Extraneural metastases of primary central nervous system tumors identified by fine needle aspiration: a retrospective analysis.

OBJECTIVE: Extraneural metastasis (EM) of primary central nervous system (PCNS) neoplasms is rare and signifies a poor clinical outcome. Due to its infrequent occurrence, relatively few reports on the cytomorphology of these neoplasms have been published. We describe a series of 19 cases from 16 patients at a single, large tertiary care center. STUDY DESIGN: A retrospective analysis of 19 cases of metastases from PCNS neoplasms identified on fine needle aspiration (FNA) in 8 male and 8 female patients aged 14-72 years (mean age 39.6) from 1989 to 2013 was conducted to further characterize the cytomorphologic features identified at metastatic sites. RESULTS: Six different PCNS neoplasms were identified: meningioma, glioblastoma, hemangiopericytoma (HPC), oligodendroglioma, medulloblastoma, and retinoblastoma. The mean latency period between the diagnoses of the primary and first metastatic tumors was 7.4 years (range 0-15). The most common PCNS malignancy responsible for EM was HPC. The most common metastatic sites were the lung (31%) and soft tissue/bone (31%). CONCLUSIONS: EM of PCNS tumors is extremely rare. FNA allows for quick, safe and accurate diagnosis. Cytomorphologic features are characteristic, and in conjunction with the clinical history and immunohistochemistry, an accurate diagnosis was obtained in 100% of the cases.

CD3 in Lewy pathology: does the abnormal recall of neurodevelopmental processes underlie Parkinson's disease.

CD3ζ is a subunit of the CD3 molecule that, until recently, appeared restricted to T cells and natural killer cells. However, experimental studies have demonstrated a role of CD3ζ in dendritic outgrowth in the visual system as well as in synaptic plasticity. Given the increasing evidence for uncharacteristic recapitulation of neurodevelopmental processes in neurodegenerative diseases, in this study, we evaluated brains from subjects with Parkinson's disease and Lewy body dementia for evidence of aberrant CD3 expression. Our data shows marked CD3ζ in association with the α-synuclein containing pathological lesions, i.e., Lewy bodies and Lewy neurites, in the brains of subjects with Parkinson's disease and Lewy body dementia. This finding raises the novel concept of CD3 dysregulation in these disorders as a pathogenic factor and also furthers the increasing evidence that the recall of aberrant neurodevelopmental processes underlies the pathogenesis of neurodegenerative diseases.

Pulmonary Pathology of COVID-19 Following 8 Weeks to 4 Months of Severe Disease: A Report of Three Cases, Including One With Bilateral Lung Transplantation.

OBJECTIVES: Current knowledge of the pulmonary pathology of coronavirus disease 2019 (COVID-19) is based largely on postmortem studies. In most, the interval between disease onset and death is relatively short (<1 month). Information regarding lung pathology in patients who survive for longer periods is scant. We describe the pathology in three patients with severe COVID-19 who underwent antemortem examination of lung tissue at least 8 weeks after initial diagnosis. METHODS: We conducted a retrospective case series. RESULTS: The first patient developed acute respiratory failure and was started on extracorporeal membrane oxygenation (ECMO) on day 21, with subsequent hemothorax. Debridement (day 38) showed extensive lung infarction with diffuse alveolar damage and Candida overgrowth. The second patient developed acute respiratory failure requiring mechanical ventilation that did not improve despite ECMO. Surgical lung biopsy on day 74 showed diffuse interstitial fibrosis with focal microscopic honeycomb change. The third patient also required ECMO and underwent bilateral lung transplantation on day 126. The explanted lungs showed diffuse interstitial fibrosis with focal microscopic honeycomb change. CONCLUSIONS: This series provides histologic confirmation that complications of COVID-19 after 8 weeks to 4 months of severe disease include lung infarction and diffuse interstitial fibrosis.

Ganglioneuroma presenting as a paraesophageal mass lesion diagnosed by endoscopic ultrasound-guided fine needle aspiration cytology: a case report.

BACKGROUND: Endoscopic ultrasound-guided fine needle aspiration is a well-established modality in detection and diagnosis of mediastinal lesions. Ganglioneuroma is a benign, rare, soft tissue neoplasm arising from sympathetic ganglion cells, and complete surgical resection is considered to be curative. Ganglioneuroma in a surgical specimen is a straightforward diagnosis; however, due to the infrequent occurrence of this entity, diagnosis by fine needle aspiration is more challenging. CASE: A case of paraesophageal ganglioneuroma was diagnosed by endoscopic ultrasound-guided fine needle aspiration. A 75-year-old man with a history of adenocarcinoma of the lung was noted to have a mediastinal mass on chest computed tomography. Upper endosonography identified a 40x17-mm mass extrinsic to the thoracic esophagus. An endoscopic ultrasound-guided fine needle aspiration of the mass revealed intermingled fragments of spindle cells and ganglion cells admixed within a fibromyxoid stroma. Immunohistochemistry showed that both the spindle and ganglion cell components were positive for S-100 protein and negative for pancytokeratin. This immunohistochemical profile established both the neurogenic origin of the spindle and ganglion cells. CONCLUSION: Our case represents 1 of the few reported cases of ganglioneuroma diagnosed by fine needle aspiration cytology and the second case diagnosed under endoscopic ultrasound guidance.

Clear cell sarcoma of soft tissue metastatic to the ovaries: a heretofore unreported occurrence.

Clear cell sarcoma of soft tissue (CCSST) is a rare soft tissue neoplasm with marked variable tumor progression and prognosis. Although morphologically similar to malignant melanoma, CCSST can be distinguished by the presence of a t(12; 22)(q13; q12) and/or associated EWSR1-ATF1 chimeric gene. CCSST has an affinity for the extremities and is capable of metastasizing to a wide variety of sites including bone, lung, and lymph nodes and rarely to skin, liver, heart, muscle, and brain. Metastases have been known to occur as late as 29 years after initial presentation. We report a case of a 33-year-old woman who presented with bilateral ovarian cystic tumors, ascites, and pulmonary nodules. Her past medical history was significant for clear cell sarcoma of the left foot 2 years earlier. Bilateral salpingo-oophorectomy was performed and the light microscopic and immunohistochemical findings coupled with the detection of an EWSR1 rearrangement by fluorescence in situ hybridization were compatible with a diagnosis of CCSST metastases to the ovaries. To the best of our knowledge, this is the first reported case of CCSST metastatic to the ovaries.

Metastatic merkel cell carcinoma of the pancreas mimicking primary pancreatic endocrine tumor diagnosed by endoscopic ultrasound-guided fine needle aspiration cytology: a case report.

BACKGROUND: Merkel cell carcinoma (MCC) is a relatively infrequent, rapidly progressive and often fatal cutaneous malignancy exhibiting neuroendocrine differentiation. It has a penchant for local recurrence and distant metastasis to various sites, including regional lymph nodes, distant skin, lung, liver, testis and other rare organs, such as the pancreas. There are only 4 cases of MCC metastatic to the pancreas reported in the English-language literature, and they were all diagnosed by histology from pancreatic resection. CASE: A 79-year-old woman with a large pancreatic tail mass underwent endoscopic ultrasound guided fine needle aspiration (EUS-FNA). She had a history of MCC of the upper extremity with wide local excision 15 months earlier. Metastatic MCC was diagnosed based on the cytomorphology, characteristic immunohistochemical staining pattern, clinical history and comparison of the morphology with that of the primary tumor. CONCLUSION: The cytomorphology and immunohistochemical profile of this neoplasm mimicked a pancreatic endocrine tumor. We discuss the diagnostic pitfalls and differential diagnoses of the metastatic pancreatic MCC, highlighting the importance of thorough clinical history, attention to cytologic detail and corroborating immunohirtochemistry in arriving at the correct diagns. This is the first case ofa metastatic pancreatic MCC diagnosed by EUS-FNA cytology.

Orbitofrontal lesions in rats impair reversal but not acquisition of go, no-go odor discriminations.

Recent evidence suggests that orbitofrontal cortex lesions cause an inability to withhold inappropriate responses particularly when learned behavior must be modified to reflect changes in the likely outcome or consequence of responding. By this account, orbitofrontal cortex should not be necessary for acquisition of simple discrimination problems, but should be critical for acquiring reversals of those problems. However, previous work in rats has shown orbitofrontal cortex to be critical for withholding responses even in a simple go, no-go discrimination task. Here we have reexamined the contribution of rat orbitofrontal cortex to acquisition and reversal of go, no-go odor discrimination problems. Contrary to prior reports, we found that rats with lesions of the orbitofrontal cortex acquired novel discrimination problems at the same rate as controls. Impairments were evident in lesioned rats when the response contingencies of the odors in the discrimination problem were reversed. These findings suggest that orbitofrontal cortex is not necessary for inhibiting responses unless responses must be altered to reflect changing relationships between cues and outcomes.

Thyroglobulin measurements in fine-needle aspiration cytology of lymph nodes for the detection of metastatic papillary thyroid carcinoma.

BACKGROUND: Ultrasound-guided fine-needle aspiration (US-FNA) cytology is a commonly used method in the surveillance of suspicious lymph nodes (LNs) in patients with papillary thyroid carcinoma (PTC). The measurement of thyroglobulin (Tg) levels in LNs during FNA has been suggested to improve the diagnosis. In the current study, the use of US-FNA-Tg in LNs that were suspicious for metastatic PTC was investigated. METHODS: A total of 208 cases from the Johns Hopkins Hospital with both US-guided FNA cytology and US-FNA-Tg measurements were included; 60 cases had follow-up surgeries performed. Tg levels were correlated with cytological and histological diagnoses. RESULTS: Of 35 cases of cytologically diagnosed metastatic PTC, 34 were confirmed by surgery. The median US-FNA-Tg concentration was 4232.7 ng/mL, whereas in 112 benign LNs the median Tg concentration was < 0.2 ng/mL (P < .0001). Receiver operating characteristic analysis (area under the curve, 0.949) demonstrated a sensitivity of 97% and a specificity of 81% at the Tg detection limit (<0.2 ng/mL), whereas cutoff values of 9.6 ng/mL to 100 ng/mL resulted in a sensitivity of 76% and a specificity of 98%. Of 15 cases with a cytological diagnosis of "suspicious for PTC," 9 cases had markedly elevated Tg levels detected on FNA. Seven of these 9 cases had follow-up surgeries confirming the diagnosis of PTC. Of 29 cases with a "nondiagnostic" cytology, 7 had markedly elevated Tg levels on FNA, with a median of 1305.5 ng/mL, and were confirmed to be metastatic PTC at surgery. CONCLUSIONS: US-FNA-Tg demonstrated a strong negative predictive value (93%-99%). It may be particularly useful for difficult cases. However, standardization of the sample collection is still needed to further improve the accuracy of the approach.

Composite signet-ring cell/neuroendocrine carcinoma of the stomach with a metastatic neuroendocrine carcinoma component: a better prognosis entity.

BACKGROUND: Mixed (composite) exocrine-neuroendocrine cell carcinomas are defined as an intimate admixture of neoplastic glandular exocrine and neuroendocrine cell types. Although gastric adenocarcinoma containing a small number of neuroendocrine cells is a relatively frequent occurrence, gastric neoplasms containing equal proportions of both cell types are rare. CASE PRESENTATION: We present a case of composite exocrine (signet-ring cell)-neuroendocrine cell carcinoma, in which the neoplastic signet-ring cell exocrine and neuroendocrine constituents occurred in fairly equivalent amounts, whereas only the neuroendocrine carcinoma portion of the tumor represented the metastatic component. Light microscopy, immunohistochemical and electron microscopic findings are described, and the literature is reviewed. CONCLUSION: This study confirms the ability of pluripotent precursor cells to differentiate into either adenocarcinoma or neuroendocrine tumor and, justifying the designation of composite exocrine-neuroendocrine cell carcinoma as the appropriate classification for this tumor. The protracted clinical course further supports the notion that composite signet-ring cell/neuroendocrine carcinoma tumors behave relatively less aggressively than the pure forms of the former cell type.

Lesions of orbitofrontal cortex and basolateral amygdala complex disrupt acquisition of odor-guided discriminations and reversals.

Recent work indicates that both orbitofrontal cortex (OFC) and the basolateral complex of the amygdala (ABL) are involved in processes by which cues are associated with predicted outcomes. To examine the respective roles of these structures in discrimination learning, rats with bilateral sham or neurotoxic lesions of either OFC or ABL were trained on a series of four 2-odor discrimination problems in a thirst-motivated go, no-go task. After acquisition of the series of odor problems, the rats were trained on serial reversals of the final odor problem. Performance on each problem was assessed by monitoring accuracy of choice behavior, and also by measuring latency to respond for fluid outcomes after odor sampling. During discrimination learning, rats in both lesioned groups had similar deficits, failing to show normal changes in response latency during learning, while at the same time exhibiting normal choice behavior relative to controls. Choice behavior was affected only during the reversal phase of training, in which OFC and ABL lesions produced distinctive deficits. Rats with ABL lesions were impaired on the first reversal (S1-/S2+), but were unimpaired at acquiring a reversal back to the original odor-outcome contigencies (S1+/S2-), whereas rats with OFC lesions were impaired on both types of reversals. These findings suggest that OFC and ABL serve partially overlapping roles in the use of incentive information that supports normal discrimination performance.