Precursor B lymphoblastic leukemia 32 months after local therapy for a primary extramedullary myeloid cell tumor.

A primary extramedullary myeloid cell tumor (pEMT) of an inguinal lymph node was completely excised without subsequent anti-tumor therapy in a 6-year-old child. Clinical observation and monitoring of blood and bone marrow (BM) did not reveal any pathologic results before 32 months, when a precursor B lymphoblastic leukemia was diagnosed. Identical T-cell receptor gamma rearrangement in nodal pEMT and in precursor B lymphoblastic leukemia in BM indicates a clonal relationship of these two tumors.

Cytogenetic characterization of Ewing tumors with high-ploidy.

The formation of a high-ploidy is rare in Ewing tumor (ET) and is in contrast to some other childhood tumors such as neuroblastoma. In a series of 37 Ewing tumors analyzed by conventional cytogenetics, 4 of the 34 tumors with an abnormal clone (11.8%) demonstrated the presence of a high-ploidy clone, with a chromosome number that ranged from hypotriploid to pentaploid. All 4 contained a t(11;22)(q24;q12) and the karyotypes had further aberrations of the type that would be generally expected in ET. Numerical aberrations represented the majority of the karyotypic events identified and gain of chromosome 8 and loss of chromosomes 3, 10, 16, 19, and 22 occurred in at least 3 tumors. However, no single mechanism could be implicated to explain the karyotypic picture of the 4 cases. It is proposed that high-ploidy subgroups exist in ET and it would be potentially erroneous to group these and other cases together when determining their clinical implications.

Three-year recurrence-free survival in a patient with recurrent medulloblastoma after resection, high-dose chemotherapy, and intrathecal Yttrium-90-labeled DOTA0-D-Phe1-Tyr3-octreotide radiopeptide brachytherapy.

BACKGROUND: Most medulloblastomas express high levels of somatostatin type 2 receptors (sst2). DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC) specifically binds sst2 in the low nanomolar range. The cytotoxic effect is mediated by the chelated, beta-emitting, metallic radionuclide Yttrium 90 (90Y). The authors applied this innovative treatment option in a boy age 8 years who presented with a recurrent medulloblastoma of the cauda equina: a prognostically poor condition. Targeted radiotherapy was administered to treat minimal sst2-expressing tumor remnants, which persisted despite conventional and high-dose chemotherapy and intercurrent resection of the lesion. METHODS: A medulloblastoma arising from the floor of the fourth ventricle had been removed surgically; then, the patient was treated with standard adjuvant chemotherapy and craniospinal irradiation according to the prospective HIT '91 protocol. Complete remission was achieved for 20 months, when a drop metastasis of the cauda equina manifested with sensorimotor lumbosacral deficits and urinary incontinence. After four cycles of neoadjuvant chemotherapy (which consisted of combined ifosfamide, carboplatinum and etoposide), two cycles of high-dose chemotherapy and autologous stem cell transplantation were performed; in between, the responding residual tumor within the lumbosacral nerve fibers was microscopically removed. Thereafter, an Indium-111-DOTATOC test injection indicated sst2-expressing tumor remnants within the cauda equina. Consequently, 4 cycles of [90Y]-DOTATOC (4x562.5 megabecquerels) were injected directly into the cerebrospinal fluid in monthly intervals. RESULTS: The consolidating intrathecal brachytherapy using [90Y]-DOTATOC was tolerated well. A complete remission was achieved for a 3-year period. The only remaining deficit was urinary incontinence. CONCLUSIONS: Intrathecal administration of targeted radiopeptide brachytherapy in combination with conventional and high-dose chemotherapy and surgical removal represents a promising new option to treat recurrent medulloblastoma and should be explored further.

Fibrolamellar hepatocellular carcinoma occurring 5 years after hepatocellular adenoma in a 14-year-old girl: a case report with comparative genomic hybridization analysis.

An unusual case of fibrolamellar carcinoma of the liver developed 5 years after removal of a hepatocellular adenoma in a 14-year-old girl belonging to a family with Carney syndrome. Both tumors were studied by light and electron microscopy, flow cytometry, and comparative genomic hybridization. The first tumor, removed at the age of 9, was a bulky well-circumscribed liver mass composed of large eosinophilic cells with a focal pseudoglandular pattern but without cytologic atypia or sclerosis. A diagnosis of hepatocellular adenoma was rendered. Five years later, another hepatic tumor was removed from the right lobe. Microscopic examination revealed polygonal cells, each with a large amount of eosinophilic cytoplasm and a round nucleus with a conspicuous nucleolus. These cells were arranged in nests and strands and separated by bands of dense fibrous tissue, leading to a diagnosis of fibrolamellar carcinoma. Comparative genomic hybridization analysis revealed no genetic alteration in the adenoma; however, several chromosomal aberrations (loss of chromosome regions 1p and 4p and gains of chromosome regions 6q, 13q, and Xq) were detected in the fibrolamellar carcinoma. To our knowledge, this is the first report of an association between hepatocellular adenoma and fibrolamellar carcinoma.

Therapeutic strategies and management of desmoplastic infantile ganglioglioma: two case reports and literature overview.

INTRODUCTION: Desmoplastic infantile gangliogliomas (DIG) are rare cerebral glioneural tumors usually occurring in early childhood. DIGs are generally benign although rare cases with poor outcome are known. Total resection, if possible, is the treatment of choice, without further adjuvant therapy. After incomplete resection, adjuvant chemo-and/or radiotherapy is generally applied, despite the potential negative side effects in such young patients. CASE REPORTS: We describe two girls with DIG, one who twice underwent subtotal resection at 3 and 5 months, the other who underwent total resection at 2 years. Neither had adjuvant therapy and there was no tumor recurrence. CONCLUSIONS: Our own experience and a review of the literature suggest that in most DIGs adjuvant therapy is not justified even after incomplete resection. After tumor recurrence a second surgical intervention should be considered instead of adjuvant therapy. An exception may be made for rare, deep-seated DIGs, which are more aggressive and have a poorer outcome.

Multiple endocrine neoplasias type 2A and thyroid medullary carcinoma: an interdisciplinary challenge.

The diagnosis and treatment of multiple endocrine neoplasias type 2A (MEN 2A) requires interdisciplinary management. The association of RET proto-oncogene mutations and medullary thyroid carcinoma (MTC) in children is well-known, but the optimal timing for elective surgery is controversial. Besides the risk of MTC, associated anomalies like hyperparathyroidism have to be considered. We report the results of molecular genetic investigations, the pentagastrin stimulation test, pre- and postoperative staging, and histologic examinations of four children who had a positive family history for MEN 2A. Histologic specimens of the removed thyroid glands showed MTC in all four cases. The patients had an uneventful postoperative clinical course. In view of the recent literature and our patients' results, we suggest a concept for diagnostic strategy and timing of the elective thyroidectomy.

Co-occurrence of neuroblastoma and nephroblastoma in an infant with Fanconi's anemia.

We report the clinical, histologic, and genetic findings of concurrent neuroblastoma and nephroblastoma in an infant with Fanconi's anemia (FA). Both tumors had characteristic chromosomal aberrations. In particular, the neuroblastoma showed a gain of chromosome 17q, considered an important factor for prognosis. But untypical genetic changes were also seen suggesting that FA as a chromosomal instability syndrome causes new and untypical chromosomal variations in different tumors. The present case is unique because the simultaneous occurrence of a neuroblastoma and nephroblastoma with FA has not yet been described.