Primary malignant neuroepithelial tumors of the kidney: a clinicopathologic analysis of 146 adult and pediatric cases from the National Wilms' Tumor Study Group Pathology Center.

Primary malignant neuroepithelial tumors of the kidney (NETKs) comprise a group of primitive, highly malignant neoplasms that histologically and clinically are not well characterized. A large cohort of 146 of these tumors, occurring in adults and children, has been collected at a single depository site, the National Wilms' Tumor Study Group (NWTSG) Pathology Center. The authors undertook a systematic retrospective review of the histologic, ultrastructural, and clinical features of these tumors, based on materials collected by the NWTSG and the consultation files of one of the authors (J.B.B.). Histologic features were generally those of primitive neural tumors with varying amounts of rosettes and neuropil; however, a large proportion of cases displayed unusual features such as spindle cells, ganglion cells, clear cell sarcoma-like foci, rhabdoid cells, epithelioid cells, and organoid foci. CD99 staining had been performed on 69 cases and showed membranous staining in 65. The NETKs were present in patients with a wide age spectrum, ranging from 1 month to 72 years (median, 18 years). EWS/FLI1 fusion analysis using reverse transcriptase-polymerase chain reaction and immunohistochemical stains for cytokeratin, chromogranin, and epithelial membrane antigen were performed successfully on a subset of 45 cases with available paraffin blocks. Only 13 of the 45 were fusion-positive, and there was no correlation between fusion status and histology, presence of rosettes, ultrastructural features, or cytokeratin positivity. CD99-negative cases were usually fusion-negative (six of seven cases), and all three chromogranin-positive cases were fusion-negative. Tumor staging, performed on 72 clearly defined and quantifiable cases by using NWTSG criteria, indicated that these are aggressive tumors, because only six were Stage 1, compared with 16 Stage 2, 31 Stage 3, and 19 Stage 4 lesions. The authors conclude that NETKs are a somewhat diverse group of generally aggressive, high-grade lesions that may present in a wide age range and are difficult to characterize without immunohistochemistry and cytogenetics/molecular biology.

Telomeric associations in the progression of chromosome aberrations in pediatric solid tumors.

Telomeric association (tas) is a cytogenetic phenomenon in which chromosome ends fuse to form dicentric, multicentric, and ring chromosomes. We observed clonal tas in six pediatric solid tumors of various types and histological grades studied using short-term in situ culture and G-banding techniques. These tumors included a neurilemoma, an undifferentiated (embryonal) sarcoma of the liver (UESL), two anaplastic astrocytomas (AA), one case of glioblastoma multiforme (GBM), and a neuroblastoma (NB) of the kidney. Cytogenetic data from all six tumors demonstrated multiple numerical and structural aberrations including tas. The tas appeared to be a secondary aberration in these tumors, however, it was possible to follow the progression of the telomeric chromosome aberrations in several cases. In all but one case (UESL) the loss of chromosome segments occurred. Tas of 11p was observed in three of the six tumors, two of which showed the subsequent loss of 11p (AA and AB). In addition, tas of 4p was seen in three tumors, two of which showed clonal tas of 4p with 22q. Tas of 10p, 21p, and 22q were all observed in at least two different tumors. The clonal telomeric fusions of 4p with 22q, recurring tas of 11p, and the subsequent loss of the short arm of 11 demonstrated here, suggests that some chromosome regions are subject to nonrandom instability and sometimes loss.

A novel reciprocal translocation (14;15)(q11;q24) in a congenital mesoblastic nephroma.

We describe a novel reciprocal translocation, t(14;15)(q11;q24), as the sole cytogenetic aberration in a congenital mesoblastic nephroma. The tumor was predominantly of "classic" morphology, but with small cellular islands of larger cells indicating early transformation to the cellular type. This is the first report of a reciprocal translocation as the sole anomaly in a congenital mesoblastic nephroma.

Karyotype evolution in a patient with Down syndrome and acute leukemia following a congenital leukemoid reaction.

We report the serial cytogenetic study of a patient with Down syndrome who experienced a congenital leukemoid reaction, underwent a spontaneous remission within four months, and subsequently developed acute myeloid leukemia at 16 months. A blood chromosome study to rule out Down syndrome performed at age 24 days, during the leukemoid reaction, revealed a 47,XX,+21 karyotype. The diagnosis of acute leukemia was made at 16 months, at which time a chromosome study, on bone marrow, was performed. This analysis revealed a clonal karyotype of 47,XX,+21,-22,+der(22)t(1;22)(q21;q13) in all but one cell studied. The single apparently nonclonal cell showed a karyotype of 49,XX,+12,-13,-19,+der(19)t(19;?)(q11;?)x2,+21,+22. A third chromosome study at 19 months indicated the original leukemic clone with t(1;22) (q21;q13) had been replaced by the clone represented by the single cell with 49 chromosomes seen in the previous chromosome study. This case of an infant with Down syndrome and acute leukemia illustrated rapid evolution and a transitory nature to clonal chromosome aberrations while retaining AML morphology and course.

Atypical mycobacterial vertebral osteomyelitis in a steroid-dependent adolescent. A case report.

Atypical mycobacterial infections are uncommon, particularly in the spine. The authors present the case of a patient with vertebral osteomyelitis secondary to Mycobacterium chelonae subspecies abscessus that was successfully treated with surgical debridement and stabilization, followed by chemotherapy.

Translocation (7;7)(p13;q21) in a Wilms' tumor.

Reports of single chromosome aberrations in Wilms' tumors are rare, with most tumors being characterized by multiple complex karyotype aberrations. An 11-month-old female patient with Wilms' tumor and a derivative chromosome 7 resulting from t(7;7)(p13;q21) as the sole cytogenetic aberration is described.

Dermoid in the filum terminale of a newborn with myelomeningocele.

Delayed occurrence of dermoid and epidermoid tumors after myelomeningocele closure has been reported in 16% of patients. Inclusion of cutaneous remnants at the time of surgical closure of the myelomeningocele has been accepted as the most common cause for the development of these intraspinal lesions. The finding of dermal elements (congenital dermoid) within the filum terminale of a newborn with myelomeningocele offers evidence of another mechanism for the delayed occurrence of these tumors in patients with myelomeningocele.

Cytogenetic findings in a case of pediatric glioblastoma.

We report a patient with glioblastoma multiforme (GBM) which showed stable and unstable telomeric associations involving the short arms of chromosomes 4 and 7. The karyotype was hyperdiploid, with chromosome numbers ranging from 84 to 87 in all cells, and showed a single stemline with variations in the number of marker chromosomes, teleomeric associations, and double minutes (dmin). The karyotype designation is 83-86,XX,-X,rea(X),-4,tas(4;7)(p16;?p22),der(6)t(6;?)(p21;?), -8, -9, der(9)t(9;?)(?p11;?), dup(9)(p12p23), -10 x 2, del(10)(p11), -11,del(11)(p11), -12, der(12)t(12;?) (p13;?),-13, -14 x 2,der(14)t(14;?) (p11;?), -16 x 2, -19, -21 x 2, -22 x 2, + 9-13mar, + dmin. Loss of the short arm of chromosome 10, structural aberrations of the short arm of chromosome 9, and dmin are consistent findings in GBM, whereas the high chromosome number is less common. Chromosome instability associated with the phenomenon of telomeric association/fusion has not been reported in GBM.

Telomeric associations evolving to ring chromosomes in a recurrent pleomorphic xanthoastrocytoma.

Telomeric associations observed in a recurrent untreated pleomorphic xanthoastrocytoma were apparently the primary cytogenetic events that evolved by fusion and breakage events, resulting in subclones with ring chromosomes. The telomeric fusions between chromosomes 15pter and 20qter, and between an extra copy of the long arm of chromosome 1 and chromosome 22qter, evolved in a stepwise fashion to ring chromosomes 20 and 22. The findings in this tumor demonstrate that telomeric association is one mechanism that can initiate chromosome instability by generating subclones with unstable chromosome intermediates and result in ring chromosomes and subsequent chromosome loss.

Molecular cytogenetic analysis of a medulloblastoma with isochromosome 17 and double minutes.

Cytogenetic analysis of a medulloblastoma revealed two abnormal cell lines of 48,XY, +8, +8, -14, +der(14)t(1;14)(q11;p11),i(17q) and 51,XY, +5, +6, +8, +8, -14 + 20, +der (14)t(1;14)(q11;p11),i(17q), + dmin. The finding of double minute chromosomes in some medulloblastomas has been associated with amplification of the c-myc or N-myc oncogenes. We were unable to detect gene amplification with these probes by Southern blot analysis.

Bilateral iris tumors in an immunosuppressed child.

A seven-year-old iatrogenically immunosuppressed girl developed simultaneous bilateral iris tumors associated with granulomatous iridocyclitis, splenomegaly, and an immunoblastic pleocytosis. Serologic studies suggested a current active Epstein-Barr virus infection. Tumor biopsy showed a polyclonal plasmacytoid lymphoproliferative process, establishing the diagnosis of posttransplant lymphoproliferative disorder. Low-dose local irradiation produced rapid and complete iris tumor regression with restoration of vision in both eyes. To our knowledge, this is the first report of ocular involvement in posttransplant lymphoproliferative disorder.

Cytogenetic findings in a pleomorphic xanthoastrocytoma.

We report a pleomorphic xanthoastrocytoma with an abnormal clonal cell line of 48,XY, +3, +5, -20, -22, +der(7)t(7;?)(p22;?), +der(20)t(15;20)(q11;q13).

Evolution of tumor chromosome abnormalities after therapy in a pediatric astrocytoma.

Chromosome studies originally performed on a patient with an untreated pontine astrocytoma showed a trisomy for 1q as the sole chromosome aberration. After the patient received radiation and chemotherapy, subsequent study indicated the presence of the original trisomy for 1q, as well as trisomy for chromosomes 2, 3q, and 17, in a tumor that now, histologically, is glioblastoma multiforme. In addition to the numerical aberrations, chromosome rearrangements were observed, involving translocation breakpoints that have been reported as "hot spots" associated with the clastogenetic effect of ionizing radiation.

Case report 667. Fibrolipomatous hamartoma of the median nerve.

Fibrolipomatous hamartoma of a nerve represents an uncommon soft-tissue tumor which typically involves the median nerve distribution near the wrist. Macrodactyly may or may not be present. The application of MRI using routine T1- and T2-weighted spin echo imaging sequences reveals serpiginous structures with low signal intensity. These structures probably represent the neural elements and associated perineural fibrosis. Further experience may allow for an accurate preoperative diagnosis of this tumor.

Trisomy for chromosome 1q in a pontine astrocytoma.

Reports of single chromosome abnormalities in pediatric brain tumors are rare. We report a 6-year-old patient with a malignant astrocytoma who had trisomy for the long arm of chromosome 1 as the sole chromosome abnormality.

Bilateral choroidal neonatal neuroblastoma.

We treated a bilateral, well-differentiated neuroblastoma of the choroid in a patient who had congenital abdominal neuroblastoma. Although orbital metastasis of neuroblastoma is common, intraocular metastasis is not. In our patient, there was no amplification of the N-myc oncogene in the tumor of either eye. This is consistent with early-stage primary neuroblastoma. Histologically, the tumors were identical in each eye and well differentiated with Homer Wright rosettes; most neuroblastoma metastases have few rosettes and are composed of more undifferentiated, anaplastic cells. We believe that our patient had bilateral primary tumors and not metastatic tumors.

Partial peritoneal alimentation in an infant.

We provided partial peritoneal alimentation to a 1.69-kg 11-month-old premature infant who had no available central venous access, depleted peripheral venous access, and gastrointestinal dysfunction. A cuffed silastic catheter was surgically inserted into the suprahepatic space. An alimentation solution was continuously infused into the peritoneum for 28 days to supplement peripheral venous and nasogastric alimentation and contributed 42 +/- 15% of total calories daily. Weight gain was achieved, but complications included hypoglycemia, hypophosphatemia, intravascular dehydration, catheter site leakage, ascites, and hydrocele. At autopsy 11 months later, lipid accumulation was present in the upper peritoneum and the hilar regions of the lungs secondary to preexisting lymphatic obstruction. Partial peritoneal alimentation may be feasible when other access routes are inadequate, but lymphatic obstruction is a contraindication to the peritoneal administration of lipid emulsions.

Immunologic control of the ascites form of murine adenocarcinoma 755. III. Efficacy of serum therapy is controlled by a single genetic locus.

We have previously described a passive serum therapy system in which potent protection against challenge of syngeneic mice with large doses (10(4) X LD100) of AD755a tumor cells can be accomplished by administration of as little as 2 to 5 microliters/mouse of hyperimmune anti-tumor cell serum. The present results demonstrate that the efficacy of the serum protection effect is strain-dependent and is under the control of a single genetic locus, denoted ADP-1. Through a series of crosses between highly protected C57BL/6J and nonprotected BALB/cJ mice, the ADP-locus has been mapped to chromosome 2 [linkage group V], approximately 23 centimorgans toward te centromere from the locus controlling agouti coat color. Thus, the protection locus is not linked to either the H-2 region or to previously described loci regulating the replication and disease induction of type-C viruses closely related to the virus associated with the AD775a tumor. The possible functions of the ADP-1 locus are discussed and further aspects of this experimental model are described in the accompanying papers.

Immunologic control of the ascites form of murine adenocarcinoma 755. IV. Characterization of the protective antibody in hyperimmune serum.

The potent capacity of B6 anti-AD755a tumor cell serum to protect mice against challenge with large doses of the homologous tumor cells has been shown to reside in the IgG2a antibody subclass. Despite their inability to protect in vivo, other IgG subclass antibodies obtained from the anti-AD755a serum demonstrated serologic reactivities in vitro comparable to those obtained with the protective IgG2a fraction. The specificity of serum protection is linked to the oncornavirus associated with the AD755a tumor and the serum immunoprecipitates only virus structural proteins from the tumor cell surface. Removal of these antibodies by specific immunoadsorbent resins eliminated nearly all of the in vitro serologic reactivity of unfractionated serum and the IgG2a subclass, but it had absolutely no effect on their protective capacity in vivo. Further target cell-binding studies suggest that nonprotective antibodies in the anti-AD755a serum bind more efficiently to the target cell in vitro than the protective fraction and have raised the possibility that the latter antibodies may only have weak affinity for the target cell itself.