Maher A. Sughayer

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.

Hotspot mutations of PIK3CA and AKT1 genes are absent in multiple myeloma

The phosphatidylinositol-3-kinases PI3K/AKT pathway regulates many growth and survival mechanisms in the cell, and it has been implicated in development and progression of many human cancers, including multiple myeloma. Recently, many reports have revealed that the PIK3CA gene which encodes the p110 catalytic subunit of PI3K kinase is mutated in many human malignancies. To investigate the oncogenic role of PI3K/AKT pathway in multiple myeloma we sequenced three hot exons: exons 9 and 20 of PIK3CA gene and exon 3 of AKT1 gene in 27 multiple myeloma patients. Our results indicate the absence of the four hot spot mutations E542K, E545K, H1047R and E17K in all studied cases. These findings suggest that PI3K/AKT mutations may not play a major role in multiple myeloma.

Prevalence of hormone receptors and HER2/neu in breast cancer cases in Jordan

The management and prognosis of breast cancer nowadays require the evaluation of Estrogen (ER), Progesterone Receptors (PR) and HER2/neu. Ethnic variation in the expression of these receptors is well documented. The aim of this study is to determine the prevalence of ER, PR and HER2/neu among Jordanian women with breast cancer of ductal and lobular types. A retrospective analysis was performed on 267 cases of breast cancer referred for treatment at King Hussein Cancer Center, Jordan between the period of June 2003 and June 2004. Standard immune stains were used for evaluation of hormone receptors and HER2/neu. In addition, evaluation of HER2/neu was done by FISH in selected cases. Of these 267 cases, 240 (89.9%) were ductal carcinomas of various histological grades, 122 (50.8%) of which were ER-positive, 138 (57.5%) PR-positive and 42 (17.5%) HER2/neu-positive. Twentytwo (8.2%) of all cases were lobular carcinomas, 15 (68%) of which were ER-positive,20 (90.9%) PR-positive and 3 (13.6%) HER2/neu-positive. Five (1.9%) of the total cases were of mixed lobular and ductal types, 4 (80%) of which were ER-positive, 3 (60%) PR-positive and none were positive for HER2/neu. The prevalence of hormone receptor positivity in breast cancer of Jordanian women is lower than that of the western populations and close to other populations such as the Chinese and the minor ethnic groups of Northern America (African Americans).(Pathology Oncology Research Vol 12, No 2, 83–86)

Malignant insulinoma in a child

Insulinomas are rare tumors with an estimated incidence of one per 250,000 person‐years. Most insulinomas are benign with less than 10% demonstrating malignant behavior, the vast majority of which occur in adults. A systemic review of the literature revealed only nine cases of malignant insulinomas occurring in children. Herein, we present a case of metastatic malignant insulinoma in a 12‐year‐old child. The occurrence of this diagnosis in a child, its unusual pattern of metastases and the challenging management of severe hypoglycemia make this case worth reporting. Pediatr Blood Cancer. 2010;55:1423–1426.

Thymoma and Thymic Carcinoma Arising in a Thymolipoma: Report of a Unique Case

Thymic carcinoma arising within a thymolipoma has not been reported previously. The authors present a unique case of thymoma and undifferentiated thymic carcinoma arising within a thymolipoma in a 36-year-old woman. The bulk of the resected mass was composed of benign fatty tissue admixed with foci of unremarkable thymic tissue; however, it also harbored a central solid mass showing undifferentiated thymic carcinoma associated with a type B2 thymoma. The carcinoma cells were positive for cytokeratin AE1/AE3, cytokeratin 19, and cytokeratin 8/18. They were negative for vimentin, cytokeratin 7, cytokeratin 20, CD5, epithelial membrane antigen, CD30, placental alkaline phosphatase, carcinoembryonic antigen, CD99, leukocyte common antigen, Epstein-Barr virus, inhibin alpha, and protein gene product 9.5. Rare tumor cells showed positive staining for chromogranin and synaptophysin.

Radiotherapy with concurrent or sequential temozolomide in elderly patients with glioblastoma multiforme

Objective: The objective of this article was to evaluate therapeutic outcomes of elderly patients with glioblastoma multiforme (GBM) treated by surgery followed by combined modality therapy and compare achievable outcomes to those of a younger age population.

INI1 (BAF 47) Immunohistochemistry is an Essential Diagnostic Tool for Children With Hepatic Tumors and Low Alpha Fetoprotein

Malignant rhabdoid tumor (MRT) of the liver is a rare malignancy with grave prognosis. This entity should be considered in the differential diagnosis of any aggressive liver tumor with low levels of alpha fetoprotein. We report 2 cases of hepatic MRT presenting in infancy. In these 2 cases, we show that loss of INI1 facilitates making the correct diagnosis of primary hepatic MRT utilizing BAF 47 (INI1 gene product) immunostains. Difficulty encountered in making this rare diagnosis, including the need for repeated biopsies, can be avoided if MRT is considered in the differential diagnosis early on and BAF 47 immunohistochemistry is ordered.

Solid (stromal predominance) hepatic mesenchymal hamartoma

Received: 25 July 2004 Revised: 9 August 2004 Accepted: 11 August 2004 Published online: 12 October 2004 Springer-Verlag 2004 A 4-year-old girl was well apart from a huge, right-upper-quadrant abdominal mass of 1-year duration that had enlarged over the previous 4 months. Contrast-enhanced CT showed a 12.5 cm·15 cm·10-cm, well-defined, upper abdominal softtissue mass, most likely arising from the quadrate lobe of the liver, with heterogeneous contrast enhancement. The mass was completely surgically removed. The histological diagnosis was hepatic mesenchymal hamartoma (HMH). Liver tumours comprise only 1–2% of all paediatric tumours; two-thirds are malignant. HMH constitutes about 8% of all paediatric hepatic tumours [1]. Two patterns are described: cystic predominant and stromal predominant, with the former being much more common [2]. The tumours are usually large at presentation, 16 cm on average, and usually present in the first 2 years of life. Boys are affected twice as often as girls [3]. Clinically, abdominal distension and a painless mass are the most common symptoms. The radiological appearances reflect the gross pattern, ranging from a predominantly cystic mass to a complex solid mass. The stromal predominant variant shows a complex solid mass on US while the CT appearances are of an enhancing solid mass (Fig. 1). Stromal predominant lesions on MRI demonstrate hypointense signal relative to normal liver on both T1and T2-weighted images due to fibrotic changes: they show intense heterogeneous contrast enhancement. The differential diagnosis includes hepatoblastoma, hepatocellular carcinoma, infantile haemangioendothelioma and undifferentiated embryonal sarcoma. In endemic areas, hydatid cyst should also be considered.

Human papillomavirus genotypes in invasive cervical cancer in Jordan

Cervical cancer is the second most common cancer affecting women worldwide [1], with persistent infection by high-risk human papillomavirus (HPV) having an important role in cervical carcinogenesis [2]. Knowledge of HPV genotypes associated with invasive cervical carcinoma is necessary for determining the impact of new HPV vaccines on the incidence of these lesions. An updated meta-analysis of the worldwide distribution of HPV types associated with both invasive cervical cancer and high-grade squamous intraepithelial lesions was recently published [3]. A total of 14 595 cases of invasive cervical cancer revealed HPV 16 to be the most common type on all continents, with HPV 18 the second most common. Types 31, 33, 35, 45, 52, and 58 were the next most common types, although there was regional variation in the relative importance of each of these 6 types. Data from the Middle East were scarce; thus, the objective of the present study was to determine the HPV genotypes involved in invasive cervical cancer in Jordan. The archives of the Pathology Department at King Hussein Cancer Center, Amman, Jordan, were searched for cases of invasive cervical cancer; all cases accessioned at the time of diagnosis between 2003 and 2007, and with available paraffin blocks, were analyzed. Using the Extra DNA Tissue kit (Sacace Biotechnologies, Como, Italy) according to the manufacturers instructions, DNA was extracted from the paraffin blocks. The adequacy and the integrity of extracted DNA were assessed via spectrophotometry and polymerase chain reaction (PCR) for the gene encoding GAPDH. An HPV typing kit (Sacace Biotechnologies, Como, Italy) containing 4mixes of multiple primers—types 16, 31, 33, and 35; types 18, 39, 45, and 59; types 52, 56, 58, and 66; and types 6 and 11—was used. Amplification was followed by electrophoresis and band identification using an ultraviolet transilluminator. Negative results were invalidated if the internal control (the gene encoding β-globin) was absent. Positive and negative controls were included in each run. Forty-eight cases of invasive cervical cancerwith 54 paraffin blocks available were identified; 7 cases failed to produce adequate DNA. Patient age in the remaining 41 cases ranged from 37 to 80 years, with Cervical cancer Genotypes Human pap lomavirus Jordan a median group of 45–49 years. There were 40 cases of squamous cell carcinoma and 1 of adenocarcinoma. The HPV types obtained are shown in Table 1. Multiple infections in a single patient were common in the present study, with 14 patients (34.1%) harboring 2 or 3 types simultaneously. The single case of adenocarcinoma involved types 16 and 18. This combined type was found in 7 cases, with types 16 and/or 18 found in 31 (75.6%) overall. Thus, singly or in combination, the other HPV types were responsible for approximately 25% of cervical cancer cases. The next most common types were 39, 56, 45, 52, and 33. In the present study, type-specific primers were used, which had a higher sensitivity when applied to tissue biopsy than did the general primers used in most earlier studies. However, the present study was limited by the small number of samples available for study, in addition to the fact that it involved a referral center with no control over the processing or storage of the referred tissue blocks. Furthermore, only limited epidemiologic information on the study population was available. Nevertheless, HPV types 16 and/or 18 were found in approximately 75% of cases of invasive cervical cancer, which is similar to the rates in Europe, North America, Australia, Algeria, and Morocco [3–5]. The relative importance of other high-risk types was slightly different from that reported in other studies, with types 39 and 56 more common than others—in contrast to findings from the HPVworldwide type distribution meta-analysis, where these types were not present among the 6 most common after types 16 and 18 (in Europe, type 56 was the eighth most common) [3]. Additionally, types 31, 33, 35, and 58 were less common in the present study. These discrepant results may be explained by the small number of specimens studied and the fact that regional variations exist in the relative importance of HPV types; for example, type 58 is the third most common type in Asia, but in other parts of the world it is the least common. Multiple high-risk HPV types were found in approximately 34% of cases, which is consistent with results from several studies [6]. The

Frequent coexistence of RAS mutations in RUNX1-mutated acute myeloid leukemia in Arab Asian children.

RUNX1 mutation plays an important role in adult leukemic transformation. However, its contribution to the development of childhood leukemia remains unclear. In the present study, we analyzed point mutations of RUNX1 gene in children and adolescents with acute myeloid leukemia (AML) from Iraq and Jordan.