Roma S. Chandra

Neuron-specific enolase in the diagnosis of neuroblastoma and other small, round-cell tumors in children

Immunocytochemical staining for neuron-specific enolase (NSE) was performed in 44 round-cell tumors from children by the improved immunoglobulin-enzyme bridge method with antiserum against NSE. The tumors studied consisted of 15 neuroblastomas showing various degrees of histologic differentiation, 13 Ewings sarcomas, ten soft tissue sarcomas of diverse origin, and six lymphomas of bone and soft tissues. Neuron-specific enolase was detected in all neuroblastomas, irrespective of the degree of histologic differentiation. None of the other round-cell tumors was positive for NSE, except one embryonal rhabdomyosarcoma that contained differentiated myoblasts. The primitive cells of this tumor were negative as well. It is concluded that immunocytochemical staining with antibodies to NSE is a practical and reliable method for distinguishing neuroblastomas from other nonneural round-cell tumors in children. This is true even for the most primitive forms of neuroblastomas, in which morphologic techniques are less reliable. Neuron-specific enolase may also be useful in delineating the neural histogenesis of other ill-defined tumors.

Solid and Papillary Epithelial Neoplasm of the Pancreas An Ultrastructural and Immunocytochemical Study of Six Cases

AbstractSolid and papillary epithelial neoplasms of the pancreas from six female patients were studied using immunohistochemistry and electron microscopy to define better their histogenesis. The tumors ranged in diameter from 5 to 15 cm (average: 9 cm), and, on cross section, most had areas of hemorrhage and necrosis, sometimes extensive. Microscopically, there was a solid and pseudopapillary pattern, with tumor cells typically having ovoid nuclei with delicate folding and indistinct nucleoli. Of note were the following: a relatively low mitotic rate (range: 0–6/20 hpf), the presence of hyaline globules (four of six cases), and collections of foam cells (three of six cases). Staining for cytoplasmic argyrophil granules was negative in each case. Ultrastructurally, the solid and papillary epithelial neoplasms of the pancreas showed evidence of acinar or ductular differentiation. Two contained zymogen granules, one had intermediate filaments (probably keratin), and three had abundant rough endoplasmic reticulum and mitochondria. Immunostaining was positive for chymotrypsin (six of six cases), trypsin (four of six), and amylase (three of six). None was positive for alpha-1-antitrypsin, neuron-specific enolase, pancreatic polypeptide, gastrin, glucagon, somatostatin, or insulin. The findings support an origin from exocrine pancreas, and follow-up indicates a low rate of malignancy, with local recurrence in two of the six patients.

Evidence for neural origin and PAS-positive variants of the malignant small cell tumor of thoracopulmonary region («Askin tumor»)

The differential diagnoses of childhood and adolescent tumors composed of small round cells include a distinctive clinicopathological entity called malignant small cell tumor (MSCT) of the thoracopulmonary region in childhood. In the present study, 15 such tumors that fulfilled the criteria by Askin et al. were examined for features of possible neural differentiation by light and electron microscopy (EM). With hematoxylin-eosin stain (H&E) the tumors were made up of small undifferentiated cells; rosette formation was noticed in four cases. By immunohistochemistry all 15 tumors were positive for neuronespecific enolase (NSE), which is a specific marker for neural elements and their tumors including neuroblastomas. Ten of 15 MSCT had positive PAS staining. Ultrastructurally dense core (neurosecretory) granules and cell processes indicative of neuronal differentiation could be recognized in 10 of 14 tumors. The dense core granules were often atypical. Filamentous cytoskeleton, never observed in Ewings sarcoma, was often present. Based on the current results, MSCT of the thoracopulmonary region can be considered a peripheral neuroectodermal tumor with the possible origin in intercostal nerves. MSCTs are generally misdiagnosed as Ewings sarcoma due to their primitive appearance in H&E sections and their periodic acid-Schiff positivity. NSE immunostaining, preferably augmented by electron microscopy, is necessary for their correct diagnosis.

ADJUNCTIVE ORAL CORTICOSTEROIDS REDUCE RENAL SCARRING: THE PIGLET MODEL OF REFLUX AND ACUTE EXPERIMENTAL PYELONEPHRITIS

PURPOSE We investigate the efficacy of antibiotics combined with corticosteroid in diminishing post-pyelonephritic renal scarring compared to standard antibiotic therapy. MATERIALS AND METHODS Bilateral vesicoureteral reflux was surgically created in 36 piglets (72 kidneys). A week later each bladder was inoculated by percutaneous injection with a standardized broth culture of Escherichia coli and molten paraffin. 99mTechnetium dimercapto-succinic acid (DMSA) scintigraphy was performed 3 days after introduction of urinary infection to detect the presence of acute pyelonephritis. Acute pyelonephritic lesions seen on DMSA scans were graded according to the percentage of renal zone involvement as grade 1--less than 33%, grade 2--33 to 66% and grade 3--greater than 66% involved. When pyelonephritis was present, piglets were randomized to receive either standard antibiotics or antibiotics and 2 mg./kg. prednisolone daily. 99mTechnetium-DMSA scintigraphy was repeated 2 months after completion of therapy, and the kidneys were harvested for gross and histopathological examination. Each kidney was divided into upper, middle and lower zones for correlation of pathological and imaging findings. Severity of renal scarring was then assessed using histopathological confirmation of gross anatomical findings as grade 1--less than 1, grade 2-1 to 2 and grade 3-greater than 2 cm. RESULTS Acute pyelonephritis was induced in 136 of 216 renal zones. The sites of renal scarring corresponded anatomically to sites of acute pyelonephritis in all but 5 cases. Overall, the prevalence of post-pyelonephritic scarring was 56.6% (77 of 136) of renal zones. The severity of scarring in both groups correlated with the severity of the initial pyelonephritic lesion. Of the 31 zones that formed grade 3 renal scars the distribution of grades 1, 2 and 3 acute pyelonephritis on the initial DMSA scan was 3, 26 and 71%, respectively. Grade 3 acute pyelonephritis was more likely to result in severe (grade 3) renal scars in the control compared to the steroid treated group (59 versus 31%). Overall, acute pyelonephritis completely resolved in 40% of controls and 51% of steroid treated animals. However, only 9% of control animals with grade 3 acute pyelonephritis demonstrated complete resolution, as opposed to 28% of those receiving steroids. CONCLUSIONS The risk of renal scarring is greatest after severe acute pyelonephritis involving greater than 66% of a renal zone. Adjunctive oral prednisolone appears to be effective in diminishing renal scarring in severely affected kidneys. In kidneys with mild and moderate acute pyelonephritis antibiotics alone appear to be equally effective in preventing scarring.

Epstein-Barr Virus-Associated Smooth Muscle Tumor of the Basal Ganglia in an HIV Child: Case Report and Review of the Literature

We describe the clinicopathologic features of an Epstein-Barr virus (EBV)-associated smooth muscle tumor arising in the basal ganglia of a 10-year-old human immunodeficiency virus (HIV)-positive child. Only a few cases of intracranial smooth muscle tumors are reported in the literature and virtually all of these have been extra-axial, involving the dura or sinuses in HIV+ adults. Our case underscores the need to include an EBV-associated smooth muscle tumor in the differential diagnosis when evaluating intracranial mass lesions in immunodeficient children.

AMEBIC OSTEOMYELITIS IN a CHILD WITH ACQUIRED IMMUNODEFICIENCY SYNDROME: A Case Report

Disseminated Acanthamoeba infection has been described in immunocompromised or debilitated patients. The usual sites of involvement are skin, sinus, and brain. Sporadic reports of Acanthamoeba infection in patients infected with the human immunodeficiency virus are present in recent literature, predominantly in adults, and one case involving an 8-year-old child. We describe a case of amebic osteomyelitis, seen in a 6-year-old child with vertically acquired human immunodeficiency virus and a 6-month history of cutaneous Acanthamoeba infection.

Pediatric renal artery dysplasia: a morphologic study.

Renal arteries from 12 pediatric patients who had stenosis due to renal artery dysplasia (9 surgical resections and 3 autopsy cases) were examined by light microscopy. The patients ranged in age from 15 months to 14 years; the male/female ratio was one. Bilateral renal artery disease was clinically diagnosed in 8 of the 12 patients; 6 of the 8 also had aortic anomalies. All of the lesions were designated as forms of dysplasia, a departure from previous reports in which dysplasia was subclassified as fibroplasia and hyperplasia. The most common lesion was medial fibrous dysplasia (6), followed by perimedial elastic dysplasia (4); intimal fibrous dysplasia (1) and medial muscular dysplasia (1) were the least common. Medial fibrous dysplasia was present as often with bilateral as with unilateral renal artery stenosis, while perimedial elastic dysplasia was seen exclusively in patients with bilateral renal artery disease. Three patients who came to autopsy had extrarenal vascular involvement by a similar dysplastic lesion. The three patients who had neurofibromatosis showed no distinctive histologic type of renal artery dysplasia.

Diffuse pulmonary arteriovenous malformation in a child with polysplenia syndrome.

Pulmonary arteriovenous malformation (PAVM) is usually seen as a well-circumscribed cystic mass. In this communication we describe a diffuse arteriovenous malformation in a 5-month-old infant. The lesion was seen only at the microscopic level and was associated with abdominal heterotaxy, atrial situs solitus, polysplenia, interrupted inferior vena cava, atrial septal defect, and atrioventricular canal. This uncommon association may be within the spectrum of polysplenia syndrome.

Rapid Tissue Diagnosis of Herpes Simplex Infections in the Newborn

The presence of intranuclear inclusions in tissues is considered to be consistent with viral infections. Further identification is done by viral cultures. In this study, the direct immunofluorescence technique was utilized to identify herpes simplex virus in the tissues. Positive fluorescence was seen in 8 of 12 specimens. In all these specimens, diagnosis was further confirmed by electron microscopy, viral cultures, or both. Thus, the technique is a specific, sensitive method of diagnosis for herpes simplex infections. Rapidity and simplicity of the technique warrant regular use.