Ayca Ersen

Diagnostic utility of SOX10 to distinguish malignant peripheral nerve sheath tumor from synovial sarcoma, including intraneural synovial sarcoma.

Synovial sarcoma and malignant peripheral nerve sheath tumor pose a significant diagnostic challenge given similar histomorphology. The distinction is further complicated by similar immunophenotype and especially by occasional synovial sarcomas that present as intraneural tumors. Although the presence of a t(X;18) rearrangement or expression of TLE1 can help confirm the diagnosis of synovial sarcoma, negative results for these tests are not diagnostic of malignant peripheral nerve sheath tumor. The SOX10 transcription factor, a putative marker of neural crest differentiation, may have diagnostic utility in this differential, but immunohistochemical data are limited. The goal of the present study was to determine the diagnostic utility of SOX10 to discriminate between synovial sarcoma and malignant peripheral nerve sheath tumor. Forty-eight cases of malignant peripheral nerve sheath tumor, all from patients with documented neurofibromatosis, and 97 cases of genetically confirmed synovial sarcoma, including 4 intraneural synovial sarcomas, were immunohistochemically stained for SOX10. The stain was scored for intensity and fraction of cells staining. Thirty-two of 48 malignant peripheral nerve sheath tumors (67%) were SOX10-positive. The majority of malignant peripheral nerve sheath tumors showed ≥2+ staining, but staining did not correlate with grade. By contrast, only 7/97 (7%) synovial sarcomas were SOX10-positive. Only three synovial sarcomas showed ≥2+ staining but, importantly, two of these were intraneural synovial sarcoma. Therefore, SOX10 is a specific (93%), albeit not very sensitive (67%), diagnostic marker to support a diagnosis of malignant peripheral nerve sheath tumor over synovial sarcoma. Furthermore, the stain needs to be interpreted with caution in intraneural tumors in order to avoid a potential diagnostic pitfall. It remains to be determined whether SOX10-positive cells in intraneural synovial sarcoma represent entrapped Schwann cells, synovial sarcoma cells or both.

Pathologic characteristics of pediatric intracranial pilocytic astrocytomas and their impact on outcome in 3 countries: a multi-institutional study.

Pilocytic astrocytoma (PA) is one of the most common glial neoplasms in the pediatric population, and its gross total resection can be curative. Treatment of partially resected or recurrent tumors is challenging, and the factors associated with increased recurrence risk are not well defined. Identification of favorable and unfavorable factors can lead to a better understanding and management of patients with PA. We studied the pathologic characteristics of 116 intracranial PAs from 4 institutions representing 3 distinct geographic regions to identify factors that may be associated with biological behavior. The study included 65 boys and 51 girls with a median age of 6 years. Median follow-up for all patients was 101 months, during which time 38 patients had recurrence. Progression-free and overall survivals were better in patients who underwent gross total resection. We were not able to identify any differences in pathologic and molecular markers among the 4 institutions from 3 different countries. However, progression-free survival varied significantly among institutions. Sox-2 was the most prevalent stem cell marker in PA, and many tumors showed synaptophysin positivity. BRAF immunostaining was not useful in determining BRAF duplication. BRAF duplication was more typical of posterior fossa tumors. There was a strong correlation between BRAF duplication and pERK immunostaining, suggesting that the RAF/MEK/ERK pathway is active in these tumors. This finding has significant implications given its role in oncogen-induced senescence and possible influence on treatment decisions of subtotally resected tumors.

Tumor deposits in gastric carcinomas

We performed this study to examine the prevalence of tumor deposits (TD) in gastric adenocarcinomas (GACa), and the relevance of their presence, size and type to clinical outcome. Ninety-six patients, histopathologically diagnosed as GACa following a total/subtotal gastrectomy were included, and clinicopathologic data were recorded. Due to the statistical analysis, the majority of TD(+) cases were of intestinal type and showed vascular invasion. In these cases, the incidence of local recurrence was significantly higher. The majority of GACa of intestinal type with TD were of high grade and showed vascular invasion. Recurrence and death were more commonly encountered among them. The recurrence-free survival (RFS) was significantly shorter in patients with TDs, which was also confirmed by multivariate analysis, and there was a significant difference between both RFS and overall survival of TD(+) and TD(-) cases of intestinal type GACa. In conclusion, in this study, we demonstrate that TDs are not infrequently observed in GACa, they are more commonly associated with the intestinal type and vascular invasive gastric cancers. Our study shows the prognostic impact of TDs, especially regarding the RFS. Therefore, the documentation of TDs might be considered for prospective studies, especially for the intestinal type GACa, a shortcoming of this study.

Non-uniform response to temozolomide therapy in a pituitary gonadotroph adenoma.

Endocrinologically active pituitary adenomas are treated either with surgery, radiotherapy or various drugs, including dopamine agonists, long-acting somatostatin analogs, growth hormone receptor antagonists, or corticosteroid secretion inhibitors. Fully 35% to 55% of pituitary adenomas invade adjacent structures. This figure is lower in gonadotroph adenomas, less than 5% compared to other adenoma types. Clinical management of invasive adenomas is challenging, and most of them tend to recur after surgery. Hormonally active pituitary adenomas may even be resistant to combined medical, surgical, and radiotherapy treatments. In comparison, pituitary carcinomas represent 0.2% of all adenohypophysial neoplasms1, and not only invade adjacent structures but give rise to cerebrospinal and/or systemic metastases with high mortality. The lack of response to aggressive pituitary adenomas, particularly carcinomas to conventional therapies, drives search for new approaches1. Temozolomide (TMZ) is a chemotherapeutic agent which can cross the blood-brain barrier and has proven utility in the treatment of glioblastoma. More recently, it has been used to treat aggressive pituitary adenomas and carcinomas2. To date, cases of such aggressive pituitary tumors have been reported in terms of clinical outcomes. The morphologic effects of therapy have been described in only three patients2. Of these, two tumors responded, both radiologically and morphologically. The first case, a prolactin cell adenoma, did not express MGMT (06methylguanine-DNA methyltransferase), a DNA repair protein that counteracts TMZ anti-neoplastic action. The second case, an aggressive silent subtype 2 corticotroph adenoma, showed no morphological change after therapy. This tumor showed highlevel immunoexpression of MGMT by immunohistochemistry. The third case, a corticotroph adenoma in a patient with Cushing’s disease, showed no MGMT immunoexpression, and 80% reduction in tumor volume was noted on magnetic resonance imaging (MRI) scan. The Ki-67 labeling index decreased after the therapy. Herein, we report a recurrent pituitary gonadotroph adenoma in which the partial response to TMZ appeared to result from non-uniform MGMT immunoexpression, portions of the tumor lacking immunoreactivity and the remainder showing high-level immunostaining.

Warthin-Like Papillary Carcinoma of the Thyroid: A Case Series and Review of the Literature Tiroidin Warthin-Benzeri Papiller Karsinomu: Olgu Serisi ve Literatür Derlemesi

ABSTRACT Warthin-like tumor of the thyroid is a recently described rare variant of thyroid papillary carcinoma. The distinguishing histological feature of this variant is papillary foldings lined by oncocytic neoplastic cells with clear nuclei and nuclear pseudoinclusions, accompanied by prominent lymphocytic infiltrate in the papillary stalks. Its prognosis has been reported to be almost similar to conventional papillary carcinoma. In this case series, we report four cases with Warthin-like papillary carcinoma of the thyroid, diagnosed at Dokuz Eylul University Faculty of Medicine Department of Pathology in 2008 and 2009. Three patients were female. The mean patient age was 39 years (range, 20-56) and the mean tumor size was 1.7 cm (range, 0.9-2.0 cm). All of the cases had lymphocytic thyroiditis in the background. None of the tumors showed lymphovascular invasion. The patients are free of any recurrence and/or distant metastasis with a mean follow-up of 25 months. This rare variant of thyroid papillary carcinoma with distinct histopathological features should be indicated in pathology reports. Further studies and long-term follow-up of patients are needed to highlight the biological behavior of this variant. ÖZ Tiroidin Warthin-benzeri tümörü son dönemlerde tanımlanan, tiroid papiller karsinomunun nadir görülen bir varyantıdır. En önemli histolojik özelliği, nükleer psödoinklüzyonlar içeren berrak nukleuslu onkositik özellikte neoplastik hücrelerle döşeli, santral stromalarında belirgin lenfositik infiltrat bulunan papiller yapılardır. Prognozunun klasik papiller karsinom ile benzerlik gösterdiği bildirilmiştir. Bu olgu serisinde, Dokuz Eylül Üniversitesi Tıp Fakültesi Patoloji Anabilim Dalı’nda 2008 ve 2009 yıllarında tanı almış dört Warthin-benzeri papiller karsinom olgusu sunulmuştur. Hastaların üçü kadın olup, ortalama yaş 39 (20-56 yaş), ortalama tümör boyutu 1.7 cm (0,9-2,0 cm) idi. Olguların tümünde zeminde belirgin lenfositik tiroidit izlendi. Olguların hiçbirinde lenfovasküler invazyon görülmedi. Ortalama 25 aylık klinik ve radyolojik izlem sonucu hastaların hiçbirinde rekürrens ya da uzak metastaz saptanmadı. Tiroidin nadir görülen Warthin-benzeri papiller karsinomu, ayırdedici histopatolojik özelliklere sahip olup patoloji raporlarında belirtilmelidir. Bu varyantın biyolojik davranışını açığa çıkarabilmek için ileri çalışmalara ve uzun dönem hasta takiplerine ihtiyaç vardır.

Intrauterine fetal loss associated with Candida glabrata chorioamnionitis: report of two cases.

Abstract Chorioamnionitis is most commonly the result of an ascending infection caused by bacteria found within the lower genital tract. Yeast infections causing chorioamnionitis are very uncommon. Candida glabrata is a yeast that is considered to be a commensal of the vagina but vaginitis and rarely upper genital tract infection have been described. We report two cases of fungal chorioamnionitis occurring in pregnancies with a history of in vitro fertilization and cervical cerclage, both resulting in fetal loss. Th e histological features in conjunction with the positive cultures enabled C. glabrata to be identified as the causative organism producing severe chorioamnionitis. C. glabrata was probably introduced into the cervix at the time of embryo transfer, and during stitching the cervix. To prevent unfavorable outcomes in pregnant women, we recommend that vaginal and in particular cervical swabs should be taken prior to cervical procedures and appropriate treatment should be provided. ÖZ Koryoamniyonitislerin büyük kısmı alt genital sistemde bulunan bakterilerin asendan enfeksiyonu sonucu gelişir. Mantar nedenli koryoamniyonitis enderdir. Kandida glabrata, vajende kommensal olarak bulunmakla birlikte nadiren vajinit ve üst genital sistem enfeksiyonuna yol açabilmektedir. Burada, in vitro fertilizasyon ile elde edilmiş, servikal serklaj uygulanmış ve fetal kayıp ile sonlanmış iki gebelikte saptanan fungal koryoamniyonitis olguları sunulmuştur. Histolojik özellikler ve pozitif kültür sonuçları ile koryoamniyonitis etkeni Kandida glabrata olarak saptanmıştır. Etkenin, embriyo transferi ve/veya servikal serklaj işlemi sırasında servikse ekilmiş olması muhtemeldir. Gebelere uygulanacak servikal işlemlerden önce vaginal ve özellikle servikal temizliğin sağlandığından emin olmak ve tedaviyi uygun planlamak bu tip istenmeyen sonuçları engelleyebilir.

Intraoperative squash cytology and histology of giant cell ependymoma: A diagnostic dilemma

Giant cell ependymomas (GCE) are extremely rare tumors, with 24 cases described in the literature. Squash cytology is a rapid, reliable, simple technique for intraoperative consultation in neurosurgical practice. We describe a rare case of GCE arising at level of L4-L5 in a 66-year-old woman and discuss the cytologic/histologic features. Intraoperative smears were highly cellular with a prominent fibrillary background and exhibited papillary structures and sheets composed of highly atypical and bizarre cells. Some of the cells showed nuclear pseudoinclusions and rarely formed pseudorosette-like arrays. Intraoperative diagnosis was high grade glial tumor. On paraffin sections, besides extensive polymorphism, there were no microvascular proliferation, necrosis, and mitosis and the final diagnosis was WHO grade II GCE. GCE may be a diagnostic challenge on intraoperative smears, frozen, and paraffin sections. It must be kept in mind in the differential diagnosis of giant cell exhibiting benign and malignant tumors of brain.

Dropped head congenital muscular dystrophy caused by de novo mutations in LMNA

BACKGROUND Dropped head syndrome is an easily recognizable clinical presentation of Lamin A/C-related congenital muscular dystrophy. Patients usually present in the first year of life with profound neck muscle weakness, dropped head, and elevated serum creatine kinase. CASE DESCRIPTION Two patients exhibited head drop during infancy although they were able to sit independently. Later they developed progressive axial and limb-girdle weakness. Creatine kinase levels were elevated and muscle biopsies of both patients showed severe dystrophic changes. The distinctive clinical hallmark of the dropped head led us to the diagnosis of Lamin A/C-related congenital muscular dystrophy, with a pathogenic de novo mutation p.Glu31del in the head domain of the Lamin A/C gene in both patients. Remarkably, one patient also had a central involvement with white matter changes on brain magnetic resonance imaging. CONCLUSION Lamin A/C-related dropped-head syndrome is a rapidly progressive congenital muscular dystrophy and may lead to loss of ambulation, respiratory insufficiency, and cardiac complications. Thus, the genetic diagnosis of dropped-head syndrome as L-CMD and the implicated clinical care protocols are of vital importance for these patients. This disease may be underdiagnosed, as only a few genetically confirmed cases have been reported.

Solid-Pseudopapillary neoplasm of the pancreas: A clinicopathological review of 20 cases including rare examples

AIMS Solid-pseudopapillary neoplasm (SPN) is an uncommon malignant tumor of the pancreas with a favorable prognosis unlike other pancreatic neoplasms. We investigated the clinicopathological features of 20 patients with SPN in details. METHODS The patients diagnosed as SPN in Dokuz Eylul University Hospital between January 2005 and March 2016 were reviewed in terms of clinical and histopathological data. RESULTS Mean age of the patients was 33. Three of our cases were male and 4 were children. Some patients had synchronuous malignancies. Nine patients were diagnosed by fine needle aspiration cytology (FNAC). One of our tumors had 2×1mm of pancreas endocrine neoplasm in addition to SPN. One case had foci of atypical and multinucleated giant cells. All cases were positive for vimentin and CD10 antibodies and most were positive for PR and β-catenin. The mean follow-up duration was 40 mo (range 2-110 mo). Only one case showed liver metastasis. CONCLUSION Herein we present a series of 20 patients with 3 male and 4 pediatric cases, almost half of which were diagnosed with FNAC findings, and most of which are clinically being followed with one patient showing progression. Our series includes rare examples like collision tumor of SPN and pancreas endocrine neoplasm, SPN with multinucleated giant cells. Also cases with no surgical treatment and no progression, as well as cases with synchronous malignancies are presented. We believe that FNAC findings of any pancreatic mass should be investigated in detail for the designation of a therapy plan especially for the patients with high operation risks. The findings in our series also show that extensive necrosis, angioinvasion, perineurial invasion and larger tumor size might be predictive for worse prognosis and these patients should be more closely followed up.

Imaging findings of an epidermoid cyst with malignant transformation to squamous cell carcinoma.

We report imaging findings of a 64-year-old male patient with a ruptured epidermoid cyst (EC) known to be constant over the 23-year follow-up and showing malignant transformation to squamous cell carcinoma (SCC). Computed tomography (CT) and magnetic resonance imaging (MRI) findings including diffusion weighted imaging (DWI), 1H+MR spectroscopy (MRS), dynamic susceptibility contrast perfusion (DSC) MRI of EC, and its rare complications are presented together with a review of the literature. Fluid-lowattenuated- inversion-recovery (FLAIR) and T1-weighted images with gadolinium are the best sequences together with DWI to show the relationship of the EC, the SCC and the border between. Primary brain SCC enhances mostly ring-like or peripherally, but diffuse enhancement is also possible. To our knowledge, no MRS and DSC findings have been reported in the literature yet.