Cytologic features of desmoplastic infantile ganglioglioma: a report of two cases.

BACKGROUND: Desmoplastic infantile ganglioglioma (DIG) is a rare intracranial tumor of infancy, characterized by solid and cystic components, voluminous size and supratentorial location. Although its histologic features have been reported, there has been no cytologic description of the tumor. Cytologic findings on imprint and aspirated material from two cases of histologically verified DIG are discussed. CASES: A 12-month-old male with cutis marmorata telangiectatica congenita and a 44-month-old female with episodes of spasm were referred to our center. Radiologic examination revealed a large, cystic, supratentorial mass in both patients. The mass was surgically removed, and histology revealed prominent desmoplasia with a mixture of astroglial and neuronal cells. Cytologic findings on imprint material and the needle aspirates taken from the cystic area of the tumor revealed a few isolated or sheetlike arrangements of small cells positive for glial fibrillary acidic protein and a few large cells with abundant cytoplasm and prominent nucleoli, positive for neuronal marker. CONCLUSION: Although distinction between ganglioglioma and DIG may be difficult by cytology alone, with the characteristic clinical presentation and radiologic findings, the possibility of DIG should be kept in mind when the specimens contain both astroglial and neuronal elements.

Frequent beta-catenin mutation and cytoplasmic/nuclear accumulation in pancreatic solid-pseudopapillary neoplasm.

Significance of Wnt signaling with beta-catenin mutations on solid-pseudopapillary neoplasm (SPN) of the pancreas was studied by immunohistochemistry and molecular analysis. On immunohistochemistry, all 18 SPNs tested showed diffuse cytoplasmic/nuclear positivity for beta-catenin. Upon direct DNA sequencing of exon 3 of the beta-catenin gene, 15 (83%) of the 18 SPNs showed 1-bp missense mutation in codons 32 (5 cases), 33 (3 cases), 34 (3 cases), 37 (3 cases), and 41 (1 case). Immunoreactivity for cyclin D1, one of the intranuclear targets of beta-catenin complexes, was found in tumor cells of more than half the tumor cells of all of the 18 SPNs. The present study strongly suggested a significant role of Wnt signaling, mostly associated with beta-catenin mutations in the tumorigenesis of SPN.

Measles virus infection in the placenta of monozygotic twins.

We report a case of monozygotic twins whose mother was infected with measles at 19 weeks' gestation. One of the twins died in utero at 32 weeks' gestation. The placenta of the stillbirth showed massive fibrin deposition, and some residual trophoblasts contained many inclusion bodies positive for measles virus antigen. Fetal organs and cells other than a few splenic lymphocytes showed no evidence of measles virus infection. The placenta of the surviving infant showed focal intervillous fibrin deposits, and only a few syncytiotrophoblasts were positive for measles virus antigen. At present, 7 months after the delivery, the surviving infant has not developed any sign of measles virus infection. Postpartum course of the mother has been uneventful, although high titers of serum anti-measles virus IgM persisted for 6 months after delivery. This case is informative in the following respects: the villous trophoblasts had diagnostic inclusion bodies and ultrastructural evidence of measles virus infection, the degree of viral involvement within the monochorionic placenta was uneven, both of the twins were virtually free from measles virus infection despite the marked involvement of the placenta, and measles virus infection had persisted in the monochorionic placenta for approximately 13 weeks.

Ewing's sarcoma family of tumor arising in the adrenal gland--possible diagnostic pitfall in pediatric pathology: histologic, immunohistochemical, ultrastructural, and molecular study.

We present an adrenal Ewing's sarcoma family of tumor (ESFT) arising in an 11-year-old Japanese boy. Although intensive chemoradiotherapy and radical surgery were performed, the patient died of obstinate disease 1 year and 3 months after the initial presentation. The primary site (adrenal gland) with radiologic findings (with foci of calcification), high titer of serum neuron specific enolase, and sheets of monotonous primitive rounded cells on histology mostly favored neuroblastoma. However, a diagnosis of ESFT was confirmed by immunohistochemical profile, including MIC2-positivity and molecular study disclosing EWS-FLI1 chimera gene verified by direct sequencing. Recognition of adrenal ESFT and use of newly developed diagnostic techniques are required for differential diagnosis of undifferentiated small round cell tumor of the adrenal gland.

Pigmented intraosseous odontogenic carcinoma of the maxilla: a pediatric case report and differential diagnosis.

We report a pigmented intraosseous odontogenic carcinoma of the maxilla occurring in a 6-year-old Japanese boy. Grossly, the tumor showed solid, gray-yellow, and markedly pigmented appearance. Histology showed neoplastic growths of atypical epithelial cells that occasionally contained melanin pigments. Melanocytes with dendritic processes were often found in the tumor cell clusters, and solitary or aggregated melanophages were scattered within the dense fibrovascular stroma. The tumor cells were diffusely positive for cytokeratins and epithelial membrane antigen, and focally positive for vimentin, neuron specific enolase, neurofilament protein, carcinoembryonic antigen, and amelogenin. Ultrastructural studies showed well-developed intercellular junctions, mainly desmosomes, and glycogen particles. In addition, some tumor cells contained melanosomes and/or a few neurosecretory granules. We consider that the present tumor suggests a close association of ectoderm, mesenchyma, and neuroectoderm in embryogenesis of the tooth, and can raise a diagnostic confusion with melanotic neuroectodermal tumor.

Late recurrence of neuroblastoma stage 4S with unusual clinicopathologic findings.

The authors present unusual clinicopathologic findings of a patient with neuroblastoma stage 4S that recurred 11 years after induction of complete remission with chemotherapy. A 12-year-old girl presented with recurrent tumor in the liver. Urinary catecholamine metabolites were within normal range in contrast to the increased values at initial presentation. She underwent left lateral segmentectomy and biopsy of the right lobe. Histologic analysis of the recurrent tumor showed undifferentiated neuroblastoma intermingled with mature ganglioneuromatous lesions. There also were scattered ganglioneuromatous lesions throughout nontumorous area of the liver. Although multimodal intensified treatments including autologous bone marrow transplantation were performed, the patient died of obstinate recurrent tumor at age 14 years. The clinicopathologic findings suggested dedifferentiation from the ganglioneuromatous lesion rather than ordinary recurrence of the primary tumor. The current case and the literature review may indicate that long-term follow-up would be necessary for neuroblastoma stage 4/4S cases. J Pediatr Surg 36:953-955.

Congenital dyserythropoietic anemia type 1 with fetal onset of severe anemia.

We report a patient with congenital dyserythropoietic anemia type 1 with characteristic anomalies and two novel clinicopathologic presentations: intrauterine onset of severe anemia resulting in cardiac failure and relatively mild dyserythropoietic features on bone marrow aspiration in contrast to severity of anemia. After repeated transfusions and a trial of erythropoietin administration, the patient died from respiratory infection at age 7 months. Autopsy revealed characteristic dyserythropoietic features of the bone marrow by light microscopy and electron microscopy, which confirmed a diagnosis of congenital dyserythropoietic anemia type 1.

Losartan and fetal toxic effects.

We report a case of maternal exposure to the antihypertensive drug losartan during weeks 20-31 of pregnancy. We saw the fetal toxic effects of oligohydramnios (decreased amniotic fluid), fetal pulmonary hypoplasia, fetal hypoplastic skull bones, and subsequent fetal death. This pattern of abnormalities is similar to those seen in exposure to angiotensin-converting-enzyme (ACE) inhibitors during pregnancy, and were probably caused by losartan.

Clinicopathological study of a hilar nodule in the livers of long-term survivors with biliary atresia.

With the application of liver transplantation for patients with biliary atresia (BA), we have had the opportunity to review the clinicopathologic features of the native livers from 10 transplanted BA patients. A single large nodule at porta hepatis (hilar nodule) was noted in three of 10 patients, and an ill-defined nodule-like lesion at porta hepatis was present in two other patients. The three BA patients with hilar nodules were long-term survivors, compared to the patients with nodule-like and those without nodules. The hilar nodules measured between 5.0 cm and 8.0 cm and histologically, they were partly surrounded by fibrous septa with relatively well-preserved liver architectures and fewer inflammatory cells at the portal triads when compared to the surrounding cirrhotic lesions. No nuclear or cellular atypia was observed. Proliferating cell nuclear antigen labeling index was higher in the surrounding cirrhotic lesions than the hilar nodules. The nodule-like lesions at porta hepatis also showed similar light microscopic and immunohistochemical features as the hilar nodules. These hilar nodules did not seem to contain any malignant potential. The benign histology with relatively well-preserved liver architecture and the preferential site of occurrence at porta hepatis where bile seemed to flow more smoothly, suggested possible residues of less-affected hepatic tissues.

Epithelioid leiomyosarcoma in a non-immunocompromised infant: additional differential diagnosis of pediatric "round cell tumors".

We report an 18-month-old Japanese girl with purely epithelioid leiomyosarcoma presenting as a huge intraabdominal mass. The patient had been well from birth and had shown no signs of immunodeficiency. She was negative for human immunodeficiency virus. Blood examination revealed elevated serum neuron specific enolase (NSE). Histologically, the tumor was comprised of solid growths of round or polygonal cells with vesicular nuclei and often vacuolated cytoplasm rich in glycogen. The tumor cells were positive for vimentin, NSE, and MIC2, and were negative for desmin and neurofilament. The age, clinical presentation, and histologic findings mostly favored Ewing's sarcoma/primitive neuroectodermal tumor. Silver stain, however, demonstrated well-developed reticulin fibers often outlining individual tumor cells. An expanded panel of immunostains showed that the tumor cells were intensely positive for smooth muscle actin, and ultrastructural study revealed abundant fine cytoplasmic filaments with focal subsarcolemmal densities, various amounts of glycogen, and irregularly arranged, thick basal lamina. The diagnosis of epithelioid leiomyosarcoma was made. Following reduction in tumor size by chemotherapy, the serum NSE level was normalized. From the surgical finding, the primary site was presumed to be the urachus or the urinary bladder dome. Although extremely rare, epithelioid leiomyosarcoma should be added in the list of differential diagnoses of pediatric "round cell tumors."

HMB-45/melan-A and smooth muscle actin-positive clear-cell epithelioid tumor arising in the ligamentum teres hepatis: additional example of clear cell 'sugar' tumors.

HMB-45-positive clear-cell epithelioid tumor arising in the ligamentum teres hepatis of a 13-year-old Japanese girl is described. The well-defined tumor was completely removed and measured 9 x 7 x 6 cm. Cut sections showed a tan-white, homogeneous appearances with no hemorrhage or necrosis. The tumor was composed of nests or sheets of polygonal or oval-shaped cells rich in clear or finely granular cytoplasm. Capillary network was well developed, and sinusoid vessels were often seen with occasional perivascular hyalinization. There was moderate nuclear atypia but mitotic figures were absent. Periodic acid-Schiff stain showed a large amount of glycogen digested by diastase. Immunohistochemical stains for smooth muscle actin, Melan-A, and HMB-45 were positive in most of the tumor cells. Stains for vimentin, muscle actin, and HAM56 were focally positive, whereas stains for desmin, cytokeratin, epithelial membrane antigen, S-100, CD34, CD68, CD99, neurofilament proteins, and estrogen/progesterone receptors were negative. Ultrastructurally, the cytoplasm contained a considerable number of mitochondria, monoparticipate or membrane-bound glycogen, and longitudinally oriented thin filaments with focal condensations and subplasmalemmal densities. The histopathology of the present case, originally interpreted as epithelioid leiomyoma, was consistent with clear cell "sugar" tumors. The present case may indicate ubiquitous distribution of clear cell "sugar tumors" of which histogenesis remains unknown but is presumed to be of perivascular epithelioid cell origin.

Mesenchymal dysplasia of the placenta.

A severe case of placental mesenchymal dysplasia occurred in association with intrauterine fetal death (IUFD). The gravida-1, para-1 mother was a 26-year-old Japanese. The first pregnancy was unremarkable and a healthy female infant was delivered. The present pregnancy had been uneventful until 34 weeks of gestation when IUFD was detected. The 1516-g (mean +/- SD, 2050 +/- 387 g) stillborn infant had no external abnormalities and the karyotype was 46,XX. The placenta was markedly enlarged (1050 g; mean +/- SD, 452 +/- 202 g), and approximately 80% was occupied by extraordinary enlarged villous structures with a myxoid appearance. Histologically, the dysplastic villi had myxoid stroma and a decreased number of, occasionally obliterated, fetal vessels. There was no abnormal trophoblastic proliferation. Large-sized fetal vessels in the chorionic plate frequently contained organized thrombi. This is the first case of placental mesenchymal dysplasia, which possibly lead to the IUFD.

Natural course of neuroblastoma detected by mass screening: s 5-year prospective study at a single institution.

PURPOSE: To describe various favorable courses of neuroblastoma (NBL) detected by mass screening and to present our observation program as a temporary treatment option, to be used until a final decision is made regarding the mass screening program for 6-month-old infants. PATIENTS AND METHODS: Between October 1993 and November 1999, 26 of 51 patients with NBL detected by mass screening were enrolled in our observation program. The criteria for observation included urinary vanillylmandelic acid (VMA) and homovanillic acid (HVA) levels less than 50 microg/mg creatinine, smaller tumor size (< 5.0 cm), preoperative status, and granted informed consent. Patients were divided into four groups according to changes in urinary VMA and HVA values and tumor size. Patients who no longer fulfilled criteria underwent surgery. RESULTS: The observation period ranged from 4 to 73 months. Urinary VMA and HVA levels decreased in 19 of 26 patients, often by age 16 months. Eighteen patients had regressing tumors, and in 10 of these cases, the tumor was undetectable or barely detectable by imaging techniques. Four patients younger than 12 months had increased tumor marker levels and tumor volume, histologically reflecting neuroblastic proliferation. The remaining three patients, all older than 18 months, had varied tumor marker levels but increased tumor volume, histologically reflecting an increase in Schwann cells. No upgrading of tumor stage or unfavorable biologic factor was noted in any patient. CONCLUSION: None of our patients showed evidence of transition from favorable to unfavorable prognosis, a finding that points to a reduction in the significance of screening as a public health measure. Until results of ongoing screening trials involving older patients have been evaluated, the observation program can be used as a temporary measure to avoid, with little risk, unnecessary surgical intervention.

Radiation-associated xanthomatous meningioma in a child.

Radiation-associated meningioma in a child is rare. We report a case of xanthomatous meningioma, a rare subtype even in the adult population, which occurred in a 10-year-old boy who had undergone irradiation therapy for ependymoma at the age of 2 years. Histological examination of the tumor revealed a mixture of meningothelial cells and abundant foamy xanthomatous cells, with no apparent atypical cellular features. Xanthomatous meningioma associated with therapeutic high-dose irradiation in a child has not yet been documented. Immunohistochemical studies and the clinical course are evaluated with a review of the literature.