Metastatic craniopharyngioma.

We report a unique case of metastatic craniopharyngioma. Initially, the patient had a right frontal craniotomy for resection of a suprasellar mass, which was determined to be an adamantinomatous craniopharyngioma. Seven years later, an MR study of the brain showed two peripheral enhancing lesions adjacent to the dura and contralateral to the craniotomy site. Pathologic examination again showed adamantinomatous craniopharyngioma. Although recurrence, both local and along surgical tracts due to implantation of craniopharyngioma tissue, has been reported, this case raises the possibility of meningeal seeding to remote sites.

Allelotype of follicular thyroid carcinomas reveals genetic instability consistent with frequent nondisjunctional chromosomal loss.

Numerous studies aimed at the identification of chromosomal regions that are frequently deleted in specific tumor types have pointed to the location and involvement of specific tumor suppressor genes. Previous studies of loss of heterozygosity (LOH) among thyroid tumors have revealed frequent allelic deletions at a few chromosomal regions. A systematic genome-wide examination of LOH in a substantial number of follicular carcinomas, however, has not been performed previously. We assessed LOH at polymorphic markers from each nonacrocentric autosomal arm in a panel of 28 follicular thyroid carcinoma tumor and normal pairs. In contrast to the results of previous allelotype studies, we found high rates of LOH at multiple chromosomal regions. The highest rate of loss in our study was at 2p (50.0%), and 2q (50.0%), and the mean rate of LOH was 20.4%. Marked genetic instability in a subset of tumors was demonstrated by high fractional allelic loss, which accounted for more than 80% of observed LOH in this study. High fractional allelic loss was significantly associated with oxyphilic features and poor differentiation of these tumors. Our data provide evidence of a prevalent phenotype of nondisjunctional whole chromosomal loss in follicular thyroid carcinomas.

Postoperative granulomas of the endometrium: histological features after endometrial ablation.

Postoperative granulomas of the male urogenital tract are a well-recognized phenomenon. Similar granulomas have also been described in the uterine cervix, fallopian tube, and other sites after various procedures, as well as in the endometrium after endometrial ablation procedures. Endometrial ablation is a procedure increasingly used by gynecologists to relieve symptoms associated with dysfunctional uterine bleeding. Occasionally, patients will not have a satisfactory result, and some will require subsequent hysterectomy. We describe the pathological findings in the hysterectomy specimens from 15 patients who had previously undergone endometrial ablation. Indications for subsequent hysterectomy included dysmenorrhea (7 patients), menorrhagia (7 patients), dysfunctional uterine bleeding (5 patients), and pelvic pain (4 patients). All patients had varying degrees of fibrosis of the endometrial cavity, with some endometrial cavities completely obliterated by fibrous tissue. Histological examination revealed fibrosis with varying degrees of granulomatous inflammation. The majority of the granulomas were associated with refractile brown hematoidin-like pigment, and most were also associated with uniform black pigment. In 8 cases, areas of faintly eosinophilic, homogenous, hyalinized material were present within the endometrium. Comparison is made to granulomas due to other causes, because the postoperative granulomas of the endometrium differ morphologically from granulomatous inflammation caused by other etiologies. As endometrial ablation gains popularity among gynecologists and their patients, it is likely that the practicing pathologist may encounter these sequelae with increasing frequency.

Infrequent CDKN2 mutation in human differentiated thyroid cancers.

We examined the frequency of cyclin-dependent kinase (CDK) N2 alterations in differentiated and anaplastic thyroid cancers to assess the involvement of CDKN2 in the development of these cancers. The CDKN2 gene, which encodes the cell-cycle regulator p16, was recently shown to be mutated or deleted in many tumor cell lines. Its role in the genesis of primary tumors is uncertain, however. Tumor and corresponding normal DNAs were prepared by microdissection of paraffin-embedded tissue blocks or from frozen surgical specimens of 15 papillary, 15 follicular, and five anaplastic thyroid carcinomas. The entire CDKN2 coding region was screened by single-strand conformational variant analysis and direct sequencing of variants. The presence of homozygous deletions was evaluated by multiplex polymerase chain reaction (PCR) analysis. Loss of heterozygosity (LOH) in the CDKN2 region was assessed by using flanking polymorphic markers. Two somatic missense mutations were found among the 35 thyroid cancers, one in a follicular tumor and one in an anaplastic tumor. Multiplex PCR suggested the presence of homozygous deletion in one anaplastic tumor and hemizygous deletions in four tumors. LOH studies revealed loss of 9p sequences in four follicular (27%) and two anaplastic (50%) cancers. Our data suggest that alterations in CDKN2 played a role in a minority of thyroid cancers (three of 35). LOH in the region of CDKN2 is seen in a significant proportion of follicular and anaplastic but not papillary cancers. Loss of 9p sequences suggests a role for a tumor suppressor gene in the development of follicular and anaplastic thyroid cancers.

Frequent mutations of CDKN2 in primary pancreatic adenocarcinomas.

The gene encoding the cell-cycle regulatory protein p16, CDKN2, is localized on chromosome band 9p21. CDKN2 is frequently deleted or mutated in a variety of tumor cell lines, including pancreatic cancer cell lines and xenografts, as well as in some primary tumors. We examined 32 primary pancreatic adenocarcinomas for CDKN2 mutations and for loss of heterozygosity of 9p21 sequences to assess the role of CDKN2 in pancreatic carcinogenesis. Single-strand conformation variant analysis (SSCV) and direct sequencing of the variants revealed somatic CDKN2 mutations in 11 of 32 tumors (five frame-shift mutations, five nonsense mutations, and one missense mutation). One tumor appeared to be characterized by homozygous deletion of CDKN2. These results suggest that CDKN2 plays an important role during tumorigenesis or tumor progression in a significant proportion of pancreatic adenocarcinomas.