Adenomatous tumors of the middle ear and mastoid

Three cases of middle ear and mastoid neoplasms are reported as "adenomatous tumors" since in their search of the literature the authors did not find any previously described lesions with a similar histologic appearance and benign biologic behavior. Microscopically, all three tumors are similarly composed of solid cords and nests of closely-packed small cells having an epithelial appearance. Two distinct cell types are present: cuboidal cells, arranged in a rudimentary gland-like pattern, and angular cells forming irregular nests with no distinct pattern. All three tumors developed in patients in their 20's, over a period of months with minimal symptoms; yet in all of the lesions the tympanic membrane was intact at the time of initial examination. None of the neoplasms was diagnosed preoperatively, and, once removed, all three tumors were pathologic enigmas and therapeutic problems in view of the initial and subsequent consultant pathologic opinions; nevertheless, total local excision with preservation of the tympanic membrane would appear to be safe treatment in these cases. The term "adenomatous tumor" is applied to these three neoplasms because: 1. a true glandular epithelial origin warranting the term adenoma or adenocarcinoma cannot be proven; and 2. the biologic behavior and prognosis is not necessarily reflected by the histologic appearance. A more specific term reflecting the origin and behavior of these tumors does not appear possible without the study of further cases.     

An experimental model for ovarian tumor invasion of cultured mesothelial cell monolayer

BACKGROUND: Peritoneal spread of tumor cells is one of the characteristic features of biologic behavior of ovarian cancers. To understand the mechanism by which human tumor cell invasion takes place, we have tried to establish an in vitro experimental model for ovarian tumor cell invasion of the mesothelial cell monolayer. EXPERIMENTAL DESIGN: Mesothelial cells were isolated from normal rat mesentery by trypsin digestion and the cells (1 x 10(5)/dish) were cultured in Eagle's minimum essential medium supplemented with 10% fetal calf serum. Cultured mesothelial cells (M cells) grew forming a pavement-like monolayer. When M cells grew to a confluent state, tumor cells (1 x 10(5)/dish) were seeded on M cell monolayers and cultured. Four tumor cell lines derived from human ovarian cancers were tested for their invasive behaviors. The penetration of M cell monolayers by the tumor cells was confirmed by a perpendicular section of the cell layers. The number of penetrated single tumor cells and colonies/cm2 was counted under a phase contrast microscope after the tumor cell seeding. RESULTS: Several hours after the tumor cell seeding, the cells adhered to M cell monolayers and started to penetrate by extending pseudopodia-like cytoplasmic processes through junctional margins of neighboring M cells, resulting in the formation of penetrated single tumor cells that then proliferated to form colonies under the monolayer. The number of penetrated single tumor cells and colonies/cm2 increased up to 24 hours after the tumor cell seeding, and thereafter stayed almost constant. The number increased with the number of tumor cells seeded, when counted at 48 hours, and therefore was taken to be the number of tumor cells invaded. The in vitro invasiveness of tumor cells varied with the tumor cell lines examined. CONCLUSIONS: Application of this system appears to provide rapid determinations of the invasive potential of ovarian tumor cells and to make it easy to screen substances that modify the invasion of mesothelial cells.     

DNA topoisomerase II alpha and Ki-67 in human adrenocortical neoplasms: a possible marker of differentiation between adenomas and carcinomas

Cell kinetic information is valuable in evaluating the diagnosis and/or biologic behavior of various human neoplasms. Monoclonal antibody Ki-67 recognizes the cells other than G0 of the cell cycle. A cell cycle-related intranuclear protein, topoisomerase II alpha (topoII alpha), separates chromosomes at the end of mitosis. Its expression is mostly limited to the S to G2/M phases of the cell cycle. We studied cell proliferative activity in adrenocortical adenomas (n = 28), carcinomas (n = 17), and normal adrenal glands (n = 6) by immunohistochemical analysis of Ki-67 and topoII alpha to evaluate their value in the diagnosis of adrenocortical malignancy. We detected Ki-67 and topoII alpha immunohistoreactivity in the nuclei of each case we examined. There was a significant positive correlation (r = 0.927) between the Ki-67 and topoII alpha labeling indexes (LIs), the percentage of positive cells. In normal adrenal cortex and adenoma, the LIs for Ki-67 and topoII alpha were 0.48 +/- 0.16 and 0.44 +/- 0.15 for normal and 0.64 +/- 0.11 and 0.72 +/- 0.12 for adenoma, respectively, with no significant differences in the LIs of adenomas and normal adrenals. The Ki-67 and topoII alpha LIs in the carcinomas were 5.84 +/- 1.33 and 6.13 +/0 1.65, respectively; these LIs were significantly higher than the LIs of adenomas. Eleven of 17 carcinomas demonstrated topoII alpha and Ki-67 LIs of more than 2.5, whereas none of the adenomas did. The topoII alpha and Ki-67 LIs in carcinomas with metastasis (11.21 +/- 3.15 and 9.75 +/- 2.31 respectively; n = 7) were significantly higher than in those without metastasis (2.58 +/- 0.61 and 3.12 +/- 0.90, respectively; n = 10). This indicates that immunohistochemical analysis of Ki-67 and topoII alpha could help to differentiate carcinoma from adenoma in resected adrenocortical neoplasms and might predict aggressive biologic behavior in carcinomas.     

Angiomyoid and follicular dendritic cell proliferative lesions in Castleman's disease of hyaline-vascular type: a study of 10 cases

Castleman's disease of hyaline-vascular type (HV CD) may rarely be associated with a confusing variety of stromal cell overgrowths and neoplasms. We report here on the pathologic and clinical findings of 10 such cases. In addition to the usual complex histoimmunophenotype of the stroma of HV CD and some unusual features that mimicked neoplasms, we observed focal proliferations of angiomyoid (five cases) and follicular dendritic cell type (five cases). The former were nonneoplastic growths featuring compact tangles of spindle cells, exhibiting immunoreactivity for smooth muscle actin and interpreted as vessel-related pericytes and myoid cells. The latter were neoplastic growths of oval to spindle cells intermixed with lymphocytes; the tumor cells grew in long, intersecting bundles, featured various degree of atypia, and expressed the markers of follicular dendritic cells (CD21, CD35, KiM4p). The two types were clinically distinct. Four of five patients with angiomyoid proliferations were young women, who presented with an abdominal mass and were cured by surgery; that is, they had a clinical profile similar to that of patients with the stroma-rich variant of HV CD. The follicular dendritic cell proliferations were in older patients of either gender presenting with masses at various sites, recapitulating the profile of follicular dendritic cell tumors arising independently from HV CD; in three patients with long-term follow-up, recurrences or metastases developed at various intervals from the initial diagnosis (1 1/6, 3 1/2, and 11 years), and one patient died as a result. This study confirms the potential for, and the variety of, stromal cell proliferations in HV CD. Because their biologic behavior differs, correct identification of these various proliferative lesions is clinically important.     

Fine needle aspiration cytology of acinar cell carcinoma of the pancreas: a report of two cases

BACKGROUND: Fine needle aspiration in lieu of needle biopsy is widely used for the diagnosis of pancreatic neoplasms. The cytologic features of ductal carcinomas are well characterized, but the appearances of less common pancreatic neoplasms, such as acinar cell carcinoma (ACC), are not well described. CASES: We present the cytologic, histologic, immunocytochemical and ultrastructural features of two cases of ACC. The tumors occurred in a 36-year-old woman and 43-year-old man. The aspirate from one case contained neoplastic cells with smooth-contoured nuclei containing one or two prominent nucleoli. The aspirated material from the second case was necrotic, with numerous neutrophils and scattered nests of tumor cells similar to those present in the first case. Histologically, both tumors manifested solid and acinar patterns, and each contained some cells with periodic acid-Schiff-positive granules that were resistant to diastase. The neoplasms were immunochemically positive for trypsin and negative for neuroendocrine markers. Ultrastructurally, the aspirate from one case demonstrated apical microvilli, zymogenlike granules and abundant rough endoplasmic reticulum. CONCLUSION: Uncommon pancreatic neoplasms may be difficult to diagnose due to their cytologic and histologic subtleties. Supplemental studies including immunocytochemistry, cytochemistry and electron microscopy are important in facilitating their identification.     

Phenotypic diversity of neoplastic chondrocytes and extracellular matrix gene expression in cartilaginous neoplasms

Chondrocyte differentiation is characterized by distinct cellular phenotypes, which can be identified by specific extracellular matrix gene expression profiles. By applying in situ analysis on the mRNA and protein level in a series of benign and malignant human chondrogenic neoplasms, we were able to identify for the first time different phenotypes of neoplastic chondrocytes in vivo: 1) mature chondrocytes, which synthesized the characteristic cartilaginous extracellular tumor matrix, 2) cells resembling hypertrophic chondrocytes of the fetal growth plate, 3) cells resembling so-called dedifferentiated chondrocytes, and 4) well differentiated chondrocytic cells, which expressed type I collagen, indicating the presence of post-hypertrophic differentiated neoplastic chondrocytes. Chondrocytes exhibiting a range of phenotypes were found to be present in the same neoplasm. The different observed phenotypes, including the dedifferentiated phenotype, were in contrast to the anaplastic cells of high-grade chondrosarcomas. Comparison of expression data with tumor morphology revealed a relationship between the cellular phenotypes, the tumor matrix composition, and the matrix and cell morphology within the neoplasms. The distinctly different phenotypes of neoplastic chondrocytes are the basis of the characteristic high biochemical and morphological heterogeneity of chondroid neoplasms and shed light on their biological and clinical behavior.     

Interleukin 2 in the treatment of acute leukemia

Recent immunohistochemical analysis of cell cycle-related proteins such as p27, a cell cycle inhibitory protein, and Ki-67, a proliferation marker, indicated their possible values in predicting the biologic behavior of various human neoplasms. In this study, we performed an immunohistochemical analysis of p27 and Ki-67 in 42 adrenocortical neoplasms (12 adrenocortical carcinomas, 24 adrenocortical adenomas) and 6 normal adrenal glands to evaluate their possible values in diagnosing adrenocortical malignancy and in predicting the biologic behavior of carcinomas. We detected Ki-67 and p27 immunoreactivity in the nuclei of all of our cases, and we observed a significant negative correlation (r = -0.572, P < .001) between the p27 and Ki-67 labeling indexes (LIs). The LIs of p27 and Ki-67 were 61.7+/-2.6 and 0.28+/-0.08 in the normal adrenal cortex and 59.4+/-6.5 and 0.33+/-0.11 in the adenomas, respectively, with no significant differences between the LIs of the adenomas and normal adrenals. The LIs of p27 and Ki-67 in the carcinomas were 48.9+/-7.5 and 630+/-6.21, respectively. The LI of p27 in the carcinomas was significantly lower than that in the adenomas. The LI of Ki-67 in the carcinomas was significantly higher than that in the adenomas (P < .01). Among carcinoma cases, the Ki-67 LI in living cases tended to be lower than that in deceased cases, and the p27 LI in living cases tended to be higher than that in deceased cases, but these differences did not reach statistical significance. These results indicated that decreased p27 protein expression might cause increased cell proliferation in adrenocortical carcinoma cells in combination with other positive and/or negative regulators of the cell cycle. These results also suggested that immunohistochemical analysis of p27 and Ki-67 might be useful in distinguishing between adrenocortical adenoma and carcinoma     

Atrioventricular junctional tissue. Discrepancy between histological and electrophysiological characteristics

BACKGROUND: Previous work has demonstrated that cells with AV nodal-type action potentials are not confined to Koch's triangle but may extend along the AV orifices. The aim of this study was to examine the histological and electrophysiological characteristics of this tissue. METHODS AND RESULTS: Studies were performed in isolated, blood-perfused dog and pig hearts. Microelectrode recordings revealed cells with nodal-type action potentials around the tricuspid and mitral valve rings. These cells were found within 1 to 2 mm of the valve annuli. A zone of cells with intermediate action potentials, approximately 1 cm wide, separated cells with nodal-type action potentials from cells with atrial-type action potentials in the body of the atria. In cells with nodal-type action potentials, adenosine caused a reduction in action potential amplitude (49 +/- 2 versus 33 +/- 2 mV, mean +/- SE; P < .001), upstroke velocity (2.5 +/- 0.2 versus 2.0 +/- 0.2 V/s, P < .05), and duration (150 +/- 4 versus 96 +/- 8 ms, P < .001). The light microscopic appearance of AV junctional cells was similar to that of myocytes in the body of the atrium. A polyclonal antibody raised against connexin-43 bound to atrial and ventricular tissue but not to the AV junctional tissue or AV nodal region. The absence of connexin-43 correlated with the sites of cells with nodal-like action potentials. With pacing techniques, the AV junctional tissue in the region of the posterior AV nodal approaches could be electrically dissociated from atrial, AV nodal, and ventricular tissue. AV nodal echoes were induced with ventricular pacing in three dog hearts. In each case, retrograde conduction was through the slow pathway, and anterograde conduction was through the fast pathway. During echoes, activation of AV junctional cells preceded atrial activation during retrograde slow pathway conduction, but these cells were not activated during anterograde fast pathway conduction. CONCLUSIONS: AV junctional cells around both annuli are histologically similar to atrial cells but resemble nodal cells in their cellular electrophysiology, response to adenosine, and lack of connexin-43. The light microscopic appearance of AV junctional cells is a poor guide to their action potential characteristics. The AV junctional cells in the posterior AV nodal approaches appear to participate in slow pathway conduction. These cells may be the substrate of the slow "AV nodal" pathway.     

A prospective view for the new classifications of malignant lymphomas

Malignant lymphomas, which are now apparently the neoplasms of the immune system, are not a single disease, but represent a group of entities. Because the cells of their normal counterparts undergo differentiation in a complex manner, the corresponding neoplasms are considerably heterogeneous in terms of clinicopathologic features and biologic behavior. Indeed, there are quite a few problems to be solved in the currently used classifications of malignant lymphomas. Their complexity and heterogeneity make it almost impossible, at present, to establish any single classification system which is both clinically useful and scientifically accurate. We, therefore, propose to establish separate clinical and scientific classifications. Our prospective view for the new scientific classification of malignant lymphomas is presented.     

Field test for mechanical efficiency evaluation in matching volleyball players

OBJECTIVE: To evaluate the histologic features and biologic behavior of unclassified sex cord-stromal tumors. PATIENTS: The eight patients' ages at presentation ranged from 14 to 83 years. Presenting symptoms and physical findings included abdominal pain, abnormal uterine bleeding, ascites, and abdominal and pelvic masses. One patient also had bilateral sex cord tumors with annual tubules and probable Peutz-Jeghers syndrome. RESULTS: The tumors ranged from 4 to 27 cm in diameter and were described as partially encapsulated, solid, and cystic. Histologically, the tumors were composed of diffuse proliferations of sex cord cells, with cords, tubules, and follicle-like structures. The stromal cells were spindle-shaped, with scanty cytoplasm. The neoplasms were vimentin-positive and, sometimes, cytokeratin CAM 5.2- and AE1/3-positive and epithelial membrane antigen-negative. Six patients were disease-free from 2 months to 6 years after operation. One patient was lost to follow-up. The patient with probable Peutz-Jeghers syndrome had a tumor with unusual morphology and died of the neoplasm 4 years after the diagnosis. Three of 32 other cases with clinical follow-up mentioned in the pathology literature have been associated with a malignant behavior. CONCLUSION: The biologic behavior of unclassified sex cord-stromal tumors resembles that of Sertoli-Leydig cell tumors of intermediate differentiation rather than poorly differentiated tumors, which might have been expected in view of the lack of specific differentiation. This finding is important with regard to postoperative management.     

Long-term care of an individual with schizophrenia: pharmacologic, psychological, and social factors

Four case reports of mesenchymal neoplasms showing chromosomal abnormalities are presented. In a case of hemangiopericytoma trisomy 2 and centric fusion 19;21 were present. In a mastocytoma a deleted chromosome 35 was seen. A homogeneously staining region (HSR) on chromosome 1 was detected in a histiocytoma. Trisomy 5 and monosomy 31 were observed in a case of granulocytic sarcoma (chloroma). The lack of mutations in exons 1 and 2 of oncogenes N-ras, K-ras, and H-ras and exons 5, 6, 7, and 8 of tumor suppressor gene p53 in these four patients and in a larger series of investigated dogs (25 hemangiopericytomas, 12 mastocytomas, and 8 histiocytomas) is highlighted.     

Structural destabilization of synaptosomal particles by lysis and sequential chemical treatments

Synaptosomes from rat brains were subjected to a sequence of treatments: osmotic lysis, buffered saline wash, nonionic detergent, EGTA and EDTA. After each treatment, particulate samples were fixed in 2% glutaraldehyde-1% formaldehyde and centrifuged to form pellets which were then processed for and examined by electron microscopy. Five morphological classes of synaptic particle were defined in terms of character and presence of synaptic vesicles, flocculent and stranded material, designated as intervesicular scaffolding (IVS), and presynaptic membrane. During osmotic lysis, the presynaptic compartment was altered by loss of most, but not all, small synaptic vesicles, by increase in proportion of large vesicles, and by disappearance of the presynaptic densities. The retention of vesicles was interpreted in terms of IVS struts interconnecting anchorage sites on synaptic vesicles and the presynaptic junctional membrane. Treatment of lysed synaptosomes with nonionic detergent or EGTA resulted in loss of vesicles and IVS from the junctional region in most particles. The apposition of pre-and postsynaptic junctional membranes along the synaptic cleft was disrupted more by EGTA than by detergent. The final result of the sequential treatments was a sediment containing a high proportion of synaptic particles, about half of which had lost their presynaptic junctional membranes.     

Polymerase chain reaction-based microsatellite polymorphism analysis of follicular and Hürthle cell neoplasms of the thyroid

Follicular and Hürthle cell carcinomas of the thyroid cannot be differentiated from adenomas by either preoperative fine needle aspiration or intraoperative frozen section examination, and yet there exist potentially significant differences in the recommended surgical management. We examined, by PCR-based microsatellite polymorphism analysis, DNA obtained from 83 thyroid neoplasms [22 follicular adenomas, 29 follicular carcinomas, 20 Hürthle cell adenomas (HA), and 12 Hürthle cell carcinomas (HC)] to determine whether a pattern of allelic alteration exists that could help distinguish benign from malignant lesions. Alterations were found in only 7.5% of informative PCR reactions from follicular neoplasms, whereas they were found in 23.3% of reactions from Hürthle cell neoplasms. Although there were no significant differences between follicular adenoma and follicular carcinoma, HC demonstrated a significantly greater percentage of allelic alteration than HA on chromosomal arms 1q (P < 0.001) and 2p (P < 0.05) by Fisher's exact test. The documentation of an alteration on either 1q or 2p was 100% sensitive and 65% specific in the detection of HC (P < 0.0005, by McNemar's test). In conclusion, PCR-based microsatellite polymorphism analysis may be a useful technique in distinguishing HC from HA. Potentially, the application of this technique to aspirated material may allow this distinction preoperatively and thus facilitate more optimal surgical management. Consistent regions of allelic alteration may also indicate the locations of critical genes, such as tumor suppressor genes or oncogenes, that are important in the progression from adenoma to carcinoma. Finally, this study demonstrates that Hürthle cell neoplasms, now considered variants of follicular neoplasms, differ significantly from follicular neoplasms on a molecular level.     

Low density lipoprotein of synovial fluid in inflammatory joint disease is mildly oxidized

The histologic diagnosis of adult renal epithelial neoplasms with prominent eosinophilic cytoplasm (renal oncocytoma, chromophobe renal-cell carcinoma (RCC), eosinophilic variant of clear-cell RCC, eosinophilic variant of papillary RCC, and collecting duct carcinoma), could be problematic in some cases because of overlapping morphologic features. Precise diagnosis is essential, however, because it often connotes a distinct biologic behavior. Proliferative activity has not been specifically investigated in this spectrum of renal tumors, so we studied the MIB-1 proliferation index in 20 renal oncocytomas, 12 chromophobe RCCs, 9 eosinophilic variants of papillary RCCs, and 13 eosinophilic variants of clear-cell RCCs. Our purpose was to identify the biologic potential of these renal tumors on the basis of MIB-1 tumor proliferation index and to ascertain whether that index had diagnostic value. Overall, nuclear grade correlated with MIB-1 tumor proliferation index (P=.03). The mean proliferation index progressively increased from renal oncocytomas (0.3) to chromophobe RCCs (0.8) to eosinophilic variants of papillary RCCs (2.2) to eosinophilic variants of clear-cell RCCs (4.1) (P=.002). None of the renal oncocytomas or chromophobe RCCs had an index greater than 2, whereas 8 of 13 eosinophilic variants of clear-cell RCCs had an index greater than 2; in 5 of these, it was more than 3. Thus, in the differential diagnosis between renal oncocytoma/chromophobe RCC and eosinophilic variant of RCC, an MIB-1 index of greater than 3 with appropriate morphologic correlation would strongly support the diagnosis of the latter. We also concluded that the progressive increase in MIB-1 tumor proliferation index across the spectrum of granular renal-cell neoplasms parallels the emerging data in the current literature concerning the biologic potential of adult renal epithelial tumors and justifies histologic categorization of adult renal epithelial neoplasms.     

Amphotericin B colloidal dispersion combined with flucytosine with or without fluconazole for treatment of murine cryptococcal meningitis

Junctional epidermolysis bullosa is a heritable, heterogeneous blistering skin disease with mechanically induced dermal-epidermal separation, mild skin atrophy, nail dystrophy, and alopecia. Four unrelated junctional epidermolysis bullosa families with different phenotypes were investigated here and four novel mutations associated with the disease were identified. Patients 1, 2, and 3 had generalized atrophic benign epidermolysis bullosa, with nonscarring blistering and varying degree of alopecia. Patient 4 had the localisata variant of junctional epidermolysis bullosa, with predominantly acral blistering and normal hair. All patients had mutations in the COL17A1 gene encoding collagen XVII, a hemidesmosomal transmembrane protein. Patients 1 and 2 carried homozygous deletions 520delAG and 2965delG, respectively. Patient 3 was compound heterozygous for a missense and a deletion mutation (G539E and 2666delTT), and patient 4 was heterozygous for a known mutation R1226X. The deletions led to premature termination codons and to drastically reduced collagen XVII mRNA and protein levels, consistent with the absence of the collagen in generalized atrophic benign epidermolysis bullosa skin. The missense mutation G539E allowed synthesis of immunoreactive collagen XVII in keratinocytes, but prevented its secretion, thus causing lack of the protein in the skin. The data suggest that different COL17A1 mutations and their combinations can result in a spectrum of biologic and clinical phenotypes of not only generalized atrophic benign epidermolysis bullosa, but also localized junctional epidermolysis bullosa.     

CDR3-independent gamma delta V delta 1+ T cell expansion in the peripheral blood of HIV-infected persons

A majority of circulating gamma delta T cells in humans express the V delta 2 variable segment associated with the V gamma 9 segment. A minor subset uses the V delta 1 gene mainly paired with a V gamma-chain from group I. Although little is known about the function and the Ags recognized by V delta 1 T cells, their expansion has been described in several diseases. Significant alterations of gamma delta subset distribution have been observed in PBMC from HIV-infected persons. In addition to their significant increase, gamma delta T cells showed an alteration in their subset representation because most of them expressed the V delta 1 receptor and, concomitantly, the V delta 2+ subset was under-represented. To gain insight into the mechanisms involved in this selective expansion, we characterized the V delta 1-J delta 1 junctional diversity in PBMC from healthy donors and HIV-infected individuals at different stages of the disease. We confirmed that the V delta 1 repertoire is restricted in most of the healthy donors. In HIV-infected subjects, we found that the increase of V delta 1 T cells is independent to a particular V gamma-chain expression, and the characterization of the TCR-delta diversity demonstrated a similar restricted V delta 1-J delta 1 rearrangement pattern, not significantly different from the pattern of healthy donors. Moreover, no amino acid junctional motif could be identified either in control or in HIV-infected donors. This report demonstrates that the V delta 1 selective expansion in the course of HIV infection is not the consequence of the emergence of some specifically CDR3-dependent expanded V delta 1 T cell clones. Interestingly, this subset showed an increased ability to be expanded in vitro in the presence of IL-2 alone and, although they did not harbor ex-vivo the phenotype of fully activated cells, they did express the activation marker CD38, a marker for disease progression. Altogether this report indicates that, although the patients' V delta 1 T cells seem to be in a pre-activated state, their selective expansion in the course of HIV infection is not the consequence of a peripheral CDR3-dependent antigenic selection.     

Intravascular large B-cell lymphoma: the CD5 antigen is expressed by a subset of cases

The CD5 antigen is a T-cell associated marker that is also usually expressed by two B-cell neoplasms, chronic lymphocytic leukemia/small lymphocytic lymphoma and mantle cell lymphoma. We observed CD5 antigen expression in a subset of cases of intravascular large B-cell lymphoma (IVLBL), and we report here five cases. The patients, two men and three women, ranged in age from 59 to 81 years. Biopsy specimens were obtained from kidney, lung, bone marrow, abdominal wall, and neck, the latter involving a lymphangioma. All of the cases had histologic features typical of IVLBL, with large and atypical lymphoid cells located predominantly within blood vessels. Immunohistochemical studies performed using routinely fixed, paraffin-embedded tissue sections showed that the neoplastic cells were B cells, positive for the CD20 antigen and negative for the CD3 or CD43 antigens. All cases were also positive for the CD5 antigen. One case had an immunoglobulin heavy chain gene rearrangement shown by using a polymerase chain reaction method. The finding of CD5 antigen expression in a subset of IVLBL cases adds to other evidence in the literature suggesting that IVLBL is a heterogeneous entity. We considered the possibility that these cases were related to or represented unusual histologic forms of transformation from either chronic lymphocytic leukemia/small lymphocytic lymphoma or mantle cell lymphoma. All of the cases, however, were negative for the CD23 antigen and cyclin D1 (bcl-1) protein, which is evidence against this interpretation. The biologic significance of CD5 antigen expression in cases of IVLBL is uncertain. These neoplasms might arise from a separate lineage of CD5-positive B cells or from a specific, early stage of B-cell differentiation. Alternatively, some investigators have suggested that CD5 antigen expression by B cells is a marker of activation.     

Biologic material in needles and cartridges after insulin injection with a pen in diabetic patients

OBJECTIVE: To evaluate the frequency of non-inert material, including cells, in needles and cartridges after insulin injection with pen-like devices in diabetic patients. RESEARCH DESIGN AND METHODS: A prospective study was conducted in 120 insulin-treated diabetic patients who used pen-like devices. The patients, 46 women and 74 men, were 20-77 years old; 60% had type 1 diabetes, and 38% were overweight. Duration of diabetes ranged from 1 month to 40 years, and insulin therapy ranged from 1 month to 30 years. Insulin injection was performed by a trained nurse, using the patient's usual pen and cartridge. A cytopathological examination was performed on the material obtained from the needle and found in the cartridge after centrifugation. All slides were read by a single investigator. RESULTS: In 62% of the patients, non-inert material was found, including squamous (32%) and epithelial (58%) cells. Biologic material was found in 30% of the needles and 58% of the cartridges, and in both needle and cartridge in 25% of the population. Biologic material was found more frequently in patients who had a longer duration of diabetes, who were treated with insulin for a longer time, and who performed injection in the thighs or upper arms (P < 0.05). In multivariate analysis, the presence of biologic material was associated with the duration of diabetes (R2 = 0.09; P < 0.01). CONCLUSIONS: Our data suggest that biologic material can be trapped in the delivery system, including the cartridge, after an insulin injection with a pen-like device. Our results emphasize the strict need for individual use of insulin delivery systems, including cartridges and nonrefillable pens, especially in clinics and hospitals.