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Martin C Mihm

Publications and source records attributed to Martin C Mihm.

At least 37 records · Page 2Linked to original sources
PubMed2005

Biomarkers in melanoma: stage III and IV disease.

The prognosis associated with Stage III melanoma is variable (17-65% 5-year survival) and primarily influenced by the number of lymph nodes involved, the presence of ulceration in a primary lesion, and the tumor burden present in each lymph node. In patients with metastatic (Stage IV) melanoma, the prognosis remains dismal (6-18% 5-year survival) and is influenced primarily by the sites (and extent) of metastatic involvement. Serum lactate dehydrogenase is the only prognostic biomarker useful in metastatic melanoma and it has been incorporated into the 2002 American Joint Committee on Cancer tumor, node, metastasis staging system. In this review, the known prognostic factors in Stage III and IV melanoma are reviewed. Selected investigational therapies and associated biomarkers are also discussed.

Biomarkers↗
PubMed2004

Is completion lymphadenectomy after a positive sentinel lymph node biopsy for cutaneous melanoma always necessary?

HYPOTHESIS: Completion lymph node dissection (CLND) has usually been recommended after metastatic disease is identified in the sentinel lymph node (SLN) biopsy to eradicate further metastases in nonsentinel nodes. We hypothesized that patients with negative lymph nodes included in the initial SLN specimen have low risk of metastases in the residual draining basin and may not require CLND. DESIGN: Chart review. SETTING: University-affiliated tertiary care referral center. PATIENTS: Between January 1, 1997, and May 31, 2003, 506 consecutive patients underwent SLN biopsy for staging of primary cutaneous melanoma. INTERVENTION: The SLN biopsy identified 87 patients (17.2%) with metastatic melanoma, of whom 80 underwent CLND. RESULTS: In 28 patients, all SLNs were found to contain metastatic melanoma. Seven (25%) of these patients had additional metastases identified in the CLND specimen. In 52 patients, 1 or more SLNs did not contain metastatic melanoma. Five (10%) of these patients had additional metastases in the CLND specimen (P =.02). CONCLUSIONS: Although no evidence of metastatic melanoma was found on CLND in most patients in whom negative nodes had been removed with positive SLNs at the initial biopsy, 10% of these patients did have further metastases. This subgroup of patients (positive SLNs and negative nodes in the SLN biopsy specimen) is at significantly lower risk for further metastasis, but CLND cannot be safely omitted even for these patients.

Adult↗
PubMed2004

Epithelial and mesenchymal hamartomatous changes in a mature port-wine stain: Morphologic evidence for a multiple germ layer field defect.

The port-wine stain (PWS) is a congenital cutaneous venulocapillary malformation of unknown pathogenesis. Many patients with facial PWS develop thickening with cobblestoning and nodularity during adult life. The histologic correlates of this maturational change are poorly documented and its mechanisms remain unclear. In this case study we present new histologic observations that may elucidate this phenomenon. An extensive PWS on the face of a 75-year-old man exhibited gross thickening with cobblestoning and nodularity. Histologic examination revealed not only the expected vascular abnormalities, but also a number of widely distributed epithelial, neural, and mesenchymal hamartomatous changes. Epithelial changes included epidermal nevus, sebaceous trichofolliculoma, and basaloid follicular hamartoma. Changes of connective tissue nevus, smooth-muscle hamartoma, neural hamartoma, and subcuticular hamartoma were also noted. The complex hamartomatous changes observed in the PWS of this patient involved multiple germ lines and were distributed in a widespread pattern. These changes not only offer an explanation for the skin thickening and nodularity of this patient, but also suggest a genetically determined, multilineage developmental field defect in the pathogenesis of this lesion. Further studies of other patients are necessary to understand the full implications of these findings in the late stage of PWS.

Aged↗
PubMed2004

Reflectance confocal microscopy may differentiate acute allergic and irritant contact dermatitis in vivo.

BACKGROUND: Acute irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD) may be difficult to distinguish by clinical or histologic assessment. Reflectance confocal microscopy (RCM) enables real-time, high-resolution skin imaging in vivo. OBJECTIVE: We sought to image, characterize, and distinguish acute ACD and ICD in vivo. METHODS: Volunteers with ACD were patch tested with an allergen and the irritant, sodium lauryl sulfate. RCM imaging and transepidermal water loss measurements were performed at 24 and 72 hours. Biopsy specimens were correlated with RCM images. RESULTS: Spongiosis, epidermal inflammatory cell infiltrate, and vesicle formation were observed in ACD and ICD. Compared with ACD, ICD showed greater disruption of the stratum corneum, and more parakeratosis. There was a significantly greater increase in transepidermal water loss for ICD compared with ACD. CONCLUSION: RCM is a promising tool for dynamic, noninvasive assessment and may help to differentiate acute ACD and sodium lauryl sulfate-induced ICD.

Adult↗
PubMed2004

Compound melanocytic nevi with granular cell changes.

Two cases of compound melanocytic nevi with granular cell changes were studied. Histological examination revealed compound melanocytic nevi with a portion of the dermal component exhibiting a sheet like proliferation of nevoid cells with granular cytoplasm. Immunohistochemically, both populations of cells stained positive for S-100 and Melan-A. However, HMB-45 was positive only for the nevus cells with granular cytoplasm. We believe this represents granular cytoplasmic changes of nevus cells and does not denote malignant transformation.

Adolescent↗
PubMed2004

Microphthalmia transcription factor and NKI/C3 expression in cellular neurothekeoma.

While the usual or myxoid-type neurothekeoma has been reasonably well established as being a tumor of neural origin, the cellular neurothekeoma remains in disputed histogenesis. We studied a series of 11 cellular neurothekeomas using paraffin immunoperoxidase staining with microphthalmia transcription factor (Mitf), NKI/C3, and S-100. The majority of the tumors in our series stained with NKI/C3 (9/11) and Mitf (9/11). All failed to stain with S-100. Furthermore, we divided our series of cellular neurothekeomas according to cytomorphology; tumors demonstrating predominantly spindled morphology, predominantly epithelioid morphology, and mixed spindle and epithelioid morphology. The two tumors that failed to stain with NKI/C3 both demonstrated predominantly spindled morphology. One of the tumors that failed to stain with Mitf showed exclusive spindled morphology, while the other showed mixed morphology (spindle and epithelioid). Two of the tumors, which stained strongly with Mitf, however, showed exclusive epithelioid morphology. This current study furthers the concept that cellular neurothekeoma is a tumor of neuroectodermal origin, and further suggests that it may express some component of melanocytic differentiation.

Adolescent↗
PubMed2004

Infantile hemangiomas are arrested in an early developmental vascular differentiation state.

Infantile hemangiomas, the most common tumors of infancy, are vascular tumors characterized by rapid proliferation of endothelial cells during the first few months of postnatal life followed by slow spontaneous involution, whose molecular pathogenesis remains unclear. The recent identification of developmental expression of vascular lineage-specific markers prompted us to characterize infantile hemangiomas for the expression of lymphatic endothelial hyaluronan receptor-1 (LYVE-1), Prox-1, CD31 and CD34. We found that LYVE-1, a specific marker for normal and tumor-associated lymphatic vessels, was strongly expressed in tumor cells of infantile hemangiomas (n=28), but not in other vascular tumors including pyogenic granulomas (n=19, P<0.0001) or intramuscular hemangiomas (n=9), using LYVE-1/CD31 double immunostains. Whereas LYVE-1 expression was detected on the endothelial cells of all proliferating infantile hemangiomas, this lymphatic marker was absent from the lesional capillaries during involution in the majority of cases (P=0.0009). The majority of LYVE-1(+) endothelial cells also expressed CD34, but were negative for the lymphatic-specific homeobox protein Prox-1. Based on coexpression of both LYVE-1 and the blood vascular marker CD34, we propose that the endothelial cells in proliferating infantile hemangioma are arrested in an early developmental stage of vascular differentiation. The immature, incompletely differentiated immunophenotype of proliferating infantile hemangiomas may contribute to their rapid growth during the first few months of life.

Adolescent↗
PubMed2004

Pigmented epithelioid melanocytoma: a low-grade melanocytic tumor with metastatic potential indistinguishable from animal-type melanoma and epithelioid blue nevus.

In the course of a study of borderline melanocytic tumors, we observed a distinctive group of lesions characterized by features very similar to those previously described in the literature as "animal-type melanoma" and epithelioid blue nevus of Carney complex. We have designated these lesions as pigmented epithelioid melanocytoma (PEM). Herein, we present a clinical-pathologic analysis of 41 consecutive PEM from 40 patients and compare them with 11 epithelioid blue nevi from patients with Carney complex. PEM occurred in both sexes of different ethnic backgrounds, including white, Hispanic, black, Asian, and Persian. The median age of occurrence was 27 years (range 0.6-78 years). Tumors had wide distribution with extremities being the most common site. The tumors were formed by deep dermal (mean Breslow's thickness 3.3 mm) proliferation of heavily pigmented epithelioid and/or spindled melanocytes. Five lesions were part of combined nevus. Ulceration was present in 7 cases. Tumor necrosis was present in 1 case. Regional lymph nodes were sampled in 24 cases (59%). In 11 cases, lymph nodes contained metastases (46%). Liver metastases occurred in 1 case. None of the patients died of disease. Clinical follow-up of more than a year (mean 32 months, range up to 67 months) was available in 27 cases (67%). We found no histologic criteria separating metastasizing and nonmetastasizing PEM. Ulceration was the only feature more common in PEM than epithelioid blue nevi of Carney complex. Otherwise, they were histologically indistinguishable. Our data show that PEM is a unique low-grade variant of melanoma with frequent lymph node metastases but indolent clinical course. We suggest that PEM be considered as a provisional histologic entity encompassing both animal-type melanoma and epithelioid blue nevus.

Adolescent↗
PubMed2004

Malignant basomelanocytic tumor manifesting as metastatic melanoma.

We report a case of an unusual basomelanocytic tumor from the scalp of a 56-year-old man. A 56-year-old white man presented with a scalp lesion that was biopsied and interpreted as a basal cell carcinoma. Fourteen months later, metastatic melanoma was discovered in a cervical lymph node and the liver. A subsequent biopsy from the area of the previously biopsied basal cell carcinoma of the scalp showed an invasive malignant melanoma. Immunohistochemical stains performed on the original scalp specimen showed biphasic immunohistochemical profile. A population of neoplastic cells was strongly positive for the melanocytic markers Melan-A, HMB-45, and tyrosinase and showed weak focal immunoreactivity for S-100. A second population of cells was strongly immunoreactive for keratin (wide-spectrum polyclonal antibody) and BerEp4. To our knowledge, this is the first description of a malignant basomelanocytic tumor complicated by metastatic melanoma.

Basal Cell Carcinoma↗
PubMed2004

Variability in nomenclature used for nevi with architectural disorder and cytologic atypia (microscopically dysplastic nevi) by dermatologists and dermatopathologists.

BACKGROUND: Although a nevus with the microscopic features of a "dysplastic nevus" is commonly seen, the nomenclature used to describe such a lesion has been thought to be inconsistent. A 1992 National Institutes of Health (NIH) Consensus Conference sought to unify nomenclature and suggested that the term "nevus with architectural disorder" be used along with a comment on melanocytic atypia. METHODS: We performed a cross-sectional mail survey to determine preferred terminology as well as the level of adherence to the NIH-recommended nomenclature. All 856 active members of the American Society of Dermatopathology (ASDP) and 1100 (13.0%) of the 8471 active members of the American Academy of Dermatology (AAD) were surveyed. RESULTS: Five hundred and thirty-three ASDP members and 483 AAD members who fulfilled eligibility criteria completed the questionnaire. The term "dysplastic nevus" was favored by the largest number of responders (favored by 39.1% of ASDP members and 62.3% of AAD members), while the 1992 NIH Consensus Conference-recommended terminology was the second most popular term (25.3% of ASDP and 15.1% of AAD members). Dermatopathologists (OR = 1.9, p = 0.0001) and those who had dual training in dermatology and dermatopathology (OR = 1.6, p = 0.02 for ASDP members; OR = 2.3, p = 0.02 for AAD members) were more likely to adhere to the 1992 NIH Consensus Conference nomenclature. CONCLUSIONS: Despite attempts to unify nomenclature for microscopically dysplastic nevi through the NIH Consensus Conference, wide variation in terminology persists.

Consensus Statements as Topic↗
PubMed2004

In vivo reflectance-mode confocal scanning laser microscopy in dermatology.

RCM offers tremendous potential for the advancement of medical research and clinical care. In research, it offers benefits both ex vivo and in vivo. Ex vivo, it can allow us to sample tissue and evaluate it noninvasively to determine what further testing--on the same exact tissue--may be helpful. In vivo RCM can be used to study normal or pathophysiologic processes in real-time noninvasively and by the same technique sequentially over time. Immunologic events previously only studied ex vivo or by static images can be traced from their inception to completion (Table 1). The potential of RCM in vivo is tremendous. How would our world change if we could noninvasively diagnose skin lesions and, with the advent of new minimally invasive therapies, administer treatment and noninvasively monitor that treatment? The potential to allow better medical care based on actual visualization of therapeutic response and healing is obvious. Much like early X-ray and ultrasound imaging, RCM is in its infancy. It is only a matter of time and continued persistent research that will lead to similar success and utility for RCM.

Dermatology↗
PubMed2003

Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients.

A large number of cancer-associated gene products evoke immune recognition, but host reactions rarely impede disease progression. The weak immunogenicity of nascent tumors contributes to this failure in host defense. Therapeutic vaccines that enhance dendritic cell presentation of cancer antigens increase specific cellular and humoral responses, thereby effectuating tumor destruction in some cases. The attenuation of T cell activation by cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) further limits the potency of tumor immunity. In murine systems, the administration of antibodies that block CTLA-4 function inhibits the growth of moderately immunogenic tumors and, in combination with cancer vaccines, increases the rejection of poorly immunogenic tumors, albeit with a loss of tolerance to normal differentiation antigens. To gain a preliminary assessment of the biologic activity of antagonizing CTLA-4 function in humans, we infused a CTLA-4 blocking antibody (MDX-CTLA4) into nine previously immunized advanced cancer patients. MDX-CTLA4 stimulated extensive tumor necrosis with lymphocyte and granulocyte infiltrates in three of three metastatic melanoma patients and the reduction or stabilization of CA-125 levels in two of two metastatic ovarian carcinoma patients previously vaccinated with irradiated, autologous granulocyte-macrophage colony-stimulating factor-secreting tumor cells. MDX-CTLA4 did not elicit tumor necrosis in four of four metastatic melanoma patients previously immunized with defined melanosomal antigens. No serious toxicities directly attributable to the antibody were observed, although five of seven melanoma patients developed T cell reactivity to normal melanocytes. These findings suggest that CTLA-4 antibody blockade increases tumor immunity in some previously vaccinated cancer patients.

Abatacept↗
PubMed2003

The nonrandom distribution of facial hemangiomas.

OBJECTIVE: To map sites of occurrence of facial infantile hemangiomas and correlate these with pattern of tumor growth, clinical complications, and proximity to structural and developmental landmarks. DESIGN: A retrospective medical record review of 205 patients diagnosed with facial infantile hemangioma. SETTING: Arkansas Children's Hospital, Little Rock, a 250-bed teaching hospital affiliated with the University of Arkansas for Medical Sciences. PATIENTS: Based on their clinical photographs, 232 of the hemangiomas were mapped on a facial schematic. Each lesion was encoded with a number reflective of its location, and this number was shared by other lesions occurring at the same site. Frequencies of complicating ulceration and airway obstruction were determined by medical record review. RESULTS: Two patterns of tumor growth were evident among the hemangiomas analyzed: focal (177 lesions [76.3%]) and diffuse (55 lesions [23.7%]). The focal hemangiomas mapped to 22 sites of occurrence, all near lines of mesenchymal or mesenchymal-ectodermal embryonic fusion. The 55 diffuse hemangiomas showed a segmental tissue distribution and thus were designated as frontonasal (15 lesions [27%]), maxillary (19 lesions [35%]), or mandibular (21 lesions [38%]). Ulceration was 3 times more common in patients with diffuse hemangiomas (21 [51%] of 41) than in patients with focal hemangiomas (28 [17%] of 164). Airway obstruction was characteristic of diffuse mandibular hemangiomas. CONCLUSIONS: Facial infantile hemangiomas occurred in 2 distinct patterns of tissue involvement: a focal type with a tumorlike appearance and a less common diffuse type with a plaquelike appearance. The diffuse lesions were more likely to be complicated by ulceration or airway obstruction and showed a strikingly segmental distribution pattern. Focal hemangiomas, in contrast, showed a predilection for regions of embryological fusion.

Facial Neoplasms↗
PubMed2003

Tumor lymphangiogenesis: a novel prognostic indicator for cutaneous melanoma metastasis and survival.

Malignant melanomas of the skin are distinguished by their propensity for early metastatic spread via lymphatic vessels to regional lymph nodes, and lymph node metastasis is a major determinant for the staging and clinical management of melanoma. However, the importance of tumor-induced lymphangiogenesis for lymphatic melanoma spread has remained unclear. We investigated whether tumor lymphangiogenesis occurs in human malignant melanomas of the skin and whether the extent of tumor lymphangiogenesis may be related to the risk for lymph node metastasis and to patient survival, using double immunostains for the novel lymphatic endothelial marker LYVE-1 and for the panvascular marker CD31. Tumor samples were obtained from clinically and histologically closely matched cases of primary melanomas with early lymph node metastasis (n = 18) and from nonmetastatic melanomas (n = 19). Hot spots of proliferating intratumoral and peritumoral lymphatic vessels were detected in a large number of melanomas. The incidence of intratumoral lymphatics was significantly higher in metastatic melanomas and correlated with poor disease-free survival. Metastatic melanomas had significantly more and larger tumor-associated lymphatic vessels, and a relative lymphatic vessel area of >1.5% was significantly associated with poor disease-free and overall survival. In contrast, no differences in the density of tumor-associated blood vessels were found. Vascular endothelial growth factor and vascular endothelial growth factor-C expression was equally detected in a minority of cases in both groups. Our results reveal tumor lymphangiogenesis as a novel prognostic indicator for the risk of lymph node metastasis in cutaneous melanoma.

Adult↗