Raja Rabah

Altered cardiac histology following apical right ventricular pacing in patients with congenital atrioventricular block.

Previous studies have demonstrated that right ventricular apical pacing inherently alters ventricular contraction, regional blood flow, wall stress, and predisposes to diminished function. However, histological consequences of chronic apical pacing potentially contributing to the observed ventricular dysfunction remain conjectural. Previous canine studies have demonstrated histopathological cellular abnormalities with apically initiated ventricular pacing that may result in the observed diminished ventricular function. To determine if comparable adverse changes also occur in the clinical setting, 16 endomyocardial biopsies were obtained from 14 age‐matched patients with congenital complete atrioventricular block (CCAVB) and otherwise normal anatomy, divided into two groups: eight biopsies (median patient age 15.5 years) from patients prior to pacemaker implant and another eight biopsies (median patient age 16 years) from patients following 3–12 years (median 5.5) of chronic ventricular pacing. In one patient, biopsy samples were obtained before and after pacing. Results demonstrated a significant (P < 0.05) increase in histopathological alterations among the patient biopsy samples following pacing, consisting of myofiber size variation, fibrosis, fat deposition, sclerosis, and mitochondrial morphological changes. These findings indicate that chronic apical right heart ventricular pacing may adversely alter myocellular growth, epecially among the young, on the cellular and subcellular level, potentially contributing to the diminished function observed clincially.

Integration of human papillomavirus type 11 in recurrent respiratory papilloma-associated cancer.

Objectives/Hypothesis: The main objective was to demonstrate that human papillomavirus (HPV) type 11 is an aggressive virus that plays a significant role in the development of laryngeal cancer in patients with a history of recurrent respiratory papillomatosis (RRP). We have done so by preliminary investigation into the molecular mechanism underlying the malignant transformation of RRP to invasive squamous cell carcinoma.

Pediatric renal carcinoma associated with Xp11.2 translocations/TFE3 gene fusions and clinicopathologic associations.

Renal cell carcinomas (RCCs) are rare in children and studies of their subtypes and clinicopathologic associations are limited to small series. We identified 8 patients with RCC treated at our institution between 1981 and 2003, reviewed their clinicopathologic features, cytogenetics findings, and evaluated the status of TFE3 expression by immunohistochemistry and numerical chromosomal alterations by interphase fluorescent in situ hybridization on paraffin-embedded tissue. These 8 patients (5 female and 3 male) had diploidy, and 5 had morphologic features compatible with the recently described RCC associated with Xp11.2 translocations/TFE3 gene fusions and demonstrated nuclear labeling for TFE3 protein by immunohistochemistry. The translocation was confirmed in 2 of these 5 patients by conventional cytogenetics. One case was a high-grade nonpapillary RCC and the other was compatible with type 2 papillary RCC. Four patients showed at least 1 chromosomal gain including trisomy 7 and/or trisomy 17. None of the tumors from male patients showed evidence of loss of the Y chromosome, but 2 patients showed numerical abnormalities of X chromosome +add(X). Two patients had sickle cell disease, and 1 of these also had stage IV-S neuroblastoma. This study suggests that many cases of RCC in children reported under the terms “papillary” and “clear cell” likely represent Xp11.2 translocation/TFE3 gene fusion-associated RCC. It also emphasizes the unusual associations of RCC with neuroblastoma and sickle cell hemoglobinopathy, which need further study.

Congenital Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins Associated with Hypoplastic LeftHeart Syndrome

Three full-term infants died in the first month of life with hypoplastic left heart syndrome (HLH) and persistent pulmonary hypertension (PPH). At postmortem examination, they were found to have alveolar capillary dysplasia with misalignment of pulmonary veins (ACD with MPV). The association of HLH syndrome, and ACD with MPV with intestinal malrotation and/or obstruction, is unique. Decreased blood flow in the ascending aorta in fetuses with left outflow tract obstruction might cause vasoconstriction of pulmonary arterioles to maintain cerebral perfusion. Vasoconstriction early during embryogenesis might lead to decreased growth and development of alveolar capillaries and pulmonary veins. This results in pulmonary hypertension, and the arterial blood is forced to bypass the deficient capillary bed and can drain only via the anomalous bronchial veins.

Diagnosis of neuroblastoma and ganglioneuroma using Raman spectroscopy.

BACKGROUND Raman spectroscopy has proven to be useful in studying premalignant and malignant lesions in adults. This is the first report to evaluate Raman spectroscopy in the diagnosis and classification of neuroblastoma in children. METHODS A biopsy or resection of fresh tissue samples from normal adrenal glands, neuroblastomas, ganglioneuromas, nerve sheath tumors, and pheochromocytoma at our hospital were equally divided between routine histology and spectroscopic studies. At least 12 spectra were collected from different regions of each sample using a Renishaw Raman microscope. Raw spectra were processed to remove noise, fluorescence, and shot noise, and then analyzed using principle component analysis and discriminant function analysis. RESULTS We collected 698 spectra from 16 neuroblastomas, 5 ganglioneuromas, 3 normal adrenal glands, 6 nerve sheath tumors, and 1 pheochromocytoma. Raman spectroscopy differentiated between normal adrenal gland, and neuroblastoma and ganglioneuroma with 100% sensitivity and 100% specificity. It correlated well with the Shimada histologic classification system with 100% sensitivity and 100% specificity. It was also able to differentiate neuroblastoma from nerve sheath tumors and pheochromocytoma with high sensitivity and specificity. CONCLUSION This technique can differentiate neuroblastoma from ganglioneuroma and other tumors. It has a potential as a noninvasive real-time diagnostic tool in classifying pediatric tumors.

Primary versus Radiation-Associated Craniofacial Osteosarcoma Biologic and Clinicopathologic Comparisons

Craniofacial osteosarcoma differs from long bone osteosarcoma in that patients are older, tumors are often low grade, and prognosis is more favorable. Although most are sporadic, some tumors occur in association with prior radiation therapy. The purpose of the current study was to compare clinicopathologic and prognostic features of primary and radiation‐associated osteosarcoma.

ORGANOTYPIC CULTURE OF HUMAN OVARIAN SURFACE EPITHELIAL CELLS: A POTENTIAL MODEL FOR OVARIAN CARCINOGENESIS

SummaryThe objective of this work was to establish an in vitro multidimensional culture system for human ovarian surface epithelial (HOSE) cells as a model for ovarian carcinogenesis. The epithelial origin of cell outgrowth from cells obtained from the ovarian surface was confirmed by keratin staining. Two cultures from two different patients were established, HOSE-A and HOSE-B. Cultures were infected with a retrovirus expressing human papillomavirus genes E6 and E7 to extend their life span. HOSE cells were seeded onto collagen gels containing NIH3T3-J2 fibroblasts as feeder cells and grown to confluence submerged in growth medium. The collagen bed was then raised to the air-medium interface for 7 d (organotypic culture). Microscopically, fixed cultures revealed a single layer of flat cells growing on the collagen surface, reminiscent of HOSE cells in vivo. Infected HOSE-A and HOSE-B cells exhibited aberrant growth because they stratified. In addition, established ovarian cancer lines grown in this fashion stratified and showed malignant phenotypes. Thus, cells grown in organotypic culture resemble their in vivo counterparts, providing a basis for establishing a system to study growth, proliferation, differential gene expression, and perhaps malignant transformation of HOSE cells.

Evaluation of pancreatic cancer with Raman spectroscopy in a mouse model.

Objectives: Detection of neoplastic changes using optical spectroscopy has been an active area of research in recent times. Raman spectroscopy is a vibrational spectroscopic technique that can be used to diagnose various tumors with high sensitivity and specificity. We evaluated the ability of Raman spectroscopy to differentiate normal pancreatic tissue from malignant tumors in a mouse model. Methods: We collected 920 spectra, 475 from 31 normal pancreatic tissue and 445 from 29 tumor nodules using a 785-nm near-infrared laser excitation. Discriminant function analysis was used for classification of normal and tumor samples. Results: Using principal component analysis, we were able to highlight subtle chemical differences in normal and malignant tissue. Using histopathology as the gold standard, Raman analysis gave sensitivities between 91% and 96% and specificities between 88% and 96%. Conclusions: Raman spectroscopy along with discriminant function analysis is a useful method to detect cancerous changes in the pancreas. Pancreatic tumors were characterized by increased collagen content and decreased DNA, RNA, and lipids components compared with normal pancreatic tissue.

Pathology of the appendix in children: an institutional experience and review of the literature

BackgroundThe appendix can be affected by a variety of congenital and acquired diseases, but acute appendicitis is the most common pathology found in the pediatric population.ObjectiveThis is a retrospective review of all appendectomies performed during a 2-year period at a major children’s hospital with a review of the literature regarding the most common pathologic findings.Materials and methodsThe pathology database was reviewed for appendectomy specimens, and patient medical records were evaluated to determine the age, gender, race and operative diagnosis. All slides were reviewed and the histologic findings were recorded.ResultsA total of 392 appendectomies were performed, including 68 incidental appendectomies and 324 performed for clinical suspicion of acute appendicitis. In 247 of the latter, acute appendicitis was confirmed histologically, and of the remainder 14 were interval appendectomies, 2 had findings suspicious for Crohn disease, 1 confirmed diverticulitis and 60 were histologically negative for appendicitis.ConclusionAcute appendicitis is the most common pathologic cause of appendectomy, but various other pathologic entities are found in children. Examination of the appendix is warranted even when it appears normal on exploration.

Granular cell tumor of the bronchus

Persistent atelectasis and recurrent pneumonia in the same location should raise suspicion of congenital anomalies or obstructing lesions of the bronchus leading to the affected area. We present an 8‐year‐old black female with a history of recurrent fever, cough, atelectasis of the right middle and lower lobes, and weight loss for several months. Flexible bronchoscopy revealed a polypoid mass obstructing the bronchus intermedius. Biopsy of the neoplasm demonstrated a granular cell tumor (GCT). The patient had a lobectomy of the right lower and middle lobes. She had no recurrence of the tumor after several years of follow‐up. Pediatr Pulmonol. 2000; 30:425–428.