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M C Mihm

Publications and source records attributed to M C Mihm.

At least 181 records · Page 10Linked to original sources
PubMed1983

Malignant melanoma and vitiligo-like leukoderma: an electron microscopic study.

We report clinical and ultrastructural results in eight patients with melanoma and widespread leukoderma. Leukoderma appears to be a good prognostic sign. Although some features of this entity are suggestive of vitiligo, the patients' age, the distribution and appearance of body lesions, and ultrastructural results show a more varied clinical and ultrastructural spectrum. The high frequency of ocular pigmentary disturbances and uveitis in this patient population is noteworthy and deserves further study. We would recommend routine use of Wood's light examination in following patients with thick stage I, stage II, or stage III melanoma to facilitate detection of this phenomenon.

Adult↗
PubMed1983

Histiocytosis-X: in situ characterization of cutaneous infiltrates with monoclonal antibodies.

Cutaneous lesions in three cases of histiocytosis-X were studied by light microscopy, electron microscopy, and immunoperoxidase technics. In each case, Birbeck granule-containing histiocytosis-X cells infiltrated the epidermis and were apposed to lymphocytes. The histiocytosis-X cells and normal Langerhans cells stained with anti-T6 and anti-I1 (Ia-like) antibodies but were negative with anti-T3, anti-T8, anti-M1, and anti-lysozyme antibodies. In addition, the histiocytosis-X cells also stained with anti-T4 antibodies, which react with T-cells associated with helper/inducer phenotype. This study supports the hypothesis that histiocytosis-X cells are abnormal Langerhans cells. The presence of T4/T6-positive cells in cutaneous disease may be a marker for abnormal Langerhans cells.

Antibodies, Monoclonal↗
PubMed1983

Lymphocyte subsets and Langerhans cells/indeterminate cells in erythema multiforme.

A peroxidase-antiperoxidase study using monoclonal antibodies directed against T and B lymphocytes and Langerhans cells/indeterminate cells (LC/IC) was undertaken in order to understand more clearly the changes observed in erythema multiforme. At the various stages of development, from normal skin to target lesions, the quantity of inflammatory cells differed, but in each case the number of T8+ (cytotoxic/suppressor) cells was greater than the number of T4+ (helper/inducer) cells in the epidermis, whereas the latter exceeded the former in the dermis. Concomitant with the initial epidermis changes, there was an increase in the number of T6+ (LC/IC) cells in the upper and lower epidermis. With slight to moderate basal unit destruction, the number of LC/IC in the upper epidermis exceeded those in the lower epidermis. With severe basal unit destruction, there was a loss of LC/IC in the lower epidermis as detected by T6 reactivity. In fully formed blisters, the LC/IC in the upper half of the epidermis were decreased in parallel with the degree of epidermal necrosis. The character of the lymphocytic inflammatory infiltrate and redistribution in LC/IC are similar to those findings described in allergic contact dermatitis. The clinical, histologic, and immunopathologic changes in erythema multiforme appear to be due in part to cellular immune mechanisms with the lymphocyte as the predominant effector cell, and our data suggest a possible role for LC/IC in this disorder.

Erythema Multiforme↗
PubMed1983

T6 is superior to Ia (HLA-DR) as a marker for Langerhans cells and indeterminate cells in normal epidermis: a monoclonal antibody study.

Previous studies in our laboratory using immunoelectron microscopy have shown that anti-T6 monoclonal antibody reacts with all epidermal Langerhans cells in normal skin. Comparison of the number of T6-positive (+) epidermal cells with Ia (HLA-DR) (+) cells, as defined by the monoclonal antibodies, anti-I1 and anti-I2, disclosed that these latter markers significantly underestimated Langerhans cell and indeterminate cell numbers (p less than 0.01 and p less than 0.001, respectively) when employed in a sensitive 4-step immunoperoxidase procedure. Thus, it appears that all epidermal Langerhans cells and indeterminate cells are not Ia-positive as defined in this system and that Ia(+)/T6(+) and Ia(-)/T6(+) subsets exist. These subsets may be analogous to the Ia(+) and IA(-) subsets of macrophages, in which the former are responsible for antigen interaction with T cells.

Adult↗
PubMed1983

Erythema multiforme: microvascular damage and infiltration of lymphocytes and basophils.

The sequence of alterations occurring in recurrent erythema multiforme was studied with clinical observations, 1-micrometer tissue sections, and immunofluorescence techniques. Lesions evolved through 3 stages: an initial red papule, a vesicle surmounting a red papule, and a target (iris) lesion. Focal endothelial cell swelling was present in clinically normal skin. In the red papule, endothelial cytoplasmic swelling, vacuolization, and nuclear hypertrophy with luminal obliteration of superficial venules developed. These venular alterations were more marked with endothelial cell necrosis, and involved deeper venules as well in vesicular and target lesions. Lymphocytes surrounded the venules and infiltrated the lower epidermis in the red papule and the vesicular lesions. Venular damage was correlated with the degree of infiltration by lymphocytes, apparently the primary effector cell, suggesting the venule as a primary target of injury. Hypogranulated basophils were noted around venules in vesicular and target lesions. Fibrin deposits were identified within and interstitially beneath the vesicles. The presence of lymphocytes, basophils, and interstitial fibrin deposition is similar to the changes of cutaneous delayed-type hypersensitivity and suggests a role for cell-mediated immunity in the pathogenesis of erythema multiforme.

Adolescent↗
PubMed1983

Location of HLA-A,B,C antigens in dendritic cells of normal human skin: an immunoelectron microscopic study.

The distribution of the major histocompatibility antigens HLA-A,B,C, (HLA) on dendritic cells of normal human skin was studied by immunoelectron microscopy and a 4-step immunoperoxidase technique utilizing monoclonal antibodies. Light microscopy revealed peripheral staining for HLA of epidermal and pilar infundibular keratinocytes. In the epidermis, the staining was present from the basal layer to the upper stratum spinosum. In the follicles below the level of the infundibulum, HLA was detected only on rare intraepithelial dendritic cells. These dendritic cells could not be identified in the epidermis due to the HLA staining of the surrounding keratinocytes. Similar cells stained diffusely with anti-T6 antibody; the keratinocytes did not. Immunoelectron microscopy demonstrated: (1) the presence of HLA staining of keratinocyte membranes from the stratum basalis to the level of the upper stratum spinosum and in the pilar infundibulum, (2) the possible absence of HLA on melanocytes, (3) the presence of focal HLA staining of the membranes of epidermal and follicular dendritic cells that contained Birbeck granules and were, therefore, Langerhans cells, (4) dendritic mononuclear cells within the follicular epithelium, which although devoid of Birbeck granules, exhibited similar reactivity with anti-HLA antibody. These findings suggest that HLA antigens are present on the membranes of Langerhans cells, but are not demonstrable on melanocytes in normal human skin.

Antibodies, Monoclonal↗
PubMed1983

Increased intraepidermal melanocyte frequency and size in dysplastic melanocytic nevi and cutaneous melanoma. A comparative quantitative study of dysplastic melanocytic nevi, superficial spreading melanoma, nevocellular nevi, and solar lentigines.

Dysplastic melanocytic nevi (DMN) are distinguished histologically by a hyperplasia of variably atypical intraepidermal melanocytes in a lentiginous epidermal pattern. In order to further characterize the intraepidermal melanocytes of DMN, 4 representative specimens each of DMN, acquired nevocellular nevi (NCN), solar lentigines (SL), and superficial spreading melanoma (SSM) were selected on the basis of predetermined criteria, confirmed in a blind histologic assessment, and compared in a quantitative morphologic study using 6 micron-thick hematoxylin and eosin stained sections of L-dihydroxyphenylalanine (dopa) preincubated vertical tissue slices of lesion and adjacent normal skin. The average melanocyte frequency, expressed as the percent of dopa-reactive perikarya among 600 consecutive basal unit cells, was significantly greater in DMN (60 +/- 23%) than in NCN (18 +/- 3%), SL (25 +/- 7%), and adjacent skin (14 +/- 3%), but similar to that in SSM (71 +/- 11%). The average mean diameter of 200 consecutive epidermal basal unit melanocytes was significantly larger in DMN (11 +/- 2 microns) than in NCN (7 +/- 0.4 microns), SL (6 +/- 0.1 microns), and adjacent skin (6 +/- 0.4 microns), but significantly smaller than in SSM (16 +/- 3 microns). The observed similarities of intraepidermal melanocytes in selected DMN and SSM, as well as distinct differences from melanocytes in selected NCN and SL, support the hypothesis that some varieties of DMN may represent potential precursors of cutaneous melanoma.

Adult↗
PubMed1983

Papular polymorphic light eruption: an immunoperoxidase study using monoclonal antibodies.

Biopsy specimens of papules taken from eight patients with polymorphic light eruption were examined by immunoperoxidase techniques employing monoclonal antibodies. In each case, most infiltrating mononuclear cells were T cells. The majority of T cells were T8-positive (cytotoxic/suppressor) in four cases and T4-positive (helper/inducer) in two. In two cases, approximately equal numbers of both T cell subsets were present. In only three cases were rare B cells identified by their reactivity with anti-IgM antibody. MI-positive mononuclear cells (macrophages) represented less than 5% of cells infiltrating the dermis. In five subjects, anti-T6 antibody stained increased numbers of dermal mononuclear cells considered to be Langerhans/indeterminate cells. The pathogenesis of papular polymorphic light eruption may involve injury to upper dermal venules mediated by T cells and Langerhans/indeterminate cells.

Adult↗
PubMed1983

Distribution of major histocompatibility antigens in normal skin.

The distribution of major histocompatibility antigens HLA-A,B,C (HLA), beta 2-microglobulin (beta 2m), and Ia-like antigens (HLA-DR; Ia) in normal skin was studied in frozen tissue sections by a four-step immunoperoxidase method and an avidin-biotin method employing monoclonal antibodies. HLA and beta 2m were present on the basal and spinous keratinocytes of the epidermis, on the outer root sheath epithelium in the infundibulum of the hair follicle, and on the excretory sebaceous duct epithelium. Ia-positive dendritic cells were found in the epidermis and hair follicles, but they were more frequent in the infundibulum and isthmus of the hair follicle than in its inferior portion or in the epidermis. In the straight eccrine duct, HLA and beta 2m-positivity was most striking in its lower portion. In the superficial duct, there was a less intense staining using the four-step procedure, but when an avidin-biotin method was used, the difference was less apparent. In contrast, the acrosyringial epithelium was markedly Ia-positive with decreasing intensity of staining as the duct penetrated the dermis. No HLA or Ia antigens were identified in eccrine glands and apocrine glands. Eccrine glands were slightly beta 2m-positive. HLA and beta 2m were uniformly present in non-dilated and dilated intradermal apocrine ducts.

Adult↗
PubMed1983

In situ identification of T6-positive cells in normal human dermis by immunoelectron microscopy.

Monoclonal anti-T6 antibody, which reacts with the majority of cortical thymocytes but not peripheral T cells, also reacts with human epidermal Langerhans cells, as shown by a four-step immunoperoxidase method and immunoelectron microscopy. To define whether T6-positive cells are also present in normal human dermis, we used these techniques to demonstrate two immunologically distinct populations of histiocyte-like cells in normal human dermis. The first population contains cells devoid of phagolysosomes or Birbeck granules. These cells react with anti-T6 antibody, but not with monoclonal anti-T3 antibody which defines peripheral T cells, and are found predominantly in and around dermal lymphatic vessels. The second is composed of phagolysosome-containing cells which do not react with anti-T6 antibody or anti-T3 antibody. Because to date, Langerhans cells are the only cells in normal human epidermis that react with anti-T6 antibody, these data provide immunological evidence for a specific link between Langerhans cells and a T6-positive dermal mononuclear cell, possibly the so-called indeterminate cell. In addition, application of these techniques should, for the first time, permit the immunological distinction of these T6-positive mononuclear cells from other cells bearing Ia antigens, such as dermal histiocytes and certain lymphocytes, in normal and diseased skin.

Antibodies, Monoclonal↗
PubMed1983

Distribution of cell surface antigens in histiocytosis X cells. Quantitative immunoelectron microscopy using monoclonal antibodies.

We have shown previously that cells comprising the cutaneous infiltrates of histiocytes X (HXCs), like Langerhans cells (LCs), react with monoclonal anti-T6 antibody. HXCs also react with anti-T4/4b and anti-Ia-like antibodies. To further define the patterns of antibody reactivity in HXCs, we performed immunoelectron microscopy on two clear-cut cases of histiocytosis X using the immunoperoxidase technique. The reaction product of diaminobenzidine, indicating anti-T6 antibody reactivity, was easily detected along cell membranes of HXCs and at sites of possible endocytosis. Anti-T4/4b and anti-Ia antibodies had less cell membrane reactivity. Computerized image analysis aided in discriminating the patterns of anti-T6 antibody in HXCs and from LCs and confirmed that anti-T6 antibody staining was the most intense of the antibodies evaluated. These findings (1) document antigenic similarities and differences between HXCs and LCs on an ultrastructural level, (2) add support to the concept that HXCs are abnormal proliferations of LCs, and (3) demonstrate the association of the cell surface antigen, T6, with apparent endocytotic activity.

Antibodies, Monoclonal↗
PubMed1983

Acral melanoma in Japan.

Clinical records and histologic materials from 81 patients with malignant melanoma at the Department of Dermatology at Tohoku University School of Medicine were reviewed. In addition, a statistical study on 1597 cases of malignant melanoma collected from the Japanese literature from 1961 to 1982 was performed. The annual mortality rate has been increasing almost linearly over the past 20 years. The mortality rate per year for 1980 was 0.21 per 100,000. Five-year survival rate at Tohoku University was 35 percent. The most common site of melanoma was acral, especially the plantar surfaces. The clinical and histologic study of acral melanomas showed that clinicopathologic features are the same as those reported for acral lentiginous melanoma in the United States.

Extremities↗
PubMed1983

Early death from clinical stage I melanoma.

We studied 13 prognostic factors in 582 patients with clinical stage I melanoma to determine which factor or combination of factors was associated with death from melanoma within the first 24 months following diagnosis. Thirty-six patients died during this period. Only 2 deaths occurred in patients with primary tumors thinner than 1.70 mm, and only 2 patients of 189 died with tumors located on the non-BANS extremities, excluding the hands and feet. Individual factors associated with high risk for death within 2 years included level V tumors, acral location, thickness greater than or equal to 3.65 mm, histologic ulceration greater than 3 mm, nodular type, presence of microscopic satellites, greater than 6 mitoses/mm2, positive elective node dissection, absence of lymphocyte response at the tumor base, and absence of an associated nevus histologically. Many of the preceding individual factors are highly correlated. By the use of logistic regression analysis, only one very high risk group was found: 71 percent of patients with level V tumors greater than 1.70 mm thick with histologic ulceration width greater than 3 mm located in an area other than the extremities (excluding hands and feet) had died within 2 years of diagnosis. The ability to select high-risk groups should be useful to investigators involved with the design and evaluation of adjuvant therapy studies.

Adult↗
PubMed1983

Factors associated with death from melanoma from 2 to 5 years following diagnosis in clinical stage I patients.

We studied 14 prognostic factors in 428 patients with clinical stage I melanoma to determine which factor or combination of factors was associated with death from melanoma from 24 to 60 months following diagnosis. Forty-eight patients (11 percent) died during this period. All 17 patients who had visceral metastases present at 24 months died during this period. All surviving patients were followed for at least 60 months. Individual high risk factors included ulceration width (as determined by histology), level IV or V tumor, recurrence other than visceral, 6 or more mitoses per square millimeter, presence of involved nodes on elective dissection, absent or slight lymphocyte response, tumor type other than superficial spreading, location other than extremities (excluding hands and feet), microscopic satellites, thickness, sex, and wide local excision. The presence of sex as a risk factor for patients dying from 2 to 5 years following diagnosis is noteworthy because no sex difference was noted in the early death (less than 24 months) group. Age, presence of a nevus, and histologic regression were not significant factors. A logistic regression analysis selected a combination of the following independent factors: (1) location on extremities excluding hands and feet (favorable), (2) thickness, (3) recurrence other than visceral, (4) positive elective nodal dissection, (5) 6 or more mitoses per square millimeter, and (6) moderate to marked lymphocyte response (favorable). Twenty-five percent of patients with level IV lesions died between 24 and 60 months compared with only a 6 percent death rate within the first 24 months.

Follow-Up Studies↗
PubMed1983

Minimal deviation melanoma: a histologic variant of cutaneous malignant melanoma in its vertical growth phase.

Minimal deviation melanomas are uncommon nevomelanocytic tumors of indeterminate risk that appear as pigmented or nonpigmented skin nodules and are clinically diagnosed as Spitz nevi, hemangiomas, or malignant melanomas. They are characterized histologically by expansile growth in the papillary dermis with reticular dermal infiltration (minimal deviation type) or without reticular dermal invasion (borderline type). The tumors exhibit lesser cytologic atypia in their vertical growth phase (histologic variance) than observed in common forms of melanoma. A retrospective study of outcome in 21 patients with minimal deviation melanoma (mean tumor thickness by Breslow's measurement = 3.6 mm) disclosed recurrent disease in only 3 patients after a mean observation period of 57 months, supporting the impression that these tumors are not as biologically aggressive as common malignant melanomas. The histologic subtypes of minimal deviation melanoma are reviewed along with a discussion of the concept of histologic variance.

Adolescent↗
PubMed1982

Skin lesions suspected to be melanoma should be photographed. Gross morphological features of primary melanoma associated with metastases.

We reviewed photographs of 256 primary cutaneous melanomas to determine the gross morphological correlates of metastases. Seven and a half years after diagnosis, the melanomas with ulceration occupying at least 80% of their surface had the highest rate of metastases (85%), and melanomas without a nodule had the lowest metastatic rate (11%). Melanomas with nodules had a metastatic rate of 62%, and this rate increased in direct proportion to nodule diameter. Even after adjusting for nodule diameter and ulceration, melanomas with single nodules located completely within the confines of an associated plaque had half of the metastatic rate of melanomas with nodules located at the periphery (abutting normal skin). These data suggest that (1) carefully recorded gross pathological data can augment the microscopic pathological data in the determination of prognosis; (2) skin lesions suspected to be melanoma should be photographed; (3) the photograph, if followed by surgical removal of the lesion, should be attached to the pathology report in the patient's permanent medical record; (4) nodule diameter is better correlated with metastases than the total lesion diameter (as traditionally held); and (5) the cytologically malignant melanocytes that constitute the less-raised portion of most melanomas may not be biologically malignant, thus enlarging the precursor concept for malignant melanoma. The TNM staging system for malignant melanoma could be modified to incorporate these data.

Biopsy↗