Biomedical subjects

C R Shea

Publications and source records attributed to C R Shea.

At least 37 records · Page 2Linked to original sources

PubMed2000

Expression of CD34 in sclerotic ("plywood") fibromas.

CD34 antigen is expressed in normal human skin on endothelium, in spindle cells located around adnexal structures, and in a subset of interstitial cells in the reticular dermis. CD34 expression has also been identified in a number of fibrohistiocytic neoplasms, such as dermatofibrosarcoma protuberans and solitary fibrous tumors of soft tissue. CD34 expression has not previously been described in sclerotic, or "plywood" fibromas. Here presented are three lesions from three patients, in which histologic examination revealed a well-circumscribed dermal nodule composed of spindled cells with focal nuclear pseudo-inclusions. There was extensive fibrosis with hypocellular, storiform areas, characteristic of sclerotic fibroma. The spindled cells strongly expressed CD34, but not factor XIIIa or markers of melanocytic, neural, or muscular differentiation. A diagnosis of Cowden syndrome was considered in one of the cases. These cases provide evidence that CD34 expression can occur in sclerotic fibromas, either solitary or associated with Cowden syndrome. When diagnosing a sclerotic fibroma, one should comment in the report regarding the possibility of Cowden syndrome.

Adult↗

PubMed2000

Indeterminate fibrohistiocytic lesions of the skin: is there a spectrum between dermatofibroma and dermatofibrosarcoma protuberans?

Routine histology and immunohistochemistry can usually distinguish dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP). DF generally expresses factor XIIIa whereas DFSP generally expresses CD34. The authors report 10 cutaneous fibrohistiocytic lesions combining clinical, histologic, and immunohistochemical features of both DF and DFSP. The lesions had an average size of 1.2 cm (range, 0.4-2.7 cm), and occurred on the trunk (n = 6), extremities (n = 3), and face (n = 1) of four men and six women (average age, 30.6 yrs; age range, 15-50 yrs). Eight lesions exhibited acanthosis and densely cellular fascicles with focal storiform areas. All had keloidal collagen, infiltrated the subcutis in a honeycomb pattern, and had low mitotic counts (0 to 4 mitoses per square millimeter). All were diffusely immunoreactive for factor XIIIa (30%-60% of the neoplastic cells) as well as CD34 (20%-70%). This series raises the possibility of a biologic spectrum between DF and DFSP; however, double-immunolabeling studies showed no notable coexpression of factor XIIIa and CD34 by individual cells, suggesting coexistence of two different cellular populations. After an average follow up of 22.3 months (range, 10-46 mos) in six cases, a single recurrence was documented. The ambiguous histologic features and the potential for local recurrence suggest that performing a complete excision may be prudent in these diagnostically indeterminate lesions.

Acanthosis Nigricans↗

PubMed2000

Malignant melanoma with paradoxical maturation.

Typically, melanocytic nevi "mature" (i.e., exhibit a morphologic shift to smaller or spindle cells with progressive depth in the dermis). In contrast, most malignant melanomas (conventional MMs) lack maturation, and are composed of large pleomorphic cells throughout. The authors describe a series of melanomas with paradoxical maturation mimicking the pattern of nevi. Seventeen primary invasive melanomas with paradoxical maturation (IMPs), two epidermotropic metastatic melanomas with maturation (EMMMs), 13 compound nevi (CN), and 14 conventional MMs without apparent maturation were analyzed by histologic, cytomorphometric, and immunohistochemical techniques. With increasing dermal depth, both CN and IMPs had smaller nuclear and cellular areas, and decreased expression of Ki-67, glycoprotein (gp)100 (with HMB-45), and tyrosinase. IMPs had significant differences from conventional MMs; namely, smaller nuclear and cytoplasmic areas (deep), and decreased expression of Ki-67 (superficial and deep), gp100 (deep), and tyrosinase (deep). IMPs also had notable differences from CN: namely, larger nuclear and cellular areas, more confluence, more mitotic figures, increased Ki-67 and gp100 expression in both the superficial and deep portions, and more melanin (deep). The two EMMMs exhibited histologic and immunohistochemical features similar to the primary IMPs. IMP, because of its mimicry of nevus, can present a diagnostic hazard. The authors propose histologic, morphometric, and immunohistochemical criteria that facilitate recognition and accurate diagnosis of this unusual variant of melanoma.

Adolescent↗

PubMed2000

Increased incidence of trisomy 8 in acute myeloid leukemia with skin infiltration (leukemia cutis).

Anecdotal literature reports and the authors' own observations suggest an association between chromosome 8 aneuploidy and leukemia cutis. The authors investigated this potential association by using fluorescence in situ hybridization (FISH) directly on skin infiltrates in a series of 11 patients with acute monocytic leukemia (AML). Seven of the 11 patients were aneuploid for chromosome 8 by FISH which was confirmed by dual color hybridization. Six of these seven patients were AML-M4 or M5 and one was M1. The majority of the cases with leukemia cutis expressed CD4 (90% of cases), CD14 (60%), and/or CD56 (50%) in bone marrow leukemic cells. The data show the utility of examination of skin infiltrates by FISH for the detection of trisomy 8 in leukemia cutis. They also suggest the importance of trisomy 8 as a factor in predisposition to skin infiltration in AML.

Chromosomes, Human, Pair 8↗

PubMed1999

High-intensity flashlamp photoepilation: a clinical, histological, and mechanistic study in human skin.

OBJECTIVE: To examine the clinical, histological, and immunohistological effects of flashlamp photoepilation. DESIGN: Nonrandomized control trial with blinded histological study and follow-up of 1 to 20 months. SETTING: Private academic practice. SUBJECTS: Sixty-seven subjects (10 males and 57 females) with areas of excess body hair. INTERVENTIONS: Single (9 subjects) or multiple (58 subjects) treatments (noncoherent, 590-1200 nm, 2.9-3.0 milliseconds, 40-42 J/cm2) to hairy skin. From subjects given a single treatment, biopsy samples were taken immediately after treatment and at different intervals for up to 20 months. MEAN OUTCOME MEASURES: Clinical measures include hair counts and morphologic features before and after treatment. Histological measures include terminal-vellus and anagen-other ratios, hair shaft diameter, and morphologic features (routine and immunohistochemical detection of bcl-2, bax, p53, Ki67, cyclin D1, and hsp70) before and after treatment. RESULTS: Mean hair loss after photoepilation was 49%, 57%, and 54% for a single treatment and 47%, 56%, and 64% for multiple treatments at follow-up of less than 3 months, 3 to less than 6 months, and 6 months or longer, respectively (P<.05 for all comparisons). Transient erythema was seen in all subjects; no scarring occurred. Histologically, treatment caused morphologic damage confined to hair follicles and shafts. Terminal-vellus and anagen-telogen ratios, mean hair shaft diameter, and immunohistochemical profiles were not significantly modified by treatment. Treatment did not alter other skin adnexa, epidermis, or vessels. CONCLUSIONS: Flashlamp treatment leads to significant, longlasting epilation. The predominant mechanism seems to be via selective photothermal damage to large, pigmented hair follicles rather than induction of a programmed state of follicular cycle arrest or follicular miniaturization.

Adolescent↗

PubMed1999

Correlating architectural disorder and cytologic atypia in Clark (dysplastic) melanocytic nevi.

Histological architecture is very important in the pathological diagnosis of Clark (also known as atypical or dysplastic) melanocytic nevi. However, few studies have attempted to quantify architectural features or to correlate them directly with cytology. In 166 consecutive Clark nevi, the presence or absence of the following features in the intraepidermal or junctional component was recorded: (1) Architecture: circumscription, symmetry, cohesiveness of nests, suprabasal melanocytes, confluence, and single-cell proliferation; (2) Cytology of melanocytes: round/euchromatic nuclei, nuclear enlargement, cell enlargement, and prominent nucleoli. Each criterion was given a value of 0 or 1, and a summation score was obtained for both architecture and cytology in each case. The chi-square test was used to determine the significance of relationships among these parameters. The degrees of architectural disorder and of cytologic atypia were positively correlated (P = .026). Scores for both parameters were distributed over a wide range of values and were concentrated toward the low-middle portion of the spectrum. Several particular architectural and cytologic variables showed significant interdependence. Clark nevi exhibit a broad spectrum of architectural disorder and cytologic atypia, which, according to our data, generally are closely related features. Because some cases displayed a relatively high score for one parameter but a low score for the other, quantification of both parameters permits a more complete histopathologic evaluation of these lesions and may provide additional information for their clinical management.

Adolescent↗

PubMed1999

Selected cutaneous vascular neoplasms. A review.

This article reviews the pathology of benign, borderline, and malignant vascular neoplasms of the skin. The classification of vascular lesions of childhood is presented. Defined variants of hemangioma (including sinusoidal, microvenular, glomeruloid, epithelioid, and targetoid hemosideric hemangioma, as well as acquired tufted hemangioma and angiofibroma) are discussed. Borderline hemangioendotheliomas are classified. Kaposi sarcoma is reviewed with an update on the role of human herpesvirus type 8 in its pathogenesis. Angiosarcoma and acquired progressive lymph-angioma are also discussed.

Biopsy, Needle↗

PubMed1999

Recent developments in the pathology of melanocytic neoplasia.

This article selectively discusses clinically relevant aspects of the pathology of cutaneous melanocytic neoplasms, from the literature of the past recent years. Topics include the changing role of immunohistochemistry in diagnosis, the controversies over dysplastic nevi, description of other specialized variants of melanocytic nevi, diagnosis of melanocytic neoplasms of acral skin, and melanoma occurring in childhood. Several variants of melanoma including desmoplastic and spindle-cell types, verrucous melanoma, epidermotropic melanoma, and melanoma of the female genitalia are reviewed. The issue of appropriate margins of resection for melanoma and the use of Mohs Micrographic surgery for this tumor are considered. Finally, a review of the sentinel node biopsy technique and of nodal nevi is presented.

Child↗

PubMed1999

Allelic and locus heterogeneity in inherited venous malformations.

Venous malformations are low-flow vascular lesions consisting of disorganized thin-walled vascular channels. These can occur sporadically but also as an autosomal dominant condition termed venous malformations, cutaneous and mucosal (VMCM; OMIM 600195). In two large unrelated kindreds mapping to chromosome 9, the identical R849W missense mutation was identified in the first kinase domain of Tie2, an endothelial cell-specific receptor tyrosine kinase. We report here the identification of four new kindreds with inherited venous malformations. Unlike the initial two families described, these four families demonstrate allelic and locus heterogeneity. In one of these families, the R849W mutation co-segregates with the disease phenotype. Three other families with venous malformations lack this mutation. One of these families is linked to markers near TIE2 on chromosome 9. In this family, we identified a novel mutation within the first kinase domain of Tie2 resulting in a Y897S change. Results from COS-1 cell transfections using expression constructs containing either the R849W or the Y897S mutation suggest that the receptors containing either mutation show ligand-independent hyperphosphorylation. These results suggest a gain-of-function mechanism for development of venous malformations in these families. Of the two remaining families, one excludes linkage to the TIE2 locus, establishing the existence of at least one additional locus for dominantly inherited venous malformations.

Amino Acid Sequence↗

PubMed1999

Desmoplastic (sclerotic) nevus: an underrecognized entity that resembles dermatofibroma and desmoplastic melanoma.

Desmoplastic (sclerotic) nevus, a benign melanocytic neoplasm characterized by predominantly spindle-shaped nevus cells within a fibrotic stroma, can be confused with fibrous lesions and other melanocytic proliferations, including desmoplastic melanoma. We compared the histologic and immunohistochemical features of 16 desmoplastic nevi, nine desmoplastic melanomas, four hypopigmented blue nevi, and six dermatofibromas. The similarities between desmoplastic nevi and dermatofibromas included epidermal hyperplasia (12 of 16), presence of keloidal collagen (15 of 16), hypercellularity (16 of 16), and increased numbers of factor XIIIa-positive dendritic cells (12 of 12). The absence of adnexal induction (0 of 16), the rarity of lesions with multinucleated cells (3 of 16) or epidermal hyperpigmentation (2 of 16), and the presence of S-100 immunoreactivity (16 of 16) and melanocytic proliferation (9 of 16) helped differentiate desmoplastic nevi from dermatofibromas. The similarities between desmoplastic nevi and desmoplastic melanomas included the presence of atypical cells (16 of 16) and HMB-45 expression in the superficial portion of the lesions (11 of 16). The infrequent location on the head or neck (1 of 16), the absence of mitotic figures (0 of 16), a significantly lower number of Ki-67-reactive cells, and a decrease in HMB-45 expression in the deep area of the lesions (8 of 11) helped distinguish desmoplastic nevi from desmoplastic melanoma. Desmoplastic nevi had overlapping features with hypopigmented blue nevi, but features tending to favor the latter included a predominance of ovoid nuclei, higher numbers of atypical cells, and homogeneous staining with HMB-45. We conclude that a combination of histologic and immunohistochemical criteria facilitates the reliable diagnosis of desmoplastic nevus from its simulators.

Adolescent↗

PubMed1999

Quantitation of intraepidermal T-cell subsets in formalin-fixed, paraffin-embedded tissue helps in the diagnosis of mycosis fungoides.

Differentiation between mycosis fungoides (MF) and cutaneous inflammatory processes can usually be made on clinical and histologic grounds. In difficult cases, immunohistochemical studies can be helpful since MF infiltrates usually contain a predominance of CD4+ lymphocytes, while most inflammatory lesions usually have a mixture of CD4+ and CD8+ lymphocytes. However, this determination has traditionally required the use of frozen tissue, thus severely limiting its usefulness. Recently, antibodies that differentially label CD4+ and CD8+ lymphocytes in formalin-fixed, paraffin-embedded tissue have become available (OPD4 and C8/144B respectively, DAKO (Carpinteria, CA, USA). This study tests the utility of these antibodies in the pathologic diagnosis of MF and inflammatory lesions with significant exocytosis. In 9 cases of MF for which both frozen and fixed tissues were available for comparison, the OPD4+ cell count in fixed tissue was significantly lower than the Leu-3a+ cell count in frozen tissue. Also, the C8/144B+ cell count in fixed tissue was higher than the Leu-2a+ cell count in frozen tissue, although this difference was not significant statistically. In a larger series for which only fixed tissue was available, epidermal CD4:CD8 ratios were significantly greater in 23 MF cases (mean 4.0+/-4.76) than in 35 inflammatory cases (mean 0.6+/-0.42; p = 0.001). Thus, although the studied antibodies appear to detect different epitopes in frozen versus paraffin-embedded tissue, demonstration of an elevated CD4:CD8 ratio in fixed tissue supports the diagnosis of MF, and is a helpful adjunct to routine histopathology.

Aged↗

PubMed1999

Epstein Barr virus-associated lymphoproliferative-disorders primarily involving the skin.

In cases of solid organ or bone marrow transplantation, up to 2 to 10% of patients may develop lymphoproliferative disorders (LPD), often induced by Epstein-Barr virus (EBV). Despite a morphology mimicking malignant lymphoma, in some cases the lesions will disappear completely after the degree of immunosuppression is lowered. Lately, similar processes have been described in non-transplant, immunosuppressed patients. A SNOMED search was performed on the database of three hospitals between 1990 and 1997, to identify patients with immunosuppression-related lymphoproliferative disorders (IR-LPD) involving primarily the skin. Two patients were identified. One was 2 years after kidney transplantation, and the other was being treated with methotrexate for dermatomyositis. In both biopsies, there was a diffuse perivascular proliferation of large lymphocytes with ample cytoplasm and pleomorphic nuclei, associated with extensive dermal and subcutaneous necrosis. Immunohistochemical studies revealed expression of CD20, CD45RO, CD43, CD30, EBV-LMP1, and EBV-NA2 by the atypical lymphocytes in both cases and, in one case, of the EBV-transcriptional replication activation protein. In both cases the lesions completely disappeared and have not recurred. Primary involvement of the skin by IR-LPD is very rare. Based on our results, it is possible that some of these cases in the skin contain EBV and co-express CD30 and T- and B-cell markers. The diagnosis of IR-LPD should be considered in cutaneous lymphoid proliferations in immunosuppressed patients. Before rendering an unequivocal diagnosis of malignant lymphoma, reduction of immunosuppression and follow-up of 4-8 weeks should be considered.

Adult↗

PubMed1999

Trichoepithelioma: a 19-year clinicopathologic re-evaluation.

Accurate histopathologic distinction between trichoepithelioma (TE) and basal cell carcinoma (BCC) may be challenging. From 97 cases diagnosed as TE during the period 1979-1997, 73 available cases were studied with regard to: 1) stroma; 2) retraction effect; 3) papillary-mesenchymal bodies (PMB); 4) amyloid; 5) mitotic figures; 6) apoptotic cells; 7) inflammation; 8) granuloma; and 9) calcification. A judgment was made regarding diagnosis. The patients' medical records were subsequently reviewed for clinical features and possible recurrence. The diagnosis of TE was confirmed histologically in 48 (65%) of 73 cases. Fifteen cases (21%) were reclassified as BCC (RC-BCC), eight other cases (11%) were reclassified as other lesions, and two additional cases (3%) could not be confidently classified as either TE or BCC. The most helpful differentiating features were the presence of retraction effect (in 100% of RC-BCC vs. 37% of TE), myxoid stroma (in 80% of RC-BCC vs. 12% of TE) and PMB (in 20% of RC-BCC vs. 81% of TE). Unexpected findings in TE were detection of amyloid in 33%, apoptotic cells in 100%, and mitotic figures in 46%. Five of the 15 RC-BCC have recurred (33%), whereas there have been no recurrences in the confirmed TE group. A constellation of histopathologic criteria may help to discriminate problematic examples of trichoepithelioma from basal cell carcinoma.

Adult↗

PubMed1999

Subcutaneous granuloma annulare: MR imaging features in six children and literature review.

PURPOSE: To describe the magnetic resonance (MR) imaging findings of subcutaneous granuloma annulare (SGA), a rare mass of early childhood. MATERIALS AND METHODS: MR imaging studies and clinical records in six children aged 2 1/2-4 years in whom SGA was diagnosed between 1993 and 1997 were retrospectively reviewed. All MR imaging examinations included T1-weighted and fast spin-echo T2-weighted sequences. Three children received intravenous contrast material. The diagnosis was established by using excisional biopsy results, with confirmation by means of characteristic features in mucin-stained specimens. RESULTS: All children presented with a nontender, nonmobile mass. The lesion in all six children was confined to the pretibial (n = 5) or prepatellar (n = 1) soft tissues. MR imaging characteristics were uniform. Masses were subcutaneous in location and had ill-defined margins. On T1-weighted images, the lesion was isointense or slightly hyperintense to muscle. On T2-weighted images, the signal intensity was more heterogeneous, but the lesion was predominantly hyperintense. In three children who received contrast material, the lesion enhanced nearly homogeneously. CONCLUSION: Although SGA can often be diagnosed on the basis of clinical characteristics, MR imaging may be requested by practitioners unfamiliar with the lesion. In these cases, with recognition of typical MR imaging features, a limited biopsy and specific histologic preparation that includes mucin staining can be recommended.

Biopsy↗

PubMed1998

Follicular mucinosis as a presenting sign of acute myeloblastic leukemia.

Follicular mucinosis is often associated with mycosis fungoides and has been rarely observed to occur with other neoplastic and inflammatory conditions. We describe a 60-year-old patient with follicular mucinosis who later developed acute myelogenous leukemia. This is the first reported case of follicular mucinosis as a presenting sign of acute myeloblastic leukemia in the absence of mycosis fungoides or leukemia cutis.

Antibiotics, Antineoplastic↗

PubMed1998

Distal pachydermodactyly.

An 80-year-old white woman had a 6-year history of enlarging, intradermal plaques on the distal, volar, and lateral surfaces of the fingers. A biopsy specimen showed whorled, densely aggregated bundles of coarsely thickened collagen within a sparsely cellular papillary and reticular dermis. The fibrosis entrapped eccrine sweat coils and focally extended into the subcutis. This case represents an unusual, predominantly acral form of acquired, progressive, cutaneous fibrosis, which we propose to call distal pachydermodactyly.

Aged↗

PubMed1998

The SCF/KIT pathway plays a critical role in the control of normal human melanocyte homeostasis.

During development, the interaction of stem cell factor (SCF) with its receptor, KIT, is critical for the survival of melanocytes. Limited in vivo human studies have suggested a possible activating role of SCF on adult human melanocytes. In order to study the impact of this pathway on normal melanocyte homeostasis, human skin xenografts were treated with serial injections of recombinant human SCF or a KIT-inhibitory antibody (K44.2). On histologic evaluation, SCF injection increased, whereas KIT inhibition decreased the number, size, and dendricity of melanocytes. Immunohistochemical expression of melanocyte differentiation antigens, including tyrosinase-related-protein-1 and gp100/pmel17, was markedly increased by treatment with SCF, and decreased by K44.2 treatment. The number of Ki67-positive melanocytes was increased in the SCF-treated tissue, suggesting a direct proliferative effect of SCF; conversely, treatment with K44.2 resulted in melanocyte loss, which did not appear reversible with prolonged treatment. These findings demonstrate that the SCF/KIT pathway remains critical in adult human skin, and that pharmacologic modulation of this single pathway can control cutaneous melanocyte homeostasis.

Animals↗

PubMed1998

Numbers and differentiation status of melanocytes in idiopathic guttate hypomelanosis.

The etiology and pathogenesis of idiopathic guttate hypomelanosis (IGH) are largely unknown. To investigate whether the pathologic alteration in IGH involves changes in melanocytic differentiation, cell number, or both, we studied nine lesions of IGH by immunoperoxidase, using monoclonal antibodies against the KIT receptor and a panel of melanocyte differentiation antigens (tyrosinase-related protein-1, tyrosinase, and gp100/pme117). In each case, compared with grossly normal non-lesional skin, IGH lesions showed markedly reduced numbers both of KIT+ cells and of cells expressing melanocyte differentiation antigens (p < 0.0001). Double immunofluorescence labeling of lesions revealed only scattered cells with a less-differentiated phenotype, i.e. cells positive for KIT but having low or undetectable TRP-1. These results indicate that the pathogenesis of IGH involves an absolute decrease in the number of melanocytes; a block in melanocyte differentiation does not appear to be a major component of the process.

Adult↗