Transformation of a primitive myxoid mesenchymal tumor of infancy to an undifferentiated sarcoma: a first reported case.

An 8-month-old girl underwent surgical resection of a cervical mass with histologic diagnosis of a primitive myxoid mesenchymal tumor of infancy (PMMTI). More than 5 years after the initial surgical intervention, the tumor recurred locally, with numerous distant metastases. The histologic morphology of this tumor was compatible with a diagnosis of an undifferentiated high-grade sarcoma. PMMTI is a recently described poorly differentiated fibroblastic soft-tissue tumor of infancy, of at least borderline biological behavior, characterized by local recurrence and a potential to metastasize. We present here the first case of a transformation of a PMMTI into an undifferentiated high-grade sarcoma.

Interface hepatitis is associated with a high incidence of late graft fibrosis in a group of tightly monitored pediatric orthotopic liver transplantation patients.

Chronic graft dysfunction, manifesting with elevated liver enzymes and histological features of interface hepatitis (IH), is being increasingly recognized as a long-term problem after liver transplantation. The aim of this study was to characterize our group of post-orthotopic liver transplantation (OLT) patients with respect to clinical, laboratory, and histological signs of IH. A retrospective study of charts and liver biopsy specimens from patients transplanted between 1986 and 1999 was used. Histological features of IH were found in 29/119 patients at a median interval of 23.9 months (95% confidence interval -28.2 to 52.6) after OLT. All patients with IH had risk factors for chronic rejection, such as steroid-resistant rejection, acute rejection later than 3 months post-OLT, female receiver of male graft, or pretransplant cytomegalovirus (CMV)-positive serology with a CMV-negative donor liver. None of the 29 had features favoring a diagnosis of de novo autoimmune hepatitis, but 4 had isolated hypergammaglobulinemia, and 4 had non-organ-specific autoantibodies without hyperimmunoglobulin G. Sixteen of 29 patients also had features of chronic rejection, such as foam cell arteriopathy, loss of bile ducts, or pericentral fibrosis. After abnormal biopsy, all but 1 patient were switched to tacrolimus. During a median follow-up of 12 years, death occurred in 5, retransplantation occurred in 7, and definite cirrhosis occurred in 4. In conclusion, IH was detected in 24.4% of our patients and was associated with a high degree of fibrosis development. Most likely, IH represents a form of chronic rejection directed against periportal hepatocytes.

Ossifying Renal Tumor of Infancy: Report of a Case With Positive WT1 Immunohistochemistry and High Mitotic Index and Review of the Literature.

Ossifying renal tumor of infancy (ORTI) is a rare, benign pediatric tumor of the kidney. Since first reported by Chatten in 1980, 23 cases have been published. Previous authors have argued that ORTI might originate from nephrogenic rests, thereby sharing a pathogenic relationship with Wilms' tumor (WT). ORTI is characterized histologically by a population of polygonal osteoblast-like cells around an osteoid core and densely cellular component of blastemal-like or spindle cells. While the immunohistochemical profile of the cellular components has been reported, to the best of our knowledge, the status of WT1 expression has only been reported once, where it showed negative marking. Mitoses have been described only sporadically in this neoplasm. We report on a case of ORTI with positive WT1 immunohistochemical marking and numerous mitoses. This case highlights a possible pitfall for misdiagnosing ORTI as a WT and provides additional insight into its pathogenesis.

Exploring the association Between DICER1 mutations and differentiated thyroid carcinoma.

CONTEXT: Carriers of germline DICER1 mutations are predisposed to a rare cancer syndrome, the DICER1 syndrome. Thyroid abnormalities are a common finding in DICER1 syndrome with multinodular goiter frequently present in many families in which a germline DICER1 mutation is segregating. Differentiated thyroid carcinoma (DTC) is infrequently seen in such pedigrees. In addition to germline DICER1 mutations, specific somatic mutations have been identified in the DICER1 ribonuclease IIIb catalytic domain in several tumor types. OBJECTIVE: We aimed to determine whether such characteristic somatic DICER1 mutations are present in DTCs that arise within germline DICER1 mutation carriers. DESIGN AND SETTING: The study involved an opportunistic collection of 3 cases of DTC arising in individuals suspected to have DICER1 syndrome and hospital-based ascertainment and testing was implemented. RESULTS: We identified somatic DICER1 mutations in 3 DTCs arising in unrelated germline DICER1 mutation carriers, all of whom had been diagnosed in infancy with pleuropulmonary blastoma (PPB), were treated with chemotherapy, exposed frequently to diagnostic radiation, and subsequently developed DTC. The somatic mutations occurred within the DICER1 ribonuclease IIIb domain, affecting highly conserved amino acid residues central to the catalytic activity of the domain. CONCLUSION: This report of somatic DICER1 mutations in DTC strengthens the association between DTC and the DICER1 syndrome. The possible association between germline DICER1 mutations, PPB treatment, and the risk of subsequent DTC must be considered by clinicians when treating PPB.

A study of calretinin in Hirschsprung pathology, particularly in total colonic aganglionosis.

INTRODUCTION: Calretinin, a calcium-binding protein, has been reported to be an important new marker in Hirschsprung's disease (HD). The aim is to study the diagnostic value of Calretinin in total colonic aganglionosis (TA), prematurity, and superficial biopsy when nerve hyperplasia may not be accessed by ACE activity. METHODS: Records of patients diagnosed with HD at our institution from 1985 to 2010 were studied and patients with TA identified. We examined tissue samples from those TA, partial colectomies for HD, biopsies for suspicion of HD, and rectal tissue from aborted fetuses. Immunohistochemical analysis of Calretinin was compared with ACE gold standard method in all cases. RESULTS: In the majority of the cases, the diagnosis was ascertained by ACE activity and Calretinin staining. However, in 9 cases, the diagnosis was possible with Calretinin staining but not with ACE: in 4 TA because of the absence of nerve hyperplasia, and in 5 cases because the biopsies were too superficial to examine the nerve hyperplasia. In addition, Calretinin was expressed in the gut as early as 22 gestational weeks. CONCLUSION: The use of Calretinin staining may be superior to ACE activity, particularly in the context of TA, superficial biopsies, and prematurity, allowing earlier diagnosis.

Coexistence of a choriocarcinoma and a gonadoblastoma in the gonad of a 46,XY female: a single nucleotide polymorphism array analysis.

Females with 46,XY complete gonadal dysgenesis are at significant risk of developing germ cell tumors, mostly gonadoblastomas. We present here the case of 2 half-sisters, sharing the same father, diagnosed with 46,XY complete gonadal dysgenesis. The 1st sister developed a gonadoblastoma and an invasive dysgerminoma, whereas the 2nd sister developed a gonadoblastoma and an invasive choriocarcinoma within the same gonad. No SRY mutation, chromosome abnormalities, or mosaicism were detected in blood. Single nucleotide polymorphism (SNP) profiling of the choriocarcinoma revealed a complex hyperdiploid pattern with gains of 1 to 4 copies of material from several autosomes, as well as the loss of the Y chromosome and a homozygous SNP profile without copy number change for the X chromosome. Our results are in agreement with the recurrent chromosome gains and losses previously published in germ cell tumors, and the coexistence of both tumors within the same gonad suggests that choriocarcinomas may derive from gonadoblastomas.

Familial association of pleuropulmonary blastoma with cystic nephroma and other renal tumors: a report from the International Pleuropulmonary Blastoma Registry.

OBJECTIVE: To characterize the association of pleuropulmonary blastoma (PPB) with cystic nephroma (CN) and other renal tumors. STUDY DESIGN: Complete clinicopathologic review of cases from the International PPB Registry and literature. RESULTS: We identified 18 patients with PPB associated with 20 renal tumors (15 CN), either in themselves or family members. All patients with PPB were <5 years of age. All but one of the renal diagnoses were made before 4 years of age. Eleven children had both PPB and renal tumor, one of whom also had a sibling with CN. Six children with PPB alone had one or more family members with CN. The mother of one child with PPB had Wilms' tumor. Pulmonary disease was bilateral in four patients. Renal disease was bilateral in three patients. Two children with PPB and bilateral renal cystic tumors also had intussusceptions because of small bowel juvenile polyps. In six families, dysplasia/neoplasia affected organs other than lung and kidney. CONCLUSIONS: CN or related tumors were found in 9.2% of 152 Registry-reviewed PPB cases. The occurrence of rare pulmonary and renal tumors together in patients and/or family members, the early age of onset, and the multiplicity of tumors is compatible with a constitutional genetic predisposition.