Use of molecular testing results to analyze the overuse of atypia of undetermined significance in thyroid cytology.

INTRODUCTION: The suggested atypia of undetermined significance (AUS) rate for thyroid fine-needle aspiration biopsies is 10% or less. Prompted by a high institutional AUS rate, we examined using molecular testing results (MTR) as a potential quality metric tool to reduce the AUS rate. We correlated MTR with AUS cytologic findings, surgical pathology follow-up, and individual pathologist AUS rates. MATERIALS AND METHODS: Demographic data, cytologic diagnoses, MTR, and surgical pathology diagnoses were retrospectively obtained. MTR were classified as either positive or negative. AUS rates and MTR proportions were compared among pathologists. The cytomorphologic features of 143 AUS cases were assessed and correlated with MTR. RESULTS: Between 2017 and 2022, 710 of 3247 thyroid fine-needle aspirations were classified as AUS, with a yearly average rate of 22% (range = 19%-26%). AUS cases included: 331 (47%) with architectural atypia; 204 (29%) with oncocytic (Hürthle cell) atypia; 99 (14%) with combined architectural and cytologic atypia; and 76 (10%) with isolated cytologic atypia. Most AUS cases with molecular testing had negative MTR (360/492, 73%). AUS with cytologic atypia had higher positive MTR risk (logarithm of odds ratio = 1.27, 95% credible interval [0.5-2.04], P = 0.001). The average positive MTR rate by pathologist was 21.5% (range 0%-35%); higher positive MTR rates had better correlation with subsequent neoplastic/malignant histologic diagnoses. The MTR sensitivity for malignant disease was 89% and the negative predictive value was 91%. CONCLUSIONS: MTR analysis reveals the importance of cytologic atypia as a determinant of malignancy risk in AUS cases. Periodic analysis of MTR data alongside individual pathologist AUS rates can help refine diagnostic criteria and potentially reduce AUS overuse.

Large-scale validation study of an improved semiautonomous urine cytology assessment tool: AutoParis-X.

BACKGROUND: Adopting a computational approach for the assessment of urine cytology specimens has the potential to improve the efficiency, accuracy, and reliability of bladder cancer screening, which has heretofore relied on semisubjective manual assessment methods. As rigorous, quantitative criteria and guidelines have been introduced for improving screening practices (e.g., The Paris System for Reporting Urinary Cytology), algorithms to emulate semiautonomous diagnostic decision-making have lagged behind, in part because of the complex and nuanced nature of urine cytology reporting. METHODS: In this study, the authors report on the development and large-scale validation of a deep-learning tool, AutoParis-X, which can facilitate rapid, semiautonomous examination of urine cytology specimens. RESULTS: The results of this large-scale, retrospective validation study indicate that AutoParis-X can accurately determine urothelial cell atypia and aggregate a wide variety of cell-related and cluster-related information across a slide to yield an atypia burden score, which correlates closely with overall specimen atypia and is predictive of Paris system diagnostic categories. Importantly, this approach accounts for challenges associated with the assessment of overlapping cell cluster borders, which improve the ability to predict specimen atypia and accurately estimate the nuclear-to-cytoplasm ratio for cells in these clusters. CONCLUSIONS: The authors developed a publicly available, open-source, interactive web application that features a simple, easy-to-use display for examining urine cytology whole-slide images and determining the level of atypia in specific cells, flagging the most abnormal cells for pathologist review. The accuracy of AutoParis-X (and other semiautomated digital pathology systems) indicates that these technologies are approaching clinical readiness and necessitates full evaluation of these algorithms in head-to-head clinical trials.

Examining longitudinal markers of bladder cancer recurrence through a semiautonomous machine learning system for quantifying specimen atypia from urine cytology.

BACKGROUND: Urine cytology is generally considered the primary approach for screening for recurrence of bladder cancer. However, it is currently unclear how best to use cytological examinations for assessment and early detection of recurrence, beyond identifying a positive finding that requires more invasive methods to confirm recurrence and decide on therapeutic options. Because screening programs are frequent, and can be burdensome, finding quantitative means to reduce this burden for patients, cytopathologists, and urologists is an important endeavor and can improve both the efficiency and reliability of findings. Additionally, identifying ways to risk-stratify patients is crucial for improving quality of life while reducing the risk of future recurrence or progression of the cancer. METHODS: In this study, a computational machine learning tool, AutoParis-X, was leveraged to extract imaging features from urine cytology examinations longitudinally to study the predictive potential of urine cytology for assessing recurrence risk. This study examined how the significance of imaging predictors changes over time before and after surgery to determine which predictors and time periods are most relevant for assessing recurrence risk. RESULTS: Results indicate that imaging predictors extracted using AutoParis-X can predict recurrence as well or better than traditional cytological/histological assessments alone and that the predictiveness of these features is variable across time, with key differences in overall specimen atypia identified immediately before tumor recurrence. CONCLUSIONS: Further research will clarify how computational methods can be effectively used in high-volume screening programs to improve recurrence detection and complement traditional modes of assessment.

Radiation-induced gastrointestinal (GI) syndrome as a function of age.

Previous studies show increased sensitivity of older mice (28-29 months) compared with young adult mice (3 months, possessing a mature immune system) to radiation-induced GI lethality. Age-dependent lethality was associated with higher levels of apoptotic stem cells in small intestinal crypts that correlated with sphingomyelinase activity, a source of pro-apoptotic ceramide. The objective of this study is to determine whether the cycling crypt base columnar cells (CBCs) in aging animals are specifically more sensitive to radiation effects than the CBCs in young adult mice, and to identify factors that contribute to increased radiosensitivity. Mortality induced by subtotal body radiation was assessed at different doses (13 Gy, 14 Gy, and 15 Gy) in young adult mice versus older mice. Each dose was evaluated for the occurrence of lethal GI syndrome. A higher death rate due to radiation-induced GI syndrome was observed in older mice as compared with young adult mice: 30 vs. 0% at 13 Gy, 90 vs. 40% at 14 Gy, and 100 vs. 60% at 15 Gy. Radiation-induced damage to crypts was determined by measuring crypt regeneration (H&E staining, Ki67 expression), CBC biomarkers (lgr5 and ascl2), premature senescence (SA-ß-gal activity), and apoptosis of CBCs. At all three doses, crypt microcolony survival assays showed that the older mice had fewer regenerating crypts at 3.5 days post-radiation treatment. Furthermore, in the older animals, baseline CBCs numbers per circumference were significantly decreased, correlating with an elevated apoptotic index. Analysis of tissue damage showed an increased number of senescent CBCs per crypt circumference in older mice relative to younger mice, where the latter was not significantly affected by radiation treatment. It is concluded that enhanced sensitivity to radiation-induced GI syndrome and higher mortality in older mice can be attributed to a decreased capacity to regenerate crypts, presumably due to increased apoptosis and senescence of CBCs.

Uncovering additional predictors of urothelial carcinoma from voided urothelial cell clusters through a deep learning-based image preprocessing technique.

BACKGROUND: Urine cytology is commonly used as a screening test for high-grade urothelial carcinoma for patients with risk factors or hematuria and is an essential step in longitudinal monitoring of patients with previous bladder cancer history. However, the semisubjective nature of current reporting systems for urine cytology (e.g., The Paris System) can hamper reproducibility. For instance, the incorporation of urothelial cell clusters into the classification schema is still an item of debate and perplexity among expert cytopathologists because several previous works have disputed their diagnostic relevance. METHODS: In this work, an automated preprocessing tool for urothelial cell cluster assessment was developed that divides urothelial cell clusters into meaningful components for downstream assessment (ie, population-based studies, workflow automation). RESULTS: In this work, an automated preprocessing tool for urothelial cell cluster assessment was developed that divides urothelial cell clusters into meaningful components for downstream assessment (ie, population-based studies, workflow automation). Results indicate that cell cluster atypia (i.e., defined by whether the cell cluster harbored multiple atypical cells, thresholded by a minimum number of cells), cell border overlap and smoothness, and total number of clusters are important markers of specimen atypia when considering assessment of urothelial cell clusters. CONCLUSIONS: Markers established through techniques to separate cell clusters may have wider applicability for the design and implementation of machine learning approaches for urine cytology assessment.

Large-scale longitudinal comparison of urine cytological classification systems reveals potential early adoption of The Paris System criteria.

INTRODUCTION: Urine cytology is used to screen for urothelial carcinoma in patients with hematuria or risk factors (eg, smoking, industrial dye exposure) and is an essential clinical triage and longitudinal monitoring tool for patients with known bladder cancer. However, urine cytology is semisubjective and thus susceptible to issues including specimen quality, interobserver variability, and "hedging" towards equivocal ("atypical") diagnoses. These factors limit the predictive value of urine cytology and increase reliance on invasive procedures (cystoscopy). The Paris System for Reporting Urine Cytology (TPS) was formulated to provide more quantitative/reproducible endpoints with well-defined criteria for urothelial atypia. TPS is often compared to other assessment techniques to justify its adoption. TPS results in decreased use of the atypical category and better reproducibility. Previous reports comparing diagnoses pre- and post-TPS have not considered temporal differences between diagnoses made under prior systems and TPS. By aggregating across time, studies may underestimate the magnitude of differences between assessment methods. MATERIALS AND METHODS: We conducted a large-scale longitudinal reassessment of urine cytology using TPS criteria from specimens collected from 2008 to 2018, prior to the mid-2018 adoption of TPS at an academic medical center. RESULTS: Findings indicate that differences in atypical assignment were largest at the start of the period and these differences progressively decreased towards insignificance just prior to TPS implementation. CONCLUSIONS: This finding suggests that cytopathologists had begun to utilize the quantitative TPS criteria prior to official adoption, which may more broadly inform adoption strategies, communication, and understanding for evolving classification systems in cytology.

Using molecular testing to improve the management of thyroid nodules with indeterminate cytology: an institutional experience with review of molecular alterations.

INTRODUCTION: Molecular testing has helped clinicians and cytopathologists to further categorize indeterminate thyroid fine needle aspiration (FNA) specimens. The purpose of the present study was to evaluate the accuracy of commercially available molecular tests, review their effects on patient treatment, and correlate the molecular alterations with the histologic findings. MATERIALS AND METHODS: A pathology laboratory information system search identified thyroid FNAs performed at our institution between January 1, 2015 and June 30, 2020. The results of surgical follow-up and ancillary molecular testing were collected. We evaluated the accuracy of these tests and whether they could reduce the number of surgeries performed. RESULTS: Our laboratory information system search identified 510 cases reported as atypia of undetermined significance, 94 as suspicious for follicular neoplasm, and 44 as suspicious for follicular neoplasm, Hurthle cell type. Of the specimens, 343 had no ancillary molecular testing, 146 were sent for ThyGenX/ThyraMIR, and 136 were sent for ThyroSeq. Of the patients without molecular testing, 50.4% had undergone follow-up surgery compared with 30.8% after ThyGenX/ThyraMIR and 38.2% after ThyroSeq testing, resulting in 38.9% and 24.2% fewer surgeries and an odds ratio of 0.04 (95% confidence interval, 0.00-0.33) and 0.14 (95% confidence interval, 0.01-0.95), respectively. For ThyGenX/ThyraMIR testing, the risk of malignancy for high and moderate to high risk alterations was 80%, 28.6% for moderate and low to moderate risk alterations, and 23.1% for low risk alterations. For ThyroSeq, the risk of malignancy was 87.5% for high risk alterations, 36.8% for intermediate to high risk alterations, 27.3% for intermediate risk alterations, and 0% for low risk alterations. The areas under the curve for ThyGenX/ThyraMIR and ThyroSeq testing were 0.65 and 0.85, respectively. CONCLUSIONS: These findings suggest that, at our institution, both ThygenX/ThyraMIR and ThyroSeq can be used to effectively stratify cytology specimens based on the risk of malignancy and reduce the number of surgeries performed at our institution.

Atypia of undetermined significance in thyroid cytology: Nuclear atypia and architectural atypia are associated with different molecular alterations and risks of malignancy.

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology contains an atypia of undetermined significance (AUS) category with heterogeneous and distinct inclusion criteria. The purpose of this study was to investigate differences in malignancy rates and molecular alterations based on the presence of different criteria. METHODS: A laboratory information search was conducted to identify thyroid fine-needle aspiration specimens signed out as AUS. The cases were reclassified as architectural atypia (3A), cytologic atypia (3C), both architectural and cytologic atypia (3B), or Hürthle cell aspirate (3H). Surgical follow-up and concurrent molecular test results, if available, were collected. RESULTS: Five hundred ten specimens, including 258 reclassified as 3A, 40 reclassified as 3B, 119 reclassified as 3C, and 86 reclassified as 3H, were identified. The risks of malignancy for the subcategories were 13.4%, 26.3%, 44.1%, and 13.8%, respectively. Additionally, BRAF V600E mutations were more prevalent in specimens with cytologic atypia (3B/3C), whereas low-risk alterations, including KRAS, PTEN, and PAX8-PPARy2, were more prevalent in those with architectural atypia (3A). CONCLUSIONS: Subdividing AUS specimens on the basis of the type of atypia can yield categories associated with distinct molecular alterations and risks of malignancy.

Applying the Paris system for reporting urine cytology to challenging cytology cases.

BACKGROUND: Implementing the Paris system for reporting urine cytology (TPS) can substantiate atypical diagnosis while improving standardization and risk stratification. This study evaluates its performance and reproducibility in challenging cases and examines whether focused education of morphological features can improve outcomes. METHODS: In our prior study, urine cytology cases diagnosed as "atypical" with surgical follow-up were used. Cases showing poor agreement in that study were collected for this one. Representative photographs of each case were taken and distributed via online questionnaires. Participants were asked to render an initial diagnosis and evaluate the presence of several morphological features. Educational material was distributed, followed by additional questionnaires. RESULTS: Three participants evaluated 40 cases before and after educational materials. TPS diagnoses were significantly more specific (0.23 vs 0.59, P = 0.004) and more accurate (0.43 vs 0.66, P = 0.0125) than diagnoses made with our institutional system. Fewer overall cases were diagnosed as "atypical" with TPS. TPS education resulted in slightly, though not significantly, more specific diagnoses (0.25 vs 0.59, P = 0.083). Interobserver agreement decreased for nuclear-to-cytoplasmic (N/C) ratio, TPS diagnoses and initial diagnoses, and increased for all other features. TPS resulted in downgrading of cases with biopsy-proven low grade urothelial neoplasm (LGUN) from "atypical" to negative for high grade urothelial carcinoma (NHGUC) (P = 0.018). CONCLUSIONS: Use of TPS in challenging urine cytology cases can improve specificity, risk stratification, and diagnostic accuracy while decreasing the number of "atypical" diagnoses. Though training can help cytopathologists better apply these criteria, it is unclear how to effectively improve evaluation of N/C ratio.

Pazopanib radio-sensitization of human sarcoma tumors.

Recent data in our laboratory indicate that engagement of host-derived microenvironmental elements impact tumor response to single high dose radiation therapy (SDRT). In these studies we showed that microvascular endothelial damage plays a critical role in tumor response as regulator of direct lethal damage of SDRT. Using a genetic model of Acid Sphingomyelinase (ASMase)-deficient mice we showed that activation of this enzyme by SDRT-induced damage in the endothelium is mandatory for tumor cure. ASMase activation triggers ceramide-mediated apoptosis, and therein microvascular dysfunction, which increased the vulnerability of tumor cells to lethal damage by radiation. Angiogenic factors repressed this activity while a monoclonal antibody targeting VEGF, de-repressed ASMase activity and radiosensitized tumor endothelium when delivered immediately prior to SDRT. In this study, we tested the effect of SDRT in combination with the short-acting anti-angiogenic agent, Pazopanib (anti-VEGFR-1/2/3, PDGF-α/ß and c-kit), in two xenograft models of human sarcoma. Pre-treatment with a single dose of Pazopanib increased SDRT-induced ASMase activity and endothelial dysfunction in vitro and in vivo, enhancing SDRT tumor cure, and exhibiting critical dependence on timing relative to SDRT exposure, suggesting a mechanism of action identical to that demonstrated for anti-VEGF/VEGFR2 antibodies. These results demonstrate the ability of Pazopanib to shift the response towards tumor cure and could therefore have a significant impact on clinical trial development in combination with SDRT for sarcoma cancer patients.

Analysis of the Cytomorphological Features in Atypical Urine Specimens following Application of The Paris System for Reporting Urinary Cytology.

BACKGROUND: This study investigates the use of The Paris System (TPS) for Reporting Urinary Cytopathology and examines the performance of individual and combined morphological features in atypical urine cytologies. METHODS: We reviewed 118 atypical cytologies with subsequent bladder biopsies for the presence of several morphological features and reclassified them into Paris System categories. The sensitivity and specificity of individual and combined features were calculated along with the risk of malignancy. RESULTS: An elevated nuclear-to-cytoplasmic ratio was only predictive of malignancy if seen in single cells, while irregular nuclear borders, hyperchromasia, and coarse granular chromatin were predictive in single cells and in groups. Identification of coarse chromatin alone yielded a malignancy risk comparable to 2-feature combinations. The use of TPS criteria identified the specimens at a higher risk of malignancy. CONCLUSION: Our findings support the use of TPS criteria, suggesting that the presence of coarse chromatin is more specific than other individual features, and confirming that cytologic atypia is more worrisome in single cells than in groups.

Utility of intraoperative frozen sections for thyroid nodules with prior fine needle aspiration cytology diagnosis.

INTRODUCTION: The objective of this study was to evaluate the role of intraoperative frozen section (IFS) in determining the course of surgery in thyroid nodules with a prior fine needle aspiration (FNA) biopsy diagnosis. In addition, reliability of FNA interpretation to guide surgical management without IFS was investigated. MATERIAL AND METHODS: This is a retrospective study of all patients who had a FNA biopsy, IFS, and final pathology performed on a thyroid nodule over a 9 month period. The extent of surgery at the time of the IFS was recorded. Subsequent change in surgical procedure following the IFS diagnosis was noted in each of the Bethesda diagnostic categories. RESULTS: 55% of the cases were deferred at IFS overall, with 68 and 86% in Bethesda III and IV categories, respectively. Overall, there was a change in management in 6% of cases. CONCLUSIONS: Our study does not support the use of IFS for nodules with prior FNA interpretation of Bethesda II, III, IV and VI as management was not significantly changed. IFS is of value for nodules with prior FNA diagnosis of Bethesda I for interpretation of nodule, and Bethesda V for planning surgery. A confirmatory diagnosis could not be rendered at IFS for lesions with follicular architecture, which comprised most of the cases in Bethesda III and IV.

Metastatic tonsillar squamous cell carcinoma masquerading as a pancreatic cystic tumor and diagnosed by EUS-guided FNA.

Metastatic carcinoma to the pancreas is uncommon and head and neck squamous carcinoma metastatic to the pancreas is extremely rare. Metastatic squamous cell carcinoma to the pancreas presents a unique diagnostic challenge: in addition to mimicking the rare primary squamous cell carcinoma of the pancreas based on cytologic, histologic, and immunohistochemical features, it may be mistaken for a cystic neoplasm of the pancreas because of its high predilection for cystic degeneration in metastatic sites. Herein, we report a case of tonsillar squamous cell carcinoma with a cystic pancreatic metastasis diagnosed by ultrasound-guided fine needle aspiration biopsy (EUS-FNA). This represents a third reported case of metastatic squamous cell carcinoma to the pancreas from the head and neck region. Metastatic squamous cell carcinoma should be considered in the differential diagnosis of EUS-FNA during evaluation of pancreatic cystic lesion.

The impact of subdividing the "atypical" category for urinary cytology on patient management.

INTRODUCTION: The purpose of the study is to determine the impact of subdividing the "atypical" cytology interpretation into two groups: Atypical urothelial cells of uncertain significance (AUC-US) and Atypical urothelial cells suspicious for high-grade urothelial carcinoma (AUC-H/SHGUC), on management of patients with no prior history of UC. MATERIALS AND METHOD: This is a retrospective study of "atypical" urine cytology with subsequent tissue examination occurring within six months. Cytology reports with "atypical" interpretation were reclassified into AUS-UC and AUC-H based on morphologic features identified by the Johns Hopkins system and the Paris system for urine cytology. Follow-up and categorical outcomes were compared between the reclassified AUC-US and AUC-H groups. RESULTS: There was no significant difference (P < 0.4539) in the rate of cytology follow-up, the follow-up cytology result (P < 0.1845), or time between follow-up cytologies (P < 0.0869) between the reclassified atypical group of AUC-H and AUC-US. There was a significant association (P < 0.0001) of rate of malignancy with the reclassified AUC-H (87.18%) compared to the AUC-US (58.68%) groups. CONCLUSION: There was no difference in follow-up between the AUC-H and AUC-US, however there was a difference in the rates of malignancy in the two groups. The AUC-H group is similar to the SHGUC group of the Paris system and can be considered as such, whereas the AUC-US group should continue to be considered atypical. We conclude that reclassification of the "atypical" category into AUC-US and AUC-H/SHGUC can reduce the rate of atypia and help in focused follow-up and targeted management. Diagn. Cytopathol. 2016;44:477-482. © 2016 Wiley Periodicals, Inc.

Two-tiered subdivision of atypia on urine cytology can improve patient follow-up and optimize the utility of UroVysion.

BACKGROUND: The annual incidence of urothelial carcinoma continues to increase, and it is projected that greater than 70,000 new cases will occur in the year 2015. However, as much as 23% of cytologic specimens will demonstrate some degree of atypia without meeting the criteria for urothelial carcinoma and thus will be reported as atypical. METHODS: The authors conducted 2 laboratory information searches and 1 survey. In total, 311 patients who had atypical cytology-biopsy pairs available were identified from the initial data search. The second data search identified 942 patients who had fluorescence in situ hybridization (FISH) results available. RESULTS: There was fair agreement between FISH results and cytology results (κ = 0.34; 95% confidence interval, 0.27-0.41). The analysis did not reveal any benefits of using additional atypical subcategories beyond the 2 suggested in the literature. It was determined that 2 strategies would provide an optimal balance: standardizing patient management and facilitating the adoption of universally recognized templates. CONCLUSIONS: When combining cytology and the 2-tiered atypical classification system with FISH testing, a marked increase in sensitivity and an accompanying decrease in specificity were observed compared with either test individually. Thus, highly sensitive FISH testing may help to identify high-risk patients among those in the group with uncertain atypical findings.

Predicting histological subtypes of follicular variant of papillary thyroid carcinoma based on cytomorphology. Can cytomorphology optimize use of molecular testing?

INTRODUCTION: Follicular variant papillary thyroid carcinoma (FVPTC) can be further subclassified into one of 3 subtypes: non-invasive encapsulated FVPTC, invasive encapsulated FVPTC, and infiltrative FVPTC. Longitudinal and molecular studies have demonstrated that, in terms of both molecular profiles and prognosis, encapsulated FVPTC is comparable to follicular adenoma, invasive FVPTC to follicular carcinoma, and infiltrative FVPTC to classic PTC. To improve triaging and prevent overtreatment of patients with FVPTC, we sought to determine cytologic features likely to occur within each subtype. METHODS: A laboratory database search from 2010-2015 was conducted to identify patients with biopsy-proven FVPTC and prior fine-needle aspiration. Surgical specimens were reviewed to determine the appropriate subcategorization. Accompanying cytology reports were reviewed for features common in classic PTC and follicular neoplasms. RESULTS: Encapsulated variants were more likely to be graded as Bethesda category 4 compared with invasive or infiltrative variants. In contrast, infiltrative variants were more likely to be graded as Bethesda categories 5 and 6 compared with invasive or encapsulated variants. Compared with the encapsulated variant, infiltrative FVPTC was more likely to have nuclear pseudo-inclusions (31.82% versus 8.11%, P = 0.0468) and less likely to have microfollicular architecture (22.73% versus 54.05%, P = 0.0374). CONCLUSION: This study identified cytomorphologic differences between encapsulated and infiltrative FVPTC. With a higher threshold of suspicion for FVPTC, improved awareness of the differences between these subtypes and incorporation of molecular testing, it is likely that the Bethesda category can be revised and patient triaging can be significantly improved.

Beta-human chorionic gonadotropin producing osteosarcoma of the sacrum in a 26-year-old woman: a case report and review of the literature.

Ectopic secretion of beta-human chorionic gonadotropin is considered a poor prognostic marker in epithelial tumors. However, very few cases have been reported in sarcomas. We present the case of a 26-year-old female who presented with a metastatic osteosarcoma. She underwent usual testing prior to starting treatment and was found to have elevated levels of beta-human chorionic gonadotropin. As the patient was not pregnant, another source of beta-human chorionic gonadotropin secretion had to be considered. The tumor cells demonstrated positive staining for beta-human chorionic gonadotropin by immunohistochemistry, and serum levels of beta-human chorionic gonadotropin were used to monitor tumor progression and response to chemotherapy. We review the literature and discuss a potential role of beta-human chorionic gonadotropin in the treatment of such patients.

Metastasis of lung adenosquamous carcinoma to meningioma: case report with literature review.

The occurrence of metastasis of a systemic neoplasm to an intracranial tumor is a rare phenomenon. Meningiomas have been reported as the most common intracranial tumor to harbor a systemic metastasis, with breast and lung carcinomas being the most common sites of origination. Here, we report a case of an adenocarcinoma metastasis of an adenosquamous lung carcinoma found within a meningioma, resulting in the patient's first clinical manifestations. We also review the literature for other cases of adenocarcinoma metastatic to a meningioma and suggest mechanisms that make meningiomas likely to harbor systemic metastases including increased vascularity, slow growth rate, increased hyaline content and expression of cell-cell adhesion molecules.