Metastatic malignant ectomesenchymoma initially presenting as a pelvic mass: report of a case and review of literature.

Pediatric soft tissue sarcomas account for approximately 10% of all pediatric malignancies. Malignant ectomesenchymoma is rare biphasic sarcomas consisting of both mesenchymal and neuroectodermal elements. Approximately 64 cases have been reported in the literature and are believed to arise from pluripotent embryologic migratory neural crest cells. We report a 4-year-old boy who initially presented with a pelvic mass and inguinal lymphadenopathy at 6 months of age. Inguinal lymph node biopsy revealed a distinct biphasic tumor with microscopic and immunophenotypic characteristics diagnostic for both alveolar rhabdomyosarcoma and poorly differentiated neuroblastoma. The patient received national protocol chemotherapy against rhabdomyosarcoma with good response and presented with a cerebellar mass 21 months later. The metastatic tumor revealed sheets of primitive tumor cells and diagnostic areas of rhabdomyosarcoma and neuroblastoma were identified only by immunohistochemistry. Cytogenetic analysis of metastatic tumor demonstrated complex karyotype with multiple chromosomal deletions and duplications. The patient received national protocol chemotherapy against neuroblastoma and adjuvant radiotherapy after surgical resection of the cerebellar tumor with good response. He is currently off from any treatment for 18 months with no evidence of tumor recurrence or metastasis.

Idiopathic infantile arterial calcification: a possible cause of refractory cardiopulmonary failure in infancy.

Idiopathic Infantile Arterial Calcification is a rare autosome recessive disease characterized by extensive calcification of medium and large arteries. Loss-of-function mutations in ectonucleotide pyrophosphatase/phosphodiesterase 1 gene have been described in more than 80% of the cases. Although the diagnosis is usually made at autopsy, it is possible to identify cases based on clinical presentation, radiology findings, and molecular studies. Appropriate treatment can be initiated and has been shown to successfully induce permanent remission. We report a 4-week-old neonate who initially presented with respiratory distress, heart failure, and Coxsackie B viremia suggestive of viral induced cardiomyopathy. His symptoms progressed to multiple organ failure and he eventually expired at four weeks of age. On autopsy, diffuse calcium deposition within the internal elastic lamina of medium and large arteries was identified, as well as narrowing of lumen due to myointimal proliferation. This case report will emphasize the importance of taking this rare curable disease into consideration in all cases of infants with cardiopulmonary failure.

t(4;19)(q35;q13.1): a recurrent change in primitive mesenchymal tumors?

We report an apparently balanced t(4;19)(q35;q13.1) as the sole cytogenetic change in a highly malignant extraskeletal sarcoma in a 12-year-old-boy. Tumor cells were negative for all immunocytochemical markers except vimentin and neuron-specific enolase. Electron microscopy indicated chondroblastic differentiation. The tumor was categorized as a malignant sarcoma with differentiation toward extraskeletal mesenchymal chondrosarcoma. Reports of a similar translocation in an embryonal rhabdomyosarcoma (RMS) and in a dedifferentiated sarcoma with both rhabdomyosarcomatous and osteosarcomatous elements suggest that this translocation can arise in a primitive mesenchymal stem cell that can differentiate along at least these three pathways.

Microdissection study of the myenteric plexus in acardia, ataxia-telangiectasia, cystic fibrosis, extrahepatic biliary atresia, pediatric AIDS and Werdnig-Hoffmann disease.

Microdissection-point count morphometric study of the myenteric (Auerbach) plexus or esophagus, small intestine, and colon was done for infants and children with acardia (2), ataxia-telangiectasia (5), cystic fibrosis of the pancreas (CFP) (25), extrahepatic biliary atresia (EBA) (17), pediatric AIDS (10), and Werdnig-Hoffmann disease (WHD) (8). Values for fractional area of neural tissue in the plane of the plexus were compared to those of control patients in same age range as those in each disease category by t-test. Statistically abnormal values included low values for small intestine and colon in Werdnig-Hoffmann disease, high values for small intestine and colon in biliary atresia, and high value for colon but a low value for small intestine in cystic fibrosis. Values for all three loci were within the normal range for ataxia telangiectasia and pediatric AIDS. The mechanisms of the low value for small and large intestines in WHD, which causes chronic constipation as a result of skeletal muscle weakness, and of the high values for colon in CFP and EBA, both causing malabsorption with bulky stools, are unclear. The value for small intestine in acardia was normal for term but lower than expected for fetal bowel of the same size, possibly because of reduced neural crest inflow to the fetal bowel.

Aggressive surgery combined with intensive chemotherapy improves survival in poor-risk neuroblastoma.

One hundred eighteen children with metastatic (Childrens Cancer Study Group [CCSG] stage IV), extensive regional (stage III), or stage II neuroblastoma with N-myc amplification received an intensive chemotherapeutic regimen of cis-platinum, etoposide, doxorubicin, and cyclophosphamide combined with persistent aggressive attempts at complete primary tumor resection. Fourteen patients were unevaluable and 42 left the study to be placed on bone marrow transplant protocols. The remaining 62 children were evaluated in detail. Complete excision was eventually accomplished in 39 patients (63%), 23 of whom are disease-free survivors after 8 to 47 months (median, 20 months). Twenty-three patients underwent partial excision or biopsy of their lesion and only 6 are alive without evidence of disease (P = .0011). Timing of surgery or site of tumor did not influence surgical outcome. N-myc oncogene expression could not predict which lesions would be completely resectable. Surgical complications occurred 21% of the time but the impact on the clinical course and chemotherapy administration was minimal. The ipsilateral kidney was removed with the tumor in 18 cases, 14 of which were during complete resection. Twelve of these children are disease-free survivors. With new intensive chemotherapy capable of eliciting an effective response from primary and metastatic neuroblastoma, aggressive surgical approaches for complete tumor resection are warranted and can be expected to improve patient outcome.

Prognostic value of immunocytologic detection of bone marrow metastases in neuroblastoma.

BACKGROUND: Morphologic evaluation of bone marrow for neuroblastoma cells is a routine and important component of clinical staging. Specific immunostaining of malignant cells with monoclonal antibodies should be more sensitive, however, and may improve the detection of metastases and provide additional prognostic information. METHODS: We looked for tumor cells in bone marrow from 197 patients with newly diagnosed neuroblastoma, using immunoperoxidase staining with monoclonal antibodies (immunocytologic analysis) and examination of smears and specimens obtained by trephine biopsy (conventional analysis). RESULTS: Routine smears and trephine-biopsy specimens were positive for tumor cells in 46 percent of the patients, whereas 67 percent were positive on immunocytologic analysis (P less than 0.0001). Immunocytologic analysis detected bone marrow metastases in 34 percent of patients considered to have only localized or regional disease (Stage I, II, or III). It also identified tumor cells that were not detected by conventional analysis in patients with widespread disease (Stage IV or IVS). Tumor content, as determined by immunocytologic analysis, predicted clinical outcome in relation to the age of the patient at diagnosis. Patients with Stage II or III disease diagnosed after one year of age who did not have occult marrow metastases did well, whereas those with metastases did poorly (P = 0.006). Patients in whom Stage IV disease was diagnosed before they were one year of age did well if bone marrow metastases were few or absent, but had poor survival if the marrow contained more than 0.02 percent tumor cells (P = 0.03). CONCLUSIONS: Immunocytologic analysis of bone marrow aspirates is more sensitive than conventional analysis in detecting tumor cells and provides prognostic information. The relations among marrow metastases, age at diagnosis, and clinical outcome illustrate the biologic heterogeneity of neuroblastoma.

Mixed carcinoma in situ: an immunohistochemical study.

A case of mixed carcinoma in situ, of the skin, is presented. The lesion, located on the right temple of a 71-year-old man, showed histologic features of Bowen's disease and extramammary Paget's disease. This case suggests that Bowen's disease and extramammary Paget's disease may arise from pluripotential adnexal epithelium capable of keratinocytic and glandular differentiation. Utilization of the peroxidase-antiperoxidase technique for demonstrating carcino-embryonic antigen was performed in order to identify the component interpreted as extramammary Paget's disease. This procedure is apparently more sensitive than the commonly employed histochemical stains for demonstrating glandular differentiation.

Renal varicosities with gross hematuria and negative arteriography. Experience with sclerosing agent in 1 patient.

For a patient with hematuria, negative excretory urography, cystoscopy, and renal arteriography, renal venography should be obtained to search for venous malformations. We present a case in which hematuria was temporarily relieved by infusion of a sclerosing agent into a renal varicose plexus.

Primary herpes simplex pneumonia in a neonate.

A 6-day-old male infant was treated for rapidly progressive pneumonia. The infection was not responsive to antibiotic and symptomatic treatment, and the infant died within 48 hours of admission. Herpes simplex type II grew from premortem respiratory and postmortem lung cultures, and immunoperoxidase staining confirmed the presence of this organism in lung tissue. Pathologic findings were limited to the lungs. A maternal origin for the virus was suspected but could not be proved. We believe this patient represents the first reported case of isolated herpes simplex type II pneumonia in a neonate.

The constellation of adult acid maltase deficiency: clinical, electrophysiologic, and morphologic features.

This report outlines the clinical, electrophysiologic, and morphologic findings in seven patients with adult acid maltase deficiency. The diagnosis was confirmed biochemically in four of these individuals. Adult acid maltase deficiency must be considered whenever clinical diagnoses of polymyositis, especially the chronic form, and limb-girdle muscular dystrophy are being entertained.

Ultrastructural studies on neuroblastoma: evaluation of cytodifferentiation and correlation of morphology and biochemical and survival data.

Fifteen cases of neuroblastoma, ganglioneuroblastoma and ganglioneuroma were studied by electron microscopy. Ultrastructural features of cytodifferentiation, including numbers of dense core neurosecretory granules (NSG) and neuritic processes, were used to evaluate variation within the neuroblastoma group to determine whether differences in cytodifferentiation exist where light microscopic variations are not evident. These studies revealed that undifferentiated neuroblastomas do show ultrastructural variations not evident by light microscopy. The ultrastructural findings for each case were compared with initial urinary catecholamine excretory patterns, the latter having recently been shown to have valuable prognostic significance. There was a positive correlation, in the undifferentiated neuroblastomas, between increased numbers of NSG and prognostically favorable biochemical excretory patterns. Conversely, low numbers of NSG were associated with an unfavorable biochemical pattern and fatal clinical course. These correlations between ultrastructural differentiation and the biochemical secretory pattern indicate that ultrastructural evaluation of undifferentiated neuroblastomas would appear to have prognostic value, particularly in cases lacking initial biochemical data or as an adjunct to biochemical studies.