Extrapancreatic solid pseudopapillary neoplasm: report of a case of primary ovarian origin and review of the literature.

Solid pseudopapillary neoplasm, an uncommon, intriguing, low-grade malignant tumor of the pancreas, can exceptionally occur in extrapancreatic sites. We report 1 such case occurring as an ovarian primary in a 25-year-old woman, who presented with abdominal fullness. She remained well 12 years after resection of the 1.7-kg right ovarian tumor. Histologically, the tumor showed a solid, dehiscent, and pseudopapillary growth, traversed by fibrous septa and arborizing blood vessels. The polygonal tumor cells had round nuclei, fine chromatin, and lightly eosinophilic granular cytoplasm. In certain areas, eosinophilic hyaline globules were present. On immunostaining, the tumor cells were positive for ß-catenin (nuclear translocation), CD10, CD56, and synaptophysin (focal), and were negative for cytokeratin, E-cadherin, and chromogranin. The morphologic and immunohistochemical features were compatible with those of solid pseudopapillary neoplasm. Review of the literature uncovered 10 cases of extrapancreatic solid pseudopapillary neoplasm with adequate data for analysis. They were seen to occur predominantly in young female patients, who presented with a large tumor mass, similar to their pancreatic counterparts. The most common sites of occurrence were the mesocolon (with ectopic pancreatic tissue) and ovary. Awareness of the existence of this tumor in various extrapancreatic sites is essential to avoid misdiagnosis.

Mutations of NFKBIA, encoding IkappaB alpha, are a recurrent finding in classical Hodgkin lymphoma but are not a unifying feature of non-EBV-associated cases.

A consistent feature of the Hodgkin and Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL) is the constitutive activation of NF-kappaB transcription factors. In Epstein-Barr virus (EBV)-associated cases of cHL, expression of viral antigens most probably leads to NF-kappaB activation but for non-EBV-associated cases, the mechanism is not clear. Previous small studies have demonstrated deleterious mutations of NFKBIA, the gene encoding IkappaB alpha, in HRS cells. In the present study, we aimed to establish the frequency of NFKBIA mutation in cHL by investigating a larger series of cases and to determine whether these mutations are a characteristic feature of non-EBV-associated cHL. Single HRS cells from 20 cases of cHL were analysed by PCRs covering all 6 exons of the gene. Clonal deleterious mutations were detected in 3 cases and in 1 case both alleles of the gene were shown to harbour mutations. NFKBIA mutations were detected only in non-EBV-associated cases but the majority of these cases had wild-type NFKBIA. It remains possible that defects in genes encoding other inhibitors of NF-kappaB, such as TNFAIP3 (A20) and CYLD, are involved in the latter cases, as described for one case in this series.

Classical Hodgkin lymphoma is associated with frequent gains of 17q.

The etiology of Hodgkin lymphoma (HL) is poorly understood, and studies of the genetics of this disease have been hampered by the scarcity of the Hodgkin and Reed-Sternberg (HRS) cells within tumors. To determine whether recurrent genomic imbalances are a feature of HL, CD30-positive HRS cells were laser-microdissected from 20 classical Hodgkin lymphomas (cHLs) and four HL-derived cells lines and subjected to analyses by comparative genomic hybridization. In primary tumors, the most frequently involved chromosomal gains were 17q (70%), 2p (40%), 12q (40%), 17p (40%), 22q (35%), 9p (30%), 14q (30%), and 16p (30%), with minimal overlapping regions at 17q21, 2p23-13, 12q24, 17p13, 22q13, 9p24-23, 14q32, 16p13.3, and 16p11.2. The most frequent losses involved 13q (35%), 6q (30%), 11q (25%), and 4q (25%), with corresponding minimal overlapping regions at 13q21, 6q22, 11q22, and 4q32. Statistical analysis revealed significantly more gains of 2p and 14q in the older adult cases; loss of 13q was associated with a poor outcome. The results suggest that there is a set of recurrent chromosomal abnormalities associated with cHL and provide further evidence that cHL is genetically distinct from nodular lymphocyte predominance Hodgkin lymphoma (NLPHL). Abnormalities of 17q are infrequent in other lymphomas or NLPHL; this finding, coupled with current knowledge of gene expression in cHL, suggests that genes present on 17q may play an important role in the pathogenesis of cHL.