Clinical presentation and extent of resection impacts progression-free survival in spinal ependymomas.

PURPOSE: Primary treatment of spinal ependymomas involves surgical resection, however recurrence ranges between 50 and 70%. While the association of survival outcomes with lesion extent of resection (EOR) has been studied, existing analyses are limited by small samples and archaic data resulting in an inhomogeneous population. We investigated the relationship between EOR and survival outcomes, chiefly overall survival (OS) and progression-free survival (PFS), in a large contemporary cohort of spinal ependymoma patients. METHODS: Adult patients diagnosed with a spinal ependymoma from 2006 to 2021 were identified from an institutional registry. Patients undergoing primary surgical resection at our institution, ≥ 1 routine follow-up MRI, and pathologic diagnosis of ependymoma were included. Records were reviewed for demographic information, EOR, lesion characteristics, and pre-/post-operative neurologic symptoms. EOR was divided into 2 classifications: gross total resection (GTR) and subtotal resection (STR). Log-rank test was used to compare OS and PFS between patient groups. RESULTS: Sixty-nine patients satisfied inclusion criteria, with 79.7% benefitting from GTR. The population was 56.2% male with average age of 45.7 years, and median follow-up duration of 58 months. Cox multivariate model demonstrated significant improvement in PFS when a GTR was attained (p <.001). Independently ambulatory patients prior to surgery had superior PFS (p <.001) and OS (p =.05). In univariate analyses, patients with a syrinx had improved PFS (p =.03) and were more likely to benefit from GTR (p =.01). Alternatively, OS was not affected by EOR (p =.78). CONCLUSIONS: In this large, contemporary series of adult spinal ependymoma patients, we demonstrated improvements in PFS when GTR was achieved.

Focal cortical dysplasia is a frequent coexistent pathology in patients with Rasmussen's encephalitis.

INTRODUCTION: Rasmussen's encephalitis (RE) is a rare, predominantly pediatric epilepsy disorder of unknown etiology. It classically affects one of the cerebral hemispheres and histologically shows cortical chronic inflammation, gliosis, and neuronal loss. The etiopathogenesis of RE remains unknown, with genetic, infectious, and autoimmune factors all speculated to play a role. Although the histologic findings in RE are well described, few studies have investigated a large cohort of cases looking for the coexistence of RE with focal cortical dysplasia (FCD). DESIGN: The study is a retrospective review of RE patients who underwent surgical resection of brain tissue between 1979 and 2021. Relevant patient history was retrieved, and available histologic slides were reviewed. The histologic severity of RE was described according to the Pardo criteria. In cases where FCD was present, the observed patterns of FCD (namely Ia, Ib, IIa, IIb, etc.) were described using the International League Against Epilepsy (ILAE) classification. RESULTS: Thirty-eight resection specimens from 31 patients formed the study cohort. Seventeen patients (54.8 %) were male; average age at surgery was 8 years (range: 2-28 years). Twenty-seven resection specimens (71.1 %) from 23 patients (74 %) showed evidence of coexistent FCD. Most cases with FCD resembled the ILAE type Ib (n = 23) pattern. Cases of RE that did not show FCD were either Pardo stage 1 (n = 5) or 4 (n = 6), with all Pardo stage 2 and 3 cases demonstrating FCD. CONCLUSIONS: FCD was found in most patients with RE (74 %). The most observed pattern of FCD was ILAE Ib.

Tumor-to-tumor metastasis of an adenocarcinoma to a glioblastoma with review of the literature on tumor-to-tumor metastasis to gliomas.

Tumor-to-tumor metastasis (TTM) is a process where one tumor metastasizes to another tumor. It is an exceedingly rare phenomenon, particularly in the central nervous system, where it most commonly occurs with meningiomas as the recipient. Herein, we present a case of tumor-to-tumor metastasis of an adenocarcinoma to a glioblastoma in a 75-year-old female. The patient had a history of high-grade ductal carcinoma in situ of the breast 8 years prior, treated with lumpectomy and radiation. She presented with a left fronto-parietal mass. Histologically, the lesion showed a glioblastoma, IDH-wildtype, WHO grade 4, associated with a metastatic adenocarcinoma (positive for estrogen receptor, progesterone receptor, and mammaglobin), suggesting a breast primary. The patient passed away 5 months after surgery. Involvement of glioblastoma by TTM is especially rare; only 1 case of TTM to glioblastoma is thus far reported in the English literature. The mechanism by which TTM occurs is poorly understood. TTM may be the first presentation of an occult malignancy and warrants thorough clinical, laboratory, and imaging investigation.

Toward a better definition of focal cortical dysplasia: An iterative histopathological and genetic agreement trial.

OBJECTIVE: Focal cortical dysplasia (FCD) is a major cause of difficult-to-treat epilepsy in children and young adults, and the diagnosis is currently based on microscopic review of surgical brain tissue using the International League Against Epilepsy classification scheme of 2011. We developed an iterative histopathological agreement trial with genetic testing to identify areas of diagnostic challenges in this widely used classification scheme. METHODS: Four web-based digital pathology trials were completed by 20 neuropathologists from 15 countries using a consecutive series of 196 surgical tissue blocks obtained from 22 epilepsy patients at a single center. Five independent genetic laboratories performed screening or validation sequencing of FCD-relevant genes in paired brain and blood samples from the same 22 epilepsy patients. RESULTS: Histopathology agreement based solely on hematoxylin and eosin stainings was low in Round 1, and gradually increased by adding a panel of immunostainings in Round 2 and the Delphi consensus method in Round 3. Interobserver agreement was good in Round 4 (kappa = .65), when the results of genetic tests were disclosed, namely, MTOR, AKT3, and SLC35A2 brain somatic mutations in five cases and germline mutations in DEPDC5 and NPRL3 in two cases. SIGNIFICANCE: The diagnoses of FCD 1 and 3 subtypes remained most challenging and were often difficult to differentiate from a normal homotypic or heterotypic cortical architecture. Immunohistochemistry was helpful, however, to confirm the diagnosis of FCD or no lesion. We observed a genotype-phenotype association for brain somatic mutations in SLC35A2 in two cases with mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy. Our results suggest that the current FCD classification should recognize a panel of immunohistochemical stainings for a better histopathological workup and definition of FCD subtypes. We also propose adding the level of genetic findings to obtain a comprehensive, reliable, and integrative genotype-phenotype diagnosis in the near future.

IDH mutations in older patients with diffuse astrocytic gliomas.

In 2016, the World Health Organization recommended that isocitrate dehydrogenase (IDH) mutation status be included in the classification of diffuse astrocytic gliomas. IDH mutations are part of the current definition of oligodendrogliomas and are predictive of a better outcome in diffuse astrocytic gliomas. A few studies, examining the role of routine IDH testing in older patients, came to differing conclusions and made differing recommendations regarding a routine IDH testing algorithm with respect to patient age. The purpose of this study was to examine IDH mutations in a series of diffuse astrocytic gliomas [N = 381; 53 diffuse astrocytomas (WHO grade II), 66 anaplastic astrocytomas (WHO grade III) and 262 glioblastomas (WHO grade IV)], paying particular attention to age of patient and any relationship between age and IDH status. IDH status was evaluated by immunohistochemistry with IDH-1 (R132H) antibody and if negative staining was noted, followup polymerase chain reaction (PCR) testing assessing for IDH-1 and IDH-2 mutations was performed. Overall, IDH mutations were discovered in 50.1% of grade II tumors, 54.4% of grade III tumors and 15.1% of grade IV tumors. Of tumors studied, 224 tumors (58.8%) arose in patients 55 years or older. Higher rates of IDH mutations were observed in the patient group less than 55 years of age versus those 55 years or older. By PCR testing in patients 55 years or older, non IDH-1 (R132H) mutations were noted in 0/4 grade II tumors, 3/11 grade III tumors and 26/37 grade IV tumors. The results of this study suggest that although IDH mutations in diffuse astrocytic gliomas are more frequently encountered in patients less than 55 years of age, a significant subset of older patients have mutations that would not be discovered on routine immunohistochemistry and therefore, followup PCR testing is recommended for all patients whose tumors are negative by immunohistochemistry.

1p/19q co-deleted fibrillary astrocytomas: Not everything that is co-deleted is an oligodendroglioma.

The presence of chromosome 1p/19q co-deletion is one of the hallmark required criteria for the diagnosis of oligodendroglioma, using the 2016 World Health Organization (WHO) Classification of Tumours of the Central Nervous System. Descriptions in the literature of astrocytomas, primarily glioblastomas, demonstrating partial losses on one or the other chromosome have been described. The significance of these small deletions is uncertain. Only rarely have cases of fibrillary astrocytoma been described as having co-deletion, which may potentially cause diagnostic confusion with oligodendroglioma. The goal of this study is to examine a large number of fibrillary astrocytomas to document how often 1p/19q co-deletions are present by Fluorescent In Situ Hybridization (FISH) testing (the testing method of choice in many institutions) and to evaluate what other markers may be helpful in avoiding misdiagnosis. This study is a retrospective evaluation of 359 fibrillary astrocytomas (55 grade II, 62 grade III and 242 grade IV) encountered between June 2016 and June 2019, we identified 11 tumors (3.1%) that had 1p/19q co-deletion by FISH testing. The clinical and pathologic features of these cases were reviewed. The 11 cases with co-deletion included 5 females who ranged in age from 37 to 86 years (median 63 years). Tumors arose in the temporal lobe in 5 patients, frontal lobe in 2, parietal lobe in 2, occipital lobe in 1, and cerebellum in 1. Final diagnoses included glioblastoma in 8 patients, anaplastic astrocytoma in 2, and diffuse astrocytoma in 1. Only 1 case (anaplastic astrocytoma) demonstrated evidence of IDH-1 immunoreactivity; none of the other 10 tumors showed evidence of an IDH1/2 mutation by PCR testing. Four tumors demonstrated p53 immunostaining of 30% or more. ATRX mutation as evidenced by loss of staining was observed in only 2 cases. Evidence of EGFR amplification by FISH testing was noted in 5 cases. Of particular note in the one case that demonstrated both 1p/19q co-deletion and an IDH-1 mutation, LOH testing was done and showed only partial losses on both chromosomes. Additionally, this tumor also demonstrated evidence of ATRX and p53 mutations by immunohistochemistry. In conclusion, co-deletions were noted in a minority of astrocytomas (3.1% of cases in the current study). Only 1 of 11 of these cases also demonstrated evidence of an IDH mutation, potentially raising differential diagnostic confusion with oligodendroglioma. Use of LOH 1p/19q testing, if available, or other markers such as ATRX, p53 and EGFR may be helpful in avoiding misclassification of such tumors as oligodendroglioma.

Pediatric clear cell meningioma involving the middle cranial fossa in the context of NF2 and SMARCE1 mutations.

Meningiomas are an uncommon entity in children and adolescents. <30 cases of pediatric clear cell meningioma (CCM), a World Health Organization (WHO) Grade II tumor, have been reported in the literature. These tumors are more likely to recur than the more common WHO Grade I meningiomas, especially with incomplete surgical resection. CCMs are most commonly found in the spine and posterior cranial fossa. Recently, SMARCE1 mutations have been linked to the development of CCM. To evaluate the progression of pediatric CCM in the context of emerging genetic knowledge, we reviewed all 45 cases of CCM at our institution for a 23 year period (1997-2019) to identify pediatric cases. Forty-four of the tumors arose in adults from age 34-81 years. The one pediatric case originally presented at age 4 years; the patient was found to have a CCM in the left cavernous sinus projecting into the posterior fossa, associated with a novel germline SMARCE1 mutation and somatic NF1 and DMD mutations. After two years, the patient had a recurrence of the tumor and underwent a second resection. This is the 5th reported case of CCM in the middle cranial fossa, and the only recurrent case, as well as the only reported case of recurrent pediatric CCM associated with a germline SMARCE1 mutation. Further study of the natural history of tumors associated with germline SMARCE1 loss could potentially inform prognosis.

Evaluation of deeper levels in initially negative temporal artery biopsies and likelihood of a positive result.

Giant cell arteritis is a vasculitis that affects large- and medium-sized vessels in patients over the age of 50 years. The demonstration of granulomatous arteritis is the criterion standard to establish a definitive diagnosis. However, temporal arteritis is known to discontinuously involve the artery, and there is no standardization of the number of sections which should be examined in a length of sampled artery. The goal of the study is to determine, if by examining additional sections from temporal artery (TA) biopsy cases initially interpreted as negative, do we uncover cases of vasculitis. We conducted a retrospective review of the clinical and histologic features of 75 consecutive temporal artery biopsy cases. Our findings showed that the vast majority (94%) of cases that were biopsy "proven" to be negative for temporal arteritis on initial examination remained negative after examination of all subsequent deeper levels (median of 337 total levels examined). These cases were less likely to show classical GCA signs and symptoms and typically presented at a younger age than the biopsy-positive cases. However, 4 (6%) of the initially "biopsy-negative" cases did turn out to be positive on deeper levels, with 56, 109, 346, and 590 total levels examined, respectively. At least 2 of these 4 patients did not receive prednisone or were weaned off prednisone treatment and experienced persistent/recurrent GCA symptoms. We conclude that routine sampling may miss the diagnosis in a subset of cases and in some cases, sectioning deeper into the paraffin block may be warranted.

Technically successful ultrasound-guided percutaneous sural nerve needle biopsy in a patient with indeterminate peripheral neuropathy.

OBJECTIVE: To determine whether ultrasound-guided percutaneous sural nerve needle biopsy yields sufficient tissue for analysis in a patient with suspected vasculitis-related peripheral neuropathy. MATERIALS AND METHODS: With real-time ultrasound guidance, a hydrodissection of the sural nerve from the adjacent small saphenous vein was first performed. A 14-gauge biopsy needle was then manipulated under real-time ultrasound guidance to obtain two transverse samples of the sural nerve at the lateral distal calf. RESULTS: The biopsy was technically successful and yielded adequate tissue for routine processing. The specimen showed mild epineurial perivascular chronic inflammation with marked loss of myelinated axons. These histologic findings are not diagnostically definitive for vasculitis-related peripheral neuropathy but were supportive of the diagnosis in combination with the patient's physical examination, laboratory, and electromyography findings. The patient suffered no immediate complications after the procedure. CONCLUSIONS: This ultrasound-guided sural nerve needle biopsy, like many surgical biopsies, did not yield a definitive result in a patient with suspected vasculitis-related peripheral neuropathy; however, the procedure was technically successful. Given that percutaneous needle procedures offer many advantages over surgical procedures, we believe that this procedure warrants further investigation.

Brain microvascular pathology in Susac syndrome: an electron microscopic study of five cases.

Susac syndrome is a rare, immune-mediated disease characterized by encephalopathy, branch retinal artery occlusion, and hearing loss. Herein, we describe the electron microscopic findings of three brain biopsies and two brain autopsies performed on five patients whose working clinical diagnosis was Susac syndrome. In all five cases, the key findings were basement membrane thickening and collagen deposition in the perivascular space involving small vessels and leading to thickening of vessel walls, narrowing, and vascular occlusion. These findings indicate that Susac syndrome is a microvascular disease. Mononuclear cells were present in the perivascular space, underlining the inflammatory nature of the pathology. Though nonspecific, the changes can be distinguished from genetic and acquired small vessel diseases. The encephalopathy of Susac syndrome overlaps clinically with degenerative and infectious conditions, and brain biopsy may be used for its diagnosis. Its vascular etiology may not be obvious on light microscopy, and electron microscopy is important for its confirmation.

IDH-1 polymorphisms in pilocytic astrocytomas.

As of 2016, isocitrate dehydrogenase (IDH)-1 and IDH-2 mutations are part of the definition of an oligodendroglioma and may be seen in a significant subset of grade II-IV fibrillary astrocytomas. Reports of IDH-1 and IDH-2 alterations in pilocytic astrocytomas have been rare. This study reports two cases of pilocytic astrocytomas which harbored IDH-1 polymorphisms (G105G) (c.315C > T) discovered on polymerase chain reaction (PCR) testing and sequencing. The first was encountered in a 21-year-old male with a right orbital frontal pole mass. The second occurred in a 19-year-old female with a right frontal tumor. Neither tumor stained with antibody to IDH-1 (R132H). No BRAF V600E immunostaining, minimal p53 staining (<5%) and no loss of ATRX staining was noted in both cases. The significance of the IDH-1 findings at this juncture is uncertain. Misdiagnosis of the tumor as a fibrillary astrocytoma or oligodendroglioma due to the presence of an IDH alteration should be avoided.

Ammonia lowering reverses sarcopenia of cirrhosis by restoring skeletal muscle proteostasis.

Sarcopenia or skeletal muscle loss is a frequent, potentially reversible complication in cirrhosis that adversely affects clinical outcomes. Hyperammonemia is a consistent abnormality in cirrhosis that results in impaired skeletal muscle protein synthesis and breakdown (proteostasis). Despite the availability of effective ammonia-lowering therapies, whether lowering ammonia restores proteostasis and increases muscle mass is unknown. Myotube diameter, protein synthesis, and molecular responses in C2C12 murine myotubes to withdrawal of ammonium acetate following 24-hour exposure to 10 mM ammonium acetate were complemented by in vivo studies in the hyperammonemic portacaval anastomosis rat and sham-operated, pair-fed Sprague-Dawley rats treated with ammonia-lowering therapy by l-ornithine l-aspartate and rifaximin orally for 4 weeks. We observed reduced myotube diameter, impaired protein synthesis, and increased autophagy flux in response to hyperammonemia, which were partially reversed following 24-hour and 48-hour withdrawal of ammonium acetate. Consistently, 4 weeks of ammonia-lowering therapy resulted in significant lowering of blood and skeletal muscle ammonia, increase in lean body mass, improved grip strength, higher skeletal muscle mass and diameter, and an increase in type 2 fibers in treated compared to untreated portacaval anastomosis rats. The increased skeletal muscle myostatin expression, reduced mammalian target of rapamycin complex 1 function, and hyperammonemic stress response including autophagy markers normally found in portacaval anastomosis rats were reversed by treatment with ammonia-lowering therapy. Despite significant improvement, molecular and functional readouts were not completely reversed by ammonia-lowering measures. CONCLUSION: Ammonia-lowering therapy results in improvement in skeletal muscle phenotype and function and molecular perturbations of hyperammonemia; these preclinical studies complement previous studies on ammonia-induced skeletal muscle loss and lay the foundation for prolonged ammonia-lowering therapy to reverse sarcopenia of cirrhosis. (Hepatology 2017;65:2045-2058).

Histopathologic subtype of hippocampal sclerosis and episodic memory performance before and after temporal lobectomy for epilepsy.

OBJECTIVE: The International League Against Epilepsy (ILAE) proposed a classification system for hippocampal sclerosis (HS) based on location and extent of hippocampal neuron loss. The literature debates the usefulness of this classification system when studying memory in people with temporal lobe epilepsy (TLE) and determining memory outcome after temporal lobe resection (TLR). This study further explores the relationship between HS ILAE subtypes and episodic memory performance in patients with TLE and examines memory outcomes after TLR. METHODS: This retrospective study identified 213 patients with TLE who underwent TLR and had histopathological evidence of HS (HS ILAE type 1a = 92; type 1b = 103; type 2 = 18). Patients completed the Wechsler Memory Scale-3rd Edition prior to surgery, and 78% of patients had postoperative scores available. Linear regressions examined differences in preoperative memory scores as a function of pathology classification, controlling for potential confounders. Fisher's exact tests were used to compare pathology subtypes on the magnitude of preoperative memory impairment and the proportion of patients who experienced clinically meaningful postoperative memory decline. RESULTS: Individuals with HS ILAE type 2 demonstrated better preoperative verbal memory performance than patients with HS ILAE type 1; however, individual data revealed verbal and visual episodic memory impairments in many patients with HS ILAE type 2. The base rate of postoperative memory decline was similar among all 3 pathology groups. SIGNIFICANCE: This is the largest reported overall sample and the largest subset of patients with HS ILAE type 2. Group data suggest that patients with HS ILAE type 2 perform better on preoperative memory measures, but individually there were no differences in the magnitude of memory impairment. Following surgery, there were no statistically significant differences between groups in the proportion of patients who declined. Future research should focus on quantitative measurements of hippocampal neuronal loss, and multicenter collaboration is encouraged.

Quantitative positron emission tomography-guided magnetic resonance imaging postprocessing in magnetic resonance imaging-negative epilepsies.

OBJECTIVE: Detection of focal cortical dysplasia (FCD) is of paramount importance in epilepsy presurgical evaluation. Our study aims at utilizing quantitative positron emission tomography (QPET) analysis to complement magnetic resonance imaging (MRI) postprocessing by a morphometric analysis program (MAP) to facilitate automated identification of subtle FCD. METHODS: We retrospectively included a consecutive cohort of surgical patients who had a negative preoperative MRI by radiology report. MAP was performed on T1-weighted volumetric sequence and QPET was performed on PET/computed tomographic data, both with comparison to scanner-specific normal databases. Concordance between MAP and QPET was assessed at a lobar level, and the significance of concordant QPET-MAP+ abnormalities was confirmed by postresective seizure outcome and histopathology. QPET thresholds of standard deviations (SDs) of -1, -2, -3, and -4 were evaluated to identify the optimal threshold for QPET-MAP analysis. RESULTS: A total of 104 patients were included. When QPET thresholds of SD = -1, -2, and -3 were used, complete resection of the QPET-MAP+ region was significantly associated with seizure-free outcome when compared with the partial resection group (P = 0.023, P < 0.001, P = 0.006) or the no resection group (P = 0.002, P < 0.001, P = 0.001). The SD threshold of -2 showed the best combination of positive rate (55%), sensitivity (0.68), specificity (0.88), positive predictive value (0.88), and negative predictive value (0.69). Surgical pathology of the resected QPET-MAP+ areas revealed mainly FCD type I. Multiple QPET-MAP+ regions were present in 12% of the patients at SD = -2. SIGNIFICANCE: Our study demonstrates a practical and effective approach to combine quantitative analyses of functional (QPET) and structural (MAP) imaging data to improve identification of subtle epileptic abnormalities. This approach can be readily adopted by epilepsy centers to improve postresective seizure outcomes for patients without apparent lesions on MRI.

Expression of LC3B and FIP200/Atg17 in brain metastases of breast cancer.

BACKGROUND: Macroautophagy/autophagy is considered to play key roles in tumor cell evasion of therapy and establishment of metastases in breast cancer. High expression of LC3, a residual autophagy marker, in primary breast tumors has been associated with metastatic disease and poor outcome. FIP200/Atg17, a multi-functional pro-survival molecule required for autophagy, has been implicated in brain metastases in experimental models. However, expression of these proteins has not been examined in brain metastases from patients with breast cancer. METHODS: In this retrospective study, specimens from 44 patients with brain metastases of infiltrating ductal carcinoma of the breast (IDC), unpaired samples from 52 patients with primary IDC (primary-BC) and 16 matched-paired samples were analyzed for LC3 puncta, expression of FIP200/Atg17, and p62 staining. RESULTS: LC3-puncta+ tumor cells and FIP200/Atg17 expression were detected in greater than 90% of brain metastases but there were considerable intra- and inter-tumor differences in expression levels. High numbers of LC3-puncta+ tumor cells in brain metastases correlated with a significantly shorter survival time in triple-negative breast cancer. FIP200/Atg17 protein levels were significantly higher in metastases that subsequently recurred following therapy. The percentages of LC3 puncta+ tumor cells and FIP200/Atg17 protein expression levels, but not mRNA levels, were significantly higher in metastases than primary-BC. Meta-analysis of gene expression datasets revealed a significant correlation between higher FIP200(RB1CC1)/Atg17 mRNA levels in primary-BC tumors and shorter disease-free survival. CONCLUSIONS: These results support assessments of precision medicine-guided targeting of autophagy in treatment of brain metastases in breast cancer patients.

TSH-STAINING PITUITARY ADENOMAS: RARE, SILENT, AND PLURIHOROMONAL.

OBJECTIVE: To characterize a single referral center experience with thyroid-stimulating hormone (TSH)-staining adenomas. METHODS: A retrospective chart review was conducted on histopathologic-proven TSH-staining adenomas resected between 2000-2015 at a single center. Tumors were classified as functional (hormonally active) or silent (hormonally inactive). Categorical variables were summarized using counts (n) and percentages; continuous variables were summarized using medians and ranges. RESULTS: From the 1,065 pituitary adenomas operated, 32 (3.0%) showed diffuse staining for TSH. Median (range) age of patients was 49 years (20 to 77 years), and 21 (66%) were male. Tumor diameter was 20 mm (2 to 37 mm), with 7 (22%) microadenomas and 25 (78%) macroadenomas. Functional tumors (n = 5, 16%) had median diameter of 10 mm (5 to 21 mm) (2 microadenomas). At diagnosis, median (range) TSH was 4.3 µU/mL (1.2 to 6.9 µU/mL), and free thyroxine (FT4) was 2.4 ng/dL (2.1 to 3.4 ng/dL). Three tumors stained for TSH alone, and 2 tumors costained with growth hormone (GH). No cavernous sinus invasion was seen, and 3 (60%) were considered cured after surgery. Silent tumors (n = 27, 84%) had median diameter of 20 mm (2 to 37 mm), with 5 (19%) microadenomas and 22 (81%) macroadenomas. Median (range) TSH was 1.2 µU/mL (0.48 to 4.6 µU/mL), and FT4 was 1.2 ng/dL (0.6 to 1.6). Only 2 (7.4%) tumors stained for TSH alone; the rest were plurihormonal, with GH being the most common. Cavernous sinus invasion was seen in 7 (27%) of the tumors, and 17 (63%) were considered surgically cured. CONCLUSION: In our series, 22% of TSH-staining adenomas were microadenomas, and 84% were silent. Most TSH-staining adenomas were plurihormonal, particularly costaining with GH. ABBREVIATIONS: αSU = alpha-subunit; ACTH = adrenocorticotropic hormone; FSH = follicle-stimulating hormone; FT3 = free triiodothyronine; FT4 = free thyroxine; GH = growth hormone; LH = luteinizing hormone; MRI = magnetic resonance imaging; PRL = prolactin; T4 = thyroxine; TSH = thyroid-stimulating hormone.

Accuracy of frozen section in determining meningioma subtype and grade.

Frozen section intraoperative consultation is a well-established means of evaluating brain tumors at the time of surgery. Limitations to the procedure are also well recognized resulting in less than perfect specificity of diagnosis. This study retrospectively reviewed 424 consecutive meningioma cases (N = 310 females; mean age 57.3 years) to examine concordance between frozen section evaluation of meningioma subtype and grade as compared with the final diagnosis subtype and grade. A discrepancy between frozen section diagnosis and final diagnosis was observed in 114 (26.9%) of cases. Of the WHO grade I subtypes, the most common discrepancy involved transitional meningiomas (N = 31) which were most commonly diagnosed at frozen section as either fibrous (N = 18) or meningothelial (N = 13) meningiomas. None of the grade I tumors were diagnosed as higher grade lesions. Of the higher grade meningiomas (WHO grade II and III) (N = 145) reviewed, concordance between tumor type and grade was seen in only 26.2% of cases; most commonly, 73/98 atypical meningiomas were under-graded as some subtype of WHO grade I meningioma (71/73 cases). In conclusion, discrepancies at frozen section with respect to accurately identifying higher grade meningiomas and higher grade meningioma subtypes are common and are generally due to tumor sampling and heterogeneity.

Pathology resident perspectives about early autopsy experiences.

The performance of autopsies remains an integral part of residency training in Anatomic Pathology. A number of medical schools no longer require an autopsy experience; therefore, a subset of pathology residents has never seen an autopsy performed prior to commencement of residency training. Although much as been written regarding student's perspectives on their medical school anatomy experiences, practically nothing has been written about resident perspectives on the autopsy experience. Surveys were sent to all Pathology resident trainees (n = 27) in a training program exploring resident perspectives on their early autopsy experiences. Of the 13 residents who completed the survey, ten indicated a discomfort level of 3 or 4 (Likert scale of 1-5 with 1 = no discomfort and 5 = very uncomfortable) associated with their first autopsy; the most commonly cited reasons included discomfort with odors/body fluids (n = 6), fear of making a mistake (n = 5), and uncertainty about what to do (n = 4). Six residents felt it would be worthwhile to engage in a discussion around the first autopsy experience to help process it. In summary, a subset of residents experience discomfort around their first autopsy experience. Sensitivity to and acknowledgement of this discomfort and an opportunity to vet feelings and concerns should be considered as part of Pathology residency education.

Neurosarcoidosis Flare with Multifocal Restricted Diffusion: Stroke, Inflammation, or Both?

Sarcoidosis is a multisystem granulomatous disease that can cause a wide range of neurologic symptoms. Leptomeningeal enhancement is frequently described but reports of stroke-like symptoms or the appearance of ischemia on magnetic resonance imaging are rare. We present a case of a patient with both leptomeningeal enhancement and multifocal restricted diffusion in a patient with sarcoidosis.

Longitudinal experience with WHO Grade III (anaplastic) meningiomas at a single institution.

To retrospectively analyze and assess the outcomes and prognostic factors in patients with anaplastic meningioma (AM) (WHO Grade III). Clinical data and outcome [overall (OS) and progression-free (PFS) survival] from 18 patients with Grade III meningioma (AM, based on World Health Organization 2016 definition) initially treated between March 2000 and June 2015 were analyzed. Eleven patients (61%) were male, median age at diagnosis was 63 (range 48-86), and 55% (10/18 patients) had good performance status (KPS ≥ 80). Eight patients (45%) had lower grade disease (Grade I-n = 2; Grade II-n = 6) prior to being upgraded to AM. Ten patients had fractionated radiation after primary surgery, eight patients had salvage fractionated RT, stereotactic radiosurgery (SRS) boost along with primary RT in 1 patient, and salvage SRS to 18 separate areas in 14 patients. Salvage chemotherapy was mainly considered in third or fourth recurrences. 13 (72%) patients recurred and 10 (56%) have died. Median PFS was 14.5 months (95% CI 6.9-22.2). The 5-year survival rate was 40 ± 15% and median OS was 55.8 months (95% CI 27.7-80.3). Of all factors examined, only Karnofsky performance status (KPS) affected outcome (PFS p = 0.0003; OS p = 0.0003). With median OS of 55 months (4.6 years) our results are consistent with existing reports of the poor outcomes for AM patients. From the available data, surgical resection followed by RT and salvage radiosurgery and/or chemotherapy can lead to extended survival; however the benefit may decrease with successive treatments.