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Biomedical subjects

M C Mihm

Publications and source records attributed to M C Mihm.

At least 163 records · Page 9Linked to original sources

Coexpression of neurofilament and keratin proteins in cutaneous neuroendocrine carcinoma cells.

Four cases of neuroendocrine carcinomas (NECA) of the skin were studied by indirect immunofluorescence, using a monoclonal antikeratin antibody and a polyclonal antineurofilament antibody. Fifty to ninety percent and 80 to greater than 95% of the NECA cells stained with the antineurofilament antibody and the antikeratin antibody, respectively. Using double-labeling indirect immunofluorescence we could also demonstrate that, in 3 cases studied, some of the NECA cells, but not all, stained with both antikeratin and antineurofilament antibodies. These results, together with the recent knowledge of the intermediate filament protein type of normal Merkel cells (MC), tend to support the hypothesis that NECA cells do not originate from epithelial MC but from dermal neuroendocrine cells. A dual concept of intraepithelial MC and extraepithelial intradermal neuroendocrine cells, "from possible distinct origin," is proposed. Such a system has already been suggested for the neuroendocrine cells of the appendix and bronchial mucosae.

Adenocarcinoma↗

Detection of DNA-psoralen photoadducts in mammalian skin.

An immunofluorescence (IF) method for the detection of 8-methoxypsoralen (8-MOP) photoadducts to DNA has been developed to assess nuclear damage in keratinocytes and melanocytes after psoralen plus UVA (PUVA) treatment, both under in vitro and in vivo conditions. Cryostat sections of the albino and pigmented guinea pig and human skin were used for in vitro studies to establish minimal and maximal drug concentration and UVA dosimetry for the detection of DNA-8-MOP photoadducts. Limits of detection were as low as 10 ng/cm2 8-MOP and 1 J/cm2 UVA for skin sections and sodium bromide-split epidermal sheets. Guinea pigs treated with topical PUVA revealed positive IF stain in epidermal cell nuclei at a threshold dose of 100 micrograms/cm2 8-MOP and 13 J/cm2 UVA. Pretreatments of cryostat cuts with ethanol and alkali before IF test enhanced the sensitivity of detection in vivo about 10-fold and enabled us to follow the repair of DNA damage after treating normal guinea pig skin with a dose of 50 micrograms/cm2 8-MOP plus 6 J/cm2 UVA. The most interesting findings were as follows: A sensitive method to detect PUVA-induced nuclear damage in epidermal and dermal cells was developed. PUVA treatment induced nuclear DNA damage to melanocytes as well as to adjacent keratinocytes, and melanocytes appeared to be 10 times less vulnerable to photo-damage than keratinocytes. There was a greater propensity for the proliferative cells to be damaged by PUVA. PUVA induced nuclear damage up to 700 micron depth in the dermis. The usefulness of the IF test in detecting DNA damage in microgram and ng amounts in vivo and in following the repair of damaged DNA induced by PUVA.

Animals↗

Prognosis of clinical stage I melanoma patients with positive elective regional node dissection.

We tested 12 clinical and histologic variables to see which ones best predicted death from melanoma in 66 patients with positive elective regional node dissections (clinical stage I, pathologic stage II [CSI, PSII]). Despite the presence of lymph node metastases, not all patients had poor prognoses. Patients with tumors less than or equal to 3.5 mm and a percentage of positive nodes less than or equal to 20% had a 7-year survival rate of 66%. Within this low-risk group the subset with primary lesions on the trunk or extremities (except hands and feet) had a 7-year survival rate of 76%. This compares with poor 7-year survivals of 29% and 30% observed in other defined high-risk groups. Our results confirm and extend earlier observations concerning the prognoses of CSI, PSII melanoma patients and are relevant to any ongoing and future studies concerning elective regional node dissection (ERND) or adjuvant therapy trials in melanoma.

Actuarial Analysis↗

Depletion and repopulation of epidermal dendritic cells after allogeneic bone marrow transplantation in humans.

We have observed marked depletion of epidermal dendritic cells, defined by monoclonal antibodies directed against HLA-DR (Ia-like) and T6 antigens, after allogeneic bone marrow transplantation. To more precisely characterize this observation, we examined a total of 39 sequential biopsies from 15 patients both before and after allogeneic bone marrow transplantation. Profound depletion of HLA-DR and T6-positive epidermal dendritic cells was observed early after transplantation (1-4 weeks), followed by gradual and variable repopulation. Transmission electron microscopy confirmed absence of dendritic cells in selected biopsies. Depletion of dendritic cells did not appear to be related to development of clinical or histologic evidence of graft-versus-host disease, suggesting that depletion may relate to pretransplant conditioning regimens. The rate of return of these cells, however, may be influenced by the presence or persistence of clinical disease. Repopulation of epidermal dendritic cells after initial depletion in bone marrow transplantation represents a human model relevant to studies concerned with the origin and kinetics of Langerhans cells.

Adolescent↗

[Unusual and unknown aspect of cutaneous malignant melanoma: minimal deviation malignant melanoma. Retrospective study of 45 cases].

Minimal deviation malignant melanoma (MDMM) is a rare melanocytic tumor of the skin that shares both malignant and benign histologic features: 1) a vertical growth phase similar to that of malignant melanomas with expansile nodules invading throughout the reticular dermis (Clark's level IV), and even the subcutaneous fat (Clark's level V); 2) but a monotonous and uniform proliferation of melanocytic cells that are only moderately atypical. A very slight cellular maturation from the top to bottom of the lesions may be observed, but usually there is no maturation at all. By themselves, the cells do not appear as malignant. A borderline variant of MDMM shows identical cytological and growth pattern features, but remains confined to a Clark's level III of invasion. Over the past 14 years, 45 cases (female to male ratio: 1.5:1.0) of MDMM, 8 of which were of the borderline variant, were observed. The lesions appeared as acquired pigmented tumors, 0.5 to 1.0 cm in size which predominated on the trunk. Young adults (mean age: 34 years) were most frequently involved. Based on the cytological characteristics of the cellular proliferation, they could be subdivided in 4 groups: 1) epithelioid and spindle cell type (15 cases); 2) epithelioid type (14 cases); 3) spindle cell type (7 cases); and 4) pigmented spindle cell type (9 cases). The mean thickness of the 45 cases was 3.06 mm (1.24 mm for the borderline lesions; 3.40 mm for the MDMM). Tumors with a spindle cell component appeared thicker than those without. Mitoses were numerous (mean: 3.2/10 high power fields). Each tumor but one showed a junctional component. This appeared as melanocytic hyperplasia or melanocytic nests at the dermoepidermal interface. Moreover, 10 cases (7 MDMM and 3 borderline tumors) disclosed intraepidermal spread of melanocytes. However, as observed with the dermal component of the lesions, these intraepidermal melanocytes never appeared cytologically malignant, although moderate atypism could be observed. At last, an association with a compound or dermal nevus was seen in 8 cases. MDMM appears as a particular subgroup of cutaneous malignant melanomas with distinct and characteristic histologic features. Its differential diagnosis includes blue nevus, especially the cellular variant, combined nevus, spindle and epithelioid cell nevus (Spitz-Allen's nevus) and cutaneous metastasis of malignant melanoma. The most important features for the differential diagnosis are the growth pattern, the absence of cellular maturation, the absence of real malignant cells and moderate cellular atypism.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Conservative surgical management of superficially invasive cutaneous melanoma.

Between 1976 and 1980, 136 patients were evaluated for primary treatment of cutaneous melanoma. Forty-nine lesions were invasive to Clark's Level II (38 patients) or III (11 patients) with a thickness of 0.3 to 1.2 mm. Conservative re-excision was advised as definitive therapy for these patients. The margin of resection was defined as the maximum excision that would allow primary closure of the wound. Pathology reports of the re-excised specimens revealed the narrowest margins to be 0.7 to 4 cm. Unexpected residual tumor was present in 2 specimens and melanocytic hyperplasia in 12 specimens. After a follow-up period of 2.5 to 7.0 years, there have been no local recurrences. One patient developed regional lymph node metastases 16 months and, then central nervous system (CNS) metastases 25 months after primary treatment. A second patient died with pulmonary metastases 4.5 years after initial therapy. Melanomas that are not deeply invasive do not require wide excision and skin grafting for local control. Occasionally these thin lesions do produce systemic metastases, emphasizing the need for long-term follow-up of even "low-risk" patients.

Adult↗

Follicular mucinosis: a detailed morphologic and immunopathologic study.

Two patients with the benign type of follicular mucinosis (FM) are presented. Their clinical features and course were characteristic for this subgroup of FM. Light and electron microscopy, direct immunofluorescence, and immunoperoxidase cell marker studies were undertaken to characterize the nature of the disease process. Light microscopy confirmed the follicular outer root sheath and sebaceous gland epithelial degenerative changes. The infiltrating inflammatory cells were morphologically benign. Electron microscopy detailed the cellular associations in the areas of degenerative change. Disattached keratinocytes were closely apposed to significant numbers of macrophages and Langerhans cells. Direct immunofluorescence studies demonstrated primarily complement (C3) and fibrinogen/fibrin in areas of reticular degeneration. Immunoperoxidase studies revealed large numbers of T cells and macrophages and a striking increase in the number of Langerhans cells in the affected follicular epithelium. The findings suggest that cell-mediated immune mechanisms may play a role in the pathogenesis of this disorder.

Adult↗

Immunopathology of pityriasis lichenoides acuta.

Eleven biopsy specimens (five papules and six dusky or crusted lesions) from four patients with pityriasis lichenoides et varioliformis acuta ( PLEVA ) were studied by direct immunofluorescence and immunoperoxidase technics. Slight vascular deposits of IgM and C3 were present in most lesions. Slight perivascular deposits of fibrin were observed in early lesions; more extensive perivascular and interstitial deposits of fibrin were detected in advanced lesions. Most of the infiltrating cells were T lymphocytes; cells with cytotoxic/suppressor phenotype (T8-positive) were generally more numerous than cells with helper/inducer phenotype (Leu-3a-positive, T4-positive). A marked increase in epidermal T8-positive cells over epidermal Leu-3a/T4-positive cells was found in late lesions. Moreover, a reduction of the ratio of circulating T4-positive to T8-positive cells was observed in most cases. The number of epidermal T6-positive (Langerhans/indeterminate) cells was decreased in the lower as compared with the upper stratum spinosum. About 5% of perivascular infiltrating cells were T6-positive. These results suggest that cell-mediated immune mechanisms are probably important in the pathogenesis of PLEVA .

Adult↗

Lentigo maligna melanoma has no better prognosis than other types of melanoma.

We studied 48 patients with lentigo maligna melanoma (LMM) and compared the clinical stage I patients with non-LMM melanoma patients (matched by site and thickness) to see if prognosis differed. There was no significant difference in mortality from melanoma between the two groups (P = .68) after a mean follow-up time of five years (67.5 months for LMM, 60.5 months for non-LMM). In addition, a Cox multivariate analysis of the entire matched group showed that only thickness was significantly associated with death from melanoma (P = .0007) while histology (LMM v non-LMM) did not make a significant contribution (P = .61). Our data suggest that after accounting for primary tumor thickness and site, LMM and non-LMM have the same prognosis and biologic behavior, in contrast to the widely held belief that LMM has a better prognosis than other forms of melanoma.

Actuarial Analysis↗

Linear IgA bullous dermatosis v dermatitis herpetiformis. Quantitative measurements of dermoepidermal alterations.

Linear IgA bullous dermatosis (LAD), also known as "atypical dermatitis herpetiformis," is a disorder that is distinct from classic dermatitis herpetiformis (DH). In eight patients with DH and six with LAD, quantitative assessment of a variety of histopathologic variables was made. The number of rete tips with neutrophils in basal vacuoles and the length of the epidermal basement membrane zone (BMZ) associated with these findings were greater in LAD than DH. The number of microabscesses of neutrophils in the dermal papillae and the length of epidermal BMZ associated with them were greater in DH than in LAD. By using the number of microabscesses and the number of rete tips with neutrophils in basal vacuoles in a probability model, we found by retrospective analysis that a correct diagnosis could be made for LAD in 75% of biopsy specimens with a probability of 97% and in all cases of DH with a probability of 92%. Using this model, we made no misdiagnoses. This is the first diagnostic probability model in dermatopathology that expresses a confidence level in diagnosis.

Adult↗

Papular polymorphous light eruption. Fibrin, complement, and immunoglobulin deposition.

Biopsy specimens of papules taken from eight patients with polymorphous light eruption ( PMLE ) were examined by a direct immunofluorescence technique. Extensive intervascular and focal perivascular deposits of fibrin were detected in each case. Slight vascular deposition of C3 and IgM were observed in five and two patients, respectively. The lupus band test was negative in all cases. The findings suggest that venular injury with activation of the clotting system is involved in the development of lesions in PMLE .

Adult↗

Multivariate analysis. Some guidelines for physicians.

"Mystified" best characterizes the feeling of many physicians as they read the results of a multivariate analysis. Much of the mystery disappears when two items are shown: (1) explicit tabulations revealing how each factor selected by the analysis relates to outcome, both singly and jointly with other factors; and (2) alternative models generated by repeating the analysis after removing the most important variables one by one from the list of factors that was initially analyzed. In this way, one can determine which variables are good stand-ins or substitutes for the best variables in the initial analysis. Showing these substitutes may expose exaggerations in benefits attributed to a particular therapy (ie, elective regional node dissection for clinical stage I malignant melanoma). We have applied these guidelines to examples in the literature, particularly studies of malignant melanoma.

Humans↗

Biochemical studies of immune complexes. II. Purification of immune complexes from sera of patients with malignant melanoma.

Circulating immune complexes (CICs) from serum samples of patients with malignant melanoma were isolated in high yield utilizing a bifunctional chromatography matrix that binds all normal serum proteins except IgG-containing immune complexes (ICs), IgG, and transferrin. Protein fractions were subsequently analyzed by polyacrylamide gel electrophoresis (PAGE) and characterized by molecular weight. By this method, one common and several unique component nonimmunoglobulin proteins of the ICs were identified. These proteins possess similar molecular weights to several previously described human melanoma antigens. This technique should permit biochemical and immunological characterization of the component antigens of CICs in melanoma and other malignancies.

Antigen-Antibody Complex↗

Dysplastic melanocytic nevi in histologic association with 234 primary cutaneous melanomas.

Dysplastic melanocytic nevi (DMN) are irregularly pigmented lesions characterized by (1) atypical melanocytic hyperplasia in a lentiginous epidermal pattern (AMHL), (2) one or more dermal mesenchymal changes, and (3) frequently a dermal nevocellular nevus. In order to determine an association between DMN and cutaneous melanoma, the dominant histologic feature of DMN (namely, AMHL) was sought in histologic contiguity with 234 primary melanomas. Of these 234 cases, 9 were lentigo maligna melanomas. Of the remaining 225 cases, 49 (21.8%) were associated with AMHL in the same histologic section as (but beyond the most lateral margin of) intraepidermal and invasive melanoma. AMHL was directly associated with the presence of dermal nevocellular nevi in histologic contiguity with melanoma, and a greater number of histologic slides with melanoma available for review. AMHL was inversely associated with nodular melanoma. Most of the AMHL cases were not associated with familial melanoma, but the total number of familial cases was low. The histologic association between AMHL and melanoma in one fifth of cases in this series supports the hypothesis that at least some cutaneous melanomas may have an origin in DMN.

Adult↗