Gino R. Somers

De Novo BRCA1 Mutation in a Patient with Breast Cancer and an Inherited BRCA2 Mutation

We thank P. van der Spek, J. Hoeijmakers, S. Venitt, M. Stratton, S. Easteal, R. Sinden and T. Kunkel for discussions; L. Trute for technical assistance; M. Gardner for genetic counseling of patients; and E. Edkins for heteroduplex analysis. This work was funded by the National Health and Medical Research Council of Australia and by the Victorian Health Promotion Foundation.

Multiple leiomyosarcomas of both donor and recipient origin arising in a heart-lung transplant patient

The occurrence of Epstein-Barr virus-associated smooth-muscle tumors in immunocompromised patients has been reported, particularly in the pediatric population. In posttransplantation tumors, the tissue of origin has been either donor or recipient. Mixed-genotype sarcomas within the same patient have not yet been reported. We describe the occurrence of multiple leiomyosarcomas of both donor (arising in the lung allograft) and recipient (arising in the host liver) origin in a 15-year-old boy 3 years after heart-lung transplantation. Analysis of premortem lung tumors demonstrated the presence of Epstein-Barr virus DNA. Despite decreasing immunosuppression and commencing acyclovir, the patient died of systemic Pseudomonas infection. Immunohistochemical analysis revealed that both lung and liver tumors were negative for the Epstein-Barr virus receptor (CD21), and suggests that Epstein-Barr virus entry into the cells was not via this receptor but via an alternate mechanism such as cell fusion.

Pediatric Undifferentiated Sarcoma of the Soft Tissues: A Clinicopathologic Study

Pediatric undifferentiated soft tissue sarcomas represent a major challenge for pathologists and clinicians. The goal of this study was to identify cases that warranted this diagnosis by current standards of analysis and then determine if there are clinicopathological commonalities that may be useful for diagnosis, management, and prognosis. Eighteen potential patients were identified using the institutional pathology database. Three cases were reclassified as specific sarcomas, and 2 cases had insufficient material for molecular analysis, leaving 13 cases for pathological review and 12 patients for radiological and clinical review. There were 7 males and 6 females. The median age at diagnosis was 11 years (1 month to 16 years). Tumors commonly involved the trunk (7 of 13; 54%) and ranged in size from 1.7 to 14.5 cm (mean, 6.7 cm). Eleven patients received ifosfamide/etoposide chemotherapy and 4 received irradiation. Five-year event-free and overall survival (EFS and OS) rates were 54% and 74%, respectively. The predominant histological pattern was round to plump spindled cells forming sheets (9 of 13; 69%) and severe atypia was associated with decreased survival (P = 0.048). Immunohistochemistry showed positivity for vimentin (92%), CD117 (92%), and vascular endothelial growth factor (69%), and 8% to 23% showed focal positivity for epithelial, neural, or myogenic markers. Tumors were uniformly negative for translocations associated with pediatric sarcomas. The presence of certain common morphological and immunohistochemical features in the absence of specific molecular genetic abnormalities allows for a diagnosis of pediatric undifferentiated soft tissue sarcoma; however, whether this group of neoplasms forms a unique category of tumors or a common precursor pathway for a number of different sarcomas awaits further study.

Association of renal adenocarcinoma and BK virus nephropathy post transplantation.

While most BK virus infections are asymptomatic, immunosuppression has been associated with BK virus reactivation and impaired graft function or ureteric ulceration in renal transplant patients and hemorrhagic cystitis in bone marrow transplant patients. Oncogenicity is also postulated and this is the first report of a child with a carcinoma of the donor renal pelvis following BK virus allograft nephropathy. Removal of the primary tumor and cessation of immunosuppression led to regression of secondary tumors and a return to health.

JUVENILE LARYNGEAL PAPILLOMATOSIS IN A PEDIATRIC POPULATION: A Clinicopathologic Study

A series of 22 children with juvenile laryngeal papillomatosis treated over a 31-year period is presented. The majority of patients were diagnosed when less than 5 years of age. Two patients died from the disease and four patients still had active disease at the completion of the study period. The duration of disease and number of recurrences were extremely variable. The number of recurrences was inversely related to the age of onset. The histologic findings were very similar in all patients, and no particular histologic feature had prognostic significance. In 20 patients, laryngeal biopsies were positive for human papillomavirus (HPV) 6/11 by either in situ hybridization (17) or polymerase chain reaction (19) or both (16). The number of patients who were HPV negative was small (two); interestingly, neither case had aggressive disease. Our findings suggest that age of onset and HPV status may be of prognostic value in determining the clinical course of the disease.

Association of the t(12;22)(q13;q12) EWS/ATF1 rearrangement with polyphenotypic round cell sarcoma of bone: a case report.

The t(12;22)(q13;q12) chromosomal rearrangement results in an EWS/ATF1 fusion transcript and is associated with clear cell sarcoma (CCS). CCS is an uncommon tumor arising in tendons and aponeuroses of the extremities and shows evidence of melanocytic differentiation at the light microscopic, immunohistochemical, and/or ultrastructural level. Only 5 cases have been reported to arise in bone, none of which had molecular confirmation of the diagnosis. The current report describes a 7-year-old girl with a primary round cell sarcoma of the left humerus showing polyphenotypic differentiation on immunohistochemical analysis. Antibodies directed at melanocytic antigens were negative, and there was no evidence of melanocytic differentiation by light microscopy or ultrastructural analysis. Cytogenetic analysis revealed rearrangement of the EWS locus within 22q12. RT-PCR and sequence analysis revealed the presence of a fusion transcript bringing together exon 7 of EWS with exon 5 of ATF1, consistent with a type 2 transcript reported in association with CCS. However, given the lack of morphologic features usually present in CCS, a diagnosis of polyphenotypic round cell sarcoma was made. This tumor thus expands the spectrum of neoplasms associated with the t(12;22)(q13;q12) rearrangement.

Squamous Cell Carcinoma of the Tongue in a Child with Fanconi Anemia: A Case Report and Review of the Literature

This report documents a case of squamous cell carcinoma (SCC) of the tongue in a child with Fanconi anemia (FA). FA is an autosomal recessive syndrome defined by chromosomal breakage in response to diepoxybutane or mitomycin C in which many patients present with pancytopenia, hypoplastic bone marrow, hyperpigmentation of the skin, skeletal malformations, small stature, hypogonadism, and chromosomal aberrations. Such patients are prone to the development of hematological malignancies and squamous cell carcinoma, especially of the head and neck. Although FA appears to be genetically heterogeneous, all cases display abnormalities of DNA repair. A gene defective in one of the four subsets of FA patients has been defined. Defects in this gene are thought to play a role in the development of neoplasia in FA patients. However, many other factors may also contribute to the development of malignancies, including immune deficiencies, therapeutic strategies, and bone marrow transplantation. This report reviews the association of FA and SCC and highlights the many factors involved in the development of neoplasia within a single patient, including FA, cyclophosphamide, immunosuppression, X-irradiation, and chronic oral graft-versus-host disease. In addition, the human papillomavirus status, although negative, is documented for the first time in such a case.

Molecular cloning and sequencing of a novel human P2 nucleotide receptor

A novel human P2 nucleotide receptor has been cloned from a T-cell cDNA library. The predicted amino acid sequence shows characteristics of a G-protein-coupled receptor, and shares 88% homology with a recently characterised rat P2 nucleotide receptor sequence. Distinctive features include an extremely short cytoplasmic tail with only one putative protein kinase C phosphorylation site. Northern blot analysis revealed a 1.9 kb transcript expressed in the placenta.

Coexistent T-Cell Lymphoblastic Lymphoma and an Atypical Myeloproliferative Disorder Associated with t(8;13)(p21;q14)

This report describes a neoplasm exhibiting both lymphoid and myeloid differentiation associated with an acquired balanced translocation between chromosomes 8 and 13 occurring in a 10-year-old boy. Serial lymph node biopsies revealed the presence of both lymphoblastic lymphoma and an atypical myeloproliferative disorder within the same node. Immunophenotyping was consistent with the presence of an immature T-cell population within the nodal biopsy specimens. Cytogenetic analysis of the bone marrow and lymph node biopsy specimens revealed a unique translocation, t(8;13) (p21;q14). Molecular analysis revealed rearrangement of the immunoglobulin heavy chain gene and germline configuration of the T-cell receptor gene. The patient had a poor response to classical T-cell acute lymphocytic leukemia/lymphoma therapy and was changed to a myeloid leukemia protocol with good response. He underwent bone marrow transplantation but died soon after of overwhelming graft-versus-host disease. We found five similar cases in the literature, suggesting the existence of a subset of mixed lymphoid/myeloid disorders with 8p;13q translocations, in which the clinical picture is dictated by the myeloid element.

Characterization of a t(8;13)(p11;q11-12) in an atypical myeloproliferative disorder

Fourteen cases of an atypical myeloproliferative disorder associated with consistent translocations involving 8p11‐12 have previously been described. A t(8;13)(p11;q11‐12) was the most common, but variant t(8;9)(p11‐12;q32‐34) and t(6;8)(q27;p12) were also reported. Here we have used a series of yeast artificial chromosomes (YACs) derived from the 8p11 and 13q11‐12 regions to analyse one of the t(8;13) cases by fluorescence in situ hybridization (FISH). YACs flanking the 13q11‐12 breakpoint and spanning the 8p11 breakpoint have been isolated. These YACs will facilitate characterization of the genes involved in this rearrangement. Genes Chromosomes Cancer 21:70–73, 1998.