Inflammatory myofibroblastic tumor (IMT) of the urinary tract, also termed postoperative spindle cell nodule, inflammatory pseudotumor, and pseudosarcomatous fibromyxoid tumor, is rare and in the past was believed to reflect diverse entities. We reviewed a series of 46 IMTs arising in the ureter, bladder, and prostate, derived primarily from a large consultation practice. There were 30 male and 16 females aged 3 to 89 years (mean 53.6). Lesions were 1.2 to 12 cm (mean 4.2). There was a history of recent prior instrumentation in 8 cases. Morphology was similar to that previously described for IMT occurring in this region, with the exception of 1 case that focally appeared sarcomatous. Polypoid cystitis coexisted in 5 patients (11%). Mitoses were typically scant (0 to 20/10 hpf, mean 1). Necrosis was seen in 14 (30%) cases. Invasion of the muscularis propria was documented in 19 (41%). By immunohistochemistry (IHC), lesions at least focally expressed anaplastic lymphoma kinase (ALK) (20/35, 57%), AE1/3 (25/34, 73%), CAM5.2 (10/15, 67%), CK18 (6/6, 100%), actin (23/25, 92%), desmin (15/19, 79%), calponin (6/7, 86%), caldesmon (4/7, 57%, rare cells), p53 (10/13, 77%), and most lacked S100 (0/14), CD34 (0/13), CD117 (2/13, 15%), CD21 (0/5), and CD23 (0/3). ALK gene alterations were detected by fluorescence in situ hybridization (FISH) in 13/18 (72%) tested cases, including 2 with prior instrumentation; 13/18 (72%) showed agreement between FISH ALK results and ALK protein results by IHC. Most bladder IMTs were managed locally, but partial cystectomy was performed as the initial management in 7 cases and cystectomy in 1 (1 IMT was initially misinterpreted as carcinoma, 1 IMT was found incidentally as a separate lesion in a cystectomy specimen performed for urothelial carcinoma). Follow-up was available in 32 cases (range 3 to 120 mo; mean 33; median 24). There were 10 patients with recurrences (2 with 2 recurrences). Recurrences were unassociated with muscle invasion or with ALK alterations. In 2 cases, tumors of the urinary tract (TURs) showing IMT preceded (1 and 2 mo, respectively) TURs showing sarcomatoid carcinoma with high-grade invasive urothelial carcinoma accompanied with separate fragments of IMT. Even on re-review the IMT in these 2 cases were morphologically indistinguishable from other cases of IMT, with FISH demonstrating ALK alterations in the IMT areas in one of them. Both these patients died of their carcinomas. Lastly, there was 1 tumor with many morphological features of IMT and an ALK rearrangement, yet overtly sarcomatous. This case arose postirradiation for prostate cancer 4 years before the development of the lesion, with tumor recurrence at 4 months and death from intra-abdominal metastatic disease at 9 months. In summary, urinary tract IMTs are rare and share many features with counterparts in other sites, displaying similar morphology and immunogenotypic features whether de novo or postinstrumentation. Typical IMTs can be locally aggressive, sometimes requiring radical surgical resection, but n...

We conclude that at doses of IL-1 alpha that can be given safely to cancer patients, significant, potentially beneficial hematopoietic effects occur.

GST pi expression is inversely related to hormone receptor status in breast cancer. This pilot study also suggests that increased GST pi expression may be an important predictor of early recurrence and death in node-negative breast cancer patients that merits additional investigation.

Increasing evidence suggests that P-glycoprotein (Pgp) expression can mediate drug resistance in refractory breast cancer. We studied 33 patients with refractory breast cancer enrolled in a pilot study of oral amiodarone as a Pgp antagonist given in combination with infusional doxorubicin or vinblastine. Whenever possible, tumors were biopsied and Pgp expression was assayed. Patients received either 60 mg/m2 doxorubicin over 96 h or 8.5 mg/m2 vinblastine over 120 h by continuous intravenous infusion. Beginning with the second cycle of chemotherapy, 600-800 mg amiodarone was given orally each day. Patients who experienced toxicity due to amiodarone but were responding to chemotherapy were placed on quinidine. Partial responses were observed in 9 of 33 patients on study and were sometimes observed after the first cycle of chemotherapy, before amiodarone was given, suggesting that some patients may have responded to treatment because of the infusional schedule. Toxicities were primarily the known side effects of the antineoplastic agents and of amiodarone. The major amiodarone toxicity was gastrointestinal, with nausea, vomiting, anorexia, or diarrhea being noted in 21 patients. Biopsy samples were obtained from 29 patients and in 21 cases, viable tumor tissue was present and the results were interpretable. Of the 21 samples, 9 had Pgp expression as determined by immunohistochemical staining; 12 were considered negative. The presence of Pgp expression was associated with an acceleration of the time to treatment failure. Whereas normal-tissue toxicities related to the combination of a Pgp antagonist with chemotherapy were not observed, amiodarone was associated with too many untoward effects to be utilized as a drug resistance-reversing agent.

We evaluated the toxic, hematopoietic, and immunomodulatory effects of recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF). The rHuGM-CSF was administered at doses up to 50 micrograms/kg by daily 2-hour intravenous infusions to 11 patients with advanced malignancy. It induced dose-related increases in cells of the myeloid series, but it had no significant effect on reticulocyte or platelet counts. Bone marrow cellularity increased with higher doses of rHuGM-CSF, but there was a dose-related decrease in the number of colony-forming units--granulocyte-monocyte--and colony-forming units--granulocyte-erythrocyte-monocyte-megakaryocyte--per 10(5) bone marrow cells. The rHuGM-CSF caused transient increased expression of CD11b and CD16 on granulocytes but increased expression of HLA-DR and decreased expression of the high-affinity Fc receptor on monocytes and no change in monocyte production of H2O2. Thus, rHuGM-CSF has potent effects on granulocyte, eosinophil, and monocyte numbers in the peripheral blood and bone marrow. In addition, it enhances the expression of monocyte and granulocyte activation-associated surface markers.