Reversible granulocytopenia in association with riluzole therapy.

OBJECTIVE: To report a case of severe neutropenia developing in association with riluzole 200 mg/d. CASE SUMMARY: A 63-year-old woman with amyotrophic lateral sclerosis (ALS) presented with nausea, anorexia, and fever two weeks following inadvertent dose escalation of riluzole from 100 to 200 mg/d. Granulocytopenia was diagnosed and evaluation for a possible causative infectious process was negative; riluzole was considered a possible offender. Blood counts returned to normal with discontinuation of riluzole and administration of filgramstim. DISCUSSION: Riluzole is a glutamate release inhibitor used in the treatment of ALS, a devastating, progressive neurodegenerative disorder affecting motor neurons. A variety of adverse effects have been described with riluzole therapy, most commonly dizziness and gastrointestinal disorders. In this patient, multiple investigations failed to reveal an infectious cause or other drug-induced cause for the granulocytopenia. CONCLUSIONS: Granulocytopenia has been reported as an adverse effect of riluzole but is not a complication well known to clinicians, and there are no detailed reports published in the literature. In this patient, several lines of evidence raise the possibility of a causal relationship between riluzole and granulocytopenia.

Omental infarction: report of three cases and review of the literature.

Omental Infarction, the end result of impaired perfusion to the greater omentum, is a rare entity (JBCM Puylaert, Radiology 1992;185:169-172). We recently encountered three patients in whom computed tomography (CT) showed the characteristic findings of omental infarction. The diagnosis was subsequently confirmed intraoperatively and pathologically in two of the cases. The third case showed partial resolution on follow-up computed tomography. All three cases are presented with a brief review of the literature.

Immunoperoxidase staining of tumors by an antibody to Xenopus pNiXa.

pNiXa, a serpin from oocytes and embryos of Xenopus laevis, was tested as a tumor marker in human and rodent tissues. A peptide corresponding to the histidine-rich domain of pNiXa was conjugated and administered to rabbits to produce a polyclonal antibody, which was purified by antigen-affinity and used for immunoperoxidase staining of formalin-fixed, paraffin-embedded tissue sections. Staining with pNiXa-antibody was positive in 23/187 human tumors (12 percent) and negative in 119 specimens of normal human tissues. Positive reactions were more frequent in liver (38 percent) and colon (34 percent) tumors than breast (18 percent), prostate (9 percent), mesothelioma (20 percent) or lung (0 percent) tumors. Staining was negative in human tumors from other sites. Rodent tumors and preneoplastic foci induced by chemical carcinogens were surveyed for staining with pNiXa-antibody. Staining was positive in 10/10 hepatic lesions (hepatocellular foci, adenomas, carcinomas) induced in hybrid D2B6F1 mice by diethylnitrosamine and phenobarbital, whereas murine mammary tumors and thyroid, pituitary, renal, and colon tumors of F-344/CNr rats were negative. Thus, immunostaining with pNiXa-antibody identifies a subset of human and murine tumors; further studies are needed to determine if reactivity of pNiXa-antibody has diagnostic or prognostic significance.

The role of flow cytometry in the diagnosis of lymphoma: a critical analysis.

Flow cytometry, now used routinely to aid in the classification of leukemias, is increasingly being evaluated as a rapid technique for determination of surface antigens on the cells teased from lymph nodes and other masses with suspected lymphoma. The present study reviews biopsy specimens from patients examined during a two year period which were sent for flow cytometry with a diagnosis of suspected lymphoma. Sixteen of 25 samples (64 percent) produced cell suspensions of sufficient quantity and quality to be diagnostically helpful. Results showed that in 9/16 (56 percent) the diagnosis of lymphoma or cancer could be suspected by flow cytometry alone, while 4/16 were consistent with the final tissue diagnosis of normal or reactive hyperplasia. Three samples that came from patients who had morphologic evidence of malignant disease on biopsy (two Hodgkin's disease and one large cell lymphoma) had flow cytometry results that were interpreted as normal. Flow cytometry is rapid and appears to be virtually diagnostic of non-Hodgkin's lymphoma when a majority of cells are B cells with an abnormal kappa/lambda ratio (> 4.0 or < 0.25). Nonhematologic malignancy can be suspected if less than 75 percent of the cells show CD45 (common leukocyte antigen). Hodgkin's disease cannot be detected by flow cytometry as it is currently used, and as many as 15 percent (1/6 in this study) of lymphomas may show normal results. It is extremely helpful when the biopsy sample actually contains the cells of interest in large proportion. Loss of architectural relationships in the course of processing specimens for flow cytometry is a major disadvantage when small foci of lymphoma or tumor cells exist together with large amounts of stroma or normal lymphocytes.

Fetal renal biopsy: technique development.

Fetal/neonate kidneys obtained at the time of autopsy were utilized to determine a suitable needle biopsy gauge to obtain renal parenchyma for histologic evaluation. Twenty-one fresh kidney specimens from 11 fetuses/neonates between 16-40 weeks gestation were used to obtain needle biopsies using 20-, 18-, 16-, and 14-gauge biopsy catheters. The specimens were graded according to the presence of normal histologic features of renal parenchyma. Seventy-five renal biopsies were obtained. The biopsy histology was interpreted using a grading system based on the presence of normal features of the renal parenchyma. Sixty-three (84%) of the samples were graded histologically as adequate (cortex or medulla present). Samples with both cortex and medullary structures present (completely adequate) were obtained in 39/63 (62%) of these adequate biopsies. The 14- and 16-gauge biopsy catheters gave the best results, respectively yielding 79 and 69% completely adequate biopsies. This is in contrast to the 20- and 18-gauge catheters that respectively yielded 35 and 25% completely adequate biopsies. Our initial results indicate that adequate kidney biopsies can be obtained. However, the current technique is associated with core sample disruption when the smaller gauge catheters are used. This could account for the low rate of completely adequate samples with the smaller gauge catheters. A different sampling technique is needed to overcome sample disruption, to determine the smallest catheter gauge that will yield a suitable tissue sample for histologic evaluation.

Immunological techniques to differentiate lymphoma from other malignancies.

Seven patients, who had lymph nodes or masses examined by both immunoperoxidase staining and flow cytometry, are presented to illustrate the value of each technique including a critical analysis of the current application of these techniques in the pathology laboratory. All seven patients had diagnoses established by immunoperoxidase staining using antibodies directed against: Leukocyte Common Antigen (LCA), Epithelial Membrane Antigen (EMA), Neuron Specific Enolase (NSE), Leu M1, B4 or chromagrafin and synaptosin. Flow cytometry, which could be more rapidly performed, when sufficient cells could be separated from the node or mass, was diagnostic in two of the seven cases. Flow cytometry failed to show abnormalities in Hodgkin's disease or solid tumors, but it was useful in rapid diagnosis of lymphoma, provided that the sample contained mostly involved tissue. Nodes in which there was a minor infiltration with lymphoma cells could only be detected by immunoperoxidase technique.

Diagnostic pitfalls in the diagnosis of soft tissue bladder tumors in pediatric patients.

This is a case report of a low-grade leiomyosarcoma of the bladder in a four-year-old girl. The pitfalls in diagnosing a soft tissue tumor of the bladder in pediatric patients are discussed. This case is particularly instructive because the differential diagnosis was broad, difficult, and of serious consequence. This report discusses the process by which histologic, immunohistologic and ultrastructural data were used to sidestep the pitfalls in diagnosing this unusual tumor. Clinical follow-up data bearing out our conclusion are also presented.

Glomerular spherical electron dense deposits in a patient undergoing long-term regional heparinization.

Spherical electron dense deposits in the glomerular capillary basement membranes and the mesangial matrix were observed in a patient undergoing long-term regional heparinization during treatment with continuous arteriovenous hemofiltration (CAVH). CAVH is a fairly new approach to renal replacement therapy and requires continuous infusion of heparin into the prefilter blood line. In order to limit systemic anticoagulation, protamine may be infused into the postfilter blood line. In the patient described, during 26 days of continuous treatment, 318,620 units of heparin and 5,204 mg of protamine had been infused. Ultrastructural studies of the kidneys obtained at autopsy revealed a striking resemblance between the electron dense deposits seen in this patient and the protamine-heparin complexes described in animal models. Heavy metals, including calcium, phosphorus, and aluminum were excluded by electron probe x-ray microanalysis.

Ectopic production of human chorionic gonadotropin by poorly differentiated transitional cell tumors of the urinary tract.

We performed a 5-year histopathological review of 41 consecutive cases of transitional cell carcinoma. Of these cases 8 were positive for human chorionic gonadotropin immunoperoxidase tissue staining. All tumors were grade III and stages ranged from A to D. Three patients presented with gynecomastia as the clinical manifestation of elevated serum levels of beta-human chorionic gonadotropin. These findings document the association of this phenomenon with lesions of an aggressive nature. As with the loss of cell surface antigens, the appearance of human chorionic gonadotropin within the tumor cells may be further evidence of dedifferentiation. Human chorionic gonadotropin production may be a potential marker to gauge tumor response to chemotherapy and, perhaps, a predictor of future aggressiveness and over-all progression.

Immunohistochemical demonstration of human chorionic gonadotropin in tumors of the urinary bladder.

All transitional cell carcinomas of the bladder diagnosed in male patients within a five year period were studied for human chorionic gonadotropin (hCG) production. Biotin-avidin immunoperoxidase analysis for hCG was performed on all paraffin blocks containing carcinoma-in-situ, grade I, grade II, and grade III transitional cell carcinoma. Of a total of 29 patients, one case of carcinoma-in-situ (1/5), and five cases of grade III transitional cell carcinoma (5/15) were found to have hCG-positive tumor cells. The findings indicate that transitional cell carcinoma should be added to the list of malignant tumors capable of producing hCG.

Embolic tubular epithelial cells in percutaneous renal biopsies.

Four percutaneous renal biopsies with intravascular embolic tubular epithelial cells are presented. This unusual finding is presumably the result of the needle biopsy procedure and can be a puzzling and misleading artifact. It is postulated that dislodged tubular epithelial cells are pushed forward into or pulled back into punctured intrarenal arteries and subsequently transported to distant glomeruli.

ABH cell surface isoantigens in invasive bladder carcinoma associated with schistosomiasis.

The immunoperoxidase technique for demonstrating blood group ABH isoantigens was used to compare 33 patients with invasive stages T2 and T3 bladder carcinoma with (18) and without (15) schistosomiasis. Of the 18 patients with schistosomiasis 11 (61 per cent) had cell surface antigens present (9 with squamous cell carcinoma and 2 with transitional cell carcinoma and areas of squamous metaplasia), while isoantigens were absent in the remaining 7 (1 with well differentiated squamous cell, 2 with moderately to poorly differentiated squamous cell and 4 with transitional cell carcinoma). Cell surface isoantigens were present in only 3 of the 15 patients (20 per cent) without schistosomiasis (2 with squamous cell and 1 with transitional cell carcinoma) and absent in the remaining 12 with transitional cell carcinoma. This preliminary study shows that a significant percentage of patients with schistosomiasis-associated invasive bladder carcinoma maintain the blood group isoantigens, in contrast to those with bladder carcinoma not associated with schistosomiasis. The better prognosis of schistosomiasis-associated carcinoma could be linked conceivably to isoantigen maintenance. If this speculation is supported by further studies the determination of blood group isoantigens in these patients would be of prognostic value.

Mesangial proliferative glomerulonephritis with IgM deposits. Clinicopathologic analysis and evidence for morphologic transitions.

To determine the natural history of mesangial proliferative glomerulonephritis (MesPGN) with IgM deposits and its relationship to minimal change disease (MC) and focal segmental glomerulosclerosis (FGS), we studied the clinical characteristics and outcome in 20 patients with MesPGN, 8 with MC, and 10 with FGS. IgM deposits were present in glomeruli of all MesPGN patients. Progression to FGS was documented in 2 patients with MesPGN, 1 of whom developed renal failure. Transition from MC to MesPGN occurred in 1 patient. 2 MC patients developed FGS, with decline in renal function in 1 of them. These data suggest the possibility of histologic transition from MC to FGS directly or through the stage of MesPGN.

A simplified method of preparing permanent tissue sections for the erythrocyte adherence test.

A method of preparing permanent sections of tissue for the erythrocyte adherence test using glutaraldehyde fixation and polylysine as the bonding agent is described. This method enables rapid staining with hematoxylin and eosin without loss of indicator erythrocytes.

Multiple oncocytic papillary cystadenomas of the larynx: a case report.

A patient had multiple oncocytic cysts of the larynx and, concurrently, epidermoid carcinoma of the larynx. Total laryngectomy for the epidermoid carcinoma made it possible to carefully examine and histologically document the multifocal and oncocytic nature of the lesions. The authors interpret the findings to represent both hyperplastic and metaplastic processes.

Oncobytic papillary cystadenomatosis of the larynx: a clinicopathologic entity.

A patient with numerous oncocytic lesions of the larynx is reported. Laryngectomy for a concurrent epidermoid carcinoma made it possible to study the entire laryngeal mucosa. A hyperplastic component to the oncocytic metaplasia of the ductal epithelium of the seromucinous glands resulted in a spectrum of lesions varying from simple oncocytic cysts to solid lesions that may be erroneously interpreted as true neoplasms (oncocytomas). Oncocytic papillary cystadenomatosis is a condition affecting the larynx in a diffuse fashion suggesting the need for follow-up on patients with biopsy proven oncocytic lesions.