Left Parietal Lesion Research Articles

Differential efficacy of SV-BR-1-GM in inducing intracranial metastasis regression.

e13119 Background: Breast cancer metastasis to the central nervous system (CNS) and intracranial area often leads to severe morbidity and mortality. While systemic treatments manage systemic tumors, their impact on CNS/intracranial metastases is limited. Cell based therapies like SV-BR-1-GM may overcome this limitation. SV-BR-1-GM is a GM-CSF secreting, antigen-presenting immortalized breast cancer cell line. We report its efficacy on CNS tumor regression. Methods: Post-hoc analysis of a subset of all advanced MBC patients with CNS/intracranial metastases from previous phase 1, 2, and an ongoing randomized phase 2, trials (n=7 subjects) of SV-BR-1-GM. Bria-IMT monotherapy (intradermal SV-BR-1-GM + cyclophosphamide 300 mg/m2, +interferon-alpha) was administered q3wks to 2 subjects; an immune checkpoint inhibitor (ICI) was administered with each cycle in the combination setting (n=5). Results: There were 7 patients with intracranial metastases at baseline of whom 5 had intracranial tumor responses. Of the 5 responders, median pt age = 66 (range 58-70), median prior lines = 5.5 (3-13), and median time from initial diagnosis = 7.5 years (3-10). 4/5 pts had ≥1 HLA class match with SV-BR-1-GM. 3 were HR + and 1 HER2 +. Pt A002 (ER+/PR+, HER2-) received 6/6 planned cycles, achieving an 83% reduction in breast lesions; after 3 months off therapy, imaging revealed multiple brain metastases and recurrence of right breast lesions. Following 3 additional cycles there was marked regression in both brain and breast lesions. Pt 02-003 (ER-/PR-, HER2 1+ (IHC)) received 5 cycles of SV-BR-1-GM and observed a 60% reduction (5mm -> 2mm) in a left parietal periventricular lesion, and complete resolution (CR) of a left parietal lobe. Pt 06-005 (ER+/PR-, HER2 1+) demonstrated a 56% (9mm -> 4mm) reduction in the thickness of a dural lesion overlying the left anterior temporal lobe after 6 cycles of SV-BR-1-GM + ICI. After 2 additional cycles of SV-BR-1-GM + ICI and 1 cycle of SV-BR-1-GM (ICI skipped on final cycle due to grade 2 AE), patient achieved CR of a left orbital mass observed at baseline (24mm -> 0m). Pt06-007’s (ER-/PR-, HER2 1+) CNS lesions showed a median reduction of 49% compared to baseline after 3 cycles. Pt 11-018 (ER+/PR-, HER2 +) showed standard progression (SD) at initial restaging; 14% increase in sum of diameters of intracranial metastasis. Subsequent imaging, after 3 cycles, showed significant orbital tumor reduction along with reported improvement in eye pain. Conclusions: This post-hoc analysis demonstrated promising efficacy of the Bria-IMT regimen either alone or in combination with ICIs in CNS/intracranial metastasis. The CNS/intracranial regression seen across all breast cancer subtypes among heavily pretreated patients highlights the potential of SV-BR-1-GM in managing CNS metastasis. Ongoing trials will further evaluate the efficacy of the Bria-IMT regimen in patients with CNS/intracranial metastasis. Clinical trial information: NCT03328026 .

Waldenstrom Macroglobulinemia Recurrence with Bing–Neel Syndrome Presentation

Bing–Neel syndrome (BNS) is a rare condition that may occur in patients with Waldenstrom macroglobulinemia (WM) and is caused by lymphoplasmacytic infiltration into the central nervous system. BNS is an extramedullary manifestation of WM which may present with various neurological signs and symptoms that make the diagnosis difficult to achieve. We present a case of BNS in a 60-year-old patient diagnosed 6 years after recovering from Waldenstrom’s macroglobulinemia. We observed the patient for a secondary generalized focal motor seizure. Unenhanced brain CT revealed slight hyperdensity of left parietal subarachnoid spaces. The MRI of the brain and spinal cord showed leptomeningeal enhancement in both parietal lobes. The presence of monoclonal bands (light chain k and IgM) was found in cerebrospinal fluid, leading to the diagnosis of BNS. The patient started treatment with ibrutinib and remains clinically stable during a 1-year follow-up. However, the MRI showed the appearance of a new subcortical left parietal lesion. BNS is an extremely rare presentation of WM that should be recognized and considered early in the presence of unexplained neurological symptoms in patients with a history of WM, even if the patient appears to have recovered.

Abstract PO2-28-04: Pregnancy-associated relapse of triple-negative breast cancer

Abstract Introduction: Pregnancy Triple-negative breast cancer(TNMC) is the absence of ER PR and HER2 receptor expression. It constitutes about 15-20% of all breast cancers and is known to be the aggressive form with a high relapse rate (1). Interestingly, it usually affects women aged < 40 and has a low survival rate in African-American females. This case is a typical presentation of a 38-year-old young woman with PMH of T2NO right triple-negative breast cancer diagnosed in 2017 s/p right mastectomy with sentinel LN biopsy, received immunotherapy and chemotherapy, has been cancer-free for two years, and developed metastatic cancer during her pregnancy. In this case, we understand the diagnostic and therapeutic challenges of TNBC during pregnancy. Case: A 38-year-old African American woman, G0, T2NO triple negative invasive ductal carcinoma, underwent a right breast mastectomy and sentinel LN biopsy. She received treatment with (Anti-PD-L1 Antibody) concomitant with weekly paclitaxel and Doxorubicin/Cyclophosphamide (AC) chemotherapy. However, she had a residual 4cm tumor for which she was treated with adjuvant therapy with capecitabine for six months. A repeat Mammogram in 2019 showed no evidence of malignancy. In 2021, the patient was G2P2L1, admitted to the hospital after having a seizure. CT reported cystic/necrotic left parietal lesion mass effect with 8mm right-sided midline shift with metastasis to lungs and abdominal wall. She underwent L parietal craniectomy with resection of the tumor. At 32 weeks of gestation , chemotherapy with carboplatin and paclitaxel was given after her C-section and Gamma knife radiosurgery for metastatic lesions. She developed super refractory seizures, was induced into a coma with therapeutically anesthetic agents, and passed eventually. Discussion: Little literature exists on pregnancy-associated relapse of triple-negative breast cancer and its deterioration. Our patient was in remission for two years and was diagnosed with metastatic cancer during her second pregnancy. John et al., (2018) discussed an interesting association between breastfeeding, parity, and occurrence of TNBC, that there is a two-fold increased risk of developing TNBC with high parity(3 full-term pregnancies) and short-term breastfeeding (< 12 months) (2). Studies have also shown that cancers during or postpartum pregnancy are aggressive with more tumor burden and metastasize to the lungs, liver, and brain, which is consistent with our patient. (3) Conclusion: Pregnancy-associated breast cancer is diagnostically and therapeutically challenging during or in the postpartum period and with a high propensity of the triple-negative type. It requires a multidisciplinary team approach, awareness in the African American population, clinical suspicion of breast mass during pregnancy warrants imaging, and prolonged breastfeeding postpartum. Diagnosis is usually delayed due to pregnancy, and more research is needed on the diagnostic modalities during pregnancy for early treatment initiation. References Almansour NM. Triple-Negative Breast Cancer: A Brief Review About Epidemiology, Risk Factors, Signaling Pathways, Treatment and Role of Artificial Intelligence. Front Mol Biosci. 2022 Jan 25;9:836417. doi: 10.3389/fmolb.2022.836417. PMID: 35145999; PMCID: PMC8824427. John EM, Hines LM, Phipps AI, et al. Reproductive history, breast-feeding and risk of triple-negative breast cancer: The Breast Cancer Etiology in Minorities (BEM) study. International Journal of Cancer. 2018;142(11):2273. doi:10.1002/ijc.31258 Amant F, Deckers S, Van Calsteren K, Loibl S, Halaska M, Brepoels L, et al. Breast cancer in pregnancy: recommendations of an international consensus meeting. Eur J Cancer (2010) 46(18):3158–68. 10.1016/j.ejca.2010.09.010 Citation Format: Vaidarshi Abbagoni. Pregnancy-associated relapse of triple-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-28-04.

Abstract CT204: Efficacy of Bria-IMT regimen in inducing CNS metastasis regression

Abstract Objectives: Breast cancer metastasis to the central nervous system (CNS) often leads to severe morbidity and mortality, and while systemic treatments manage primary tumors, their impact on CNS metastases is limited. This retrospective analysis evaluates the efficacy of Bria-IMT as a monotherapy or in combination with an immune checkpoint inhibitor (ICI) on CNS tumor regression. Methods: Post-hoc analysis of a subset of advanced MBC patients with CNS metastases from previous phase 1 and 2, and ongoing randomized phase 2 trials involving SV-BR-1-GM. SV-BR-1-GM is a GM-CSF secreting, antigen-presenting immortalized breast cancer cell line. Bria-IMT (SV-BR-1-GM ~20x106 cells, intradermally 48-72 hours after cyclophosphamide 300 mg/m2, followed by interferon-alpha at the inoculation sites 2 days later) was administered q3wks. In the combination setting, an ICI was administered with each cycle. Patients A002 and 02-003 received Bria-IMT as monotherapy. Patients 06-005 and 06-007 received Bria-IMT in combination with an ICI. Results: Median pt age of 65 (range 58-70). All pts had ≥1 HLA match with SV-BR-1-GM. Significant CNS tumor regression was observed in all pts. Pt A002 (ER+/PR+, HER2-) received 6 cycles, achieving an 83% reduction in breast lesions. ~3 months after the last cycle, imaging revealed the onset of multiple brain metastases and recurrence of right breast lesions. Following 3 additional cycles, marked measurable regression in both brain metastases and breast lesions was noted. Pt 02-003 (ER-/PR-, HER2 1+ (IHC)) received 5 cycles and observed a 60% reduction (5mm ->2mm) in a left parietal periventricular lesion, and complete resolution (CR) of a left parietal lobe lesion. Pt 06-005 (ER+/PR-, HER2 1+(IHC)) demonstrated a 56% (9mm -> 4mm) reduction in the thickness of a dural lesion overlying the left anterior temporal lobe after 6 cycles of SV-BR-1-GM + ICI (pembrolizumab). After 2 additional cycles of SV-BR-1-GM + ICI (retifanlimab) and 1 cycle of SV-BR-1-GM (ICI was skipped on final cycle due to grade 2 AE), patient achieved CR of a left orbital mass observed at baseline (24mm -> 0m). Circulating cancer-associated macrophage-like cells (CAMLs) varied throughout the treatment, with levels ranged from a baseline of 90 to 24 by Cycle 13. Pt 06-007 (ER-/PR-, HER2 1+ (IHC)) demonstrated significant reductions in CNS lesions after 3 cycles of SV-BR-1-GM + ICI (pembrolizumab): a 67% reduction in a right frontal lobe lesion, 29% in the right parietal, 30% in the right thalamus, and 67% in the right precentral gyrus lesions. CAML levels remained low throughout treatment. Conclusions: This review consolidates evidence for the efficacy of the Bria-IMT regimen in CNS metastasis regression, both alone and with ICIs. The consistent regression seen across all breast cancer subtypes among heavily pretreated patients highlights the potential of SV-BR-1-GM in managing CNS metastasis. Ongoing trials will determine the full extent. Citation Format: Sailaja Kamaraju, Blaise Bayer, Mingjin Chang, William Williams, Charles Wiseman, Giuseppe Del Priore. Efficacy of Bria-IMT regimen in inducing CNS metastasis regression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT204.

Inadvertent Discovery of Gerstmann's Syndrome During a Skull MRI and Its Anatomical Basis: A Case Report

A rare neurological disorder in which an individual is unable to perform tasks related to language, spatial recognition,mathematics, and cognition is known as Gerstmann's syndrome(GS). Gerstmann hypothesised that the four symptoms thatmakeup Gerstmann's syndrome are caused by a shared cognitive problem (Grundstörung). Gerstmann asserted that it is a bodyschema disorder that only affects the hand and fingers. Since then, the existence of a Grundstörung has been disputed. The studyproposed a shared psychoneurological element, but it should be connected to changes in mental pictures rather than the bodilyschema. The significant facts appear to be the common simultaneous impairment of writing, computation, and bodily awarenessafter left parietal lesion, beyond the diagnostic label of "pure" and "non-pure" Gerstamann's syndrome instances. Some functionaldomains can be linked to patients' symptoms despite being heterogeneous. A 65-year-old male was brought to the hospital witha history of injury to the head and complaints of confusion, speech difficulty, inability to perform simple calculations, severeheadache, and drowsiness. The patient was sent to the radiology department of Sree Balaji Medical College and Hospital,Chennai, for a Magnetic Resonance Imaging of Skull (MRI). The MRI study revealed chronic ischemic changes in periventricularand subcortical white matter in the parietal lobes. Certain ischemic changes were also observed in the frontal lobe, suggestingage-related changes and Gerstmann's syndrome. By cutting off various portions of the inferior parietal cortex, a lesion affectingsubcortical and subangular bundles of fibers affects many circuits with distinct roles. Therefore, the deficits seen in the patientare best explained by this anatomical explanation.

Mitral Valve Replacement for Enlarged Libman-Sacks Endocarditis in a Patient with Persistent Primary Antiphospholipid Syndrome and Recurrent Stroke: A Case Report.

BACKGROUND Anticardiolipin antibodies in patients with Libman-Sacks endocarditis (LS) are indicative of comorbid antiphospholipid syndrome (APS) and can result in cerebral infarctions. We describe a case of LS and primary APS with recurrent cerebral infarctions despite anticoagulation treatment. The patient underwent surgery for enlarged LS vegetation with high titers of antiphospholipid antibodies. CASE REPORT A 41-year-old Japanese man was admitted to hospital for small cerebral infarction recurrence in a left parietal lesion. At age 35, the patient had suffered multiple cerebral infarctions. He was found to have high serum titers of all 3 antiphospholipid antibodies. Transesophageal echocardiography (TEE) findings were normal. Differential diagnosis ruled out other autoimmune diseases and a clinical diagnosis of primary APS was made. Warfarin anticoagulation was started. When cerebral infarction recurred 6 years after the first episode, serum titers of antiphospholipid antibodies remained high, and TEE showed a 7×8 mm area of mitral vegetation. A TEE results from his first admission revealed a 5×6 mm area of mitral vegetation, which was believed to be related to the current vegetation. As anticoagulation produced no improvement, the mitral valve was replaced with a mechanical valve. Examination of the excised vegetation found it to be consistent with LS. The patient made good progress within 3 years after surgery. CONCLUSIONS LS size can increase despite anticoagulation in cases with high titers of all 3 antiphospholipid antibodies and cerebral infarction. Such patients require ongoing TEE follow-up and surgical treatment should be considered.

Intracranial Extramedullary Hematopoiesis: a Rare Entity

Abstract Introduction/Objective Extramedullary hematopoiesis (EMH) is characterized by ectopic proliferation and differentiation of hematopoietic precursor cells outside the bone marrow. In postnatal life, EMH occurs due to hematopoietic disorders, infection or advanced tumors and is usually seen in the spleen, liver, and lymph nodes. Intracranial EMH is an extremely rare entity that has been reported to be associated with hematological disorders, meningioma, subdural hematoma and pilocytic astrocytoma. Methods/Case Report To highlight the significance of identifying EMH as one of the differential diagnoses of brain lesions, we present a 67-year-old female with a history of headaches and generalized malaise. Her past medical history was significant for hypertension and mild anemia. As part of the headache workup, magnetic resonance imaging (MRI) of the brain showed a 3.7cm cystic mass in the right inferomedial parietal lobe with medial mural enhancement, associated with edema and mass effect. A similar 3mm left parietal lobe enhancing focus was also noted. These findings were suggestive of a hemangioblastoma. Resection of the larger mass showed a benign vascular lesion with endothelial hyperplasia without the appearance of cavernous hemangioma or vascular malformation. Foci of erythroid and myeloid precursors, and megakaryocytes were seen. Immunohistochemical stains were negative for GFAP, CK AE1/AE3 and inhibin ruling out glial neoplasms, metastatic carcinoma and hemangioblastoma. Hematopoietic cells were positive for CD45, while immature red cells were positive for E-cadherin and endothelial cells were positive for CD31, consistent with EMH. Further workup was negative for any underlying hematological disorders, resulting in the diagnosis of idiopathic intracranial EMH. The patient received intensity- modulated radiation therapy (IMRT) for her remaining left parietal lesion. After 3 months of regular follow-up, her headache and malaise significantly improved. Results (if a Case Study enter NA) NA. Conclusion To our knowledge, this is the first reported case of idiopathic intracranial EMH.

S1676 Things Are Not Always What They Seem: A Rare Case of Pancreatic Carcinoma Manifesting Through Cutaneous Metastasis

Introduction: Pancreatic cancer is an aggressive disease that commonly metastasizes to the liver, lung, and peritoneum. Cutaneous metastasis is a rare occurrence with an incidence of only 2.0%. We present a case of metastatic pancreatic adenocarcinoma primarily presenting as a cutaneous nodule. Case Description/Methods: A 50-year-old male was undergoing outpatient evaluation for a raised, left scalp lesion along with neck nodules. Associated symptoms included an unintentional 30lb weight loss. Outpatient CT soft tissue neck revealed numerous necrotic lateral neck lymph nodes, lytic lesion with epidural soft tissue extension at C2-4, and occlusion/thrombosis of the left subclavian, brachiocephalic, and left internal jugular veins (Figure). Given these findings, the patient was referred to the Emergency Department (ED). At time of ED arrival, vital signs were stable along with initial laboratory values. CTA PE study showed no pulmonary embolism but revealed numerous pulmonary and bilateral adrenal nodules, multifocal liver and osseous lesions, and widespread lymphadenopathy. Additionally, CT head demonstrated a left scalp soft tissue lesion. Follow up CT abdomen/pelvis revealed a 2.8 x 2.2 x 1.8 cm ill-defined pancreatic lesion and confirmed widespread metastasis including to the muscles. Additional testing revealed elevated cancer markers with Cancer antigen 19-9 (CA 19-9) of 5418 U/mL and carcinoembryonic antigen (CEA) of 63.8 ng/mL. Pathology from initial scalp lesion biopsy showed fragments of necrotic dermis with small foci of poorly differentiated carcinoma. Biopsies of the right and left neck masses revealed poorly differentiated adenocarcinoma of uncertain primary. Therefore, liver biopsy was performed and confirmed non-small cell carcinoma of pancreatobiliary origin. Further imaging to determine treatment course discovered intracranial metastasis and cervical spine disease resulting in cord compression. Ultimately, the patient underwent 4 out of 10 fractions of palliative radiation to the cervical spine but passed away after transitioning to comfort care one month after diagnosis. Discussion: There are less than 25 documented cases of pancreatic cancer with cutaneous involvement; however, it is even more rare that cutaneous involvement prompts initial diagnosis. The umbilicus is the most common site of cutaneous involvement and is referred to as the Sister Mary Joseph Nodule. Involvement of the soft tissue of the scalp and neck is much less common and poorly documented making this case extremely unique.Figure 1.: Axial contrast enhanced CT of the abdomen shows a 2.8 cm ill-defined hypoattenuating mass in the pancreatic tail (A) with multifocal metastatic liver lesions and bilateral adrenal metastasis (B). Axial CT image of the pelvis shows a metastatic lesion in the right rectus femoris muscle (C). On liver biopsy, H&E, 40X,(S21-41666) revealed high grade carcinoma with vesiculated nuclei, prominent nucleoli (D), CA 19-9 IHC 20X diffuse positivity in tumor cells (E) and CK AE1/3 IHC, 20X, diffusely positivee for pancytokeratin in tumor cells confirming carcinoma (F). Axial CT of the head shows a 2.4 cm nodular left parietal scalp soft tissue lesion (G) which was also seen on clinical examination (H). Biopsy of the scalp lesion (H&E, 40X) demonstrated high grade carcinoma with vesiculated nuclei, prominent nucleoli and mitoses (I), histologically similar to liver biopsy findings.

Tumefactive demyelination-A Rare Presentation of Multiple Sclerosis

Background: Multiple Sclerosis is an inflammatory demyelinating disease having varied manifestations in terms of clinical featuresand radiological features. Rarely it may present as a large demyelinating lesionwith accompanying edema and mass effect, thereby simulating an intracranial tumor, known as Tumefactive Demyelination. Symptoms are usually related to the pressure of a focal mass lesion. When it manifests in a patient without pre-existing MS, it poses a diagnostic challengeas it may mimic a neoplasm, infarct or abscess. Thus, it is essential to recognize this rare clinical entity for proper patient management. Case Presentation: We report here a case of 40 years old female who presented with right sided hemiparesis. The initial brain imaging (CT) suggested left parietal lobe lesion suggestive of glioma. But MRI of the brain showed a cortical based lesion in left parietal lobe in parasaggital location which appeared hyperintense on both T2WI and FLAIR sequences. Further evaluation by MR spectroscopy suggested the lesion to be tumefactive demyelination. She was administered IV Methylprednisolone (1gm daily for 5 days) and responded well to treatment. The characteristic magnetic resonance findings of the patient, its acute onset, and its clinical improvement after corticosteroid therapy finally set the diagnosis of Tumefactive Demyelination. Conclusion: Tumefactive demyelinating lesions pose a unique diagnostic challenge in defining differential diagnosis and management and should always be considered in young patients presenting with tumour like lesions on imaging. Bangladesh Journal of Medical Science Vol. 21 No. 04 October’22 Page : 931-934

LUNG CANCER METASTASES IN THE BRAIN: MAJOR RESPONSE WITH AFATINIB

TYPE: Late Breaking Abstract TOPIC: Lung Cancer INTRODUCTION: Lung cancer (LC) is the leading cause of cancer-related death worldwide and it is responsible for nearly 50% of brain metastasis (BM) cases. Afatinib is a second-generation irreversible EGFR tyrosine kinase inhibitor, indicated in the treatment of metastatic LC with activating EGFR mutations. CASE PRESENTATION: A 71-year-old woman, ECOG PS 1, was diagnosed with stage IVb LC (T3N0M1b), EGFR mutated (exon 18: Glu790Lys, Lys744Asn, Gly719Ser). Staging brain MRI showed 2 left brain lesions, suggestive of BM, not surgically approachable: one in the parietal region (20x16mm) and another (3mm) in the temporo-occipital transition. In the Multidisciplinary Tumor Board was decided treatment with afatinib and stereotactic brain surgery (SBS). To plan SBS another brain MRI was performed showing a significant reduction of the left parietal lesion (10x8mm; figure 1) and complete disappearance of the other lesion, after 8 days of treatment, and SBS was canceled. Reevaluation after 3 months revealed partial imaging response on the lung and brain (BM with 9mm, major axis). Due to grade 2-3 skin rash and paronychia, the treatment dose was reduced until 20mg/day, with good tolerance. DISCUSSION: Despite having incomplete blood-brain barrier penetration, afatinib has the potential to treat LC BM, with a reported intracranial response rate ranging from 35%-72.9%. This efficacy was demonstrated in this case report, allowing brain radiation sparing strategy. CONCLUSIONS: This case report shows the effectiveness of afatinib in BM from EGFR mutated lung adenocarcinoma. DISCLOSURE: No significant relationships. KEYWORD: Brain metastases

Cerebellar contributions to orthographic working memory: A single case cognitive neuropsychological investigation

Single case cognitive neuropsychological investigations involve the precise characterization of cognitive impairment at the level of an individual participant. This deep data precision affords a more fine-grained understanding of the cognitive and neural underpinnings of complex tasks, and continues to provide unique insights that inform theory in cognitive neuroscience. Here, we present a single case study of an individual, F.R., who suffered a stroke that led to chronic reading and writing problems that include an impairment to the orthographic working memory system proposed to be involved in both written language production and comprehension. Individuals who have been previously reported with a similar cognitive impairment commonly have left parietal lesions. However, F.R.’s orthographic working memory deficit resulted from damage to the right cerebellum, specifically to a region that is both structurally and functionally connected to the left parietal lobe and has been identified as part of the spelling network in previous meta-analyses of writing fMRI studies. From this lesion-symptom association, we argue that orthographic working memory is subserved by a cortical-cerebellar circuit, with damage at any point in the circuit resulting in an impairment to this function. Such a conclusion is warranted by observations from this single case approach, and we argue that these observations would likely have been missed if F.R. had been included in a larger, shallower group study. In addition to elucidating our understanding of the neural basis of spelling, this case study demonstrates the value that single case neuropsychology can continue to bring to cognitive neuroscience.

Concomitant pulmonary and neurological embolisation in a Down patient after SARS-CoV-2 vaccine: what is missing?

A 40-year-old Down patient without previous cardiological history was admitted to our institution for dyspnoea after COVID-19 vaccine. CT scan revealed a pulmonary thromboembolism. One week later, he developed neurological impairment and CT scan evidenced a left parietal ischaemic lesion. Concomitantly, he underwent echocardiography showing an atrioventricular septal defect typically associated to Down syndrome and never diagnosed earlier. The diagnosis of paradoxical embolisation was then supposed. Echocardiography also revealed a severe right heart section dilatation, with bidirectional shunt on the septal defects and systemic right heart pressure. Down patients affected by CHD are more prone to develop pulmonary vasculopathy than non-syndromic patients. In this case, the pulmonary vasculopathy was further exacerbated by the pulmonary embolism and by the late diagnosis of CHD. Finally, an appropriate timely diagnosis of atrioventricular septal defect could potentially avoid the neurological complication in this patient.

INNV-29. BILATERAL PARIETAL LYMPHOMA LESIONS RESPONDED DIFFERENTLY TO HD-MTX AND RITUXIMAB/TEMOZOLOMIDE THERAPY

Abstract INTRODUCTION Primary CNS lymphoma is a rare aggressive hematological malignancy. Current chemotherapy for induction phase is HD-MTX single agent or HD-MTX based combination regimen. We report a rare case whose left and right parietal lymphoma lesions in the brain responded to different induction therapy regimens during the induction phase. CASE REPORT A 43-year-old female presented with seizure and her brain MRI showed bilateral parietal brain lesions in January of 2020. Biopsy and work-up revealed primary CNS diffuse large B-cell lymphoma (DLBCL). The patient underwent HD-MTX therapy. Brain MRI showed clear progression of left parietal lymphoma but stable right parietal lymphoma after two cycles of HD-MTX at 8 g/m2. The treatment was switched to a rituximab 750 mg/m2 weekly and temozolomide 150 mg/m2 daily one-week-on and one-week-off regimen. After 8 weeks, her brain MRI showed nearly complete response of her left parietal lymphoma to rituximab/temozolomide but progression of her right parietal lymphoma. She was switched back to HD-MTX and completed total 8 cycles. Her right parietal lymphoma lesion showed complete response to HD-MTX. The patient is doing well and has been off the treatment over the past 10 months and is waiting for consolidation therapy with autologous stem cell transplantation that has been postponed due to the COVID pandemic. DISCUSSION Our case highlights the very rare heterogenous feature of primary CNS lymphoma responding to different treatment regimen. Biopsy of bilateral heterogeneous lesions may be indicated to compare the different molecular features of the lymphoma to find underlying mechanism if they respond to treatment differently. Specific treatment regimen should be selected based on the responsiveness of CNS lymphoma lesions or combination therapy is selected to cover the heterogeneous susceptibility to chemotherapy regimens.

Relationship Between rhTSH Administration and Thyroid Cancer Progression: A Case Report

Abstract Introduction: The relationship between the administration of recombinant TSH (rhTSH) and the progression of thyroid cancer has been described in some case reports (1). There are scant data suggesting that rhTSH acts as a growth factor that stimulates metastatic tumor expansion. Case Report: A 55 year old male patient who 3 years ago reported an evident mass at cervical level. The ultrasound documented a large thyroid mass with an endothoracic component. The FNA reported BETHESDA IV, suspicious for follicular neoplasia. Extension studies showed lytic left parietal bone lesion and liver metastatic compromise. The pathology of the total thyroidectomy showed a follicular carcinoma with a micronodular pattern and capsular invasion, of 19x9x7 cm, vascular and esophageal involvement T4BN0M1. He was sent to radioiodine therapy with 100 MCI with previous suspension of LT4 (Preablative TGL> 300 ng / ml (<50 ng / ml) Abs-TGL 2 IU / ml (<2 IU / ml) TSH 31.3 mIU / L (0.37-4.7 mIU / L) and body scan documenting uptake of the radiotracer at the left parietal, the anterior costal grating, and liver. A second dose of iodine was applied, with 150 MCI after stimulation with thyrotropin (Preablative TGL> 300 ng / ml, Abs-TGL 1.76 IU / ml, TSH 83 mIU / L) Immediately after the administration of rhTSH, the patient described the appearance of alopecic plaques on the scalp, sensation of mass at the right upper quadrant of the abdomen and bone pain in the right rib cage and at the right hip, which progressively worsened the following days until they were incapacitating. The scan report showed a new uptake in dorsal vertebrae, the MRI showed new bone injury at the innominate bone, as well as increase in the sum of its maximum dimensions by 22%, indicative of progression. The cerebral angio-MRI showed hypervascularized metastasis at the left parietal level. Bone scintigraphy documented foci of hyper uptake in both parietals, manubrium and sternal body, 5-8 right anterior costal arches, right scapula, both humeral heads, vertebral bodies T3-T5-T7L4, right acetabulum, left proximal femur and the entire length of the right femur. The clinical and imaging worsening of the bone lesions after the application of rhTSH was striking, for this reason radiotherapy and embolization of the liver lesion was performed. The patient was not a candidate for neurosurgical management due to the vascular component of the cranial lesions. Conclusion: rhTSH is a very well-tolerated method that avoids symptoms associated with severe hypothyroidism. However, it has been associated with neoplastic progression. This is one of the few cases documented in the literature where there is a direct association between the administration of rhTSH and the progression of bone metastases.

A unique case of multiple calvarial hemangiomas with one large symplastic hemangioma

BackgroundSymplastic hemangioma is a benign superficial abnormal buildup of blood vessels, with morphological features which can mimic a pseudo malignancy. A few cases have been reported in the literature. We report here, a unique case of calvarial symplastic hemangioma, which is the first case in the calvarial region.Case presentationA 29-year-old male patient, with a left occipital calvarial mass since childhood, that gradually increased in size with age, was associated with recurrent epileptic fits controlled by Levetiracetam (Keppra), with no history of trauma. He presented to the emergency room with a recent headache, vomiting, frequent epileptic fits and a decrease in the level of consciousness 1 day prior to admission. A CT scan showed three diploic, expansile, variable sized lytic lesions with a sunburst appearance; two that were biparietal, and one that was left occipital, which were all suggestive of calvarial hemangiomas. However, the large intracranial soft tissue content, within the hemorrhage of the occipital lesion was concerning. The patient had refused surgery over the years; however, after the last severe presentation, he finally agreed to treatment.The two adjacent, left parietal and occipital lesions were treated satisfactorily using preoperative embolization, surgical resection, and cranioplasty. Histopathology revealed cavernous hemangiomas, in addition to symplastic hemangioma (pseudo malignancy features) on top at the occipital lesion. The right parietal lesion was not within the surgical field; therefore, it was left untouched for follow-up.ConclusionsHistopathology and radiology examinations confirmed the diagnosis as symplastic hemangioma, on top of a pre-existing cavernous hemangioma. To the best of our knowledge, this is the first case of a calvarial symplastic hemangioma, which we report here.

Abstract 697: Improvement in quality and length of life following treatment with mifepristone in women with stage IV non-small cell lung cancer, positive for the epidermal growth factor receptor (EGFR) mutation, that previously progressed on targeted therapy

Abstract Treatment with the oral single agent progesterone receptor modulator, mifepristone, has been demonstrated to significantly increase the quality and length of life in a patient with stage IV non-small cell lung cancer (NSCLC) that progressed despite multiple rounds of chemotherapy, when no markers existed for specific targeted therapy. The purpose of the present study was to determine if mifepristone could similarly provide palliative benefits to patients with NSCLC, that were positive for EGFR mutation, who had progressed despite targeted therapies. Patient 1, a 59 year old woman presented with 6 months of upper back pain and dyspnea, was found to have innumerable tiny lung nodules (miliary pattern), bone metastases, and a single brain metastasis (left occipital lobe). The tumor was an adenocarcinoma, with an EGFR exon leu858 arg identified. The brain metastasis was treated with palliative radiation therapy and erlotinib was started. She remained stable for 1 ½ years, but then her lung nodules started to increase in size. Erolotinib was stopped, and osimertinib was started. However, she progressed 6 months later, with continued growth of pulmonary nodules bilaterally and a new brain metastasis, in the right lateral cuneus. Her dyspnea, which had improved on erlotinib, returned to pre-treatment status. She was started on oral single agent mifepristone, 200mg per day. Patient 2, a 46 year old woman, had presented with headaches, difficulty with executive function, and memory loss. She was diagnosed with stage IV NSCLC, with extensive lung lesions and brain metastases. A MRI of the brain revealed innumerable supratentorial rim enhancing lesions, with one dominant left parietal lobe lesion measuring 3 × 2.1cm (treated with palliative radiation). CT scans showed innumerable bilateral pulmonary nodules with evidence of lymphangitic spread and multiple bone lesions. Because the tumor was positive for the EGFR1 exon 19 mutations (E746/751 mutation), she was started on afatinib, which was stopped 8 months later. She then had a second course of brain radiation and 5 months after stopping afatinib she began osimertinib. After 10 months of osimertinib, it seemed to be losing effectiveness, and so 200mg oral mifepristone was added. Both women have had stable disease, with no growth of previous nodules and no new nodules, or new brain metastases after 6 months and 14 months of mifepristone therapy, respectively. More importantly they both feel much better, with no dyspnea, or pain, and remain ECOG-0. Thus, similar to small cell lung cancer and NSCLC devoid of tumor markers, or with the PD-L1 mutation, patients with advanced NSCLC with EGFR mutation also seem to respond to the progesterone receptor modulator, mifepristone. Citation Format: Jerome H. Check, Diane Check, Trina Poretta, James Aikins, Carrie Wilson. Improvement in quality and length of life following treatment with mifepristone in women with stage IV non-small cell lung cancer, positive for the epidermal growth factor receptor (EGFR) mutation, that previously progressed on targeted therapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 697.

Structural representations of fingers rely on both anatomical and spatial reference frames.

Finger agnosia refers to a neurological condition in which patients with left posterior parietal lesions fail to identify their fingers, despite having relatively preserved abilities in sensation and skilled action. This dissociation suggests that the structural body representations (BSRs) may be distinct from sensorimotor representations. However, recent research has reported that postural changes modulate representation of hand structure, revealing dynamic interactions between structural and sensorimotor body representations. However, it is unknown how and to what extent anatomical and spatial proximity contribute to shape the hand structural representation. We investigate this question using the "in-between" test in which participants estimate how many unstimulated fingers are in between 2 touched fingers of the left hand placed palm down. The first phalange of the participants' fingers was touched on the left or right side. Judged finger numerosity was greater when fingers were stimulated on far sides (i.e., opposite sides of the 2 fingers) compared to when they were stimulated on close (i.e., sides facing each other's) or middistance (i.e., sides facing in the same direction) sides. Therefore, finger identification was modulated by anatomical and spatial proximity in external space between touches. This demonstrates that BSRs rely on both anatomical and external reference frames. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

52. FGFR3-TACC3: Case report and review of a potentially targetable diagnostic marker in high grade gliomas

Background: FGFR3-TACC3 fusion has been identified in IDH wild-type WHO grade III and IV astrocytomas, with an incidence of 2–3% in most case series and a range of 1–8%. These tumours have characteristic histopathological features and a poor prognosis. The aberrant CD34 immunohistochemical staining and glial and neuronal marker co-expression may lead to a misdiagnosis of a glioneuronal tumour with a better prognosis. An immunohistochemistry antibody to FGFR3 is commercially available which may serve as a more cost-effective screening test for identification of possible FGFR3-TACC3 cases. These tumours may also be amenable to treatment by FGFR tyrosine kinase inhibitors, or through inhibition of oxidative phosphorylation as a down-stream functional target of FGFR3-TACC3 fusion. Aims: A report highlighting common pitfalls in the diagnosis of high grade astrocytoma with FGFR3-TACC3 gene fusion. Methods: A single case study and review of the supporting literature. Results and conclusions: A 64-year-old male with a four month history of focal sensory abnormalities had a solitary 24 mm, intra-axial, contrast-enhancing left parietal lobe brain lesion on MRI. A stereotactic craniotomy and tumour resection was performed. Histopathology showed a malignant heterogeneous tumour. The cellular morphology included gemistocytic features, larger pleomorphic cells and numerous mitotic figures. Additional findings were psammomatous calcifications and thin-walled branching blood vessels with perivascular lymphoid cuffing. Many of the lesional cells co-expressed neuronal and glial protein markers on immunohistochemistry and there was also patchy aberrant CD34 staining. IDH1, IDH2 and BRAF genes were wild-type on molecular pathology testing. There was no loss of chromosome 1p or 19q or EGFR amplification by cytogenetic analysis. The Illumina TP170 next-generation sequencing assay identified a FGFR3-TACC3 gene fusion, a TERT promoter mutation (C250T) and a gain of FGFR3. The diagnosis of anaplastic astrocytoma, WHO grade III, IDH wild-type with FGFR3-TACC3 fusion, TERT promoter mutation and FGFR3 gain was made.

Tumefactive multiple sclerosis: Emerging role of MR spectroscopy

Tumefactive multiple sclerosis (TMS) is a rare variant of multiple sclerosis (MS) comprising of large demyelinating lesions that frequently mimic intracranial neoplasm or abscess. MR Spectroscopy (MRS) is an exciting new tool to differentiate radiologically. We present three cases with TMS who were diagnosed with MRS brain. A 24-years-old male presented with sensory symptoms that resolved after steroid pulse therapy. MRI spine and brain showed lesions consistent with MS and CSF showed Oligoclonal bands. Despite disease modifying therapy, he developed new symptoms. A repeat MRI brain was static and MRS showed evidence of elevated peaks of Choline and lactate with mild reduction of NAA consistent with demyelination. A 32-years-old male came for lower limb weakness and numbness with progressive gait impairment. He had history of urinary symptoms, imbalance, dizziness, ataxia and excessive fatigue. CSF analysis was normal. MRI brain revealed multiple lesions consistent with MS along with a left frontal lesion with perilesional edema and faint rim enhancement. MRS showed elevation of lactate and choline consistent with TMS. NAA was reduced. He was started on Cladribine with good response. A 37-years-old female known to have MS, on Fingolimod, developed a new relapse. MRI brain showed a left parietal cystic lesion with no contrast enhancement along with other lesions consistent with MS. MRS of the cystic lesion shows low NAA and high Choline. She was switched to Natalizumab. MR spectroscopy may serve as a helpful diagnostic tool to differentiate TMS from other counterparts.

Exploring the neural correlates of the reversed letter effect: Evidence from left and right parietal patients

To investigate the hemispheric lateralization of attentional processes during visual search tasks depending on the stimulus material embedding the target, twelve patients with unilateral left (n = 7) or right (n = 5) parietal lesions and 20 age and education matched healthy controls (HC) were recruited. We used a visual search task for a uniquely tilted oblique bar embedded in an object shape 'N' or in its mirror reversal 'И'. The accuracy and the averaged reaction times (RTs) in each stimulus type ('N' or 'И') were analysed.HC presented significantly longer RTs when the target bar was embedded in 'N' among its mirror reversed 'И' (p < .05). This “reversed letter effect” was also found in the right parietal patients (p < .001), while no evidence of a reversed letter effect was found in the left parietal patients.