Metastatic breast cancer masquerading as sarcoidosis.

Malignancies can cause mediastinal and hilar lymphadenopathy that is easily mistaken for sarcoidosis. We report a patient with breast cancer who initially had respiratory symptoms and thoracic lymphadenopathy. Despite the rarity of breast cancer manifesting in this way, the importance of obtaining histologic confirmation of suspected sarcoidosis is stressed.

DNA ploidy, proliferative activity, and concanavalin A reactivity in breast cancer.

Paraffin-embedded primary tumor specimens from 48 patients with breast cancer were examined for DNA ploidy, S-phase fraction (SPF), and concanavalin A (Con A) reactivity. The results were correlated with clinicopathological prognostic factors, including patients' age and menopausal status, stage of disease, nuclear grade, and size of the primary tumor. There were no associations among ploidy, SPF, Con A reactivity, and menopausal status, stage of disease, or size of the primary tumor. However, among patients who were 50 years or older, 81% had diploid tumors and 73% had good reactivity (3+ or better staining score) with Con A. In contrast, among patients who were younger than 50 years, 45% had diploid tumors (P < 0.05) and 21% had good Con A reactivity (P < 0.05). Seven of 19 (37%) poorly differentiated tumors and 7 of 9 (78%) moderately differentiated tumors had good reactivity with Con A (P < 0.05). Reactivity of tumor cells with Con A in primary breast cancer tissues deserves further evaluation as a potential biomarker of prognosis.

Non-Hodgkin's lymphomas in Turkey.

Between 1982 and 1986, 185 adult patients with non-Hodgkin's lymphoma (NHL) were studied at Cukurova University Hospital (CUH), Adana, Turkey. This constituted 13% of all malignant neoplasms diagnosed in the oncology clinic. The mean age for men was 45.5 years and 41 years for women. Fifty-four percent of the cases were nodal lymphoma and the remaining 46% were extranodal lymphoma. Sixty-six percent of the extranodal lymphoma cases were gastrointestinal lymphoma. The stomach was the most common localization (43%), followed by intestinal involvement (30%) and abdominal mass (27%). The mean age of the patients with gastric lymphoma was 49 years, and 36 years for patients with abdominal mass. The following conclusions were reached: (1) the relative frequency rate of NHL in South Turkey is higher than Turkey averages, but similar to other Middle East countries; (2) extranodal lymphomas account for more than 40% of all lymphomas; (3) gastric lymphoma is more prevalent than intestinal lymphoma in our region; and (4) compared with western gastric lymphomas, our patients were 10 years younger and had a higher incidence of small lymphocytic and immunoblastic lymphoma.

Lower extremity vasospasm associated with ischemic neuropathy, dermal fibrosis, and digital gangrene in a patient with carcinoid syndrome.

Bilateral lower extremity vasospasm associated with severe pain and hyperesthesias in the legs, and digital gangrene in both feet developed in a 50-year-old man with carcinoid syndrome. Nifedipine and chemical lumbar sympathectomy were partially effective in relieving the vasospasm. Electromyographic findings were consistent with ischemic neuropathy. A skin biopsy specimen showed striking dermal fibrosis. Serotonin and other vasoconstrictor substances released from the tumor may be responsible for the vasospasm, the dermal sclerosis, and the ischemic neuropathy. The early use of lumbar sympathectomy in patients with lower extremity vasospasm may prevent these irreversible ischemic complications.

Incomplete Behçet's syndrome with unusual manifestations.

We report a case of incomplete Behçet's syndrome with two major criteria plus interstitial pneumonia. The patient had also hypoplastic bone marrow and disseminated intravascular coagulation developed during the terminal stage.

Early diagnosis of spinal-epidural metastasis by magnetic resonance imaging.

Sixteen patients with various types of cancer who developed pain along the axial spine were prospectively studied by magnetic resonance imaging (MRI). The studies were performed with a Fonar Beta-3000 (Fonar Co., Melville, NY) permanent magnet operating at 0.3 Tesla (T). Detailed neurologic examinations were followed by bone x-rays, bone scans, and MRI. In 12 patients there were focal neurologic findings. Bone x-rays and bone scans were diagnostic for metastatic disease in 10 cases; MRIs were consistent with metastatic spinal-epidural disease in all 16 patients. Magnetic resonance imaging revealed bone involvement in three patients whose x-rays and bone scans were both negative indicating a higher degree of sensitivity. In six patients thecal compression was obvious on MRI; in three of these previous myelograms had been interpreted as negative. These early results suggest that MRI can serve as a useful tool for diagnosing early spinal-epidural metastases.

Hypogammaglobulinemia and hemophagocytic syndrome associated with lymphoproliferative disorders.

Four patients with lymphohistiocytic disorders had or subsequently experienced severe hypogammaglobulinemia and pancytopenia due to hemophagocytosis. The percentages of B- and T-lymphocytes and the ratios of helper (OKT4) cells to suppressor (OKT8) cells in the peripheral blood were variably altered. Mitogenic response to pokeweed mitogen and phytohemagglutinin was depressed but could be restored to near normal by the in vitro addition of indomethacin or interleukin-2. The half-life of intravenously administered immunoglobulin was markedly shortened. The data indicate that hyperactive monocytes/histiocytes are capable of simultaneously ingesting apparently normal blood cells and immunoglobulin, leading to pancytopenia and hypogammaglobulinemia. The monocytes with suppressor activity (which could be abrogated with indomethacin or interleukin-2) appeared to additionally contribute to the hypogammaglobulinemia, possibly by interfering with the terminal differentiation of the B-lymphocytes. Hemophagocytosis occurs frequently in histiocytic and occasionally in lymphoproliferative disorders or viral diseases. More frequent and serial determination of serum immunoglobulin levels in such situations may lead to the discovery of additional cases.

Serum cyclophosphamide activity in patients treated for small cell carcinoma of the lung.

Cyclophosphamide requires in vivo activation for its cytotoxicity. A bioassay of serum cyclophosphamide activity based on inhibition of normal peripheral blood CFU-C by serum from cyclophosphamide-treated patients was developed. Seventeen patients with small cell cancer of the lung were studied before and after cyclophosphamide administration in an attempt to correlate serum cytotoxicity in vitro with clinical response to chemotherapy. A correlation (r = 0.61, p less than 0.01) was discovered between serum cytotoxicity in vitro and subsequent leukopenia in vivo. However, a dose-response relationship was not found between serum cytotoxicity and response to chemotherapy. Besides drug dosage and blood level, other factors govern the sensitivity of small cell lung cancer to chemotherapy.

Kinetics and effects of activated cyclophosphamide in serum.

The effects of sera containing in vivo activated cyclophosphamide were tested on macrophage granulocyte colony growth (CFUc) and mixed leukocyte cultures (MLC). Bone marrow reconstitution and the growth of a canine tumor after incubation of transplanted cells with active sera were studied in vivo. The following experiments were performed: 1) peripheral blood CFUc values were determined in 6 dogs 5 min to 72 h after intravenous administration of 100 mg/kg cyclophosphamide. Inhibition was apparent at 5 min and lasted for 24 h. 2) Sera samples were obtained from 10 dogs after cyclophosphamide administration. The half life of serum inhibitory activity measured against normal dog cells was approximately 6 h. Inhibitory effects were noted 5 min following drug administration and complete at 30 min. 3) Timed incubation with 1 h postcyclophosphamide sera revealed preferential inhibition of MLC activity compared to CFUc activity, 4) In vitro incubation for 30 min in active sera did not affect the bone marrow repopulating potential of hematopoietic cells compared to nonincubated cells. 5) At least a tenfold reduction in the growth potential of a transplantable canine tumor could be produced by in vitro incubation of tumor cells with active sera. It is concluded that varying sensitivities of hematopoietic, immunocompetent and tumor cell populations to cyclophosphamide metabolites may provide a basis for in vitro chemoseparation of mixtures of these cell types.

Autologous bone marrow infusion following high dose chemotherapy of the canine transmissible venereal tumor (TVT).

The present study was undertaken to evaluate infusion of cryopreserved autologous bone marrow following supralethal chemotherapy in canines bearing a solid tumor thought to be moderately sensitive to cytotoxic agents. Initial studies in 5 dogs established a combination of busulfan (Bu) 3 mg/kg X 2 days and cyclophosphamide (Cy) 50 mg/kg on day 3 to produce bone marrow lethality within 14 days (high dose regime). Bu 1 mg/kg, Cy 20 mg/kg produced tolerable toxicity (low dose regime). Eight pairs of dogs were challenged with 3 X 10(8) transmissible venereal tumor cells. Measurable progressive tumor growth occurred in all instances. Marrow aspirated from the femoral shafts of the animals was cryopreserved in 10% DMSO. One dog of each pair received the high dose Bu + Cy regime followed in 30 h by marrow infusion and his partner received the low dose regime without marrow. Tumors were measured serially for at least 2 months. Infusion of marrow resulted in evidence of hematologic recovery within 2 weeks following the high dose regime. Tumor responses occurred in both groups when compared to 8 untreated tumor challenged controls. High dose animals had greater initial responses than low dosed dogs but long term responses were not significantly different. Eight dogs rechallenged with tumor cells after initial successful therapy failed to develop tumors. It was concluded that: a) cryopreserved autologous bone marrow infusion was effective in protecting tumor bearing canines from otherwise lethal chemotherapy; b) the transmissible venereal tumor of canines responded to both high and low dose regimes; c) the rescue of dogs by stored autologous marrow did not offer additional benefits in tumor control over a standard regime; d) chemotherapy treated dogs resisted tumor rechallenge. This model may offer a large animal system to study the autologous marrow rescue concept during controlled periods of tumor evolution.

The collection, preservation and function of peripheral blood hematopoietic cells in dogs.

Semicontinuous flow centrifugation (SFC) was employed in canines to obtain adequate numbers of cells for autologous marrow repopulation following supralethal cyclophosphamide administration (100 mg per kg). Four cycles using a 225 ml bowl and 30 ml per minute flow rate were carried out for procurement. Collections averaged 8.4 +/- 0.4 x 10(9) (n = 30) leukocytes. Mononuclear cells (MNC) comprised 75 +/- 2% of the population and granulocyte colony-forming units (CFU-C) totaled 1.9 +/- 0.09 x 10(5) colonies per collection. Eighty-six percent of mononuclear cells were "T" cells in the 30 to 90 second fraction compared to 49% at 150 to 120 seconds. CFU-C fractionation revealed a peak at 30-210 seconds and a second peak at 120-210 seconds. Following programed freezing and rapid thawing 77.7 +/- 11.4% of CFU-C were recovered. Using a dose of 1 x10(9) MNC per kg for reinfusion, marrow repopulation and clinical recovery occurred in four out of four dogs. It was concluded that 1) SFC was effective for obtaining adequate numbers of peripheral blood stem cells for autologous marrow repopulation. 2) A rapid thawing and direct transfusion technique appears satisfactory for administration. 3) Some separation of "T", "B" and CFU-C peripheral blood components is possible by centrifugation.

Processing of peripheral blood stem cells for transplantation.

Canines were studied to determine the efficacy of peripheral blood collection by semicontinuous centrifugation to procure sufficient numbers of hematopoietic cells for marrow reconstitution. CFU-C assays on fresh and cryopreserved peripheral blood cells were compared to bone marrow aspirates. Attempts were made to partially separate hematopoietic cells from immunocompetent cells during buffy coat collection and by incubation with activated cyclophosphamide. Yields from 4 runs of semicontinuous centrifugation averaged 1.7 x 10(5) CFU-C compared to 1.9 x 10(5) CFU-C for standard marrow aspiration. Ratios of approximately 5/1 marrow to peripheral blood mononuclear cells (MNC) were found. Autologous transplantation with 1.6 x 10(4) CFU-C per kg resulted in evidence of marrow reconstitution within two weeks following otherwise lethal chemotherapy. Recovery of CFU-C following cryo-preservation was 82% for marrow and 78% for peripheral blood. Selective depression of MLC activity occurred when peripheral blood MNC were incubated for 30 minutes with activated cyclophosphamide. MLC was inhibited by greater than 90% while 70% of CFU-Cs were retained. It was concluded that peripheral blood may be a practical alternative to marrow for transplantation studies.

Subacute constrictive uremic pericarditis. Survival after pericardiectomy.

Uremic pericarditis progressed to subacute constriction despite intensive medical treatment in two patients with concomitant metabolic stress of surgery and infection. Total pericardiectomy was successful and should be done as soon as medical measures fail to resolve the pericarditis.