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Biomedical subjects

E Scheffer

Publications and source records attributed to E Scheffer.

At least 37 records · Page 2Linked to original sources

Prognostic significance of CD30 (Ki-1/Ber-H2) expression in primary cutaneous large-cell lymphomas of T-cell origin. A clinicopathologic and immunohistochemical study in 20 patients.

The histologic and immunophenotypical features of 20 primary cutaneous large-cell lymphomas of T-cell origin were investigated and correlated with clinical data to obtain prognostically relevant criteria. Histologic evaluation, using the updated Kiel classification, showed that these large-cell lymphomas represent a morphologic spectrum, often making classification rather arbitrary. It is therefore concluded that the clinical relevance of histologic subtyping is limited for this group of lymphomas. Immunophenotypical studies revealed significant differences between CD30-positive and CD30-negative lymphomas. CD30-positive lymphomas generally presented with localized skin disease, and had a favorable prognosis (9 of 10 patients alive and in complete remission; median survival, 37 months). In contrast, CD30-negative lymphomas often presented with or rapidly developed generalized disease; all patients died of lymphoma (median survival, 17 months). These findings suggest that CD30 expression is an important prognostic parameter for this group of primary cutaneous large-cell lymphomas.

Antigens, CD↗

Melanocytic atypia in dysplastic nevi. Immunohistochemical and cytophotometrical analysis.

In a double-blind study a correlation was found between the histologically assessed degree of nevomelanocytic atypia in 58 dysplastic nevi (DN) and the presence of two markers associated with malignant transformation. The markers included a marked expression of histocompatibility locus Class I antigens on nevomelanocytes (P less than 0.01) and abnormalities in the nuclear DNA content as measured by DNA cytophotometry (P = 0.01). Both markers were present in most of the markedly atypical DN, in about half of the moderately atypical DN, and in less than 30% of the mildly atypical DN. These findings suggest that a DN with marked or moderate melanocytic atypia indicates a premalignant condition and identifies a patient at risk for melanoma.

Antigens, Neoplasm↗

Drug-induced pseudolymphomatous skin reactions.

We present two patients with generalized and three with localized skin eruptions due to various non-anticonvulsant drugs, with a histological picture of a pseudolymphoma of the skin. Cessation of the causative drugs resulted in disappearance of the lesions in all cases.

Adult↗

The efficacy of histopathological criteria required for diagnosing dysplastic naevi.

The efficacy of specific histopathological features for diagnosing dysplastic naevi was established by comparing their frequency in 62 dysplastic naevi, from 36 patients with the dysplastic naevus syndrome, with those in 326 ostensibly benign naevocellular naevi derived from a group of 67 autopsy cases. Individual diagnostic features had a low sensitivity, a low specificity or low predictive values. Discriminant analysis showed that the presence of dust-like melanin, irregular naevoid nests, markedly increased junctional activity and melanocytic nuclei equal or larger in size than overlying keratinocyte nuclei were the most discriminating features. Using two or more of these criteria plus a lymphocytic infiltrate as an obligatory diagnostic criterion, a reasonable efficacy could be reached for dysplastic naevi. Based on these combinations of criteria the prevalence of histologically proven dysplastic naevi in the autopsy group would be 10%. Lesions with all these four discriminating features were found in half of the patients from the dysplastic naevus syndrome group, but were absent in the autopsy group. We suggest that such severely atypical dysplastic naevi may be indicative of patients at high risk for developing malignant melanoma.

Adolescent↗

The course of Legionella pneumonia in guinea pigs after inhalation of various quantities of L. pneumophila.

The course of legionella pneumonia in guinea pigs after infection with various quantities of virulent L. pneumophila serogroup 1 organisms by aerosol exposure was investigated. The clinical course, histopathological characteristics, manifestations in the lungs and clearance of the legionella organisms from the lungs and spleen were followed. Four groups were exposed to 4.3 X 10(4), 4.7 X 10(5), 5.0 X 10(6) and 1.0 X 10(8) aerosolized legionellae, respectively. The most striking clinical symptoms were fever and weight loss, which were found in 67-94% and 33-100% of the animals, depending on the dose of L. pneumophila organisms administered. Spontaneous death occurred only in animals receiving the highest dose and always within 10 days. All animals exhibited exponential growth of legionella organisms in the lungs. Maximal growth occurred 5 to 7 days after exposure and varied from 9.3 X 10(7) to 7.4 X 10(8) organisms/both lungs. Twenty-two days after exposure, legionellae could still be cultured from lung tissue. Between 2 and 7 days after exposure, the spleen cultures were positive for legionellae in 41% of the animals receiving the lowest dose and in 83% of all other animals; legionellae could no longer be cultured from spleen tissue after day 7. Depending on the dose, peripherally localized areas of bronchopneumonia increased in size with time, tending to become confluent lobar pneumonia. The microscopic changes were not related to the number of inhaled organisms. In the cellular infiltrate, PMN predominated until day 7 and macrophages thereafter. Seroconversion was found in all animals that survived greater than 7 days. The present animal model closely mimics the course of events in human legionella pneumonia, thus enabling us to further study the factors involved in host resistance against legionella as well as the efficacy of various antimicrobial agents in normal and immunosuppressed animals.

Animals↗

Primary cutaneous large cell lymphomas of follicular center cell origin. A clinical follow-up study of nineteen patients.

In this study the clinical characteristics and follow-up data of nineteen patients with a diffuse large cell lymphoma of follicular center cell (B cell) origin, with only skin lesions at presentation, are reported. Sixteen of nineteen patients came to us with localized nodules or tumors, preferentially on the trunk, scalp, and lower legs. Remarkably, eight of eleven patients with disease confined to a limited area on the trunk had a history of slowly progressive papular lesions that had been present for 1 to 20 years prior to the development of rapidly growing skin tumors. Initial treatment, generally radiotherapy and/or polychemotherapy, resulted in complete remissions in seventeen of nineteen patients. Only three patients developed extracutaneous disease, whereas two other patients had recurrent disease in the skin at sites distant from the original skin lesions. Excluding three patients who had just finished initial treatment at the time of writing, twelve of sixteen patients were currently alive and in complete remission with a median survival of 44 months. Four patients died, three of whom were elderly women who had skin tumors on the lower legs when first seen. These results suggest that patients with a primary cutaneous large cell lymphoma of follicular center cell origin with disease confined to the trunk of scalp have a very favorable prognosis.

Adult↗

Diffuse large cell lymphomas of follicular center cell origin presenting in the skin. A clinicopathologic and immunologic study of 16 patients.

This report describes the clinical, histologic, and immunologic characteristics of 16 diffuse large cell lymphomas of follicular center cell origin with only skin lesions at presentation. These patients presented with nodular and tumorous skin lesions, which in 10 of 16 cases were confined to a circumscribed area on the trunk. Four patients, all elderly women, presented with skin tumors on the lower legs. Histologically, these 16 lymphomas showed nonepidermotropic diffuse dermal infiltrates, mainly consisting of large follicular center cells, with a variable admixture of small cleaved cells, immunoblasts, T-lymphocytes, and macrophages. The relative numbers of large cleaved and large noncleaved cells, respectively, varied considerably in these lymphomas. Immunophenotypically, almost all lymphomas expressed monotypic surface immunoglobulins and HLA-DR antigens, whereas all lymphomas were reactive with B-cell-associated monoclonal antisera B1, Leu-14, and/or To15. Three of four elderly female patients presenting with disease on the lower legs died. Of the 12 other patients, 11 are currently alive and in complete remission, which suggests a favorable prognosis for this type of cutaneous large cell lymphoma.

Adult↗

A histologic study of lymph nodes from patients with the Sézary syndrome.

Lymph node sections from 12 patients with Sézary syndrome (SS) were studied histologically. The histopathologic alterations were compared with those in lymph nodes from four patients with (erythrodermatic) mycosis fungoides (MF) and two patients with a benign form of erythroderma. Most SS lymph nodes showed a rather monotonous and diffuse infiltration of cerebriform mononuclear cells (CMC), which tended to efface the normal lymph node architecture. By contrast, in lymph nodes involved by MF there was not only an increase in the number of CMC, but also a marked increase in the number of interdigitating reticulum cells that often showed a considerable degree of nuclear polymorphia. In the advanced stages of lymph node involvement by MF, blastic transformation was much more pronounced than in the SS lymph nodes. These histologic differences between MF and SS lymph nodes suggest that different pathogenetic mechanisms may be operative in the development of either of these conditions.

Adult↗

Histopathologic studies in Sézary syndrome and erythrodermic mycosis fungoides: a comparison with benign forms of erythroderma.

Histologic sections from eleven patients with Sézary syndrome were reviewed and compared with those of four patients with erythrodermic mycosis fungoides and twenty-four patients with a benign form of erythroderma, including fifteen patients with chronic dermatitis, four with a generalized drug eruption, and five with an erythrodermic psoriasis. The most important discriminating histologic feature in patients with Sézary syndrome was the presence of a monotonous bandlike or perivascular infiltrate in the papillary dermis, mainly composed of large cerebriform-mononuclear cells, as seen in seven of eleven Sézary syndrome patients. Pautrier's microabscesses were observed in seven of eleven Sézary syndrome patients, two of four patients with erythrodermic mycosis fungoides, but not in any of the patients with a benign form of erythroderma; their presence was therefore considered a reliable criterion in differentiating erythrodermic cutaneous T cell lymphoma from benign forms of erythroderma. However, features of chronic dermatitis were often found superimposed on those of Sézary syndrome and were even predominating in four of eleven Sézary syndrome patients. Moreover, four patients with a benign form of erythroderma showed a histologic picture suggestive of cutaneous T cell lymphoma. Therefore, in dubious cases repeated skin biopsies, additional investigations of lymph nodes and peripheral blood, and careful follow-up are mandatory for the achievement of a correct diagnosis.

Adult↗

Clinical and histologic differentiation between lymphomatoid papulosis and pityriasis lichenoides.

The relationship between lymphomatoid papulosis and pityriasis lichenoides is a matter of considerable debate. Differentiation between these two conditions is, however, important because patients with lymphomatoid papulosis, unlike those with pityriasis lichenoides, may develop systemic lymphoma and thus require long-term follow-up. In our study the clinical and histologic features of eighty-two patients with pityriasis lichenoides and twenty-six patients with lymphomatoid papulosis were reviewed and compared. Clinical and histologic differences were recognized, not only allowing differentiation between the two conditions, but also suggesting that they are pathogenetically distinct diseases. Finally, evidence is presented to suggest that the different views on the relationship between these diseases mainly result from differences in patient selection.

Adolescent↗

Mycosis fungoides simulating acanthosis nigricans.

In this paper, an unusual papillomatous variant of the plaque stage of mycosis fungoides with clinical similarities to acanthosis nigricans is described. In contrast to the classic plaque stage of mycosis fungoides, the dermal infiltrates in this patient showed a rather monomorphous proliferation of blast-like cells that had little or no tendency to infiltrate the epidermis.

Acanthosis Nigricans↗

Immunohistochemical studies using monoclonal antibodies on lymph nodes from patients with mycosis fungoides and Sézary's syndrome.

Using an indirect immunoperoxidase technique and a panel of monoclonal antibodies with well-defined specificities, the authors studied the distribution of lymphoid and nonlymphoid cells in the T-cell areas of both involved and uninvolved lymph nodes from patients with mycosis fungoides (MF) and Sézary's syndrome (SS) and dermatopathic lymph nodes from patients with generalized benign skin disease. The distribution of the different T-cell subsets, HLA-DR+ interdigitating cells and OKT6+ Langerhans cells, in the paracortical areas of MF lymph nodes showing features of dermatopathic lymphadenopathy with early involvement, as assessed after conventional histologic examination, was similar to that of dermatopathic MF lymph nodes without early involvement and lymph nodes from patients with generalized benign skin disease, indicating that these studies do not provide additional criteria for the early diagnosis of MF involvement. MF lymph nodes showing partial or complete obliteration of the normal architecture tended to have lower numbers of HLA-DR+ interdigitating cells and OKT6+ Langerhans cells, but showed increased numbers of blast cells, part of which had lost their mature helper-T-cell phenotype. These differences between the early and advanced stages of lymph node involvement by MF were analogous to those observed in the different stages of cutaneous involvement, as described previously. The lymph nodes from patients with SS were diffusely infiltrated by neoplastic T cells that had retained their mature helper-T-cell phenotype (Leu-1+, 3a+, 4+), contained very low numbers of Leu-2+ T-cells and relatively few HLA-DR+ interdigitating cells and OKT6+ Langerhans cells. These different staining patterns in MF and SS lymph nodes may reflect different pathogenetic mechanisms.

Antibodies, Monoclonal↗

Immunohistochemical and histochemical tools in the diagnosis of amelanotic melanoma.

The histologic diagnosis of (metastatic) oligomelanotic or amelanotic melanoma may be difficult. In most cases this diagnosis can be established with conventional light and electron microscopic examination, supplemented with staining for melanin on ultrathin sections, but in other cases it remains equivocal. Therefore, the melanoma-associated monoclonal antibody NKI/C-3, effective on paraffin sections, was tested with an indirect immunoperoxidase technique. All 19 metastatic melanomas, used as positive controls, were stained. Seventeen of 23 primary melanomas and 8 of 9 initially equivocal eventually unequivocal melanomas (Group I) were stained with a diffuse cytoplasmic and in some cases locally peripheral pattern. Only two large cell undifferentiated carcinomas of 58 histogenetically unrelated but differential diagnostically relevant tumors showed localized staining in few tumor cells. Furthermore, 10 of 20 histogenetically related tumors (neuroendocrine tumors and clear cell sarcomas) were positive. These tumors however, can easily be differentiated from melanomas by other means. Of 15 equivocal melanomas (Group II) 9 cases reacted with NKI/C-3, suggesting that it may be a useful marker for difficult metastatic tumors suspect for amelanotic melanoma. Although sensitivity of NKI/C-3 for metastatic melanomas is high, its specificity is not sufficient. It therefore can be applied most properly in a selected panel of different tumor-associated antibodies that are reactive in formaldehyde fixed, paraffin-embedded tissue.

Adolescent↗

Immunohistochemical analysis of malignant melanomas and nevocellular nevi with monoclonal antibodies to distinct monomorphic determinants of HLA antigens.

Using an indirect immunoperoxidase technique, 20 nevocellular nevi, 5 dysplastic nevi, 14 primary cutaneous melanomas, and 24 metastatic melanomas were tested with a panel of monoclonal antibodies to monomorphic determinants of Class I (HLA-A,B,C) and Class II (la-like) major histocompatibility complex antigens. Class I HLA and beta 2-microglobulins were not detected on the majority of nevus cells but were expressed by 3 of 5 dysplastic nevi, by the majority of tumor cells in 12 of 14 primary cutaneous melanomas, and in 13 of 24 metastases. The different expression of Class I HLA and beta 2-microglobulins in primary and metastatic lesions suggests that loss of these antigens may be associated with progression of malignancy. Class II HLA were not detected in common nevi but were locally present in 1 of 5 dysplastic nevi, 7 of 14 cases of primary cutaneous melanoma, and all 24 cases of metastatic lesions tested. These findings suggest that increase in Class II HLA expression may be associated with progression of malignancy. The staining patterns obtained with monoclonal antibodies to distinct determinants of Class I HLA and Class II HLA were superimposable within each type of antigen. Therefore, the discrepancies in the literature about the expression of histocompatibility antigens by lesions of melanocytic origin are not likely to reflect the different specificity of the antibodies used by the various investigators.

Adolescent↗

Lymphomatoid papulosis and Hodgkin's disease: are they related?

Two different characteristic types of lymphomatoid papulosis (type A and type B) can be histologically distinguished, that represent the ends of a spectrum. In the present report, two patients are described. One patient with both lymphomatoid papulosis type A and type B lesions for more than 25 years developed Hodgkin's disease (nodular sclerosing type) in the para-aortic and para-iliac lymph nodes. Histologic examination of the skin lesions in the second patient, who had Hodgkin's disease (nodular sclerosing type) in many supradiaphragmatic lymph nodes, showed the characteristic features of lymphomatoid papulosis type A. These findings, together with the results of recent immunohistochemical investigations showing many similarities between the large atypical cells in lymphomatoid papulosis type A lesions and Reed-Sternberg cells in Hodgkin's disease, support the view that lymphomatoid papulosis type A and Hodgkin's disease are closely related conditions. The results of recent studies indicate a close relationship between lymphomatoid papulosis type B and the early stages of mycosis fungoides. Accordingly, the possible relationship between lymphomatoid papulosis types A and B, mycosis fungoides, and Hodgkin's disease is discussed.

Adult↗

Immunological, cytochemical and ultrastructural studies in lymphomatoid papulosis.

In lymphomatoid papulosis two histological types can be distinguished, i.e. type A and type B. In the present study various immunological, enzyme-histochemical and ultrastructural techniques were used to investigate the cellular infiltrate in both types of lymphomatoid papulosis. The type A lesions showed a predominance of large atypical cells, relatively few T cells and few or no Langerhans or related cells, as defined by a positive staining for OKT6 and NA I/34 antisera. The immunological, cytochemical and ultrastructural characteristics of these large atypical cells resembled those of the Langerhans cell/interdigitating reticulum cell series. The morphology and marker profile of these large cells resembled those of Reed-Sternberg cells, which suggests a relationship between lymphomatoid papulosis type A and Hodgkin's disease. The type B lesions showed a predominance of small, medium-sized and large cerebriform mononuclear cells with the phenotype of activated T helper cells, and numerous Langerhans and/or related cells. Their cellular composition was similar to that observed in the early stages of mycosis fungoides.

Antibodies, Monoclonal↗