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Martin C Mihm

Publications and source records attributed to Martin C Mihm.

At least 55 records · Page 3Linked to original sources
PubMed2003

Malignant melanoma arising in a sebaceous nevus of the scalp.

This is the first report of malignant melanoma arising from sebaceous nevus (SN) of the scalp, although it has been known that various benign and malignant neoplasms may develop in association with SN. After the excisional biopsy for SN with 5 mm free margin, pathological examination revealed the coexistence of nodular melanoma invading to the reticular dermis (IV level of Clark) for a maximal depth of 4 mm. After resection with another 20 mm free margin, there has been no evidence of local recurrence or distant metastasis for nine years.

Female↗
PubMed2003

Pathology of malignant melanoma.

Understanding the fundamental aspects of the pathology of melanoma is crucial for the surgeon to deliver optimal care to the patient with melanoma. Pathology provides diagnostic data, offers prognostic information, and, to a large extent, directs management. This article reviews several aspects of the pathology of melanoma, with special relevance to the surgeon, including benign clinicopathologic simulators of melanoma, fundamental concepts of the pathology of melanoma, histopathologic prognostic factors of melanoma, approach to lymph nodes, and implications of the revised staging system.

Diagnosis, Differential↗
PubMed2003

Cutaneous manifestations of Crohn's disease, its spectrum, and its pathogenesis: intracellular consensus bacterial 16S rRNA is associated with the gastrointestinal but not the cutaneous manifestations of Crohn's disease.

The classic pathology of skin disease discontinuous from the inflamed gastrointestinal (GI) tract in patients with Crohn's disease (CD) includes pyoderma gangrenosum (PG), erythema nodosum (EN), and so-called metastatic Crohn's disease. The purpose of this study was two-fold: First, we explored the full spectrum of cutaneous lesions associated with Crohn's disease, and second, we sought to explore a potential molecular basis of the skin lesions in patients with CD. In this regard, we analyzed skin and GI tract biopsies from affected patients for the consensus bacterial SrRNA to determine whether direct bacterial infection was associated with either condition. Formalin-fixed, paraffin-embedded sections were studied and correlated to clinical presentation and histories from 33 patients with CD. Consensus bacterial RNA sequences were analyzed using an RT in situ PCR assay on both skin biopsy and GI biopsy material. The GI tract material included biopsies from 3 patients who had skin lesions and from 7 patients in whom there were no known skin manifestations. There were 8 cases of neutrophilic dominant dermal infiltrates, including pyoderma gangrenosum, 6 cases of granuloma annulare/necrobiosis lipoidica-like lesions, 5 cases of sterile neutrophilic folliculitis, 5 cases of panniculitis, 4 cases of vasculitis, 2 cases of psoriasis, 2 cases of lichenoid and granulomatous inflammation, and 1 case of classic metastatic CD. Intracellular bacterial 16S rRNA was detected in 8 of 10 tissues of active CD in the GI tract, of which 3 of the cases tested were from patients who also developed skin lesions at some point in their clinical course; in contrast, none of the skin biopsies had detectable bacterial RNA. The dermatopathological manifestations of CD discontiguous from the involved GI tract mucosa have in common a vascular injury syndrome, typically with a prominent extravascular neutrophilic and/or histiocytic dermal infiltrate. In addition, this study, the first to document in situ intracellular consensus bacterial SrRNA in the GI tract in CD, suggests that hematogenous dissemination of viable microbes is not associated with the cutaneous manifestations of this disease. Bacteria do, however, appear to play a role in bowel lesions of patients with CD.

Adolescent↗
PubMed2003

PTEN expression in normal skin, acquired melanocytic nevi, and cutaneous melanoma.

BACKGROUND: Although various studies have shown mutations of the tumor suppressor gene, PTEN/MMAC1, in primary, metastatic, and cultured cutaneous melanoma specimens, little is known about the pattern of PTEN protein expression in early melanocytic tumor progression. OBJECTIVE: To further investigate the role of PTEN in melanocytic tumor development. METHODS: We assessed the level and distribution of PTEN in normal skin, 39 acquired melanocytic nevi, and 30 primary cutaneous melanomas, including lentigo malignas, by immunostaining. RESULTS: We found high levels of PTEN expression in cutaneous muscles, nerves, and muscular arteries, and moderate-to-high amounts of PTEN in the epidermis, follicular epithelium, and sebaceous and eccrine glands. PTEN staining in cutaneous lymphatics, dermal and periadnexal adventitial fibroblasts, and chondrocytes were variably absent. Junctional melanocytes and chondrocytes frequently exhibited preferential nuclear staining. We found uniformly strong PTEN expression in the cytoplasm of almost all benign and dysplastic nevi. However, there was some evidence of nuclear PTEN loss even in the benign melanocytic proliferations. In addition, out of 30 primary cutaneous melanomas and lentigo malignas, we detected diffuse expression of PTEN in 11 (37%) tumors, widespread loss of PTEN in 11 (37%) tumors and mixed PTEN expression in 8 (27%) lesions. In the primary cutaneous melanomas, PTEN was largely localized to the cytoplasm. CONCLUSIONS: The presence of PTEN in benign melanocytic tumors and the absence of PTEN in a significant proportion of primary cutaneous melanomas support a role for PTEN loss in the pathogenesis of melanoma.

Humans↗
PubMed2003

Pyoderma gangrenosum: a review.

Since its first description in 1930, the pathogenesis of pyoderma gangrenosum (PG) has remained obscure even as an ever-widening array of systemic diseases has been described in association with it. The histopathologic distinction of PG from other ulcerative processes with dermal neutrophilia is challenging and at times impossible. In consequence, when confronted with a biopsy from such a lesion, the pathologist has an obligation to obtain a full and detailed clinical history. In short, as a diagnosis of PG does not hinge exclusively upon the biopsy findings in isolation from other studies, a solid knowledge of the clinical features, the systemic disease associations and the differential diagnosis will help the pathologist to avoid diagnostic pitfalls or the generation of a report which is non-contributory to patient care. In this review, we describe in detail the different clinicopathologic forms of PG, summarize the diseases associated with this process in the literature and in our experience, and briefly review the treatment options.

Adult↗
PubMed2003

Cutaneous vasculitis: a review.

As the skin is commonly involved in systemic vasculitic disorders as well as those hypersensitivity states whose expression is largely skin-confined, cutaneous vasculitic lesions offer a window to diagnosis and a ready source of accessible tissue for biopsy. In this review, we discuss the pathologic manifestations of chronic vasculitic syndromes such as granuloma faciale and erythema elevatum diutinum; IgA-associated vasculitis including Henoch-Schonlein purpura; vasculitis seen in the setting of cryoglobulinemia and hypergammaglobulinemia of Waldenstrom, hereditary deficiencies of complement, and IgA deficiency; those leukocytoclastic vasculitides resulting from hypersensitivity reactions to drug, chemical and foodstuff ingestion; and those vasculitides seen in patients with systemic diseases such as polyarteritis nodosa, rheumatoid arthritis, mixed connective tissue disease, systemic lupus erythematosus, Sjogren's syndrome, relapsing polychondritis, Behcet's disease, Wegener's granulomatosis, and allergic granulomatosis of Churg and Strauss.

Humans↗
PubMed2003

Photodynamic therapy for cutaneous proliferative vascular tumors in a mouse model.

Photodynamic therapy with benzoporphyrin derivative monoacid ring A and red light (PDT-BPD) has been used to treat human choroidal hemangiomas, and may be useful for cutaneous vascular lesions. The potential for PDT-BPD to inhibit selectively vascular tumor growth was tested in a mouse angiosarcoma model, of which the tumor growth mimics the proliferative phase of hemangiomas. Vascular tumors arising after intradermal injection of immortalized murine endothelial cells were exposed to 50 to 150 J per cm2 of 690 nm laser light 15 min after intravenous injection of 1 mg per kg BPD. Tumor volume and gross response were followed after PDT-BPD and compared with control tumors receiving no treatment, light alone, or BPD alone. At 2 wk, hematoxylin-eosin and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling stained tumor sections was performed. There was a selective, fluence-dependent inhibition of tumor growth after PDT-BPD (p< or =0.05), typically with eradication of tumors exposed to higher fluences. A common effect was the replacement of tumor by small scar. Surrounding PDT-BPD exposed normal skin showed no changes. Based on these results, we conclude that PDT-BPD can lead to selective eradication of these tumors. Further studies investigating the efficacy of PDT-BPD for human hemangiomas are warranted.

Animals↗
PubMed2003

Immunologic escape and angiogenesis in human malignant melanoma.

BACKGROUND: Melanoma escape mechanisms include immunosuppressive and angiogenic cytokine production. OBJECTIVE: We sought to determine vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) expression by immunohistochemistry, and soluble circulating plasma levels of VEGF, bFGF, IL-10, and transforming growth factor-beta2 in patients with different stages of melanoma. METHODS: Biopsy specimens from 42 patients with primary melanoma and 9 with cutaneous metastases were studied by immunohistochemistry. In another 46 patients with melanoma (8 stage I and II; 18, III; and 20, IV) and in 10 healthy control participants, bFGF, VEGF, IL-10, and transforming growth factor-beta2 circulating levels were analyzed. RESULTS: bFGF was positive in 85% and VEGF in 47.5% of 42 primary melanomas. Of 10 patients with primary melanoma (Breslow depth 1.5-3 mm) 6 were VEGF positive and had metastases develop, whereas 4 were VEGF negative and had no metastases at 5 years of follow up. VEGF, bFGF, and IL-10 plasma levels in patients with stages III and IV melanoma were higher than the control group (P <.05 and P <.01, respectively). An inverse relationship was found between VEGF and IL-10. Specifically, in 7 patients with IL-10 levels higher than 10 pg/mL, VEGF levels were less than 49 pg/mL (P <.05); in 9 patients with VEGF levels higher than 100 pg/mL, IL-10 levels were less than 6.7 pg/mL (P <.01). CONCLUSION: VEGF expression in 1.5- to 3.0-mm Breslow depth melanomas may be considered as an unfavorable prognostic factor. Immunosuppressive (IL-10, transforming growth factor-beta2) and proangiogenic (bFGF, VEGF) cytokines are increased in metastatic melanoma. Inverse plasma levels between IL-10 and VEGF in patients with metastatic melanoma are shown in vivo for the first time, the significance of which must be further investigated.

Adult↗
PubMed2003

Malignant melanoma 2003: predisposition, diagnosis, prognosis, and staging.

The incidence and mortality of melanoma has seemed to level off for certain groups after a steady increase during the last 50 years. This trend is suspected to be secondary to education efforts aimed at prevention and better detection and removal of thin, biologically benign melanomas. Since no effective systemic therapies exist for metastatic melanoma, early detection and removal of thin melanomas offer the best chance of cure. For thicker melanomas, sentinel lymph node biopsy has improved the accuracy of staging and prognostic evaluation. However, approximately one third of patients diagnosed with metastatic melanomas present without previous regional lymph node metastases. As the genomic understanding of melanoma's pathogenesis grows, new methods likely will be developed to more accurately identify the people at risk for melanoma, those who have high-risk melanomas, and those who have disseminated disease. We review current and potential biomarkers useful for the screening for and prevention, diagnosis, staging, and prognosis of melanoma.

Cytodiagnosis↗
PubMed2003

Biomarkers in melanoma: predisposition, screening and diagnosis.

Melanoma's incidence and mortality for certain groups has appeared to level off after a steady increase over the last half century. This trend is suspected to be due to better detection and removal of thin, biological early melanomas. However, to date, no prospective evidence exists to clearly demonstrate the efficacy of prevention and early detection in decreasing melanoma mortlity. Nonetheless, many studies suggest that both self-assessment of risk factors or clinician examination can identify a proportion of patients at highest risk for melanoma who may benefit from behavior modification (primary prevention) and routine screening (secondary prevention). Compromising these goals is the fact that neither the clinical or histologic diagnosis of melanoma is 100% accurate. Clinical diagnosis of melanoma, based on evaluation of a skin lesion's color and shape, correlates best with the experience of the clinician. Ancillary technologies have been developed to improve clinical accuracy of suspicious skin lesions but a subset of melanomas exist that do not fall in the spectrum of the 'ABCDE' guidelines commonly used for melanoma identification. Similarly, at the histologic level (the 'gold standard' of diagnosis), overlap exists between benign and malignant melanocytic proliferations leading to both over and underdiagnosis of melanoma. A better understanding of melanoma's pathogenesis has identified disease-related biomarkers that may more reliably differentiate a melanocytic nevus from melanoma. In this paper, we review current and novel, potentially more accurate, biomarkers and supplementary technologies that can be used for the prevention, screening and diagnosis of melanoma.

Animals↗
PubMed2003

Biomarkers in melanoma: staging, prognosis and detection of early metastases.

Currently, melanoma remains a surgical disease since early detection and excision of thin melanomas offers the best chance of a cure. Despite intensive clinical investigation, no effective systemic therapies exist for metastatic melanoma. Sentinel lymph node biopsy has greatly aided the staging and prognostic evaluation of primary cutaneous melanoma, however, approximately a third of patients diagnosed with metastatic melanomas present without prior regional lymph node involvement. Additional prognostic biomarkers exist which help determine the risk of advanced melanoma but the accuracy for each current marker is less than 100%. A greater understanding of the biology of melanomas and the development of new methods to identify patients with early (subclinical) metastatic disease may allow for selective and more effective therapy for patients at-risk for advanced disease. In this paper, current and novel potentially more accurate biomarkers for the staging and prognostic evaluation of melanoma patients, and for the detection of subclinical metastases are reviewed.

Biomarkers, Tumor↗
PubMed2002

Melanocytic proliferations associated with lichen sclerosus.

OBJECTIVES: To describe the clinicopathologic features of melanocytic proliferations associated with lichen sclerosus (LS) and to compare these findings with those in controls. DESIGN: Cohort study. SETTING: Academic and private practice dermatology and dermatopathology services. PATIENTS: Cases of melanocytic proliferations associated with LS and consecutive controls with persistent (recurrent) melanocytic nevi, persistent malignant melanomas, and compound melanocytic nevi. MAIN OUTCOME MEASURES: Diagnostic criteria and disease recurrence. RESULTS: Eleven patients, all female, with a mean age of 40 years (range, 8-83 years), presented with pigmented lesions clinically suspected to be malignant melanoma or atypical melanocytic nevi affecting the vulva (7 patients), perineum (3 patients), or chest (1 patient). Lichen sclerosus was first identified in the biopsy specimen and subsequently confirmed clinically. In 10 cases, a melanocytic nevus was superimposed on LS (overlying or entrapped by sclerosis), whereas LS was found at the periphery of vulvar malignant melanoma. After complete excision, no recurrences have been reported for the melanocytic nevi in LS (mean follow-up, 29 months; range, 4-60 months). Compared with control lesions, the LS melanocytic nevi most closely resembled persistent melanocytic nevi and could be distinguished from persistent malignant melanoma histologically. Melanocytes, nevoid or malignant, proliferating contiguously with fibrotic or sclerotic collagen, contained abundant melanin, diffusely expressed HMB-45, and had a higher Ki-67 labeling index than ordinary melanocytic nevi. However, persistent malignant melanoma exhibited mitotic figures, significantly higher Ki-67 labeling index, and deep dermal HMB-45 expression compared with LS melanocytic nevi and persistent melanocytic nevi. CONCLUSIONS: Melanocytic nevi occurring in LS have features in common with persistent melanocytic nevi and can mimic malignant melanoma. An "activated" melanocytic phenotype is seen in LS melanocytic nevi, implicating a stromal-induced change.

Adolescent↗
PubMed2002

Prevalence of melanoma clinically resembling seborrheic keratosis: analysis of 9204 cases.

OBJECTIVE: To estimate the prevalence of melanoma clinically mimicking seborrheic keratosis. DESIGN: Retrospective review of cases submitted for histological examination with a clinical diagnosis of seborrheic keratosis or with a differential diagnosis that included seborrheic keratosis. SETTING: A tertiary medical care center-based dermatopathology laboratory serving academic dermatology clinics that have a busy pigmented lesion clinic. MATERIALS AND METHODS: A total of 9204 consecutive pathology reports containing a diagnosis of seborrheic keratosis in the clinical information field were identified between the years 1992 and 2001 through a computer database search. Reports with a final histological diagnosis of melanoma were selected for further review and clinicopathological analysis. MAIN OUTCOME MEASURE: Histological diagnosis, which was correlated with the preoperative clinical diagnosis. RESULTS: Melanoma was identified in 61 cases (0.66%) submitted for histological examination with a clinical diagnosis that included seborrheic keratosis. Melanoma was in the clinical differential diagnosis of 31 cases (51%). The remaining lesions had a differential diagnosis of seborrheic keratosis vs melanocytic nevus (17 cases, 28%), basal cell carcinoma (7 cases, 12%), or a squamous proliferation (3 cases, 5%). In 3 cases (5%), seborrheic keratosis was the only clinical diagnosis. All histological types of melanoma were represented. CONCLUSIONS: Our results confirm that melanoma can mimic seborrheic keratosis. These data strongly support the current policy of submitting for histological examination all specimens that have been removed from patients.

Adult↗
PubMed2002

The precursors of malignant melanoma.

The precursors to melanoma are generally considered to be related to nevi of different types. Here we emphasize the dysplastic nevus, the congenital nevus, and lentigo maligna as specific lesions. The dysplastic nevus is discussed not only as a formal precursor but also as a marker of cutaneous melanoma. The clinical and histologic characteristics are outlined, as well as evidence of progression in dysplastic nevi. The congenital nevus is briefly reviewed and emphasis is placed upon clues to malignant degeneration. The concept of lentigo maligna as a precursor as distinct from an in situ phase is detailed.

Cell Transformation, Neoplastic↗
PubMed2002

In vivo examination of lentigo maligna and malignant melanoma in situ, lentigo maligna type by near-infrared reflectance confocal microscopy: comparison of in vivo confocal images with histologic sections.

In vivo confocal microscopy can noninvasively image thin en face sections within living intact human tissue with high resolution and contrast. This evolving technique may provide clinicians with tools to help detect lentigo maligna lesion progression in vivo and may be important in defining tumor margins, thus providing a more definitive surgical eradication of lentigo maligna and malignant melanoma in situ, lentigo maligna type. We present a case of malignant melanoma in situ, lentigo maligna type, and we describe the images seen with confocal microscopy in correlation with routine histopathology.

Aged↗
PubMed2002

Congenital and infantile melanoma: review of the literature and report of an uncommon variant, pigment-synthesizing melanoma.

Congenital and infantile types of melanoma are uncommon conditions for which there are limited epidemiologic data. The number of reported cases is small with several ascribed etiologies. We review the literature and report the first documented case, to our knowledge, of pigment-synthesizing melanoma in an infant. Reported cases of congenital and infantile melanoma were identified and categorized on the basis of disease origin. Dermatopathologic specimens from an infant given a diagnosis of pigment-synthesizing melanoma are described. Disease arising from medium and large/giant congenital nevi was most common, whereas reports of de novo and transplacental disease were infrequent. Death of approximately 40% of patients was noted within 18 months of diagnosis. Male infants accounted for approximately 74% of cases. The most commonly affected anatomic sites were the head and neck. The prognosis for congenital and infantile melanoma is poor. The high incidence of head-and-neck involvement and male predominance for disease suggest dispositions for both anatomic disease localization and sex.

Biopsy, Needle↗