Biomedical subjects

Martin C Mihm

Publications and source records attributed to Martin C Mihm.

At least 19 recordsLinked to original sources

PubMed2006

Markers and tissue resources for melanoma: meeting report.

The Markers and Tissue Resources for Melanoma meeting convened by the Cancer Diagnosis Program, Division of Cancer Treatment and Diagnosis, Specialized Programs of Research Excellence at the Organ Systems Branch of the National Cancer Institute (NCI), and the Melanoma Research Foundation was held in Gaithersburg, MD on October 2005. The meeting reviewed the current status of biomarkers for early- and advanced-stage melanoma and addressed some of the challenges scientists and clinicians face as they unravel the biology of melanoma and try to apply these findings to patient care. Specifically, the participants focused on molecular changes associated with melanoma progression, potential diagnostic and prognostic markers emerging from molecular profiling studies, and new treatment targets for current and future clinical trials. They also highlighted the ongoing challenges about translational research in melanoma, including availability of tissue resources, and summarized the status of nevus and melanoma tissue microarrays, recently developed as a collaborative project between the melanoma research community and the NCI. The meeting report is intended to provide a perspective on emerging scientific approaches in translational research that can enhance the progress in discovery and validation of markers for melanoma. (Cancer Res 2006; 66(22): 10652-7).

Biomarkers, Tumor↗

PubMed2006

Melanoma.

Explore the source record for details and available documents.

Cadherins↗

PubMed2006

Molecular mechanisms of metastasis.

A major topic covered at the First International Symposium on Cancer Metastasis and the Lymphovascular System was the molecular mechanisms of metastasis. This has become of major interest in recent years as we have discovered new metastasis-related genes and gained understanding of the molecular events of lymphatic metastasis. The symposium covered new aspects and important questions related to the events of metastasis in both humans and animals. The basic and clinical related research covered in this topic represented many disciplines. The presentations showed novel findings and at the same time, raised many new unanswered questions, indicating the limited knowledge we still have regarding the molecular events of metastasis. The hope is that further unraveling of the direct and indirect molecular events of lymphatic metastasis will lead to new approaches in developing effective therapeutics.

Animals↗

PubMed2006

Unusual histologic and clinical variants of melanoma: implications for therapy.

Unusual histologic variants of melanoma may prove problematic to the histopathologist. Several of these variants are sufficiently rare that their biological behavior remains obscure. Because identification of some of these melanoma subtypes has specific implications for the therapeutic approach and some may mimic other forms of epithelial or mesenchymal neoplasia, their recognition is key to patient management.

Diagnosis, Differential↗

PubMed2006

Clinical and histopathologic observations of the action of imiquimod in an epithelioid hemangioendothelioma and Paget's mammary disease.

An epithelioid hemangioendothelioma and Paget's disease of the breast were treated with topical imiquimod 5% cream with very impressive results. In both of the tumors complete disappearance of the lesions occurred. In this article, in addition to describing the treatment approach, the findings in biopsy specimens of the epithelioid hemangioendothelioma and the Paget's disease before, during, and after therapy will be described. The histologic findings show ample evidence that there is both a lymphocytic T helper 1-like and T helper 2-like response from imiquimod. Direct evidence of lymphocytotoxicity was found. Furthermore, mast cells appear to be involved in the development of regression in the vascular tumor. Although the study is very limited and reports only two cases, the results are striking. We considered it important to describe these findings because of their possible use in developing strategies for the application of imiquimod in the treatment of other tumors in human beings.

Adult↗

PubMed2006

Malignant adnexal neoplasms.

Malignant cutaneous adnexal neoplasms are one of the most challenging areas of dermatopathology. Tumors of the pilosebaceous apparatus can occur as single-lineage neoplasms or may manifest as complex proliferations with multilineal differentiation patterns including not only the germinative component of the hair bulb, the inner or outer root sheath epithelium and the sebaceous gland and duct, but also the sweat duct components that relate to the apocrine secretory apparatus which empties into the follicle near the follicular bulge. Eccrine and apocrine neoplasms present a bewildering array of morphologies, which often defy precise classification. The purpose of this review is to discuss in detail the malignant neoplasms of the cutaneous adnexae and their benign and prognostically indeterminate mimics.

Diagnosis, Differential↗

PubMed2006

Unusual variants of malignant melanoma.

A potential diagnostic pitfall in the histologic assessment of melanoma is the inability to recognize unusual melanoma variants. Of these, the more treacherous examples include the desmoplastic melanoma, the nevoid melanoma, the so-called 'minimal-deviation melanoma,' melanoma with prominent pigment synthesis or 'animal-type melanoma,' and the malignant blue nevus. Also problematic are the unusual phenotypic profiles seen in vertical growth phase melanomas; these include those tumors whose morphological peculiarities mimic cancers of nonmelanocytic lineage and those melanomas that express aberrant antigenic profiles not commonly associated with a melanocytic histogenesis. Metaplastic change in melanoma, balloon cell melanoma, signet-ring cell melanoma, myxoid melanoma, small cell melanoma and rhabdoid melanoma all have the potential to mimic metastatic and primary neoplasms of different lineage derivations. Abnormal immunohistochemical expression of CD 34, cytokeratins, epithelial membrane antigen, and smooth muscle markers as well as the deficient expression of S100 protein and melanocyte lineage-specific markers such as GP100 protein (ie HMB-45 antibody) and A103 (ie Melan-A) also present confusing diagnostic challenges. In this review, we will discuss in some detail certain of these novel clinicopathologic types of melanoma, as well as the abnormal phenotypic expressions seen in vertical growth phase melanoma.

Antigens, Neoplasm↗

PubMed2006

Prognosticators of melanoma, the melanoma report, and the sentinel lymph node.

Since the 1960s, the clinical characteristics of melanoma, its histopathology and its biological basis have been the subject of intense study at pigmented lesion clinics in North America, Europe, and Australia. More recently, the immense database of the Melanoma Committee of the American Joint Committee on Cancer (AJCC) has been exploited through complex mathematical models to measure the impact of various histologic features of primary melanomas and of sentinel lymph node deposits and to correlate these parameters with patient survival. The wealth of modern information available to pathologists and clinicians has become of vital interest to the prognostication of the individual patient with melanoma. The purpose of this review is to bring to the attention of anatomic pathologists the essential characteristics of the pathology report for primary cutaneous melanoma in the modern era.

B7-1 Antigen↗

PubMed2005

Biology of desmoplastic melanoma: a case-control comparison with other melanomas.

PURPOSE: Previous studies have established that patients with desmoplastic melanoma (DM) have thicker primary tumors. Consequently, comparisons with other forms of melanoma have been strongly biased by differences in Breslow stage. This is the first case-matched control study comparing DM with other forms of melanoma. PATIENTS AND METHODS: From a database of 3,202 melanoma patients treated at one institution, 89 patients with DM and 178 case-matched control patients (2:1) were identified by matching for tumor thickness, age, sex, and year of diagnosis. Clinical, pathologic, and outcome information was obtained from chart review. RESULTS: Controls were matched successfully to patients for tumor thickness, age, sex, and year of diagnosis. Presentation with American Joint Committee on Cancer stage III or IV disease is less common in patients with DM compared to case-matched control patients (5% v 21%; P < .001). Re-excisions to obtain clear surgical margins are required more often in patients with DM compared to case-matched control patients (21% v 6%; P < .001). Risk of positive sentinel nodes is lower in patients with DM compared to case-matched control patients (8% v 34%; P = .013). Despite these differences, survival rates of patients with DM are the same as case-matched control patients. CONCLUSION: Use of case-matched control patients matched for tumor thickness avoids biases introduced by the advanced Breslow stage of DMs. DMs are more locally aggressive than thickness-matched controls, and positive sentinel nodes are limited to patients with thick primary tumors. Importantly, patients with DM have survival rates similar to patients with other melanomas of similar thickness.

Adult↗

PubMed2005

Congenital melanocytic nevi: clinical and histopathologic features, risk of melanoma, and clinical management.

Congenital melanocytic nevi occur in approximately 1% of newborns and are usually classified according to their size. Giant congenital melanocytic nevi are most simply defined as melanocytic nevi that are greater than 20 cm in largest dimension; whereas small congenital nevi are defined as melanocytic nevi less that 1.5 cm in largest dimension. Congenital nevi can exhibit distinctive histologic features that can help in differentiating them from common acquired nevi. Giant congenital melanocytic nevi are associated with an increased risk of the development of melanoma. On the other hand, there is evidence of an increased melanoma risk in patients with small congenital nevi. Nevertheless, the risk of malignant transformation in small congenital nevi and the lifetime melanoma risk in patients with small congenital nevi remain controversial. In large part due to inconsistency in the reported literature describing patients with congenital melanocytic nevi, the risk of melanoma in these patients remains unclear and consistent guidelines for clinical management do not exist. We review the literature and comment on the course of management for these patients at the Massachusetts General Hospital Pigmented Lesion Clinic.

Abnormalities, Multiple↗

PubMed2005

Melanocytic lesions associated with dermatofibromas: a spectrum of lesions ranging from junctional nevus to malignant melanoma in situ.

Dermatofibromas are common lesions that are often associated with epidermal hyperplasia and basal layer hyperpigmentation. A single case of lentiginous melanocytic hyperplasia overlying a dermatofibroma has been reported, however, nevi and melanoma have to the best of our knowledge, not been previously reported. We present 14 cases of melanocytic lesions associated with dermatofibromas. The clinical data and hematoxylin- and eosin- stained sections were obtained and formalin-fixed, paraffin-embedded tissue was immunostained with antibodies against S-100, Mart-1, Factor XIIIa, and CD117. There were nine females and five males ranging in age from 30 to 64 years and anatomic sites included back (five), arm (six), flank (two), and leg (one). The clinical diagnosis ranged from dermatofibroma to desmoplastic melanoma. Histologically, the melanocytic lesions included junctional, compound, and dermal nevi, and malignant melanoma in situ. In four cases the dermal component appeared to merge with the dermatofibroma. In the case of the melanoma in situ, the dermatofibroma abutted the epidermis. Immunohistochemically, the melanocytic lesions were S-100/ Mart-1+, FXIIIa-, and the dermatofibromas were S-100/Mart-1-, FXIIIa+. Melanocytic neoplasia may appear in association with dermatofibromas. The fibrohistiocytic proliferation may be misinterpreted as a spindle or pleomorphic melanocytic process. Awareness of this association will aid in the correct diagnosis, and immunohistochemical studies will help in the differentiation of these two cell populations.

Adult↗

PubMed2005

Tumor lymphangiogenesis predicts melanoma metastasis to sentinel lymph nodes.

Cutaneous melanoma is a common melanocytic neoplasm that can quickly metastasize to regional lymph nodes. Currently, prognosis is determined by measuring tumor thickness but more reliable markers for metastatic spread are urgently needed. We investigated whether the extent of tumor lymphangiogenesis can predict melanoma metastasis to sentinel lymph nodes. We quantified the extent of tumor lymphangiogenesis, as well as other factors, in excised primary tumors and in sentinel lymph node biopsy samples from 45 patients with primary cutaneous melanoma. The results were correlated with histological and clinical outcome. Primary melanomas from patients whose tumors had metastasized to the sentinel lymph nodes contained prominent 'hot spots' of increased lymphatic vessel density, compared to nonmetastatic tumors. Multivariate risk analysis revealed that the lymphatic vascular area of primary melanomas, an index of tumor lymphangiogenesis, was the most sensitive prognostic marker for sentinel lymph node metastasis, and was even able to more accurately predict which tumors were metastatic to sentinel lymph nodes than the currently used method of measuring tumor thickness. Highly lymphangiogenic melanomas maintained their lymphangiogenic activity after metastasis to the sentinel lymph node. The extent of tumor lymphangiogenesis is a highly sensitive (83%) and specific (89%) prognostic marker of lymph node metastasis. Assessment of lymphangiogenesis in primary melanomas may be a more effective approach than the currently used technique of measuring tumor thickness in selecting patients with early metastatic disease for aggressive therapy.

Adult↗

PubMed2005

Lentiginous melanoma: a histologic pattern of melanoma to be distinguished from lentiginous nevus.

Atypical lentiginous melanocytic proliferations in elderly patients continue to pose a diagnostic dilemma with lesions variably categorized as dysplastic nevus, atypical junctional nevus, melanoma in situ (early or evolving) and premalignant melanosis. We present pigmented lesions from 16 patients (seven male and nine female) and with the exception of one case, all were older than 50 years of age. The anatomical sites included trunk (7), head and neck (6) and upper extremity (3). The clinical diagnosis was variable and included lentigo maligna, atypical nevus, pigmented basal cell carcinoma, seborrheic keratosis and lentigo. The initial biopsies mimicked lentiginous nevus or dysplastic nevus and were characterized by a lentiginous proliferation of melanocytes at the dermoepidermal junction both as single cells and as small nests with areas of confluent growth, extending to the edges of the biopsy. The retiform epidermis was maintained and pagetoid spread of melanocytes was not prominent in hematoxylin- and eosin- stained sections. Dermal fibrosis was variably present and the melanocytic proliferation demonstrated cytological atypia. The subsequent re-excisions demonstrated similar atypical melanocytic proliferation occurring over a broad area flanking the prior biopsy sites. The diagnosis of melanoma was more easily recognized in the complete excision specimens. Immunohistochemical stains for Mitf and Mart-1 highlighted the extent of the basalar melanocytic proliferation as well as foci of pagetoid spread by melanocytes. Familiarity with this pattern of early melanoma should facilitate proper classification of lentiginous melanocytic proliferations in biopsies from older adults.

Adult↗

PubMed2005

Endocrine mucin-producing sweat gland carcinoma: twelve new cases suggest that it is a precursor of some invasive mucinous carcinomas.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is an underrecognized low-grade carcinoma with predilection to the eyelid. Only 4 cases of this entity have been described in the literature. Here, we describe 12 cases of EMPSGC. The lesions were twice as frequent in females than males with an average age of 70 years (range, 48-84 years). Clinically, they presented as a slowly growing cyst or swelling. The most common site of occurrence was the lower eyelid (8 cases). Two lesions occurred on the upper eyelid and 2 on the cheek. Histologically, they were well-circumscribed, typically multinodular tumors with solid or partially cystic nodules, frequently showing areas of papillary architecture. Focal cribriform arrangements were also present. The nodules were formed by uniform small- to medium-sized oval to polygonal epithelial cells with lightly eosinophilic to bluish cytoplasm. The nuclei were bland with diffusely stippled chromatin and inconspicuous nucleoli. Intracytoplasmic and extracellular mucin was usually present. Mitotic activity was present but never brisk. All tumors examined immunohistochemically expressed at least one neuroendocrine marker, synaptophysin or chromogranin. CD57 and neuron specific enolase, secondary markers of neuroendocrine differentiation, were expressed in most cases. All tumors tested expressed estrogen and progesterone receptors, cytokeratin 7, low molecular cytokeratin Cam5.2, and epithelial membrane antigen and were negative for cytokeratin 20 and S-100 protein. Calponin, smooth muscle actin, and p63 immunohistochemical stains did not disclose myoepithelial cells around larger tumor nests in most cases, supporting the notion that EMPSGC is an invasive carcinoma. In 10 cases, cystic areas lined by benign epithelium indistinguishable from eccrine ducts were present. In some foci, the benign ductal epithelium was undermined or replaced by carcinoma in situ with similar cytologic features to the solid or papillary areas of EMPSGC. Myoepithelial cells were preserved in the areas of in situ carcinoma. In 6 cases, EMPSGC was associated with invasive mucinous carcinoma. In situ carcinoma and mucinous carcinoma also expressed neuroendocrine markers. Clinical follow-up showed no recurrences or metastases, consistent with low-grade carcinoma. The series provides histologic evidence for a multistage progression of noninvasive sweat gland neuroendocrine carcinoma to EMPSGC and then to mucinous carcinoma of the eyelid. Although the data from this series support the notion that the prognosis of EMPSGC and mucinous carcinoma is good, longer follow-up is needed for better understanding of their pathogenesis and clinical behavior.

Adenocarcinoma, Mucinous↗

PubMed2005

Pilomatrix carcinomas contain mutations in CTNNB1, the gene encoding beta-catenin.

Mutations in beta-catenin are present in benign pilomatrixomas. beta-catenin is a downstream effector in the WNT-signalling pathway, acting as a signal for differentiation and proliferation. Mutations in CTNNB1, the gene encoding beta-catenin, are present in a wide variety of benign and malignant neoplasms. We examined beta-catenin in a series of pilomatrix carcinomas (15 cases) by using immunohistochemistry and DNA sequencing of exon 3 from CTNNB1, and compared these to a series of benign pilomatrixomas (13 cases). All 11 pilomatrix carcinomas available for examination showed nuclear localization of beta-catenin and mutations in exon 3 similar to those demonstrated in benign pilomatrixomas. Two of 11 pilomatrix carcinomas showed significant nuclear accumulation of p53, whereas this was absent in all 13 benign pilomatrixomas. Expression of nuclear cyclin D1 was similar in both benign pilomatrixomas and pilomatrix carcinomas. Clinical follow-up from the 15 malignant cases reported in this study and by others indicates that wide excision offers superior control of local recurrence, compared to simple excision. Immunohistochemical and molecular analysis of beta-catenin reveals that both pilomatrix carcinomas and benign pilomatrixomas harbour mutations in beta-catenin. This implies a common initial pathogenesis and is compatible with the proposition that pilomatrix carcinomas may at least on occasion arise from their benign counterparts.

Adolescent↗

PubMed2005

De novo intraepidermal epithelioid melanocytic dysplasia as a marker of the atypical mole phenotype -- a clinical and pathological study of 75 patients.

BACKGROUND: We encountered a distinctive pattern of dysplastic intraepidermal melanocytic proliferation, which defies classification as a dysplastic melanocytic nevus, but in which the morphologic features fall short of a diagnosis of melanoma in situ. We designate such lesions as de novo intraepidermal epithelioid melanocytic dysplasia. METHODS: From 75 patients, 82 skin biopsies were encountered that showed this distinctive morphology. Hematoxylin- and eosin-stained histologic sections were studied and the features were correlated with personal and family histories of dysplastic nevi and melanoma. RESULTS: The diagnosis of de novo melanocytic dysplasia was made in 27 male patients and 48 female patients (mean age: 44 years). The histologic hallmark was a pagetoid (single-cell) array of moderately to severely atypical epithelioid melanocytes within the epidermis. Seventy-three lesions were located on sun-exposed skin and nine on sun-protected skin. In 41 patients, there was an atypical mole phenotype, whereas 20 patients had a prior or subsequent diagnosis of melanoma with five of 16 patients questioned revealing a family history of melanoma. CONCLUSIONS: De novo intraepidermal epithelioid melanocytic dysplasia is a distinct entity associated with an atypical mole phenotype and a personal and/or family history of melanoma.

Adolescent↗

PubMed2005

Drug-induced linear IgA bullous dermatosis.

We report the case of a 69-year-old Japanese woman with multiple blistering lesions covering almost her whole body. Linear IgA and C3 depositions were seen at the basement membrane zone on direct immunofluorescence (IF). Linear IgA bullous dermatosis (LABD) is one of the autoimmune diseases resulting in subepidermal blisters. It is clinically similar to bullous pemphigoid and IF is required to distinguish the two diseases. In this case, the blistering lesions appeared after vancomycin treatment. This drug was strongly suspected as a cause of LABD in light of the clinical course of the patient even though a drug-lymphocyte stimulating test was negative. Among the various implicated causative drugs, vancomycin is the most commonly associated with LABD.

Aged↗

PubMed2005

Treatment of synchronous mucinous carcinoma and endocrine mucin-producing sweat gland carcinoma with Mohs' micrographic surgery.

BACKGROUND: Endocrine mucin-producing sweat gland carcinoma is a very rare cutaneous tumor that has been reported only in three patients previously. We report a case of an endocrine mucin-producing sweat gland carcinoma associated with mucinous carcinoma treated by Mohs' micrographic surgery. OBJECTIVE: The purpose of this report is to test the utility of Mohs' micrographic surgery in the treatment of mucinous carcinomata. METHODS: A 79-year-old female with a 2-year history of four lesions of biopsy-proven endocrine mucin-producing sweat gland carcinomas and mucinous carcinoma was treated with Mohs' micrographic surgery. RESULTS: Three of the lesions were completely cleared by Mohs' micrographic surgery. The fourth lesion, in the right lateral canthus, was not cleared by the Mohs' technique because of its location within the orbit and the difficulty of retraction of the globe for appropriate visualization and excision. The patient underwent wide excision of the remaining orbital tumor and reconstruction, which was successfully accomplished. The patient did not experience a recurrence in any of her four lesions over a 2-year follow-up period. CONCLUSION: Mohs' micrographic surgery is an appropriate treatment for mucinous carcinomata, including endocrine mucin-producing sweat gland carcinoma and mucinous carcinoma.

Adenocarcinoma, Mucinous↗