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Sinonasal mucosal melanoma is a rare tumor arising within the nasal cavity, paranasal sinuses, or nasopharynx (sinonasal tract). This study evaluated 90 cases diagnosed in 29 males and 61 females with median age 68 years. Most tumors involved the nasal cavity and had an epithelioid morphology. Spectrum of research techniques used in this analysis includes targeted-DNA and -RNA next-generation sequencing, Sanger sequencing, fluorescence in situ hybridization and immunohistochemistry. Sinonasal melanomas were commonly driven by RAS (38/90, 42%), especially NRAS (n = 36) mutations and rarely (4/90, 4%) displayed BRAF pathogenic variants. BRAF/RAS mutants were more frequent among paranasal sinuses (10/14, 71%) than nasal (26/64, 41%) tumors. BRAF/RAS-wild type tumors occasionally harbored alterations of the key components and regulators of Ras-MAPK signaling pathway: NF1 mutations (1/17, 6%) or NF1 locus deletions (1/25, 4%), SPRED1 (3/25, 12%), PIK3CA (3/50, 6%), PTEN (4/50, 8%) and mTOR (1/50, 2%) mutations. These mutations often occurred in a mutually exclusive manner. In several tumors some of which were NRAS mutants, TP53 was deleted (6/48, 13%) and/or mutated (5/90, 6%). Variable nuclear accumulation of TP53, mirrored by elevated nuclear MDM2 expression was seen in50% of cases. Furthermore, sinonasal melanomas (n = 7) including RAS/BRAF-wild type tumors (n = 5) harbored alterations of the key components and regulators of canonical WNT-pathway: APC (4/90, 4%), CTNNB1 (3/90, 3%) and AMER1 (1/90, 1%). Both, TERT promoter mutations (5/53, 9%) and fusions (2/40, 5%) were identified. The latter occurred in BRAF/RAS-wild type tumors. No oncogenic fusion gene transcripts previously reported in cutaneous melanomas were detected. Eight tumors including 7 BRAF/RAS-wild type cases expressed ADCK4::NUMBL cis-fusion transcripts. In summary, this study documented mutational activation of NRAS and other key components and regulators of Ras-MAPK signaling pathway such as SPRED1 in a majority of sinonasal melanomas.

Striated duct adenoma (SDA) is a rare salivary gland neoplasm defined by histologic similarity to normal striated ducts. However, doubt persists about whether SDA represents a genuine entity distinct from canalicular adenoma and if a malignant counterpart exists. This study aims to evaluate the molecular underpinnings of SDA to clarify its pathogenesis and classification. We identified 10 SDA and 2 tumors called low-grade adenocarcinoma not otherwise specified that were retrospectively recognized to resemble SDA. All cases showed recurrent histologic features including (1) discrete monophasic tubules, (2) tall columnar eosinophilic cells, (3) monotonous oval nuclei, and (4) scant fibrous stroma, and most were positive for S100 protein (91%), SOX10 (80%), and CK7 (80%). Although 1 case was previously called adenocarcinoma based on interdigitation with normal acini, this pattern was also seen in some SDA, and likely does not indicate malignancy; the significance of growth surrounding nerve in 1 other case is less clear. Targeted sequencing identified IDH2 R172X mutations in all 8 cases with sufficient tissue, with positivity for IDH1/2 mutation-specific immunohistochemistry in 9 cases stained. In contrast, 5 canalicular adenomas lacked IDH2 mutations or other oncogenic alterations. Overall, IDH2 R172X mutations are a defining feature of SDA that, in combination with its recognizable pathologic profile, confirm it is a unique entity separate from canalicular adenoma. IDH1/2 mutation-specific immunohistochemistry may provide a convenient tool to facilitate diagnosis. Both morphology and IDH2 mutations raise parallels between SDA and breast tall cell carcinoma with reverse polarity.

Syphilis is a sexually transmitted infectious disease caused by Treponema pallidum and characterized by a complex and variable clinical presentation. Cases of unexpected oral syphilis presenting as non-healing ulcers are uncommonly reported. We report 3 cases (one female and two males, aged 35, 35, and 56 years, respectively) in which patients presented with non-healing oral ulcers. Biopsies revealed surface ulceration and a significant neutrophilic infiltrate rather than the more conventional plasma cell infiltrate seen with most reported syphilis infections, potentially leading to an inaccurate diagnosis. Treponema pallidum immunohistochemistry highlighted spirochetes within the epithelium, with additional diagnostic confirmation by serum T. pallidum particle agglutination assay. Sexual history documentation by the clinician with nonspecific oral ulcers is paramount to aiding diagnosis and leading to proper management. Further, it is important to perform immunohistochemistry for T. pallidum in oral biopsies from non-healing ulcers, especially when clinical history raises the differential diagnosis or when other clinical manifestations may support this consideration.

Sinonasal papilloma (SP), formerly Schneiderian papilloma, represents a rare group of benign epithelial neoplasms, most commonly identified in the sinonasal tract, while less frequently identified in the pharynx, lacrimal sac, and middle ear. Within temporal bone sinonasal-type papilloma (TBSP), there seems to be a much higher recurrence and malignant transformation risk than those identified in the sinonasal tract. Based on this clinical report and a review of the cases reported in the English literature, 49% of the 57 cases developed in the setting of concurrent or antecedent sinonasal or nasopharyngeal SP. There is an equal sex distribution (26 females and 31 males), with a broad age range (19–81 years) at presentation (median 56 years; average 54 years). Three patients had bilateral disease. Symptoms include a mass lesion with hearing loss, otitis media, otorrhea, otalgia, and tinnitus, among others. Inverted SP was identified in 42 patients, oncocytic SP in six, and exophytic SP in four (undefined in the remainder). Recurrence was identified in 38 of 49 patients with follow-up (78%), often with multiple recurrences over time, with carcinoma developing in the temporal bone in 19 patients (33%), with males developing carcinoma by a 1.7:1 ratio over females. Surgery was the treatment of choice (radical mastoidectomy) with 6 patients (10%) dead of disease (median 30 months, mean 38 months), while 47 patients were alive at last follow-up: 31 without disease (mean 33 months); 7 with locally recurrent disease (mean 20 months); 9 patients alive but with unknown disease status; and 4 patients without follow-up. In conclusion, TBSP is frequently identified in the setting of concurrent sinonasal tract disease, showing similar histologic features to sinonasal tract counterparts. There is no sex predilection, with patients most commonly presenting in the sixth decade of life. Recurrences are common, with carcinoma developing much more frequently than in sinonasal tract papilloma (33%), but recognizing that carcinoma may be documented in either or both anatomic sites. Overall outcome is excellent, with long term clinical follow-up warranted to manage recurrence or malignant transformation.

Inflammatory myofibroblastic tumor (IMT) is a distinctive fibroblastic and myofibroblastic spindle cell neoplasm with an accompanying inflammatory cell infiltrate and frequent receptor tyrosine kinase activation at the molecular level. The tumor may recur and rarely metastasizes. IMT is rare in the head and neck region, and limited information is available about its clinicopathologic and molecular characteristics in these subsites. Therefore, we analyzed a cohort of head and neck IMTs through a multi-institutional approach. Fourteen cases were included in the provisional cohort, but 1 was excluded after molecular analysis prompted reclassification. Patients in the final cohort included 7 males and 6 females, with a mean age of 26.5 years. Tumors were located in the larynx (n=7), oral cavity (n=3), pharynx (n=2), and mastoid (n=1). Histologically, all tumors showed neoplastic spindle cells in storiform to fascicular patterns with associated chronic inflammation, but the morphologic spectrum was wide, as is characteristic of IMT in other sites. An underlying fusion gene event was identified in 92% (n=11/12) of cases and an additional case was ALK-positive by IHC but could not be evaluated molecularly. ALK represented the driver in all but 1 case. Rearrangement of ALK, fused with the TIMP3 gene (n=6) was most commonly detected, followed by 1 case each of the following fusion gene partnerships: TPM3-ALK, KIF5B-ALK, CARS-ALK, THBS1-ALK, and a novel alteration, SLC12A2-ROS1. The excluded case was reclassified as spindle cell rhabdomyosarcoma after detection of a FUS-TFCP2 rearrangement and retrospective immunohistochemical confirmation of rhabdomyoblastic differentiation, illustrating an important diagnostic pitfall. Two IMT patients received targeted therapy with crizotinib, with a demonstrated radiographic response. One tumor recurred but none metastasized. These results add to the growing body of evidence that kinase fusions can be identified in the majority of IMTs and that molecular analysis can lead to increased diagnostic accuracy and broadened therapeutic options for patients.

Bone and soft tissue tumors of the head and neck are relatively uncommon tumors that often represent a diagnostic challenge because of the wide range of entities that must be considered in the differential diagnosis. Over the past few years, classification of bone and soft tissue tumors has evolved primarily because of substantial contributions from molecular genetics, with the identification of new markers that are increasingly used to complement histopathologic findings in the routine diagnostic workup. This review focuses on the recently described mesenchymal tumors that preferentially involve the head and neck region, with a focus on the most relevant novel immunohistochemical and molecular findings, including gene fusions and mutations, that can help in the diagnosis and in the assessment of clinical behavior.

Summay Complete resection of adrenal cortical carcinoma (ACC) with or without adjuvant therapy offers the best outcome. Recurrence is common, and in individual cases, the long-term outcome is difficult to predict, making it challenging to personalize treatment options. Current risk stratification approaches are based on clinical and conventional surgical pathology assessment. Rigorous and uniform pathological assessment may improve care for individual patients and facilitate multi-institutional collaborative studies. The International Collaboration on Cancer Reporting (ICCR) convened an expert panel to review ACC pathology reporting. Consensus recommendations were made based on the most recent literature and expert opinion. The data set comprises 23 core (required) items. The core pathological features include the following: diagnosis as per the current World Health Organization classification, specimen integrity, greatest dimension, weight, extent of invasion, architecture, percentage of lipid-rich cells, capsular invasion, lymphatic invasion, vascular invasion, atypical mitotic figures, coagulative necrosis, nuclear grade, mitotic count, Ki-67 proliferative index, margin status, lymph node status, and pathological stage. Tumors were dichotomized into low-grade ( 20 mitoses per 10 mm2) ones. Additional noncore elements that may be useful in individual cases included several multifactorial risk assessment systems (Weiss, modified Weiss, Lin-Weiss-Bisceglia, reticulin, Helsinki, and Armed Forces Institute of Pathology scores/algorithms). This data set is now available through the ICCR website with the hope of better standardizing pathological assessment of these relatively rare but important malignancies.

Fibroinflammatory lesions of the sinonasal tract are one of the most common head and neck lesions submitted to surgical pathology. When the fibroinflammatory pattern represents the lesion (i.e., not surface reactive ulceration), an algorithmic approach can be useful. Separated into reactive, infectious, and neoplastic, and then further divided based on common to rare, this logical progression through a series of differential considerations allows for many of these lesions to be correctly diagnosed. The reactive lesions include chronic rhinosinusitis and polyps, granulomatosis with polyangiitis, and eosinophilic angiocentric fibrosis. Infectious etiologies include acute invasive fungal rhinosinusitis, rhinoscleroma, and mycobacterial infections. The neoplastic category includes lobular capillary hemangioma, inflammatory myofibroblastic tumor, and NK/T-cell lymphoma, nasal type. Utilizing patterns of growth, dominant cell types, and additional histologic features, selected ancillary studies help to confirm the diagnosis, guiding further clinical management.

Lymphoepithelial carcinoma of salivary glands (LECSG) is an uncommon neoplasm. This article summarizes the findings of 438 cases in a review of the literature. Concurrent lymphoepithelial lesions may suggest a primary tumor. The tumor shows a nonkeratinizing carcinoma intimately associated with a rich lymphohistiocytic infiltrate, destroying adjacent salivary gland tissue. Irrespective of race or ethnicity, the tumors usually express Epstein-Barr virus, with Epstein-Barr virus encoded small RNA (EBER) and/or latent membrane protein-1 (LMP-1), although a subset does not. There is an overall good prognosis of about 80% at 5 years.

Sclerosing polycystic adenoma (SPA) is the more appropriate name for sclerosing polycystic adenosis. SPA is an uncommon salivary gland lesion with a constellation of unusual histologic findings that were originally interpreted as analogous to breast fibrocystic changes. The histologic findings in SPA include fibrosis, cystic alterations, apocrine metaplasia, and proliferations of ducts, acini, and myoepithelial cells in variable proportions. Because of its unusual mixed histology, SPA may be confused with a variety of lesions, ranging from reactive conditions to benign or even malignant neoplasms. The features of SPA are reviewed, with an emphasis on resolving its differential diagnosis.

Mucin-producing salivary adenocarcinomas were historically divided into separate colloid carcinoma, papillary cystadenocarcinoma, and signet ring cell carcinoma diagnoses based on histologic pattern, but have recently been grouped together in the adenocarcinoma not otherwise specified category. It is currently unclear if these tumors represent 1 or more distinct entities and how they are related to well-circumscribed papillary mucinous lesions with recurrent AKT1 E17K mutations that were recently described as salivary intraductal papillary mucinous neoplasm. Here, we sought to evaluate the clinicopathologic and molecular features of salivary mucinous adenocarcinomas to clarify their classification. We identified 17 invasive mucin-producing salivary adenocarcinomas, 10 with a single histologic pattern, and 7 with mixed patterns. While most tumors demonstrated papillary growth (n=15), it was frequently intermixed with colloid (n=6) and signet ring (n=3) architecture with obvious transitions between patterns. All were cytokeratin 7 positive (100%) and cytokeratin 20 negative (0%). Next-generation sequencing performed on a subset demonstrated recurrent AKT1 E17K mutations in 8 cases (100%) and TP53 alterations in 7 cases (88%). Of 12 cases with clinical follow-up (median: 17 mo), 4 developed cervical lymph node metastases, all of which had colloid or signet ring components. Overall, overlapping histologic and immunohistochemical features coupled with recurrent AKT1 E17K mutations across patterns suggests that mucin-producing salivary adenocarcinomas represent a histologically diverse single entity that is closely related to tumors described as salivary intraductal papillary mucinous neoplasm. We propose a unified mucinous adenocarcinoma category subdivided into papillary, colloid, signet ring, and mixed subtypes to facilitate better recognition and classification of these tumors.

Olfactory carcinoma is one of many names applied to sinonasal malignancies with histologic similarity to olfactory neuroblastoma (ONB) but cytokeratin expression or gland formation. It is unclear whether these neuroepithelial tumors represent a unified category and if they are separate from ONB and currently-recognized sinonasal carcinomas. This study aims to explore their clinicopathologic characteristics based on a large collective experience. A total of 53 sinonasal tumors with neuroepithelial differentiation were identified affecting 41 men and 12 women, median age 47 years (range: 12 to 82 y). The vast majority arose in the superior nasal cavity and presented at the high Kadish-Morita stage. Frequent histologic findings included (1) lobulated and solid growth, (2) rosettes and/or neurofibrillary stroma, (3) high-grade cytology, (4) complex, often ciliated glands, (5) nonfocal pancytokeratin expression, (6) neuroendocrine pos+itivity, and (7) variable S100-positive sustentacular cells. Twelve patients with available follow-up (48%) developed progressive disease at a median 8 months (range: 0 to 114 mo to progression), and 7 (28%) died of disease. Despite disparate historical terminology, neuroepithelial differentiation is a recurrent and recognizable histologic pattern that is associated with aggressive behavior in sinonasal tumors. While tumors with this phenotype may originate from olfactory mucosa, well-developed epithelial features warrant separation from conventional ONB and neural elements distinguish them from most sinonasal carcinomas. Although their full histogenesis remains uncertain and some heterogeneity may exist, we propose that this pattern is sufficiently distinctive to merit separate recognition as olfactory carcinoma. Use of consistent nomenclature may facilitate greater recognition of tumors with this phenotype and understanding of their pathogenesis and classification.

Tumor-to-tumor metastasis (TTM) is a rare, but well-described phenomenon occurring in patients with multiple synchronous or metachronous primary malignancies. Olfactory neuroblastoma (ONB) is a rare malignant, neuroectodermal sinonasal tract tumor that occurs within the ethmoid sinus involving the cribriform plate. Very few cases of ONB have been documented to metastasize to other primary malignancies, but the reverse scenario is exceptional. During an evaluation for anosmia, a right nasal polyp was identified on imaging and endoscopy in a 66-year-old woman, with a polypectomy performed. Histologic examination showed classical features of a low-grade olfactory neuroblastoma, but within the tumor were isolated epithelioid cells which were strongly pancytokeratin immunoreactive. Review of the clinical history revealed lobular breast carcinoma treated 10 years earlier. Further evaluation with immunohistochemistry showed strong and diffuse nuclear estrogen and progesterone receptor reactivity, along with GATA3. These results confirmed TTM of an invasive lobular breast carcinoma to ONB. By employing a limited immunohistochemistry panel for all small round blue cell tumors that includes pancytokeratin, p40, S100 protein, SOX10, synaptophysin, desmin, CD99, and CD45, one is able to more accurately diagnose the classical tumor types, while also showing potentially unusual tumor features or exceptionally rare events like metastatic lobular breast carcinoma to ONB.

Introduction Primary thyroid gland malignant teratomas are extremely rare and can pose diagnostic challenges on fine needle aspiration (FNA) due to their cytomorphologic heterogeneity. Recent next generation sequencing studies have identified recurrent DICER1 hotspot mutations in these tumors, suggesting that malignant teratomas of the thyroid should be considered a distinct pathological entity. Herein, we review the clinico-radiologic and FNA findings in a series of DICER1 mutated malignant teratomas. Methods We performed a retrospective case review of 9 FNAs from 5 patients with a histologically confirmed malignant teratoma of the thyroid gland from 2 large tertiary care pathology practices. Results The patients included 4 females and 1 male, with an average age of 43 years (22-65 years). The nodules were centered within the thyroid gland and ranged from 1.7 to 10 cm in diameter. FNAs of primary thyroid teratomas demonstrate marked cellularity, epithelial proliferations, an absence of colloid, and a predominance of immature spindled cells, representing the mesenchymal and neural ectodermal components of these tumors. The FNA interpretations ranged from atypia of undetermined significance to overtly malignant. Three patients died of their disease and 2 are alive with no evidence of disease. Conclusions Malignant thyroid teratoma is a rare entity with cytomorphologic overlap with other high-grade neoplasms of the thyroid. Recent molecular studies have defined recurrent DICER1 mutations in malignant thyroid teratomas and propose these as a distinct clinicopathological entity. The features described here may be helpful in providing a correct prospective interpretation.

Background Fungal prostatitis is exceedingly rare with mostly case reports. Methods Electronic medical records at three medical centers were searched for cases of fungal prostatitis due to endemic mycoses and Cryptococcus over the preceding 10 years. Results Seven cases were identified from 105 600 prostate biopsies within the Southern California Permanente Medical Group for an incidence of 0.0066%. An additional eight cases were identified from two other health care systems. Excluding four patients without available clinical data, 11 patients were reviewed, most of whom underwent biopsy due to elevated prostate-specific antigen. Four were asymptomatic and the remainder had nonspecific signs or symptoms. All biopsies revealed granulomatous inflammation and fungal organisms. Seven patients had coccidioidomycosis, three patients had cryptococcosis (confirmed in two cases and suspected by organism morphology in the other), and one patient had likely histoplasmosis based on organism morphology. Prolonged antifungal treatment was standard; outcomes were favorable. Conclusion Fungal prostatitis due to endemic mycoses and Cryptococcus is uncommon and associated with favorable outcomes but generally involves prolonged therapy.

Solitary fibrous tumors (SFTs) of the orbit are rare. In order to further characterize the clinical and pathologic features of solitary fibrous tumor arising at this anatomic site, 12 cases of orbital SFTs were analyzed in conjunction with a review of 263 cases reported from the English literature in order to develop a risk prediction model. SFTs of the orbit were equally distributed between males (n = 5) and females (n = 7) with a mean patient age of 46.8 years (median 44.5 years; range 18–76 years) at initial diagnosis. The patients typically presented with swelling or mass around the orbit, with proptosis (n = 10), ptosis (n = 5), and visual changes (n = 6). Tumors were orbital (n = 10) or upper eyelid (n = 2). Mean tumor size was 2.5 cm (median 2.6 cm). Microscopically, the tumors were characterized by cytologically bland spindle cells with patternless growth, hypocellular and hypercellular areas, variable amounts of collagen, and ectatic, branching blood vessels. By immunohistochemistry, all cases had a strong nuclear STAT6 expression. All patients were initially managed with excision or biopsy, three with presurgical embolization. The two patients with biopsy only had persistent disease (mean 37.2 months), but a third patient developed distant bone metastasis at 86.9 months. Overall mean follow-up was 73.1 months: 9 patients are alive or dead without disease (mean 77.9 months), two patients with persistent disease, and one patient with metastatic disease at last follow-up (102 months). Incorporating cases sufficiently reported in the literature, a risk prediction model based on age > 45 years, tumor size > 3 cm, tumor necrosis, mitoses of > 4/2 mm(2), moderate to high cellularity, and moderate to severe pleomorphism allows for risk stratification for the development of local recurrence and distant metastasis. In conclusion, orbital SFTs are rare, but can be reliably diagnosed based on the presence of characteristic morphologic features and STAT6 immunohistochemistry. Orbital tumors tend to show a higher frequency of local recurrence than distant metastasis, which can be predicted by a risk stratification model unique to orbital tumors. With late disease common, long term clinical follow-up is recommended.

Lymphoepithelial carcinoma of salivary glands (LECSG) are rare neoplasms, reported in endemic populations (southeastern Chinese) with a strong Epstein-Barr virus (EBV) association. A retrospective series comparing EBV status within an ethnically diverse population (endemic vs. non-endemic patients) has not been reported. Sixteen LECSG were equally distributed between males (n = 8) and females (n = 8) with a median age of 54 years (range 18 to 85 years) at initial diagnosis. Ten patients were white, 4 Asian, and 2 black. The patients typically presented with swelling or mass for an average of 11.6 months. Tumors affected only major salivary glands: parotid (n = 13); submandibular (n = 3). Tumors were an average of 2.9 cm (range 1.5 to 5.8 cm). Nine of 16 (56%) patients had cervical lymph node metastases at presentation. No patients had nasopharyngeal or oropharyngeal tumors. Microscopically, the tumors were widely infiltrative, characterized by large polygonal to spindled cells arranged in a syncytial, lattice-like network in a background of lymphoplasmacytic cells. The neoplastic cells showed an open-vesicular nuclear chromatin to a more basaloid-morphology, the latter showing hyperchromatic nuclei and less cytoplasm, while nearly all of the cases had associated lymphoepithelial lesions/sialadenitis. By in situ hybridization, 8 of 16 cases had a strong, diffuse EBER expression (4 of 4 Asians; 4 of 12 non-Asians), while with immunohistochemistry all cases tested were pan-cytokeratin, CK5/6 and p63 reactive; none of the cases tested were p16 reactive. All patients were managed with wide or radical excision, 4 with concurrent chemoradiation, and 6 with radiation alone. Distant metastasis (lung, brain, and bone) developed in 2 patients. Overall follow-up (mean 3.8 years) revealed 12 patients alive and 2 dead, none with evidence of disease (mean 4.3 years); one white male alive with disease at 1.9 years, and one Asian female dead of disease at 4.2 years; both of these latter patients had Group IV stage disease. High stage (Group IV) patients had a shorter mean survival than lower stage patients: 3.1 versus 4.8 years, respectively. In conclusion, LECSG are uncommon primary neoplasms. Concurrent lymphoepithelial lesions may help suggest a primary tumor. The tumors, irrespective of race or ethnicity, may express EBER. There is an overall good survival, perhaps better for EBV-negative patients and for those with lower stage disease.

Contains fulltext : 220759.pdf (Publisher’s version ) (Open Access) During the last 60 years numerous significant attempts have been made to achieve a widely acceptable terminology and histological grading for laryngeal squamous intraepithelial lesions. While dysplasia was included in the pathology of the uterine cervix already in 1953, the term dysplasia was accepted in laryngeal pathology first after the Toronto Centennial Conference on Laryngeal Cancer in 1974. In 1963 Kleinsasser proposed a three-tier classification, and in 1971 Kambic and Lenart proposed a four-tier classification. Since then, four editions of the World Health Organisation (WHO) classification have been proposed (1978, 1991, 2005 and 2017). Several terms such as squamous intraepithelial neoplasia (SIN) and laryngeal intraepithelial neoplasia (LIN) are now being abandoned and replaced by squamous intraepithelial lesions (SIL). The essential change between the 2005 and 2017 WHO classifications is the attempt to induce a simplification from a four- to a two-tier system. The current WHO classification (2017) thus recommends the use of a two-tier system with reasonably clear histopathological criteria for the two groups: low-grade and high-grade dysplasia. Problems with interobserver variability apart, subjectivities and uncertainties remain, but to a lesser degree. Ongoing and additional molecular studies may help to clarify underlying events that will increase our understanding and possibly can facilitate our attempts to obtain an even better classification. The classification needs to be easier for the general pathologist to perform and easier for the clinician to interpret. These two objectives are equally important to provide each patient the best personalised treatment available for squamous intraepithelial lesions.

Polymorphous adenocarcinoma (PAC) shows histologic diversity with streaming and targetoid features whereas cribriform adenocarcinoma of salivary gland (CASG) demonstrates predominantly cribriform and solid patterns with glomeruloid structures and optically clear nuclei. Opinions diverge on whether CASG represents a separate entity or a variant of PAC. We aimed to assess the level of agreement among 25 expert Head and Neck pathologists in classifying these tumors. Digital slides of 48 cases were reviewed and classified as: PAC, CASG, tumors with ≥50% of papillary architecture (PAP), and tumors with indeterminate features (IND). The consensus diagnoses were correlated with a previously reported molecular alteration. The consensus diagnoses were PAC in 18/48, CASG in16/48, PAP in 3/48, and IND in 11/48. There was a fair interobserver agreement in classifying the tumors (κ= 0.370). The full consensus was achieved in 3 (6%) cases, all of which were classified as PAC. A moderate agreement was reached for PAC (κ= 0.504) and PAP (κ= 0.561), and a fair agreement was reached for CASG (κ= 0.390). IND had only slight diagnostic concordance (κ= 0.091). PAC predominantly harbored PRKD1 hotspot mutation, whereas CASG was associated with fusion involving PRKD1, PRKD2, or PRKD3. However, such molecular events were not exclusive as 7% of PAC had fusion and 13% of CASG had mutation. In conclusion, a fair to moderate interobserver agreement can be achieved in classifying PAC and CASG. However, a subset (23%) showed indeterminate features and was difficult to place along the morphologic spectrum of PAC/CASG among expert pathologists. This may explain the controversy in classifying these tumors.

Muon radiography is a technique that harnesses naturally occurring cosmic radiation to noninvasively determine the density of an object of interest. The technique has many similarities to that of medical X-ray examinations and can supply detailed density maps of the object. We propose the application of muon radiography to aspects of the long-term monitoring of nuclear waste. In particular, muon radiography would provide valuable information on the overburden of a prospective underground geological repository and would be able to identify unknown features, such as undocumented underground passages. Similarly, muon tomography is capable of confirming that containers that have nominally been emptied are in fact empty. Such safeguard measures are important to maintain continuity of knowledge and to develop robust deterrent strategies against the removal of monitored nuclear material. The presentation focuses on the results of simulations that address some of these questions. Details of assumptions regarding the detector requirements and run times necessary to perform the imaging are discussed and results from the various removal and misuse scenarios are presented.

Cosmic Ray Neutron Sensing (CRNS) is a powerful technique that allows non-invasive monitoring of soil moisture on length scales well matched for agricultural applications. One factor limiting the use of the technique within industrial agriculture settings is the high initial cost of Helium-3 or BF3 tubes typically used for ground level neutron monitoring. This paper discusses the use of Geant4 to design and optimise an alternative scintillator based epi-thermal neutron detector that may be applicable for challenges where cost is a higher driving factor than temporal resolution.

Tidal measurements are of great significance since they may provide us with essential data to apply towards protection of coastal communities and sea traffic. Currently, tide gauge stations and laser altimetry are commonly used for these measurements. On the other hand, muography sensors can be located underneath the seafloor inside an undersea tunnel where electric and telecommunication infrastructures are more readily available. In this work, the world’s first under-seafloor particle detector array called the Tokyo-bay Seafloor Hyper-Kilometric Submarine Deep Detector (TS-HKMSDD) was deployed underneath the Tokyo-Bay seafloor for conducting submarine muography. The resultant 80-day consecutive time-sequential muographic data were converted to the tidal levels based on the parameters determined from the first-day astronomical tide height (ATH) data. The standard deviation between ATH and muographic results for the rest of a 79-day measurement period was 12.85 cm. We anticipate that if the length of the TS-HKMSDD is extended from 100 m to a full-scale as large as 9.6 km to provide continuous tidal information along the tunnel, this muography application will become an established standard, demonstrating its effectiveness as practical tide monitor for this heavy traffic waterway in Tokyo and in other important sea traffic areas worldwide.

The radioactivity background are among the most dangerous background for low energy neutrino analysis in Super-Kamiokande (SK), like the solar neutrino analysis. Among them, the main contribution is coming from $^{222}$Rn, which is spread in the detector's water due to the water source and to the photo multiplier (PMT) emanations. Up to now, its exact distribution in the detector was not known. Using our knowledge of the radon concentration in the detector water, and the SK-IV solar data, we developed a model of the radon distribution in the detector. The uncertainty on the Rn concentration associated with this model was estimated to be $\sim0.1$ mBq/m$^{3}$

This paper reports the first T2K measurement of the transverse kinematic imbalance in the single-$\pi^+$ production channel of neutrino interactions. We measure the differential cross sections in the muon-neutrino charged-current interaction on hydrocarbon with a single $\pi^+$ and at least one proton in the final state, at the ND280 off-axis near detector of the T2K experiment. The extracted cross sections are compared to the predictions from different neutrino-nucleus interaction event generators. Overall, the results show a preference for models which have a more realistic treatment of nuclear medium effects including the initial nuclear state and final-state interactions.

This study evaluates the prognostic impact of several factors in oropharyngeal squamous cell carcinoma (OPSCC), controlling for human papillomavirus (HPV)-associated tumors and stage (American Joint Committee on Cancer 8th edition). All patients in Southern California Permanente Medical Group diagnosed with OPSCC between 2006 and 2012 tested for p16 immunohistochemistry were included. Review of all pathology materials was combined with central p16 testing. Multivariable analyses were performed. The cohort of 390 patients included 342 p16-positive and 48 p16-negative tumors. For all-comers, on univariate analysis, the following factors, when present, were associated with improved patient survival: p16-positive tumor (n = 324, p

SUMMARY Cosmic ray muons are highly penetrating, with some reaching several kilometres into solid rock. Consequently, muon detectors have been used to probe the interiors of large geological structures, by observing how the muon flux varies with direction of arrival. There is an increasing need to discriminate between materials differing only slightly in bulk density. A particularly demanding application is in monitoring underground reservoirs used for CO2 capture and storage, where bulk density changes of approximately 1 per cent are anticipated. Muon arrival is a random process, and it is the underlying expectation values, not the actual muon counts, which provide information on the physical parameters of the system. It is therefore necessary to distinguish between differences in muon counts due to real geological features, and those arising from random error. This is crucial in the low-contrast case, where the method can reach the information theoretic limit of what a data source can reveal, even in principle. To this end, methods to analyse information availability in low-contrast muon radiography have been developed, as have means to optimally interpret the available data, both for radiography and for tomography. This includes a method for calculating expectation values of muon flux for a given geological model directly, complementing existing Monte Carlo techniques. A case study, using a model of carbon capture is presented. It is shown that the new data analysis techniques have the potential to approximately double the effective sensitivity of the detectors.

Intraductal carcinoma (IC) is the new WHO designation for tumors previously encompassed by "low-grade cribriform cystadenocarcinoma" and "low-grade salivary duct carcinoma." The relationship of IC to salivary duct carcinoma (SDC) is controversial, even though they are considered to be distinct entities. IC is a rare low-grade malignant salivary gland neoplasm with histopathological features reminiscent of atypical ductal hyperplasia or ductal carcinoma in situ of the breast, showing diffuse S100 protein and mammaglobin positivity, while it is partially defined genetically. Recently, RET rearrangements including NCOA4-RET and TRIM27-RET have been described in IC. Here, we genetically characterize the largest cohort of IC to date (33 cases) including 8 cases with focal or widespread invasive growth and 1 case with lymph node metastasis. Thirty-three cases of IC were analyzed by next-generation sequencing (NGS) using the FusionPlex Solid Tumor kit (ArcherDX). Identified gene fusions were confirmed using fluorescence in situ hybridization break-apart and fusion probes and an reverse transcription polymerase chain reaction designed specifically for the detected breakpoints. Ten cases of SDC were analyzed for comparison using NGS panels that detect mutations and fusion transcripts. NGS analysis detected an NCOA4-RET fusion transcript in 11 cases of intercalated duct-type IC joining exon 7 or 8 of NCOA4 gene and exon 12 of the RET gene. Eight cases of IC had an invasive growth pattern, including one with widespread invasion and lymph node metastasis. Three invasive ICs harbored an NCOA4-RET fusion transcript, while 1 case was negative, and 2 cases were not analyzable. In addition, a novel TRIM27-RET fusion transcript between exon 3 of TRIM27 and exon 12 of RET was identified in 2 cases of IC with apocrine features, and one of them displayed invasive growth. Two IC cases with invasive growth harbored novel fusions TUT1-ETV5 and KIAA1217-RET, respectively. A total of 42.4% of the cases in this series of IC harbored fusions involving RET. Such fusion transcripts were not detected in any of the 10 SDC cases. We have confirmed NCOA4-RET as a predominant fusion in intercalated duct-type IC, including 3 cases with invasive growth pattern. A novel finding in our series was a case of widely invasive intercalated duct-type IC, with a single lymph node metastasis that revealed an NCOA4-RET fusion transcript. We also demonstrated that a subset of apocrine ICs harbored a TRIM27-RET gene fusion, including one case with invasive growth. In contrast, neither NCOA4-RET nor TRIM27-RET fusions were detected in any tested SDCs. Thus, the distinct molecular findings in IC and SDC support that the tumors are separate malignant salivary tumor entities. The presence of tumor-type-specific NCOA4-RET or TRIM27-RET translocations in a subset of widely invasive carcinomas with intercalated duct-like immunoprofiles suggests that a recharacterization of IC including its redesignation as "intercalated duct carcinoma, invasive or noninvasive" may be appropriate.

Schwannomas commonly occur in the head and neck but infrequently involve the oral cavity and rarely affect the tongue. The clinical and pathologic features of 19 cases of schwannoma arising in the tongue were analyzed. There were 13 males and 6 females ranging in age from 12 to 82 years (mean 34 years; median 29 years). The majority of tumors presented as an asymptomatic mass localized to the anterior two-thirds of the tongue. Histologically, 18 schwannomas exhibited characteristic Antoni A and B areas with the former pattern predominating. One tumor was composed exclusively of cellular Antoni A tissue and was classified as a cellular schwannoma. Tumor encapsulation was variable with nearly half of the lesions lacking a well-defined fibrous capsule. All were strongly and diffusely positive for S-100 protein. No recurrences were observed on clinical follow-up. Schwannoma of the tongue, although rare, should be separated from other types of lingual nerve sheath proliferations and tumors.

Objectives Although human papilloma virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is typically associated with a good prognosis, patients with T4 disease experience relatively high rates of treatment failure. Our aim was to identify predictors of relapse among patients with clinical T4 disease. Material & Methods A retrospective review was conducted of 93 consecutive patients who underwent definitive concurrent chemoradiation for HPV-associated OPSCC with clinical T4 disease from July 2006 to December 2015. Three-year outcomes, including locoregional recurrence (LRR), distant metastasis (DM), overall survival (OS), and cancer-specific survival (CSS), were examined and reported from the date of treatment completion. Multivariable analysis using a Cox proportional hazards model was performed to test associations between outcome and patient and disease characteristics as well as chemotherapy regimen (high-dose cisplatin (HDC) vs. other). Results Median follow-up for surviving patients was 50 months (range 18–133). For all-comers, 3-year rates of LRR, DM, OS, and CSS were 15%, 19%, 79%, and 86%, respectively. On multivariable analysis, the only factor prognostic for patient outcomes was the chemotherapy regimen. For patients who received HDC vs. an alternative regimen, 3-year LRR, DM, OS, and CSS, were 9% vs. 20% (p = 0.09), 10% vs. 28% (p = 0.04), 89% vs. 67% (p = 0.04), and 96% vs. 77% (p = 0.02), respectively. Conclusion In patients with HPV-associated OPSCC bearing clinical T4 disease, receipt of a concurrent systemic agent other than HDC resulted in increased treatment failure and inferior survival. This analysis suggests that HDC should remain the preferred concurrent regimen for these patients.

To recognize that thyroid nodules with atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS; Bethesda III) have different risks of malignancy based on genetic mutation and to consider molecular testing of nodules with AUS/FLUS to help avoid unnecessary morbidity or cost.Retrospective cohort study.Multiple locations within Southern California Permanente Medical Group.Patients included those with indeterminate thyroid nodules and AUS/FLUS on 2 separate fine-needle aspirations with positive ThyGenX testing from 2014 to 2017 who underwent thyroid surgery. Patients were classified as having benign or malignant disease. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features was considered benign.A total of 231 patients had repeat AUS/FLUS with positive molecular testing and surgery. The most frequent type of malignancy was papillary carcinoma, followed by follicular carcinoma. The overall prevalence of malignancy in nodules with mutations was 74.0%, although there was considerable variation:Not all molecular mutations in thyroid nodules with AUS/FLUS have a high risk of malignancy. Of note, patients with

The use of diverse terminology may lead to inconsistent diagnosis and subsequent mistreatment of lesions within the proliferative verrucous leukoplakia (PVL) spectrum. The objectives of this study were: (a) to measure inter-observer variability between a variety of pathologists diagnosing PVL lesions; and (b) to evaluate the impact of diverse terminologies on understanding, interpretation, and subsequent treatment planning by oral and maxillofacial surgeons (OMFS). Six oral pathologists (OP) and six head and neck pathologists (HNP) reviewed 40 digitally scanned slides of PVL-type lesions. Inter-observer agreement on diagnoses was evaluated by Fleiss’ kappa analysis. The most commonly used diagnostic terminologies were sent to ten OMFS to evaluate their resulting interpretations and potential follow-up treatment approaches. The overall means of the surgeons’ responses were compared by Student t test. There was poor inter-observer agreement between pathologists on the diagnosis of PVL lesions (κ = 0.270), although there was good agreement (κ = 0.650) when diagnosing frankly malignant lesions. The lowest agreement was in diagnosing verrucous hyperplasia (VH) with/without dysplasia, atypical epithelial proliferation (AEP), and verrucous carcinoma (VC). The OMFS showed the lowest agreement on identical categories of non-malignant diagnoses, specifically VH and AEP. This study demonstrates a lack of standardized terminology and diagnostic criteria for the spectrum of PVL lesions. We recommend adopting standardized criteria and terminology, proposed and established by an expert panel white paper, to assist pathologists and clinicians in uniformly diagnosing and managing PVL spectrum lesions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12105-019-01035-z) contains supplementary material, which is available to authorized users.

Somatic mutations have been identified in aldosterone-producing adenomas (APAs) in genes that include KCNJ5 , ATP1A1 , ATP2B3 , and CACNA1D . Based on independent studies, there appears to be racial differences in the prevalence of somatic KCNJ5 mutations, particularly between East Asians and Europeans. Despite the high cardiovascular disease mortality of blacks, there have been no studies focusing on somatic mutations in APAs in this population. In the present study, we investigated genetic characteristics of APAs in blacks using a CYP11B2 (aldosterone synthase) immunohistochemistry-guided next-generation sequencing approach. The adrenal glands with adrenocortical adenomas from 79 black patients with primary aldosteronism were studied. Seventy-three tumors from 69 adrenal glands were confirmed to be APAs by CYP11B2 immunohistochemistry. Sixty-five of 73 APAs (89%) had somatic mutations in aldosterone-driver genes. Somatic CACNA1D mutations were the most prevalent genetic alteration (42%), followed by KCNJ5 (34%), ATP1A1 (8%), and ATP2B3 mutations (4%). CACNA1D mutations were more often observed in APAs from males than those from females (55% versus 29%, P =0.033), whereas KCNJ5 mutations were more prevalent in APAs from females compared with those from males (57% versus 13%, P CACNA1D . Determination of racial differences in the prevalence of aldosterone-driver gene mutations may facilitate the development of personalized medicines for patients with primary aldosteronism.

Tidal measurements are of great significance since they may provide us with essential data to apply towards protection of coastal communities and sea traffic. Currently, the tide gauge stations, satellite-based, pressure-based and ultrasonic-based techniques are commonly used. However, with these techniques, sensors have to be either floated on the sea surface or sunk onto the seafloor. The former option makes it difficult to conduct the tide measurements in high traffic maritime sea channels, and the latter option requires the construction of undersea electric and telecommunication infrastructures to support real time monitoring. On the other hand, with muography, sensors can be located underneath the seafloor inside, for example, an undersea tunnel where the electric and telecommunication infrastructures are more readily available. In this work, the world’s first under-seafloor particle detector array called the Tokyo-bay Seafloor Hyper-Kilometric Submarine Deep Detector (TS-HKMSDD) was deployed underneath the Tokyo-Bay seafloor for conducting submarine muography. Time-sequential muographic data were converted to the tidal levels above the detector and compared with the data acquired from the nearby tide gauge station. The results were consistent, indicating that submarine muography could be an alternative tool for tide measurements. We anticipate that if the length of the TS-HKMSDD is extended from 100 m to a full-scale as large as 9.6 km to provide continuous tidal information along the tunnel, muography will become an established standard, demonstrating its effectiveness as practical tide monitor for this heavy traffic waterway in Tokyo and in other important sea traffic areas worldwide.

In the cranio-facial skeleton, a heterogeneous group of well characterized fibro-osseous lesions can be distinguished. Whereas fibrous dysplasia can affect any skeletal bone, ossifying fibroma and cemento-osseous dysplasia exclusively develop in the cranio-facial region, with most subtypes restricted to the tooth bearing areas of the jaws. Herein we present a series of 20 fibro-osseous lesions that developed mostly in the frontal bone and in the mandible, presenting as expansile intramedullary tumors with a unique histologic appearance and an indolent clinical course. We provide evidence that these tumors are distinct from the categories included in the WHO classification and are therefore currently unclassifiable. The definition of cemento-ossifying fibroma as an odontogenic neoplasm developing only in close proximity to teeth should be re-considered and incorporate also extragnathic lesions as shown here.

Background Human papillomavirus (HPV)–associated oropharyngeal squamous cell carcinoma (OPSCC) has excellent control rates compared to nonvirally associated OPSCC. Multiple trials are actively testing whether de-escalation of treatment intensity for these patients can maintain oncologic equipoise while reducing treatment-related toxicity. We have developed OP-TIL, a biomarker that characterizes the spatial interplay between tumor-infiltrating lymphocytes (TILs) and surrounding cells in histology images. Herein, we sought to test whether OP-TIL can segregate stage I HPV-associated OPSCC patients into low-risk and high-risk groups and aid in patient selection for de-escalation clinical trials. Methods Association between OP-TIL and patient outcome was explored on whole slide hematoxylin and eosin images from 439 stage I HPV-associated OPSCC patients across 6 institutional cohorts. One institutional cohort (n = 94) was used to identify the most prognostic features and train a Cox regression model to predict risk of recurrence and death. Survival analysis was used to validate the algorithm as a biomarker of recurrence or death in the remaining 5 cohorts (n = 345). All statistical tests were 2-sided. Results OP-TIL separated stage I HPV-associated OPSCC patients with 30 or less pack-year smoking history into low-risk (2-year disease-free survival [DFS] = 94.2%; 5-year DFS = 88.4%) and high-risk (2-year DFS = 82.5%; 5-year DFS = 74.2%) groups (hazard ratio = 2.56, 95% confidence interval = 1.52 to 4.32; P Conclusions OP-TIL can identify stage I HPV-associated OPSCC patients likely to be poor candidates for treatment de-escalation. Following validation on previously completed multi-institutional clinical trials, OP-TIL has the potential to be a biomarker, beyond clinical stage and HPV status, that can be used clinically to optimize patient selection for de-escalation.

BACKGROUND: Patients with p16(+) oropharyngeal squamous cell carcinoma (OPSCC) are potentially cured with definitive treatment. However, there are currently no reliable biomarkers of treatment failure for p16(+) OPSCC. Pathologist-based visual assessment of tumor cell multinucleation (MN) has been shown to be independently prognostic of disease-free survival (DFS) in p16(+) OPSCC. However, its quantification is time intensive, subjective, and at risk of interobserver variability. METHODS: We present a deep-learning–based metric, the multinucleation index (MuNI), for prognostication in p16(+) OPSCC. This approach quantifies tumor MN from digitally scanned H&E-stained slides. Representative H&E-stained whole-slide images from 1094 patients with previously untreated p16(+) OPSCC were acquired from 6 institutions for optimization and validation of the MuNI. RESULTS: The MuNI was prognostic for DFS, overall survival (OS), or distant metastasis–free survival (DMFS) in p16(+) OPSCC, with HRs of 1.78 (95% CI: 1.37–2.30), 1.94 (1.44–2.60), and 1.88 (1.43–2.47), respectively, independent of age, smoking status, treatment type, or tumor and lymph node (T/N) categories in multivariable analyses. The MuNI was also prognostic for DFS, OS, and DMFS in patients with stage I and stage III OPSCC, separately. CONCLUSION: MuNI holds promise as a low-cost, tissue-nondestructive, H&E stain–based digital biomarker test for counseling, treatment, and surveillance of patients with p16(+) OPSCC. These data support further confirmation of the MuNI in prospective trials. FUNDING: National Cancer Institute (NCI), NIH; National Institute for Biomedical Imaging and Bioengineering, NIH; National Center for Research Resources, NIH; VA Merit Review Award from the US Department of VA Biomedical Laboratory Research and Development Service; US Department of Defense (DOD) Breast Cancer Research Program Breakthrough Level 1 Award; DOD Prostate Cancer Idea Development Award; DOD Lung Cancer Investigator-Initiated Translational Research Award; DOD Peer-Reviewed Cancer Research Program; Ohio Third Frontier Technology Validation Fund; Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering; Clinical and Translational Science Award (CTSA) program, Case Western Reserve University; NCI Cancer Center Support Grant, NIH; Career Development Award from the US Department of VA Clinical Sciences Research and Development Program; Dan L. Duncan Comprehensive Cancer Center Support Grant, NIH; and Computational Genomic Epidemiology of Cancer Program, Case Comprehensive Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, the US Department of VA, the DOD, or the US Government.

Laryngeal mesenchymal neoplasms are rare, with smooth muscle tumors comprising a small subset. Specifically, Epstein-Barr virus (EBV)-associated smooth muscle tumors are exceptionally rare, lacking a comprehensive evaluation of their clinical and histologic features. Two patients (a 59 year old male and 51 year old female) had received renal transplants 156 and 240 months, respectively prior to onset of laryngeal symptoms. Supraglottic polypoid masses were identified and removed conservatively. Histologically, the tumors were hypercellular, showing alternating light and dark areas, the latter composed of primitive appearing round cells, while a more characteristic spindled tumor cell population was noted in the remaining areas. Cytoplasmic vacuoles were noted adjacent to the nucleus. There was no tumor necrosis or pleomorphism, but increased mitotic figures (11–12/2 mm(2)) were seen, without atypical forms. The tumor cells were strongly immunoreactive with smooth muscle actin and smooth muscle myosin heavy chain and with Epstein-Barr virus encoded RNA (EBER) by in situ hybridization. These patients were reviewed in the context of a thorough English literature review, which demonstrates a wide age range at presentation without a sex predilection, but with most patients from specific ethnic groups (Chinese, Thai, Pilipino). Three-quarters of patients are part of multifocal disease and the majority are post-renal transplantation patients. Conservative management seems to yield the best overall outcome for these indolent tumors. In conclusion, EBV-associated smooth muscle tumors should be considered in any immunocompromised patient with a head and neck smooth muscle tumor, especially when EBER is documented by in situ hybridization. Conservative management may be employed, even when multifocal tumors are documented.

Thyroid nodules are a very common clinical condition. The 2015 American Thyroid Association (ATA) guidelines recommend surgical excision for Bethesda IV nodules. The use of intraoperative frozen section (FS) has been recommended as a strategy to tailor the extent of the initial surgery. We critically evaluated the literature that discusses the utility and cost-effectiveness of FS to make an intraoperative decision in patients with thyroid nodules classified as follicular neoplasm. FS should not be recommended as a routine intraoperative test to assess for malignancy in thyroid follicular patterned lesions due to its low performance; the high number of deferred results; the inability to adequately assess histologically defining features; the improvements in risk stratification guiding total thyroidectomy; and the low cost-effectiveness of FS.

In this paper we demonstrate that it is possible to produce low cost neutron-sensitive detectors using stereo-lithography additive manufacturing. A curable scintillating resin is made by mixing BN:ZnS with a commercially available UV resin. This resin is used to print several small area neutron detectors made of arrays of BN:ZnS cones that can be directly coupled to a photo-multiplier tube., 7 pages, 6 figures