A 34-year-old man presented with tumor of his cervical spinal meninges and bone and the dura over the right frontal lobe, which was shown on biopsy to be Hodgkin's lymphoma. Extensive noninvasive evaluation failed to reveal any other sites of disease. Central nervous system involvement with Hodgkin's disease is extremely rare and is almost always a late complication in patients who have widely disseminated disease in the usual nodal sites. The current patient is unique in that his initial symptoms were due to involvement of the central nervous system and he had no evidence of Hodgkin's disease elsewhere.Cancer 581745 Case ReportIn March 1984 a 34-year-old white man presented to Forbes Regional Health Center with a chief complaint of upper extremity weakness and severe radicular pain from the cervical spine over the preceding year. This was accompanied by a greater than 20-pound weight loss and progressive fatigue. Physical examination revealed point tenderness over the C3-C4 region without a palpable mass. There was partial paresis of both upper extremities with the right worse than the left. There were no deficits of Accepted for publication February 14, 1986. the lower extremities. Bowel and bladder function were normal. He had no palpable lymphadenopathy or splenomegaly. A careful pharyngeal examination failed to reveal any evidence of a mass.Cervical spine x-rays, including myelogram and computerized tomography (CT), showed extensive erosion of the C4 vertebral body and an extradural mass that caused almost total block at C5-6. The extent of destruction was such that it was impossible to tell whether the process started in the bone or within the epidural space. There was paravertebral soft tissue swelling without an apparent soft tissue mass. Some narrowing of nerve sleeves at L4-5, without bony changes, was seen. Computerized tomography scan of the brain with contrast enhancement demonstrated a 5 X 3.5 X 1.5 cm mass which appeared to arise from the right frontal bone with displacement of the right frontoparietal lobes (Fig. 1). There were no other bony abnormalities in the skeleton. A chest x-ray and CT scan of the chest, spine, abdomen, and pelvis all were reported as unremarkable.Biopsy of the vertebral mass was undertaken through an anterior approach. The lesion was gray and firm. No bone could be identified and only a small piece of the mass was excised for diagnosis. The tissue obtained consisted of fibrous stroma with many eosinophils and occasional atypical Reed-Stemberg-like cells. Because this piece was not considered to be diagnostic, the intracranial lesion was excised. It was primarily dural and could be separated from the adjacent bone and brain by blunt dissection. This specimen consisted of approximately 10 X 5 X 1 cm of material. There was a large fragment of dura to which a nodular mass of firm yellow tumor was attached (Fig. 2).Portions of both specimens were used to make imprints, blocks embedded in glycol methacrylate, and paraffin-embedded blocks. Zeihl-Neelsen stain was performed o...
A trial of surgery, irradiation, and adjuvant chemotherapy was offered to patients with extracapsular spread of squamous cell carcinoma in cervical metastases. Following surgery and irradiation, methotrexate, 5-fluorouracil, and leucovorin were administered 18 times over 6 months. Fifty patients undertook chemotherapy, while 47 patients declined further therapy. Comparison of the two groups according to stage, site, and Karnofsky performance status demonstrated no significant differences. The number of nodes encountered and the number and percentage of nodes with extracapsular spread were similar in the two groups. The minimum 5-year adjusted survival for patients undergoing adjuvant chemotherapy is 54% (20 of 37 patients), while survival of patients who failed to undertake adjuvant chemotherapy was 17% (5 of 30 patients). These data suggest the efficacy of methotrexate-5-fluorouracil adjuvant chemotherapy and support the need for a prospective randomized clinical trial.
A prospective clinical trial was developed to evaluate efficacy, toxicity, and patient compliance to adjuvant chemotherapy following surgery and postoperative radiation therapy in patients with squamous-cell carcinoma of the head and neck with extracapsular spread of tumor in cervical metastases. Following postoperative radiation therapy, 18 courses of methotrexate (MTX) and 5-fluorouracil (5-FU) were administered over 6 months. Fifty patients were registered. A total of 771 doses were administered. Dose reduction was required 72 times. Therapy was stopped in one patient (2%) because of toxicity. Three patients (6%) refused to complete the adjuvant therapy. Adjusted 2-year no evidence of disease (NED) survival is 66%. This study demonstrates that patients with advanced squamous-cell carcinoma of the head and neck can undertake an aggressive program of adjuvant MTX/5-FU with acceptable compliance and toxicities. Preliminary data generated in this nonrandomized study support the call for a prospective randomized multiinstitutional trial of this program.
Interleukin 1 (IL-1) is generally regarded as a major regulator of T lymphocyte proliferation. Macrophages from animals and cloned tumor cell lines have been shown to produce this monokine in response to a variety of stimuli. The ability of human monocytes and macrophages to generate IL-1 is much less well characterized. We previously demonstrated that human monocytes cultured for 1-6 days transformed to macrophages but retained their capacity to support concanavalin A-driven T cell proliferation. However, cultured macrophage capacity to support antigen-driven T cell proliferation began to decline after 3 days of culture and was markedly deficient by 6 days of culture. To determine if this loss of accessory cell function was due to the inability to secrete IL-1, we measured the monokine produced by normal fresh human monocytes and macrophages cultured in vitro from monocytes. IL-1 was assayed by the mouse thymocyte proliferation method. Fresh monocytes secreted IL-1 readily in response to lipopolysaccaride and latex particles. Macrophages cultured from fresh monocytes, however, lost this ability after greater than or equal to 2 days in culture. Mixing experiments failed to demonstrate an inhibitor present in the macrophage supernatants that would suppress thymocyte proliferation. Stimulated T cells incubated with monocytes and 3-day cultured macrophages failed to prolong or promote IL-1 secretion.
Patients with locally advanced, inoperable squamous cell carcinoma of the head and neck were offered three courses of cisplatin and 96-h 5-fluorouracil (5-FU) infusion. Subsequent therapy included surgery when feasible, irradiation therapy, and a maintenance program of methotrexate (MTX)-5-FU. Thirty-three patients were evaluated prospectively. Seven patients underwent a single course of chemotherapy. Five patients underwent two courses of chemotherapy. Twenty-one patients underwent three courses of adjuvant chemotherapy. The overall response rate was 48% (16 of 33). Fifteen of 21 patients (76%) receiving three courses of chemotherapy evidenced a response; this included three complete responses (CRs) (9%). No responses were seen in patients receiving only one or two courses of chemotherapy. Among responding patients, the initial favorable response to chemotherapy was apparent after the first course of chemotherapy. Patients who failed to demonstrate any response after two courses of chemotherapy did not respond after a third course. A significant group of patients fail to respond and should be offered participation in other investigational protocols as they become available.
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