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Biomedical subjects

M C Mihm

Publications and source records attributed to M C Mihm.

At least 19 recordsLinked to original sources
PubMed1992

Multiple primary cutaneous melanomas.

BACKGROUND: Development of multiple primary cutaneous melanomas is a well-recognized phenomenon. As with single primary melanoma, personal and family histories of melanoma and dysplastic nevi (DN) are considered important risk factors. The natural history and impact of regular follow-up evaluation of this entity were examined. METHOD: Through a search of the computerized data bank of the Pathology Department and the Melanoma Registry of the Pigmented Lesion Clinic at Massachusetts General Hospital, 41 patients with multiple cutaneous melanomas were identified. RESULTS: Mean (+/- standard error) age at first diagnosis was 49 +/- 2 years (range, 21-75 years). The male to female ratio was 2:1. The median number of primary melanomas was two (88%). Three patients had three and one had five. Melanoma types included superficial spreading (70%), nodular (8%), lentigo maligna (2%), and unclassified (10%), and in 7% the type was unknown. Nineteen (46%) patients had histologic and/or clinical evidence of DN. For the group with DN, the mean age at first diagnosis (44 +/- 3 years) was significantly less than that of patients without DN (54 +/- 3 years) (P less than 0.05). Family history of melanoma was found in 10 patients (24%). Multiple melanomas were diagnosed concurrently in 16 patients (39%), whereas in 25 (61%) diagnosis was sequential. For the latter group, the mean tumor thickness from the first (1.21 +/- 0.28 mm) to the second melanoma (0.51 +/- 0.08 mm) decreased significantly (P less than 0.05); the median time interval was 36 months (range, 2-372 months). CONCLUSION: These data confirm the need for complete skin examination for patients with newly diagnosed melanoma; and, with subsequent melanomas appearing as long as 31 years after the first melanoma, continued follow-up with complete skin examinations seems prudent.

Adult↗
PubMed1992

Integrin expression in malignant melanoma and their role in cell attachment and migration on extracellular matrix proteins.

The interaction between melanoma cells and extracellular matrix (ECM) components may be important for invasion and metastasis. The integrins belong to a family of protein heterodimers composed of alpha and beta subunits and the beta 1-integrins are especially important as ECM receptors. We investigated the expression of beta 1-integrins on four human melanoma cell lines (two primary, one from the radial growth phase (RGP) and another from the vertical growth phase (VGP), and two metastatic) and examined their attachment and migration on laminin (LN), type IV collagen (CN) and fibronectin (FN). Among LN and/or CN integrin receptors, only alpha 2 beta 1 (VLA2) was expressed at significantly higher levels in the VGP and metastatic cell lines in comparison to the RGP cell line. In addition, enhanced attachment and migration on LN and CN were significantly inhibited by anti-VLA2 monoclonal antibody (mAb). As to FN receptors, alpha 4 beta 1 and alpha 5 beta 1 expression was heterogeneous among the cell lines, however, it was directly related to enhanced attachment and migration on FN, which also could be inhibited by anti-VLA4 and anti-VLA5 mAbs. Our findings provide evidence for a role in beta 1-integrins, in particular alpha 2 beta 1, in melanoma progression and metastasis.

Cell Adhesion↗
PubMed1992

Actin organization and cell migration of melanoma cells relate to differential expression of integrins and actin-associated proteins.

We have recently described marked differences in cell migration rates and organization of actin in human melanoma cell lines isolated from various stages of tumor progression. Metastatic lines derived from lymph node metastases organized actin into stress fiber arrays and had high mean migration rates in vitro when compared to lines from other stages. Melanoma cells also reveal marked differences in localization of alpha-actinin and beta 1 integrins at stress fiber termination sites (focal contacts). Disruption of this organization is induced by antibodies against beta 1 integrins, alpha-actinin, recently postulated as having a role in linkage of actin to beta 1 integrins, is differentially expressed in melanoma cells by Northern blot analysis and a relatively high alpha-actinin to actin ratio is associated with stress fiber formation and increased cell migration. Furthermore, actin-binding protein, which cross-links actin filaments, is also significantly increased in lines exhibiting high migration rates. Control of migration and actin organization may be mediated by extracellular matrices and/or modulation of actin-associated proteins including alpha-actinin and actin binding protein. These findings provide evidence that an interaction of transmembrane adhesion molecules and elements of the cytoskeleton in melanoma cells may be responsible for differences in migration rates and capacity for metastasis.

Actinin↗
PubMed1992

Desmoplastic melanoma.

Desmoplastic melanoma is a rare tumour of which a limited number of cases have been described. The clinical and histopathological features of desmoplastic melanoma and its variants may give rise to perplexing diagnostic and therapeutic dilemmas. In the past decades, some insight has been gained into the histogenesis of these lesions and discriminating clinical and morphological features are now recognized. Review of the literature reveals an extensive list of differential diagnoses. Adequate surgical excision and close follow-up of these radioresistant, frequently-recurring tumours is strongly advocated.

Diagnosis, Differential↗
PubMed1992

Image analysis of stage 1 melanoma (1.00-2.50 mm): lymphocytic infiltrates related to metastasis and survival.

Image analysis of histologic sections of 11 patients with clinical Stage 1 melanoma, 1.00 mm-2.50 mm, who developed metastasis, was done to determine the significance of lymphocytic infiltrates relative to metastasis and survival. An age, sex, site, and thickness matched control group of non-metastasizing clinical Stage 1 melanoma revealed no significant difference in the lymphocytic infiltrate parameters from the metastasizing group with the exception of the ratio of lymphocyte infiltrate width to the tumor width (p = 0.003). Increased lymphocytic infiltrates within the tumor and subjacent to its base significantly correlated with delayed time to metastasis (p = 0.014 and p < 0.001, respectively) and longer survival period (p = 0.045 and p < 0.001, respectively). Lymphocytic infiltrate area at the tumor base in relation to tumor area was of prognostic value: the larger the ratio, the greater the time interval from metastasis to death (p = 0.008).

Humans↗
PubMed1992

Occurrence of melanoma in "dysplastic" nevus spilus: report of case and analysis by flow cytometry.

We report a case of melanoma arising in a large nevus spilus. On histologic examination, the nevus spilus had diagnostic features of melanocytic dysplasia. Further characterization by flow cytometry showed DNA-aneuploidy within the melanoma as well as in one of the darker pigmented papules within the nevus spilus. The significance of this finding and a review of melanomas originating in nevi spili are presented.

Adult↗
PubMed1992

Desmoplastic melanoma: clinicopathologic aspects of six cases.

We report 6 cases of desmoplastic melanoma. Upon removal and histologic examination, each lesion consisted of a dermal nodule of fascicles of spindle cells, many of which showed pleomorphic and hyperchromatic nuclei. Fascicles, as well as single cells, were seen infiltrating the dermal collagen. Lentiginous hyperplasia of melanocytes with varying but usually slight cellular atypia overlay the dermal proliferations in all cases. Melanophages and some pigmented cells, albeit few in number, were present in the infiltrate, whereas mitotic figures were also noted. These features are most consistent with desmoplastic melanoma, a rare tumor of which a limited number of cases has been described. The clinical and histopathologic features of the lesions presented exemplify the diagnostic and therapeutic dilemma associated with desmoplastic melanoma.

Adult↗
PubMed1992

Angiogenesis and tumor progression of melanoma. Quantification of vascularity in melanocytic nevi and cutaneous malignant melanoma.

BACKGROUND: The capacity of cutaneous malignant melanoma (CMM) to induce angiogenesis is well established. In addition, dysplastic melanocytic nevi (DMN) have been reported to display prominent vascularity relative to common acquired nevi; but this observation has never been verified objectively. EXPERIMENTAL DESIGN: In the following studies, papillary dermal or tumor vascularity was quantified in 10 examples of normal skin, and in a series of 18 melanocytic nevi, 29 DMN, 37 primary CMM and 5 melanoma metastases. Microvessels were identified with the lectin Ulex europaeus agglutinin I. The number of microvessels were counted with an ocular grid (area 7.84 x 10(-2) mm2) at x400 magnification, and the mean vascularity recorded for five fields for each specimen. RESULTS: Mean vascular counts were as follows: normal skin 5.9, common acquired nevus 9.1, nevus with features of DMN 10.3, DMN, slight atypia 11.8; DMN, moderate atypia 12.2; DMN, severe atypia 14.8; primary CMM 25.4; and metastatic melanoma 29.5). Significant differences were recorded for DMN, severe atypia versus melanoma (p less than 0.01), DMN, severe versus common nevi (p less than 0.02) and versus nevi with features of DMN (P less than 0.05). When microvessel counts from CMM in the radial growth phase were compared with those from CMM in the vertical growth phase, or CMM less than 1.0 mm versus those greater than 1.0 mm, no significant differences were found. However, CMM in radial growth did differ from severely atypical DMN (22.4 versus 14.8, p less than 0.05). CONCLUSIONS: These results quantify for the first time a gradual rise in vascularity with tumor progression in the melanocytic system and onset of angiogenesis during the radial growth phase of CMM. Other than severely atypical DMN, DMN did not differ substantially from common nevi with reference to overall vascularity.

Capillaries↗
PubMed1991

Melanoma and the sun: the effect of swimsuits and a "healthy" tan on the risk of nonfamilial malignant melanoma in women.

The authors examined the relation between sun exposure and melanoma risk and tested the previously published site-specific association of bikini use and melanoma of the trunk in a study of 130 cases incident between 1976 and 1984 and 300 controls nested within the Nurses' Health Study. A summary variable derived from four measures of sun sensitivity was more closely associated with melanoma than any component measure. There was no association of bikini use at ages 15-20 years with trunk melanoma risk (relative risk (RR) = 0.8, p = 0.7), and the 95% confidence interval (CI) (0.3-2.6) excludes the previously published estimate. High frequency of swimsuit use outdoors at ages 15-20 years was associated with increased melanoma risk among sun-sensitive women (RR = 6.4, 95% CI 1.7-23.8, p = 0.006), but appeared to be protective among sun-resistant women (RR = 0.3, 95% CI 0.1-1.0, p = 0.06). These findings suggest that the risk of trunk melanoma associated with bikini use is at most modest and that sun-sensitive women may increase their risk of melanoma with frequent sun exposures, but that sun-resistant women do not, presumably because they develop a photoprotective tan.

Adolescent↗
PubMed1991

The histologic spectrum of pigmented spindle cell nevus: a review of 120 cases with emphasis on atypical variants.

The histopathologic features of 120 cases of pigmented spindled nevus (PSCN) from the years 1973 through 1988 were reviewed from a consultative practice heavily weighted with difficult nevomelanocytic lesions. The patients' mean age was 25.2 years, and females outnumbered males (68 versus 52). Extremity lesions made up 69.6% of the total, with the thigh the most common site. The lesions were categorized into one of four variants of PSCN, based on the presence or absence of various architectural and cytologic parameters and involvement of the reticular dermis. Thirteen cases (10.8%) were designated typical PSCN, and were characterized by fascicles of uniform pigmented spindle cells without cellular atypia and limited to the epidermis or papillary dermis. Ninety-five cases (79.2%) were classified as atypical PSCN (PSCN with architectural and/or cytologic atypia). Some of the latter also demonstrated substantial numbers of epithelioid cells, thus exhibiting some overlap with Spitz nevus. Eight cases showed striking features of dysplastic nevus. Ten cases had fascicles of pigmented spindle cells involving the reticular dermis ("plexiform" PSCN). Two cases were designated as combined PSCN because of the presence of banal nevus cells in addition to the spindle cell component. Clinical follow-up of a small group of patients has not suggested, to date, any aggressive behavior. Knowledge of PSCN and its atypical variants is important for discrimination from malignant melanoma.

Adolescent↗
PubMed1991

Histopathologic diagnosis of dysplastic nevi: concordance among pathologists convened by the World Health Organization Melanoma Programme.

Dysplastic nevi are an important indicator of risk of cutaneous malignant melanoma. The study of and, particularly, international communication regarding this group of lesions have been hindered by a lack of precision in diagnosis. In an effort to broaden understanding, a panel of pathologists agreed upon a set of criteria for the diagnosis of dysplastic melanocytic nevi. Two major and four minor criteria were defined. The major criteria are (1) basilar proliferation of atypical nevomelanocytes (extending at least three rete ridges or "pegs" beyond any dermal nevo-cellular component), and (2) organization of this proliferation in a lentiginous or epithelioid-cell pattern. Minor criteria are (1) the presence of lamellar fibrosis or concentric eosinophilic fibrosis, (2) neovascularization, (3) inflammatory response, and (4) fusion of rete ridges. Diagnosis required presence of both major criteria and at least two minor criteria. One hundred fourteen histologic specimens of benign acquired nevi, dysplastic nevi, and radial-growth-phase melanomas were examined by the members of this panel; their diagnoses were compared to determine degree of concordance. The established criteria yielded 92% mean concordance overall.

Diagnosis, Differential↗
PubMed1991

Studies on the cellular origin of neurothekeoma: clinical, light microscopic, immunohistochemical, and ultrastructural observations.

The clinical, histopathologic, and immunohistochemical features of 11 cases of neurothekeoma are reported. One case was examined by electron microscopy. The mean age of the patients was 27.1 years; the study comprised eight female and three male patients. Most lesions were nondescript papules and located on the upper part of the body, seven cases of neurothekeoma on the head. Eight cases were classified as cellular neurothekeoma on the basis of a striking fascicular pattern and three cases as myxomatous neurothekeoma because of prominent myxoid stromal change. All cellular neurothekeomas failed to express S-100 protein, whereas the three myxomatous types were strongly positive for this marker. Other than vimentin, there was no significant immunoreactivity with other immunohistochemical markers. Ultrastructural study of one case of cellular neurothekeoma was inconclusive for cell type although a perineurial origin could not be excluded. On the basis of these results, we conclude that cellular neurothekeoma differs from myxomatous neurothekeoma not only by clinical and histologic findings but also by immunoreactivity with S-100 protein. These findings also suggest the existence of two distinct subtypes of neurothekeoma and possible origin of the two variants of neurothekeoma from different cell types or at least variation in phenotypic expression of a common cell type. On the other hand, it cannot be excluded that these two variants are different stages in the natural history of neurothekeoma.

Adolescent↗
PubMed1991

Plexiform spindle cell naevus: a distinctive variant of plexiform melanocytic naevus.

Twelve cases of a unique plexiform melanocytic naevus that we have termed plexiform spindle cell naevus are reported. The lesions affected young individuals (mean age 22.5 years) of both sexes and were most frequently located on the shoulders and back. The lesions clinically were slightly raised and blue or darkly pigmented, suggesting blue naevus. Histologically these tumours had a symmetrical wedge-shaped configuration, as seen in typical Spitz naevus, with the apex directed toward the deep reticular dermis or subcutis. The pigmented spindle cells were disposed in fascicles in association with neurovascular bundles and adnexal structures, imparting a plexiform architecture to the lesion. The predominant cell type consisted of spindle cells containing a granular melanin and elongated nuclei. Low-grade cellular atypia was commonly noted. Varying numbers of epithelioid cells were observed in most of the cases. In two cases studied, the naevus cells showed S-100 protein and HMB-45 immunoreactivity. The differential diagnosis of plexiform spindle cell naevus includes malignant melanoma, and spindle and epithelioid cell (Spitz) naevus, blue naevus and combined naevus. Plexiform spindle cell naevus is a distinctive type of pigmented spindle naevus distinguished from the above entities by its striking plexiform architecture, predominance of melanin-containing spindle cells and lack of significant cellular atypia.

Adolescent↗
PubMed1991

Cell migration and actin organization in cultured human primary, recurrent cutaneous and metastatic melanoma. Time-lapse and image analysis.

Random cell migration and actin organization in seven human primary, recurrent cutaneous, and metastatic melanoma cell lines were studied by time-lapse video recording and image analysis. The migration of over 800 randomly selected cells from the cell lines were recorded using an inverted microscope with an attached incubator housing. The fraction of cells with random migration rates greater than 10 microns/hour was 8% in an established primary melanoma cell line, 2% and 34% in two recurrent cutaneous melanoma cell lines, and 5%, 30%, 31%, and 60% in four metastatic cell lines. The three metastatic cell lines with significantly higher mean migration rates (P less than 0.001) were derived from lymph node metastases, whereas the fourth metastatic cell line was derived from a visceral metastasis. The cellular morphology and presence of cell nests in the original tissue correlated with in vitro cell morphology and the formation of colonies. The ability of cells to organize actin into stress fibers directly correlated with significantly higher random migration rates and lack of colony formation. Characterization of random migration rates and actin organization of human melanoma cells that are isolated from different stages of tumor progression may lend insight into metastasis.

Actins↗
PubMed1990

Cellular neurothekeoma. A distinctive variant of neurothekeoma mimicking nevomelanocytic tumors.

We describe the clinical, histopathologic, and immunohistochemical characteristics of five examples of a distinctive subtype of neurothekeoma we term "cellular neurothekeoma" (CNT). These lesions are nondescript papules or nodules primarily involving the head and neck areas of young adults. Histopathologically, CNT are fairly well-defined proliferations involving the reticular dermis; they consist of fascicles of polygonal and spindle cells with eosinophilic or pale-staining cytoplasm and neuroid characteristics. Low-grade cytologic atypia and mitotic activity are common. All immunohistochemical markers--including S-100 protein, myelin basic protein, epithelial membrane antigen, and histiocytic antigens--have failed to show positivity in our laboratory. Separation from myxomatous variants of neurothekeoma is based on greater cellularity, less myxomatous change, and less pronounced plexiform compartmentalization by fibrous septae, which resemble perineurium. The differential diagnosis usually includes spindle and epithelioid cell (Spitz) nevus, malignant melanoma (particularly desmoplastic-neurotropic melanoma), cellular blue nevus, and fibrohistiocytic proliferations. The recognition of CNT and its differentiation from melanoma are important so that overly aggressive therapy is avoided.

Adolescent↗