Lymphomatoid granulomatosis after childhood acute lymphoblastic leukemia: report of effective therapy.

Lymphomatoid granulomatosis, a rare condition in children, affects the lungs primarily but may have significant extrapulmonary manifestations, especially in the central nervous system. We report a case of lymphomatoid granulomatosis with onset after the completion of chemotherapy for childhood acute lymphoblastic leukemia. Two months after treatment ended, the 7-year-old girl developed splenomegaly, cervical adenopathy, and bilateral interstitial pulmonary infiltrates. She improved on cefotaxime but experienced a seizure 1 month later. A computed tomography scan of the head was normal, but her pulmonary infiltrates had become nodular. A computed tomography-guided biopsy of 1 of the nodules revealed cellular interstitial pneumonitis. One month later, she had persistent pulmonary infiltrates, marked splenomegaly, and new seizures. Magnetic resonance imaging of the head revealed cerebral nodules. Itraconazole was begun, and the pulmonary infiltrates resolved. Five months after her initial symptoms, she developed tonic pupil and a decreased level of consciousness. Dexamethasone was initiated. Needle biopsies of the brain were carried out, yielding the diagnosis of severe chronic inflammatory changes focally consistent with granuloma. The child redeveloped splenomegaly and fever, and then suffered an acute decompensation with hypoxemia, tachypnea, splenomegaly, and cardiac gallop. Open-lung biopsy revealed lymphomatoid granulomatosis. Lymphoma-directed therapy was initiated, and the patient had complete resolution of pulmonary and cerebral nodules 5 months later. No intrathecal chemotherapy was administered, and radiation therapy was not necessary. Neuropsychological testing obtained after completion of therapy revealed an improvement in attention, coordination, and fine motor speed over time. She is now in good health and attending school.

Perfluorocarbon priming and surfactant: physiologic and pathologic effects.

OBJECTIVE: To test the hypothesis that perfluorocarbon (PFC) priming before surfactant administration improves gas exchange and lung compliance, and also decreases lung injury, more than surfactant alone. DESIGN: Prospective, randomized animal study. SETTING: Animal research laboratory of Children's Hospital of St. Paul. SUBJECTS: Thirty-two newborn piglets, weighing 1.55 +/- 0.18 kg. INTERVENTIONS: We studied four groups of eight animals randomized after anesthesia, paralysis, tracheostomy, and establishment of lung injury using saline washout to receive one of the following treatments: a) surfactant alone (n = 8); b) priming with the PFC perflubron alone (n = 8); c) priming with perflubron followed by surfactant (n = 8); and d) no treatment (control; n = 8). Perflubron priming was achieved by instilling perflubron via the endotracheal tube in an amount estimated to represent the functional residual capacity, ventilating the animal for 30 mins, and then removing perflubron by suctioning. After all treatments were given, animals were mechanically ventilated for 4 hrs. MEASUREMENTS AND MAIN RESULTS: We evaluated oxygenation, airway pressures, respiratory system compliance, and hemodynamics at baseline, after induction of lung injury, and at 30-min intervals for 4 hrs. Histopathologic evaluation was carried out using a semiquantitative scoring system and by computer-assisted morphometric analysis. After all treatments, animals had decreased oxygenation indices (p < .001) and increased respiratory system compliance (p < .05). Animals in PFC groups had similar physiologic responses to treatments as animals treated with surfactant only; both the PFC-treated groups and the surfactant-treated animals required lower mean airway pressures throughout the experiment (p < .001) and had higher pH levels at 90 and 120 mins (p < .05) compared with the control group. Pathologic analysis demonstrated decreased lung injury in surfactant-treated animals compared with animals treated with PFC or the controls (p < .02). CONCLUSIONS: Priming the lung with PFC neither improved the physiologic effects of exogenous surfactant nor improved lung pathology in this animal model.

Exogenous surfactant and partial liquid ventilation: physiologic and pathologic effects.

We compared the effects of surfactant and partial liquid ventilation (PLV), and the impact of administration order, on oxygenation, respiratory system compliance (Crs), hemodynamics, and lung pathology in an animal lung injury model. We studied four groups: surfactant alone (S; n = 8); partial liquid ventilation alone (PLV-only; n = 8); surfactant followed by partial liquid ventilation (S-PLV; n = 8); and partial liquid ventilation-followed by surfactant (PLV-S; n = 8). Following treatments, all animals had improved oxygenation index (OI) and Crs. Animals in PLV groups showed continued improvement over 2 h (% change OI: PLV-S -83% versus S -47%, p < 0.05; % change Crs: S-PLV 73% versus S 13%, p < 0.05). We also saw administration-order effects: surfactant before PLV improved Crs (0.92 ml/cm H2O after surfactant versus 1.13 ml/cm H2O after PLV, p < 0.02) without changing OI, whereas surfactant after PLV did not change Crs and OI increased (5.01 after PLV versus 8.92 after surfactant, p < 0.03). Hemodynamics were not different between groups. Pathologic analysis demonstrated decreased lung injury in dependent lobes of all PLV-treated animals, and in all lobes of S-PLV animals, when compared with the lobes of the S animals (p < 0.05). We conclude that surfactant therapy in combination with PLV improved oxygenation, respiratory system mechanics, and lung pathology to a greater degree than surfactant therapy alone. Administration order affected initial physiologic response and ultimate pathology: surfactant given before PLV produced the greatest improvements in pathologic outcomes.

Prolonged partial liquid ventilation using conventional and high-frequency ventilatory techniques: gas exchange and lung pathology in an animal model of respiratory distress syndrome.

OBJECTIVE: To evaluate the effect of prolonged partial liquid ventilation with perflubron (partial liquid ventilation), using conventional and high-frequency ventilatory techniques, on gas exchange, hemodynamics, and lung pathology in an animal model of lung injury. DESIGN: Prospective, randomized, controlled study. SETTING: Animal laboratory of the Infant Pulmonary Research Center, Children's Health Care-St. Paul. SUBJECTS: Thirty-six newborn piglets. INTERVENTIONS: We studied newborn piglets with lung injury induced by saline lavage. Animals were randomized into one of five treatment groups: a) conventional gas ventilation (n = 8); b) partial liquid ventilation with conventional ventilation (n = 7); c) partial liquid ventilation with high-frequency jet ventilation (n = 7); d) partial liquid ventilation with high-frequency oscillation (n = 7); and e) partial liquid ventilation with high-frequency flow interruption (n = 7). After induction of lung injury, all partial liquid ventilation animals received intratracheal perflubron to approximate functional residual capacity. After 30 mins of stabilization, animals randomized to high-frequency ventilation were changed to their respective high-frequency modes. Hemodynamics and blood gases were measured before and after lung injury, after perflubron administration, and then every 4 hrs for 20 hrs. Histopathologic evaluation was carried out using semiquantitative scoring and computer-assisted morphometric analysis on pulmonary tissue from animals surviving at least 16 hrs. MEASUREMENTS AND MAIN RESULTS: All animals developed acidosis and hypoxemia after lung injury. Oxygenation significantly (p < .001) improved after perflubron administration in all partial liquid ventilation groups. After 4 hrs, oxygenation was similar in all ventilator groups. The partial liquid ventilation-jet ventilation group had the highest pH; intergroup differences were seen at 16 and 20 hrs (p < .05). The partial liquid ventilation-oscillation group required higher mean airway pressure; intergroup differences were significant at 4 and 8 hrs (p < .05). Aortic pressures, central venous pressures, and heart rates were not different at any time point. Survival rate was significantly lower in the partial liquid ventilation-flow interruption group (p < .05). All partial liquid ventilation-treated animals had less lung injury compared with gas-ventilated animals by both histologic and morphometric analysis (p < .05). The lower lobes of all partial liquid ventilation-treated animals demonstrated less damage than the upper lobes, although scores reached significance (p < .05) only in the partial liquid ventilation-conventional ventilation animals. CONCLUSIONS: In this animal model, partial liquid ventilation using conventional or high-frequency ventilation provided rapid and sustained improvements in oxygenation without adverse hemodynamic consequences. Animals treated with partial liquid ventilation-flow interruption had a significantly decreased survival rate vs. animals treated with the other studied techniques. Histopathologic and morphometric analysis showed significantly less injury in the lower lobes of lungs from animals treated with partial liquid ventilation. High-frequency ventilation techniques did not further improve pathologic outcome.

Cystic renal lymphangiectasia: a distinctive clinicopathologic entity in the pediatric age group.

This report describes the features of unilateral cystic renal lymphangiectasia in a 2-year-old child who presented with hypertension, massive ascites, a left flank mass, and no evidence of familial renal cystic disease. The child became normotensive and is now asymptomatic more than 3 years after surgery. The clinical presentation and diffuse pathologic involvement are similar to findings for the few pediatric patients with cystic lymphangiectasia described in the literature and appear distinct from the more localized form of the disease seen in adults.

Primary mediastinal hemangiopericytoma with fatal outcome in a child.

Hemangiopericytoma occurs infrequently in children, and mediastinal sites are exceedingly rare. We report a case of mediastinal hemangiopericytoma in a 4-year-old child, which resulted in the patient's death due to large size, anatomic location, and associated perioperative bleeding. The pathologic diagnosis was established on the basis of light microscopic, immunohistochemical, and electron microscopic features. The presentation and clinical course of this case contrast with those of congenital or infantile hemangiopericytoma, which generally has a favorable outcome. Hemangiopericytoma should be considered in the differential diagnosis of large mediastinal masses in children.

Follicular large cell lymphoma of the testis in a child.

BACKGROUND: A unique case of primary testicular lymphoma in a child is reported. METHODS: Tumor tissue was studied using immunohistochemical techniques and southern blot hybridization to detect immunoglobulin and bcl-2 gene rearrangement and in situ hybridization for the Epstein-Barr virus (EBV) genome. RESULTS: Light microscopy revealed a lymphocytic infiltrate with a follicular pattern. Immunohistochemical staining revealed lambda light chain restriction and gene rearrangement studies revealed a clonal rearrangement of the immunoglobulin heavy chain, confirming a clonal neoplastic process. Immunostaining failed to detect bcl-2 protein expression, and no evidence of bcl-2 gene rearrangement was noted on southern blot analysis. In situ hybridization for EBV nucleic acid in tumor tissue was negative. CONCLUSIONS: To the authors' knowledge, this is the first report of a case of a primary testicular lymphoma with follicular histology in a child. Despite the follicular histology, no evidence of bcl-2 expression or gene rearrangement was detected.

Inherited factor H deficiency and collagen type III glomerulopathy.

A non-immune complex-mediated glomerulonephritis associated with persistent hypocomplementemia occurred in a young boy. Measurement of complement components revealed complete factor H deficiency, inherited as an autosomal recessive trait. Evaluation of the renal lesion revealed extensive deposition of type III collagen suggestive of collagen type III glomerulopathy, a recently identified cause of chronic renal insufficiency in children and adults. This report represents the first association of inherited factor H deficiency with collagen type III glomerulopathy.

Fatal brain stem necrosis after standard posterior fossa radiation and aggressive chemotherapy for metastatic medulloblastoma.

A 3-year-old girl received conventional-dose external beam posterior fossa irradiation (5400 cGy in 30 fractions over 40 days) for good-risk medulloblastoma. Soon thereafter, she experienced an extraneural (occipital scar, cervical lymph nodes) and central nervous system (CNS) recurrence. Intensive cisplatin and cyclophosphamide chemotherapy led to rapid disappearance of the extraneural disease. Methotrexate was administered via a ventricular reservoir. After 2 months of chemotherapy, CNS toxicity progressed rapidly from ataxia to paraplegia to quadriplegia to central respiratory failure. Radiographic scans and autopsy material revealed brain stem necrosis. This unusual toxicity raises concern about the safety of aggressive systemic chemotherapy and intrathecal therapy, when given after conventional radiotherapy.

Transoral labiomandibular approach to basiocciput chordomas in childhood.

Many excellent reports have dealt with the various aspects of cranial chordoma. It remains a relatively rare neoplasm, particularly in younger children. The authors have had the opportunity to treat a 5-year-old child harboring a basiocciput chordoma. It extended from the mid-clivus to C3. A transoral labiomandibular approach was used, allowing its resection. No evidence of recurrence was noted 3 years later. A literature search confirmed the rarity of basiocciput chordoma in young children. The perioperative difficulties encountered prompted this report.

Spinal abnormalities in camptomelic dysplasia.

Significant spinal abnormalities were found in eight patients (average age of 6 years, 5 months) with camptomelic dysplasia. The late ossification of the midthoracic pedicles served as a clear diagnostic criterion for the syndrome. Scoliosis averaging 63 degrees was found in all seven nonquadriplegic cases. Thoracic hyperkyphosis averaging 126 degrees was seen in six (75%) of the patients, while cervical kyphosis averaging 66 degrees was noted in three (38%). Vertebral body hypoplasia appeared to be a major cause of deformity. This study clarifies that patients with camptomelic dysplasia are surviving longer than previously expected and therefore should have their spinal deformities treated aggressively.

Clear cell sarcoma of the kidney: report of a case with mandibular metastasis simulating a benign myxomatous tumor.

The clear cell sarcoma of the kidney (CCSK) is one of the histologically unfavorable types of childhood renal tumors that has a propensity for osseous metastasis. We have presented the clinical and pathologic findings of the first well-documented case of a CCSK with mandibular metastasis, which was recognized approximately 18 months after the original diagnosis. Microscopically, the mandibular lesion had the features of a benign myxomatous neoplasm with the exception of occasional atypical spindle cells. Electron microscopic observation confirmed the undifferentiated nature of the neoplastic cells. It was concluded that the intensive chemotherapy that was administered to our patient very likely affected the histologic appearance of the mandibular metastasis as well as other recurrent lesions in the abdomen. Our review of the literature revealed only five previous examples of Wilms' tumor that had metastasized to the mandible. At least one of these earlier cases also represented a CCSK.

Cutaneous busulfan effect in patients receiving bone-marrow transplantation.

Epidermal keratinocytes with abnormally large nuclei were found in 12 of 13 patients who received high-dose busulfan and cyclophosphamide prior to receiving bone-marrow transplantation for treatment of hematological malignancies. These cells were similar to those previously described in the lungs, cervix and bladder of patients on long-term busulfan therapy. Marked keratinocyte nuclear abnormalities were not observed in bone-marrow transplant recipients who received a preparatory regimen of cyclophosphamide and total-body irradiation. This histologic cutaneous busulfan effect was transient and was unrelated to the development of graft-versus-host reaction.