Hemorrhagic choroidal detachment as the presenting sign of uveal melanoma.

PURPOSE: To describe two cases of medium-sized uveal melanoma presenting with hemorrhagic choroidal detachments. OBSERVATIONS: The first case is a 39-year-old man who presented with choroidal hemorrhage and angle closure glaucoma. The second case is a 42-year-old man who presented with choroidal hemorrhage and posterior scleritis. Vitrectomy with transvitreous fine needle aspiration biopsy was ultimately required to diagnose malignant uveal melanoma in each case. CONCLUSIONS AND IMPORTANCE: Intraocular hemorrhage is a rare presenting sign of uveal melanoma. When it does occur, it is typically associated with large tumors. Hemorrhagic choroidal detachments are particularly rare in uveal melanoma, and can limit the diagnostic utility of clinical exam, B-scan ultrasonography, and magnetic resonance imaging. Although it is uncommon, it is important to maintain a high index of suspicion for choroidal melanoma in any patient with unexplained choroidal hemorrhage.

Phosphoproteomic and Kinomic Signature of Clinically Aggressive Grade I (1.5) Meningiomas Reveals RB1 Signaling as a Novel Mediator and Biomarker.

PURPOSE: Most World Health Organization (WHO) grade I meningiomas carry a favorable prognosis. Some become clinically aggressive with recurrence, invasion, and resistance to conventional therapies (grade 1.5; recurrent/progressive WHO grade I tumors requiring further treatment within 10 years). We aimed to identify biomarker signatures in grade 1.5 meningiomas where histopathology and genetic evaluation has fallen short. EXPERIMENTAL DESIGN: Mass spectrometry (MS)-based phosphoproteomics and peptide chip array kinomics were used to compare grade I and 1.5 tumors. Ingenuity Pathway Analysis (IPA) identified alterations in signaling pathways with validation by Western blot analysis. The selected biomarker was evaluated in an independent cohort of 140 samples (79/140 genotyped for meningioma mutations) by tissue microarray and correlated with clinical variables. RESULTS: The MS-based phosphoproteomics revealed differential Ser/Thr phosphorylation in 32 phosphopeptides. The kinomic profiling by peptide chip array identified 10 phosphopeptides, including a 360% increase in phosphorylation of RB1, in the 1.5 group. IPA of the combined datasets and Western blot validation revealed regulation of AKT and cell-cycle checkpoint cascades. RB1 hyperphosphorylation at the S780 site distinguished grade 1.5 meningiomas in an independent cohort of 140 samples and was associated with decreased progression/recurrence-free survival. Mutations in NF2, TRAF7, SMO, KLF4, and AKT1 E17K did not predict RB1 S780 staining or progression in grade 1.5 meningiomas. CONCLUSIONS: RB1 S780 staining distinguishes grade 1.5 meningiomas, independent of histology, subtype, WHO grade, or genotype. This promising biomarker for risk stratification of histologically bland WHO grade I meningiomas provides insight into the pathways of oncogenesis driving these outlying clinically aggressive tumors.

ENvironmental Dynamics Underlying Responsive Extreme Survivors (ENDURES) of Glioblastoma: A Multidisciplinary Team-based, Multifactorial Analytical Approach.

Although glioblastoma (GBM) is a fatal primary brain cancer with short median survival of 15 months, a small number of patients survive >5 years after diagnosis; they are known as extreme survivors (ES). Because of their rarity, very little is known about what differentiates these outliers from other patients with GBM. For the purpose of identifying unknown drivers of extreme survivorship in GBM, the ENDURES consortium (ENvironmental Dynamics Underlying Responsive Extreme Survivors of GBM) was developed. This consortium is a multicenter collaborative network of investigators focused on the integration of multiple types of clinical data and the creation of patient-specific models of tumor growth informed by radiographic and histologic parameters. Leveraging our combined resources, the goals of the ENDURES consortium are 2-fold: (1) to build a curated, searchable, multilayered repository housing clinical and outcome data on a large cohort of ES patients with GBM; and (2) to leverage the ENDURES repository for new insights into tumor behavior and novel targets for prolonging survival for all patients with GBM. In this article, the authors review the available literature and discuss what is already known about ES. The authors then describe the creation of their consortium and some preliminary results.

Intraoperative assessment of skull base tumors using stimulated Raman scattering microscopy.

Intraoperative consultations, used to guide tumor resection, can present histopathological findings that are challenging to interpret due to artefacts from tissue cryosectioning and conventional staining. Stimulated Raman histology (SRH), a label-free imaging technique for unprocessed biospecimens, has demonstrated promise in a limited subset of tumors. Here, we target unexplored skull base tumors using a fast simultaneous two-channel stimulated Raman scattering (SRS) imaging technique and a new pseudo-hematoxylin and eosin (H&E) recoloring methodology. To quantitatively evaluate the efficacy of our approach, we use modularized assessment of diagnostic accuracy beyond cancer/non-cancer determination and neuropathologist confidence for SRH images contrasted to H&E-stained frozen and formalin-fixed paraffin-embedded (FFPE) tissue sections. Our results reveal that SRH is effective for establishing a diagnosis using fresh tissue in most cases with 87% accuracy relative to H&E-stained FFPE sections. Further analysis of discrepant case interpretation suggests that pseudo-H&E recoloring underutilizes the rich chemical information offered by SRS imaging, and an improved diagnosis can be achieved if full SRS information is used. In summary, our findings show that pseudo-H&E recolored SRS images in combination with lipid and protein chemical information can maximize the use of SRS during intraoperative pathologic consultation with implications for tissue preservation and augmented diagnostic utility.

Effects of tumor grade and dexamethasone on myeloid cells in patients with glioma.

Efforts to reduce immunosuppression in the solid tumor microenvironment by blocking the recruitment or polarization of tumor associated macrophages (TAM), or myeloid derived suppressor cells (MDSCs), have gained momentum in recent years. Expanding our knowledge of the immune cell types, cytokines, or recruitment factors that are associated with high-grade disease, both within the tumor and in circulation, is critical to identifying novel targets for immunotherapy. Furthermore, a better understanding of how therapeutic regimens, such as Dexamethasone (Dex), chemotherapy, and radiation, impact these factors will facilitate the design of therapies that can be targeted to the appropriate populations and retain efficacy when administered in combination with standard of care regimens. Here we perform quantitative analysis of tissue microarrays made of samples taken from grades I-III astrocytoma and glioblastoma (GBM, grade IV astrocytoma) to evaluate infiltration of myeloid markers CD163, CD68, CD33, and S100A9. Serum, flow cytometric, and Nanostring analysis allowed us to further elucidate the impact of Dex treatment on systemic biomarkers, circulating cells, and functional markers within tumor tissue. We found that common myeloid markers were elevated in Dex-treated grade I astrocytoma and GBM compared to non-neoplastic brain tissue and grade II-III astrocytomas. Cell frequencies in these samples differed significantly from those in Dex-naïve patients in a pattern that depended on tumor grade. In contrast, observed changes in serum chemokines or circulating monocytes were independent of disease state and were due to Dex treatment alone. Furthermore, these changes seen in blood were often not reflected within the tumor tissue. Conclusions: Our findings highlight the importance of considering perioperative treatment as well as disease grade when assessing novel therapeutic targets or biomarkers of disease.

Giant Pediatric Rhabdoid Meningioma Associated with a Germline BAP1 Pathogenic Variation: A Rare Clinical Case.

BACKGROUND: Rhabdoid meningiomas are rare World Health Organization grade 3 tumors that tend to follow an aggressive course, with an increased likelihood for local recurrence, remote metastasis, and cerebrospinal fluid dissemination. Genetic testing has found certain genes associated with reduced time to tumor recurrence. BAP1 (BRCA1-associated protein 1) is a tumor suppressor gene that is associated with multiple tumors, including rhabdoid meningiomas. CASE DESCRIPTION: We present a case of a pediatric patient who presented with a rhabdoid meningioma occurring in the right tentorium and invading multiple venous structures, including the right jugular vein. The patient underwent 5 separate operations for management of this tumor. The first surgery was an intracranial tumor debulking with reconstruction of venous structures. Postoperatively, the patient was unable to have the ventricular catheter removed and underwent placement of a ventriculoperitoneal shunt. Significant recurrence of the intracranial portion of tumor was found during preoperative imaging for her second stage procedure. She underwent a second craniotomy for resection of the tumor. Her postoperative magnetic resonance imaging showed significant residual tumor and the patient therefore underwent a third craniotomy for total tumor resection, which involved reconstruction of the superior sagittal sinus. She did well after this surgery, with no new neurologic deficits. Her final operation involved resection of the residual tumor in the neck and chest by both otolaryngology and cardiothoracic surgery. This surgery involved opening the jugular vein and resecting residual tumor from the intima. Pathologic results from all surgeries were consistent with rhabdoid meningioma; however, the tissue from the biopsy and first craniotomy lacked the high-grade features that were found on subsequent resections. Genetic analysis found loss of both BAP1 tumor suppressor genes. Peripheral blood testing showed that this patient was a germline carrier of a pathogenic BAP1 variant. DISCUSSION: Pediatric rhabdoid meningiomas represent a rare disease and are found on recurrent tumors in conjunction with lower-grade meningioma disease. Our patient presented with what was initially believed to be a low-grade meningioma with rhabdoid features, which then transformed into a World Health Organization grade III rhabdoid meningioma on recurrence. This tumor was discovered to have a biallelic loss of BAP-1 mutation and the patient was found to have a germline mutation in 1 of her BAP-1 alleles. Germline mutations in BAP-1 are associated with a cancer syndrome that involves uveal and cutaneous melanoma, malignant mesothelioma, atypical Spitz tumors, and clear-cell renal cell carcinoma. Patients with this mutation are encouraged to undergo annual eye examinations starting at the age of 11 years. The BAP-1 tumor predisposition syndrome is most commonly an inherited mutation associated with incomplete penetrance and variation with nonoverlapping tumor types. CONCLUSIONS: Rhabdoid meningiomas are unlikely to be found in children and have a high rate of local recurrence. Gross total resection has to be balanced with risk of postoperative deficit. Genetic testing of this rare entity should be performed to identify any hereditary germline mutations.

Neutral lipid storage disease with myopathy: Further phenotypic characterization of a rare PNPLA2 variant.

Neutral lipid storage disease with myopathy is a rare disorder of lipid metabolism caused by variants in the Patatin-Like Phospholipase Domain Containing 2 (PNPLA2) gene. Diagnosis is often delayed due to variable presentations, which is of concern due to increased risk of cardiomyopathy. Better phenotype-genotype characterization is necessary to improve speed and accuracy of diagnosis. Here, we describe a 32-year-old woman of Hmong descent with progressive muscle pain and weakness who had a muscle biopsy with characteristic features of a lipid storage myopathy. Genetic testing revealed a homozygous splice site variant in PNPLA2, c.757 + 1G > T. This case, in combination with the one previously reported case of this PNPLA2 variant, also in a family of Hmong descent, suggests this particular variant may be unique to the Hmong population, a Southeast Asian minority group living in the United States, who immigrated to the United States as refugees after the Vietnam War.

Endothelial Activation and Blood-Brain Barrier Disruption in Neurotoxicity after Adoptive Immunotherapy with CD19 CAR-T Cells.

Lymphodepletion chemotherapy followed by infusion of CD19-targeted chimeric antigen receptor-modified T (CAR-T) cells can be complicated by neurologic adverse events (AE) in patients with refractory B-cell malignancies. In 133 adults treated with CD19 CAR-T cells, we found that acute lymphoblastic leukemia, high CD19+ cells in bone marrow, high CAR-T cell dose, cytokine release syndrome, and preexisting neurologic comorbidities were associated with increased risk of neurologic AEs. Patients with severe neurotoxicity demonstrated evidence of endothelial activation, including disseminated intravascular coagulation, capillary leak, and increased blood-brain barrier (BBB) permeability. The permeable BBB failed to protect the cerebrospinal fluid from high concentrations of systemic cytokines, including IFNγ, which induced brain vascular pericyte stress and their secretion of endothelium-activating cytokines. Endothelial activation and multifocal vascular disruption were found in the brain of a patient with fatal neurotoxicity. Biomarkers of endothelial activation were higher before treatment in patients who subsequently developed grade ≥4 neurotoxicity.Significance: We provide a detailed clinical, radiologic, and pathologic characterization of neurotoxicity after CD19 CAR-T cells, and identify risk factors for neurotoxicity. We show endothelial dysfunction and increased BBB permeability in neurotoxicity and find that patients with evidence of endothelial activation before lymphodepletion may be at increased risk of neurotoxicity. Cancer Discov; 7(12); 1404-19. ©2017 AACR.See related commentary by Mackall and Miklos, p. 1371This article is highlighted in the In This Issue feature, p. 1355.

Clival paragangliomas: a report of two cases involving the midline skull base and review of the literature.

Head and neck paragangliomas are rare neuroendocrine tumors that arise from paraganglion cells of the parasympathetic nervous system. Paragangliomas arising from the midline skull base have only rarely been reported. Surgery is the mainstay of treatment and adjuvant radiation is often recommended. These tumors can rarely secrete metanephrines and normetanephrines which can complicate operative management. Here we present two cases of clival paragangliomas with unique clinical presentations and review the previous literature on skull base paragangliomas.

Primary Gliosarcoma of the Optic Nerve: A Unique Adult Optic Pathway Glioma.

A 90-year-old woman presented with 1-year history of right-sided progressive proptosis, neovascular glaucoma, blindness, and worsening ocular pain. No funduscopic examination was possible because of a corneal opacity. Head CT scan without contrast demonstrated a heterogeneous 4.1 cm (anterior-posterior) by 1.7 cm (transverse) cylindrical mass arising in the right optic nerve and extending from the retrobulbar globe to the optic canal. She underwent palliative enucleation with subtotal resection of the orbital optic nerve and tumor. Pathological examination showed effacement of the optic nerve by an infiltrative high-grade glial neoplasm with biphasic sarcomeric differentiation. Invasion into the uvea and retina was present. The neoplasm was negative for melan-A, HMB45, tyrosinase, synaptophysin, smooth muscle actin, and epithelial membrane antigen. The glioma had strongly intense, but patchy immunopositivity for glial fibrillary acidic protein. Multiple foci of neoplastic cells had pericellular reticulin staining. The overall features were diagnostic of a gliosarcoma (World Health Organization grade IV) of the optic nerve. Postoperative MRI demonstrated postsurgical changes and residual gliosarcoma with extension into the optic chiasm. The patient died 2 and a half months after her enucleation surgery at her nursing home. Autopsy was unavailable due to the caregiver wishes, making a definitive cause of death unknown. Gliosarcoma is a rare variant of glioblastoma, and this is the first documented case presenting as a primary neoplasm of the optic nerve.

Lack of BRAF-V600E Mutation in Papillary Tumor of the Pineal Region.

BACKGROUND: Papillary tumor of the pineal region (PTPR) is a rare central nervous system tumor with a variably aggressive clinical behavior, corresponding to World Health Organization grade II/III. Very little is known about the genetic mutations comprising PTPR. Recent studies have shown that other papillary tumors harbor BRAF-V600E mutations, namely papillary thyroid carcinoma and papillary craniopharyngioma, the latter of which is a midline central nervous system papillary tumor like PTPR. OBJECTIVE: To determine whether PTPR may contain the BRAF-V600E mutation. METHODS: A search of our institutional files was conducted for PTPR cases. Chart review was performed to obtain demographics and pertinent clinical information when possible. Immunohistochemistry was performed with an anti-BRAF-V600E antibody for cases with additional material for testing. RESULTS: We identified 19 PTPR cases occurring in 16 patients. The patient age range was 1 to 73 years (average, 32.2 years). The male-to-female ratio was 1:1. Thirteen patients presented with symptoms of obstructive hydrocephalus, and the other 3 had unknown presenting symptoms. Initial magnetic resonance imaging characteristics tended to include partially cystic masses with heterogeneous postcontrast enhancement. The tumor size ranged from 1.1 to 4.4 cm (average, 2.5 cm). CONCLUSION: Of the 16 patients, 13 had additional material for BRAF-V600E immunohistochemistry, all of which demonstrated negativity for BRAF-V600E. This rate is unlike that of other midline papillary tumors and suggests that these tumors, despite their papillary phenotype, may have a distinctive molecular background.

Gene therapy enhances chemotherapy tolerance and efficacy in glioblastoma patients.

BACKGROUND: Temozolomide (TMZ) is one of the most potent chemotherapy agents for the treatment of glioblastoma. Unfortunately, almost half of glioblastoma tumors are TMZ resistant due to overexpression of methylguanine methyltransferase (MGMT(hi)). Coadministration of O6-benzylguanine (O6BG) can restore TMZ sensitivity, but causes off-target myelosuppression. Here, we conducted a prospective clinical trial to test whether gene therapy to confer O6BG resistance in hematopoietic stem cells (HSCs) improves chemotherapy tolerance and outcome. METHODS: We enrolled 7 newly diagnosed glioblastoma patients with MGMT(hi) tumors. Patients received autologous gene-modified HSCs following single-agent carmustine administration. After hematopoietic recovery, patients underwent O6BG/TMZ chemotherapy in 28-day cycles. Serial blood samples and tumor images were collected throughout the study. Chemotherapy tolerance was determined by the observed myelosuppression and recovery following each cycle. Patient-specific biomathematical modeling of tumor growth was performed. Progression-free survival (PFS) and overall survival (OS) were also evaluated. RESULTS: Gene therapy permitted a significant increase in the mean number of tolerated O6BG/TMZ cycles (4.4 cycles per patient, P < 0.05) compared with historical controls without gene therapy (n = 7 patients, 1.7 cycles per patient). One patient tolerated an unprecedented 9 cycles and demonstrated long-term PFS without additional therapy. Overall, we observed a median PFS of 9 (range 3.5-57+) months and OS of 20 (range 13-57+) months. Furthermore, biomathematical modeling revealed markedly delayed tumor growth at lower cumulative TMZ doses in study patients compared with patients that received standard TMZ regimens without O6BG. CONCLUSION: These data support further development of chemoprotective gene therapy in combination with O6BG and TMZ for the treatment of glioblastoma and potentially other tumors with overexpression of MGMT. TRIAL REGISTRATION: Clinicaltrials.gov NCT00669669. FUNDING: R01CA114218, R01AI080326, R01HL098489, P30DK056465, K01DK076973, R01HL074162, R01CA164371, R01NS060752, U54CA143970.

Cheek cell-derived α-synuclein and DJ-1 do not differentiate Parkinson's disease from control.

Recently, α-synuclein (α-syn) and DJ-1, 2 proteins critically involved in Parkinson's disease (PD), have been shown to be present in saliva, suggesting their potential utility as biomarkers of PD. However, the origin and influence of demographic characteristics (e.g., age or sex) on these proteins are unknown. We identified cheek epithelium, which forms the majority of the cellular component of saliva and is readily accessible clinically, as 1 of several potential sources of salivary α-syn and DJ-1. However, no PD-related trend in the cellular component was present. In the supernatant collected from 198 healthy subjects, no correlation was seen between salivary DJ-1 or α-syn with age. When male and female subjects were analyzed separately, a weak age-dependent increase in DJ-1 level was present in male subjects, along with slightly increased α-syn in female subjects. These results, albeit largely negative, provide critical information for understanding the salivary gland pathology and saliva as a PD biomarker source, and must be considered in future investigations of salivary changes in PD.

Deep sequencing of multiple regions of glial tumors reveals spatial heterogeneity for mutations in clinically relevant genes.

BACKGROUND: The extent of intratumoral mutational heterogeneity remains unclear in gliomas, the most common primary brain tumors, especially with respect to point mutation. To address this, we applied single molecule molecular inversion probes targeting 33 cancer genes to assay both point mutations and gene amplifications within spatially distinct regions of 14 glial tumors. RESULTS: We find evidence of regional mutational heterogeneity in multiple tumors, including mutations in TP53 and RB1 in an anaplastic oligodendroglioma and amplifications in PDGFRA and KIT in two glioblastomas (GBMs). Immunohistochemistry confirms heterogeneity of TP53 mutation and PDGFRA amplification. In all, 3 out of 14 glial tumors surveyed have evidence for heterogeneity for clinically relevant mutations. CONCLUSIONS: Our results underscore the need to sample multiple regions in GBM and other glial tumors when devising personalized treatments based on genomic information, and furthermore demonstrate the importance of measuring both point mutation and copy number alteration while investigating genetic heterogeneity within cancer samples.

Multiplex immunoassays of peptide hormones extracted from formalin-fixed, paraffin-embedded tissue accurately subclassify pituitary adenomas.

BACKGROUND: The current gold standard for diagnostic classification of many solid-tissue neoplasms is immunohistochemistry (IHC) performed on formalin-fixed, paraffin-embedded (FFPE) tissue. Although IHC is commonly used, there remain important issues related to preanalytic variability, nonstandard methods, and operator bias that may contribute to clinically significant error. To increase the quantitative accuracy and reliability of FFPE tissue-based diagnosis, we sought to develop a clinical proteomic method to characterize protein expression in pathologic tissue samples rapidly and quantitatively. METHODS: We subclassified FFPE tissue from 136 clinical pituitary adenoma samples according to hormone translation with IHC and then extracted tissue proteins and quantified pituitary hormones with multiplex bead-based immunoassays. Hormone concentrations were normalized and compared across diagnostic groups. We developed a quantitative classification scheme for pituitary adenomas on archived samples and validated it on prospectively collected clinical samples. RESULTS: The most abundant relative hormone concentrations differentiated sensitively and specifically between IHC-classified hormone-expressing adenoma types, correctly predicting IHC-positive diagnoses in 85% of cases overall, with discrepancies found only in cases of clinically nonfunctioning adenomas. Several adenomas with clinically relevant hormone-expressing phenotypes were identified with this assay yet called "null" by IHC, suggesting that multiplex immunoassays may be more sensitive than IHC for detecting clinically meaningful protein expression. CONCLUSIONS: Multiplex immunoassays performed on FFPE tissue extracts can provide diagnostically relevant information and may exceed the performance of IHC in classifying some pituitary neoplasms. This technique is simple, largely amenable to automation, and likely applicable to other diagnostic problems in molecular pathology.

Sudden unexpected death in lymphocytic hypophysitis.

Lymphocytic hypophysitis is an unusual inflammatory condition of the pituitary gland, classically seen in females during the peripartum periods. The clinical presentation is varied and depends on hormonal deficiencies and pathophysiological effects on the target organs. Although involvement of the neurohypophysis and secondary diabetes insipidus are rare, progression to multiple organ endocrinopathies is common. Pathologically, the condition is characterized by lymphocytic infiltration of the hypophysis with occasional involvement of the thyroid and adrenal glands. Here, we present the case of a 23-year-old woman diagnosed at autopsy with lymphocytic hypophysitis, with concomitant infiltrates in the thyroid gland and adrenal medulla, who died suddenly and unexpectedly with no other apparent cause of death. This case stresses the importance of greater awareness of the entity, and prompt treatment. Moreover, although the precise mechanism of death is unclear, this case raises the possibility of endocrine dysfunction as a contributing factor to sudden death and emphasizes the need to routinely sample the pituitary gland in young women with sudden unexpected death and no apparent cause.

Angiolymphoid hyperplasia with eosinophilia developing in a patient with history of peripheral T-cell lymphoma: evidence for multicentric T-cell lymphoproliferative process.

BACKGROUND: Angiolymphoid hyperplasia with eosinophilia (ALHE) is a vasocentric process characterized by infiltrates of lymphocytes and eosinophils, usually affecting the muscular arteries of the head and neck. Currently it is unclear whether it is a reactive or neoplastic process. REPORT: We present a 61-year-old African American male with a twenty year history of superficial skin patches involving the head and neck region. An excisional biopsy of a right submental lymph node revealed an atypical T-cell lymphocytic process, diagnosed as peripheral T-cell lymphoma after immunophenotyping and molecular studies. Three months later the patient underwent a biopsy of a left temporal nodule that was diagnosed as ALHE. Subsequently, at two year follow-up, the patient was diagnosed with Mycosis Fungoides. Polymerase chain reaction for T cell receptor gamma showed the same T-cell receptor gene rearrangement in both the temporal mass and the right submental lymph node. CONCLUSION: ALHE with molecular evidence of monoclonality is extremely unusual, as is the association with nodal peripheral T-cell nodal lymphoma. The findings of this case support our hypothesis that ALHE might be an early form of T-cell lymphoma.

Plasmablastic lymphoma of the oral cavity: a rapidly progressive lymphoma associated with HIV infection.

Plasmablastic lymphoma of the oral cavity is a form of non-Hodgkin lymphoma (NHL) and was first described in 1997. We describe a case of plasmablastic lymphoma in an HIV-infected patient who presented with an expanding oral lesion and symptoms of a toothache. We review all cases of plasmablastic lymphoma that have been reported in the literature. Plasmablastic lymphoma is strongly associated with immunodeficiency, and most particularly, with HIV infection. The pathophysiological origin of plasmablastic lymphoma has not been fully characterised, but the presence of Epstein-Barr virus (EBV) has often been documented in biopsy specimens, supporting a role for EBV in the pathogenesis of this lymphoma. The differential diagnosis for an expanding oral lesion includes both infectious and malignant processes. Biopsy is essential for making a correct and prompt diagnosis. Treatment usually involves chemotherapy, but antiretroviral therapy may also have an important role. Infectious disease clinicians should be aware of this newly described and increasingly encountered lymphoma, since it is prominently associated with immunosuppression and may be mistaken for other entities.

Bilateral internal carotid absence: a case report of a rare congenital anomaly.

BACKGROUND: Bilateral internal carotid artery agenesis (ICAA) is a rare developmental anomaly of unknown etiology that is often associated with disruption of adequate perfusion to the central nervous system. Nevertheless, some patients remain asymptomatic due to collateral circulation involving the communicating arteries of the Circle of Willis. Secondary to the hemodynamical stress through the collateral circulation, affected patients are at an increased risk of developing subarachnoid hemorrhage and intracranial aneurysms. METHODS AND RESULTS: We report an unusual case of a 62-year-old man with bilateral ICAA who expired following two asystolic events during minor surgery. CONCLUSION: This case emphasizes the plasticity of the cerebral collateral circulation during development, to the point of normal cerebral perfusion throughout life with no ischemic complications.