Novel MIR143HG::PLAG1 gene fusion identified in a rectal myxoid leiomyosarcoma.

Myxoid leiomyosarcoma (MLS) is a rare but well-documented tumor that often portends a poor prognosis compared to the conventional leiomyosarcoma. This rare sarcoma has been reported in the uterus, external female genitalia, soft tissue, and other locations. However, a definite rectal MLS has not been reported. Recently five cases of MLS were reported to harbor PLAG1 fusions (TRPS1::PLAG1, RAD51B::PLAG1, and TRIM13::PLAG1). In this report, we present a case of rectal MLS with a novel MIR143HG::PLAG1 fusion detected by RNA next-generation sequencing.

Synovial Sarcoma of the Gastrointestinal Tract.

We report the clinicopathologic and immunohistochemical features of 18 cases of confirmed primary synovial sarcoma of the gastrointestinal tract. The neoplasms arose in 10 women and 8 men ranging in age from 23 to 81 years (mean: 50; median: 57.5 years). The tumors for which size was known ranged from 1.8 to 15.0 cm (mean: 5.2; median: 5.1 cm). Microscopically, 14 synovial sarcomas were of the monophasic type, 2 were biphasic, and 2 were poorly differentiated. Immunohistochemical analysis of 4 cases showed strong, diffuse staining for SS18::SSX (4/4 cases). Pancytokeratin and EMA immunohistochemistry were performed on 13 and 9 tumors, respectively, and each showed patchy-to-diffuse staining. By reverse-transcription PCR, 3 cases were positive for the SS18::SSX1, and 2 cases were positive for the SS18::SSX2 gene fusion. Six cases contained an SS18 gene rearrangement by fluorescence in situ hybridization, and next-generation sequencing identified an SS18::SSX2 gene fusion in one case. Clinical follow-up information was available for 9 patients (4 months to 4.6 years; mean, 2.8 y; median: 29 months), and one patient had a recent diagnosis. Three patients died of disease within 41 to 72 months (mean, 56 months) of their diagnosis. Five patients were alive without evidence of disease 4 to 52 months (mean, 17.6 months) after surgery; of whom 1 of the patients received additional chemotherapy treatment after surgery because of recurrence of the disease. A single patient was alive with intraabdominal recurrence 13 months after surgery. We conclude that synovial sarcoma of the gastrointestinal tract is an aggressive tumor, similar to its soft tissue counterpart, with adverse patient outcomes. It is important to distinguish it from morphologically similar gastrointestinal tract lesions that may have different treatment regimens and prognoses.

The Morphologic Spectrum of Gastric Type 1 Enterochromaffin-Like Cell Neuroendocrine Tumors.

Although most well-differentiated gastric neuroendocrine tumors (gNETs) arise from enterochromaffin-like (ECL) cells in patients with autoimmune metaplastic atrophic gastritis (AMAG), the morphologic spectrum of these type 1 ECL-cell gNETs is not well defined. The extent of metaplastic progression in the background mucosa of AMAG patients with gNETs is likewise unclear. Here we report the histomorphology of 226 gNETs, including 214 type 1 gNETs (78 cases from 50 AMAG patients) pooled from a population with high AMAG prevalence. Most type 1 gNETs were ≤1.0 cm, of low grade, and multifocal, consistent with the results of previous reports. However, a high proportion (70/214, 33%) displayed unusual gNET morphologies not previously appreciated in AMAG patients. Unlike other type 1 gNETs with conventional neuroendocrine tumor morphologies, unconventional type 1 gNETs displayed cribriform networks of atrophic cells embedded within myxoid matrix (secretory-cribriform variant, 59%), sheets of deceptively bland discohesive cells resembling inflammatory infiltrates (lymphoplasmacytoid variant, 31%), or wreath-like arrangements of columnar cells wrapped around collagenous cores (pseudopapillary variant, 14%). Another unusual feature was that unconventional gNETs grew laterally within the mucosa (50/70, 71%) and were only rarely sampled from the submucosa (3/70, 4%). These features also differed from the conspicuous radial nodules (99/135, 73%) and frequent submucosal involvement (57/135, 42%) observed for conventional gNETs (P < .0001). Irrespective of morphology, type 1 gNETs were nearly always detected at first AMAG diagnosis (45/50, 90%) and tended to persist thereafter (34/43, 79%), despite similar clinical symptoms and laboratory values between AMAG patients with gNETs and those without. However, unlike AMAG patients without gNETs (n = 50), the background mucosa in patients with gNETs (n = 50) had already progressed to the morphologic equivalent of end-stage metaplasia (P < .0001). This included diffuse loss of parietal cells (92% vs 52%), complete intestinal metaplasia (82% vs 40%), and pancreatic metaplasia (56% vs 6%). Thus, type 1 ECL-cell gNETs are morphologically heterogeneous with a high prevalence of unconventional gNET morphologies. They tend to present silently at first AMAG diagnosis as multifocal lesions that persist within fields of mature metaplasia.

Sinonasal Myxoma: A Distinct Entity or a Myxoid Variant of Desmoid Fibromatosis?

Sinonasal myxoma (SNM) is a rare benign mesenchymal tumor that arises in the sinonasal cavity or maxilla and almost exclusively affects young children. Currently, it is considered a specific entity, but its molecular characteristics have not been reported. Lesions diagnosed as SNM and odontogenic myxoma/fibromyxoma were identified from the participating institutions, and the clinicopathologic features were recorded. Immunohistochemistry for ß-catenin was performed in all cases with available tissue. Next-generation sequencing was performed in all cases with SNM. Five patients with SNM were identified, including 3 boys and 2 girls with an age range of 20-36 months (mean: 26 months). The tumors were well defined, centered in the maxillary sinus, surrounded by a rim of woven bone, and composed of a moderately cellular proliferation of spindle cells oriented in intersecting fascicles in a variably myxocollagenous stroma that contained extravasated erythrocytes. Histologically, the tumors resembled myxoid desmoid fibromatosis. Three tested cases showed nuclear expression of ß-catenin. In 3 tumors, next-generation sequencing revealed intragenic deletions of APC exons 5-6, 9 and 15, or 16, respectively, with concurrent loss of the other wild-type copy of APC predicted to result in biallelic inactivation. The deletions were identical to those that occur in desmoid fibromatosis, and copy number analysis raised the possibility that they were germline. In addition, 1 case showed the possible deletion of APC exons 12-14, and another case exhibited a CTNNB1 p. S33C mutation. Ten patients with odontogenic myxoma/fibromyxoma were identified, including 4 women and 6 men (mean age: 42 years). Seven tumors involved the mandible and 3 the maxilla. Histologically, the tumors differed from SNM, and all cases lacked nuclear expression of ß-catenin. These findings suggest that SNM represents a myxoid variant of desmoid fibromatosis that often arises in the maxilla. The APC alterations might be germline, and therefore, genetic testing of the affected patients should be considered.

Intraosseous hibernoma: clinicopathologic and imaging analysis of 18 cases.

AIMS: Intraosseous hibernomas are rarely reported tumours with brown adipocytic differentiation of unknown aetiology, with only 38 cases documented in the literature. We sought to further characterise the clinicopathologic, imaging and molecular features of these tumours. METHODS AND RESULT: Eighteen cases were identified occurring in eight females and 10 males (median age = 65 years, range = 7-75). Imaging indication was cancer surveillance/staging in 11 patients and clinical concern for a metastasis was raised in 13 patients. The innominate bone (7), sacrum (5), mobile spine (4), humerus (1) and femur (1) were involved. Median tumour size was 1.5 cm (range = 0.8-3.8). Tumours were sclerotic (11), mixed sclerotic and lytic (4) or occult (1). Microscopically, tumours were composed of large polygonal cells with distinct cell membranes, finely vacuolated cytoplasm, central or paracentral small bland nuclei with prominent scalloping. Growth around trabecular bone was observed. Tumour cells were immunoreactive for S100 protein (15/15) and adipophilin (5/5), while negative for keratin AE1/AE3(/PCK26) (0/14) and brachyury (0/2). Chromosomal microarray analysis, performed on four cases, did not show clinically significant copy number variation across the genome or on 11q, the site of AIP and MEN1. CONCLUSION: Analysis of 18 cases of intraosseous hibernoma, to our knowledge, the largest series to date, revealed that these tumours are most often detected in the spine and pelvis of older adults. Tumours were generally small, sclerotic and frequently found incidentally and can raise concern for metastasis. Whether or not these tumours are related to soft tissue hibernomas is uncertain.

Gastrointestinal and Hepatobiliary Immune-related Adverse Events: A Histopathologic Review.

Immune checkpoint inhibitors have been increasingly used to treat various malignant neoplasms. Despite their superior efficacy in treating certain ones, their global immune-activation effect leads to systemic side effects, referred to as immune-related adverse events. Immune-related adverse events affect a variety of organs, including the skin, gastrointestinal, hepatobiliary, and endocrine organs. Gastrointestinal tract immune-related adverse events present with a wide range of symptoms with variable severity, which may lead to treatment interruption and administration of immunosuppression therapy in many cases. Histopathologic changes are diverse, overlapping with many other conditions. Therefore, recognizing these changes is crucial in diagnosing immune-related adverse events. This review discusses the pathologic manifestations of gastrointestinal immune-related adverse events and discusses the primary differential diagnoses.

Current concepts in the diagnosis and pathobiology of intraepithelial neoplasia: A review by organ system.

Answer questions and earn CME/CNE In this report, a team of surgical pathologists has provided a review of intraepithelial neoplasia in a host of (but not all) anatomic sites of interest to colleagues in various medical specialties, namely, uterine cervix, ovary, breast, lung, head and neck, skin, prostate, bladder, pancreas, and esophagus. There is more experience with more readily accessible sites (such as the uterine cervix and skin) than with other anatomic sites, and the lack of uniform terminology, together with divergent biology in various sites, makes it difficult to paint a unifying, relevant portrait. The authors' aim was to provide a framework from which to move forward as we care for patients with such precancerous lesions. CA Cancer J Clin 2016;66:408-436. © 2016 American Cancer Society.

Utility of ancillary studies in the diagnosis and risk assessment of Barrett's esophagus and dysplasia.

Barrett's esophagus (BE) is a major risk factor for the development of esophageal adenocarcinoma (EAC). BE patients undergo periodic endoscopic surveillance with biopsies to detect dysplasia and EAC, but this strategy is imperfect owing to sampling error and inconsistencies in the diagnosis and grading of dysplasia, which may result in an inaccurate diagnosis or risk assessment for progression to EAC. The desire for more accurate diagnosis and better risk stratification has prompted the investigation and development of potential biomarkers that might assist pathologists and clinicians in the management of BE patients, allowing more aggressive endoscopic surveillance and treatment options to be targeted to high-risk individuals, while avoiding frequent surveillance or unnecessary interventions in those at lower risk. It is known that progression of BE to dysplasia and EAC is accompanied by a host of genetic alterations, and that exploration of these markers could be potentially useful to diagnose/grade dysplasia and/or to risk stratify BE patients. Several biomarkers have shown promise in identifying early neoplastic transformation and thus may be useful adjuncts to histologic evaluation. This review provides an overview of some of the currently available biomarkers and assays, including p53 immunostaining, Wide Area Transepithelial Sampling with Three-Dimensional Computer-Assisted Analysis (WATS3D), TissueCypher, mutational load analysis (BarreGen), fluorescence in situ hybridization, and DNA content abnormalities as detected by DNA flow cytometry.

Limited sinonasal Rosai-Dorfman disease presenting as chronic sinusitis.

AIMS: The sinonasal tract is a common extranodal site for Rosai-Dorfman disease (RDD). Recently, histiocytes with features of RDD were identified in the clinical setting of chronic sinusitis. This study evaluates whether this phenomenon should be considered part of the RDD spectrum or classified separately as RDD-like histiocytes. METHODS AND RESULTS: We prospectively collected 13 cases showing histological features of RDD in chronic sinusitis patients and identified 14 with similar findings (3.5%) via retrospective review of 403 sinus contents over 2 years. All 27 cases displayed nodular aggregates of eosinophilic histiocytes with intermixed lymphoplasmacytic inflammation, prominent eosinophils and emperipolesis. The histiocytes were positive for S100 protein and cyclin D1 and negative for CD1a and CD207. All patients presented with severe chronic sinusitis without tumour formation or systemic symptoms. Twelve patients with follow-up (55%) required repeat sinus surgery compared with just 43 other sinusitis patients evaluated (11%); features of RDD were present in their additional specimens. Two cases that underwent targeted next-generation sequencing (20%) had oncogenic mutations in NF1 and KEAP1. CONCLUSIONS: Overall, these findings confirm diagnostic histological and immunohistochemical features of RDD in a subset of chronic sinusitis specimens. While patients uniformly lack systemic involvement or tumefactive growth, they have a high risk of recurrent sinus disease. Although the relatively subtle nature of the findings raises consideration of separate classification, the presence of occasional oncogenic mutations and evidence of consistent MAPK/ERK pathway activation via cyclin D1 positivity suggests that this phenomenon represents a unique limited manifestation of RDD.

Gastrointestinal and Hepatobiliary Immune-related Adverse Events: A Histopathologic Review.

Immune checkpoint inhibitors have been increasingly used to treat various malignant neoplasms. Despite their superior efficacy in treating certain ones, their global immune-activation effect leads to systemic side effects, referred to as immune-related adverse events. Immune-related adverse events affect a variety of organs, including the skin, gastrointestinal, hepatobiliary, and endocrine organs. Gastrointestinal tract immune-related adverse events present with a wide range of symptoms with variable severity, which may lead to treatment interruption and administration of immunosuppression therapy in many cases. Histopathologic changes are diverse, overlapping with many other conditions. Therefore, recognizing these changes is crucial in diagnosing immune-related adverse events. This review discusses the pathologic manifestations of gastrointestinal immune-related adverse events and discusses the primary differential diagnoses.

Low to Intermediate (Borderline) Grade Breast Spindle Cell Lesions on Needle Biopsy: Diagnostic Approach and Clinical Management.

Spindle cell proliferations of the breast are a heterogeneous group of lesions ranging from benign or reactive lesions to aggressive malignant neoplasms. Diagnosis on core biopsy can be particularly challenging as lesions displaying different lineages associated with variable outcomes share overlapping morphologies (scar vs. fibromatosis-like metaplastic carcinoma) whereas individual entities can exhibit a large variety of appearances (myofibroblastoma). In this review, lesions are grouped into lineage, when possible, including those showing fibroblastic/myofibroblastic differentiation, ranging from entities that require no additional management, such as scar and nodular fasciitis, to those with unpredictable clinical outcomes such as fibromatosis and solitary fibrous tumor or locally aggressive behavior such as dermatofibrosarcoma protuberans. The review of low-grade vascular lesions includes atypical vascular lesion and low-grade angiosarcoma. Also discussed are various adipocytic lesions ranging from lipoma to liposarcoma, and rare smooth muscle and neural entities more commonly encountered in locations outside the breast, such as leiomyoma, neurofibroma, schwannoma, or granular cell tumor. Optimal histological evaluation of these entities merges clinical and radiologic data with morphology and ancillary testing. We present our approach to immunohistochemical and other ancillary testing and highlight issues in pathology correlation with imaging. Recent updates in the management of breast spindle cell lesions are addressed. In a well-sampled lesion with radiographic concordance, the core biopsy diagnosis reliably guides management and we advocate the inclusion of management recommendations in the pathology report. Precise characterization using up to date guidelines is important to identify a subset of patients who may safely avoid unnecessary surgical procedures. A multidisciplinary approach with close collaboration with our clinical colleagues is emphasized.

Novel fusion genes in spindle cell rhabdomyosarcoma: The spectrum broadens.

Rhabdomyosarcoma (RMS) encompasses a heterogeneous group of tumors with striated muscle differentiation. RMSs are classified as alveolar, embryonal, spindle cell/sclerosing, and pleomorphic types and molecular analysis of these tumors has identified aberrations that are useful in their further subclassification. Spindle cell rhabdomyosarcoma (SpRMS) is uncommon and has been described with VGLL2 fusions, EWSR1/FUS-TFCP2 rearrangements, and myoD1 mutations-the mutations are associated with significantly different prognoses. In addition, the NCOA2-MEIS1 fusion gene was recently described in two primary intraosseous RMS that contained spindle cell components. Herein, we report three cases of SpRMS harboring different novel fusion genes, one possessing EP300-VGLL3, a second with NCOA2-MEIS1 and CAV1-MET, and the third case had HMGA2-NEGR1 and multiple amplified genes.

Perianal Paget's disease as spread from non-invasive colorectal adenomas.

AIMS: Paget's disease of the perianal skin is a rare form of extramammary Paget's disease, and may be a primary intraepithelial adnexal neoplasm or secondary due to spread from an underlying colorectal lesion, nearly always colorectal adenocarcinoma. Secondary perianal Paget's disease associated with non-invasive colorectal adenomas is exceedingly uncommon, with only a few reported cases. METHODS AND RESULTS: Herein, we present the clinical and pathological features of the largest series of secondary perianal Paget's disease arising in association with colorectal adenomas. There was gender parity and the median age was 72 years (range = 68-76 years). In all cases, perianal Paget's disease was associated with colorectal adenomas, including three (75%) conventional tubular adenomas and one (25%) tubulovillous adenoma with serrated foci. All adenomas had high-grade dysplasia and one had intramucosal adenocarcinoma (lamina propria invasion; Tis), but all lacked submucosal invasion. The intraepithelial Paget's cells showed a colorectal phenotype by immunohistochemistry in all cases. At follow-up, two patients had no evidence of disease at 6 and 87 months, one had residual perianal Paget's disease at 8 months and one developed invasive adenocarcinoma of the perianal tissue at 36 months. CONCLUSIONS: Similar to its mammary analogue, secondary perianal Paget's disease may arise in association with invasive and/or in-situ colorectal lesions. Although the latter is an uncommon presentation of a recognised rare disease, knowledge of this phenomenon is important to forestall overdiagnosis of invasion and potential overtreatment. The clinical course is variable, such that close follow-up is required.

Cell polarity (the 'four lines') distinguishes gastric dysplasia from epithelial changes in reactive gastropathy.

AIMS: Gastric dysplasia is a risk factor for synchronous and subsequent gastric carcinoma. Distinguishing gastric dysplasia from reactive changes is subject to interobserver disagreement and is a frequent reason for expert consultation. We previously used assessment of surface cell polarity (the 'four lines') as a key feature to decrease equivocal diagnoses in Barrett oesophagus. In the current study, we examined for the presence or absence of the four lines in gastric dysplasia and reactive gastropathy. MATERIALS AND METHODS: The study includes all (n = 91) in-house biopsies with at least gastric dysplasia from the surgical pathology archives of two academic institutions during a 5-year period from 2008 to 2012. A reactive gastropathy group (n = 60) was created for comparison. RESULTS: The dysplasia/neoplasia group was comprised of 14 biopsies of gastric foveolar-type dysplasia, 59 of intestinal-type dysplasia, 14 with dysplasia in fundic gland polyps, three pyloric gland adenomas and one oxyntic gland adenoma. Loss of surface cell polarity was seen in all 88 dysplasia cases with evaluable surface epithelium. All 57 reactive gastropathy cases with evaluable surface epithelium showed intact surface cell polarity except in focal areas directly adjacent to erosions in 17 cases, where the thin wisp of residual surface mucin could not be appreciated on haematoxylin and eosin. CONCLUSION: Surface cell polarity (the four lines) was lost in all gastric dysplasia biopsies with evaluable surface epithelium and maintained in all biopsies of reactive gastropathy. Caution should be taken in using this feature adjacent to erosions in reactive gastropathy.

GEAMP, a novel gastroesophageal junction carcinoma cell line derived from a malignant pleural effusion.

Gastroesophageal junction (GEJ) cancer remains a clinically significant disease in Western countries due to its increasing incidence, which mirrors that of esophageal cancer, and poor prognosis. To develop novel and effective approaches for prevention, early detection, and treatment of patients with GEJ cancer, a better understanding of the mechanisms driving pathogenesis and malignant progression of this disease is required. These efforts have been limited by the small number of available cell lines and appropriate preclinical animal models for in vitro and in vivo studies. We have established and characterized a novel GEJ cancer cell line, GEAMP, derived from the malignant pleural effusion of a previously treated GEJ cancer patient. Comprehensive genetic analyses confirmed a clonal relationship between GEAMP cells and the primary tumor. Targeted next-generation sequencing identified 56 nonsynonymous alterations in 51 genes including TP53 and APC, which are commonly altered in GEJ cancer. In addition, multiple copy-number alterations were found including EGFR and K-RAS gene amplifications and loss of CDKN2A and CDKN2B. Histological examination of subcutaneous flank xenografts in nude and NOD-SCID mice showed a carcinoma with mixed squamous and glandular differentiation, suggesting GEAMP cells contain a subpopulation with multipotent potential. Finally, pharmacologic inhibition of the EGFR signaling pathway led to downregulation of key downstream kinases and inhibition of cell proliferation in vitro. Thus, GEAMP represents a valuable addition to the limited number of bona fide GEJ cancer cell lines.

Phase II Study of Preoperative Chemoradiotherapy with Oxaliplatin, Infusional 5-Fluorouracil, and Cetuximab Followed by Postoperative Docetaxel and Cetuximab in Patients with Adenocarcinoma of the Esophagus: A Trial of the ECOG-ACRIN Cancer Research Group (E2205).

BACKGROUND: A standard approach to treating resectable esophageal adenocarcinoma is chemoradiotherapy (CRT) followed by surgery; however, recurrence is common. To improve this, we designed a single-arm, phase II trial that added an epidermal growth factor receptor (EGFR) inhibitor, cetuximab (C), to CRT, with the hypothesis that EGFR inhibition would improve pathologic complete response (pCR) rate. MATERIALS AND METHODS: We aimed to increase the pCR rate from 25% to 45%. A Simon two-stage design (α and ß of 0.10) required pCR/enrolled 5/18 for stage 1 and 14/40 total. CRT: oxaliplatin 85 mg/m2 days 1, 15, and 29; infusional 5-fluorouracil 180 mg/m2 /24 hours × 35 days; C 400 mg/m2 day 1 then 250 mg/m2 days 8, 15, 22, and 29 and radiation (intensity modulated radiotherapy [IMRT] allowed) 180 cGy/day × 25 fractions (Monday through Friday). Following esophagectomy, adjuvant chemotherapy (CT): weekly docetaxel 35 mg/m2 and C 250 mg/m2 5 out of 6 weeks for two cycles. RESULTS: Of 21 eligible patients enrolled, 17 had surgery; 4 died before operation (due to pulmonary embolism 4 days after CRT, G3 diarrhea, progressive disease during CRT, sepsis/hypoxia during CRT, and acute respiratory distress syndrome [ARDS]). pCR = 7/17. Three postoperative deaths due to ARDS resulted in seven total study-related deaths. Of the 14 remaining patients, 12 started and completed adjuvant CT. Two of seven patients with pCR died, both of ARDS. Out of the 21 eligible subjects in this study, 13 have died and 8 remain alive. The use of IMRT did not correlate with ARDS. CONCLUSION: This regimen demonstrated promising activity. Toxicity was significant, with seven study-related deaths leading to closure after stage 1. All postoperative deaths were due to ARDS. This regimen is not recommended. IMPLICATIONS FOR PRACTICE: Esophageal cancer is a disease with a high death rate. The current treatment involves giving chemotherapy plus radiation followed by surgery, but this cures only a quarter of patients. In order to improve survival, better treatments are needed. This trial evaluated the addition of a novel drug, cetuximab, to chemotherapy plus radiation. Unfortunately, the side effects were too great and the study was stopped early.

Intracranial cellular schwannomas: a clinicopathological study of 20 cases.

AIMS: Cellular schwannoma is a specific subtype of schwannoma, prone to misinterpretation as a malignant neoplasm. Involvement of the intracranial compartment by these tumours is extremely rare. We aim to characterise this clinicopathological subgroup. METHODS AND RESULTS: We identified a total of 20 cellular schwannomas with predominant intracranial involvement. The mean age of the patients at the time of surgery was 37 years (range = 16-81), with a slight female predominance (1.5:1 ratio). The most common sites were the eighth (n = 8) and fifth (n = 6) cranial nerves. Three tumours involved the anterior cranial fossa/olfactory groove, and a single case involved the glossopharyngeal nerve. All tumours met established criteria for cellular schwannoma, and were composed of interlacing fascicles of spindle cells lacking Verocay bodies with minimal Antoni B pattern and variable chronic inflammation and foamy histiocytes. Rare findings included haemosiderin deposition (n = 6), necrosis (n = 4), brisk mitotic activity (>10 mitoses per 10 high-power fields) (n = 2), focal epithelioid morphology (n = 2), myxoid areas (n = 2), neuroblastoma-like pattern (n = 1) and granular cells (n = 1). Immunohistochemical stains demonstrated expression of Schwann cell markers (S100 protein, SOX10, collagen IV) and preserved H3 K27 trimethylation in all cases tested. Fourteen patients had postoperative follow-up, ranging from 2 months to 21 years (mean = 66 months). In patients with follow-up, local recurrence/persistence developed in six cases; five tumours were initially incompletely resected. No metastatic disease or deaths were reported. CONCLUSIONS: Intracranial cellular schwannomas share morphological and immunophenotypical features with cellular schwannomas at others sites may demonstrate locally aggressive growth but appear to lack metastatic potential.

American Registry of Pathology Expert Opinions: Evaluation of poorly differentiated malignant neoplasms on limited samples - Gastrointestinal mucosal biopsies.

This review reflects a collaboration between the American Registry of Pathology (the publisher of the Armed Forces Institute of Pathology Fascicles) and Annals of Diagnostic Pathology. It is part of a series of expert recommendations on topics encountered in daily practice. The authors, three pathologists with expertise in gastrointestinal tract pathology and immunohistochemistry, met on 30 July 2019 tasked with developing expert recommendations for evaluating poorly differentiated and undifferentiated malignant neoplasms encountered on mucosal biopsies of the gastrointestinal tract. We focused on esophageal, gastric, small intestinal, colorectal, and anal (i.e., tubal gut) samples. When faced with diagnostic uncertainty on the initial H&E, it is best to begin by trying to assign the broad tumor class with screening markers such as pankeratin, S100 protein or SOX10, and CD20 or CD45. Once a broad tumor class is established, more specific differentiation markers can be pursued (e.g., lineage-restricted transcription factors for adenocarcinoma; p40 for squamous cell carcinoma; chromogranin A and synaptophysin or INSM1 for neuroendocrine neoplasms). Every small biopsy containing tumor should be considered a potential molecular pathology sample; cutting extra unstained slides with this testing in mind is strongly encouraged.

Efficacy and Safety of Curcumin in Treatment of Intestinal Adenomas in Patients With Familial Adenomatous Polyposis.

BACKGROUND & AIMS: Familial adenomatous polyposis is an autosomal dominant disorder characterized by the development of hundreds of colorectal adenomas and eventually colorectal cancer. Oral administration of the spice curcumin has been followed by regression of polyps in patients with this disorder. We performed a double-blinded randomized trial to determine the safety and efficacy of curcumin in patients with familial adenomatous polyposis. METHODS: This study included 44 patients with familial adenomatous polyposis (18-85 years old) who had not undergone colectomy or had undergone colectomy with ileorectal anastomosis or ileal anal pouches, had at least 5 intestinal adenomatous polyps, and had enrolled in Puerto Rico or the United States from September 2011 through November 2016. Patients were randomly assigned (1:1) to groups given 100% pure curcumin (1,500 mg orally, twice per day) or identical-appearing placebo capsules for 12 months. The number and size of lower gastrointestinal tract polyps were evaluated every 4 months for 1 year. The primary outcome was the number of polyps in the curcumin and placebo groups at 12 months or at the time of withdrawal from the study according to the intention-to-treat principle. RESULTS: After 1 year of treatment, the average rate of compliance was 83% in the curcumin group and 91% in the placebo group. After 12 weeks, there was no significant difference in the mean number of polyps between the placebo group (18.6; 95% CI, 9.3-27.8) and the curcumin group (22.6; 95% CI, 12.1-33.1; P = .58). We found no significant difference in mean polyp size between the curcumin group (2.3 mm; 95% CI, 1.8-2.8) and the placebo group (2.1 mm; 95% CI, 1.5-2.7; P = .76). Adverse events were few, with no significant differences between groups. CONCLUSIONS: In a double-blinded randomized trial of patients with familial adenomatous polyposis, we found no difference in the mean number or size of lower intestinal tract adenomas between patients given curcumin 3,000 mg/day and those given placebo for 12 weeks. Clinicaltrials.gov ID NCT00641147.