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Biomedical subjects

L M Duncan

Publications and source records attributed to L M Duncan.

At least 19 recordsLinked to original sources
PubMed2001

Melastatin expression and prognosis in cutaneous malignant melanoma.

PURPOSE: Melastatin (MLSN-1), a novel melanocyte-specific gene recently identified using a genomic approach, is expressed in murine and human melanoma cells at levels inversely proportional to metastatic rates in vivo. We studied the relationship between expression of melastatin mRNA in the primary cutaneous tumor and prognosis in patients with localized malignant melanoma. PATIENTS AND METHODS: Melastatin mRNA was evaluated by in situ hybridization in primary cutaneous melanoma from 150 patients with localized disease (American Joint Committee on Cancer [AJCC] stage I and II). Multivariate Cox proportional hazards regression analysis was performed to assess the prognostic utility of melastatin mRNA expression while adjusting for other prognostic indicators. RESULTS: Uniform melastatin mRNA expression in the primary tumor was correlated with prolonged disease-free survival (P < .0001). Multivariate analysis revealed that melastatin status, mitotic rate, and tumor thickness influence disease-free survival independently. The 8-year disease-free survival rate in AJCC stage I patients whose tumors diffusely expressed melastatin mRNA was 100%, whereas in stage I patients with melastatin loss, the disease-free survival rate was 77% +/- 15% (median +/- SE). In patients with stage II disease whose tumors diffusely expressed melastatin mRNA, the 8-year disease-free survival rate was 90% +/- 7%, whereas in patients with melastatin loss, the disease-free survival rate was 51% +/- 8%. CONCLUSION: Downregulation of melastatin mRNA in the primary cutaneous tumor is a prognostic marker for metastasis in patients with localized malignant melanoma and is independent of tumor thickness and other variables. Used in combination, melastatin status and tumor thickness allow for the identification of subgroups of patients at high and low risk of developing metastatic disease.

Adult↗
PubMed2001

Cutaneous b-cell lymphomas of follicular and marginal zone types: use of Bcl-6, CD10, Bcl-2, and CD21 in differential diagnosis and classification.

Cutaneous follicular lymphomas (FLs) and cutaneous B-cell lymphomas of extranodal marginal zone (MZL)/mucosal-associated lymphoid tissue (MALT) type may have morphologic overlap, despite the fact that they are thought to be of distinct derivation (germinal center vs. postgerminal center). The problem is compounded by the reported absence of bcl-2 expression by many cutaneous FLs, leading to speculation that cutaneous FL may be unrelated to nodal FL. The authors analyzed the expression of the germinal center-associated antigens bcl-6 and CD10 and of bcl-2 in 18 cutaneous B-cell lymphomas (10 FLs and eight MZLs), in relationship to CD21+ follicular structures, to clarify the relationship of nodal to cutaneous FLs and to explore the value of these antigens in differential diagnosis. The authors studied 10 cutaneous FLs (seven primary and three secondary) and eight MZLs (six primary and two secondary). The FLs (found in six men and four women age 45-75 years) involved the trunk (n = 3) and scalp, face and neck (n = 7). The MZLs (found in five women and three men age 34-81 years) involved the trunk (n = 4), face and neck (n = 2), and arm (n = 2). Immunostaining for CD21, bcl-6, CD10, and bcl-2 allowed the delineation of compartments within the tumors and yielded distinct patterns of staining in FL and MZL. In both follicular and interfollicular/diffuse areas of FL the neoplastic cells were bcl-6+ (10 of 10), often CD10+ (seven of 10, four of seven primary), and bcl-2+ (nine of 10, six of seven primary). Only three of seven cases (one of five primary) had bcl-2 rearrangement detectable by polymerase chain reaction. In the MZLs, the neoplastic B-cells were bcl-6-, CD10-, and bcl-2+ (eight of eight). Three patterns of CD21+ follicles were identified in MZL: reactive germinal centers, uniformly bcl-6+, CD10+, and bcl-2- (five of eight MZLs); colonized follicles, both bcl-6-, bcl-2+, and L26+ cells, and bcl-6+ and bcl-2- cells (five of eight MZLs); and expanded/colonized follicular dendritic cell meshworks, bcl-6- and bcl-2+ B cells with rare residual bcl-6+ and bcl-2- cells (four of eight MZLs). The authors conclude that cutaneous FLs express bcl-6 uniformly, usually express CD10 and bcl-2, and have a follicular pattern similar to nodal FL and consistent with a germinal center origin. The immunophenotype of cutaneous FL is distinct from that of cutaneous MZL, which is negative for bcl-6 and CD10. Colonized follicles in MZL, identified by CD21+ follicular dendritic cell meshworks, contained numerous bcl-6- and bcl-2+ B cells, and were readily distinguished from neoplastic follicles in FL. Conversely, CD21- interfollicular and diffuse areas in FLs contained bcl-6+ and CD10+ cells, which were not seen in diffuse areas of MZLs. Thus, the combination of bcl-2, bcl-6, and CD21 staining is useful for the distinction of cutaneous MZL from cutaneous FL.

Adult↗
PubMed2000

Lymphoma- and leukemia-associated cutaneous atypical CD30+ T-cell reactions.

Cutaneous CD30+ lymphoid infiltrates appear cytologically atypical and occasionally may be misinterpreted as recurrent disease when they occur in patients treated for other primary hematologic malignancies. We recently encountered two such cases and present our findings. One patient with B-cell lymphoma and another with myeloid leukemia developed cutaneous eruptions after chemotherapy displaying highly atypical perivascular lymphoid cells on histology that mimicked recurrent disease. In both cases, the lymphocytes were CD30+ T cells by immunohistochemistry. The skin lesions spontaneously resolved and have not recurred. Because one case was initially misinterpreted as recurrent leukemia, we conclude that close clinical correlation and immunophenotypic confirmation should be done for atypical cutaneous lymphoid infiltrates in patients with primary hematologic malignancies. We discuss the differential diagnosis of atypical CD30+ infiltrates in this setting, which include recurrent lymphoma or myeloid leukemia, primary cutaneous anaplastic large cell lymphoma (ALCL), lymphomatoid papulosis (LyP), carbamazepine-induced CD30+ pseudolymphoma, viral infection and an atypical eruption of lymphocyte recovery.

Carbamazepine↗
PubMed2000

Progression to invasive melanoma from malignant melanoma in situ, lentigo maligna type.

We have previously hypothesized that lesions that have been termed lentigo maligna can be divided into 2 categories: 1 represents a pigmented lesion that is a precursor to melanoma, and the other melanoma in situ. We and others have hypothesized that there is a progressive acquisition of attributes in pigmented lesions that results in malignant melanoma. Based on these 2 hypotheses, we have predicted that the intraepidermal component of invasive malignant melanomas, lentigo maligna type, should be similar to those lesions that we have termed malignant melanoma in situ, lentigo maligna type rather than lentigo maligna. The intraepidermal component of 42 consecutive cases of invasive malignant melanoma, lentigo maligna type was evaluated by all of the authors. Malignant melanoma in situ, lentigo maligna type is characterized by pagetoid spread, confluence, and nesting of atypical melanocytes. All of the cases evaluated showed features diagnostic of malignant melanoma in situ, lentigo maligna type, in the epidermis overlying the invasive dermal component. We conclude that invasive lentigo maligna melanoma arises in association with those lesions that we have termed malignant melanoma in situ, lentigo maligna type, which may represent a step in the progression between atypical melanocytic hyperplasia (lentigo maligna) and invasive melanoma. This finding supports the distinction of these entities and may have therapeutic implications.

Aged↗
PubMed2000

Rapidly progressing mycosis fungoides presenting as follicular mucinosis.

Follicular mucinosis can occur as a primary idiopathic disorder or can arise in association with benign or malignant disease, most notably mycosis fungoides. We describe a patient with an aggressive folliculotropic variant of mycosis fungoides that initially presented as follicular mucinosis with alopecia. One month after the diagnosis of follicular mucinosis, a diagnosis of mycosis fungoides was made, and 3 months later inguinal lymph node involvement with mycosis fungoides developed. A skin biopsy specimen demonstrated prominent follicular mucinosis with folliculotropism of atypical cells and intrafollicular Pautrier's microabscesses. As demonstrated in this case, follicular mucinosis can be a presenting sign of rapidly progressive mycosis fungoides. In our review of follicular mucinosis and its association with mycosis fungoides, we found that the folliculotropic variant of mycosis fungoides appears more commonly to have an aggressive course than classic mycosis fungoides.

Adult↗
PubMed2000

Patterns of melastatin mRNA expression in melanocytic tumors.

The melanocyte-specific gene Melastatin (MLSN1) shows an inverse correlation of mRNA expression with metastatic potential in human and murine cell lines in vitro. Melastatin mRNA expression in primary cutaneous melanoma also has been found to correlate with disease-free survival. The histologic patterns of Melastatin mRNA expression in nevi, primary melanoma, and melanoma metastases have not been described previously. Using in situ hybridization with (35)S-labeled probes, we examined Melastatin mRNA expression in 64 cases of normal skin, benign melanocytic nevi, primary cutaneous melanomas, and melanoma metastases. Ubiquitous melanocytic expression of Melastatin mRNA was observed in all benign melanocytic proliferations (14 of 14), although some nevi showed a gradient of reduced Melastatin expression with increased dermal depth (3 of 14). Uniform expression of Melastatin mRNA was observed in 49% of primary cutaneous melanomas (18 of 37 cases, including 1 case of in situ melanoma). Melastatin mRNA loss by a portion of the melanoma was identified in 53% of the invasive melanoma samples (19 of 36) and 100% of the melanoma metastases (11 of 11). Primary melanomas without mRNA loss ranged in thickness from 0.17 to 2.75 mm (median, 0.5 mm; mean, 0.73 mm), whereas tumors that showed Melastatin mRNA down-regulation ranged in thickness from 0.28 to 5.75 mm (median, 1.7 mm; mean, 2.13 mm). A focal aggregate or nodule of melanoma cells without detectable signal was the most commonly observed pattern of Melastatin loss (13 of 19 cases), whereas complete loss of Melastatin mRNA expression by all of the dermal melanoma cells was observed in only 4 of the 19 cases. Two invasive melanomas displayed a scattered, nonfocal pattern of Melastatin mRNA loss. Of the 11 melanoma metastases examined, 64% displayed focal Melastatin mRNA loss, and 36% had complete loss of Melastatin mRNA expression. We observed several patterns of Melastatin mRNA expression in primary melanoma that may be distinguished from expression in benign melanocytic nevi. Melastatin mRNA expression appears to correlate with melanocytic tumor progression, melanoma tumor thickness, and the potential for melanoma metastasis. HUM PATHOL 31:1346:1356.

Disease Progression↗
PubMed1999

Detection of microscopic melanoma metastases in sentinel lymph nodes.

BACKGROUND: Sentinel lymph node biopsy following radioisotope labeling is a recently developed, minimally invasive surgical staging procedure used in the management of primary cutaneous malignant melanoma. If histologic analysis reveals melanoma metastasis in the sentinel lymph node, completion lymphadenectomy is performed and adjuvant therapy considered. The routine pathologic assessment of the sentinel lymph node consists of bisecting the lymph node along its long axis and histologic examination of one hematoxylin and eosin-stained section of each cut surface. METHODS: In this study, the authors reexamined 235 sentinel lymph nodes reported as negative for melanoma metastasis following routine histologic examination, from 94 patients with American Joint Committee on Cancer (AJCC) Stage I and II cutaneous melanoma. RESULTS: Deeper sections into the lymph node and immunohistochemical stains with antibodies to S-100, HMB-45, NK1C3, and MART-1 led to the identification of microscopic metastases in 11 sentinel lymph nodes from 11 patients and capsular nevi in 9 sentinel lymph nodes from 8 patients. CONCLUSIONS: Deeper serial sections and immunohistochemical stains detected microscopic metastases in approximately 12% of cases that would be reported as negative for metastasis by routine pathologic analysis. These techniques also allowed for the identification of capsular melanocytic nevi in the sentinel lymph nodes of 9% of patients. [See editorial on pages 551-2, this issue.]

Adult↗
PubMed1999

Outcome of patients with melanoma and histologically negative sentinel lymph nodes.

HYPOTHESIS: Patients with melanoma and histologically negative sentinel lymph nodes identified by lymphatic mapping have a very good prognosis. DESIGN: Cohort study with follow-up information obtained from medical records and telephone interviews. SETTING AND PATIENTS: Of all patients with cutaneous melanoma who underwent intraoperative sentinel lymph node mapping between November 15, 1993, and April 18, 1997, at the Massachusetts General Hospital, Boston, 89 were found to have no evidence of melanoma in their sentinel nodes. Forty-six lesions (51%) were on an extremity and 44 (49%) were of axial location. The median tumor thickness was 1.8 mm (range, 0.36-12.0 mm) and 11 tumors (12%) were ulcerated. INTERVENTIONS: Patients underwent intraoperative sentinel lymph node mapping with lymphazurin and radiolabeled sulfur colloid. Sentinel lymph nodes were analyzed by standard hematoxylin-eosin staining. Only 2 patients received adjuvant therapy following wide excision of the primary lesion. MAIN OUTCOME MEASURES: Site of initial recurrence and time to initial recurrence. RESULTS: The median follow-up for all patients was 23 months (range, 2-54 months). Eleven patients (12%) developed melanoma recurrences, and 78 (88%) patients remain disease free. Regional lymph nodes were the initial site of recurrence in 7 (8%) of 89 patients, and 7 (7%) of 106 mapped basins. Four patients had recurrence without involvement of regional lymph nodes: 2 with distant metastases and 2 with in transit metastases. The median time to recurrence was 12 months (range, 2-35 months). Sentinel lymph nodes were reanalyzed using serial sections and immunoperoxidase stains in 7 patients with recurrence and metastatic melanoma was identified in 3 (43%). CONCLUSIONS: The risk for melanoma recurrence is relatively low in patients with histologically negative sentinel nodes identified by lymphatic mapping. Longer follow-up will improve our understanding of the prognostic value of this procedure.

Adult↗
PubMed1999

Syringolymphoid hyperplasia and follicular mucinosis in a patient with cutaneous T-cell lymphoma.

Syringolymphoid hyperplasia with alopecia is an uncommon chronic dermatosis of which 9 cases have been reported, with or without follicular mucinosis or cutaneous T-cell lymphoma. We report a patient with cutaneous T-cell lymphoma and syringolymphoid hyperplasia and follicular mucinosis and review the previously reported cases. All reported cases with syringolymphoid hyperplasia were men (10 of 10), with the clinical findings of alopecia (9 of 10) and anhidrosis (3 of 10). Only 3 of 10 cases had associated follicular mucinosis. Of the 7 cases investigated, 6 were found to hve cutaneous T-cell lymphoma. Three patients were not investigated for cutaneous T-cell lymphoma. Although syringolymphoid hyperplasia can be idiopathic, it can also reflect a syringotropic cutaneous T-cell lymphoma. Careful follow-up with a biopsy of persistent lesions is recommended to evaluate for the presence of lymphoma.

Aged↗
PubMed1999

Cutaneous lymphoma. Understanding the new classification schemes.

Both the REAL and EORTC classification schemes classify lymphomas according to their cell of origin. These schemata also incorporate clinical features that allow for the distinction of some of these disorders. The EORTC classification scheme for primary cutaneous tumors uses terminology similar to that of the REAL classification and should allow for the recognition of teleologically similar tumors in cutaneous and extracutaneous sites. Future investigations will no doubt yield information regarding the true nature of the low-grade B-cell lymphomas of the skin and sort out the ever-increasing number of tumors found to express CD30. Most important, the continued expansion of knowledge regarding cutaneous lymphomas should enhance the ability of physicians to predict prognosis and to arrive at the most effective therapy for patients with these diseases.

Diagnosis, Differential↗
PubMed1999

Cutaneous lymphoid hyperplasia and cutaneous marginal zone lymphoma: comparison of morphologic and immunophenotypic features.

Cutaneous marginal zone lymphoma (MZL) is a recently described low-grade B-cell lymphoma that usually follows an indolent course. This tumor shares many histologic and clinical features with cutaneous lymphoid hyperplasia (CLH), a benign reactive lymphoid proliferation. Sixteen biopsy specimens from 14 patients with CLH were studied, and compared with 16 cases of cutaneous MZL (9 primary cutaneous, 7 with secondary involvement of the skin) to determine whether there were features that would permit their distinction on routinely fixed, paraffin-embedded tissue sections. Both disorders showed a female preponderance (CLH: 9 F, 5 M; MZL: 11 F, 5 M). The median age was also similar (CLH: 54 years; cutaneous MZL: 55 years). CLH was most common on the arm (8) and the head and neck (7) but also involved the trunk (1); primary cutaneous MZL most often involved the limbs (3), trunk (3), and head and neck (3). Lymphoma did not develop in any of the 14 CLH patients (follow-up ranging from 9 to 246 months, mean 62 months). Six of 9 patients with primary cutaneous MZL and all 7 patients with secondary cutaneous MZL experienced relapses, most commonly isolated to skin or a subcutaneous site. On hematoxylin-eosin stained sections, a diffuse proliferation of marginal zone cells (p < 0.0001), zones of plasma cells (p = 0.01), the absence of epidermal change (p = 0.01), reactive germinal centers (p = 0.03), and a diffuse pattern of dermal or subcutaneous infiltration (p = 0.03) were more often seen in cutaneous MZL. A dense lymphocytic infiltrate, bottom-heavy or top-heavy growth pattern, eosinophils, and a grenz zone were seen equally often in both disorders. Dutcher bodies were observed only in cutaneous MZL. Immunoperoxidase stains on formalin-fixed paraffin-embedded tissue sections showed monotypic expression of immunoglobulin light chains by plasma cells in 11 of 16 MZL cases. By definition, no case with monotypic plasma cells was diagnosed as CLH. In CLH, T cells usually outnumbered B cells, and a B:T cell ratio > or = 3:1 was not observed in any case. By contrast, 40% of the MZL cases showed a B:T cell ratio > or = 3:1. No coexpression of CD20 and CD43 was seen in any case of either MZL or CLH. In summary, the clinical presentations of CLH and MZL are similar. In contrast to historical criteria for diagnosing cutaneous lymphoid infiltrates, the presence of reactive follicles favors a diagnosis of cutaneous B-cell lymphoma (CBCL). In addition, a bottom-heavy or top-heavy growth pattern is not a distinctive finding. Marginal zone cells and zones or sheets of plasma cells are strong morphologic indicators of marginal zone lymphoma. The diagnosis of CBCL can be supported in 40% of the cases by demonstrating a B:T cell ratio of > or = 3:1, and confirmed in 70% of the cases by demonstrating monotypic light chain expression of plasma cells on paraffin sections.

Adult↗
PubMed1999

Tools of the trade: statistical analysis in dermatopathology articles.

Statistical analysis of research results provides powerful tools for understanding the data from projects. A prospective review of the statistical methods utilized in 100 consecutive articles in the recent literature relevant to dermatopathology was performed. The majority of papers, 75%, did not contain statistical analyses. A wide variety of methods were utilized in the papers that did have statistical analyses including methods in the following categories: t-test, contingency tables, multiple regression, multiple comparisons, nonparametric tests, life tables, and survival tests. Nine of the 25 papers utilizing statistical analysis had problems in the methods. These problems included treating categorical data as a continuous variable, multiple comparisons, subgroup analysis, and discordance of statistics and conclusions. It is important to understand the underlying assumptions of statistical methods to use the appropriate tets. These are tools of the trade for dermatopathology investigators.

Data Interpretation, Statistical↗
PubMed1998

Down-regulation of the novel gene melastatin correlates with potential for melanoma metastasis.

We have used differential cDNA display to search for genes whose expression correlates with an aggressive phenotype in variants of the B16 murine melanoma line, B16-F1 and B16-F10. This analysis identified a novel gene, termed melastatin, that is expressed at high levels in poorly metastatic variants of B16 melanoma and at much reduced levels in highly metastatic B16 variants. Melastatin was also found to be differentially expressed in tissue sections of human melanocytic neoplasms. Benign nevi express high levels of melastatin, whereas primary melanomas showed variable melastatin expression. Melastatin transcripts were not detected in melanoma metastases. Within the set of human primary cutaneous melanomas examined, melastatin expression appeared to correlate inversely with tumor thickness. The expression pattern observed suggests that loss of melastatin expression is an indicator of melanoma aggressiveness.

Amino Acid Sequence↗
PubMed1998

Increased mast cell density in invasive melanoma.

Mast cell participation in immune responses, tumor progression, and vascularization has been studied extensively in vitro. In situ investigation of mast cells in routinely processed tissues is hampered by difficulty in reliable detection of mast cells. We studied the tissue density of mast cells using a morphometric point-counting technique in 1 microm-thick, Giemsa-stained, tissue sections from epon-embedded samples of skin biopsies. This technique has been demonstrated to be an accurate and reproducible method for determining mast cell density. Mast cell density in 15 cases of invasive melanoma was compared to that of 9 cases of benign melanocytic nevi and 4 cases of melanoma in situ. Mast cell density was greatest in invasive melanoma (mean density = 0.61 vol.%). The mean density of mast cells in nevi and in situ melanoma was 0.33 and 0.5 respectively. Six of 15 cases of melanoma had mast cell densities > 0.6, whereas mast cell density did not exceed 0.6 in any cases of melanoma in situ or benign melanocytic nevi (p < 0.02). Our findings confirm an increase in mast cell tissue density in some cases of invasive melanoma when compared to mast cell density in benign nevi and in situ melanoma.

Adult↗
PubMed1997

Necrobiosis lipoidica in a diabetic intravenous drug user.

Necrobiosis lipoidica occurs most commonly on the lower extremities in patients with diabetes; lesions typically occur in the pretibial region. Although the pathogenesis of necrobiosis lipoidica remains unclear, both external trauma and vascular damage have been proposed as contributing to the development of this disorder. We report polarizable foreign material in small blood vessels and multinucleated histiocytes in lesions of necrobiosis lipoidica. This phenomenon occurred in a patient who was both diabetic and an intravenous drug user.

Diabetes Complications↗