Lymphomatoid papulosis. Histologic and immunohistochemical studies in a patient with a scaly pigmented eruption

A patient with lymphomatoid papulosis type A showed a peculiar, scaly pigmented eruption on the broad skin areas as well as papulonodular lesions. Large atypical cells characteristic of the infiltrate of the disease were observed not only in the dermal infiltrate of papular lesions, but also in the perivascular infiltrate of the scaly pigmented lesions, indicating that the latter was one of the skin manifestations of lymphomatoid papulosis. Immunohistochemical studies showed that these atypical cells expressed Ki-1 and cellular activation-associated antigens such as HLA-DR, Tac, and T9, but were not reactive with T-cell specific antibodies Leu-1, Leu-3a, and Leu-2a.     

Analysis of major histocompatibility antigens and the mononuclear cell infiltrate in halo nevi

A series of monoclonal antibodies was used to characterize the nevomelanocytes and the inflammatory infiltrate of 11 halo nevi in different stages of resolution, employing an immunoperoxidase technique. Three of the 11 halo nevi histologically showed signs of mild or moderate nevomelanocytic atypia. It was found that the vast majority of the nevomelanocytes in halo nevi with a dense inflammatory infiltrate markedly expressed HLA-A,B,C antigens, while expression was not demonstrable in nevocellular nests not adjacent to the mononuclear infiltrate. No difference in expression of HLA-A,B,C antigens was found between the 3 cases with mild or moderate nevomelanocytic atypia and the other cases lacking atypia. Expression of HLA-DR (Ia-like) antigens was found on few nevomelanocytes in only 2 of 11 lesions. The cellular composition of the mononuclear inflammatory infiltrate showed a predominance of T cells (80% or more) with a relatively high proportion of cytotoxic/suppressor T cells. Most of the T cells showed signs of activation as judged by staining for HLA-DR antigens. These results demonstrate that the expression of HLA-A,B,C antigens on the nevomelanocytes and the cellular composition of the mononuclear inflammatory infiltrate in halo nevi are very similar to that in malignant melanomas and dysplastic neiv. These findings also indicate the expression of HLA-A,B,C antigens on nevomelanocytes is primarily dependent on the presence of T-cell immune response and not necessarily related to the presence of nevomelanocytic atypia.     

PUVA treatment of erythrodermic and plaque type mycosis fungoides

Five patients with plaque type mycosis fungoides (MF) and five patients with erythrodermic MF responded favorably to oral psoralen photochemotherapy (PUVA). The mean total UVA irradiation dose was less for erythrodermic than for plaque type MF, but the mean number of treatments to achieve clearing was greater in the erythrodermic patients. Histologic examination at clearing revealed persistence of an inflammatory infiltrate in the lower dermis in most cases. Subsequent recurrent lesions in five patients revealed a more extensive dermal inflammatory infiltrate, although findings were not always diagnostic of MF due to a lack of epidermal involvement. Resumption of more intensive PUVA therapy again resulted in clinical clearing in all five patients. The follow-up period for six patients who received long-term PUVA maintenance ranged from 1 1/2 to 3 1/2 years. During PUVA therapy, five of ten patients developed epithelial malignancies or premalignancies, and one patient developed a malignant fibrous histiocytoma. Most of these patients had received prior treatment with electron beam and topical nitrogen mustard.     

Expression of eotaxin, interleukin 13 and tumour necrosis factor-alpha in dermatitis herpetiformis

BACKGROUND: The dermal and perivascular infiltrate in dermatitis herpetiformis (DH), which is mainly composed of CD4+ lymphocytes, neutrophils and eosinophils, is believed to play an important part in the pathogenesis of the disease. Previous studies suggest that cytokines such as interleukin (IL) -8, granulocyte-macrophage colony-stimulating factor, IL-4 and IL-5 could be involved in the pathogenesis of DH. These cytokines appear to drive tissue infiltration and maturation of eosinophils. Part of the effect of T-helper (Th) 2-type cytokines (IL-4, IL-5) on eosinophils could be mediated by eotaxin, which is a highly specific chemotactic protein induced by various cytokines [IL-4, IL-13, tumour necrosis factor (TNF) -alpha and interferon-gamma]. OBJECTIVES: To evaluate the expression of eotaxin and its inducers, IL-13 and TNF-alpha, in DH. METHODS We examined lesions collected from 10 DH patients with active disease. Sections from each specimen were incubated with anti-IL-13, anti-TNF-alpha and anti-eotaxin antibodies. Chloroacetyl esterase reaction was performed to show mast cell infiltration. RESULTS: Eotaxin was mainly expressed at the tips of the dermal papillae, within the microabscesses. Positivity was also found in the lymphomonocytic infiltrate in the dermis. IL-13 was expressed in the dermal infiltrate and TNF-alpha was found in the inflammatory infiltrate and in dermal vascular cells. CONCLUSIONS: These findings confirm the importance of the lymphomonocytic infiltrate and of Th2 cytokines in the pathogenesis of this disease, suggesting that tissue infiltration in DH is mediated by cell-specific chemokines such as eotaxin and not only by non-specific chemokines such as IL-8.     

Histologic changes associated with ultraviolet A-induced erythema in normal human skin

We have examined the effects of a standardized, moderately erythemogenic dose of long-wave ultraviolet (UVA) radiation on normal human skin, with the use of an appropriately filtered solar simulator and sequential biopsy specimens processed as 1-μm Epon-embedded sections. Histologic changes were present immediately after irradiation and evolved slowly during the 48-hour study. The epidermis manifested slight intracellular and intercellular edema and progressive loss of Langerhans cells to approximately one-fifth control values. A dermal infiltrate of neutrophilic polymorphonuclear leukocytes was present in all postirradiation specimens and peaked at 3 hours. A perivascular lymphocytic infiltrate, moderate endothelial cell enlargement, mast cell hypogranulation, occasional massive venular dilation, and sparse red blood cell extravasation were also noted. Overall, our findings expand and quantify earlier impressions that, compared to UVB, UVA has a relatively greater histologic effect on the dermis than on the epidermis, depletes epidermal Langerhans cells, and recruits neutrophils into irradiated human skin.     

Histopathological study of the mosquito-bite infiltrate in patients with various underlying diseases and different medications]

A histologic study was carried out on tissue-reactions after insect bits in 9 patients with various primary diseases. The clinical and cellular reactions to the bite in the epidermis varied, according to the length, intensity of toxity of the insect bit. The dermal infiltrate was similar in almost all cases and corresponded to a cellular immunologic reaction of the early or late type, as is also to be seen in trichophytin and tuberculin-reactions. Tere was clearly no relationship between the character of the dermal infiltrate and the basic disease. We also found no change in the dermal infiltrate due to special medicaments. Even corticosteroids did not suppress the dermal cellular reactions. There was also a striking absence of eosinophil leucocytes in the dermal infiltrate.     

An absence of human leukocyte antigen-DR and a decreased expression of beta 2-microglobulin on tumor cells of basal cell carcinoma: no influence on the peritumoral immune infiltrate

The expression of human leukocyte antigen-DR (HLA-DR) and beta 2-microglobulin on the tumor cells and their correlation (if any) to the degree and the composition of the peritumoral mononuclear infiltrate were studied in 37 basal cell carcinomas from 32 patients with an indirect immunoperoxidase technique. In 36 of 37 basal cell carcinomas (97%) there was no expression of HLA-DR on tumor cells of basal cell carcinoma. In 13 of 37 basal cell carcinomas (35%) beta 2-microglobulin was expressed on the tumor cells. Both a diffuse cytoplasmic and a membrane staining were observed in only six of these 13 basal a diffuse cytoplasmic and a membrane staining were observed in only six of these 13 basal cell carcinomas; in the other seven basal cell carcinomas only a diffuse cytoplasmic staining was observed. In all 37 basal cell carcinomas there was membrane staining for beta 2-microglobulin in the normal epidermis. The intensity of staining in the normal epidermis was always stronger than that in the tumor nests. There was a varying degree of peritumoral immune infiltrate in all basal cell carcinomas. It comprised mainly T cells (mean percentage 57 +/- 15). In the group of patients with basal cell carcinoma with moderate to heavy infiltrate the mean percentage of T cells was 63 +/- 13, which was significantly higher than the mean percentage of T cells (46% +/- 14%) in the group of patients with basal cell carcinoma with a mild infiltrate. This difference was mainly the result of an increase in T helper cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

A scanning microscopic clue to the diagnosis of arthropod assault reaction: alteration of interstitial tissue is more common than a wedge-shaped inflammatory infiltrate

Background:  A scanning microscopic clue to the diagnosis of arthropod assault reactions is a wedge-shaped inflammatory infiltrate. However, to describe an inflammatory infiltrate as wedge-shaped or not involves a high degree of subjectivity.
Methods:  We studied hematoxylin and eosin-stained sections of 137 biopsies of arthropod assault reactions for epidermal and dermal changes and for the composition, density and depth of the inflammatory infiltrate.
Results:  We found a wedge-shaped inflammatory component in only 10.2% of the cases. A much more common feature is an alteration of the interstitial tissue present in 85.4% of the biopsies. It consisted of a narrowing of the spaces between the collagen bundles, which was readily observable on scanning magnification. On higher magnification, a loosely textured basophilic material was often noted within the dermis.
Conclusions:  The hitherto often emphasized wedge-shaped configuration of the inflammatory component of arthropod assault reactions is not of great diagnostic value. The altered interstitial tissue is easily recognizable by its diminished interstitial spaces at low power magnification and can serve as a scanning magnification clue to the diagnosis of arthropod assault reactions.     

Interleukin 2 and granulocyte-macrophage colony-stimulating factor induce a perivascular lymphocytic infiltrate in a skin explant model.

Cutaneous eruptions displaying perivascular inflammatory cell infiltrates histologically may develop with the intravenous administration of cytokines. Similar findings are seen spontaneously in some patients on recovery of peripheral blood lymphocytes after profound marrow aplasia. To investigate the production of a cutaneous perivascular infiltrate further, the ability of several cytokines to induce a perivascular lymphocytic infiltrate was studied in vitro using a skin explant model. A skin biopsy specimen obtained at the time of peripheral blood lymphocyte recovery after chemotherapy-induced marrow aplasia (n = 10) was divided and incubated for 3 days with and without a series of cytokines plus various peripheral blood mononuclear cell populations. Skin incubated with interleukin 2 and granulocyte-macrophage colony-stimulating factor induced a perivascular lymphocytic infiltrate, while control samples did not. Immunophenotypic analysis revealed that the lymphocytes were predominantly CD3+/CD4+. An infiltrate was not observed when skin was incubated with cytokines alone, without the addition of simultaneously isolated peripheral lymphocytes. A perivascular pattern was not observed with the addition of interferon gamma. Only interferon gamma induced keratinocyte intercellular adhesion molecule 1 expression in experimental tissue. Certain cytokines that affect a range of cell types are capable of inducing a common cutaneous histologic pattern, the perivascular lymphocytic infiltrate.     

The in vivo effects of lymphokines on mitotic activity and keratinization in guinea pig epidermis

Lymphokines may alter epidermal growth and differentiation contributing to changes such as acanthosis and hyperkeratosis. The main in vivo effects of lymphokines on epidermal mitotic activity were therefore investigated. Guinea pigs were injected intradermally with antigen-stimulated lymphocyte culture supernatants and a partially purified lymphokine preparation in phosphate buffered saline (PBS) 18, 24, 36 and 48 hr prior to biopsy. Control sites were injected with unstimulated supernatants and PBS respectively and the mitotic activity determined by use of a stathmokinetic agent. Both lymphokine injected areas and controls showed significantly increased mitotic indices compared to untreated skin which was apparent only at 24 hr. However mitotic activity in lymphokine lesions was significantly higher than in control lesions. There was no difference in the effect on mitotic activity between PBS and unstimulated culture supernatants. Lymphokine lesions at 24 hr also exhibited marked epidermal edema and acanthosis compared to minimal changes in controls. A variable patchy parakeratosis developed between 18 and 24 hr in areas injected with partially purified lymphokine but not in control sites or after injection with unpurified supernatants. The lymphokine-induced inflammatory infiltrate was mild and consisted mainly of neutrophils not differing significantly from that of the control lesions. This strongly suggests that lymphokines induce an alteration in epidermal kinetics and keratinization by a direct effect on keratinocytes and not indirectly via the dermal inflammatory infiltrate.     

Interstitial heparan sulfate in granulomatous inflammatory skin diseases

BACKGROUND: Heparan sulfate (HS) is a glycosaminoglycan that is anchored to the outside of cell membranes. Under ordinary circumstances, it is not present in the interstitium, but under certain circumstances, mainly in the setting of inflammation and tissue repair, HS can be shed from the cell surface into the interstitium in a regulated fashion. Under these circumstances, interstitial HS seems to have an immunomodulatory function because of its binding of many cytokines. However, it is not known which cell types present at an inflammatory site are responsible for this shedding. OBJECTIVE: We have investigated the presence of interstitial HS by immunohistochemistry in various inflammatory skin diseases characterized by different compositions of the inflammatory infiltrate. RESULTS: Strong interstitial HS immunoreactivity was present only in diseases with a predominantly histiocytic infiltrate but not in diseases with a predominantly lymphocytic or neutrophilic infiltrate. CONCLUSIONS: This indicates that histiocytes have a direct or indirect role in the HS shedding process. In the well-formed granulomas of sarcoidosis, interstitial HS immunoreactivity was spatially associated with the fibrotic ring at the periphery of the granulomas, but not with the center harboring the histiocytes. This suggests that histiocytes can stimulate fibroblasts to shed HS into the interstitium.     

Characterization of the mononuclear infiltrate in basal cell carcinoma: a predominantly T cell-mediated immune response with minor participation of Leu-7+ (natural killer) cells and Leu-14+ (B) cells

We investigated the peritumoral inflammatory infiltrate in 22 basal cell carcinoma (BCC) from 18 patients using a series of monoclonal antibodies. In all the 22 BCC the infiltrate consisted mainly of T cells (55 +/- 15%) and only in three cases an invasion of the tumor nests by these cells was observed. The T helper (TH) subset predominated over the T suppressor/cytotoxic (TS/C) subset (TH/TS/C ratio of 1.9 +/- 0.8). In 8 of 22 BCC mild infiltrate was observed with 48 +/- 13% T cells and a TH/TS/C ratio of 1.5 +/- 0.6. In 14 of 22 BCC moderate to heavy infiltrate with 59 +/- 15% T cells and a TH/TS/C ratio of 2.0 +/- 1.0 was observed. There was a significant difference in the percentage of T cells in BCC with moderate to heavy infiltrate and that in BCC with mild infiltration. The mean percentage of HLA-DR+ cells was 54 +/- 11%; Langerhans cells (LC) 4 +/- 5%; and Leu-M5+ (monocytes and macrophages) 16 +/- 11%. Less than 2% Leu-14+(B) cells were seen in the infiltrate. The mean percentage of Leu-7+ (natural killer) cells was 4 +/- 4%, and only 1 of 22 BCC Leu-7+ cells invaded tumor nests, contacting with tumor cells. From these results we concluded that T cells play a major role in the defence against BCC proliferation. The main role of Langerhans cells and Leu-M5+ cells may be that of antigen presentation. B cells and NK cells probably play a minor role in the local defence against BCC proliferation.     

FS04.8The U.S. Cosmetic Ingredient Review: process and products

Methyl(chloro)isothiazolinone is an effective preservative and a major cause of cosmetic allergy in most European countries. On the face unusual clinical presentations are seborrhoeic dermatitis, lupus erythematosus, lymphocytic infiltrate, photodermatosis or atopic dermatitis. Three patients who suffered a chronic, recurrent, itchy and generalized cutaneous erytematous‐desquamative and eczematous eruption with a common pathologic event, an atypical lymphoid infiltrate, whose induction by a contact allergen can be discussed are presented. The first, a 59 years old man showed a biopsy with an atypical dermal‐epidermal T cell infiltrate of mycosis fungoides and monoclonal TCR‐rearrangement. The second, a 74 years old man showed an atypical lymphoid infiltration with polyclonal TCR‐rearrangement and a second biopsy showed an eczematous pattern. The third, a 50 year old man with pathology of plaque parapsoriasis with atypical lymphoid infiltrate. The three patients showed strong positive reaction to methyl(chloro)isothiazolinone (0.01%aq.) Trolab,,μ. Avoiding the allergen the cutaneous eruption disappeared and any recurrence has been observed yet. Pathologic criteria for mycosis fungoides remains controversial and could not be done only on the basis of cellular density or the percentage of atypical T‐cells. Autoinvolutive mycosis fungoides shows the unknowledge of its pathogenesis. How some allergens could affect on the cellular life needs further studies. We highly recommend to patch test all patients with atypical cutaneous T‐cell infiltrates.     

Childhood Jessner's lymphocytic infiltrate of the skin

We report a case of Jessner's lymphocytic infiltrate of the skin in an 11-year-old boy. This benign lymphocytic infiltrate was originally described in 1953, and classically occurs in middle-aged men. Its occurrence in children appears to be very rare, and there are only two other case reports in the literature.     

Plasma cell infiltrate in common acquired melanocytic nevus

The presence of plasma cells in melanocytic lesions has been considered in literature as a sign of concern, when evaluated in the appropriate context. Plasma cells have been evaluated in halo nevus, but they are not frequently reported in non-halo common acquired nevus. Our claim was to study how common and frequent plasma cells are in the latter type of nevi. Therefore, we examined 280 of these nevi and selected the cases with an inflammatory infiltrate, even if mild. We then looked for plasma cells in the inflammatory infiltrate in the hematoxylin-eosin routine sections and selected 17 cases in which plasma cells (even if only occasional) could be found in the hematoxylin-eosin staining. Out of these 17, plasma cells were easily found in four cases, which were then further studied with immunohistochemistry for epithelial membrane antigen. The percentage of plasma cells varied in these four cases from 0.5% to 7%. No relation between the amount of plasma cells and either the location of the nevus or the location of the inflammatory infiltrate could be established. We conclude that the main point of this study is not to trust the presence of plasma cells as a solid criterion on its own, when evaluating a melanocytic lesion.     

Lymphocyte subsets and Langerhans' cells in toxic epidermal necrolysis. Report of a case

Toxic epidermal necrolysis is a life-threatening disease, the pathogenesis of which remains largely unknown. Histologically, in addition to the characteristic epidermal alterations, there is a sparse mononuclear cell infiltrate in the dermis. The immunologic characteristics of this infiltrate are not well known. In a case of drug-induced toxic epidermal necrolysis with fatal outcome in a 48-year-old man, we demonstrated that the majority of the inflammatory cells were of helper/inducer T-lymphocyte subsets, having only a minority of cytotoxic/suppressor T-lymphocytes and rare cells with natural killer cell phenotype. The significance of these observations is discussed, with reference to the occurrence of lesions at epithelial sites bearing local networks of antigen-presenting cells (Langerhans' cells).     

Actinic cheilitis: histopathology and p53

BACKGROUND: Chronic actinic cheilitis (AC) is a precursor of squamous cell carcinoma (SCC) of the lip. OBJECTIVES: To evaluate the histopathological characteristics that may help to identify AC more susceptible to carcinomatous transformation, to assess the p53 protein expression in AC, and to determine the value of the p53 expression as a marker of transformation into SCC of the lip. METHODS: Seventy cases of chronic AC were reviewed, 31 of which were associated with SCCs. The samples were obtained from pathology reports of AC and SCC of the lip. Histopathology and immunohistochemical expression of the p53 protein were evaluated in isolated AC and in AC adjacent to SCC. RESULTS: The intensity of the inflammatory infiltrate in the corium was the only histopathological finding significantly associated both with the presence of an invasive tumor and with the degree of epithelial atypia. Most AC (85%) were immunoreactive to the p53 protein. The p53 protein expression in cheilitis was not statistically associated with any other histopathological criteria. CONCLUSIONS: An intense inflammatory infiltrate in AC was predictive of an adjacent invasive SCC. In this study, the p53 protein immunoreactivity was not a marker of malignant transformation.     

Identification of subpopulations of lymphocytes and macrophages in the infiltrate of lichen planus lesions of skin and oral mucosa

The mononuclear cells of the infiltrate in lichen planus lesions of skin and oral mucosa have been identified by detection of their membrane receptors in frozen-tissue sections. By this method, the infiltrate would appear to consist of predominantly T lymphocytes, some macrophages and only a few B cells. The pathogenesis of lichen planus is discussed in the light of these findings.     

Ultrastructure of Halo Nevi

An ultrastructural study was conducted on eight halo nevi. Some of them were of recent onset. Others had an evolution of several months. The distribution of the population of the dendritic cells in the depigmented epidermis of the halo was more polymorphous at the early stage when few melanocytes with abundant cytofilaments and some Langerhans cells were seen. At an advanced clinical stage, only Langerhans cells were present in the basal layer. In the dermis abnormal nerves as in vitiligo were observed. The inflammatory infiltrate does not seem to appear at the early stage of involution of the nevus. At the advanced clinical stage, small mononuclear cells were also noticed among the inflammatory cells (lymphocyte-like cells, macrophages, mast cells). It is suggested that an initial stage of inhibition of both the melanocytes and the nevus cells may be responsible for the development of the depigmented halo. This stage precedes the appearance of a dermal lymphomacrophagic infiltrate that leads to the destruction of the nevus.     

Growth and regression of molluscum contagiosum

The spontaneous evolution of molluscum contagiosum was studied on autoradiograms after incorporation of tritiated thymidine. Three patterns of distribution and intensity of labeling were distinguished and interpreted as three successive stages in the evolution of the lesions, corresponding to growth, steady-state, and regression. The association of an inflammatory cell infiltrate with the traumatic disruption of the infected epithelium may occur during any of the three stages. It is concluded that spontaneous regression of molluscum contagiosum may depend upon two distinct mechanisms that belong to spontaneous noninflammatory and traumatic-inflammatory processes.