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Context.—A large percentage of cases of perianal Paget disease are associated with an internal cancer, most commonly rectal adenocarcinoma. Immunostains for cytokeratin 7, cytokeratin 20, and gross cystic disease fluid protein 15 are useful in identifying cases associated with rectal adenocarcinoma. The Paget cells and rectal adenocarcinoma cells of these lesions typically have a cytokeratin 7+/cytokeratin 20+/gross cystic disease fluid protein 15− immunophenotype. It is not known whether rectal adenocarcinoma unassociated with perianal Paget disease has the same cytokeratin profile as rectal adenocarcinoma associated with perianal Paget disease. Objective.—To evaluate the immunohistochemical cytokeratin 7 and 20 profile of resected rectal adenocarcinoma unassociated with perianal Paget disease as well as that of normal anal glands from hemorrhoidectomy specimens. Design.—We performed immunohistochemistry for cytokeratins 7 and 20 on tissues from 30 cases of rectal adenocarcinoma unassociated with perianal Paget disease and 12 hemorrhoidectomy specimens from 12 cases with normal anal glands. We defined positive staining as any immunoreactivity within the neoplastic cells. Results.—Twenty-six of 30 cases of rectal adenocarcinoma (87%) had a cytokeratin 7−/cytokeratin 20+ immunophenotype, similar to the immunophenotype of cases of nonrectal large intestine adenocarcinoma. In 4 cases (13%), neoplastic cells coexpressed cytokeratins 7 and 20. Anal glands stained strongly for cytokeratin 7 but were negative for cytokeratin 20 in all cases, and the anal transitional zone mucosa had a similar immunophenotype. Conclusions.—Rectal adenocarcinoma unassociated with perianal Paget disease has a cytokeratin profile similar to that of nonrectal large intestine adenocarcinoma. These data suggest that rectal adenocarcinoma unassociated with perianal Paget disease has a different cytokeratin profile than rectal adenocarcinoma associated with perianal Paget disease.

A specific TLS-CHOP fusion gene resulting from the t(12;16) is present in at least 95% of myxoid liposarcomas (MLS). Three common forms of the TLS-CHOP fusion have been described, differing by the presence or absence of TLS exons 6-8 in the fusion product. Type 5-2 (also known as type II) consists of TLS exons 1-5 fused to CHOP exon 2; type 7-2 (also known as type I) also includes TLS exons 6 and 7 in the fusion, whereas type 8-2 (also known as type III) fuses TLS exons 1-8 to CHOP exon 2. We sought to determine the impact of TLS-CHOP fusion transcript structure on clinical outcome in a group of well-characterized MLS cases. We also analyzed P53 status, because this parameter has been found to have a significant prognostic impact in other sarcomas with chromosomal translocations.We analyzed TLS-CHOP fusion transcripts by reverse-transcription PCR using RNA extracted from frozen tissue in 82 MLS confirmed previously to harbor a CHOP rearrangement either by Southern blotting or by cytogenetic detection of the t(12;16). Parameters analyzed included age, location, size, percentage of round cell (RC) component, areas of increased cellularity, necrosis, and surgical margins. In 71 (87%) cases, adequate tumor tissue was available for immunohistochemical analysis of P53 status, using DO7 antibody. The Kaplan-Meier method, log-rank, and Cox regression tests were used for survival analyses.Most MLS were10 cm (73%), arising in the thigh (70%), and localized at presentation (89%). RC component was5% in 47 (57%) cases andor =5% in 35 (43%). The TLS-CHOP fusion transcript was type 5-2 in 55 (67%), type 7-2 in 16 cases (20%), and type 8-2 in 8 (10%). One tumor had a unique variant fusion, between exon 6 TLS and exon 2 CHOP. Two other cases (2%) showed an EWS-CHOP fusion transcript. Overexpression of P53 (defined asor =10% nuclear staining) was detected in 12 (17%) cases. High histological grade (defined asor =5% RC; P0.01), presence of necrosis (or =5% of tumor mass; P0.05), and overexpression of P53 (P0.001) correlated with reduced metastatic disease-free survival in localized tumors. The presence of negative surgical margins (P0.01) and extremity location (P = 0.02) were found to be significant in predicting local recurrence in the entire group as well as localized cases by univariate and multivariate analysis. Although there was no significant correlation between TLS-CHOP transcript type and histological grade or disease-specific survival, an association was found between the P53 status and type 5-2 fusion (P0.01).In contrast to some other translocation-associated sarcomas, the molecular variability of TLS-CHOP fusion transcript structure does not appear to have a significant impact on clinical outcome in MLS. Instead, high histological grade (or =5% RC), presence of necrosis, and P53 overexpression are predictors of unfavorable outcome in localized MLS.

Giant cell fibroblastoma (GCF) is a rare mesenchymal neoplasm, which is classified as a fibrohistiocytic tumor of intermediate malignancy owing to its propensity for local recurrence, although metastasis has not been documented. Prior reports have linked GCF to dermatofibrosarcoma protuberans (DFSP), given overlapping clinical and histologic features.This report documents three additional cases of GCF that further support the contention that this lesion is histogenetically related to DFSP.All three lesions occurred on the trunk of patients whose ages were 4, 28, and 38 years. One case that histologically resembled a GCF on initial excision recurred with areas of both GCF and DFSP. A second recurrence was composed entirely of DFSP. Another case contained areas of both GCF and DFSP, as well as a focus that was felt to be undergoing fibrosarcomatous change. The third case consisted entirely of GCF. Immunohistochemically, all three lesions showed intense immunoreactivity for CD34 in the GCF component. CD34 also strongly marked the cells in those cases with a DFSP component.Although GCF may not represent the "juvenile form" of DFSP, as previously suggested, the evidence strongly supports a histogenetic relationship between these two lesions, even though the cell of origin remains obscure.

Plexiform schwannomas are relatively rare, benign peripheral nerve sheath tumors, which usually arise in either the dermis or subcutaneous tissue, although rare cases originate in skeletal muscle or other deep somatic soft tissue sites. These tumors may occur singly or as multiple lesions and may be localized to one anatomic site or diffusely distributed. Rare cases have been associated with "schwannomatosis" as well as type 1 neurofibromatosis (von Recklinghausen's disease). We report an unusual case of multiple cutaneous plexiform schwannomas associated with bilateral acoustic neuromas as well as other intracranial and intraspinal neoplasms. In addition, we examine the relationship between the various forms of cutaneous schwannoma, particularly the plexiform variant, and both types 1 and 2 neurofibromatosis; we also examine several purported cases of schwannomatosis.

We report a case of a giant bilateral extra-adrenal myelolipoma. To our knowledge this is only the second reported case of either giant or bilateral extra-adrenal myelolipoma and the first in which both features are present. The tumor is also notable for having areas of fibromyxoid degeneration histologically similar to those seen in low-grade fibromyxoid sarcomas. This feature, previously unreported, expands the differential diagnosis of extra-adrenal myelolipomas.

We report a case of primary renal carcinoid, which is a very rare neoplasm: to our knowledge, only 19 cases have been previously reported. The tumor displayed histologic features typical of carcinoid tumors from other sites, including growth in nests and ribbons, uniform cells with finely granular, eosinophilic cytoplasm, and stippled chromatin. Electron microscopy confirmed the presence of membrane-bound dense-core granules. Immunohistochemical analysis revealed staining for chromogranin A, neuron-specific enolase, Leu-7, and synaptophysin, as well as pancreatic polypeptide. An interesting finding was the positive staining for prostatic acid phosphatase, while staining for prostate-specific antigen was negative. Although prostatic acid phosphatase is commonly seen in primary gastrointestinal hindgut carcinoids, in this case a primary hindgut carcinoid was ruled out by clinical examination and endoscopy. The patient developed metastases to the liver, but was well and without symptoms 15 months after diagnosis.

The 21-aminosteroids represent a new class of compounds that serve as potent inhibitors of iron-dependent lipid peroxidation, the latter being an important component of ischemia-reperfusion tissue injury. It is hypothesized that reperfusion injury accompanies renal ischemia, and postischemic administration of one of these steroids, U74006F, will reduce renal damage in a rodent model, as assessed by renal function (plasma creatinine), histologic evidence of renal injury, and animal survival during a 72-hour interval.Fifty-one rats subjected to 45 minutes of renal ischemia were treated on clamp release with 3 or 10 mg/kg U74006F intravenously (n = 5 and 19, respectively), an inactive vehicle (n = 23), or sham operation (n = 4).Both doses of U74006F improved morphologic outcome compared with vehicle-treated animals. Statistically significant improvement in renal function was observed with the 10 mg/kg dose of U74006F (p = 0.029, 0.014, and 0.065 at 24, 48, and 72 hours, respectively) but not with the 3 mg/kg dose. Only one (5.2%) of 19 rats receiving high-dose U74006F (10 mg/kg) died within 72 hours after ischemia, compared with five deaths (29.4%) in 17 rats receiving citrate vehicle alone (p = 0.060). All sham-operated animals survived 72 hours with normal morphology and plasma creatinine levels.These data suggest that iron-dependent lipid peroxidation is a component of reperfusion injury and indicate that U74006F may be useful in reducing this form of renal ischemic damage.