Anthony Varelzidis

Mycosis fungoides: Evaluation of immunohistochemical criteria for the early diagnosis of the disease and differentiation between stages

Lesional skin specimens from twenty-eight patients with mycosis fungoides were studied by evaluating immunohistochemical criteria, primarily with monoclonal antibodies. It was demonstrated that significant differences exist between the control and the premycotic-stage group in regard to the monoclonal antibodies BE1, BE2, and OKT9. The detection of specific antigenic determinants on the surface of cell populations early in the course of the disease seems to be of considerable value for the early diagnosis of the disease. Statistically significant differences were found between the premycotic stage and the plaque stage in regard to T lymphocytes, macrophages, OKT6+, OKT4+, OKT8+, and BE2+ cells in the dermal infiltrate. Significant differences were also shown between the plaque and tumorous groups, concerning macrophages, T cells, and OKT9+ cells in the dermis, as well as epidermal dendritic cells. Differences between stages may supplement histologic data for the follow-up of the disease with or without treatment.

Antigenic alterations in tumors of epidermal origin

One hundred tumors of epidermal origin were studied by means of indirect immunofluorescence technique with sera from patients with proven pemphigus and bullous pemphigoid. We found that in tumors of epidermal origin, there was a loss of antigenicity of the intercellular substance and basement membrane; this was minimal for benign tumors, greater for premalignant tumors, and very clear for malignant tumors. We also found a gross correlation between the histologically proven malignancy of squamous cell carcinoma and the grade of antigenic loss; both for the intercellular substance and for the basement membrane antigens. However, this did not yield definite results in the group with basal cell carcinoma. With regard, especially, to the intercellular substance antigen, it seemed to be completely independent of histologic type of basal cell carcinoma. We found that the duration of the epidermal tumor did not correlate with the percentage of intercellular substance and basement membrane antigenic loss. This suggested that the antigenic loss was an early feature of neoplastic behavior. The deeper parts of the malignant tumors in the dermis showed a lower percentage of antigenicity for both antigens.

TREATMENT OF ALOPECIA AREATA WITH DIPHENCYPRONE

Forty‐five patients with extensive alopecia areata were treated by local application of diphencyprone. Only eleven had satisfactory regrowth of hair. Six had moderate regrowth, and of the remaining 28 some showed regrowth of vellus hair and others had no response. The side effects of the treatment consisted of intense allergic or irritant reactions, febrile reactions, anaphylactic reaction with fainting, and vitiligo. In twelve patients progressive desensitisation was observed. As the effectiveness of this treatment is low and side effects are common and sometimes severe, we conclude that diphencyprone has no advantage in the treatment of alopecia areata.

Immunohistochemistry in lichen planus

An immunohistochemical study has been undertaken on 25 biopsy specmens taken from lichen planus lesions, using antisera against human fibrin, immunoglobulins IgG, IgA, IgM and C3 (B1C/B1A) complement component. The findings of the present research are discussed and evaluated in relation to the problem of the etiopathogenesis of the disease.

THE ROLE OF POLYMORPHONUCLEAR CELLS IN PSORIASIS

Neutrophil cell function in psoriasis was studied through polymorphonuclear cell adherence to nylon wool, chemotaxis under agarose, and phagocytosis of Candida albicans. Differences in PMN adherence were not found between psoriatics and controls. The chemotactic response to zymosan activated serum (ZAS) did not differ between psoriatic and normal PMNs. The psoriatic serum exhibited chemoattracting properties equal to ZAS. Psoriatic serum was shown to be chemoattracting to psoriatic and normal PMNs whereas normal serum was only to psoriatic cells. Differences in recognition mechanisms between psoriatic and normal cells are proposed. Phagocytosis of Candida by psoriatic PMNS was earlier and more prolonged and candidacidal activity was earlier and definetely increased at given times compared to normal PMNs. A protective role of psoriatic PMNs in Munros microabcesses against bacterial invasion is postulated.

Antigenic Differences and Further Perspectives on the Differential Diagnosis of Skin Tumors

Frozen sections from squamous cell carcinomas (SCCs), basal cell carcinomas (BCCs), precancerous lesions (P.C.) and normal skin adjacent to lesions (N.S.) were studied by indirect immunoperoxidase for the detection of epithelial membrane antigen (EMA) and by PAP (peroxidase‐antiperoxidase) for total keratin (T.K.) and laminin (LM) to determine the significance of the appearance of neoantigens and the behavior of normal epidermal antigens during the process of carcinogenesis of the skin. Significant antigenic differences in all three antigens were revealed between SCCs and BCCs in the epidermis (EP) and tumor islands (T.I.). There were also significant differences in total keratin and laminin between SCCs and N.S. epidermis. SCCs did not show any significant differences in EMA from P.C. lesions, but T.K. was lower in P.C. lesions than in normal skin.

Mononuclear cell versus monocyte chemotaxis in psoriasis.

Chemotaxis under agarose of psoriatic mixed mononuclear cells (MNs) and pure monocytes against Zymosan treated sera (ZAS), fresh psoriatic serum, and fresh normal serum was studied and compared with that of normal cells. Purification of monocytes was achieved on microexudate coated BHK flasks. Psoriatic MNs were found to be more chemotactic against psoriatic serum (P.S.) than normal MNs against normal serum (N.S.). Psoriatic cells were chemotactically more active than normal ones against psoriatic and normal serum but not against ZAS. Mixed mononuclear cells showed definitely increased chemotaxis over that of pure monocytes. When culture supernatants with lymphocyte derived factor (LDCF) activity were mixed with normal pure monocytes, the chemotactic activity of the monocytes recovered. It is, therefore, proposed that the LDCF from in vivo stimulated psoriatic lymphocytes by antigenic or mitogenic substances of psoriatic plaque might be an essential factor for the increased chemotaxis of mixed psoriatic MNs compared to pure monocytes. This hypothesis also explains the increased chemoattracting capacity of psoriatic serum for psoriatic and normal MNs as due to the in vivo release of lymphokine.

Immunological study of keratoacanthomas

SummaryTwelve patients with keratoacanthoma were studied to assess the role and importance of immunological factors in tumor regression. Direct immuno-fluorescence was determined with immunoglobulins, complement (C3), and fibrin to estimate the deposition of these factors in the lesion area. Indirect immunofluorescence was also undertaken using pemphigus and bullous pemphigoid sera against the keratoacanthoma lesion to study the presence or absence of tissue-specific antigens (T.S.A.) in intercellular substance and basement membrane. Finally, the cell-mediated immunity was studied using two in vitro parameters: (a) The estimation of T-lymphocytes through the formation of E-rosettes and (b) the estimation of the leukocyte migration inhibition factor (LIF). Our findings show that specific humoral immune mechanisms are apparently not involved in the spontaneous regression of keratoacanthoma. Cell-mediated immune mechanisms are evidently not responsible for the resolution of the tumor.ZusammenfassungZwölf Patienten mit Keratoakanthomen wurden hinsichtlich immunologischer Faktoren und deren Bedeutung für die Regression der Tumoren untersucht. Die direkte Immunofluorescenz wurde mit Immunglobulinen, Komplement und Fibrin bestimmt. Zusätzlich wurde die indirekte Immunofluorescenz durchgeführt. Benutzt wurden Sera von Patienten mit Pemphigus und Pemphigoid, um die gewebsspezifischen Antigene in der interzellulären Substanz und an der Basalmembran zu untersuchen. Die celluläre Immunität wurde bestimmt a) Formation von E-Rosetten durch T-Lymphocyten und b) Bestimmung des Leukocytenmigrations-Inhibitionsfaktors. Nach unseren Ergebnissen scheint die spezifische humorale immunologische Reaktion bei der spontanen Regression des Keratoakanthoms keine Rolle zu spielen. Offenbar sind auch keine cellulären Immunitätsmechanismen bei der Abheilung dieser Tumoren beteiligt.