Firearm Ownership: A Key Factor to Consider in Firearm Suicide Deaths in Children, Despite State Gun Laws.

INTRODUCTION: Firearm-related suicides among children present a significant public health concern and a tragic loss of young lives. This study explores the relationship between firearm-related suicides, gun ownership, and state-specific gun laws. METHODS: This retrospective cohort study collected data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research on children under 18 who died by firearm-related suicides between 2009 and 2016 in all 50 states and D.C. It also utilized data from the RAND State-Level Estimates of Household Firearm Ownership. The study focused on the rate of child firearm suicide deaths per 100,000 individuals. The key variable of interest was the percentage of guns owned per household in each state. Univariable analysis was conducted to examine the association between individual gun laws and child firearm suicide mortalities, while multivariable regression, adjusting for household gun ownership and significant firearm legislation, was employed to assess connection to child firearm suicide mortality. RESULTS: From 2009 to 2016, 3903 children died from firearm-related suicides in the United States. In our analysis, 15 out of 44 firearm laws were found to be associated with reducing the rates of firearm suicides among children (P < 0.05). However, multivariable regression showed that higher state gun ownership rates were the primary predictor of increased child fatalities from firearms, with children in such states being 325% more likely to die when analyzing handgun laws and 337% more likely when analyzing long gun laws, as indicated by coefficients of 4.25 and 4.37, respectively. No state laws alone notably improved death rates. CONCLUSIONS: Gun ownership has a stronger association with child suicide rates than state-specific gun laws. Given the weight of gun ownership, future research should prioritize comprehensive public health initiatives to prevent child firearm-related suicides.

Systematic Literature Review of Health-Related Quality-of-Life Measures for Caregivers of Older Adult Trauma Patients.

INTRODUCTION: As the older adult population increases, hospitals treat more older adults with injuries. After leaving, these patients suffer from decreased mobility and independence, relying on care from others. Family members often assume this responsibility, mostly informally and unpaid. Caregivers of other older adult populations have increased stress and decreased caregiver-related quality of life (CRQoL). Validated CRQoL measures are essential to capture their unique experiences. Our objective was to review existing CRQoL measures and their validity in caregivers of older adult trauma patients. METHODS: A professional librarian searched published literature from the inception of databases through August 12, 2022 in MEDLINE (via PubMed), Embase (via Elsevier), and CINAHL Complete (via EBSCO). We identified 1063 unique studies of CRQoL in caregivers for adults with injury and performed a systematic review following COnsensus-based Standards for the selection of health Measurement Instruments guidelines for CRQoL measures. RESULTS: From the 66 studies included, we identified 54 health-related quality-of-life measures and 60 domains capturing caregiver-centered concerns. The majority (83%) of measures included six or fewer CRQoL content domains. Six measures were used in caregivers of older adults with single-system injuries. There were no validated CRQoL measures among caregivers of older adult trauma patients with multisystem injuries. CONCLUSIONS: While many measures exist to assess healthcare-related quality of life, few, if any, adequately assess concerns among caregivers of older adult trauma patients. We found that CRQoL domains, including mental health, emotional health, social functioning, and relationships, are most commonly assessed among caregivers. Future measures should focus on reliability and validity in this specific population to guide interventions.

Clinico-pathological and molecular characterization of diffuse midline gliomas: is there a prognostic significance?

PURPOSE: H3K27M mutant diffuse midline gliomas (DMGs) are considered grade IV irrespective of histological features and have dismal prognosis. We evaluated clinico-pathologic, radiological, and molecular characteristics of DMGs across all ages. METHODS: One twenty-six DMGs were identified over 10 years. Immunohistochemistry was done for H3K27M, ATRX, IDH1, and p53, and Sanger sequencing performed for IDH1 and H3K27M mutation. Patient demographics and clinico-radiologic characteristics were reviewed and survival analysis performed. RESULTS: DMGs comprised 5.3% of all gliomas with 49.2% H3K27M mutant and 50.8% wild types. Majority (75.68%) of pediatric and 38.20% of adults were H3K27M mutant (p = 0.0001). Amongst H3K27M mutants, brainstem (46.43%) was the commonest location in pediatric and thalamus (61.76%) in adults. H3K27M mutation was mutually exclusive with IDH mutation in 93.55%, while p53, ATRX mutation were seen in 56.4% and 30.6% cases respectively. Software-based immunohistochemistry evaluation (H-scoring) showed 99.2% concordance with sequencing for H3K27M mutation. Radiologically, no significant difference in contrast enhancement was seen between mutant and wild types (p = 0.05). The difference in overall survival (OS) was not significant in mutant versus wild types, with age or location. Tumor resection independently and on correlation with H3K27M did not influence OS (p = 0.51 and p = 0.47). Adjuvant therapy impacted survival significantly in adults (p = 0.0009), however, not in pediatric cases (p = 0.06). CONCLUSIONS: The study highlights the differences in frequency and location of pediatric and adult DMGs. IHC (H-scoring) for H3K27M mutation is an excellent surrogate for sequencing. Prognosis remains dismal irrespective of age, location, and H3K27M status. Potential therapeutic targets need to be explored.

Approach to molecular subgrouping of medulloblastomas: Comparison of NanoString nCounter assay versus combination of immunohistochemistry and fluorescence in-situ hybridization in resource constrained centres.

INTRODUCTION: Molecular classification of medulloblastomas (MB) is prognostically and therapeutically relevant and helps in better risk-stratification. Translation of this subgrouping to routine practice still remains a challenge. The most pathologist accessible techniques for molecular subgrouping include immunohistochemistry (IHC), fluorescent in-situ hybridization (FISH) and NanoString. OBJECTIVES: (1) Molecular subgrouping of MBs by IHC and FISH, and NanoString assay (2) To compare their efficacy and cost for applicability in resource constrained centers. METHODS: Ninety-five cases of MB with adequate tissue were included. Molecular subgrouping was performed by IHC for ß-catenin, GAB1 and YAP1; FISH for MYC amplification, and sequencing for CTNNB1, and by NanoString Assay on the same set of MBs. A subset of cases was subjected to 850k DNA methylation array. RESULTS: IHC + FISH classified MBs into 15.8% WNT, 16.8% SHH, and 67.4% non-WNT/non-SHH subgroups; with MYC amplification identified in 20.3% cases of non-WNT/non-SHH. NanoString successfully classified 91.6% MBs into 25.3% WNT, 17.2% SHH, 23% Group 3 and 34.5% Group 4. However, NanoString assay failure was seen in eight cases, all of which were > 8-years-old formalin-fixed paraffin-embedded tissue blocks. Concordant subgroup assignment was noted in 88.5% cases, while subgroup switching was seen in 11.5% cases. Both methods showed prognostic correlation. Methylation profiling performed on discordant cases revealed 1 out of 4 extra WNT identified by NanoString to be WNT, others aligned with IHC subgroups; extra SHH by NanoString turned out to be SHH by methylation. CONCLUSIONS: Both IHC supplemented by FISH and NanoString are robust methods for molecular subgrouping, albeit with few disadvantages. IHC cannot differentiate between Groups 3 and 4, while NanoString cannot classify older-archived tumors, and is not available at most centres. Thus, both the methods complement each other and can be used in concert for high confidence allotment of molecular subgroups in clinical practice.

Analysis of PD-L1 expression and T cell infiltration in different molecular subgroups of diffuse midline gliomas.

Diffuse midline gliomas (DMGs) are rare and devastating tumors with limited therapeutic options. Programmed death-ligand 1 (PD-L1) expression represents a potential predictive biomarker for immunotherapy. One hundred and twenty-six DMGs (89 adult and 37 pediatric) were assessed for immune profile (PD-L1, cluster of differentiation (CD3, CD8) and genetic markers (mutation in 27th amino acid of histone H3 (H3K27M), alpha thalassemia/mental retardation syndrome X-linked (ATRX), isocitrate dehydrogenase 1 (IDH1), p53) by immunohistochemistry. Sanger sequencing was done for IDH1 and H3K27M. The thalamus was the commonest site. Four molecular subgroups of DMGs were identified. H3K27M mutation was more frequent in children (P = 0.0001). The difference in median overall survival (OS) was not significant in any of the four molecular subgroups (P > 0.05). PD-L1 expression was significantly higher in H3K27M/IDH1 double-negative adult glioblastomas (GBMs) (P = 0.002). Strong PD-L1 expression was more frequent in grade IV tumors and thalamic location, although the difference was not significant (P = 0.14 and P = 0.19 respectively). Positive PD-L1 expression was significantly associated with high tumor-infiltrating lymphocytes count (P < 0.05). There was no significant difference in median OS in PD-L1-positive versus negative cases among four genetic subgroups (P > 0.05). On univariate analysis, there was no direct correlation of PD-L1 with any genetic alteration, except H3K27M mutation (P = 0.01). CD3 infiltration was similar in both adults and pediatric ages (84.3% and 78.4%, respectively) while CD8 expression was significantly greater in adults compared to children (74.1% vs 37.8%, P = 0.0001). This is the first comprehensive analysis highlighting molecular and immune profiles of DMGs. Despite molecular and clinicopathological diversity, overall survival in DMGs remains dismal. Multicentric studies with larger numbers of cases should be undertaken for stratifying DMGs according to their age, immune and molecular profiles, to develop effective immunotherapies.

ATRX loss in glioneuronal tumors with neuropil-like islands indicates similarity to diffuse astrocytic tumors.

Glioneuronal tumor with neuropil-like islands (GTNI) is a rare, recently described neoplasm, whose pathogenesis has not been studied extensively. The role of ATRX mutations, a class-defining alteration in diffuse astrocytic neoplasms, has not been assessed in GTNIs previously. We therefore aimed to assess the status of ATRX, along with IDH1, 1p/19q and p53, in cases of GTNI in order to evaluate the molecular profile of these tumors. All cases of GTNI diagnosed at our Institute were retrieved and clinicopathological features were reviewed. Immunohistochemistry for ATRX, IDH1 and p53 was performed. We identified four cases of GTNI, majority of which occurred in young adults. Loss of ATRX immunoexpression, a surrogate marker for ATRX mutation, was seen in all four cases. All cases were immunopositive for p53, while IDH1 positivity was seen in all three cases assessed. 1p/19q codeletion was absent in the three cases analyzed. These results indicate that the molecular pathogenesis of GTNIs similar to that of diffuse astrocytic tumors. Further, the loss of ATRX expression is seen in both the glial as well as neuronal components, indicating that both arise from the same tumor stem/progenitor cell and that the latter may be a metaplastic change. Thus, loss of ATRX immunoexpression, shown for the first time in these tumors, along with immunopositivity for p53 and IDH1, indicates that these tumors are molecular astrocytomas, and their clinical behaviour is likely to recapitulate that of ATRX-mutant and IDH-mutant diffuse astrocytomas of the same grade.

Clinicopathological characteristics, molecular subgrouping, and expression of miR-379/miR-656 cluster (C14MC) in adult medulloblastomas.

Medulloblastoma (MB) is a childhood tumor comprising four molecular subgroups: WNT, SHH, group 3 and group 4, with diagnostic and prognostic connotations. Very few studies are available on molecular subgrouping of adult MBs due to their rarity. Recently, loss of chromosome14q has been reported in SHH MBs, with downregulation of miR-379/miR-656 cluster (C14MC) in pediatric SHH MBs. Hence, the present study on adult MBs was undertaken to enumerate clinicopathological characteristics and molecular subgroups, and to analyze expression of C14MC and its transcriptional regulators, MEF2, JUN and ESRRG. Immunohistochemistry for ß-catenin, GAB1 and YAP1 was performed to identify molecular subgroups. MYC amplification was evaluated by FISH. Expression profiling of 47 miRNAs from C14MC was performed using customized Taqman low-density array. Expression of transcriptional regulators was examined using RT-PCR. Seventy-one adult MBs were analyzed. They had male predominance and majority were located laterally (52 %). A significant proportion of cases were of Desmoplastic/nodular histology (32 %); MBEN was not seen. WNT tumors constituted 4.2 %, SHH 62 %, and non-WNT/non-SHH 33.8 %. MYC amplification was identified in 11.1 % cases. Patient outcome was worse in adults. Significant downregulation of C14MC was observed in all MB subgroups, and MEF-2 expression was downregulated. Adult MBs are distinct from childhood MBs in terms of location, histopathological subtypes, molecular subgroups, as well as prognosis. Silencing of C14MC in all MB subgroups suggests its role as a tumor suppressor locus in tumorigenesis. Deregulation of C14MC can possibly be attributed to repression of MEF2.

Intracranial interhemispheric osteochondrolipoma: Diagnostic and surgical challenges in an extremely rare entity.

Intracranial lipomas are rare developmental lesions, predominantly occurring in the interhemispheric location. Osteochondrolipoma is an extremely rare variant of lipoma with osseous and chondroid differentiation. We present a case of interhemispheric osteochondrolipoma, in a 2.5-years-old male child which was detected antenatally, in association with corpus callosum agenesis. The lesion progressively increased in size with resulting compression of surrounding structures, and was subjected to microsurgical decompression. To the best of our knowledge, this is the first case of intracranial interhemispheric osteochondrolipoma in the existing medical literature. Peculiarities of this case and the diagnostic and surgical challenges are discussed.

Neuroblastoma-like schwannoma of the skull base: an enigmatic peripheral nerve sheath tumor variant.

Neuroblastoma-like schwannoma is an extremely rare histological variant of schwannoma, which histologically mimics a malignant small round cell tumor. Only 19 cases have been reported in the literature to date. We report a case of this tumor located at the skull base in a 44-year-old woman who presented with symptoms of right-sided earache and hearing loss. MRI revealed a large, lobulated, extra-axial mass measuring 8.8 cm × 3.6 cm × 4.2 cm in the floor of the middle and posterior cranial fossa. Microscopic examination revealed a perplexing histopathology with peculiar collagenous rosettes. Differential diagnoses included a broad range of benign and malignant tumors. Typical schwannoma seldom poses a difficulty in diagnosis; however, this unusual variant is a diagnostic challenge which requires an extensive clinico-radiological correlation and immunohistochemical work-up. Hence, knowledge of this entity is a must to avoid erroneous diagnosis and inappropriate treatment.

High-mobility group box 1 is a novel deacetylation target of Sirtuin1.

High-mobility group box 1 (HMGB1) undergoes acetylation, nuclear-to-cytoplasmic translocation, and release from stressed kidneys, unleashing a signaling cascade of events leading to systemic inflammation. Here, we tested whether the deacetylase activity of Sirtuin1 (SIRT1) participates in regulating nuclear retention of HMGB1 to ultimately modulate damage signaling initiated by HMGB1 secretion during stress. When immunoprecipitated acetylated HMGB1 was incubated with SIRT1, HMGB1 acetylation decreased by 57%. Proteomic analysis showed that SIRT1 deacetylates HMGB1 at four lysine residues (55, 88, 90, and 177) within the proinflammatory and nuclear localization signal domains of HMGB1. Genetic ablation or pharmacological inhibition of SIRT1 in endothelial cells increased HMGB1 acetylation and translocation. In vivo, deletion of SIRT1 reduced nuclear HMGB1 while increasing its acetylation and release into circulation during basal and ischemic conditions, causing increased renal damage. Conversely, resveratrol pretreatment led to decreased HMGB1 acetylation, its nuclear retention, decreased systemic release, and reduced tubular damage. Thus, a vicious cycle is set into motion in which the inflammation-induced repression of SIRT1 disables deacetylation of HMGB1, facilitates its nuclear-to-cytoplasmic translocation, and systemic release, thereby maintaining inflammation.

Primary Sjögren's Syndrome Presenting as Flaccid Quadriparesis.

Primary Sjögren's syndrome is an autoimmune disease presenting classically as keratoconjunctivitis sicca. Renal involvement in Sjögrens's syndrome is less common, and the initial presentation with renal complications without any sicca symptoms is extremely rare. The renal involvement may present with symptoms arising from interstitial nephritis, mainly distal renal tubular acidosis.

Frequent Immunohistochemical Expression of Transcriptional Repressor GATA Binding 1 in Salivary Gland Neoplasms: A Sensitive but Nonspecific Marker.

CONTEXT.­: Salivary gland (SG) neoplasms (SGNs) display considerable immunophenotypic diversity. A significant proportion of SG carcinomas develop metastases with increased diagnostic difficulty at metastatic sites. Transcriptional repressor GATA binding 1 (TRPS1), a novel immunohistochemical marker for breast cancer, has been found to stain certain SGNs. OBJECTIVE.­: To investigate TRPS1 and SRY-related HMG-box 10 (SOX10) immunoexpression in various SGNs and non-SG carcinomas, head and neck paragangliomas, and head and neck mucosal melanomas. DESIGN.­: TRPS1 immunoreactivity score (IRS) was determined as negative or low, intermediate, or high positive; SOX10 was reported as negative or positive. RESULTS.­: One hundred forty-eight SGNs, 5 breast carcinomas, 105 nonbreast-non-SG carcinomas, including 33 head and neck squamous cell carcinomas (HNSCCs), 6 head and neck paragangliomas, and 6 head and neck mucosal melanomas, were assessed for TRPS1. All 23 benign SGNs showed TRPS1 positivity, with the majority having high-positive IRS (17 of 23 cases; 74%). Among 125 SG carcinomas, 115 of 125 (92%) were TRPS1 positive, with high-positive IRS in 94 of 125 (75%), intermediate positive in 15 of 125 (12%), and low positive in 6 of 125 (5%). Among nonbreast-non-SG carcinomas, HNSCC, lung, thyroid, kidney, and ovarian carcinomas showed frequent TRPS1 staining. Nearly half of HNSCCs had high (11 of 18; 33%) or intermediate (4 of 18; 12%) positive IRS. Mean IRS in SG carcinomas was significantly higher than that in nonbreast-non-SG carcinomas (P < .001). None of the TRPS1-positive nonbreast-non-SG carcinomas expressed SOX10. CONCLUSIONS.­: TRPS1 is positive in most benign and malignant SGNs. Its expression in several nonbreast-non-SG carcinomas indicates that it lacks specificity for breast and SG carcinomas, even if considering only high-positive IRS. Addition of SOX10 can increase discriminatory utility of TRPS1.

Child Firearm-Related Homicide and Suicide by State Legislation in the US (2009-2020).

BACKGROUND: Firearms are the leading cause of death among U.S. children and adolescents. This study evaluates whether state gun laws are associated with firearm suicides and homicides in children. STUDY DESIGN: This is a cross-sectional database study comparing childhood firearm mortality with 36 state firearm laws using data from CDC WONDER and the RAND state firearm law database. Primary outcomes were firearm-related suicide and homicide mortalities per 100,000 persons. We examined suicide deaths by all firearms, including intentional self-harm by handguns only, intentional self-harm by rifles, shotguns, or large firearms only, and intentional self-harm by other or unspecified firearms, as well as homicide deaths for the same firearm types in each state. Welch's t-tests compared mean rates of suicide and homicide mortalities between states with and without these laws. States that either enacted or rescinded firearm legislation during this period were excluded. RESULTS: From 2009-2020, there were 6,735 suicides and 10,278 homicides by firearm totaling 17,013 child deaths (<18) by firearm. States with "child access prevention- negligent storage" laws demonstrated lower suicide mortality rates across all firearm types (handguns) N=13, M (mean per 100,000)=0.68, SD=0.27, p<0.001; (long guns) N=12, M=0.65, SD=0.25, p<0.001). There were no significant differences in mean suicide death rates across all firearm types when comparing states with or without firearm laws related to "minimum age youth possession", "minimum age youth purchase and sale", or "child access prevention - intentional." Comparing homicide mortality rates for all firearm types revealed no notable distinctions between states with and without the identified laws. CONCLUSIONS: Firearm legislation is associated with decreased suicide rates for individuals under 18, but its influence on homicides is less certain. Comprehensive research and thoughtful policy formulation are essential for addressing this pressing public health concern.

MYCN immunohistochemistry as surrogate marker for MYCN-amplified spinal ependymomas.

MYCN (master regulator of cell cycle entry and proliferative metabolism) gene amplification defines a molecular subgroup of spinal cord ependymomas that show high-grade morphology and aggressive behavior. Demonstration of MYCN amplification by DNA methylation or fluorescence-in situ hybridization (FISH) is required for diagnosis. We aimed to (i) assess prevalence and clinicopathological features of MYCN-amplified spinal ependymomas and (ii) evaluate utility of immunohistochemistry (IHC) for MYCN protein as a surrogate for molecular testing. A combined retrospective-prospective study spanning 8 years was designed during which all spinal cord ependymomas with adequate tissue were subjected to MYCN FISH and MYCN IHC. Among 77 spinal cord ependymomas included, MYCN amplification was identified in 4 samples from 3 patients (3/74, 4%) including two (1st and 2nd recurrences) from the same patient. All patients were adults (median age at diagnosis of 32 years) including two females and one male. The index tumors were located in thoracic (n = 2) and lumbar (n = 1) spinal cord. One of the female patients had neurofibromatosis type 2 (NF2). All four tumors showed anaplastic histology. Diffuse expression of MYCN protein was seen in all four MYCN-amplified samples but in none of the non-amplified cases, thus showing 100% concordance with FISH results. On follow-up, the NF2 patient developed widespread spinal dissemination while another developed recurrence proximal to the site of previous excision. To conclude, MYCN-amplified spinal ependymomas are rare tumors, accounting for ~ 4% of spinal cord ependymomas. Within the limitation of small sample size, MYCN IHC showed excellent concordance with MYCN gene amplification.

Handoffs and transitions of care: A systematic review, meta-analysis, and practice management guideline from the Eastern Association for the Surgery of Trauma.

BACKGROUND: The Joint Commission reports that at least half of communication breakdowns occur during handovers or transitions of care. There is no consensus on how best to approach the transfer of care within acute care surgery (ACS). We conduct a systematic review and meta-analysis of the current data on handoffs and transitions of care in ACS patients and evaluate the impact of standardization and formalized communication processes. METHODS: Clinically relevant questions regarding handoffs and transitions of care with clearly defined patient Population(s), Intervention(s), Comparison(s), and appropriately selected Outcomes were determined. These centered around specific transitions of care within the setting of ACS, specifically perioperative interactions, emergency medical services and trauma team interactions, and intra/interfloor and intensive care unit (ICU) interactions. A systematic literature review and meta-analysis were conducted using the Grading of Recommendations Assessment, Development, and Evaluation methodology. RESULTS: A total of 10 studies were identified for analysis. These included 5,113 patients in the standardized handoff group and 5,293 in the current process group. Standardized handoffs reduced handover errors for perioperative interactions and preventable adverse events for intra/interfloor and ICU interactions. There were insufficient data to evaluate outcomes of clinical complications and medical errors. CONCLUSION: We conditionally recommend a standardized handoff in the field of ACS, including perioperative interactions, emergency medical services and trauma team interactions, and intra/interfloor and ICU interactions. LEVEL OF EVIDENCE: Systematic Review/Meta-analysis; Level III.

Kimura disease of naso-orbito-ethmoid region and review of surgical approaches to naso-orbito-ethmoid region.

SummaryA man in 30s had complaints of glabellar and upper nasal swelling for 8 years. It was insidious in onset and gradually progressive causing epiphora and restriction of nasal visual field. Fine-needle aspiration cytology and biopsy revealed features which were suggestive of Kimura's disease (KD). CT scans showed a well-defined subcutaneous swelling in the naso-orbito-ethmoid (NOE) region. KD presents as lymphoglandular swelling; however, NOE region is an uncommon site of occurrence. A thyroid-shaped tumour was excised by H-shaped incision approach to the NOE region.

Fluorescence in situ hybridization for ETV6 gene rearrangements on destained cytological smears: Role in diagnosis of secretory carcinoma of salivary gland.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is the first-line diagnostic procedure for salivary gland masses. Secretory carcinoma (SC) is characterized by ETV6 and RET rearrangements detected by fluorescence in situ hybridization (FISH) or reverse transcriptase-polymerase chain reaction optimized for paraffin-embedded and fresh-frozen tissue, respectively. The authors performed FISH on cytological material to assess its role in the diagnosis of SC. METHODS: FNACs with SC as a diagnostic consideration and cases diagnosed as SC on histology with a corresponding FNAC with any diagnosis were evaluated for ETV6 rearrangement by FISH. If acinic cell carcinoma (ACC) was a differential diagnosis and ETV6 rearrangement was absent, NR4A3 FISH was performed. FISH results were compared with those on histological specimens, where available. RESULTS: Fifteen cases were included. FISH initially performed on three cell blocks did not yield good results, was then performed on direct smears, and was interpretable in 14 cases (93.3%). An ETV6 rearrangement was identified in seven cases (50%), and an NR4A3 rearrangement was identified in three cases (21.4%), providing a confirmatory diagnosis in 10 of 15 cases (66.7%). The Milan System for Reporting Salivary Gland Cytopathology category was altered in two cases (6.7%). Complete correlation (100%) was seen with FISH on corresponding histological specimens. CONCLUSIONS: With minor modifications, the FISH procedure can be optimized for FNAC smears with results comparable to those on histological specimens. ETV6 FISH testing on cytological smears in cases suspected as SC improves the diagnostic accuracy of FNAC and can help lower the proportion of the Milan categories salivary gland neoplasm of uncertain malignant potential and suspicious for malignancy, maximizing diagnostic information from less invasive samples and aiding in patient management.

Fine needle aspiration cytology of metastatic SMARCA4-deficient sinonasal teratocarcinosarcoma: First report in literature.

Inactivating mutations of SMARCA4 and accompanying loss of BRG1 immunoexpression were recently identified in majority of sinonasal teratocarcinosarcomas (TCS). These rare and aggressive neoplasms have potential for nodal metastasis, presenting opportunities for diagnosis on fine needle aspiration cytology (FNAC). However, their cytological features have not been described till date. A 22-year-old male was diagnosed to have SMARCA4-deficient TCS on a nasal mass biopsy, and was started on neoadjuvant chemotherapy. Four months later, FNAC from cervical lymph nodes showed predominantly discohesive tumor cells with moderate to abundant cytoplasm and enlarged vesicular nuclei with prominent nucleoli. Occasional cohesive fragments showed ovoid to spindled tumor cells attached to fibrovascular cores. Few loosely cohesive cells with scant cytoplasm and nuclei having stippled chromatin, and rhabdoid cells were also seen. Frequent mitoses, apoptosis and nuclear streaking were evident. Overt squamous or glandular differentiation was absent. Tumor cells showed loss of BRG1 immunostaining and ß-catenin immunopositivity on a cell block, consistent with metastatic SMARCA4-deficient TCS. The diversity of cell types in SMARCA4-deficient TCS can result in a broad spectrum of cytological features that overlap with that of other regional metastatic tumors including neuroendocrine carcinoma, olfactory neuroblastoma and melanoma. Further, all components of TCS as seen in the primary tumor may not be present in nodal metastases. Thus, SMARCA4-deficient TCS should be considered in the differential diagnosis of metastatic poorly/undifferentiated malignancies in cervical lymph node aspirates, and appropriate ancillary tests viz. BRG1 immunostaining employed for accurate diagnosis.

Cytological diagnosis of olfactory neuroblastoma at metastatic sites, with emphasis on role of insulinoma-associated protein 1 immunocytochemistry.

BACKGROUND: Olfactory neuroblastoma (ONB) is a rare neuroectodermal tumor with a propensity for lymph node and distant metastases in a proportion of cases, presenting opportunities for cytological diagnosis. Insulinoma-associated protein 1 (INSM1) is a recently identified marker of neuroendocrine differentiation with higher sensitivity and specificity than traditional neuroendocrine immunostains used in diagnosis of ONB. METHODS: Archival aspirates diagnosed as metastatic ONB were retrieved and reviewed for described characteristics of ONB. Spare direct smears with sufficient cellular material from each case were selected, if available, and immunocytochemistry for INSM1 was performed on the destained alcohol-fixed smears. INSM1 was also performed on non-neuroendocrine malignant round cell tumors (MRCT). RESULTS: Seven fine needle aspirates (FNA) from five patients were identified, all of which showed a small round cell tumor with fine to coarse granular chromatin. Most cases had moderate to high cellularity, comprised of loosely cohesive clusters and dispersed cells. While two-cell pattern, nuclear streaking and moulding were frequent, background neuropil, fibrillary cytoplasm, and rosettes were uncommon. INSM1 immunostaining performed on spare direct smears showed strong positivity in 30%-100% of tumor cells (mean: 62%) in all aspirates tested (100%). In comparison with other immunostains, INSM1 showed more robust staining, and was easier to interpret. All non-neuroendocrine MRCTs were negative for INSM1. CONCLUSION: Metatstatic ONB can resemble other small round cell tumors, as all the diagnostic features of ONB may not be readily evident. INSM1 immunocytochemistry has high sensitivity and specificity and can reliably be used as a single marker to support the cytomorphology for a confirmatory diagnosis of ONB, even on direct smears if a cell block is not available.

Pleural metastasis from parotid secretory carcinoma: First report of morphology on effusion cytology, and role of pan-TRK immunohistochemistry.

Distant metastasis from salivary gland secretory carcinoma (SC) is rare, with lung and pleura being the most frequent site. While cytological features of SC on fine needle aspirates are well documented, its morphology in serous effusions has not been described. We describe the cytomorphological features on effusion cytology of two patients with ETV6::NTRK3 fusion-positive SC, who subsequently developed pleural metastases. Cytospin preparations of pleural fluid showed tightly cohesive, irregularly shaped and ball-like clusters of large tumor cells with scant to abundant uni- and multi-vacuolated cytoplasm. Nuclei were eccentrically placed, round to oval, vesicular, with finely granular chromatin, irregular nuclear membranes and conspicuous to prominent nucleoli. With these features, the tumors resembled an adenocarcinoma, indistinguishable from a lung primary. Cell blocks from both cases showed tumor fragments, some of which had the hollow appearance of transversely sectioned cell spheres as seen in lung and breast adenocarcinomas. Immunohistochemistry on cell blocks revealed nuclear pan-TRK positivity in both cases. Case 1 also showed focal mammaglobin staining, and TTF1 negativity. Pleural metastases from SC may mimic other adenocarcinomas. As targeted therapy, that is, selective TRK inhibitors are available for treatment of metastatic disease, NTRK3 fusion status is not only diagnostic, but also required to plan treatment. Pan-TRK immunohistochemistry serves as a viable cost-effective, easy to apply surrogate marker for NTRK3 fusion, particularly in diagnostic laboratories lacking easy access to molecular testing on cytological material.