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M C Mihm

Publications and source records attributed to M C Mihm.

At least 91 records · Page 5Linked to original sources
PubMed1995

Choriocarcinoma presenting as a cutaneous metastasis.

The rare presentation of choriocarcinoma as a cutaneous metastasis in a 23-year-old male is reported. Histological and immunohistochemical analysis of the biopsy material demonstrated two distinct cell populations, syncytiotrophoblasts and cytotrophoblasts, with syncytiotrophoblasts strongly positive for human chorionic gonadotropin antigen. Subsequent clinical evaluation revealed a testicular tumor with metastases to lungs, brain, liver and kidney and increased serum levels of human chorionic gonadotropin. The patient died shortly after diagnosis due to complications of metastatic disease despite chemotherapy.

Adult↗
PubMed1994

Clear cell eccrine carcinomas of the skin. A clinicopathologic study of nine patients.

BACKGROUND: Sweat gland carcinomas with clear cell features are extremely rare neoplasms, with few well documented cases reported in the literature. METHODS: Data on nine patients with malignant eccrine adnexal neoplasms characterized by a prominent clear cell neoplastic component were studied. Immunohistochemical stains with a panel of antibodies against epithelial, stromal, and neural antigens were performed on five tumors and electron microscopic examination of one. RESULTS: The tumors showed a spectrum of histologic features and growth patterns that ranged from well differentiated, low grade malignant neoplasms to poorly differentiated, highly aggressive, recurrent, and metastasizing tumors. All tumors contained a varied proportion of cells with abundant clear cytoplasm, similar to those seen in a group of benign eccrine adnexal neoplasms that have been variously designated as clear cell hidradenoma, nodular hidradenoma, clear cell myoepithelioma, and eccrine acrospiroma. Immunohistochemical stains on five tumors and ultrastructural examination in one were consistent with eccrine differentiation. Clinical follow-up of eight patients showed local recurrence in six, followed by metastases in three, despite local excision, radiation, and chemotherapy. Criteria for differentiating these tumors from their benign counterparts and from other types of malignant adnexal neoplasms and metastatic lesions are presented. CONCLUSIONS: The findings indicate that clear cell eccrine carcinomas comprise a heterogeneous group of lesions that may range from locally recurring, low grade well differentiated tumors to highly aggressive, high grade tumors with a definite potential for uncontrollable local recurrence and metastasis. Wide surgical excision is recommended as the primary treatment for such neoplasms.

Adenocarcinoma, Clear Cell↗
PubMed1994

Estrogen and progesterone receptor analysis in pregnancy-associated melanoma: absence of immunohistochemically detectable hormone receptors.

The role of estrogen in the initiation and progression of melanoma remains unclear. Some findings that suggest a hormonal role in melanoma initiation or progression include the following: (1) melanomas arising during pregnancy are thicker than those in nonpregnant women, (2) pregnant women with stage II (regional nodal metastases) melanoma have a worse prognosis than nonpregnant women of similar stage, and (3) melanoma is rare prior to puberty. Although biochemical assays have shown that estrogen-binding proteins are present in malignant melanoma, studies using a sensitive and more specific immunohistochemical technique have not found estrogen receptors (ERs) in melanoma. In our laboratory an immunohistochemical technique using monoclonal antibody H222 can detect ER in tumors with receptor levels lower than 9 fmol/mg protein and detects ER in a variety of tissues and species. In addition, monoclonal antibody KD68 is used to detect progesterone receptors immunohistochemically. We studied 14 cases of pregnancy-associated melanoma. None of our cases, ranging from melanoma in situ to metastatic melanoma, showed positive nuclear staining for ER, nor did any of these cases show positive immunohistochemical staining for progesterone receptor. Despite the wide tissue and species distribution of ER detected by the monoclonal antibody H222, this immunohistochemical technique does not appear to be useful in the study of possible hormonal effects on the progression of malignant melanoma. The estrogen-binding proteins in melanoma detected by biochemical techniques in previous studies probably are distinct from the well-defined human ER.

Adult↗
PubMed1994

Actin-binding protein expression in benign and malignant melanocytic proliferations.

Studies on melanoma cell lines indicate the expression of actin-binding protein (ABP), a peripheral cytoplasmic protein that crosslinks actin, is important for melanoma cell motility. We used an ABP-specific monoclonal antibody to characterize ABP expression in 18 benign nevi and 28 primary and metastatic malignant melanomas. Heterogeneous expression of ABP staining was observed in metastatic melanoma. No clear differences in ABP staining were identified among compound nevi, dysplastic nevi, and superficial spreading melanoma; however, the lentiginous intraepidermal component of the benign and malignant lesions and the pagetoid cells of superficial spreading malignant melanoma were negative for ABP. In contrast, the nested intraepidermal and dermal components of both benign nevi and primary malignant melanoma were positive. The differential expression of ABP of the lentiginous component as opposed to the intraepidermal nests and pagetoid cells of benign nevi or melanoma may represent a capacity of the nested melanocytes to migrate from the epidermis to the dermis during maturation or invasion. Taken together, the findings support that ABP may be important for cell-cell adhesion during tumorigenesis and may play a role in tumor cell ameboid motility during tissue invasion.

Antibodies, Monoclonal↗
PubMed1994

Inter-observer variability among pathologists' evaluation of malignant melanoma: effects upon an analytic study.

This study examined whether inter-observer variability in rating tumor characteristics affected results of an investigation of surveillance bias and malignant melanoma at the Lawrence Livermore National Laboratory. The 20 cases from the Laboratory and their 36 non-Laboratory controls belonged to the same pre-paid health plan and were diagnosed with melanoma between 1970 and 1984. Tumors were independently and then jointly rated by three dermatopathologists blind to the subjects' Laboratory status. The mean difference between the reviewers and the consensus reading for tumor thickness was small, ranging from -0.06 mm (95% confidence interval [CI]--0.12, 0.00) to 0.00 mm (95% CI--0.07, 0.07). Agreement was much lower for histologic type (kappa = 0.48, 95% CI 0.37, 0.58). Because the inter-observer variability, the study's hypothesis was rejected by analyses based on data from the consensus reading and two reviewers, but not on data from the third reviewer. These findings suggest that epidemiologists using data subject to inter-observer variability may want to employ consensus instead of individual ratings.

Dermatology↗
PubMed1994

Severely atypical medium-sized congenital nevus with widespread satellitosis and placental deposits in a neonate: the problem of congenital melanoma and its simulants.

We describe a neonate with a highly atypical melanocytic proliferation that arose in a medium-sized congenital nevus, in association with multiple cutaneous satellite lesions and placental deposits. The patient's pathologic findings and benign clinical course to date raise the problem of diagnosis of congenital melanoma and the importance of clinical follow-up to determine the biologic behavior of severely atypical, histologically malignant proliferations in congenital melanocytic nevi.

Cell Nucleus↗
PubMed1994

Differential effect of magnesium and calcium on integrin-mediated melanoma cell migration on type IV collagen and fibronectin.

We characterized the effects of extracellular Mg2+ and Ca2+ on the regulation of integrin-mediated cell migration of melanoma cells on type IV collagen and fibronectin. Melanoma cell motility was studied using transmembrane migration in modified Boyden chambers and time-lapse video image analysis. Increasing Mg2+ or Ca2+ ion concentration from 0.1 to 10 mM produces distinct effects on melanoma cell migration on type IV collagen. Increasing Mg2+ ion concentration increased cell migration to a maximum at 5 mM, followed by a decrease at 10 mM. In contrast, Ca2+ alone did not support cell migration on this substrate. Combinations of both cations indicate that Ca2+ decreases cell migration in the presence of Mg2+. However, as opposed to the findings on collagen, peak migration on fibronectin was observed at 1 mM and Ca2+ alone was able to support migration on fibronectin. The Mg(2+)-enhanced migration was inhibited by function-blocking monoclonal antibodies anti-alpha 2 or anti-beta 1 integrin subunit on the type IV collagen and anti-alpha 5 and anti-beta 1 on fibronectin. Taken together, the data indicate that Mg2+ promotes the integrin-mediated cell migration, whereas Ca2+ has the opposite effect. The Ca2+ and Mg2+ concentration in the tumour extracellular microenvironment may modulate integrin-mediated functions and melanoma metastasis.

Antibodies, Monoclonal↗
PubMed1994

Differential effects of interleukin 1-alpha (IL-1 alpha) or tumor necrosis factor-alpha (TNF-alpha) on motility of human melanoma cell lines on fibronectin.

Interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF-alpha) induce a motogenic response in a number of benign and malignant cells. We examined the chemokinetic effects of these cytokines on the cell migration of four melanoma cell lines on fibronectin using modified Boyden chambers and video-time lapse analysis. Flow cytometry analysis of IL-1 receptors, TNF receptors, and shifts in beta 1 integrin expression were correlated with the effects of these cytokines on cell migration on fibronectin. The four melanoma cell lines exhibited heterogeneous expression of types I and II IL-1 receptors as well as p60 TNF receptors. Scant p80 TNF receptor expression was detected on only one cell line. Three of four melanoma cell lines demonstrated type I IL-1 receptors by Western blotting. IL-1 alpha and TNF-alpha induced heterogeneous modulation of beta 1 integrin expression in the four melanoma cell lines tested; downward shift of the alpha 2, alpha 3, alpha 4, and beta 1 integrin subunits was detected among three of the melanoma cell lines as were upward shifts of the alpha 4, alpha 5, and alpha 6 integrin subunits among three of the melanoma cell lines. IL-1 alpha and TNF-alpha induced enhanced migration on fibronectin in one of the melanoma cell lines and were related to an upward shift in the alpha 4 and alpha 5 integrin subunit expression. Taken together, the findings indicate that expression of a particular receptor for IL-1 or TNF does not necessarily signal a motogenic response in melanoma cells, but induces heterogeneous shifts in beta 1 integrin expression. However, upregulation in alpha 4 and alpha 5 integrin subunits appears to relate to enhanced migration on fibronectin.

Blotting, Western↗
PubMed1994

Acantholytic dermatosis localized to genitalia and crural areas of male patients: a report of three cases.

A series of 3 cases of acantholytic dermatosis localized to the male genitalia and perineal area with distinct clinical and histological features is presented. These patients did not have a family history of similar disorders and had no evidence of rash elsewhere. Clinically, the eruption was characterized by multiple discrete papules or macerated patches involving the genitalia and the perineum. Histologically, the acantholytic dermatosis had features that resembled both Hailey-Hailey disease and Darier's disease. Similar clinical and histological findings have been reported in females. To the best of our knowledge, this is the first report of these lesions described confined to the genital and perineal areas in male patients. We agree with other authors that this condition may represent a distinct acantholytic eruption in the perineal area that should be distinguished from other generalized blistering acantholytic dyskeratotic disorders that may also involve the genitalia.

Acantholysis↗
PubMed1994

Very late metastasis (27 years) of cutaneous malignant melanoma arising in a halo giant congenital nevus.

We report a case of primary cutaneous melanoma with the incidental finding of a lung metastasis 27 years following the original diagnosis. The case is exceptional in that it is a late metastasis of a melanoma that arose in association with a halo giant congenital nevus. The original tumor was a large dermal/subcutaneous nodule composed of very well-differentiated cells reminiscent of type B nevomelanocytes. The metastasis displayed similar histology. This case emphasizes the unpredictable behavior of malignant melanoma. In cases with 'unusual' histology such as this one, the usual prognostic parameters are less helpful in predicting survival. Melanoma should be included in the differential diagnosis of an undiagnosed lesion suspicious for metastasis even if the primary was removed in the remote past.

Biopsy↗
PubMed1994

Pedunculated lipofibroma. A clinicopathologic study of thirty-two cases supporting a simplified nomenclature.

Thirty-two cases are described of a relatively rare form of benign connective tissue proliferation characterized by ectopic fatty tissue in the dermis. The lesions usually appear as large, solitary, slow-growing, pedunculated to dome-shaped, skin-colored nodules or plaques showing predilection for the buttock and upper thigh. Other areas involved include the back, shoulder, knee, neck, and ear. Twenty patients were women and 12 were men, 19 to 78 years of age (mean, 46.9 years). The size of the lesions ranged from 4 to 69 mm (mean, 49 mm). Histologically, the lesions were characterized by the presence of mature adipose tissue infiltrating around the periadnexal adventitial dermis and between adnexal structures and admixing with dense stromal collagen. Marked deposition of mucopolysaccharides was noted in the majority of the lesions. Clinical follow-up in all 32 patients showed no evidence of recurrence. Because of their distinctive clinicopathologic features, we prefer to designate these lesions as solitary, pedunculated lipofibroma. In addition, seven of the patients had diabetes mellitus, suggesting a possible relation between the two conditions.

Adipose Tissue↗
PubMed1994

Atypical melanosis of the foot. A report of three cases in Japanese populations.

BACKGROUND: Acral lentiginous melanoma is the most common type of malignant melanoma in the Japanese population. In most instances, classic acral lentiginous melanoma or acral lentiginous melanoma in situ can be readily distinguished from other benign pigmented lesions by virtue of its atypical clinical appearance. OBSERVATION: We present three cases of seemingly malignant pigmented lesions on the foot, all arising in Japanese females. Clinically, the lesions are characterized by irregular borders and variegated pigmentation closely mimicking those of acral lentiginous melanoma in situ. However, the histologic findings revealed only focal slight melanocytic hyperplasia with minimal cytologic atypia along the basal layer. Despite the malignant clinical features, thorough histologic examination failed to disclose any area with significant melanocytic atypia or evidence of malignancy. CONCLUSIONS: To the best of our knowledge, similar lesions with the clinical appearance of melanoma in situ and completely lacking histologic evidence of malignancy have not been reported. We, therefore, prefer to designate these lesions as atypical melanosis of the foot to highlight the clinically apparent atypical findings and to distinguish them from malignant melanoma in situ of the foot.

Diagnosis, Differential↗
PubMed1994

Melanoma risk in individuals with clinically atypical nevi.

BACKGROUND AND DESIGN: A lack of consensus as to the clinical and histologic characteristics of dysplastic nevi has resulted in the recommendation to abandon the term dysplastic nevus for the more descriptive atypical nevus or atypical mole. The significance of the presence of one or more such lesions, histologic features notwithstanding, has not been carefully examined. The risk of melanoma was assessed in individuals with atypical nevi monitored regularly in our Pigmented Lesion Clinic. Any patient enrolled in this subspecialty clinic between 1980 and 1985 without the diagnosis of melanoma who had at least one sufficiently atypical-appearing nevus and who was followed up for a minimum of 5 years was entered in the study. RESULTS: A total of 155 such individuals were identified. The mean (+/- SEM) age of the patients at first evaluation was 26 +/- 1 years. The group was followed for 7 +/- 1 years. The male-female ratio was 1:1. A family history of melanoma was present in 71 subjects (46%). Of the 155 patients, two developed melanoma. The thickness of the tumors in both patients was less than or equal to 0.8 mm. Twenty-five patients (16%), including the two with melanoma, had at least one nevus removed that showed "severe nuclear atypia." CONCLUSIONS: The risk of melanoma in individuals with atypical nevi is significantly greater than expected. The elevated risk was demonstrated even though careful, regular evaluations and removal of more atypical lesions were performed. This study provides evidence that, compared with no surveillance, the meticulous monitoring of patients with clinically atypical nevi is more likely to result in the detection of melanoma at thin stages, with an attendant improved prognosis.

Adolescent↗
PubMed1993

Efficacy of 2-cm surgical margins for intermediate-thickness melanomas (1 to 4 mm). Results of a multi-institutional randomized surgical trial.

BACKGROUND: A prospective, multi-institutional, randomized surgical trial involving 486 localized melanoma patients was conducted to determine whether excision margins for intermediate-thickness melanomas (1.0 to 4.0 mm) could be safely reduced from the standard 4-cm radius. METHODS: Patients with 1- to 4-mm-thick melanomas on the trunk or proximal extremities were randomly assigned to receive either a 2- or 4-cm surgical margin. RESULTS: The median follow-up time was 6 years. The local recurrence rate was 0.8% for 2-cm margins and 1.7% for 4-cm margins (p value not significant [NS]). The rates of in-transit metastases were 2.1% and 2.5%, respectively (p = NS). Of the six patients with local recurrences, five have died. Recurrence rates did not correlate with surgical margins, even among stratified thickness groups. The overall 5-year survival rate was 79.5% for the 2-cm margin patients and 83.7% for the 4-cm margin patients (p = NS). The need for skin grafting was reduced from 46% with 4-cm surgical margins to 11% with 2-cm surgical margins (p < 0.001). The hospital stay was shortened from 7.0 days for patients receiving 4-cm surgical margins to 5.2 days for those receiving 2-cm margins (p = 0.0001). This reduction was largely due to reduced need for skin grafting, since the hospital stay for those who had a skin graft was 2.5 days longer than that for those who had a primary wound closure (p < 0.01). CONCLUSION: Margins of excision can be safely reduced to 2 cm for patients with intermediate-thickness melanomas. The narrower margins significantly reduced the need for skin grafting and shortened the hospital stay.

Adolescent↗
PubMed1993

Surveillance bias and the excess risk of malignant melanoma among employees of the Lawrence Livermore National Laboratory.

To assess the role of surveillance bias in the observed three-fold excess of cutaneous malignant melanoma (CMM) at the Lawrence Livermore National Laboratory (LLNL) in California, we examined the thickness of CMMs among all 20 laboratory employees who were members of a large prepaid health plan and whose CMM was diagnosed from 1970 through 1984. For comparison, we reviewed slides of 36 other members of the same health plan matched (usually 2:1) to the laboratory case by age, sex, facility, and year of diagnosis. Three expert dermatopathologists read the slides using a multiheaded microscope to reach a consensus; they were blind to the laboratory employment status of the subjects. We found that from 1970 to 1976, before there was widespread publicity about the excess incidence of CMM at LLNL, lesion thickness was greater for non-LLNL employees (mean difference = 1.5 mm; 95% confidence interval 0.1-2.9). From 1977 through 1984, however, there was no appreciable difference [mean difference = -0.3 mm; 95% confidence limits (CL) = -1.4, 0.9]. Dropping the matching to adjust for histologic type of melanoma as well as gender, year, and age at diagnosis yielded substantially the same results. These data are compatible with an effect of surveillance bias up to around 1976, but in this health plan population, they do not support a role for surveillance bias in the continuing excess incidence observed since that time.

Bias↗
PubMed1993

Role of alpha 3 beta 1 and alpha 2 beta 1 integrins in melanoma cell migration.

Recent findings indicate that variable expression of beta 1 integrins may play a role in differential melanoma cell motility. Primary melanoma (PM) and metastatic melanoma (MM) cultures, derived from the same patient, were tested for their beta 1, alpha 2, alpha 3 and alpha 6 integrin subunit expression and cell migration on type IV collagen (CN IV) or laminin (LN). The MM cell line expressed markedly increased levels of the beta 1, alpha 2 and alpha 3, but not alpha 6 subunit compared to the PM cell line. The MM cell migration rate was significantly higher than that of the PM cell line on LN- or CN IV-coated substrates. Furthermore, the cell migration rate of both lines was significantly higher (p < 0.001) on these substrates than on the control substrates. The MM and PM cell migration was significantly inhibited by function-blocking anti-beta 1 and anti-alpha 3 MAbs, but not by the anti-alpha 6 MAb tested. In contrast, the anti-alpha 2 MAb significantly inhibited MM but not PM cell migration. These data show that the alpha 3 subunit plays a significant role in melanoma cell motility on CN IV and LN and that the alpha 2 subunit has a significant contribution to the motility of the MM cell line.

Antibodies, Monoclonal↗