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M C Mihm

Publications and source records attributed to M C Mihm.

At least 127 records · Page 7Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Application of immunohistochemistry in the differential diagnosis of skin tumors.

As with neoplasms in any tissue, skin tumors may be categorized as epithelial or mesenchymal, benign or malignant, and primary or metastatic. Immunoperoxidase stains are useful in elucidating the nature of the tumor cells, especially in poorly differentiated tumors. It is important to consider that tumors may exhibit staining patterns different from the typical or reported results. This may be because of intrinsic features of the neoplasm such as the aberrant expression of antigens (markers). Furthermore, the staining of the tumor may be affected by tissue preservation and fixation as well as by the selection of antibodies used for staining. For this reason, the pathologist should be vigilant in comparing the results of unknown tumors with standard controls, with results in the literature, and with his or her own experience. Unusual neoplasms may require additional tissue for analysis, study by other ancillary methods such as electron microscopy, or consultation by more experienced laboratories. These guidelines should be helpful in providing accurate diagnosis of skin tumors.

Biomarkers, Tumor↗

Frequency of dysplastic nevi among nevomelanocytic lesions submitted for histopathologic examination. Time trends over a 37-year period.

All cutaneous nevomelanocytic specimens accessioned for histopathologic examination at Massachusetts General Hospital, Boston, in 1950, 1960, 1970, and 1987 were reviewed. The specimens were categorized as malignant melanoma, acquired or congenital benign nevi, blue nevi, spindle and epithelioid cell nevi, and dysplastic nevi. Other processes such as lentigines were excluded. There was a threefold increase in percentage of patients having nevomelanocytic lesions removed (1.5% in 1950 to 4.6% in 1987) compared with total surgical cases over the 37-year period. A progressive increase in numbers and percentages of dysplastic nevi (among nevomelanocytic surgical cases) was noted over a 37-year interval--2 cases (1% of nevomelanocytic cases) in 1950, 4 cases (2%) in 1960, 23 cases (5%) in 1970, and 189 cases (12%) in 1987. These findings confirm the existence of dysplastic nevi by histopathologic criteria as early as 1950 and illustrate the frequencies of various nevomelanocytic surgical specimens among all surgical specimens at four points in time over a 37-year period at a major referral center for pigmented lesions.

Cell Nucleolus↗

Origin of cutaneous melanoma in a congenital dysplastic nevus spilus.

Cutaneous melanoma developed in contiguity with a congenital nevus spilus on the leg of a 79-year-old white woman. The unique features of the nevus spilus in this case were its relatively large size (diameter, 8 cm), irregular gross appearance, lifelong stability until the recent appearance of a tumor nodule, and the presence of intraepidermal melanocytic dysplasia appearing as multifocal elements within darkly pigmented speckles distributed throughout a lightly pigmented background of lentigo simplex. Based on this observation, we suggest that the presence of intraepidermal melanocytic dysplasia in nevus spilus may be a predisposing factor for the development of melanoma. The malignant potential of "dysplastic" nevus spilus requires further study.

Aged↗

Moles and site-specific risk of nonfamilial cutaneous malignant melanoma in women.

We examined the relationship between self-reported mole counts and cutaneous melanoma with respect to anatomic site in 110 case and 231 control female nurses. Counts of moles on the lower leg were better predictors of melanoma risk than were counts of moles on the arm. The relative risk for the highest quintile of lower leg mole counts versus no lower leg moles was 4.2. Mole counts at each site (arm, thigh, and lower leg) were associated with risk of melanoma of the trunk and lower leg, but none were associated with the risk of melanoma of the upper extremity. The absence of direct site-specificity suggests that mole counts primarily indicate systemic melanoma risk, rather than direct risk from the moles themselves.

Adult↗

Comparison of acral nevomelanocytic proliferations in Japanese and whites.

The preponderance of malignant melanomas that occur in the Japanese population affect the palmar and plantar areas, in contrast to those of whites, which occur predominantly on the head, neck, and trunk. Furthermore, a precursor lesion, the dysplastic nevus, has been well defined in nonacral white skin but not in the Japanese. In this paper, a similarity between benign and atypical acral nevomelanocytic proliferations in Japanese and whites is described. However, it appears that in the Japanese group the melanocytes in benign and atypical proliferations are less dendritic than those noted in whites, and, in both groups, extensive pigmentation was noted in both the epidermal and dermal components of benign and malignant lesions in this limited review. A practical approach to classifications of atypism is, likewise, offered.

Female↗

Pigmented spindle cell naevus and its variants: distinction from melanoma.

We report seven examples of pigmented spindle cell naevus (PSCN) and variants, emphasizing their histopathologic differentiation from malignant melanoma (CMM). Confusion with CMM may occur because of upward migration (pagetoid spread) of cells, prominent lateral extension of lentiginous melanocytic hyperplasia, and cytological atypia in spindle cell naevi. However, these proliferations are usually associated with a symmetrical and orderly growth pattern, confinement of the pagetoid spread to the lower epidermis, 'maturation' of the dermal component, and lack of marked cytological atypia.

Adult↗

Juvenile xanthogranuloma. Clinical and pathologic characterization.

The changing name of the juvenile xanthogranuloma bears witness to the evolution of knowledge and experience of its varied clinical and histologic presentations. This study characterizes the clinical, microscopic, and some immunohistochemical features of 34 cases. The salient clinical findings include a bimodal age distribution inclusive of adults, a male:female ratio of 4:1, occasional multiplicity of lesions (20%), and common presentation in the cephalad area. Histologic findings include varied architectural patterns, cellular participation in various proportions by foamy histiocytes, epithelioid monocytes, lymphocytes, plasma cells, eosinophils, Touton giant cells, and spindle cells of two forms (dendritic and fusiform). S100-positive dendritic cells comprised a minor, but important, component at expansion zones. The significance of these findings is described.

Adolescent↗

Primary cutaneous aspergillosis mimicking dermatophytosis.

We recently reviewed a skin biopsy specimen obtained from a child with acute monocytic leukemia that demonstrated abundant mycelia present within a keratin plug of a hair follicle, a granulomatous dermal inflammatory infiltrate, and focal dermal invasion by fungi. These histologic findings were suggestive of an invasive dermatophyte infection; however, Aspergillus flavus was identified by culture. This case illustrates the need for care in interpreting biopsy specimens of cutaneous fungal infection in the immunocompromised host, since proper treatment is determined by the specific agent present. The morphological features of fungi in tissue sections and histopathologic patterns of host response in the immunocompromised patient may be misleading in trying to identify fungal pathogens. At present, culture is the most reliable method for identifying pathogenic fungi and should be utilized to confirm appropriate therapy.

Amphotericin B↗