Mixed carcinoma in situ: an immunohistochemical study

A case of mixed carcinoma in situ , of the skin, is presented. The lesion, located on the right temple of a 71–year-old man, showed histologic features of Bowen's disease and cxtramammary Paget's disease. This case suggests that Bowen's disease and extramammary Paget's disease may arise from pluripotential adnexal epithelium capable of keratinocytic and glandular differentiation. Utilization of the peroxidase-antiperoxidase technique for demonstrating carcino-embryonic antigen was performed in order to identify the component interpreted as extramammary Paget's disease. This procedure is apparently more sensitive than the commonly employed histochcmical stains for demonstrating glandular differentiation.     

Trichilemmoma: an immunohistochemical study of cytokeratins

BACKGROUND: The histogenesis of trichilemmoma remains unclear. OBJECTIVES: To clarify the histogenesis of trichilemmoma by evaluating its cytokeratin (CK) expression. METHODS: In three cases of trichilemmoma, CK expression was studied immunohistochemically using seven antikeratin antibodies against CK1, 10, 14-17 and 19, respectively. RESULTS: CK1 and CK10 were present in keratinizing ductal epithelium. CK14 was present in the whole layer. CK15 was present in suprabasal layers in two cases. CK16 was present in the suprabasal layer, but was absent in keratinizing ductal epithelium. CK17 was present in suprabasal layers and the sebaceous duct-like structure. CK19 was totally absent. CONCLUSIONS: These results showed that trichilemmoma may differentiate mainly towards two directions: infundibular keratinization and proliferation of the outer root sheath with undifferentiated and pluripotent characteristics.     

Giant cell fibroblastoma: an immunohistochemical study

Giant cell fibroblastoma is a rare, benign soft tissue tumor occurring in childhood. A 34-year-old woman presented with a giant cell fibroblastoma involving the chest wall. Histologic features include an infiltrating spindle-cell tumor involving the dermis and subcutaneous fat containing characteristic sinusoidal spaces rimmed by spindle cells and multinucleate giant cells. Immunohistochemical studies support a fibrohistiocytic differentiation.     

Cutaneous nerves in diabetic neuropathy: an immunohistochemical study

Background Diabetic neuropathy is usually investigated using the invasive sural nerve biopsy technique; while little is known about dermal nerve alteration in diabetic neuropathy. Patients and Methods Skin biopsies from the lower leg of five diabetics (mean age, 55 years)with autonomic and sensorimotor peripheral neuropathy were compared to biopsies from five non-diabetic controls (mean age, 47 years). Immunohistochemical methods were employed using the anti-neurofilament monoclonal antibodies 127.11 and UJ 13A. The dermal nerve profile areas were counted with a Quantimet image analyser. Results he diabetic biopsies gave significantly lower readings than the controls (P < 0.05, Mann-Whitney U-test). Conclusion Skin biopsy is a simple and reliable method for evaluating distal nerves in diabetes.     

Cytokine alterations in lichen sclerosus: an immunohistochemical study

BACKGROUND: Although the histology of lichen sclerosus is characteristic, the precise nature of the inflammatory changes and the signals provoking them is uncertain. OBJECTIVES: To delineate the inflammatory changes in lichen sclerosus more accurately by studying cytokine changes. METHODS: An immunohistochemical study of 12 specimens of genital lichen sclerosus and one specimen of extragenital lichen sclerosus was undertaken using monoclonal antibodies to interferon (IFN)-gamma, IFN-gamma receptor, tumour necrosis factor (TNF)-alpha, interleukin (IL)-1alpha, IL-2 receptor (CD25), intercellular adhesion molecule-1 (ICAM-1) and its ligand CD11a. Control specimens were seven specimens of normal vulva obtained during gynaecological procedures, three specimens of normal skin, adjacent uninvolved thigh from three of the patients with lichen sclerosus, five specimens of nonvulval psoriasis, four specimens of nonvulval lichen planus and two specimens from chronic wounds. RESULTS: The lichen sclerosus specimens demonstrated slightly increased staining for IFN-gamma within the epidermis compared with the normal vulva and nonvulval skin. There was increased dermal staining for IFN-gamma both within the pale zone of the upper dermis and within the inflammatory zone below this. We confirmed our previous demonstration that in lichen sclerosus HLA-DR immunostaining is increased in association with vascular endothelium, the inflammatory cell infiltrate and around the keratinocytes. The areas of the epidermis with the strongest immunostaining for HLA-DR generally also had the strongest staining for IFN-gamma. In the lichen sclerosus specimens the zone of inflammation also demonstrated increased immunostaining for TNF-alpha, IL-1alpha, IFN-gamma receptor, CD25, CD11a and ICAM-1 while the zone of sclerosus demonstrated a smaller increase in immunostaining for IFN-gamma receptor, TNF-alpha, CD11a and ICAM-1, and the epidermis demonstrated increased staining for ICAM-1. CONCLUSIONS: The increased staining for IFN-gamma, TNF-alpha, IL-1alpha, IFN-gamma receptor, CD25, CD11a and ICAM-1 suggest that the cytokine response in lichen sclerosus shares characteristics of the cytokine response in lichen planus and chronic wounds.     

Kaposi's sarcoma in homosexual men: an immunohistochemical study

A recent outbreak of disseminated Kaposi's sarcoma has been recognized in homosexual men in New York, San Francisco, and Los Angeles. Biopsy specimens of skin lesions were obtained from nine of these homosexual men in Los Angeles and San Francisco. T lymphocyte subset antigens, factor VIII-related antigen, and HLA-Dr antigen were evaluated in situ in frozen sections using immunoperoxidase technics. Factor VIII-related antigen and HLA-Dr antigen were present on tumor cells, supporting a vascular endothelial origin of this neoplasm. Langerhans cells and T lymphocytes were present in numbers similar to that of normal skin in skin specimens from seven patients with Kaposi's sarcoma with visceral dissemination, but were increased in specimens from two patients with only cutaneous involvement.     

Lichen planus annularis: an immunohistochemical study.

Lichen planus annularis is a relatively rare skin manifestation of lichen planus. The mechanisms in the formation of annular lesions are not fully understood. We reported here a 57-year-old female with this disease. The eruption initially occurred as lichen-papules, then enlarged (bean-sized, umbilicated small plaques), and finally developed annular manifestations. We performed immunohistochemical examinations of specimens taken from different types of eruptions. In all specimens, HLA-DR was expressed in the focal keratinocytes adjacent to the dermal HLA-DR positive cell infiltration. Both in the initial papule and in the final annular lesion, expression of ICAM-1 was present only in the keratinocytes above the dermal cell infiltration, similar to HLA-DR. It is of interest that, in the umbilicated small plaques, the peripheral epidermis other than the central site extensively reacted to ICAM-1. LFA-1 expression was most prominent in the mononuclear cells impinging on the dermo-epidermal junction in all specimens. In addition, in the periphery of the umbilicated small plaques, which showed no bandlike dense cell infiltration nor degeneration of basement membrane, TNF-alpha, but not LFA-1, was positive in the infiltrated cells of the upper dermis. These results suggest that expressions of ICAM-1 and TNF-alpha in the peripheral keratinocytes and dermal infiltrated cells are important molecular events in the mechanisms of formation of the annular lesions.     

Very late antigen-1 in psoriasis: an immunohistochemical study

Background Currently, psoriasis is thought to be an inflammatory response to an antigenic stimulation, in which angiogenesis plays a fundamental role. Very late antigen‐1 (VLA‐1) is a β₁ integrin collagen receptor that is up‐regulated in many angiogenic processes. Data on its role in psoriasis are sparse. Objective In a prospective study, we evaluated the staining of VLA‐1 in lesional skin from patients with psoriasis and atopic dermatitis. Material and methods Frozen sections from skin biopsies of patients with chronic plaque‐type psoriasis (n = 18) and chronic atopic dermatitis (n = 7) were stained with a monoclonal antibody to VLA‐1. The number of blood vessels stained with VLA‐1 and the staining intensity were evaluated. These were correlated with the histologic features. Results The absolute number of blood vessels was found to be similar in the atopic and psoriatic samples. However, the number of vessels stained with anti‐VLA‐1, as well as the staining intensity, was shown to be significantly higher in the psoriasis group (P < 0.05). Differences between psoriatic lesions showing typical histological features of psoriasis and those showing features that overlap with dermatitis were found as well. Conclusions Expression of VLA‐1 was found significantly higher in lesional dermal blood vessels of psoriatic patients compared with atopic patients. These findings suggest a possible role for VLA‐1 in the pathological angiogenesis of psoriasis. It may be an additional tool for establishing the diagnosis of psoriasis and provide a basis for new strategies in the treatment of psoriasis.     

Merkel cells are integral constituents of Desmoplastic trichoepithelioma: an immunohistochemical and electron microscopic study

The incidence of Merkel cells has previously been investigated in a number of inflammatory and tumorous lesions of the skin. Special attention was given to tumors with follicular differentiation. In the present study we examined the localization of Merkel cells in another adnexal tumor, the desmoplastic trichoepithelioma (n= 15), as well as in its main differential diagnosis, the morpheiform basal-cell carcinoma (n=30). Using immunohistochemical methods, we found Merkel cells as a stable constituent in desmoplastic trichoepitheliomas, but failed to detect them in morpheiform basal-cell carcinomas. These findings might therefore be an important tool in the sometimes very difficult but clinically imperative distinction between these two conditions. Furthermore, our study may be of interest in the discussion about the origin of desmoplastic trichoepitheliomas. High numbers of Merkel cells in desmoplastic trichoepitheliomas indicate a bulge-derived origin of this adnexal tumor, since high numbers of Merkel cells, especially in the bulge, were recently discovered. Although the significance of Merkel cell hyperplasia in desmoplastic trichoepithelioma is not presently understood, a regulatory role of the Merkel cell in growth and development of this adnexal tumor is suggested.     

Delayed postburn blisters: an immunohistochemical and ultrastructural study

This study was performed in an attempt to further elucidate the pathogenesis of delayed postburn blistering. Two cases were studied ultrastructurally and immunohistochemically, 1 with blisters on the recipient site of autologous split-thickness skin grafts and the other on the donor site. Ultrastructurally, the basement membrane was on the roof of the blisters in both cases, except for a single small blister in the first case where it was on the dermal floor. In the blister roofs, the basement membrane showed small or marked segments of discontinuity. In the adjacent non-blistered healed skin, the basement membrane was usually continuous, and anchoring fibrils were present. Immunoperoxidase staining on frozen sections, using antibodies to laminin, laminin 5, collagen IV, and collagen VII, showed a mostly continuous linear pattern in the adjacent non-blistered skin, which often became discontinuous near the blisters and markedly discontinuous in the blister roofs. In the blister floors, weakly stained linear or granular deposits of some of these components were sometimes also present. The results of this study support discontinuity of the basement membrane as the main anomaly in delayed postburn blistering. Disturbance in die reassembly or local breakdown of the basement membrane components might be the underlying defect.     

Eccrine syringofibroadenoma (Mascaro): an immunohistochemical study

Eccrine syringofibroadenoma is an uncommon benign eccrine tumor, which was first described by Mascaro in 1963. It usually develops on the extremities of elderly persons. We report on a 74-year-old man who presented with a 2-year history of a slowly growing lesion on his face. A detailed histologic and immunohistochemical study was performed on the biopsy material. The tumor consisted of epidermal-derived anastomosing thin epithelial cords embedded in a fibrovascular stroma. The epithelial cords contained ductal and cystic structures lined by luminal cells, which were decorated by antibodies against carcinoembryonic antigen, keratin K19, K8, and K18. Antibody to keratin K6 decorated the luminal walls of the acrosyringia. Antibodies to filaggrin decorated the superficial luminal structures. These results suggest dual acrosyringial and dermal duct differentiation in syringofibroadenoma.     

Cyclin D1 overexpression in Spitz nevi: an immunohistochemical study

The morphologic distinction between Spitz nevus and malignant melanoma can be difficult. Because cyclin D1 has been reported to be overexpressed in malignant melanomas, but not in common acquired nevi, we hypothesized that cyclin D1 might be a useful marker to distinguish Spitz nevi from malignant melanoma. Thus, we assessed for cyclin D1 expression in 11 Spitz nevi (10 compound and 1 intradermal) and 9 malignant melanomas (4 Clark stages I-III and 5 Clark stages IV-V) using an immunohistochemical method and routinely fixed and processed tissues. The cyclin D1 results were arbitrarily divided into three groups: 0% to 10%, >10% to 25%, and >25%. We confirmed the observations reported previously by others that cyclin D1 is expressed in malignant melanomas but not in common acquired nevi. Unexpectedly, a relatively high number of cyclin D1-positive cells (i.e., >10%) was also found in all cases of Spitz nevus. However, unlike malignant melanoma, the cyclin D1 positivity in Spitz nevi was present in a zonal pattern. In other words, the number of cyclin D1-positive cells decreased as the lesion extended more deeply, with the number of positive cells in the reticular dermis being less than that in the papillary dermis. Fluorescence in situ hybridization methods were used to assess amplification of 11q13, the locus harboring the cyclin D1 gene, in four cases of Spitz nevus; all were disomic. Using the antibody MIB-1, we compared cyclin D1 expression to the proliferation rate in Spitz nevi. Despite the high cyclin D1 positivity, all Spitz nevi had a relatively low number of MIB-1-positive cells (mean=3.2%), which was significantly lower than that of malignant melanomas (mean=15.3%) (p < 0.001). Thus, unlike malignant melanoma, there appears to be a dissociation between cyclin D1 overexpression and cell proliferation in Spitz nevi.     

The basement membrane zone in lichen sclerosus: an immunohistochemical study

The alteration in expression of basement membrane zone (BMZ) components in lichen sclerosus was investigated by immunohistochemical staining of skin biopsies from seven patients with histologically confirmed disease compared with controls. Monoclonal antibodies and polyclonal sera directed against proteins of the hemidesmosomes, anchoring fibrils, lamina lucida, lamina densa and BMZ collagens were used. Characteristic histological appearances at the dermo-epidermal junction were reflected in widespread alterations in antigen expression in the epidermal basement membrane and the papillary dermis. Expression of the proteins which constitute the structural scaffold (collagen IV and VII) were increased in lichen sclerosus. Expression of hemidesmosomal proteins which mediate adhesion and cell to matrix interaction (α6/β4 and hullous pemphigoid antigen) and expression of anchoring filament components were markedly reduced, suggesting that the epidermal cells are exposed to selective damage.     

Expression of neuropeptide-degrading enzymes in alopecia areata: an immunohistochemical study

BACKGROUND: Much clinical evidence suggests that the nervous system, including psychological factors, can influence the course of alopecia areata (AA). However, there has been little substantial evidence of specific participation of cutaneous neurogenic factors in the disease process. OBJECTIVES: As previous studies have demonstrated that stress elicits the release of the neuropeptide substance P (SP) from peripheral nerves and that some patients with AA show prominent SP expression in nerves surrounding their hair follicles, we aimed to evaluate the role of SP in AA. METHODS: We used immunohistochemistry to examine the expression of SP and SP-degrading enzymes in scalp biopsies from patients with AA and from healthy controls. RESULTS: Affected hair follicles in the centre of the areas of hair loss of patients with AA were richly innervated by SP-staining nerve fibres. Strong expression of the SP-degrading enzyme, neutral endopeptidase (NEP), was observed in hair follicles not only in the acute progressive phase of AA but also in the chronic stable phase. Expression of NEP in hair follicles from the margins of areas of hair loss was stronger than in normal controls, but was weaker than in the centre of the areas of hair loss. In addition, endothelial immunoreactivity for angiotensin-converting enzyme (also capable of degrading SP) was not observed in the centre of the areas of hair loss, which was in significant contrast to normal controls as well as to the margins of areas of hair loss where it was expressed. Further, intense expression of endothelial leucocyte adhesion molecule-1 on vessels and many degranulating mast cells was observed adjacent to affected hair follicles in AA, in admixture with dense lymphocytic inflammation. CONCLUSIONS: These findings suggest that SP is endogenously released by dermal nerve fibres around hair follicles and that it may play an important part in epithelial-mesenchymal-neuroectodermal interactions in AA. This study reveals that SP and its degrading enzymes are involved in the pathogenesis of AA, which in turn might explain the pathological significance of neurogenic and psychogenic aspects in the disease process.     

Mutant p53 expression in solar keratosis: an immunohistochemical study

Thirty-eight solar keratoses from 32 patients were studied for expression of mutant p53 protein by an immunohistochemical technique. Twenty-eight of the 38 solar keratoses (73.7%) showed positive and variable nuclear labelling, whereas 10 specimens were immunonegative. The nuclear immunopositivity which was seen in all variants was mostly diffuse in distribution. The adjacent "normal" epidermis of 8 keratoses showed positive mutant p53 labelling. Eight of the keratoses were associated with invasive squamous cell carcinoma of which only two were immunopositive. Cytoplasmic labelling was never a feature. The study demonstrates that mutant p53 protein is commonly expressed in all variants of solar keratosis and that its expression correlates with atypical keratinocyte proliferation. It is proposed that the demonstration of mutant p53 in the adjacent normal epidermis may be a potential marker of early neoplastic transformation.     

Cathepsin D expression in chronic plaque psoriasis: an immunohistochemical study

Cathepsins are lysosomal cysteine proteases, which are involved in a variety of physiologic processes such as proenzyme activation, antigen presentation, tissue remodeling, bone matrix resorption, and pathologic processes such as facilitating tumor invasion and modulating the process of programmed cell death. This study aimed to evaluate the pattern of cathepsin D (CD) expression in chronic plaque psoriasis in comparison to normal skin by means of immunohistochemistry. The study included 34 patients presenting with chronic plaque psoriasis and 10 age- and sex-matched normal subjects as control group. Sixty percent of normal skin showed granular positivity for CD confined to basal layer. CD is upregulated in psoaritic lesion with 94.1% positivity making a significant difference between psoriasis and normal skin as regards the percentage and distribution of CD expression, where the latter was predominantly diffuse in psoriatic lesion. The eight cases exposed to PUVA therapy showed reduction of CD positivity to 62.5% with a predominance of mild staining and focal expression compared to pretreatment biopsies. CD may have a role in the pathogenesis of psoriasis in view of its high percentage and diffuse expression in psoriatic epidermis. CD degradative capacity may be responsible for disordered differentiation and scale formation characteristic of psoriasis. Reduction of CD expression may be one of the pathways of PUVA mechanism of action.