Ossicular fusion and cholesteatoma in auriculo-condylar syndrome: in vivo evidence of arrest of embryogenesis.

Auriculo-condylar syndrome (ACS) is a rare condition affecting first branchial arch structures. The types of hearing loss and temporal bone findings in ACS have not been reported. We describe a 14-year-old male with constricted pinnae, mandibular dysostosis, glossoptosis, a high-arched palate, hearing loss, and cholesteatoma. Computed tomography imaging demonstrated malleoincudal joint ankylosis. The fused malleoincudal complex was removed during mastoidectomy for cholesteatoma. Electron microscopy and histopathology of the joint suggested the fusion was congenital. This is the first report of ossicular fusion and cholesteatoma in ACS and the most detailed in vivo evidence of disruption of embryogenesis during malleoincudal joint formation.

Thymic mucosa-associated lymphoid tissue lymphoma in an adolescent girl.

Mucosa-associated lymphoid tissue (MALT) lymphoma is very rare in children. We report the first case of pediatric thymic MALT lymphoma in an adolescent Asian girl. She presented with chest pain, dyspnea, and low-grade fever. A large anterior mediastinal mass was biopsied that confirmed the diagnosis of MALT lymphoma with trisomy 18. The patient had secondary immunodeficiency with low NK cell count and high IgA and IgG levels. Because of the advanced stage and the presence of trisomy 18, she was treated with cyclophosphamide, vincristine, prednisone, and rituximab, followed by involved-field radiotherapy. She is currently undergoing maintenance therapy with rituximab and remains in complete remission at 13 months from diagnosis. Thymic MALT lymphoma should be suspected in any Asian child with a cystic thymic mass and autoimmune disease or hyperglobinemia. Because of the slow proliferation rate of this type of lymphoma, a long-term follow-up is needed.

Prospective evaluation of the prevalence and clinical significance of positive autoantibodies after pediatric liver transplantation.

BACKGROUND AND OBJECTIVES: De novo autoimmune hepatitis (AIH) recently was recognized as an important cause of late graft dysfunction after pediatric liver transplantation (LT). However, the significance of isolated elevation of autoantibodies in children after LT without history of prior autoimmune liver disease scarcely has been studied. The aim of the present study was to determine the prevalence and risk factors for autoantibodies production in pediatric LT recipients and to assess the impact of isolated elevation of autoantibodies over time on graft function. METHODS: Sixty-eight children without history of autoimmune disease were recruited over the course of 1 year into this cross-sectional study. A single blood specimen was drawn at study entry to determine titers of autoantibodies. Clinical and laboratory assessment and medical history were obtained at study entry as well. Patients were then divided into positive and negative autoantibodies groups, and prospectively followed for 18 months for evidence of abnormal liver function tests. RESULTS: One or more autoantibodies were detected in 18 (26%) patients. Anti-smooth muscle was the most common (n = 13) antibody. Time since transplant (>4 years) was the only risk factor identified for the presence of autoantibodies (univariate risk ratio, 3.3; 95% confidence interval, 1.2-9). During the follow-up period, 5 patients with positive autoantibody screen developed de novo AIH (n = 3) or chronic rejection (n = 2), compared with 0 in the negative autoantibody group. Children with positive autoantibody screen were at higher risk for development of de novo AIH or chronic rejection (univariate risk ratio 13.9; 95% confidence interval, 1.7-111; P = 0.004). CONCLUSIONS: Positive autoantibodies are common in children after LT and their presence may denote a higher risk for the development of de novo AIH or chronic rejection over time.

Primary subcutaneous primitive neuroectodermal tumor with aggressive behavior and an unusual karyotype: case report.

Primitive neuroectodermal tumor/Ewing sarcoma (PNET/ES) rarely occurs in the skin and subcutaneous tissues. We present a case of a 16-year-old girl with primary cutaneous and subcutaneous PNET/ES of the abdominal wall. Despite wide local excision and chemotherapy, she rapidly developed cranial bone and brain metastases, followed by lung and skeletal metastases, and died shortly thereafter. The recurrent tumor exhibited light microscopic features of a small, round, blue cell tumor with intracytoplasmic glycogen. Immunohistochemical analysis showed positivity for CD99, CD56, S100, and glial fibrillary acid protein, and ultrastructural features included cytoplasmic glycogen and focal complex interdigitating synaptic junction-like cytoplasmic folds. Cytogenetic analysis of the relapsed tumor showed a complex karyotype: 47,XX,i(1)(q10), der(4)t(4;19) (q33 approximately q35;q13.1), + 8,t(15;17)(q24;p11.2 approximately p12),der(19)t (19;20)(q13.1;p11.2),der(22)t(20;22)(q13;q13). Cytogenetic, interphase fluorescence in situ hybridization, and molecular genetic analyses failed to show t(11:22) (q24;q12) or abnormalities of chromosome region 22q12. The clinical behavior and atypical and complex cytogenetic abnormalities exhibited by the tumor in this patient are unusual and represent the most aggressive end of the clinical spectrum of cutaneous and subcutaneous PNET/ES.

Myxomatous lesions of the maxilla in children: a case series and review of management.

OBJECTIVE: A paucity of data exists in the literature regarding the pediatric bony myxoma. Controversy exists regarding both its histopathologic origins and surgical management. The purpose of this study was to report on our experience in managing these patients, including diagnostic work-up, histopathologic findings and an evaluation of surgical treatment outcomes. METHODS: A retrospective review was undertaken of all consecutive cases of pediatric bony myxoma treated between 1988 and 2001. Tumors were analyzed in terms of clinical data, imaging studies, histopathology and surgical treatment. A selective review of the literature regarding management of the bony myxoma is also presented. RESULTS: Five lesions were identified, all of which occurred in the maxillary bone. Histopathologically our cases did not show a strong association with odontogenic epithelium. All cases were treated by surgical resection with conservative margins. No recurrences were documented over a mean follow-up period of 8.5 years. CONCLUSION: The bony myxoma is a rare lesion in the pediatric population, and initial clinical or radiological misdiagnoses are not uncommon. The presupposed odontogenic origin of these tumors may need reassessment. Conservative resection with narrow margins is a safe and effective therapy for myxomas of the pediatric maxilla.

Gastrointestinal cancers and neurofibromatosis type 1 features in children with a germline homozygous MLH1 mutation.

Heterozygous germline DNA mismatch repair gene mutations are typically associated with hereditary nonpolyposis colorectal cancer. The molecular hallmark of this syndrome is high-frequency microsatellite instability in the tumors. Rare childhood cases with homozygous or compound heterozygous DNA mismatch repair gene mutations have a described predisposition to leukemia, lymphoma, and brain tumors but not to gastrointestinal cancer. We have now characterized a family in which 2 children with a homozygous germline DNA mismatch repair gene mutation developed early-onset gastrointestinal cancers. The 11-year-old proband had café-au-lait macules and developed metastatic duodenal adenocarcinoma that arose in a tubulovillous adenoma. His 9-year-old sister with café-au-lait macules and axillary freckling presented with malignant colon polyps. A 6-year-old sister with café-au-lait macules, hairy nevi, and a plexiform neurofibroma of the tongue has no malignancies to date. The family history did not fulfill the Amsterdam criteria for hereditary nonpolyposis colorectal cancer, but 2 relatives in their 60s had gastric cancer and colorectal cancer, whereas the parents, who are first cousins, remain cancer free. The proband's metastatic duodenal cancer and his sister's malignant colon polyps had high-frequency microsatellite instability but had detectable MLH1, MSH2, and MSH6 proteins by immunohistochemistry. Because some germline DNA mismatch repair gene deficiencies are associated with apparently intact immunohistochemical DNA mismatch repair gene expression in tumors, we proceeded to DNA sequencing, which showed that all 3 children had a germline homozygous MLH1 missense mutation (exon 18, codon 687, CGG-->TGG), whereas both parents were heterozygous for this mutation.

Nasopharyngeal teratocarcinosarcoma.

Congenital germ cell tumors are uncommon. The most common site of origin is in the saccrococygeal region. Teratomas arising from the head and neck comprise a small proportion of this entity, and of these, nasopharyngeal lesions are rare. Also known by various synonyms such as hamartoma and hairy polyp, the teratoma is a well-recognized, and generally benign, clinical and histopathological entity. We present a case of a nasopharyngeal teratocarcinosarcoma associated with a cleft palate and the congenital replacement or absence of the ipsilateral Eustachian tube.