EMA Positivity Research Articles

Rare Presentation of Anaplastic Carcinoma as a Mural Nodule in Mucinous Cystadenoma with Concurrent Benign Brenner Tumor

Abstract Introduction/Objective Mural nodules in ovarian mucinous tumors, particularly which are anaplastic carcinomas, represent an exceedingly rare and complex diagnostic category. The literature documents only a few such tumors, predominantly sarcoma-like, with favorable prognoses. In contrast, malignant mural nodules, including anaplastic carcinoma and sarcomatous or carcinosarcomatous types, are notably rare, with fewer than ten cases reported. The co-occurrence of an anaplastic carcinoma mural nodule with a benign Brenner tumor presents distinct diagnostic and treatment complexities stemming from mixed tumor pathology and associated genetic mutations like KRAS and p53, critical in the development of these unusual nodules. This report deepens our insight into rare ovarian tumors. Methods/Case Report A 60-year-old woman with persistent lower abdominal pain underwent surgery for a suspected benign ovarian cyst based on initial imaging. The removed ovary contained a 10.5 x 10 x 8 cm unilocular cyst lined with benign, mucin-containing columnar epithelium. However, a 2 cm anaplastic carcinoma mural nodule was identified within the cyst, exhibiting cellular pleomorphism, nuclear atypia, and high mitotic activity. Immunohistochemical staining confirmed the carcinoma with diffuse cytokeratin and EMA positivity. The fallopian tube was free of tumor involvement, and no capsular or lymphovascular invasion was seen. The cancer was staged as PT1a, pNx, pMx. Results (if a Case Study enter NA) NA Conclusion Anaplastic carcinoma, when present as a mural nodule within a benign-looking mucinous cystadenoma, demands an aggressive treatment strategy due to its poor prognosis and aggressive nature. Such cases require a deviation from standard benign treatment protocols to include extensive surgery, possibly, depending on disease progression, chemotherapy or radiation.

Endomysial antibodies or anti-tissue transglutaminase type 2 IgA antibodies as a confirmatory test in children with celiac disease.

The no-biopsy approach to diagnose celiac disease (CD), introduced in the 2012 European Society for Gastroenterology and Hepatology and Nutrition guidelines, requires an anti-endomysial antibody (EMA) confirmatory serology test following a high-positive immunoglobulin A anti-tissue transglutaminase-2 (anti-TG2) antibody ≥10 times the upper limit of normal (ULN). The aim of this retrospective study is to compare EMA positivity and high-positive anti-TG2 in patients who had their confirmatory test within two month of their first high-positiveanti-TG2 test. Among 933 patients who had high-positive anti-TG2 serology more than 10 times the ULN in their first sample, all had both high-positive anti-TG2 and positive EMA, most of them with very high EMA titers (99.6%) in their confirmatory test. In conclusion, we suggest that a repeated anti-TG2 test can replace the EMA test as the confirmatory serology test for the confirmation of the diagnosis of CD in the no-biopsy approach.

Epidemiology, characteristics, and prognostic factors of lymphoplasmacyte-rich meningioma: a systematic literature review

BackgroundsLymphoplasmacyte-rich meningioma(LPM) is a rare subtype of meningioma with a low degree of malignancy and an overall preferable prognosis. The purpose of this article is to increase the understanding of the disease, reduce misdiagnosis, and improve prognosis.MethodsA search was conducted in the PubMed database for English articles published from 1993 to 2023. The keywords were "lymphoplasmacyte-rich (all fields) and meningioma (all fields) and English (lang)" and "lymphoplasmacyte-rich meningioma (title/abstract) and English (lang)".We further analyzed the clinical manifestations, imaging manifestations, pathological features, treatment strategies, and prognosis of LPM.The possible prognostic indicators were analyzed by the log-rank test and Pearson’s chi-squared test.ResultsFourteen reports with 95 LPM patients were included in this report, including 47 males and 48 females who were diagnosed between the ages of 9 and 79, with an average age of 45 years. The most common clinical manifestations are headache and limb movement disorders. In most cases, the tumor occurred on the convex portion of the brain. All tumors showed significant enhancement, with homogeneous enhancement being more common, and most patients showed peritumoral edema. Postoperative pathological EMA, LCA, and vimentin positivity were helpful for the final diagnosis of the patient. Log-rank tests showed a correlation between complete resection and better prognosis and recurrence.ConclusionThere is a lack of significant differences in the clinical symptoms and imaging manifestations of LPM compared to other diseases that need to be differentiated, and a clear diagnosis requires pathological examination. After standardized surgical treatment, the recurrence rate and mortality rate of LPM are both low. Complete surgical resection of tumors is associated with a better prognosis and lower recurrence rate.

Serological screening for celiac disease, by endomysial antibodies, in patients with rheumatoid arthritis.

Celiac disease (CD) and rheumathoid arthritis (RA) are both multi-factorial chronicinflammatory auto-immune diseases. In this retrospective study, we determined the frequency of CD in patients with RA using IgA anti-endomysial antibodies (EmA) and tried to explain this association. Indirect immunofluorescence on human umbilical cord was used to detectEmA in 215 patients withseropositive RA collected over a 4-year-period. Two thousand and five hundred healthy blood donors (HBD) served as control group. Among the 215 patients with RA, 12 (9 females) were found positive for EmA while only 7 were positive for EmA in control group, EmA are significantly more frequent in RA patients than in HBD (5.58% vs. 0.28%, p <10-6; 95% CI [8.21-54.01]; odds ratio: 21.05). In RA patients, the frequency of EmA was not statistically different between males and females. The frequency of EmA was significantly higher in female patients than in healthy females (5.32% vs. 0.40%, p <10-3). Patients with RA can be considered as a high-risk group for CD based on the high frequency of EmA positivity observed in our study.

Non-cutaneous syncytial myoepitheliomas are identical to cutaneous counterparts: a clinicopathologic study of 24 tumors occurring at diverse locations.

Cutaneous syncytial myoepithelioma (CSM) is a rare myoepithelioma variant of skin, characterized by intradermal syncytial growth of spindle cells with a distinct immunophenotype of EMA and S100 positivity and infrequent keratin expression. While CSM was first described as a cutaneous tumor, singular non-cutaneous cases have since been reported in bone. We aimed to investigate the clinicopathological features of this variant across all anatomic sites through a large multi-institutional study. We complied a total of 24 myoepitheliomas with syncytial growth from our files. The tumors occurred in 12 male and 12 female patients (M:F = 1:1), with a median age of 31 years (range, 9-69 years). While the majority of tumors (75%, n = 18) occurred in skin, a significant subset (25%, n = 6) arose in non-cutaneous sites, including bone (n = 3), bronchus/trachea (n = 2), and interosseous membrane of tibia/fibula (n = 1). Tumor size ranged from 0.4 to 5.9 cm. Clinical follow-up (7 patients; range 14-202 months; median 56.5 months) showed a single local recurrence 8 years after incomplete skin excision but no metastases; all patients were alive at the time of last follow-up without evidence of disease. Histologically, all tumors were pink at low-power and characterized by a syncytial growth of bland ovoid, spindled, or histiocytoid cells with eosinophilic cytoplasm and prominent perivascular lymphoplasmacytic inflammation. One-third displayed adipocytic metaplasia (8/24). Rare cytologic atypia was seen but was not associated with increased mitotic activity. All tumors expressed S100, SMA, and/or EMA. Keratin expression was absent in most cases. Molecular analysis was performed in 16 cases, all showing EWSR1-rearrangments. In total, 15/15 (100%) harbored an EWSR1::PBX3 fusion, whereas 1 case EWSR1 FISH was the only molecular study performed. Syncytial myoepithelioma is a rare but recognizable morphologic variant of myoepithelioma which may have a predilection for skin but also occurs in diverse non-cutaneous sites. Our series provides evidence supporting a reappraisal of the term "cutaneous syncytial myoepithelioma," as 25% of patients in our series presented with non-cutaneous tumors; thus, we propose the term "syncytial myoepithelioma" to aid pathologist recognition and avoidance of potentially confusing terminology when referring to non-cutaneous examples. The behavior of syncytial myoepithelioma, whether it arises in cutaneous or non-cutaneous sites, is indolent and perhaps benign with a small capacity for local recurrence.

A Clinicopathological and Immunohistochemical Profile of Primary Extra Mammary Paget's Disease in Skin of Colour: A Case Series.

Extramammary Paget's disease is an intraepithelial neoplasm, usually found in areas rich in apocrine gland concentration. The clinical features, histopathology, immunohistochemistry and management details of five patients (F = 3, M = 2) have been described here. While a well-defined persistent plaque with crusting and erosion was the most common presentation, hyperpigmentation, hypopigmentation and depigmentation were also observed in two patients. Characteristic Paget's cells with cytokeratin 7 and EMA positivity were seen on histopathology examination. Authors conclude that pigmentary alterations may be under-reported in extra mammary Paget's disease in the skin of colour.

The role of serology in the diagnosis of coeliac disease.

Serology has significantly revolutionized the knowledge of celiac disease (CD), leading to the identification of unsuspected patients in at-risk CD groups, thereby increasing the number of CD diagnoses compared to the pre-screening era. Several markers for CD with a progressive diagnostic accuracy have been identified over the years, but only three of them, i.e. anti-tissue transglutaminase (anti-tTG), anti-endomysial (EmA) and anti-deamidated gliadin antibodies (DGP) are currently assessed in the daily clinical practice. A thorough review of the literature identified 44 original studies published between 1998 to 2022 for a total of 5098 pediatric and adult CD patients (without selective IgA deficiency) and 11930 disease controls. The results highlighted that anti-tTG IgA exhibited a higher sensitivity for CD (93.4%) than EmA IgA (92.8%), DGP IgG (81.8%) and DGP IgA (83.8%). The specificity of EmA IgA (99%) resulted to be higher than those of anti-tTG IgA (95.8%), DGP IgG (96.4%) and DGP IgA (92.1%). In patients with selective IgA deficiency, a condition closely related to CD, serological screening should include one of the three antibodies of IgG class, since anti-tTG, DGP and EmA have a very similar diagnostic accuracy in this clinical setting. According to age, there are two main diagnostic strategies for CD detection. In children, the revised ESPGHAN 2020 guidelines established that CD could be diagnosed in both symptomatic and asymptomatic children by high anti-tTG IgA titers (>10 times the cut-off) and EmA positivity with no need to obtain duodenal biopsy and HLA typing. In adult patients, although high tTG IgA titers (confirmed by EmA IgA positivity) correlate with villous atrophy, an intestinal biopsy is still considered mandatory for confirming CD diagnosis. Currently, a case finding approach in at-risk groups is preferred to mass screening for CD detection.

Unique Clinical and Pathologic Characteristics of Poorly Differentiated Primary Pleuro-Pulmonary Synovial Sarcoma

Primary pleuro-pulmonary synovial sarcoma is rare and poses a diagnostic challenge particularly when poorly differentiated. We present 15 cases of poorly differentiated primary pleuro-pulmonary synovial sarcoma and compare and contrast results with previously published series on usual better differentiated tumors. Clinical and radiologic findings were similar to usual pulmonary synovial sarcoma with typical imaging features. 7 of 10 patients with outcome data died of disease within 5 years. Histologically, tumors had densely cellular fascicles, hyalinized stroma, hemangiopericytoma-like vasculature, and focal myxoid change. Round cell and rare rhabdoid morphology were unique to poorly differentiated tumors. Immunohistochemistry demonstrated at least focal expression of pancytokeratin, EMA, CK7, CK5/6, calretinin, and CD56, and diffuse positivity with CD99 and bcl-2. Ten primary pulmonary synovial sarcomas with tissue available for study were positive for t(x;18), with a more even distribution of SS18/SSX1 and SS18/SSX2 tumors compared with better differentiated lung synovial sarcomas. In conclusion, our study confirms that clinical, histological, and immunohistochemical data from poorly differentiated primary pleuro-pulmonary synovial sarcoma is similar to better differentiated tumours but special caveats remain for accurate histopathologic diagnosis.

Buzdağının görünmeyen yüzü: Ekstraintestinal Bulgular ve Çölyak Hastalığı

Aim: Clinical manifestations of celiac disease (CD) can be quite different and varying. The number of CDs presenting with atypical symptoms is increasing day by day. Hence, we aimed to determine how many patients with CD were atypical celiac through examining their admission complaints, clinical characteristics, laboratory results, endoscopic findings, and pathological findings. &#x0D; Material and Methods: Eighty-nine patients with CD aged over 18 years who were followed-up in Ankara Kecioren Training and Research Hospital Internal Medicine Clinic between 2007 and 2014 were included in the study. The files of the patients were reviewed retrospectively. Sex, age, hospital admission complaints, clinical characteristics, laboratory results, endoscopy findings, and pathology results of the patients were recorded.&#x0D; Results: The median age of the patients in the study was 36, and 68.5% of them were female. The most common symptoms of the patients were fatigue (49.4%), anorexia (33.7%), and dyspepsia (22.5%), while diarrhea (19.1%), which is among the classical symptoms, was less common. 7.8% of the patients had no complaints at the time of admission, whereas 47.1% of them had only extraintestinal symptoms. At admission, 47% of the patients had anemia, 73.4% had iron deficiency, and 55.4% of them had vitamin B12 deficiency. When hemoglobin, ferritin, and vitamin B12 levels were compared before and after a gluten-free diet, a significant increase was determined. Transaminase elevation was detected in 25.3% of our patients at the time of diagnosis. When pre-treatment and post-treatment values were compared, a significant decrease was determined in those with high transaminase levels. In the pre-treatment serological test results of the patients, Ig A EMA positivity was the most common finding with a rate of 90.2%, followed by IgG EMA with 88.9%. In terms of pre-treatment endoscopy findings, 50.2% of our patients had normal appearance, 25.4% had a mosaic pattern, 12.6% had effacement of the duodenal folds, 12.6% had a nodular appearance, and 9.5% had a scalloping of the duodenal folds. When the pathology results of our patients were examined, 83.4% of them were at the advanced stage and with Marsh Type 3. &#x0D; Conclusion: CD may present with atypical complaints such as extraintestinal findings, as in more than half of the patients in this study. Celiac disease should be taken into consideration, particularly in conditions such as iron deficiency, osteoporosis, and transaminase elevations, which are prevalent in the community. The prevalence of CD in our country is estimated to be around 1-2%; however, it is considered that there are more asymptomatic patients with atypical celiac disease. When diagnosing CD, the most crucial step is to consider the potential presence of CD during pre-diagnoses. Thus, CD should be included in the differential diagnosis, specifically in patients presenting with atypical symptoms.

Ependymoma-like tumor with mesenchymal differentiation harboring C11orf95-NCOA1/2 or -RELA fusion: A hitherto unclassified tumor related to ependymoma.

Recurrent fusion genes involving C11orf95, C11orf95‐RELA, have been identified only in supratentorial ependymomas among primary CNS tumors. Here, we report hitherto histopathologically unclassifiable high‐grade tumors, under the tentative label of “ependymoma‐like tumors with mesenchymal differentiation (ELTMDs),” harboring C11orf95‐NCOA1/2 or ‐RELA fusion. We examined the clinicopathological and molecular features in five cases of ELTMDs. Except for one adult case (50 years old), all cases were in children ranging from 1 to 2.5 years old. All patients presented with a mass lesion in the cerebral hemisphere. Histologically, all cases demonstrated a similar histology with a mixture of components. The major components were embryonal‐appearing components forming well‐delineated tumor cell nests composed of small uniform cells with high proliferative activity, and spindle‐cell mesenchymal components with a low‐ to high‐grade sarcoma‐like appearance. The embryonal‐appearing components exhibited minimal ependymal differentiation including a characteristic EMA positivity and tubular structures, but histologically did not fit with ependymoma because they lacked perivascular pseudorosettes, a histological hallmark of ependymoma, formed well‐delineated nests, and had diffuse and strong staining for CAM5.2. Molecular analysis identified C11orf95‐NCOA1, ‐NCOA2, and ‐RELA in two, one, and two cases, respectively. t‐distributed stochastic neighbor embedding analysis of DNA methylation data from two cases with C11orf95‐NCOA1 or ‐NCOA2 and a reference set of 380 CNS tumors revealed that these two cases were clustered together and were distinct from all subgroups of ependymomas. In conclusion, although ELTMDs exhibited morphological and genetic associations with supratentorial ependymoma with C11orf95‐RELA, they cannot be regarded as ependymoma. Further analyses of more cases are needed to clarify their differences and similarities.

Endolymphatic Sac Tumor: A Rare Case

Endolymphatic sac tumor is rare, locally aggressive and non-metastasizing neoplasm arising from the endolymphatic sac of the petrous portion of the temporal bone. Most occur in adult and present with ipsilateral hearing loss. They can be sporadic or associated with Von-Hippel-Lindau disease. Patient with endolymphatic sac tumor should be screened for VHL disease. We report a case of 52-year-old female with dizziness and headache. Histopathology was consistent with typical features of endolymphatic sac tumor. This was confirmed by cytokeratin and EMA positivity and TTF-1 negativity. This case is presented for its rarity with only few cases reported.

MYCN amplification drives an aggressive form of spinal ependymoma

Spinal ependymal tumors form a histologically and molecularly heterogeneous group of tumors with generally good prognosis. However, their treatment can be challenging if infiltration of the spinal cord or dissemination throughout the central nervous system (CNS) occurs and, in these cases, clinical outcome remains poor. Here, we describe a new and relatively rare subgroup of spinal ependymal tumors identified using DNA methylation profiling that is distinct from other molecular subgroups of ependymoma. Copy number variation plots derived from DNA methylation arrays showed MYCN amplification as a characteristic genetic alteration in all cases of our cohort (n = 13), which was subsequently validated using fluorescence in situ hybridization. The histological diagnosis was anaplastic ependymoma (WHO Grade III) in ten cases and classic ependymoma (WHO Grade II) in three cases. Histological re-evaluation in five primary tumors and seven relapses showed characteristic histological features of ependymoma, namely pseudorosettes, GFAP- and EMA positivity. Electron microscopy revealed cilia, complex intercellular junctions and intermediate filaments in a representative sample. Taking these findings into account, we suggest to designate this molecular subgroup spinal ependymoma with MYCN amplification, SP-EPN-MYCN. SP-EPN-MYCN tumors showed distinct growth patterns with intradural, extramedullary localization mostly within the thoracic and cervical spine, diffuse leptomeningeal spread throughout the whole CNS and infiltrative invasion of the spinal cord. Dissemination was observed in 100% of cases. Despite high-intensity treatment, SP-EPN-MYCN showed significantly worse median progression free survival (PFS) (17 months) and median overall survival (OS) (87 months) than all other previously described molecular spinal ependymoma subgroups. OS and PFS were similar to supratentorial ependymoma with RELA-fusion (ST-EPN-RELA) and posterior fossa ependymoma A (PF-EPN-A), further highlighting the aggressiveness of this distinct new subgroup. We, therefore, propose to establish SP-EPN-MYCN as a new molecular subgroup in ependymoma and advocate for testing newly diagnosed spinal ependymal tumors for MYCN amplification.

Genetic and molecular reappraisal of spindle cell adamantinoma of bone reveals a small subset of misclassified intraosseous synovial sarcoma

Adamantinoma represents a distinct group of bone tumors showing both mesenchymal and epithelial differentiation most commonly involving the tibial diaphysis. Most adamantinomas contain a fibro-osseous component and an epithelial component consisting of squamous or basaloid cells. Adamantinomas are considered malignant neoplasms requiring en bloc excision that frequently recur locally and can rarely metastasize. Rare adamantinomas show an epithelial component consisting predominantly of monomorphic spindle cells, which, combined with an epithelial immunophenotype, can mimic monophasic synovial sarcoma. Synovial sarcoma is very rare in bone. It is considered a high-grade sarcoma that typically necessitates chemotherapy. However, the relationship between spindle cell adamantinoma and intraosseous synovial sarcoma has not been investigated. The current study was prompted by identification of a presumed spindle cell adamantinoma of the tibia with diffuse keratin expression that harbored a SS18 gene region rearrangement. FISH of eight additional bone tumors initially classified as spindle cell adamantinoma based on clinicoradiopathologic findings revealed one additional case with SS18 rearrangement. Histologically, both intraosseous synovial sarcoma and spindle cell adamantinoma demonstrated uniform fusiform nuclei with scant cytoplasm, short fascicles and low mitotic activity. The adamantinomas, but not the synovial sarcomas, were more likely to show overt epithelial differentiation in the form of pseudoglands or squamous nests. Immunohistochemistry of all cases, irrespective of SS18 status, showed diffuse keratin positivity in the spindle cell component, and less consistent EMA positivity. Clinical follow-up was available in both intraosseous synovial sarcomas, one of which recurred and the other metastasized. Two of the six spindle cell adamantinomas with follow-up metastasized. The above findings highlight the morphologic and immunophenotypic overlap between spindle cell adamantinoma and intraosseous synovial sarcoma of the tibia. Investigation of SS18 status to exclude synovial sarcoma is suggested prior to rendering a diagnosis of spindle cell adamantinoma.

SEROLOGICAL SCREENING FOR CELIAC DISEASE IN CHILDREN WITH COLCHICINE-RESISTANT FAMILIAL MEDITERRANEAN FEVER

Familial Mediterranean fever and celiac disease share some common clinical features such as abdominal pain, diarrhea, arthralgia and arthritis. Also, both of the diseases are associated with many inflammatory and autoimmune diseases. Previous studies have shown the association between familial Mediterranean fever (FMF) and different clinical conditions. We aimed to investigate the relationship between celiac disease and colchicine-resistant familial Mediterranean fever (crFMF) disease. This prospective study was conducted at the Department of Pediatric Gastroenterology and Pediatric Rheumatology from October 2015 to August 2016. A total of 24 patients with crFMF were included in the study. We used 60 sex- and age-matched healthy subjects as a control group. Levels of total IgA and tissue transglutaminase (tTG) IgA antibody were measured in both groups. Those with increased level of tTG IgA were tested for anti-endomysium IgA antibodies (EMA). Gastroduodenoscopy and intestinal biopsy were planned for a definite diagnosis of celiac disease in patients with positive EMA. Of the 24 patients in this study, 18 (75.0%) were female. Only 4 (16.6%) of 24 patients were positive for tTG IgA. Patients with positive tTG IgA were then tested for EMA IgA antibodies and none of them had a positive result. Only one (1.6%) subject from the control group was positive for tTG IgA but EMA positivity was not detected. We did not found celiac disease in 24 children with crFMF. Since crFMF disease is rarely seen in general population, further studies with more patients are needed to provide more precise interpretation.

Extracranial invasion of a recurrent, transformed anaplastic pleomorphic xanthoastrocytoma: a case report

Pleomorphic xanthoastrocytoma (PXA) is a rare tumour comprising &lt;1% of all primary central nervous system tumours and the majority (~98%) occur supratentorially. We report on a 40-year-old female with a past medical history of a rare posterior fossa/cerebellar PXA who presented with a right-sided neck mass, decreased shoulder power and longstanding right tongue deviation with right-sided hemi-atrophy. The patient had prior tumour debulking. Recent MRI demonstrated an enhancing posterior fossa mass extending to the skull base at the jugular foramen and another mass in the upper neck along the jugular bulb with displacement and encasement of the right common carotid artery down to C5. Resection of the neck mass reveals an anaplastic PXA. The tumour has close approximation with adjacent peripheral nerves and is positive in 2 lymph nodes. Comparison with the original tumour molecular and immunohistochemical profiles reveals a conserved BRAF V600E mutation but the transformed malignant glioma now expresses dot-like EMA positivity and ATRX is completely lost (mutated). Transformation of a PXA (WHO Grade II) into an anaplastic PXA (WHO Grade III) has been well documented, but extracranial extension is extraordinarily rare. We report herein the first documented case of a posterior fossa PXA that underwent malignant transformation and extracranial invasion to the parapharyngeal space.

Clear cell papulosis: report and review

A 12-month-old boy presented with three months of asymptomatic hypopigmented flat-topped papules on the suprapubic skin and lower abdomen. Emollients and topical steroids offered no improvementand the patient was referred to the dermatology department. Shave biopsy revealed a papillated epidermis with scattered solitary mononuclearclear cells at all levels of the epidermis and an overlying basket weave orthokeratosis. The cells were epithelioid with increased amphophilic cytoplasm. Immunohistochemical staining was positive for CK7,CEA, and CAM5.2 and negative for S100, CD1a, and Mart-1. These findings were consistent with clear cell papulosis. No treatment was recommended as these lesions were asymptomatic. However, yearlyfollow up was recommended given the resemblance of these cells to those of Paget disease. Review of the literature demonstrates a total of 31 biopsy confirmed cases with AE1, CEA, and EMA positivity and S100negativity as the most consistent staining properties. A recent retrospective review of 19 cases documents long term follow-up of at least six years and up to 21 years. The results suggested a tendency toward selfresolution and an absence of malignant progression, supporting the benign nature of these lesions.

Immunohistochemical Approach to the Differential Diagnosis of Meningiomas and Their Mimics.

The differential diagnosis between meningioma and others tumors can be challenging. This study aimed to evaluate different immunohistochemical markers for the differential diagnosis between meningioma and their morphological mimics. Immunohistochemistry was performed on tissue microarray with antiepithelial membrane antigen (EMA), progesterone receptor, somatostatin receptor 2A (SSTR2A), CD34, STAT6, S100, SOX10, HMB45, MelanA, GFAP, inhibin, and BCL2 antibodies. One hundred and twenty-seven meningiomas, 26 solitary fibrous tumor/hemangiopericytomas (SFT/HPC), 39 schwannomas, 17 hemangioblastomas, 21 melanomas, 9 gliosarcomas, 5 neurofibromas, 9 peripheral primitive neuroectodermal tumors, 7 synovial sarcomas, and 5 malignant peripheral nerve sheath tumors were included in the microarray. SSTR2A was the most sensitive (95.2%) and specific (92%) marker of meningiomas. In combination, SSTR2A and/or EMA positivity reached maximal sensitivity (100%). Coexpression of SSTR2A and EMA was the most specific (94.8%) for the diagnosis of meningioma, regardless of the grade or subtype, with the exception of the differential diagnosis with synovial sarcoma. All synovial sarcomas were EMA-positive and 6/7 SSTR2A-positive. STAT6 showed optimum sensitivity and specificity (100%) for SFT/HPC. SOX10 was the most sensitive (94.3%) and specific (100%) marker to discriminate meningiomas from schwannomas. In conclusion, SSTR2A, STAT6, and SOX10 were the most sensitive and specific markers to distinguish meningiomas from their morphological mimics.

Diagnostic value of STAT6 immunohistochemistry in solitary fibrous tumor/meningeal hemangiopericytoma

To investigate the diagnostic role of STAT6 immunohistochemistry in solitary fibrous tumors (SFT)/meningeal hemangiopericytomas (HPC). Evaluated the expression of STAT6, vimentin, CD34, EMA, PR, S-100, CD56, GFAP and Ki-67 in a cohort of 37 SFT/meningeal HPC, 30 meningiomas and 30 schwannomas by immunohistochemistry staining. All SFT/meningeal HPC demonstrated nuclear positivity for STAT6, and the proportion of positive tumor cells ranged from 60% to 95%, with no significant difference cases.Vimentin was strongly positive in all cases. CD34, EMA and PR positivity was found in 32 cases, 1 case and 4 cases, respectively.S-100 protein, CD56 and GFAP were negative; Ki-67 labeling index was 1%-8%. However, the meningiomas and schwannomas were negative for STAT6. STAT6 is a relatively specific biomarker for SFT/meningeal HPC, and may be used in the diagnosis and differential diagnosis of SFT/meningeal HPC, especially for the atypical cases, and allows the precise pathologic diagnosis of SFT/meningeal HPC.

Are ESPGHAN "biopsy-sparing" guidelines for celiac disease also suitable for asymptomatic patients?

In 2012, European Society of Pediatric Gastroenterology, Hepatology, and Nutrition published novel guidelines on celiac disease (CD) diagnosis. Symptomatic children with serum anti-transglutaminase (anti-tTG) antibody levels ≥10 times upper limit of normal (ULN) could avoid duodenal biopsies after positive HLA test and serum anti-endomysial antibodies (EMAs). So far, both asymptomatic and symptomatic patients with anti-tTG titer <10 times ULN should undergo upper endoscopy with duodenal biopsies to confirm diagnosis. The aim of this study was to assess the accuracy of serological tests to diagnose CD in asymptomatic patients. We retrospectively reviewed data of 286 patients (age range: 10 months to 17 years) with CD diagnosis based on elevated titer of anti-tTG, EMA positivity, and histology. All patients were distinguished between symptomatic and asymptomatic; histological lesions were graded according to the Marsh-Oberhuber (MO) criteria. Fisher exact test was applied to analyze both groups in terms of diagnostic reliability of serological markers. A total of 196 patients (68.53%) had anti-tTG titers ≥10 times ULN. Among them, a group of 156 patients (79.59%) also had symptoms suggestive of CD ("high-titer" symptomatic); of these, 142 patients (91.02%) showed severe lesion degree (3a, 3b, 3c MO). Conversely, 40 out of 196 patients (20.40%) were asymptomatic ("high-titer" asymptomatic) and 37 patients (92.5%) of them showed severe lesion degree (3a, 3b, 3c MO). No difference in histological damage was found between "high-titer" symptomatic and "high-titer" asymptomatic children (Fisher exact test, P=1.000). If confirmed in large multicenter prospective studies, the "biopsy-sparing" protocol seems to be applicable to both symptomatic and asymptomatic patients with anti-tTG titer ≥10 times ULN, positive EMA, and HLA-DQ2/DQ8.

Low-Grade Fibromyxoid Sarcoma of the Head and Neck: A Clinicopathologic Series and Review of the Literature.

Low-grade fibromyxoid sarcoma (LGFMS) is a deceptively bland malignancy with potential for late recurrence and metastasis, which usually occurs in the deep soft tissues of the extremities and trunk. Most LGFMSs harbor a characteristic gene fusion of FUS-CREB3L2, and recently MUC4 immunostaining has been found to be highly sensitive and specific for the diagnosis. We present a dedicated series of head and neck LGFMS, including the first reported laryngeal case, as well as a review of reported head and neck cases. The surgical pathology archives of our three institutions were searched for cases of LGFMS arising within the head and neck, and four cases were identified. The H&E slides were reviewed, and immunohistochemistry were performed for pancytokeratin, p63, p40, EMA, S100 protein, β-catenin, actin, CD34, and MUC4. The patients were 6, 43, 45, and 73 years old (mean 41.8 years) and included three males and one female. The tumors were located in the posterior cervical spine, facial skin, mandible, and larynx. The tumors were treated with surgical excision, and all four had histologic features typical for LGFMS including alternating myxoid and fibrous areas with prominent curvilinear vasculature. All tumors were MUC4 positive (100%), 2/4 (50%) were p63 positive, 1/4 (25%) showed focal EMA positivity; all 4 were negative for pancytokeratin, p40, S100 protein, β-catenin, actin, and CD34. LGFMS is a low grade sarcoma that rarely develops in the head and neck. Due to its rarity, a pathologist may not consider LGFMS in the differential diagnosis of spindle cell neoplasms within the head and neck. Immunohistochemical staining is helpful, but stains should be selected carefully to avoid misdiagnosis.