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Biomedical subjects

C R Shea

Publications and source records attributed to C R Shea.

At least 55 records · Page 3Linked to original sources
PubMed1997

Primary malignant melanoma of the esophagus.

A 48-year-old woman presented with a 6-month history of dysphagia, often associated with retrosternal chest pain. Upper endoscopy revealed an unusual pigmented lesion within the middle portion of the esophagus, and multiple biopsies were obtained. The histopathology and immunohistochemical profile of the tissue specimens were diagnostic of malignant melanoma. A thorough clinical and radiographic evaluation was performed, providing no additional findings or alternative primary source. Of approximately 11,500 melanoma patients entered in the Duke University melanoma database since 1970, this represents the only case of primary esophageal melanoma. The case is described and a review of the literature is presented.

Endosonography↗
PubMed1996

CD34-reactive fibrous papule of the nose.

In human skin, the CD34 antigen is expressed on endothelium, periadnexal cells, and a population of reticular dermal interstitial cells. CD34 expression is characteristic of dermatofibrosarcoma protuberans and several other neoplasms, but not of typical fibrous papules of the nose. We describe a 16-year-old white girl with a slowly growing papule on the nose. Histopathology showed a dermal tumor with a superficial component of branched, thin-walled blood vessels and a deeper component of benign-appearing, spindle-shaped cells. These cells uniformly and strongly expressed CD34, but not factor XIIIa or markers of melanocytic, neural, muscular, vascular, or histiocytic differentiation. We consider this lesion a CD34-reactive fibrous papule. This benign tumor must be clearly distinguished from dermatofibrosarcoma protuberans, which also is composed of bundles of CD34-reactive spindle-shaped cells in most cases but has locally aggressive behavior.

Adolescent↗
PubMed1996

KIT expression reveals a population of precursor melanocytes in human skin.

Human skin is believed to harbor a reservoir population of precursor melanocytes. It has been difficult to identify these putative cells experimentally, because they lack phenotypic features that define mature melanocytes. We have evaluated expression of the KIT tyrosine kinase receptor, which is critical for melanocyte development, as a possible marker of these cells. Sections of human skin were evaluated with single- and double-immunolabeling techniques. KIT-reactive dendritic cells were identified in the basal layer of the epithelia and were most numerous in the follicular infundibula and the rete ridges. These cells were located on the epithelial side of the basement membrane and lacked expression of cytokeratin and mast cell tryptase. The location of the KIT-reactive cells was distinctly different from that of Langerhans cells (identified with anti-CD1a) or Merkel cells (identified with CAM 5.2). Within the epidermis and upper follicular infundibulum the majority of the KIT-reactive dendritic cells also coexpressed TRP-1, a marker present in differentiated melanocytes. In the deeper follicular regions, the coexpression of TRP-1 in the KIT-reactive cells was absent. Throughout the epidermis and follicle, however, the KIT-reactive cells coexpressed BCL-2, a marker known to be increased in melanocytes. Thus, KIT expression reveals a population of intraepithelial cells that have immunophenotypic characteristics of mature melanocytes within the upper epithelial regions, but lack the differentiated melanocytic phenotype within the deeper follicular regions. We propose that these KIT(+), BCL-2(+), and TRP-1(-) cells constitute a precursor melanocyte reservoir of human skin.

Adult↗
PubMed1996

Neutrophilic spongiosis in pemphigus.

BACKGROUND: Acantholysis is the histologic hallmark in the diagnosis of all forms of pemphigus. However, biopsy specimens of early lesions may lack acantholysis and show only eosinophils in the epidermis in areas of spongiosis (eosinophilic spongiosis). We report two cases of pemphigus foliaceus and two cases of unclassified pemphigus (foliaceus vs vulgaris) in which neutrophilic spongiosis was the prominent histologic finding. OBSERVATIONS: Four patients developed blistering skin disorders that spared the mucous membranes. Skin biopsy specimens in all four patients showed striking infiltration of neutrophils into the epidermis. Acantholysis was focal and was absent in some sections. Direct immunofluorescence demonstrated intercellular deposition of IgG and C3 within the epidermis in all cases. There was no IgA deposition. Gram's stains were negative for bacteria in three cases and revealed Gram-positive cocci overlying an eroded area in one case. However, the neutrophilic spongiosis in this case extended well beyond the area of impetiginization. CONCLUSIONS: The histologic differential diagnosis of neutrophils in the epidermis includes pustular psoriasis, subcorneal pustular dermatosis, intraepidermal neutrophilic IgA dermatosis, superficial IgA pemphigus, toxic shock syndrome, Sweet's syndrome, and superficial fungal and bacterial infections. We conclude that pemphigus be added to this differential diagnosis and recommend direct immunofluorescence when neutrophilic spongiosis is observed.

Acantholysis↗
PubMed1996

Dermatologic diseases of the external auditory canal.

The external auditory canal is the only cul-de-sac lined with skin in the human body. Accordingly, most diseases of the external auditory canal, including infections and tumors, could rightly be considered dermatologic. This article, however, discusses only the involvement of the canal by primary dermatologic conditions that typically have a more general distribution as well as local dermatologic reactions to environmental insults.

Acne Vulgaris↗
PubMed1995

Loss of expression of the p16/cyclin-dependent kinase inhibitor 2 tumor suppressor gene in melanocytic lesions correlates with invasive stage of tumor progression.

Sporadic and familial malignant melanoma susceptibility has been linked to defects in the chromosomal region 9p21. Recently, a putative 9p21 tumor suppressor gene, the cyclin dependent kinase inhibitor 2 (CDKN2) or p16 gene, has been shown to be deleted, mutated, or rearranged in a high percentage of sporadic melanoma cell lines, as well as mutated in the germline of a proportion of familial melanoma patients. CDKN2 encodes a M(r) 16,000 protein (p16) that plays a key role in cell cycle control by binding to the cyclin-dependent kinase 4 enzyme and inhibiting its ability to phosphorylate critical substrates necessary for transition past the G1 phase of the cell cycle. Thus, mutations or deletions of the CDKN2 gene could result in abnormal proliferation via defective cell cycle control. The correlation of 9p21 cytogenetic and molecular alterations with the clinical stages of melanoma progression suggests that dysfunction of a gene within this chromosomal region is critical to the evolution of melanoma. However, it remains unclear whether this gene is the CDKN2 gene. If so, then loss of p16 is potentially an initiating or early event in melanoma progression. To address the issues of what is the potential involvement of the CDKN2 gene in sporadic melanoma and precisely when during the clinically evident stages of melanoma progression defects in CDKN2 occur, we have evaluated by immunohistochemistry the expression of p16 protein in 103 melanocytic lesions representing all stages in the progression of melanoma. Our results suggest that loss of p16 protein expression is (a) not necessary for tumor initiation in malignant melanoma because all melanomas in situ and the majority of primary invasive melanomas retain expression of this protein; and (b) potentially more related to invasiveness or the ability to metastasize, because 52% of primary invasive tumors and 72% of metastatic lesions show partial or complete loss of expression of p16.

Blotting, Western↗
PubMed1995

Congenital erosive and vesicular dermatosis with reticulated, supple scarring: a neutrophilic dermatosis.

Congenital erosive and vesicular dermatosis with reticulated, supple scarring is a rare disease seen at birth with blisters that become eroded and crusted and then heal with characteristic scars. We report the seventh case in the American literature, and the first description of biopsy specimens of early lesions. The acute skin lesions were characterized by sterile, neutrophilic infiltrates in the dermis.

Humans↗
PubMed1995

Rapid detection and distinction of cutaneous herpesvirus infections by direct immunofluorescence.

BACKGROUND: Optimal management of cutaneous herpes simplex virus (HSV) and varicellazoster virus (VZV) infections requires rapid, accurate distinction between these pathogens. OBJECTIVE: In a mixed-case series of suspected cutaneous herpesvirus infections, we compared the diagnostic utility of viral culture and direct immunofluorescence (DIF) using a panel of fluoresceinated monoclonal antibodies against HSV and VZV. METHODS: Epifluorescence microscopy of smears and viral culture were performed in parallel on 58 lesions. RESULTS: DIF and culture were equally sensitive (88%) in HSV infections, whereas DIF was four times as sensitive as culture (100% vs 18%) in VZV. DIF either refuted an incorrect clinical diagnosis or permitted definitive laboratory diagnosis of a clinically indeterminate lesion in 7 (12%) of 58 lesions tested. CONCLUSION: DIF is a rapid, simple, sensitive, specific, cost-effective, and clinically useful technique for detecting and distinguishing cutaneous HSV and VZV infections.

Antibodies, Monoclonal↗
PubMed1995

Angiotropic metastatic malignant melanoma.

Three years after excision of a primary malignant melanoma from the lower back, a mass was noted in the right scapular region of a 51-year-old man. Histopathology revealed a malignant spindle-cell neoplasm invading the wall of a deep cutaneous blood vessel. Immunohistochemistry confirmed the diagnosis of angiotropic metastatic melanoma and ruled out primary leiomyosarcoma. Angiotropism is a rare pattern of metastasis of melanoma; the biochemical mechanisms that permit melanoma cells to undergo hematogenous dissemination, and the favorable milieu that the vascular wall offers for melanoma cells, may be responsible for this unusual growth pattern.

Blood Vessels↗
PubMed1995

p53 expression is rare in cutaneous melanomas.

Alterations in the tumor-suppressor gene p53 are common in many types of human malignancies, but the potential role of p53 in the pathogenesis of cutaneous melanoma is controversial. The gene product, p53 protein, is normally present in very small amounts in noncancerous tissues. Missense mutations lead to accumulation of mutant p53 in the cells, which makes it detectable immunohistochemically in many cancers. Formalin-fixed, paraffin-embedded sections of 14 primary invasive melanomas, 3 cutaneous melanoma metastases, and 10 predominantly intradermal melanocytic nevi were reacted with a panel of three anti-p53 monoclonal antibodies (mAbs) (PAb240, PAb1801, and DO7) and a mAb against Ki-67 (MIB-1), a marker of cellular proliferation. p53 was not detected in morphologically normal epidermal melanocytes or nevus cells. A single primary invasive melanoma, having a very high index of proliferation (Ki-67 expression in > 50% of cells), had diffuse nuclear labeling with all three anti-p53 mAbs used. Abnormalities of p53 expression occur rarely in cutaneous melanomas, but overexpression of p53 may occur in a subset of melanomas with a high index of proliferation.

Aged↗
PubMed1995

Differential expression of CD44 in malignant cutaneous epithelial neoplasms.

The CD44 antigen (ECMRIII, Hermes antigen) is a highly glycosylated cell-surface polypeptide involved in diverse cellular functions, including cell adhesion and lymphocyte-homing receptor activity. CD44 is also expressed in vivo by several tumors, including astrocytomas, meningiomas, and colonic adenocarcinomas. In addition, it has been shown that expression of CD44 appears to confer metastatic potential to cell lines derived from certain adenocarcinomas. In the skin, CD44 is normally expressed in epidermal keratinocytes and hair follicular, sebaceous, and eccrine epithelial cells. However, there have been few data with regard to the expression in vivo of CD44 in primary cutaneous neoplasms. Furthermore, there have not been studies in vivo of the possible differential expression of CD44 in primary versus metastatic tumors in the skin. We have examined by immunohistochemistry the expression of CD44 in cutaneous invasive and metastatic squamous cell carcinomas, metastatic adenocarcinomas, and basal cell carcinomas. All invasive and metastatic squamous cell carcinomas, as well as metastatic adenocarcinomas, strongly expressed CD44; however, basal cell carcinomas were nonreactive or showed only focal, minimal reactivity. Adjacent normal skin demonstrated CD44 immunoreactivity throughout the epidermis, including the basal layer. In addition, hair follicles and sebaceous and eccrine glands expressed CD44. The results suggest that expression of CD44 in these cutaneous epithelial tumors is not related to malignant transformation, but instead may be related to tumor progression and the ability to metastasize.

Adenocarcinoma↗
PubMed1995

Immunohistochemical expression of retinoblastoma protein in cutaneous melanomas.

Retinoblastoma protein (pRB) is the product of a tumour-suppressor gene (rb) mapped to chromosome 13q14. pRB acts as a control checkpoint at the G1 phase of the cell cycle, preventing cells from entering into the S phase. Mutational inactivation of both normal alleles leads to loss of pRB expression and the development of malignant neoplasms. Absence of pRB occurs in retinoblastomas, sarcomas and several other types of tumours. The potential role of pRB in the pathogenesis of cutaneous melanoma is unknown, and was the subject of this investigation. Formalin-fixed, paraffin-embedded sections of four cutaneous melanoma metastases, 17 primary invasive melanomas and 10 predominantly intradermal melanocytic naevi were studied. Monoclonal antibodies directed against pRB and Ki-67 antigen were used after microwave heating of sections to restore antigenicity. pRB was not detected in morphologically normal epidermal melanocytes. In five naevi, only scattered cells (1%) expressed pRB, whereas in the other five naevi, pRB expression was undetectable. In contrast, pRB was detected in all primary and metastatic melanomas (5-70% of cells). Expression was always localized to nuclei. Ki-67 expression was detected only in the melanomas, with both cellular staining and regional localization similar to that shown by pRB in 13 of the 20 melanomas studied with both antibodies. pRB appears to be expressed at higher levels in melanomas than in benign naevi. It therefore seems unlikely that loss of rb expression is an important factor in the pathogenesis of melanoma.

Humans↗
PubMed1995

Immunohistochemistry of dermatofibromas and benign fibrous histiocytomas.

Dermatofibromas (DF) are common, benign skin tumors composed predominantly of cells having elongated nuclei and very scant cytoplasm (i.e., fibroblasts) and capillaries in a collagenous stroma. Some authors distinguish DF from benign fibrous histiocytomas (BFH), which are composed of cells with round to oval nuclei and abundant cytoplasm (i.e., histiocytes). In general, this group of tumors expresses factor XIIIa but not the antigen recognized by MAC 387. However, immunohistochemical differences specifically between DF and BFH have not been reported. We have studied the immunophenotype of 23 lesions having morphologic features predominantly either of DF (17 cases) or BFH (6 cases) using antibodies against desmin (muscle marker), alpha-smooth-muscle actin (muscle and myofibroblast marker), CD68 and HAM56 antigen (markers commonly expressed by macrophages, so called "histiocytic" markers), CD34 (a marker present in hematopoietic, vascular, and occasional dermal dendritic cells), and factor XIIIa (a transglutaminase present in many cells including dermal dendrocytes). Many spindle-shaped cells expressed alpha-smooth-muscle actin while many large, round cells expressed the histiocytic markers. However, most lesions expressed at least focally both alpha-smooth-muscle actin and "histiocytic" markers. Thus a clear-cut distinction between DF and BFH could not be made based on immunophenotype alone. Additionally, the prominent alpha-smooth-muscle actin immunoreactivity and desmin non-reactivity suggests myofibroblastic differentiation in the spindle-cell regions of these tumors, and indicates that expression of alpha-smooth-muscle actin cannot be used as definitive proof of muscle differentiation in spindle-cell tumors. We conclude that DF and BFH are not discrete entities, but represent polar expressions of one nosologic entity exhibiting both myofibroblastic and "histiocytic" differentiation.

Actins↗
PubMed1994

Mutation and expression of the p53 gene in human malignant melanoma.

Derangement of the p53 tumor suppressor gene has been implicated in the aetiology of a wide range of human neoplasias. We have previously determined that overexpression and mutation of the p53 gene in cultured metastatic melanomas is low (11%). However, two recent immunohistochemical studies have reported that > 85% of malignant melanoma specimens overexpress mutated p53 protein. In an effort to resolve this contradiction in the published literature, we have re-evaluated a range of cultured and non-cultured melanocytic lesions for the occurrence of point mutations in the p53 gene using DNA- and RNA-dependent single strand conformation polymorphism (RNA-SSCP) and direct DNA sequencing of polymerase chain reaction (PCR) amplified DNA, and overexpression of the p53 protein using immunohistochemistry. We found point mutations in 25% (9 of 36) of cultured melanomas and 0% in 34 fresh melanoma biopsies; however, increased p53 expression was found in 42% of paraffin-embedded melanoma specimens and 7% of benign lesions. The low frequency of p53 point mutations and high frequency of p53 expression suggests that derangement of the p53 gene by point mutations is not a common perturbation in the majority of melanoma cells, and that overexpression of p53 in this tumour type is due to a mechanism other than point mutation.

Adult↗
PubMed1994

Mast cells in angiolipomas and hemangiomas of human skin: are they important for angiogenesis?

To characterize the potential role of mast cells (MC) in angiogenesis, this study tests the hypothesis that MC may be more abundant in angiolipomas than in classic lipomas. MC counts were compared in 13 subcutaneous angiolipomas and 15 subcutaneous classic lipomas stained with Giemsa. Angiolipomas had ten times as many MC as did classic lipomas (25.34 +/- 2.83 versus 2.41 +/- 0.37 per mm2, mean +/- SE). To clarify whether this difference was primary (angiogenic activity) or secondary to the increased vascularity, MC were counted in 8 longstanding cutaneous capillary hemangiomas versus 13 cutaneous capillary hemangiomas of recent onset (pyogenic granulomas). If MC were mediating primary angiogenesis, one would expect them to be present in greater numbers in early than in late hemangiomas. To the contrary, however, long-standing hemangiomas were found to have significantly more MC than had those of recent onset (52.48 +/- 14.99 versus 6.59 +/- 3.37 per mm2, mean +/- SE). These results suggest that MC may not play an essential, early role in the proliferation of blood vessels in angiolipomas and hemangiomas, but rather may be related to maturation of blood vessels in these tumors.

Angiolipoma↗