection approach is analyzed in terms of sensitivity, specificity, Jaccard Similarity Index (JSI), Dice Similarity Index DSI) and accuracy. The reported results showed that an accuracy of 98.5%, sensitivity 91.5% and specificity 98.6 %was achieved from the finely Curvelet Transform and ANFIS Model.

Spinal Meningothelial Meningioma In a Dog

The objective of this study is to report clinical, MRI, surgical and histological findings of spinal meningothelial meningioma in a dog. Study material was a 9 years old, spayed dog with history of progressive non ambulatory tetra paresis. The dog had intact cranial and spinal reflexes, and deep pain perception. Magnetic resonance images revealed a mass located at left side C2-C3 level, hyperintense in T1W, isointense on T2W, well contrast enhancing on postcontrast T1. The mass was microsurgically resected sub gross totally. The dog’s neurological status was improved at one week and survived for 15 months without signs of metastasis. Histological and histochemical workup revealed grade I, meningothelial meningioma. Surgical intervention for spinal meningioma can be suggested as a sole treatment in dogs.

Spinal meningiomas.

Spinal meningiomas (SM) are lesions with a mostly favorable oncological and surgical prognosis and a low incidence of tumor recurrence. SM account for approximately 1.2-12.7% of all meningiomas and 25% of all spinal cord tumors. Typically, SM are located in the intradural extramedullary space. SM grow slowly and spread laterally into the subarachnoid space, stretching and sometimes incorporating the surrounding arachnoid but rarely the pia. Standard treatment is surgery with the primary aims of achieving complete tumor resection as well as improving and recovering neurologic function. Radiotherapy may be considered in case of tumor recurrence, for challenging surgical cases, and for patients with higher-grade lesions (World Health Organization grade 2 or 3); however, radiotherapy is mostly used as an adjuvant therapy for SM. New molecular and genetic profiling increases the understanding of SM and may uncover additional treatment options.

P.135 Dura splitting technique for surgical resection of spinal meningioma

Background: Spinal meningiomas are intradural extramedullary tumors that account for 25–46% of all primary spinal tumors. A growing body of literature suggests that the extent of resection significantly affects the recurrence rate of spinal meningiomas and that Simpson grade II resection may not be as adequate as previously thought. Dura Splitting Technique (DST) can be used with no major perioperative complications. Methods: Retrospect review of six cases of spinal meningiomas where DST was used. The patients ranged in age at presentation from 38 to 80 years. All presented with symptoms including gait unsteadiness and lower limbs weakness. Spinal MRI was used to establish the diagnosis. All of the tumors were located ventral or ventrolateral to the spinal cord. Results: DST was applying to spinal meningioma cases,complete tumor resection by separating the involved dura into inner and outer layer. Preserving the dura outer layer and avoiding the need for dural graft reconstruction and CSF leak. A total of six cases, four in thoracic spine and two in cercical spine one anterior and one posterior, all four cases had no reported surgical complications or tumor recurrenc. Conclusions: We confirm that DST is safe and a superior method in the treatment of spinal meningiomas.

Human epidermal growth factor receptor 2/3 (HER2/HER3) expression in higher-grade meningioma.

e14063 Background: Meningiomas are the most frequently diagnosed primary central nervous system (CNS) tumors in adults. Although most meningiomas can be cured by resection, higher-grade lesions (CNS WHO grades 2 & 3) tend to recur, with limited systemic treatment options after exhaustion of local therapies. Antibody drug conjugates (ADCs) targeting human epidermal growth factor receptors 2 and 3 HER2/HER3) have shown remarkable clinical activity in solid tumors including breast cancer brain metastases and are under investigation in various malignancies. Methods: 64 patients with WHO grade 2 (atypical) and 3 (anaplastic) meningioma have been included. DNA methylation analysis has been performed using Illumina EPIC methylation arrays. Panel sequencing for NF2, PIK3CA, SMO, ARID1A, ARID1B, KLF4, SUFU, TERT promotor, and TRAF7 has been executed applying the Illumina NextSeq 500 platform. HER2 and HER3 expression was evaluated by immunohistochemical analysis using PATHWAY HER2 (4B5, Roche) and HER3 #12708 (Cell Signaling) antibodies on a Ventana Benchmark Ultra staining system. Results: In total, 44/64 (68.8%) patients with WHO grade 2 and 20/64 (31.2%) patients with WHO grade 3 meningioma were included. Median age at surgery was 60 years (range: 19-83), and 37/64 (57.8%) patients were female. DNA methylation classes according to the Molecular Neuropathology classifier were benign-1 in 10 (15.6%), benign-2 in 10 (15.6%), benign-3 in 4 (6.3%), intermediate-A in 26 (40.6%), intermediate-B in 4 (6.3%), and malignant in 10 (15.6%) out of 64 tumors. Weak membranous HER2 expression was observed in 1/64 (1.6%) tumor, which was categorized as WHO grade 3/intermediate-B meningioma characterized by infiltration of adjacent bone and fat tissue as well as positive Ki-67 staining of up to 39% of cells. Similarly, only one sample (1.6%) was HER3-positive which was diagnosed as WHO grade 2 tumor of methylation class benign-2, showing meningothelial morphology with elevated mitotic activity and a mutation in TRAF7. The single HER2+ as well as the HER3+ sample were from two distinct female patients. Conclusions: In our cohort, HER2 and HER3 were only infrequently expressed in a small subset of samples of different WHO grade, methylation class, and genetic background. Exploration of further targets of ADCs which are approved or under investigation in other tumors is currently ongoing.

The Role of Immunotherapy in the Treatment of Rare Central Nervous System Tumors.

Establishing novel therapies for rare central nervous system (CNS) tumors is arduous due to challenges in conducting clinical trials in rare tumors. Immunotherapy treatment has been a rapidly developing field and has demonstrated improvements in outcomes for multiple types of solid malignancies. In rare CNS tumors, the role of immunotherapy is being explored. In this article, we review the preclinical and clinical data of various immunotherapy modalities in select rare CNS tumors, including atypical meningioma, aggressive pituitary adenoma, pituitary carcinoma, ependymoma, embryonal tumor, atypical teratoid/rhabdoid tumor, and meningeal solitary fibrous tumor. Among these tumor types, some studies have shown promise; however, ongoing clinical trials will be critical for defining and optimizing the role of immunotherapy for these patients.

Recurrent Anaplastic Meningioma with Metastasis

Meningioma is the commonest primary intracranial tumor in adults, with the majority being benign. Malignant meningioma is exceedingly rare and carries a poor prognosis because of its tendency for local recurrence and distant metastasis. We present the case of a 53 years old male with anaplastic malignant meningioma, which recurred after excision and radiotherapy and later metastasised to pleura, bones and brain. Keywords: Metastatic meningioma, Anaplastic meningioma, Pleural metastasis, Intracranial tumor, Extracranial metastasis

Incidental Detection of Dual Spinal Meningiomas on 68Ga-DOTATATE PET/CT Masquerading as Metastatic Disease in a Patient With Pulmonary Carcinoid Tumor.

Simultaneous occurrence of multiple meningiomas of the spine appearing at different neuroaxial levels is extremely rare event. We present the scintigraphic findings of incidentally detected multiple meningiomas of the spine on 68Ga-DOTATATE PET/CT during the evaluation of a patient with pulmonary carcinoid tumor. These scintigraphic findings could result in a "false-positive" interpretation by exhibiting highly increased uptake similar to that of metastases of neuroendocrine neoplasm. Nuclear medicine physicians should be aware of this potential pitfall in somatostatin receptor imaging to prevent misinterpretation.

Expression of neuroendocrine markers in meningeal and extrameningeal solitary fibrous tumors: a potential diagnostic pitfall

Solitary fibrous tumors (SFTs) may show unusual morphologies, and in such circumstances, an unexpected immunoprofile can be misleading. Following an index case of myxoid meningeal SFT with a neuroendocrine immunoprofile, we decided to assess a neuroendocrine profile in SFTs from various locations. The cohort of 9 meningeal and 28 extrameningeal SFTs was evaluated for CNS WHO grade (G1-G3) and 4-tiered Demicco risk stratification. Immunohistochemical detection of synaptophysin, chromogranin, INSM1, CD56, and CD57 was performed in each case and semiquantitatively assessed (0: no expression; 1+: <10% positive; 2+: 11-50%; and 3+: >51%); whole sections (meningeal SFTs) or tissue microarray (extrameningeal SFTs) were used for immunohistochemistry. The cohort included 13 men and 24 women. Meningeal SFTs included 5 WHO G1, 3 WHO G2, and 1 WHO G3 tumors. Extrameningeal SFTs included 21 low-risk, 4 intermediate-risk, and 2 high-risk tumors. INSM1 immunoreactivity was observed in 12 of 37 cases (32%; 8 cases 1+, 3 cases 2+, and 1 case 3+); synaptophysin was positive in 6 of 35 cases (19%; 5 cases 1+ and 1 case 2+); CD56 was positive in 20 of 37 cases (54%; 16 cases 1+, 3 cases 2+, and 1 case 3+); and CD57 was expressed in 14 of 36 cases (39%; 5 cases 1+, 4 cases 2+, and 5 cases 3+). Chromogranin positivity was not observed. No significant association was observed between expression of neuroendocrine markers and tumor grade, Demicco risk group or meningeal and extrameningeal location. Extrapleural SFTs showed a tendency for positivity of INSM1 (P=.014, χ2) and CD57 (P=.017, χ2)compared to pleural SFTs.

SMARCE1-related meningiomas: A clear example of cancer predisposing syndrome

We report the case of a 16-year-old girl presenting with spinal clear-cell multiple meningiomas (CCMs). In view of this presentation, we sequenced a bioinformatic panel of genes associated with susceptibility to meningioma, identifying a germline heterozygous variant in SMARCE1. Somatic DNA investigations in the CCM demonstrated the deletion of the wild-type allele (loss of heterozygosity, LOH), supporting the causative role of this variant. Family segregation study detected the SMARCE1 variant in the asymptomatic father and in the asymptomatic sister who, nevertheless, presents 2 spinal lesions. Germline heterozygous loss-of-function (LoF) variants in SMARCE1, encoding a protein of the chromatin-remodeling complex SWI/SNF, have been described in few familial cases of susceptibility to meningioma, in particular the CCM subtype. Our case confirms the role of NGS in investigating predisposing genes for meningiomas (multiple or recurrent), with specific regard to SMARCE1 in case of pediatric CCM. In addition to the age of onset, the presence of familial clustering or the coexistence of multiple synchronous meningiomas also supports the role of a genetic predisposition that deserves a molecular assessment. Additionally, given the incomplete penetrance, it is of great importance to follow a specific screening or follow-up program for symptomatic and asymptomatic carriers of pathogenic variants in SMARCE1.

Retrospective histomorphologic study of meningeal masses in Benin City, Nigeria

Background: The rarity of many histologic entities and the common discordance between histologic appearance and biologic behaviour make the diagnosis of meningeal masses challenging. Except for a few common entities like meningioma and meningeal metastases, data on the prevalence of meningeal mass lesions is limited, and most exist as case reports and small case series. This study presents the pattern of meningeal masses in our environment, in the hope of adding to knowledge and awareness of the differential diagnoses of meningeal masses in our environment.&#x0D; Materials and methods: A retrospective study of meningeal masses histologically diagnosed at the the University of Benin Teaching Hospital, Benin city, Nigeria, based on clinical, demographic and histomorphologic data obtained over a 15-year period.&#x0D; Results: Total of 140 meningeal masses; 137 neoplastic and 3 non-neoplastic mass lesions. Ages ranged from 3-86 years. Mean age was 45.85 ± 18.16 years. There were 52 males and 88 females with an overall male-female ratio of 1:1.7; but non-meningothelial tumours were more common amongst males. Most common tumour was Meningioma (78.6%), then metastatic tumours (15%), non-meningothelial mesenchymal tumors (4.3%), and hypertrophic pachymeningitis (2.1%). Meningioma, hemangioblastoma and embryonal rhabdomyosarcoma were the most common tumours in children.&#x0D; Conclusion: Rare histologic entities arising in the meninges, can easily be overlooked in the differential diagnosis of meningeal mass lesions, while the common ones like meningioma and meningeal metastases, are at risk of becoming ‘waste basket’ or ‘safety net’ diagnoses for meningeal tumours. There is need for continuous evaluation and audit of histological diagnoses of meningeal tumours to avoid missing the rare entities that may occasionally be encountered.