Selection of metastatic variants from heterogeneous tumor cell lines using the chicken chorioallantoic membrane and nude mouse.

The chicken chorioallantoic membrane was used to select variant tumor cell subpopulations from the murine melanoma B16-BL6 and the rat glioma C6 cell lines. Tumor cells were deposited on the chicken chorioallantoic membrane of eggs 10 days postfertilization. Upon hatching, chickens were autopsied, and organs were removed, minced, and implanted s.c. in C57BL/6J mice (for melanoma) or nude mice (for glioma). A glioma growing s.c. from a chicken lung implant metastasized to the liver of the recipient nude mouse, and a melanoma growing s.c. from a chicken liver implant metastasized to the lung of its murine host. The s.c. melanoma contained distinct black and gray areas. Cell lines were established from the s.c. glioma (C6-V-1), from a metastasis of the C6-V-1 tumor (C6-V-2), and from the black and gray regions of the melanoma. Marked differences in lung colonization were seen 14 days after 1 X 10(5) parent BL6, Black, or Gray cultured cells were injected by tail vein into C57BL mice. In four separate experiments, fewer than 15 lung foci per mouse were found when BL6 cells were injected, whereas 100 to several hundred lung melanoma colonies per mouse were observed when Black or Gray cells were inoculated. Four of 18 nude mice bearing the s.c. C6-V-1 glioma developed liver metastases; no metastases have been observed in 15 nude mice bearing the s.c. parent C6 glioma. Significant differences in sensitivities to antineoplastic drugs were demonstrated between parent and variant glioma cell lines. The 33-fold increase in sensitivity to vincristine determined for C6-V-1 cells compared to parent C6 cells was particularly striking. Results suggest that the use of the chicken chorioallantoic membrane in situ, together with the nude mouse, might provide a method suitable for the selection and isolation of aggressive variants in heterogeneous human tumors.

Characterization of two metastatic subpopulations originating from a single human colon carcinoma.

Two separate cell lines originating from distinct metastatic deposits in a patient with a primary colonic carcinoma have been established both in vivo and in vitro. One metastasis, OM-1, was found in the omentum, and the other, HOT-3, was located on the ovary. These two metastases differ in several significant characteristics, including growth kinetics and the production of carcinoembryonic antigen by the cultured cells. OM-1 xenograft tumors contain about 8-fold more colonic mucin antigen than do HOT-3 heterografts. Similarities also exist. Both cell lines contain extra chromosomes in the A group, and both are missing chromosomes in Pair 14 of the D group and in Pair 18 of the E group. Xenograft tumors from these two metastases contain equivalent amounts of carcinoembryonic antigen and nonspecific cross-reacting antigen. These metastases developed through a process of progression and natural selection that occurred during the course of the patient's disease. Thus, the cell lines established from them provide material which may be used to study functional intraneoplastic diversity.

Treatment of schistosome-induced glomerulonephritis. A case report and review of the literature.

A patient with membranoproliferative glomerulonephritis and renal dysfunction caused by Schistosoma mansoni was treated with oxamniquine. High levels of circulating immuno-complexes returned to normal following treatment, although renal function for the long term was unchanged. Specific antischistosomal therapy may be of partial benefit to patients with this disease.

Acute quadriplegic myopathy: a complication of treatment with steroids, nondepolarizing blocking agents, or both.

We studied two patients who were given high-dose intravenous steroid therapy and were intubated for status asthmaticus. Both became quadriplegic and wasted within 2 weeks. EMG had myopathic abnormalities. Muscle biopsy revealed severe atrophy of most muscle fibers, with disorganization of myofibrils and selective loss of thick (myosin) filaments. Immunohistologic stains for myosin isoforms confirmed the decrease or absence of this protein. Both patients clinically improved over several months.

C-cell hyperplasia of the thyroid in a patient with goitrous hypothyroidism and Hashimoto's thyroiditis.

A 63-year-old man with a goiter and primary hypothyroidism due to Hashimoto's thyroiditis was found to have hypercalcitonemia and, though hypothyroid, markedly elevated serum total and free T3 levels. The latter findings were attributable to circulating T3 autoantibodies and interference with radioimmunoassay. An infusion of calcium and pentagastrin resulted in abnormal increases in serum calcitonin levels. Because there was no evidence of a nonthyroidal cause for the hypercalcitonemia, the patient had a total thyroidectomy. Pathological examination of the thyroidectomy specimen revealed typical Hashimoto's thyroiditis and extensive C-cell hyperplasia symmetrically distributed throughout the upper and middle thirds of each lobe. The C cells stained strongly with immunoperoxidase stains for calcitonin, chromogranin, and CEA using absorbed polyclonal anti-CEA antibody. Less extensive staining for CEA was obtained using the monoclonal antibodies for CEA, 374/14, 250/183, and 431/31; only a few reactive cells were noted using 431/31. Postoperatively, serum calcitonin levels fell to normal and did not rise with a repeat calcium-pentagastrin infusion test. This patient appears to be the first instance of C-cell hyperplasia associated with Hashimoto's thyroiditis, while elsewhere an association with medullary thyroid carcinoma has been reported. These observations raise questions regarding a possible pathogenetic relationship between Hashimoto's thyroiditis and C-cell neoplasia.

The clinical spectrum of renal osteodystrophy in 57 chronic hemodialysis patients: a correlation between biochemical parameters and bone pathology findings.

Fifty-nine chronic hemodialysis patients who had been on dialysis for an average of 77 months underwent bone biopsies and the pathologic findings were correlated with biochemical and demographic data. All but two had evidence of renal osteodystrophy, 23 with osteitis fibrosa (OF), 19 with osteomalacia and/or adynamic disease (OM/AD), and 15 with mixed osteodystrophy (MOD). Patients in each group were similar with regard to age, sex distribution, duration of dialysis, unstimulated serum aluminum, calcium and phosphorus. Patients with osteitis fibrosa (OF) had statistically higher DFO stimulated aluminum, alkaline phosphatase and PTHC levels than the other two groups although there was marked individual variation. The bone biopsies were also evaluated for the amount of aluminum deposited in the osteoid seam. All 23 of the patients with OF and 11 of the 15 patients with MOD had no, mild, or minimal aluminum deposition but 12 of the 19 patients with OM/AD had moderate to marked aluminum deposition. Patients with minimal to mild aluminum deposition were similar in age, duration of dialysis, sex distribution, unstimulated and DFO stimulated aluminum levels, calcium, phosphorus, alkaline phosphatase to those with moderate to marked deposition but had significantly higher parathormone levels. All patients had been treated in a similar fashion regarding diet, oral phosphate binders and vitamin D; therefore, the observed differences in bone pathology were not readily explicable. However, patients who were found to have osteitis fibrosa and those with minimal to mild aluminum deposition had significantly higher parathormone levels when compared with patients in the other groups at the inception of dialysis.

The relevance of mineralization lag time in the evaluation of histologic changes in renal osteodystrophy.

We examined bone biopsies from 47 patients on chronic hemodialysis, and analyzed the histomorphometric and biochemical findings and histologic quantitation of bone aluminium, looking primarily at mineralization lag time (Mlt) to evaluate its usefulness in categorization of renal osteodystrophy (ROD). The patients were categorized as having either relatively normal Mlt (< 35 days, n = 21 patients), moderately prolonged Mlt (35-100 days, n = 13 patients) or markedly prolonged Mlt (> 100 days, n = 13 patients). The group with relatively normal Mlt showed significantly higher C-terminal parathyroid hormone (PTHc) levels (26,141 +/- 19,270 vs 7,226 +/- 6,073 and 4,434 +/- 4,000 pg/ml) than the moderately or markedly prolonged Mlt groups (p < .01) and was associated with histologic characteristics of osteitis fibrosa or mild hyperparathyroidism (BFR/BS range 0.146-0.947 mcm3/mcm2/d). The group with markedly prolonged Mlt included one patient with classic and 11 with adynamic osteomalacia (BFR/BS range 0.009-0.099) and had greater bone aluminum (Al.S/OS 35.3 +/- 26.7% vs 7.2 +/- 9.0%) than the normal Mlt group (p < .01). The group with moderately prolonged Mlt included two patients with aplastic bone disease (Mlt 80.0 and 84.6 days, and Al.S/OS 100.0 and 72.3%) and 11 patients with features of hyperparathyroidism and osteomalacia (BFR/BS range 0.068-0.243) with variable but generally intermediate bone aluminum deposition (Al.S/OS 22.5 +/- 19.9%). Like BFR/BS and other dynamic parameters Mlt correlates with morphologic types of ROD which primarily reflect bone turnover, but it may also suggest varying degrees of mineralization impairment in a spectrum ranging from high to low turnover types of ROD. Its usefulness in this respect should not be overlooked.

Xanthogranulomatous salpingitis and oophoritis: a case report and review of the literature.

A case of xanthogranulomatous salpingitis and oophoritis in a 47-year-old woman is presented. Xanthogranulomatous inflammation is an uncommon form of chronic inflammation that is destructive to affected organs; it is characterized by the presence of lipid-filled macrophages with admixed lymphocytes, plasma cells, and neutrophils. Only a few cases of xanthogranulomatous salpingitis and oophoritis have been reported to date. The case presented here is associated with Escherichia coli infection, endometriosis, and an intrauterine device.

Renal osteodystrophy and dialysis artifacts as indicators of identification.

Evidence of rare disease may be useful in the identification of unknown remains. Osteodystrophy is a condition commonly associated with chronic renal failure. The presence of renal osteodystrophy and medical artifacts associated with the treatment of kidney failure in human remains may provide information about the individual's medical history. Currently, there are more than 100,000 patients with end stage renal disease in the United States receiving dialysis treatments to replace kidney function, and hundreds of thousands more who have significant chronic kidney failure and are not yet treated with dialysis. Chronic renal failure frequently leads to disorders in the metabolism of vitamin D, calcium, and parathyroid hormone which are extremely difficult to correct. At least three patterns of skeletal change may result: osteitis fibrosa, characterized by increased bone remodelling, increased osteoclastic activity, peritrabecular fibrosis, and a normal mineralization pattern; osteomalacia, with a markedly increased osteoid surface and volume, and impaired mineralization; and mixed osteodystrophy, with increased bone remodelling and moderately impaired mineralization. While these bone changes may not have any clinical manifestations in most patients, they can been seen radiographically and histologically. This evidence may be useful in identifying remains which have been skeletonized, burned, decomposed, or dismembered. Medical artifacts associated with dialysis treatment, such as catheters, polytetrafluoroethylene grafts, and evidence of surgical procedures, are also useful for identification.

Hepatocellular carcinoma. Polygonal cell type with fibrous stroma--an atypical variant with a favorable prognosis.

Hepatocellular carcinoma, even when treated with operative resection, is generally regarded as uniformly fatal. Isolated reports of an unusual histologic variant characterized by polyglonal cells with a fibrous stroma (PCFS) suggest a more favorable outcome. Twelve cases of PCFS, representing the largest reported group, are presented. The mean age of the patients at the time of onset was 23.1 years and the male to female ratio was 1:2. Successful operative resection of the primary neoplasm and metastatic foci has resulted in a significant percentage of long-term survivors with a mean survival time of 68 months and two- and five-year survival rates of 82% and 63%, respectively. The variant shows cytologic similarity to differentiated hepatocellular carcinoma with a unique stromal appearance suggesting a pattern of fibrosis associated with focal nodular hyperplasia. Focal nodular hyperplasia is noted occasionally in the liver adjacent to PCFS. The possibility that PCFS represents an intermediate stage between focal nodular hyperplasia and the more malignant variants of hepatocellular carcinoma is discussed.

Diagnosis and management of giant intrasacral schwannoma.

Giant intrasacral schwannoma is a rare cause of a retrorectal mass in an adult patient. Only 21 such tumors have been reported. The diagnosis of this intraosseous nerve sheath tumor is heralded by its minimal symptoms in relation to its often striking radiographic findings and is verified by its unique morphology. Surgical resection is complex because of its anatomic location and propensity for local recurrence. The need for adequate tumor removal must be balanced against the preservation of nerve function. The presentation, diagnosis, and management of intrasacral schwannomas are reviewed, as exemplified in this case presentation and literature review.

Giant condyloma acuminatum (Buschke-Lowenstein tumor) of the anorectal and perianal regions. Analysis of 42 cases.

PURPOSE: Giant condyloma acuminatum or Buschke-Loewenstein tumor of the anorectal and perianal regions is an uncommon entity that has not been extensively reviewed. We analyzed 42 known cases of giant condyloma acuminatum in the English literature and reviewed their behavior and management. METHODS: All reported cases of giant condyloma acuminatum in the English literature were selected. The relevant clinicopathologic features of this uncommon entity were examined and discussed. RESULTS: These tumors are generally large with the propensity to ulcerate and infiltrate into deeper tissues. The hallmark of the disease is the high rate of recurrence (66 percent) and malignant transformation (56 percent). No distant metastases have been reported. The overall mortality was 20 percent, all occurring in patients with recurrences. Fifty percent of the patients who were initially treated with radical surgery developed recurrences. The average duration of disease was longer in patients with recurrences than in patients without recurrences (9.6 years vs. 2.8 years). The median number of recurrences was two (range, one to seven) recurrences, and the median time before first recurrence was ten months. Recurrences were treated by radical surgery in 17 patients and chemoradiotherapy +/- local excision in 5 patients. Follow-up information for the remaining five patients was not available. The cure rate in the radical surgery group was 61 percent compared with 25 percent in the chemoradiotherapy +/- local excision group. CONCLUSIONS: Giant condyloma acuminatum of the anorectal and perianal regions is a highly aggressive tumor with the propensity for recurrences and malignant transformation, but without metastatic potential. A high rate of recurrence is seen in patients with long duration of the disease. Salvage of patients with recurrences can be achieved successfully with radical surgery.

Seronegative symmetric polyarthritis in Sezary syndrome.

We describe a patient with Sezary syndrome and seronegative symmetric polyarthritis. Detailed analysis of the synovial membrane, including T lymphocyte subset delineation, demonstrated that malignant synovial infiltration was the direct cause of arthritis in this patient.