Search

Anaplastic large-cell lymphomas (ALCLs) are a group of clinically and biologically heterogeneous diseases including the ALK(+) and ALK(-) systemic forms. Whereas ALK(+) ALCLs are molecularly characterized and can be readily diagnosed, specific immunophenotypic or genetic features to define ALK(-) ALCL are missing, and their distinction from other T-cell non-Hodgkin lymphomas (T-NHLs) remains controversial. In the present study, we undertook a transcriptional profiling meta-analysis of 309 cases, including ALCL and other primary T-NHL samples. Pathway discovery and prediction analyses defined a minimum set of genes capable of recognizing ALK(-) ALCL. Application of quantitative RT-PCR in independent datasets from cryopreserved and formalin-fixed paraffin-embedded samples validated a 3-gene model (TNFRSF8, BATF3, and TMOD1) able to successfully separate ALK(-) ALCL from peripheral T-cell lymphoma not otherwise specified, with overall accuracy near 97%. In conclusion, our data justify the possibility of translating quantitative RT-PCR protocols to routine clinical settings as a new approach to objectively dissect T-NHL and to select more appropriate therapeutic protocols. (Blood. 2012;120(6):1274-1281) Anaplastic large-cell lymphomas (ALCLs) are a group of clinically andbiologically heterogeneous diseases including the ALK(+) and ALK(-) systemicforms. Whereas ALK(+) ALCLs are molecularly characterized and can be readilydiagnosed, specific immunophenotypic or genetic features to define ALK(-) ALCLare missing, and their distinction from other T-cell non-Hodgkin lymphomas(T-NHLs) remains controversial. In the present study, we undertook atranscriptional profiling meta-analysis of 309 cases, including ALCL and otherprimary T-NHL samples. Pathway discovery and prediction analyses defined aminimum set of genes capable of recognizing ALK(-) ALCL. Application ofquantitative RT-PCR in independent datasets from cryopreserved and formalin-fixedparaffin-embedded samples validated a 3-gene model (TNFRSF8, BATF3, and TMOD1)able to successfully separate ALK(-) ALCL from peripheral T-cell lymphoma nototherwise specified, with overall accuracy near 97%. In conclusion, our datajustify the possibility of translating quantitative RT-PCR protocols to routineclinical settings as a new approach to objectively dissect T-NHL and to selectmore appropriate therapeutic protocols

The accumulation of T cells and monocytes at sites of ongoing inflammation represents the earliest step in the series of events that lead to granuloma formation in sarcoidosis. In this study, we evaluated the pulmonary production of IFN-inducible protein 10 (IP-10), a CXC chemokine that stimulates the directional migration of activated T cells. Striking levels of IP-10 were demonstrated in the bronchoalveolar lavage (BAL) fluid of 24 patients with pulmonary sarcoidosis and lymphocytic alveolitis, as compared with patients with inactive disease or control subjects. A positive correlation was demonstrated between IP-10 levels and the number of sarcoid CD45R0+/CD4+ cells in the BAL. Immunochemistry, performed with an anti-human IP-10 polyclonal Ab in lymph nodes displaying prominent sarcoid granulomas, showed that cells bearing IP-10 were mainly epithelioid cells and CD68+ macrophages located inside granulomatous areas. Macrophages recovered from the BAL of sarcoid patients stained positive for IP-10 protein. Furthermore, alveolar macrophages isolated from sarcoid patients with T cell alveolitis and cultured for 24 h in presence of IFN-γ secreted definite levels of IP-10 capable of inducing T cell chemiotaxis. Interestingly, alveolar lymphocytes recovered from patients with active sarcoidosis were CD4+ T cells expressing Th1 cytokines (IL-2 and IFN-γ) and high levels of CXCR3. Taken together, these data suggest the potential role of IP-10 in regulating the migration and activation of T cells toward sites of sarcoid inflammatory process and the consequent granuloma formation.

The p63 gene has high homology with p53, but more complex physiologic functions, including the regulation of the maintenance of basal cells in stratified epithelia. These cells in fact express high levels of the DeltaN-terminal truncated isoforms of the p63 gene that can act as dominant-negative inhibiting the activity of p53. Basal cells in human bronchi and bronchioli seem to use the same strategy, since they constitutively express high levels of p63, at variance with alveolar pneumocytes. Over-expression of these isoforms in airway basal cells can inhibit important functions of the p53-pathway, including cell cycle arrest and apoptosis. This finding underlines the key role of p63 in epithelial renewal in human lung, with important implications in the understanding of the mechanisms of tissue remodelling occurring in diffuse lung diseases. Z8 0 ZR 0 ZS 0 ZB 10

We describe an emerging entity, recently recognized as a pitfall in the diagnostic practice among eosinophilic renal cell tumours.A 60-year-old male underwent enucleation of a 1.2 cm nodule. Immunohistochemistry and FISH analysis were performed.Histology revealed a neoplasm composed of large cells with eosinophilic cytoplasm, Fuhrman grade 3, arranged in papillae. At the immunohistochemical level, cells showed positivity for AMACR and CD10. Fluorescence in situ hybridization (FISH) demonstrated gains of chromosomes 7 and 17 and loss of Y. A diagnosis of oncocytic papillary renal cell carcinoma was made.The distinction between renal oncocytoma and oncocytic papillary renal cell carcinoma is of substantial importance because of their different behaviour and prognosis, since the latter has malignant potential. Although the available evidence supporting tumour enucleation as the surgical treatment for renal cortical tumoursor = 4 cm, due to aforementioned clinicopathological features such tumours need to be evaluated using appropriate immunophenotypical and cytogenetic analyses.

Immunological defence mechanisms of the lung are provided by several different types of immunocompetent cell. Among these, the most important are lymphocytes, alveolar macrophages and neutrophils. This review focuses mainly on the pattern of physiological activities of pulmonary lymphocytes in the local host defences. The article provides an overview of the events leading to the recruitment, homing and activity of lymphocytes in the lower respiratory tract. The pathways through which the pulmonary lymphoid system recognizes, destroys and contributes to removing potentially harmful inhaled antigenic materials are also briefly discussed. The final section of the article highlights the pathogenetic role envisaged for lymphoid cells in disease states, in the context of the known biology of these cells.

Renal cell neoplasms are a heterogeneous group of tumours in terms of pathological features and prognostic behaviour. The genetics of these tumours may aid in correct diagnosis and accurate assessment of prognosis. In ambiguous cases it may be necessary to utilise new markers that are capable of further discerning renal cell neoplasms. Fluorescence in situ hybridization (FISH) on formalin-fixed, paraffin-embedded tissue is an increasingly useful technique in the detection of many diagnostic chromosomal abnormalities, among which chromosomes 1, 2, 3p, 6, 7, 10, 17 and Y are the most common. The addition of FISH to histological evaluation improves the diagnostic accuracy of core biopsies from renal masses, which may have an important impact in clinical management of many cases due to newer therapeutic approaches, including cryo- or radiofrequency ablation, nephron-sparing surgeries and target therapies.

At present, no studies have evaluated the role of bronchoscopic transbronchial lung biopsy (TBLB) in the diagnosis of diffuse drug-induced lung disease (DILD), and there is no consensus for a definite diagnostic workup approach for this rare clinical entity. The aim of the present study was to evaluate the clinical usefulness of TBLB in diffuse DILD. This study was a retrospective analysis of patients with diffuse DILD, who underwent bronchoscopy. The role of TBLB was assessed to determine whether the histological results are useful for the final diagnosis. Over a 5-yr period, 44 patients underwent bronchoscopy, and all had a bronchoalveolar lavage (BAL). Thirty-three of the 44 patients underwent TBLB (75%), and the results of TBLB were diagnostically helpful in 25 (75.7%) of the procedures. No histopathologic abnormality was identified in 6 (18%) of the 33 patients. In 2 patients (6%) the obtained samples were not adequate, since no lung parenchyma was obtained. No severe complications related to bronchoscopic procedures occurred. In conclusion, TBLB is a safe procedure, and is diagnostically helpful in the majority of cases of patients with diffuse DILD. Histological data obtained by TBLB further corroborate clinical, laboratory, radiologic and BAL results for a definitive diagnosis of diffuse DILD.

EBV-latent membrane protein-1 (LMP-1) is often expressed in Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin's lymphoma (cHL), but its clinical significance is controversial. We correlated LMP-1 with presenting features, including serum interleukin 10 levels and clinical outcome.Patients were eligible if they had biopsy-proven cHL, were untreated, HIV-1 negative, and had available archival tissue. LMP-1 expression was determined by immunohistochemistry.We identified 577 patients with cHL with a median age of 30 years, 55% of whom were male. LMP-1 was expressed in HRS cells of 124 patients (21%) and was detected in 78 of 461 (17%) patients with nodular sclerosis compared with 44 of 112 (39%) with mixed cellularity (P0.001 by Fisher's exact test). Patients with tumors with LMP-1-positive HRS cells had higher serum interleukin 10 levels (P = 0.009 by Mann-Whitney test). For the 303 patients treated with doxorubicin, bleomycin, vinblastine, and dacarbazine or equivalent regimens, the 5-year failure-free survival (FFS) for those with LMP-1-positive tumors was 74% compared with 81% for those with LMP-1-negative tumors (P = 0.23, by log-rank test). Overall survival (OS) at 5 years for patients with LMP-1-positive tumors was 90 versus 91% for patients with LMP-1-negative tumors (P = 0.8 by log-rank test). Expression of LMP-1 was not associated with different FFS and OS in patients treated with other regimens or with radiotherapy alone.LMP-1 was expressed by HRS cells in 21% of cHL and correlated with mixed cellularity type and higher serum interleukin 10 levels. The presence of LMP-1 was not associated with FFS or OS in uniformly treated patients.

Epstein-Barr virus (EBV) infection in infectious mononucleosis (IM) is associated with lymphocyte activation leading to the expansion of cells expressing activation-associated antigens. Most of these antigens are released as soluble molecules in vitro and in vivo.We investigated the serum levels of the soluble forms of the CD8 (sCD8), p55-IL-2R alpha (sIL-2R alpha), and CD30 (sCD30) molecules in 55 patients following primary EBV infection. These data were compared with the phenotypic pattern of circulating lymphoid subsets.In all cases at presentation, lymphocytosis, mainly characterized by the expansion of a CD8+, HLA-DR+, p75-IL-2R beta+, p55-IL-2R alpha- population, was associated with high levels of the investigated soluble molecules. Their mean values (+/- SD) were: 17,172 +/- 12,885 U/mL for sCD8 (vs 334 +/- 95 in controls), 2,922 +/- 2,813 U/mL for sIL-2R alpha (vs 331 +/- 115 in controls), and 477 +/- 451 U/mL for sCD30 (vs 4.9 +/- 6.4 in controls). Follow-up study (15 cases, up to 60 days) showed a progressive decline of all soluble molecules, associated with a reduction of activated CD8+/HLA-DR+/p75-IL-2R beta+ T-cells. By the 30th day, values of sIL-2R alpha and sCD30 (729 +/- 333 U/mL and 20 +/- 21 U/mL, respectively) were only slightly higher than in normal controls, whereas sCD8 levels remained consistently higher (1,777 +/- 1,385 U/mL, p.001).sCD8, sIL-2Ra and sCD30 serum levels in IM reflect the total bulk and/or the activation-related events of infected and reactive cells. The variations in these soluble molecules during the follow-up provide useful information on the in vivo biological modifications occurring after EBV infection.

Tenascin is a major extracellular matrix glycoprotein that can interfere with the action of fibronectin by inhibiting cell adhesion and spreading. Although tenascin is able to exert important immunomodulatory activities on T and B cells and macrophages, little is known about its distribution in different lymphohemopoietic tissues. In this study we have analyzed tenascin immunoreactivity on cryostat and paraffin sections of normal and pathological lymphoid tissues using two different monoclonal antibodies. We demonstrated strong tenascin expression in all peripheral lymphoid tissues, whereas it was barely detectable in the thymus and in bone marrow. In reactive lymph nodes, tenascin was mainly found in T-dependent zones, forming a variably close-woven reticular network corresponding to fibroblastic reticulum cells and blood vessels basal laminae, showing a partial co-localization with fibronectin. In B-dependent zones, tenascin was restricted to blood vessels. Using double-marker analysis, we performed a thorough study comparing tenascin expression in different compartments of lymphoid microenvironments. Tenascin network appeared much thicker in chronically stimulated tissues, where CD4+ lymphocytes with "memory" phenotype (CD45RO+/CD45RA-) were predominant, and at sites of ongoing inflammation. In particular, a striking increase of tenascin was observed in sarcoid lymph node, as well as in myasthenic hyperplastic thymuses. In addition, tenascin can be abnormally synthesized in tissue involved by various types of lymphomas, including Hodgkin's disease and hairy cell leukemia.

In this study 27 transbronchial biopsy specimens obtained from patients with clinical and/or laboratory features suggestive for sarcoidosis were analysed with conventional morphology and immunohistochemistry comparing the sensitivity and reproducibility of the two methods. A limited panel of monoclonal antibodies recognizing epitopes resistant to conventional fixation and embedment procedures were used (CD45R0, CD68, anti-cheratin, anti-collagen IV). All specimens were independently observed by two different pathologists. On the basis of the recognition of bona-fide noncaseating granulomas, 9 cases were uniformly judged as positive, 10 cases as negative, but 8 cases were considered doubtful. Immunohistochemical analysis reliably demonstrated the presence of epithelioid cells in 3 of these cases and absence in 5. These data suggest that the use of a limited immunohistochemical analysis can significantly improve histological diagnosis of sarcoidosis on small transbronchial biopsies using conventional routine material.

Cells recovered from bronchoalveolar lavage (BAL) and tissue sections from transbronchial lung biopsies were studied in 16 patients with symptomatic hypersensitivity pneumonitis (HP) and in six subjects with a similar history of exposure but without features of disease by using a series of monoclonal antibodies (MoAb) detecting different lymphocyte subpopulations, including T and T subsets, B lymphocytes, and natural killer (NK) cells. Their functional activities in cytotoxic and suppressor assays and the microenvironment in the lung by using immunohistological techniques were also evaluated. It has been demonstrated that the majority of cells recovered from BAL of HP patients are represented by T8 lymphocytes, with a relevant imbalance of the T4/T8 ratio (p less than 0.001). HNK-1+ cells were markedly increased (p less than 0.001), whereas the frequency of cells bearing other NK-related markers (NK-15, VEP 13, Ab8.28, T10, M1, and Fc gamma R) were not significantly increased with respect to controls. Immunohistological study confirmed that the majority of cells infiltrating lung parenchyma are T8+ lymphocytes. The number of HNK-1+ cells detected on lung biopsies was very low in all cases, even in patients with the highest values on BAL suspensions. The evidence of cells bearing the proliferation-associated markers (Tac and T9 antigens) seems to support the hypothesis of a local proliferation in the lung. In terms of phenotypic analysis, the results observed in the group of asymptomatic individuals are qualitatively superimposable on those observed in the HP group, but the magnitude of the phenomenon is less prominent and therefore the data are not as statistically significant as that produced by the comparison between HP patients and the same controls. Functional analysis of BAL T cells from both HP patients and asymptomatic individuals showed suppressor activity in vitro, as determined by the ability to influence a pokeweed mitogen (PWM)-driven B cell differentiation assay. BAL cells from HP patients were also able to display a definite cytotoxic function in vitro, whereas BAL lymphocytes from asymptomatic subjects did not. Taken together, these data demonstrated that cells responsible for the alveolitis in patients with HP are characterized by the expansion of T cells with the phenotype and functions of both suppressor and/or cytotoxic lymphocytes. This expansion is likely to be related to a local immunologic response to the antigenic stimulus and may provide new insights into the pathogenetic mechanisms of this disease, its pathological pattern, and its management.

The lung is prone to develop various complications in patients with hematological disorders due to its structural and functional properties. Genetic predisposition, although probably involved, is not yet well understood. The secondary involvement of lung parenchyma by a lymphoproliferative malignancy is not an unusual event. Furthermore, the advances in treatment options such as hematopoietic stem cell transplantation, radiation therapy, newer polychemotherapeutic regimens even including the most recent drugs, have significantly widened the spectrum of non-neoplastic complications that can rise up in these patients. Infections, drug/radiation-induced toxicity, and graft versus host disease account by now for most pulmonary problems in hematologic patients and represent a diagnostic challenge for the clinician. A specific diagnosis is, however, important for prompt initiation of the correct therapy. High resolution computed tomography followed by bronchoalveolar lavage and/or transbronchial lung biopsy have proved to be the most helpful diagnostic tools within the multidisciplinary approach to these disorders. The aim of this review is to highlight the clinico-pathologic spectrum of lung diseases which can occur in the setting of hematologic neoplasms, pointing up the clinical approach with the different diagnostic tools avaible. Pulmonary amyloidosis and lung complications in hemoglobinopathies, erythrocyte and coagulation disorders will not be examinated.

To determine whether bronchoalveolar lavage reflects the histologic aspects of the lung histology in patients with sarcoidosis and hypersensitivity pneumonitis, cells recovered from lavage fluid were compared with tissue sections from transbronchial lung biopsies in 33 patients. The evaluation of cellular types and their topographic distribution in situ was determined by using monoclonal antibodies in combination with immunohistochemical techniques. Cell counts in bronchoalveolar lavage and lung biopsies were significantly correlated both in sarcoidosis and hypersensitivity pneumonitis. In fact, the relative proportions of inflammatory and immunocompetent cells recovered from lavage fluid accurately overlapped those observed in lung tissue sections. However, in patients with more pronounced alveolitis, the frequency of macrophages in tissue sections was higher than that observed in the bronchoalveolar lavage, and the degree of lymphocytes in the lavage was higher than that observed in the corresponding biopsy. Specifically, in these patients the lavage underestimated the amount of macrophages in the lung biopsies and overestimated the number of lymphocytes that were present in the lung parenchyma. This was more evident in patients with hypersensitivity pneumonitis, where the intensity of alveolitis was higher than in sarcoidosis. Our data support the idea that, at least in patients with sarcoidosis and hypersensitivity pneumonitis, bronchoalveolar lavage correctly samples the alveolitis. Discrepancies in patients with very high intensity alveolitis could be due to a more pronounced recirculation of lymphocytes from the parenchyma to the alveolar spaces.

High levels of soluble IL-2 receptor (sIL-2R) are detectable in the serum of HCL patients. To determine the cell source of this molecule, we evaluated the presence of sIL-2R in the supernatants obtained from in vitro cultures of leukemic (hairy cell, HC) and non-leukemic lymphocytes from six untreated HCL patients and from an additional four patients under therapy with rIFN-alpha 2. We demonstrated that cultured HCs at resting conditions were able to spontaneously release the sIL-2R, whereas control enriched B cells did not. This phenomenon was present only when culturing HCs recovered from patients observed at the time of diagnosis but was not observed during treatment with rIFN-alpha 2. Following activation in vitro with a series of different stimulatory agents including BCGF, phorbol myristate acetate, and anti-human IgM antibody, cultured HCs increased their capability to shed the IL-2R molecules. On the other hand, the release of sIL-2R from enriched T cell populations from HCL patients did not significantly differ from the value obtained in controls. Taken together, these findings provide evidence that leukemic B cells represent the main source of sIL-2R in HCL patients and further emphasize the importance of evaluating this parameter as a relevant marker for monitoring the effectiveness of rIFN-alpha 2 therapy.

To elucidate the mechanisms of alpha-interferon's (alpha-INF) therapeutic effect on clinical and laboratory findings in hairy cell leukemia, we sequentially monitored different immunologic parameters in three patients treated with recombinant alpha-INF. The most evident effect of this treatment on the immune system was the recovery of natural killer (NK) cell in vitro activity of peripheral blood lymphocytes, which was severely impaired before therapy. In particular, NK function began to improve after 3 months, and a complete recovery was obtained after 6 months in all cases. This increase parallels the improvement in clinical and laboratory findings.

A case of angiofollicular lymph node hyperplasia (Castleman's disease) characterized by nionotypic (1gG + , 1arnbda-t) plasrnacytosis is described. I'resh tissue was available and a thorough iiiiunohistocheniical analysis of lymphoid and noiilyniphoid cells was performed on cryostat sections. Although lyrnphoid follicles were nurnerous and exhibited sonie abnormal features they did not appear part of the nionocloiial cell proliferatiun. Follicular lymphocytes were niixtures of Kappai and 1arnbda-t cells. Vessels penetrating within these abnormal follicles expressed reduced levels of FVlll and Leu-M5 antigens and exhibited thicker layer oí collagen type IV. The analysis of T-cell subsets showed a normal (3:l) T4/T8 ratio. This case extends to the mixed variant of hyaline-vascular Castleman's disease, the neoplastic potential previously associated to the plasrria cell variant of the disease.

Context.Lymphangioleiomyomatosis (LAM) is a cystic lung disease that can be included in the wide group of proliferative lesions named PEComas (perivascular epithelioid cell tumors). These proliferative tumors are characterized by the coexpression of myogenic and melanogenesis-related markers. In all these lesions, genetic alterations related to the tuberous sclerosis complex (TSC) have been demonstrated. Striking improvements in the understanding of the genetic basis of this autosomal dominant genetic disease are coupled to the understanding of the mechanisms that link the loss of TSC1 (9q34) or TSC2 (16p13.3) genes with the regulation of the Rheb/m-TOR/p70S6K pathway. These data have opened a new era in the comprehension of the pathogenesis of LAM and have also suggested new therapeutic strategies for this potentially lethal disease.Objective.To present and discuss the pathologic and molecular features of LAM within the spectrum of PEComas, providing a rational approach to their diagnosis.Data Sources.The published literature and personal experience.Conclusions.The inclusion of LAM within the PEComa category is supported by a variety of biologic data and can significantly help in providing a comprehensive view of this interesting and clinically relevant group of lesions. The demonstration of molecular alterations of the mTOR pathway in LAM and other PEComas represents a rational basis for innovative therapeutic approaches with inhibitors of mTOR signaling.

The serum levels of a soluble form of the interleukin-2 receptor (sIL-2R) were investigated in 92 patients with human immunodeficiency virus (HIV) infection, ranging from asymptomatic cases to full-blown AIDS. Increased values were found in 69.5% of cases. The overall mean was significantly higher (p less than 0.001) in HIV-infected patients (mean +/- SD = 709.3 +/- 369.4 U/ml) than in the seronegative risk group controls (383.9 +/- 140.5) and normal controls (256.4 +/- 114.5). No major differences were found among the patient groups (asymptomatic infection, persistent generalized lymphadenopathy, symptomatic infection, and full-blown AIDS). These data suggest that the measurement of serum sIL-2R levels may represent a useful biological tool for evaluating T-cell activation phenomena occurring in HIV infection. Since the soluble interleukin-2 receptor maintains the capacity of binding interleukin-2, the increased levels found in HIV infection may play a contributory role towards the in vitro and in vivo impairment of a number of interleukin-2-dependent functions described in this disease. On clinical grounds, the excess of sIL-2R could help to explain the lack of therapeutic effect and little immunological variations following the in vivo administration of interleukin-2.

Signet-ring cell ependymoma is a rare variant of ependymoma with only seven cases described in literature. Biological behavior and prognosis of this entity are not well-known until now. We present a case of a 49-year-old female with a history of headache and gait instability. Magnetic resonance imaging showed an upper cervical tumor with cystic component and mural nodule. The patient underwent surgery. Microscopically some cells displayed an eccentric nucleus compressed to the periphery by vacuolated cytoplasm. Perivascular pseudorosettes and ependymal rosettes were seen only focally. The cells were positive for glial fibrillary acidic protein and epithelial membrane antigen. The diagnosis was ependymoma with diffuse signet-ring features, grade II according to the World Health Organization. It may be difficult to diagnose this unusual variant of ependymoma especially on small biopsies or frozen sections. A complete examination of the specimen is recommended with immunohistochemical confirmation to rule out potential morphologic mimics, such as metastatic adenocarcinomas and gliomas in the differential diagnosis.

The homeodomain-containing transcription factor pancreatic duodenal homeobox 1 (PDX-1) plays a key role in pancreatic development and β-cell function. It is a major regulator of transcription in pancreatic cells, and transactivates the insulin gene by binding to a specific DNA motif in its promoter region. Glucose also regulates insulin gene transcription through PDX-1. It has been shown that PDX-1 is required for maintaining pancreatic islet functions by activating gene expression and has a dual role in pancreatic development. It initially contributes to pancreatic formation during embryogenesis and subsequently regulates the pancreatic islet cell physiology in mature islet cells. Because of this key role in the embryologic development of the pancreas, PDX-1 expression has been investigated in pancreatic cancer cell lines and human tumors. Moreover, a few reports have described expression of PDX-1 in other human neoplasms and have investigated its potential role in differential diagnosis, but data on normal human tissues are lacking. Understanding the molecular mechanisms of pancreas formation, and especially the function of PDX-1, may contribute to the improved treatment and prevention of debilitating diseases such as diabetes, insulinomas and pancreatic carcinomas. Nevertheless, further studies are needed concerning its possible application in routine practice.

Eight cases of human thymoma have been analyzed on cryostat sections with the monoclonal antibody Ki67, which reacts with cells in the proliferative phases of the cell cycle. The aim was to assess the proportion of proliferating thymocytes among lymphoid cells in the thymoma samples. In all cases a large number of cells (mean, 58.75%; range, 35-80%), recognized as thymocytes by morphology and lack of cytokeratin expression in a combined immunohistochemical assay, exhibited nuclear Ki67 staining. These findings differ from the reactivity pattern observed in age-matched nonneoplastic thymuses where lower growth activity of cortical thymocytes was observed (15-20% Ki67+ cells). Intensive thymocyte proliferation in thymomas may represent one of the factors which lead to autoimmunity in myasthenia gravis and thymomas.