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Biomedical subjects

L M Duncan

Publications and source records attributed to L M Duncan.

At least 37 records · Page 2Linked to original sources
PubMed1996

Marginal zone lymphoma (low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type) of skin and subcutaneous tissue: a study of 15 patients.

Extranodal low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type occurs in the gastrointestinal tract, salivary gland, thyroid, orbit, lung, and breast. We report 15 patients with MALT-type lymphomas involving skin and subcutaneous tissue. All patients had tumors with histologic features of low-grade B-cell lymphoma of MALT type, including marginal zone cells (15 of 15 cases), plasmacytic differentiation (10 of 15 cases), Dutcher bodies (three of 15 cases), and reactive germinal centers (10 of 15 cases). All expressed pan B-cell antigens and monotypic immunoglobulin. Seven patients (five women, two men) aged 29 to 86 years (median, 53 years) had primary MALT-type lymphoma of skin (6) or subcutaneous tissue (1). One patient had persistent disease, and four patients had relapses involving skin, subcutaneous tissue, breast, orbit, and lymph node. At last follow-up (11-121 months; median, 36 months), one patient was alive with disease, and six patients had no evidence of disease. Three patients (two women, one man) aged 36 to 67 years (median, 57 years) had concurrent MALT-type lymphoma involving both subcutaneous tissue and extracutaneous sites at primary diagnosis, including lung, breast, orbit, lymph node, and bone marrow. One patient responded to treatment but relapsed with lymphoma of the skin and breast. The other two patients had persistent disease despite treatment. One patient died of disease at 25 months, and, at last follow-up (7 and 46 months), two patients were alive with disease. Five patients (four women and one man) aged 29 to 72 years (median, 63 years) had secondary skin or subcutaneous involvement by MALT-type lymphoma with primary tumors of ocular adnexa (3) or parotid gland (2). All five patients had relapses, which involved skin or subcutaneous tissue, parotid gland, lacrimal gland, breast, and lymph node. At last follow-up (61-137 months), two patients were alive with disease and three were alive with no evidence of disease. Low-grade B-cell lymphomas of MALT type may arise in or secondarily involve the skin and subcutaneous tissue and have a tendency to affect middle-aged to older women. These tumors are characterized by multiple extranodal relapses and are associated with long patient survival. Patients with primary MALT-type lymphoma of skin or subcutaneous tissue without extracutaneous involvement at diagnosis were more likely to experience prolonged disease-free survival than patients with extracutaneous spread at presentation (p < 0.03).

Adult↗
PubMed1996

In situ distribution of integrin alpha 2 beta 1 and alpha-actinin in melanocytic proliferations.

Integrin alpha 2 beta 1 is a transmembrane protein receptor for collagen and laminin previously reported as a melanoma tumor progression antigen. alpha-Actinin is an actin-binding protein reported to interact with the cytoplasmic domain of the beta 1-integrin chain of alpha 2 beta 1. In vitro, both alpha 2 beta 1 and alpha-actinin play a role in melanoma cell motility. In turn, increased melanoma cell line motility (measured as mean migration rates), correlates with metastasis. To determine the in situ distribution of these proteins, we used monoclonal antibodies directed against the alpha 2-integrin subunit of alpha 2 beta 1 and alpha-actinin on frozen sections of 33 melanocytic proliferations, which included dermal nevi, primary melanomas, and metastatic melanomas. We found that the superficial portion of all of the melanocytic proliferations tested stained for alpha-actinin. In benign nevi and superficial spreading melanoma, there was a notable loss of staining for alpha-actinin in the cells in the deep reticular dermis. In contrast, alpha-actinin was present on almost all of the tumor cells in the nodular melanomas and the melanoma metastases. Tumors stained either uniformly positive or uniformly negative for alpha 2 beta 1; the expression of this protein correlated with the later stages of melanoma progression. Our findings suggest that alpha-actinin protein levels initially decrease and then increase during melanocytic tumor progression, whereas the alpha 2 subunit protein appears in the later stages of melanoma progression. The variable distribution of these proteins is evidence for the differential adhesive and motile properties of subpopulations of cells in melanocytic proliferations.

Actinin↗
PubMed1995

Nevoid melanoma: a clinicopathological study of seven cases of malignant melanoma mimicking spindle and epithelioid cell nevus and verrucous dermal nevus.

We report seven cases of a distinctive type of malignant melanoma characterized by a deceptively benign histological appearance with an architecture resembling that of benign melanocytic nevi on scanning magnification. Two predominant architectural patterns were observed: a dome-shaped pattern (two specimens) and a verrucoid pattern (five specimens). The specimens with a dome-shaped pattern of growth were characterized by a smooth epidermal surface and a proliferation of epithelioid melanoma cells with an inconspicuous intraepidermal component resembling spindle and epithelioid cell nevi (Spitz nevi). Gradual diminution in the size of dermal nests toward the bases of the lesions simulating the maturation phenomenon of benign nevi was observed; however, the dermal organization in cords and strands of melanoma cells and the persistence of cellular atypia extending to the bases of the tumors allowed their recognition as malignant melanomas. On the other hand, the specimens with a verrucoid growth pattern consisted of broad, exophytic tumors with a verrucous epidermal surface resembling that of papillomatous dermal nevi but distinguished from them by the presence of a continuous proliferation of melanocytes along the dermal-epidermal junction and by confluent sheets of melanoma cells in the dermis without evidence of true maturation. Clinical follow-up showed local recurrence in three patients after intervals ranging from 5 months to 5 years and regional metastasis in one patient after 2 years. The lesions described here may constitute a serious pitfall for diagnosis because of their innocent silhouette on scanning magnification and their superficial resemblance to spindle and/or epithelioid cell nevi and benign verrucous melanocytic nevi. Proper attention to cytological detail and subtle architectural features will aid in recognizing this unusual variant of malignant melanoma.

Adult↗
PubMed1995

Increased thickness of pregnancy-associated melanoma.

The effects of pregnancy on the pathophysiology of melanoma remain unclear. Although a gender-specific advantage for women vs. men is seen for characteristics such as stage at presentation, site of primary tumour, and survival time, an adverse effect of pregnancy on melanoma development and progression has been reported. In a retrospective study, we investigated the tumour characteristics of women who developed pregnancy-associated melanoma, and compared them with melanomas arising in non-pregnant women of child-bearing age. The patient records of the Massachusetts General Hospital Pigmented Lesion Clinic were reviewed, and 465 women of reproductive age (16-45 years) who developed melanoma were identified. Of these, in 45 women (age 21-42 years) there was a close temporal relationship between diagnosis of the tumour and pregnancy. Clinical and histological characteristics of the primary tumours were recorded. Differences in tumour thickness, site and histological type were analysed. The mean thickness of pregnancy-associated melanomas was significantly greater than that of non-pregnancy-associated tumours (2.28 vs. 1.22 mm, respectively; P < 0.007). No differences in histological type (P = 0.64) or site (P = 0.74) of the primary tumours were found between the two patient groups. Not surprisingly, multivariate analysis revealed that tumour thickness was a statistically significant variable in determining prognosis (P = 0.001). An unexpected finding, on multivariate analysis, was a possible pregnancy-associated prognostic advantage (P = 0.08). Melanomas arising during pregnancy are thicker, but are not necessarily associated with a less favourable prognosis than tumours arising in non-pregnant women of child-bearing age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Leukocytoclastic vasculitis following staphylococcal protein A column immunoadsorption therapy. Two cases and a review of the literature.

BACKGROUND: Protein A immunoadsorption is a novel therapy for the treatment of diseases mediated by pathogenic autoantibodies. This procedure consists of circulating patients' plasma through a column containing staphylococcal protein A, which binds to the Fc portion of IgG, enabling removal of IgG. Presently, protein A immunoadsorption is used in the treatment of idiopathic thrombocytopenic purpura, but may be more widely used as an immunomodulator in human immunodeficiency virus infection and metastatic carcinoma. OBSERVATIONS: We present two histologically documented cases of leukocytoclastic vasculitis in the setting of protein A immunoadsorption. This potentially severe adverse effect is probably more common than the literature reflects and should be recognized by physicians who are treating patients with protein A column pheresis. CONCLUSIONS: The pathogenesis of protein A therapy-associated leukocytoclastic vasculitis remains unclear. Further study of vasculitis in the setting of protein A column pheresis may lead to modifications of this therapy, resulting in fewer adverse effects. Protein A-associated leukocytoclastic vasculitis may serve as a useful model of the relation of immune complexes and vasculitis.

Aged↗
PubMed1994

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

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

Adenocarcinoma, Clear Cell↗
PubMed1994

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

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

Adult↗
PubMed1994

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

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

Antibodies, Monoclonal↗
PubMed1993

Histopathologic recognition and grading of dysplastic melanocytic nevi: an interobserver agreement study.

Before the controversies surrounding dysplastic melanocytic nevi are resolved, dermatopathologists must be able to reliably distinguish dysplastic nevi from common acquired nevi and malignant melanoma. To establish whether grading of melanocytic dysplasia has any biologic relevance, dermatopathologists must be able to consistently recognize two or more grades of atypia. We studied the concordance among five dermatopathologists for recognition and grading of 60 nevomelanocytic lesions. Ten cases from each of the following categories of melanocytic proliferation were retrieved from the Massachusetts General Hospital files: 1) common melanocytic nevi, 2) melanocytic nevi with features of dysplastic nevi, 3) dysplastic nevi with slight cytologic atypia, 4) dysplastic nevi with moderate cytologic atypia, 5) dysplastic nevi with severe cytologic atypia, and 6) primary malignant melanoma. The slides were reviewed independently; no discussion of diagnostic criteria preceded the review. Overall concordance for diagnosing dysplastic nevi was 77%, with a kappa statistic of 0.55-0.84. Furthermore, in grading dysplastic nevi, experienced dermatopathologists had a concordance ranging from 35% to 58% (kappa value 0.38-0.47). Those with less experience in grading dysplastic nevi had a concordance of 16-65% (kappa value 0.05-0.24). The five observers in this study reliably distinguished dysplastic nevi from common acquired nevi and malignant melanoma. Further refinement of the criteria for grading of nevo-melanocytic dysplasia and experience in grading are critical for accuracy in subcategorization of dysplastic nevi. Consistent, reproducible subcategorization of dysplastic nevi is a requisite before the issue of biologic or prognostic relevance of grading (dysplastic nevi) can be addressed. This study supports the validity of existing criteria for the diagnosis of dysplastic nevi because the problems in diagnosis were at the limits of the spectrum, namely, discrimination of slightly atypical dysplastic nevi from common nevi and severely atypical dysplastic nevi from radial growth phase melanoma.

Dysplastic Nevus Syndrome↗
PubMed1993

A simple G-banding technique following nonradioactive in situ hybridization.

A simple G-banding protocol has been found to be compatible with a nonisotopic in situ hybridization technique utilizing a biotin-streptavidin-polyalkaline phosphatase complex. The chromosomes are banded following detection of the hybridization signal, the procedure requires no pretreatment of cultures or special optical equipment, and it produces permanent preparations.

Chromosome Banding↗
PubMed1991

IL-1 gene expression in lymphoid tissues.

We examined the expression of IL-1 mRNA in vivo by in situ hybridization. RNA probes for murine IL-1 alpha and IL-1 beta were used to detect IL-1 mRNA in frozen sections of spleen, lymph node, and thymus of mice injected with Salmonella typhi LPS or SRBC. No IL-1 was detected in lymphoid tissues from un-injected mice. This lack of expression correlated with the absence of IL-1 biologic activity. However, after LPS injection, IL-1 alpha and beta mRNA expression was found in macrophages of the red pulp and marginal zone of the spleen. The periarteriolar lymphoid sheath contained cells that only expressed IL-1 beta mRNA. These cells were not lymphocytes and did not stain with the macrophage marker F4/80. A similar cellular response was found after SRBC injection. Scattered macrophages in lymph nodes and thymus were positive, but only after LPS or SRBC injection. The spleens of mice injected with LPS had megakaryocytes containing IL-1 mRNA.

Animals↗
PubMed1991

Severe perinatal liver disease and Down syndrome: an apparent relationship.

Down syndrome (DS) is not usually thought of in association with significant infantile liver disease. We present clinical and histopathologic data from 10 patients with DS who presented with severe liver disease at birth or within the first few weeks of life, and summarize the findings of eight previously reported cases. The liver disease was fatal in all but one case. Diffuse lobular fibrosis surrounding proliferating ductular elements and residual hepatocytes characterized the pathologic findings in the liver in all patients. A large number of megakaryocytes were present in the liver in nine of 12 patients. The phenotype of "perinatal hemochromatosis" was documented in eight of nine cases in which the presence of iron was investigated. Since only a fraction of the patients with this phenotype have DS, the patients we describe seem to represent a relatively well-defined subset of the perinatal hemochromatosis phenotype. The existence of such a subset suggests that the perinatal hemochromatosis phenotype does not represent a single etiopathogenetic disorder. The association between DS, megakaryocytic infiltrates in the liver, and fatal subacute/chronic liver disease gives rise to the speculation that fibrosis-promoting factors and/or metabolic abnormalities, such as those resulting from a gene dosage effect, may play a role in the genesis of the liver disease, perhaps due to a particular susceptibility of fetal liver.

Down Syndrome↗
PubMed1989

Regulation of antigen presentation. II. Anti-Ig and IL-2 induce IL-1 production by murine splenic B cells.

Murine splenic B cells did not constitutively express IL-1 activity. After culture with anti-Ig and T cell-conditioned media and then fixation, B cells expressed membrane IL-1 and were able to stimulate growth of the IL-1-dependent T cell clone D10. Expression of membrane IL-1 required stimulation of B cells for 2 days before fixation. Significant IL-1 activity was detectable in freeze-thaw lysates of identical B cell preparations by 12 h. B cells also released IL-1 into the culture media. In situ hybridization studies by using probes to murine IL-1 alpha and IL-1 beta genes supported these observations. Thus, messenger RNA for IL-1 alpha and IL-1 beta rose in parallel, were detected between 6 and 24 h of culture, and declined to low levels by 30 h. Despite the presence of mRNA for IL-1 alpha and IL-1 beta, only IL-1 alpha had functional activity as determined by the use of a mAb to IL-1 alpha. IL-2 was found to be an essential component of the T cell-derived supernatant. Although IL-4 or TNF did not induce significant B cell IL-1 expression, they both caused a modest, but reproducible enhancement when added in combination with IL-2. IFN-gamma, by contrast, partially inhibited IL-1 induction.

Animals↗
PubMed1989

T cell induction of macrophage IL-1 during antigen presentation. Characterization of a lymphokine mediator and comparison of TH1 and TH2 subsets.

We described in a previous study two pathways by which Th cells induced macrophage membrane IL-1(mIL-1) during Ag presentation. One pathway was lymphokine-independent and mediated by cell-cell contact. The second was lymphokine-dependent. We have now characterized this lymphokine and show that it belongs to the TNF family of proteins. All TH1 and most TH2 clones produced the lymphokine, although TH1 levels were markedly greater. Both types of clones also induced macrophage mIL-1 by cell-cell contact (i.e., in the absence of lymphokine release). Examination of macrophages by in situ hybridization showed that both IL-1 alpha and IL-1 beta mRNA were coordinately induced during Ag presentation to either TH1 or TH2 clones.

Adjuvants, Immunologic↗
PubMed1988

Congenital heart defect in a patient with deletion of chromosome 7q.

We describe a premature male infant with a terminal deletion of 7q [del(7) (pter----q34:)]. Manifestations include low birth weight, hypertelorism, bilateral cleft lip and palate, cryptorchidism, and a complex congenital heart defect. The latter consisted of hypoplasia of the main pulmonary artery, absent pulmonary valve, ventricular septal defect, and anomalous right pulmonary artery. We briefly review the spectrum of heart defects seen with chromosome 7 deletions, and comment on the incidence of this unusual heart lesion.

Chromosome Aberrations↗
PubMedDate not supplied

Melanoma and pregnancy: eight questions with discussion.

In a question-and-discussion format, the authors summarize the major studies on melanoma and pregnancy. The laboratory studies reviewed give conflicting results; however, excellent epidemiologic studies suggest that pregnancy and melanoma are not closely linked. Specifically, the prognosis of pregnant women with melanoma is similar to the prognosis of nonpregnant women with melanoma of equal tumor thickness, and melanoma is neither more nor less likely to occur in previously pregnant women. Some studies have shown that pregnant women have melanomas that are thicker than nonpregnant women's melanomas. The reason is unclear, but it may be because malignant changes in pigmented lesions during pregnancy have been ignored. Treatment options for pregnant women with melanoma are limited, but early detection and surgical excision of thin melanomas is the goal. Changes in mole size or color during pregnancy can be normal, but all changing moles warrant careful examination, and irregular or asymmetric change is suspicious for melanoma.

Female↗