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The role of antibodies in the destruction of pathogenic cells is a basic concept in immunology. The advent of monoclonal antibodies (MCA) has renewed interest in cancer immunotherapy because of their specificity, and because they can be linked to radionuclides, drugs and toxins. MCA of defined specificity are continuously produced by permanent cell lines using the hybridoma method. These MCA are chemically homogeneous, react with constant avidity to single antigenic determinants, and can be isolated in quantities previously not obtainable by conventional methods. There are many problems associated with the therapeutic use of MCA. In this paper such problems and possible solutions are described, followed by a review of the literature on monoclonal antibody therapy.

Plasma cell proliferations in specific cutaneous lesions of angioimmunoblastic T-cell lymphoma( AITL) are very uncommon. Here, we report a case of clonal plasma cell proliferation in skin with heavy-chain-immunoglobulin-isotype-switch after cutaneous disease progression. Histopathologically, initial plaque lesions were suggestive of marginal-zone B-cell-lymphoma. Nevertheless, this 77-year-old lady was diagnosed with AITL after the progression of skin lesions from plaques to nodular tumors. A lymph node biopsy confirmed the diagnosis. Both cutaneous specimens showed a polymorphic cellular infiltrate with atypical T-cell-lymphocytes arranged in a pseudonodular pattern that expressed CD3, PD1 and BCL6, with patchy expression of CD30. Interestingly, a slight IgG-Lambda plasma cell component was seen at the periphery of the infiltrate in the first specimen which increased in number in the later nodular lesion, showing not only Lambda light chain restriction and IgG but also IgG4. PCR studies for IgH and TCR genes showed an IgH clonal peak on both skin lesions but not on lymph node biopsy. On the contrary, the same clonal TCR peak was found in the three specimens. Neoplastic follicular helper T-cells within cutaneous-specific microenvironment could be responsible for the modulation of the immunoglobulin isotype class switch change. Further studies are needed to support this hypothesis. [ABSTRACT FROM AUTHOR]

The article presents the author's comments on the use of S100 immunostains in dermatopathology. He remarks that it is over-utilization when a pathologist or dermatopathologist orders S100 and Melan-A immunostains on a lesion that is obviously melanocytic in lineage. He comments that the effective or crucial elements of good dermatopathology care are not defined. He states that an unsustainable approach in most practice environments is represented by doing immunostains for a routine case.

Background: Neonatal lupus erythematosus (NLE) is a disease associated with the transplacental transfer of maternal anti-Ro/SSA. The histopathologic characteristics of neonatal lupus have been described as compatible with cutaneous lupus based on isolated cases. Methods: We retrospectively review the available literature and compare them with findings obtained in seven biopsies of five cases. Results: Erythematous-desquamative lesions and urticaria-like lesions were observed in our series. Two cases showed both type of lesions. Vacuolar alterations at the dermoepidermal interface and adnexal structures were the histopathologic findings on erythematous-desquamative lesions, and a superficial and deep perivascular and periadnexal lymphocytic infiltrate was the major pattern in urticaria-like lesions. One case showed prevalence of eosinophils in the inflammatory infiltrate. Sixty cases have been reported previously. Sixty-five percent presented erythematous-desquamative and 29% urticaria-like lesions. Pathologic findings of erythematous-desquamative lesions were similar to those found in our series, but epidermal vacuolar changes were the predominant histopathologic finding in urticaria-like lesions of cases reported in the literature. Conclusions: The majority of cases of NLE show vacuolar alteration at the dermoepidermal interface and adnexal structures. Some cases exhibit a superficial and deep perivascular and periadnexal lymphocytic infiltrate without epidermal alteration, and rare cases may have eosinophils in the infiltrate. [ABSTRACT FROM AUTHOR]

Introduction: Paraneoplastic pemphigus (PNP) is considered an autoimmune, multiorgan disease caused by antiplakin antibodies. We present three PNP patients who had negative epithelial direct immunofluorescence (DIF) findings in one or more biopsies. Patients: An early lip biopsy of uninvolved oral epithelia in patient 1 was negative. A later biopsy from foreskin showed intense intercellular immunoglobulin G (IgG) deposits in the epithelia. In the early phase of the disease in patient 2, the intercellular fluorescence was negative in the epidermis, while intercellular IgG and C3 were observed in the sweat ducts. A later biopsy showed weak intercellular epidermal IgG and C3 fluorescence. Patient 3 showed intercellular IgG and/or C3 in follicular, sebaceous and sweat duct structures in several biopsies. No intercellular IgG or C3 was observed in the epithelia. Discussion: The presence of immunoreactants in adnexal structures suggests that desmoplakins can be more strongly expressed in adnexa than in the epidermis, facilitating visualization of antibody deposits. Conclusions: Negative DIF findings in epithelia do not rule out the diagnosis of PNP, and the presence of IgG and/or C3 at the intercellular level of adnexal structures can help establish this diagnosis. [ABSTRACT FROM AUTHOR]

Biologically uncommon d-aspartyl residues have been reported in the elderly tissues such as tooth, eye lens, aorta, and brain. We have previously prepared the antibody against d-aspartyl residue-containing peptide and found that it reacted with elastotic material of actinic elastosis. Immunoreactivity of the normal skins obtained from sun-exposed and sun-protected skins of varied ages with this antibody was studied. In the sun-exposed skins, the antibody showed negative reaction with the skin specimens of young donors, whereas it reacted with elastotic materials of actinic elastosis of the elderly. In the sun-protected skins, the antibody recognized elastic fiber-like structures and inner layer of vessels found from the mid to lower dermis of old donors but showed no positive reaction to skin specimens of young donors. The results suggest that the antibody is a potent marker for chronological and ultraviolet (UV)-induced skin aging. Unusual eosinophilic bodies seen in the superficial dermis in the sun-exposed area of the elderly skins were also immunoreactive with the antibody, suggesting that the eosinophilic bodies resulted from UV-induced skin damage. Miura Y, Fujimoto N, Komatsu T, Tajima S, Kawada A, Saito T, Fujii N. Immunohistochemical study of chronological and photo-induced aging skins using the antibody raised against d-aspartyl residue-containing peptide. [ABSTRACT FROM AUTHOR]

Urokinase-type plasminogen activator (uPA) has been well documented in the development of pemphigus acantholysis. The function of its receptor (uPA-R) in pemphigus acantholysis has only recently attracted attention. Increased expression of uPA-R has been demonstrated in pemphigus vulgaris. In this study, we have further explored the functional involvement of uPA-R in pemphigus acantholysis. Our results show that uPA-R expression is significantly increased in acantholytic foci of pemphigus vulgaris and pemphigus foliaceus but not in bullous pemphigoid or normal skin specimens; the expression of uPA-R in cultured human keratinocytes is subjected to regulation by pemphigus vulgaris IgG but not by pemphigoid IgG or normal human IgG; furthermore, anti-uPA-R monoclonal antibody effectively inhibits pemphigus vulgaris IgG induced acantholysis in skin organ cnltures. These data suggest that uPA-R may play an important role in the pathogenesis of pemphigus acantholysis. [ABSTRACT FROM AUTHOR]

The expression of cytokeratins in 10 cases of clear cell hidradenoma, including 3 cases of solid cystic hidradenoma, were examined using 21 kinds of monoclonal antibodies. We divided them into three histologic patterns: massive nests with a few lumina (M nests), nests with some tubular lumina (L nests), and nests in solid cystic hidradenomas (S nests). All hidradenomas showed similar immunoreactivities to those in the lower dermal ducts or secretory cells of normal eccrine glands. With antibodies against simple epithelial cytokeratins (CKs 7, 8, 18, and 19), however, different immunostaining was noted among the three histologic patterns. Namely, the M nests failed to react to them, although some luminal cells in the L nests revealed a positive staining. Furthermore, a majority of luminal cells in the S nests revealed a positive staining with them. Therefore, we think that the luminal cells in solid cystic hidradenoma mainly differentiate toward the secretory cells, and that the M nests mainly differentiate toward the dermal duct. Those in the L nests are thought to differentiate toward the dermal duct and the secretory cells. The proportion of the differentiation toward luminal cells of dermal ducts to the differentiation toward secretory cells was the main difference among the three nests. In addition, there was no difference in immunophenotypes between clear cells and epidermoid cells in the two kinds of hidradenomas. [ABSTRACT FROM AUTHOR]

Reactive angioendotheliomatosis (RA) is a rare, benign disease. Affected patients present with self-limited, erythematous to violaceous plaques. The clinical lesions are due to intravascular hyperplasia of cytologically banal endothelial cells in the dermis. We report 2 patients who presented with ulcerated, violaceous plaques on the lower extremities. Both had severe peripheral vascular atherosclerotic disease requiring bypass grafts. Unlike previously described cases of RA, our patient's lesions were due to a diffuse proliferation of endothelial cells in the reticular dermis with only minimal, focal intravascular proliferation of these cells. Positive immunostaining with antibodies to Factor VIII-related and CD34 antigens adds evidence that the proliferated cells in the dermis were endothelial cells. [ABSTRACT FROM AUTHOR]

Immunostaining with the monoclonal antibodies PCNA and Ki-67 provides a simple method for the assessment of growth fractions of tumors. Contrary of Ki-67, PCNA antibody can be applied on aldehyde- or alcohol-fixed and paraffin-embedded tissues, thus allowing studies on archival material. For 77 melanocytic skin lesions, we compared PCNA immunostaining on formalin-fixed tissue with Ki-67 immunostaining on frozen material of the same lesion. 16 benigri melanocytic nevi (BMN, from 16 patients), 43 primary malignant melanomas (PMM, 42 patients), and 18 skin metastases fo malignant melanoma (MMM, 12 patients) were included in the study. Maximum nuclear density (ND[SUBmax]) of PCNA- and Ki-67-positive nuclei was assessed using interactive image analysis. ND[SUBmax] values for both PCNA and Ki-67 differed significantly between the three diagnostic groups (Kruskal-Wallis H-test: p≪ 0.001). Mean values (given as 1000 nuclei/mm[SUP3] tissue) increased considerably from benign to malignant lesions (PCNA: BMN: 23.8 ± 28.4 [mean ± standard deviation], PMM: 48:1 ± 41.0, MMM: 117.0 ± 64.6; Ki067: BMN: 6.4 ± 3.3; PMM 25.0 ± 31.1, MMM: 95.2 ± 47.2-. Correlation between ND[SUBmax] values of PCNA- and Ki-67-positive nuclei was significant 9Linear regression analysis: r = 0.51, p ≪ 0.001). Furthermore, for PMM a significant correlation between histologic parameters related to prognosis (Breslow index and mitotic rate) and PCNA as well as Ki-67 expression was found (PCNA - Breslow index: r = 0.60, p ≪ 0.001; PCNA - mitotic rate: r = 0.40, p < 0.001; Ki-67 - mitotic rate: r = 0.50, p < 0.001). Concerning patients'/survival, ND[SUBmax] values of PCNA- and Ki-67-positive nuclei as a single prognostic parameter were not superior to Breslow index. We conclude that PCNA- and Ki-67 expression as assessed by interactive image analysis may be suitable for tumor grading in melanocytic skin lesions. [ABSTRACT FROM AUTHOR]

A histochemical investigation of lectin-binding sites was carried out on formalin-fixed paraffin-embedded sections of 60 skin appendage tumors and adjacent normal skin appendages, using four different biotinylated lectins, peanut agglutinin (PNA), Dolichos biflorus agglutinin (DBA), soybean agglutinin (SBA), and Ulex europaeus agglutinin-1 (UEA-1), and avidin-biotin-horseradish peroxidase labeling. In the secretory segments of eccrine sweat glands, the superficial dark cells showed strong cytoplasmic staining with UWA-1, whereas DBA and SBA strongly stained the plasma membranes of basal clear cells. The acinar cells of apocrine sweat glands revealed sporadic apical membrane staining with all four lectins. In some cases, the luminal membranes of sweat gland ducts showed apical membranous staining with all four lectins. In the hair follicles, the inner root sheath was positive for all four lectins, and the outer root sheath was stained by PNA. The sebaceous ducts, as well as the outer root sheath at the level of sebaceous duct insertion, were also labeled by all four lectins. Sebaceous lobules showed cytoplasmic and membrane staining of mature sebocytes with PNA and SBA. Although sweat gland tumors revealed differences in lectin binding when compared to their corresponding normal tissues, the lectin-binding pattern of pilosebaceous tumors was analogous to the pilosebaceous apparatus. [ABSTRACT FROM AUTHOR]

HMB-45 is a monoclonal antibody directed against human melanoma cells and which stains epidermal and dermal melanoma cells, the junctional components of common and dysplastic melanocytic nevi, and melanocytes in fetal skin. In addition, melanocytes in a variety of reactive conditions have been shown to label with HMB-45, as have dermal melanocytes within Spitz and dysplastic nevi. No melanocytes in normal adult epidermis or in the dermis of common nevi have stained with HMB-45. In order to better understand the properties of this antibody, and of the melanocytes that react with it, we stained cultured human melanocytes grown in a variety of conditions. Melanocytes from human foreskins were grown for 2-3 weeks in MCDB 153 medium supplemented with insulin, epidermal growth factor, and bovine pituitary extract as a mixed population of keratinocytes and melanocytes. Some cells were transferred to basal medium MCDB 153 (unsupplemented) for periods ranging from 3-5 days, and a subset of these were returned to growth-factor supplemented medium. In all cases, S100 staining was used to confirm the presence of melanocytes. Melanocytes grown in complete medium showed strong granular cytoplasmic staining with HMB-45. Cells transferred to basal medium showed a markedly diminished staining intensity which was reversible within 3 days upon return of the cells to complete medium. The findings suggest that expression of the protein recognized by HMB-45 may be related to a growth factor present in complete medium, but missing from basal MCDB 153. Additional studies, supplementing medium with phorbol esters, markedly enhanced HMB-45 staining and essentially removed keratinocytes from cell cultures. As determined by measurement of melanocyte proliferation, staining of HMB-45 did not correlate with mitogenic activation but may correlate with biochemical activation by specific growth factors. [ABSTRACT FROM AUTHOR]

Epidermotropic neuroendocrine carcinoma (NEC) is rare. Based on such a case in an 88-year-old woman with a facial NEC showing epidermotropism with a pagetoid growth pattern, we asked whether several similar tumors involving the epidermis could be easily differentiated by immunohistochemical methods. We constructed a panel of control cases (2 each) for NEC, clear cell Bowen's disease (CCBD), Paget's disease (PD), superficial basal cell carcinoma (SBCC), cutaneous T-cell lymphoma (CTTL), and superficial spreading malignant melanoma (SSMM) to compare with our patient. A panel of antibodies including epithelial membrane antigen (EMA), neuron specific enolase (NSE), AE1/3 cytokeratin (CK), carcinoembryonic antigen (CEA), leukocyte common antigen (LCA), S-100, and HMB-45 were applied. Cutaneous NEC controls and our patient's tumor were strongly positive for EMA and NSE and had paranuclear dot-like cytoplasmic positivity for CK. CCBD was moderate to strong for CK. PD was strong for CEA. SBCC was essentially negative for all. CTTL was strong for LCA. SSMM was strong for S-100 and HMB-45. Controls were either negative or weak for the antibodies not mentioned. We conclude that this antibody panel can reliably differentiate these epidermotropic or juxtaepidermal tumors in diagnostic dermatopathology and should be applied to lesions requiring separation beyond H&E capabilities, especially with superficial shave biopsies showing small cell "Pagetoid" growth patterns. [ABSTRACT FROM AUTHOR]

A typical case of infantile digital fibromatosis (IDF) was studied with antibodies raised against actin, vimentin, desmin and several species of cytokeratin. Strong reactions were observed for desmin, cytokeratin and CK-5, and moderate reactions for vimentin and actin. The diagnostic intracytoplasmic inclusion bodies within the tumor cells were ultrastructurally composed of aggregations of dense microfilaments. Immunoelectron microscopy showed that these filament aggregations are positively stained with anti-actin antibody. From these results, we suggest that' the large tumor cell of IDF is a myofibroblast and may originate from or differentiate toward vascular smooth muscle cells, because only this type of smooth muscle can coexpress desmin, vimentin and cytokeratin. [ABSTRACT FROM AUTHOR]

Plasma cell orificial mucositis is a benign idiopathic condition of orificial mucous membranes characterized histologically by a dense band-like plasmacytic infiltrate. We studied 8 cases of this disease by immunohistochemical methods for subsets of immunoglobulin-producing cells. The infiltrating plasma cells were found to produce mostly IgG and IgA with the predominance of kappa chain-producing cells over lambda chain-producing cells. This polyclonal plasma cell infiltrate composed of IgG- and IgA-producing cells is in accordance with the pattern observed in the inflammatory infiltrate around certain epidermal neoplasms accompanied by the plasmacytic infiltrate, such as actinic keratosis, Bowen's disease, squamous cell carcinoma, and syringocystadenoma papilliferum. [ABSTRACT FROM AUTHOR]

Circulating immune complexes (CIC) containing Treponema pallidum proteins have been preliminarily implicated as inducers of a neutrophilic vascular reaction in early human cutaneous lesions of secondary syphilis. To clarify the role of specific GIG in producing cutaneous and renal lesions, 12 rabbits were studied at the following intervals after induction of disseminated syphilis: 20 days (4 rabbits: biopsies of normal and lesional skin for direct immunofluorescence (IMF) for (IgG, IgM, IgA, Clq, C[sub3], C[sub4]), fibrin, and T. pallidum proteins; routine histology; and immunoblots of serum for CIC containing T. pallidum proteins); 21 days (4 rabbits: as at 20 days without IMF for T. pallidum protein); 23 days (4 rabbits: as at 20 days without IMF); 30 days (same 12 rabbits restudied with routine histology of normal and lesional skin; kidneys from 4 rabbits removed for routine, IMF, and electron microscopy (EM). Treponemal polypeptide antigen (MW-87kd) was demonstrated in CIC from rabbits. Routine cutaneous histology showed evolution of lesions from an early neutrophilic vascular reaction to the typical lymphoplasmacytic reaction. IMF showed vessel-based immunoreactants in 3 of the 4 rabbits tested at 20 days and 1of 4 at 21 days, and T. pallidum proteins in 3 of 4 rabbits at 20 days. Routine histology, IMF, and EM studies of glomeruli showed glomerular abnormalities, but no evidence of immune deposits containing specific T. pallidum protein. Skin and kidney studies of 4 controls were all negative. These data indicate a role for specific immune complexes in the pathogenesis of cutaneous lesions in this rabbit model. [ABSTRACT FROM AUTHOR]

Immunohistochemical distribution of human epidermal growth factor (hEGF) was described in 17 cases of mixed tumour of the skin with monoclonal antibody. In normal sweat glands, epithelial cells in the secretory portion and in the transitional area between secretory portion and duct showed prominent staining for hEGF. In the salivary pleomorphic adenoma type of mixed tumour of the skin, luminal tumour cells of tubular and duct-like structures gave a very characteristic hEGF staining reaction. The tumour cells showing strong staining for hEGF were scattered throughout the solid foci in this type of mixed tumour. Tubular epithelial cells in the clear cell adenoma type also displayed a positive hEGF reaction. And apocrine mixed tumours strong staining for hEGF occurred on the apical side of tubular and ductal tumour cells. In view of the immunohistochemical staining patterns for hEGF, the histologic origin of mixed tumours of the skin is suggested to be cells in the secretory portion and those in the transitional portion between secretory portion and duct of the sweat gland. [ABSTRACT FROM AUTHOR]

A patient with figurated, erythematous skin lesions which histologically showed eosinophilic spongiosis and an epithelial intercellular staining with IgG, but no acantholysis, developed erythromelanoderma. This case and a review of the pertinent literature indicate that the diagnosis of pemphigus does not seem to be justified even in the presence of eosinophilic spongiosis and epidermal intercellular antibodies. when the clinical signs of this disease and the typical histological feature, i.e., acantholysis, are lacking. [ABSTRACT FROM AUTHOR]

Using histochemistry and electron microscopy, it is possible to identify varying degrees of differentiation towards normal apocrine or eccrine structures. One would argue that this does not establish certain origin from these structures, as reserve cells or pluripotential cells could give rise to tumors with intermediate features, or characteristics different from those of the gland in which they were resident. These problems are not yet completely resolved, although the development of monoclonal antibodies directed against eccrine or apocrine antigens may help elucidate this matter.

Antibodies against the cytoplasm of squamous epithelial basal cell (BCab) have been reported by many authors. Although BCab do not appear to be specific, they have been described in different pathological condition. BCab have been shown to be of the Immunoglobulin G type and to be organ-specific not species-specific, as no reaction has been shown in other organ. This study shows a new autoautibody specificity of monoclonal Immunoglobulin M reinforcing the theory that monoclonal immunoglobulins do have antibody activity; it's detection probably depending on the correct selection of the antigen.

Sera of patients with various types of vitiligo have been found to contain circulating antibodies for the cytoplasmic components of human melanoma cell lines. This incidence is high, especially in generalized vitiligo vulgaris with or without Sutton's phenomenon. There is good correlation between the antibodies and positive microsome test, thyroid test, DNA test, as well as the effect of steroid ointment. [ABSTRACT FROM AUTHOR]

The term cutaneous T-cell lymphoma embraces a heterogeneous group of tumors unified by 2 common features: They represent tumors of T-cells arrested at some stage in their ontogeny from bone-marrow-T-cell precursors to functional helper T-cells. They originate in, or predominantly involve, the skin. A major problem in the management of these patients is establishing the diagnosis at an early stage in the disease. At this stage, the tumor cells may be restricted to the skin, and intensive cutaneous therapy may be curative.

The use of immunofluorescence in both diagnosis and research is well recognized in dermatology, dating from the description of the granular deposition along the dermo-epidermal junction in lesions of lupus erythematosus. Immunofluorescence techniques are an immunological method, which may be used to demonstrate cellular antigens, either in tissue section or cell suspension. The fluorescent dyes used routinely are fluorescein and rhodamine, which can be coupled to antibodies without destroying the specificity of the latter. Non-antibody proteins are removed by washing, and the resultant antigen-antibody complex formed is visualized using the fluorescence microscope.

Classical dermatopathology is the foundation stone of diagnosis and understanding of dermatological disease. Clinico-pathologic correlation and awareness of the microscopic changes that occur as a disease progresses have led to greater insight into the disease process. New techniques and reagents have become available providing additions to the armamentarium of the classical dermatopathologist, electron microscopist and enzyme histochemist. The presence of immunoglobulin and C3 deposits at the dermo-epidermal junction in lesions of lupus erythematosus was reported in 1963. Circulating antibodies in the serum and immunoglobulin deposition in the cutaneous lesions of patients with pemphigus are described.

Antibodies prepared against the collagen C-chain derived from human placenta specifically stain the epidermal basement membrane of normal human skin as well as the basement membrane surrounding the skin appendages and capillaries. Using the antibodies, it was observed that all basement membranes in untreated psoriatic plaques appear fragmented and separated into several layers. The results suggest that psoriatic lesions are associated with a general loss of basement membrane integrity which may play a crucial role in the pathogenesis of the disease. [ABSTRACT FROM AUTHOR]

Two patients are reported with clinical symptoms of systemic lupus erythematosus associated with centrally ulcerated hypertrophic plaques and lip lesions. Histological findings from various sites were features of both lupus erythematosus and lichen planus. An increase in acid mucopoly-saccharides and a thickened basement membrane which were present in some biopsies were interpreted as lupus erythematosus. The deposition of immunoglobulins and fibrinogen seemed to favor lupus erythematosus but these findings may also be seen in lichen planus. Four possible interpretations of the findings are discussed. The term "mixed lichen planus - lupus erythematosus disease" may be appropriate for these patients. [ABSTRACT FROM AUTHOR]

Two immunohistochemical methods, using the enzyme horseradish peroxidase, the direct immunoperoxidase (DIP) and the immunoglobulin-enzyme bridge (IEB) method were applied on 129 skin specimens of 81 patients with lupus erythematosus, bullous pemphigoid, pemphigus vulgaris and rosacea. These methods were compared with each other and with the immunofluorescence (IF) method. The DIP method was preferred to the IEB method because of the greater contrast between the specific staining and the nonspecific staining of the former. The results obtained with both peroxidase methods were comparable with those of the IF method. [ABSTRACT FROM AUTHOR]

Two cases are reported, one of multiple myeloma and the other of erythrodermia (malignant reticulosis?), the former associated with a Bence-Jones paraprotein and the latter with IgM paraproteinemia. With an in vitro culture technique and/or the immunofluorescence method it could be demonstrated that the paraprotein present in the serum was synthesized not only in the bone marrow but also in the lesional skin. [ABSTRACT FROM AUTHOR]