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Here we present the case of a patient with diagnosis of chronic lymphocytic leukaemia (CLL) on routine protocol biopsy 3 months following kidney transplantation. Genetic analysis confirmed the origin of the malignancy, being the recipient. Differential diagnosis with post-transplant lymphoproliferative disorder (PTLD) is extremely important in order to avoid unnecessary devastating treatment. This case is challenging, both in terms of making the correct diagnosis and in terms of optimal treatment. The case underscores that it is extremely important to distinguish between a pre-existing lymphoma diagnosis after transplantation and a true PTLD as the treatment options of both are very divergent.

Analysis of non-Hodgkin lymphoma (NHL) involvement of bone marrow trephine biopsy specimens by morphologic features and immunohistochemistry is often difficult, and the criteria for involvement are ill defined. We compared the morphologic and immunohistochemical analysis of B-cell NHL involvement with immunoglobulin heavy chain gene (IgH) rearrangement analysis by polymerase chain reaction (PCR) amplification of the complementarity determining region 3 (CDR3) in bone marrow biopsy specimens from patients with mantle cell lymphoma (n = 53) or hairy cell leukemia (n = 71). By combing morphologic features and phenotype, 54 specimens were considered positive, 62 negative, and 8 inconclusive. PCR analysis showed clonal IgH rearrangements in 46 positive and 6 inconclusive specimens. No clonal IgH rearrangements were present in 61 negative specimens. The 1 false-positive and most false-negative PCR results were likely due to sampling error or DNA degradation of the fixed tissues. In most cases, bone marrow involvement by NHL can be identified by histologic and immunohistochemical examination. Furthermore, clonality of the B-cell population can be detected by amplification of the IgH CDR3 on DNA extracted from bone marrow trephine biopsy sections, which can be helpful in cases diagnosed as inconclusive.

Representational difference analysis (RDA) is a differential hybridization method which can effectively isolate unique DNA sequences from complex and highly related genomes or cDNA libraries. A major drawback of the RDA analysis is the requirement for pure driver and relatively pure tester samples, ruling out the analysis of whole tissue biopsies. To circumvent this problem, we have modified the technique for the analysis of very small quantities of DNA so that pure cell populations isolated by micromanipulation from tissue sections can be analyzed. Using this modified technique, as few as 50 diploid cells ( approximately 500 pg of DNA) can be analyzed.

Epithelium-lining macrophages are spindle-shaped cells which line the epidermis and hair follicles. We studied the distribution and phenotype of this hitherto neglected member of the dermal monocyte/macrophage system in 25 lesional psoriatic, and five normal skin biopsies. Epithelium-lining macrophages were inconspicuous in normal skin, whereas their number was increased in almost two-thirds of psoriatic cases; in nine out of 25 lesional skin biopsies, these flattened cells formed an almost continuous single-cell row at the dermo-epidermal junction. Immunophenotyping revealed that these cells expressed the leucocyte common antigen CD45, and the macrophage markers CD14, CD36 and CD4, but not CD11b. Epithelium-lining macrophages strongly expressed HLA-DR-antigens and CD11a, but lacked the Langerhans cell marker CD1, and CD34. The dermal dendrocyte marker factor XIIIa was expressed in only a minority of these cells. It is concluded that epithelium-lining macrophages represent a separate subset of dermal monocytes/macrophages with a distinct tissue localization and immunophenotype. Their restricted distribution and close association with the epidermis may suggest a role in the regulation of epidermal growth. Alternatively, the expression of several immune-associated molecules may indicate that epithelium-lining macrophages are involved in the antigen-dependent or -independent activation of T cells.

The present study reports a rare case of systemic M. scrofulaceum infection in an AIDS patient and analyses the inflammatory infiltrate in a lymph node by immunohistochemistry. Special emphasis is put on the histiocytes. The diffuse infiltrate consists mainly of large histiocytes that contain numerous bacilli. These cells display the phenotype of mature histiocytes and in addition coexpress the antigens recognized by RFD7 and RFD9, both markers of different subsets of histiocytes which have been reported to be co-expressed by the infected histiocytes in the infiltrate of lepromatous lepra. Interdigitating reticulum cells are rare as well as T cells which are mainly of the suppressor/cytotoxic type. These findings are similar to those reported for lepromatous lepra and might indicate common deficiencies in T cell-macrophage interactions in both conditions. Superimposed on the diffuse infiltrate of large histiocytes we observed 'monocytic granulomas', the presence of which might be related to a reactional state comparable to erythema nodosum leprosum, a reactional state of lepromatous lepra.

The histological features of biopsies from 18 previously unreported cases of Sweet's syndrome are reported. The dermal infiltrate in the majority of the cases contained numerous histiocytes that at first sight appeared to mimic neutrophils. The immunophenotype of these histiocytes was consistent with monocytes that have freshly infiltrated into the lesions. Only two of the cases in this series, associated with leukaemia, displayed the histological features of Sweet's syndrome with a predominant neutrophilic infiltration. We suggest that the initiating mechanisms in Sweet's syndrome are that monocyte/histiocyte-derived cytokines such as the interleukins IL-1 and IL-8, secreted either by infiltrating histiocytes in the non-leukaemia-associated cases of Sweet's syndrome or by tumoural myelomonocytic cells in those associated with leukaemia, are responsible for the systemic manifestations and the infiltration with neutrophils in the skin lesions.

MRP14 and MRP8 are well-characterized calcium-binding proteins present in myeloid cells and mononuclear phagocytes. These antigens can easily be visualized in paraffin-embedded tissue, making use of monospecific polyclonal antibodies. This study evaluates MRP14 and MRP8 expression in mononuclear phagocytes in various granulomatous conditions. MRP14 is strongly expressed in all granulomatous conditions. MRP8 is variably expressed. Mononuclear phagocytes in granulomas of foreign body type, cat-scratch disease and erythema nodosum strongly express MRP8. In contrast, MRP8 expression is weak or absent in mononuclear phagocytes of sarcoidosis and tuberculosis. These results show differences in immunophenotype between non-phagocytic mononuclear phagocytes in delayed hypersensitivity type granulomas and phagocytic mononuclear phagocytes in non-hypersensitivity and non-immunological granulomas.

Three cases of Kikuchi's lymphadenitis were studied immunohistochemically on paraffin-embedded material in order to compare the plasmacytoid monocyte aggregates occurring in this disorder with plasmacytoid monocyte clusters in nonspecific reactive lymphadenitis. One of the cases was also analyzed on frozen material. In Kikuchi's lymphadenitis, plasmacytoid monocytes expressed the CD38 and LN1 antigens in addition to their monocyte/macrophage antigens found in nonspecific reactive lymph nodes. These plasmacytoid monocyte aggregates contained large numbers of Mac387+ lysozyme+ macrophages, scattered HLADR+ dendritic cells, and high numbers of CD8+ T-lymphocytes. Collections of T-immunoblasts or areas of necrosis were observed within these aggregates. The authors speculate that the histologic feature of Kikuchi's lymphadenitis is the morphologic substrate of a T-cell-mediated cytotoxic immune reaction occurring in plasmacytoid monocyte aggregates and resulting in plasmacytoid monocyte damage and necrosis.

In a previous paper from this laboratory, the production of monoclonal antibodies recognizing antigenic determinants common to the alpha and beta chains of bovine brain S-100 protein was reported. In the present study, the immunohistochemical labeling patterns of these monoclonal antibodies against a wide range of normal and pathologic human tissues are described, and these results are compared with those obtained using polyclonal anti-S-100 antiserum. Although many of the reactions of the monoclonal antibodies were very similar to those of the polyclonal antiserum (and the previously reported sites of S-100 immunoreactivity) several additional cell types (e.g., thyroid follicular cells, biliary epithelium, pancreatic cells, renal tubules) were labeled by one or both of the monoclonal antibodies. Blocking experiments prove that immunohistochemical differences obtained with monoclonal and polyclonal antibodies are at least partly caused by differences in the repertoire of antigenic determinants on S-100 protein that are recognized by the two species (i.e., mouse and rabbit, respectively). These results indicate that S-100 may be more widespread in human tissues than previously thought, and that its value as a marker of the histogenetic origin of human tumors should be reappraised. It is suggested that the marked variability observed in the reactivity of different tissues in the present study may indicate that S-100 is a heterogeneous group of molecules, and its expression may be related to the functional activity of cells.

The presence and localization of the marginal zone (MZ) in the human lymph node is controversial. The authors analyzed the distribution of sIgM+sIgD- MZ lymphocytes (MZL) expressing alkaline phosphatase (ALP) activity in a series of reactive lymph nodes and spleens with the use of immuno- and enzymehistochemistry, and a combination of both technics. MZL were found scattered in lymphocytic coronas composed of densely packed, small, round lymphocytes. In the lymphocytic coronas showing prominent zonal layering into an inner, densely packed rim and outer, loosely arranged rim, the latter area proved to be composed of sIgM+sIgD-ALP+ MZL, in contrast to the inner rim, which was composed of sIgM+sIgD+ALP- small, round lymphocytes. It is concluded that the human reactive lymph node, like the spleen, contains MZL. These MZL apparently belong to a dynamic B-cell compartment, the morphologic expression of which may vary from scattered singular cells hidden in the lymphocytic corona to a clearly recognizable peripheral rim of medium-sized lymphoid cells.

A series of monoclonal and polyclonal antibodies was used to determine the distribution of lymphocyte subsets in frozen tissue sections of a case of angiofollicular lymph node hyperplasia (ALNH), intermediate type. Primary follicles and mantle zones of secondary follicles consisted of BA1+OKIa1+-C3RTo5+sIgM+sIgD+ lymphocytes. Poorly developed follicular centers reacted with OKIa1, C3RTo5, DRC-1 and anti-IgM but contained no OKT4+Leu-3a+ or Leu-7+ cells. Mantle zones and primary follicles contained more OKT4+Leu-3a+ and less OKT8+ cells than normally observed. The interfollicular area consisted mainly of OKT4+Leu-3a+OKIa1- helper/inducer T-cells, admixed with some OKT8+ suppressor/cytotoxic T-cells and OKIa1+ interdigitating reticulum cells. Polyclonal plasma cells were found both in follicular centers and interfollicular areas. Based on the analogy to the peripheral lymphoid tissue in nude mice and in children with variable thymic dysfunction, it is suggested that the abnormal distribution of immunoregulatory T-cells may be of pathogenetic significance and may account for the morphology of the lymphoid follicles in ALNH.

Nuclear particles, morphologically similar to those seen in hepatocytes during non-A, non-B (NANB) hepatitis, were detected in several types of nonparenchymal cells in 10 human liver-biopsy specimens, including cases of hepatitis A and B and nonviral hepatic disease. They were also found in nonparenchymal cells of the liver in two of four normal chimpanzees and in two of four chimpanzees during experimental NANB viral hepatitis. In nonparenchymal cells the particles formed loose-to-intermediate aggregates, similar to those first described in hepatocytes during NANB hepatitis. Tightly packed aggregates, the predominant pattern in hepatocytes, were generally missing. The high prevalence of morphologically identical particles in various liver diseases and their presence in healthy livers, both in hepatocytes and in nonparenchymal cells not presumed to support the growth of hepatitis viruses, speak against their specificity for NANB hepatitis viruses. It is proposed that the particles represent a newly recognized and widespread cellular feature, of as yet unknown function.

Using an in situ immunohistochemical technic and a panel of monoclonal antibodies directed to lymphocytes, dendritic reticulum cells, HLA-DR antigen and killer/natural killer cells, the cellular composition of progressively transformed follicular centers (PTFCs) was analyzed. PTFCs are large lymphoid aggregates, composed of BA1+B1+sIgM+sIgD+ small B-lymphocytes, admixed with randomly arranged OKT4+Leu-3a+ helper/inducer T-cells and Leu-7+ cells. Small islands of B1+BA1-sIgD- follicular center cells are present in the central part of PTFCs, but fail to form a true follicular center. DRC1+ dendritic reticulum cells are arranged abnormally, forming small, separate clusters or a loosely arranged network lacking the typical concentric pattern. Moreover, dendritic reticulum cells have less extensively developed cytoplasmic extensions and are devoid of surface-bound immunoglobulins. Based on these findings, it is suggested that blastic transformation of B-cells in PTFCs is incomplete. The occurrence of PTFCs among numerous well-formed, secondary lymphoid follicles, and their exclusive association with exaggerated follicle formation speaks against an intrinsic inability of dendritic reticulum cells to bind antigen-antibody complexes, but rather suggests that PTFCs represent early, transient stages in the transformation of primary into secondary lymphoid follicles.