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Biomedical subjects

A Neil Crowson

Publications and source records attributed to A Neil Crowson.

At least 19 recordsLinked to original sources
PubMed2006

Imiquimod as an antiaging agent.

BACKGROUND: Topical imiquimod therapy has proven to be effective for a variety of infectious, neoplastic, and inflammatory dermatologic diseases. Several published reports have validated the benefit of imiquimod therapy for actinic keratoses and superficial melanoma and nonmelanoma skin cancers. There is, however, limited evidence demonstrating the use of topical imiquimod application as an antiaging treatment. OBJECTIVES: We examined the effectiveness of imiquimod 5% cream in the treatment of photoaging by evaluating pretreatment and posttreatment biopsy specimens and documenting the histologic changes. METHODS: This study represents an extension of an earlier project in our department in which patients with biopsy-proven lesions of lentigo maligna (LM) were recruited from a university dermatology service, a hospital, and referrals from private practitioners for an open-labeled efficacy trial with daily topical application of 5% imiquimod for 3 months. Biopsy of clinically affected skin was carried out on all patients before and after treatment. Using a semiquantitative method, biopsy specimens were analyzed for changes in the dermal collagen table (solar elastosis vs papillary dermal fibroplasia). Additional parameters analyzed included epidermal changes (atrophy vs acanthosis, melanin content, and hypergranulosis) and inflammatory effects (epidermal and dermal cell populations along with presence of pigment incontinence). Variables were compared using paired Wilcoxan rank sums. RESULTS: Of 26 evaluable patients who completed 3 months of daily application, 24 (>92.3%) showed a significant increase in papillary dermal fibroplasia (P < .0001) with associated reduction in solar elastosis (P = .0036). Other noteworthy findings were restoration of normal epidermal thickness (P = .0073) and melanization (P < .0001). LIMITATIONS: This study only evaluates the effect of imiquimod in the lesional skin of LM. It is not known whether the results are applicable to nonlesional, photoaged skin. CONCLUSION: Topical imiquimod appears to induce reparative changes to the epidermis and the dermal collagen table in chronically sun-damaged skin associated with LM, indicating its potential use as an antiaging treatment. These findings need to be confirmed in photodamaged skin not associated with LM.

Aminoquinolines↗
PubMed2006

Cytomegalovirus-associated cutaneous vasculopathy and scleroderma sans inclusion body change.

Viruses have long been held to be of pathogenetic importance in the evolution of autoimmune connective tissue disease. We describe 7 adults who developed cutaneous connective tissue disease stigmata in temporal association with recent cytomegalovirus (CMV) infection but without the classic cytopathic changes of CMV infection. We examined 7 adults with clinical presentations encompassing cutaneous vasculitis in 4 and scleroderma in 3. In all 7 patients, there was either IgM seropositivity for CMV and/or CMV DNA isolation from peripheral blood. Although no CMV inclusions were seen, in situ hybridization studies revealed very focal CMV RNA transcript expression with localization mainly to the endothelium. The patients with vasculitis treated with ganciclovir had improvement or resolution of symptoms, whereas only 1 patient with scleroderma received antiviral therapy, without benefit. Another scleroderma patient responded to infliximab therapy. Abortive/partial CMV reactivation can be associated with a syndrome complex mimicking and/or triggering a primary immune-based cutaneous microvascular injury syndrome. Antiviral therapy appears to be of therapeutic value in those cases associated with active necrotizing vasculitic changes. The role of tumor necrosis factor alpha blockers in scleroderma cases temporally associated with CMV infection requires further evaluation.

Adult↗
PubMed2006

Unusual histologic and clinical variants of melanoma: implications for therapy.

Unusual histologic variants of melanoma may prove problematic to the histopathologist. Several of these variants are sufficiently rare that their biological behavior remains obscure. Because identification of some of these melanoma subtypes has specific implications for the therapeutic approach and some may mimic other forms of epithelial or mesenchymal neoplasia, their recognition is key to patient management.

Diagnosis, Differential↗
PubMed2006

Malignant adnexal neoplasms.

Malignant cutaneous adnexal neoplasms are one of the most challenging areas of dermatopathology. Tumors of the pilosebaceous apparatus can occur as single-lineage neoplasms or may manifest as complex proliferations with multilineal differentiation patterns including not only the germinative component of the hair bulb, the inner or outer root sheath epithelium and the sebaceous gland and duct, but also the sweat duct components that relate to the apocrine secretory apparatus which empties into the follicle near the follicular bulge. Eccrine and apocrine neoplasms present a bewildering array of morphologies, which often defy precise classification. The purpose of this review is to discuss in detail the malignant neoplasms of the cutaneous adnexae and their benign and prognostically indeterminate mimics.

Diagnosis, Differential↗
PubMed2006

Basal cell carcinoma: biology, morphology and clinical implications.

Basal cell carcinoma (BCC) is the most common malignant neoplasm of humans. Rising dramatically in incidence in North America, as likely reflects changing habits of the population and a move from more northerly climes to the sunbelt of the Southern and Southwestern United States, the incidence is surely to rise even higher in the future. The last decade has seen significant advances in our understanding of BCC biology and novel approaches to therapy, which hinge upon accurate diagnosis and subclassification by pathologists. The purpose of this review article is to summate the research advances in our understanding of BCC biology and to acquaint pathologists and clinicians to the practical issues in BCC diagnosis and subclassification which flow there from.

Basal Cell Carcinoma↗
PubMed2006

The future of dermatopathology.

Of the major issues that dermatopathology will face in the immediate future, two powerful challenges loom large. The first is the application of novel nondestructive imaging technologies to in vivo diagnosis in humans. The second is the application of molecular technologies to a diagnostic arena which formerly belonged exclusively to the light microscopist. The first to be considered in this context is the application of near infrared spectroscopy to the noninvasive in vivo diagnosis of neoplastic skin disease. The second will be a discussion of application, methodology and the current state of the art in microarray technologies as they apply to neoplastic dermatopathology and, in particular, the diagnosis and prognostication of melanoma.

Dermatology↗
PubMed2006

Unusual variants of malignant melanoma.

A potential diagnostic pitfall in the histologic assessment of melanoma is the inability to recognize unusual melanoma variants. Of these, the more treacherous examples include the desmoplastic melanoma, the nevoid melanoma, the so-called 'minimal-deviation melanoma,' melanoma with prominent pigment synthesis or 'animal-type melanoma,' and the malignant blue nevus. Also problematic are the unusual phenotypic profiles seen in vertical growth phase melanomas; these include those tumors whose morphological peculiarities mimic cancers of nonmelanocytic lineage and those melanomas that express aberrant antigenic profiles not commonly associated with a melanocytic histogenesis. Metaplastic change in melanoma, balloon cell melanoma, signet-ring cell melanoma, myxoid melanoma, small cell melanoma and rhabdoid melanoma all have the potential to mimic metastatic and primary neoplasms of different lineage derivations. Abnormal immunohistochemical expression of CD 34, cytokeratins, epithelial membrane antigen, and smooth muscle markers as well as the deficient expression of S100 protein and melanocyte lineage-specific markers such as GP100 protein (ie HMB-45 antibody) and A103 (ie Melan-A) also present confusing diagnostic challenges. In this review, we will discuss in some detail certain of these novel clinicopathologic types of melanoma, as well as the abnormal phenotypic expressions seen in vertical growth phase melanoma.

Antigens, Neoplasm↗
PubMed2006

Prognosticators of melanoma, the melanoma report, and the sentinel lymph node.

Since the 1960s, the clinical characteristics of melanoma, its histopathology and its biological basis have been the subject of intense study at pigmented lesion clinics in North America, Europe, and Australia. More recently, the immense database of the Melanoma Committee of the American Joint Committee on Cancer (AJCC) has been exploited through complex mathematical models to measure the impact of various histologic features of primary melanomas and of sentinel lymph node deposits and to correlate these parameters with patient survival. The wealth of modern information available to pathologists and clinicians has become of vital interest to the prognostication of the individual patient with melanoma. The purpose of this review is to bring to the attention of anatomic pathologists the essential characteristics of the pathology report for primary cutaneous melanoma in the modern era.

B7-1 Antigen↗
PubMed2006

Medicolegal aspects of neoplastic dermatology.

Medical malpractice litigation is rising at an explosive rate in the US and, to a lesser extent, in Canada. The impact of medical malpractice litigation on health care costs and the cost of insurance is dramatic. Certain specialist categories are becoming uninsurable in some parts of the US, while in others, clinicians are retiring early, restricting or changing practice or changing states of residence in consequence of medical malpractice claims and of the cost and availability of insurance. This, in turn, has had the real effect of denying care to patients in some communities in the US. Some 13% of all medical malpractice claims relate to one area of neoplastic dermatopathology, specifically, melanocytic neoplasia. Certain steps can be taken by pathology laboratories to reduce, but never completely eliminate, the risk of medical malpractice claims. In this review, attention is paid to the source of medical malpractice claims and an abbreviated approach to specific strategies for risk management is presented.

Dermatology↗
PubMed2006

CD8+ lymphomatoid papulosis and its differential diagnosis.

We describe 5 cases (4 males, 14-43 years old; 1 female, 61 years old) of primary cutaneous T-cell lymphoproliferative lesions expressing a CD8/granzyme/CD30-positive phenotype. Four cases were compatible with lymphomatoid papulosis (LyP) based on the clinical course, which was recurrent asymptomatic papular nodular lesions over years responding to methotrexate; granulomatous inflammation and lack of other inflammatory cell elements were characteristic. In 1 case, an initial erroneous diagnosis was made of aggressive epidermotropic CD8+ T-cell lymphoma. The fifth case in this series was first interpreted as representing primary cutaneous anaplastic large cell lymphoma but was later recategorized as primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma owing to the extent of extracutaneous dissemination, including testicular involvement and disease progression despite chemotherapeutic intervention. Although all cases of LyP showed sharp cytoplasmic membrane staining with perinuclear Golgi accentuation with CD30, the recategorized case of aggressive epidermotropic CD8 cytotoxic T-cell lymphoma manifested only a weak cytoplasmic staining pattern. CD8 LyP defines a distinctive entity with characteristic light microscopic and phenotypic findings and has a predilection for young males. CD30 expression can occur in other forms of CD8 lymphoproliferative disease unrelated to primary cutaneous anaplastic large cell lymphoma or LyP.

Adolescent↗
PubMed2005

Epstein-Barr virus- and human herpesvirus 8-associated primary cutaneous plasmablastic lymphoma in the setting of renal transplantation.

BACKGROUND: Plasmablastic lymphoma (PBL) is a recently recognized entity most often reported in the oral cavity, mainly in the setting of underlying human immunodeficiency viral infection whereby a role for Epstein-Barr virus (EBV) and more recently human herpesvirus 8 (HHV8) has been described. Although EBV has been implicated in a variety of lymphoproliferative lesions, until recently HHV8 has only been associated with primary effusion lymphoma, multicentric Castleman's disease, and Kaposi's sarcoma. We describe a case of PBL occurring in the setting of renal transplantation. METHODS: We encountered a case of PBL occurring in the setting of renal transplantation. We characterized the tumor by routine immunohistochemistry and evaluated for the presence of immunoglobulin light chain restriction and EBV RNA by in situ hybridization. We assessed for the presence of HHV8 RNA by reverse transcriptase in situ hybridization. RESULTS: The tumor showed a histomorphology compatible with a PBL. In addition, there was strong RNA expression in the neoplastic cells for EBER-1, EBER-2, and HHV8. CONCLUSION: This case suggests a possible role of both viruses in the pathogenesis of PBL in sites other than the oral cavity and expands the spectrum of post-transplantation lymphoproliferative disease to include PBL.

Adult↗
PubMed2005

The application of a monoclonal antibody to CD62L on paraffin-embedded tissue samples in the assessment of the cutaneous T-cell infiltrates.

BACKGROUND: A reduction in the expression of the pan T-cell markers CD7 and CD62L supports an endogenous T-cell dyscrasia. Previously, clone availability for CD62L restricted its application to frozen tissue sections. MATERIALS AND METHODS: A nonavidin/biotin technique to examine CD3, CD62L, and CD7 in paraffin formalin-fixed tissue in non-neoplastic and neoplastic T-cell infiltrates. RESULTS: In the reactive group, CD62L manifested a 15 and 22% reduction in epidermal and dermal staining, respectively; there was a 42 and 31% reduction in epidermal and dermal CD7 staining. In lymphomatoid hypersensitivity, CD62L showed a 24 and 9% reduction in epidermal and dermal staining, respectively; CD7 staining demonstrated reduced staining by 70 and 66% in the epidermis and dermis. In the non-lymphomatous endogenous T-cell dyscrasia and lymphoma categories, an 80% diminution in CD62L and CD7 expression was seen. CONCLUSIONS: CD62L can be successfully applied in formalin-fixed tissue and exhibits enhanced specificity compared to CD7 in the evaluation of cutaneous T-cell infiltrates. Both CD62L and CD7 in paraffin-embedded, formalin-fixed tissue are useful diagnostic adjuncts, especially in regard to the discrimination of lymphomatoid hypersensitivity reactions from true endogenous T-cell dyscrasia.

Antibodies, Monoclonal↗
PubMed2005

De novo intraepidermal epithelioid melanocytic dysplasia as a marker of the atypical mole phenotype -- a clinical and pathological study of 75 patients.

BACKGROUND: We encountered a distinctive pattern of dysplastic intraepidermal melanocytic proliferation, which defies classification as a dysplastic melanocytic nevus, but in which the morphologic features fall short of a diagnosis of melanoma in situ. We designate such lesions as de novo intraepidermal epithelioid melanocytic dysplasia. METHODS: From 75 patients, 82 skin biopsies were encountered that showed this distinctive morphology. Hematoxylin- and eosin-stained histologic sections were studied and the features were correlated with personal and family histories of dysplastic nevi and melanoma. RESULTS: The diagnosis of de novo melanocytic dysplasia was made in 27 male patients and 48 female patients (mean age: 44 years). The histologic hallmark was a pagetoid (single-cell) array of moderately to severely atypical epithelioid melanocytes within the epidermis. Seventy-three lesions were located on sun-exposed skin and nine on sun-protected skin. In 41 patients, there was an atypical mole phenotype, whereas 20 patients had a prior or subsequent diagnosis of melanoma with five of 16 patients questioned revealing a family history of melanoma. CONCLUSIONS: De novo intraepidermal epithelioid melanocytic dysplasia is a distinct entity associated with an atypical mole phenotype and a personal and/or family history of melanoma.

Adolescent↗
PubMed2005

Chondrodermatitis nodularis helicis as a marker of internal disease [corrected] associated with microvascular injury.

Chondrodermatitis nodularis helicis (CNH) is held to be an idiopathic degenerative process involving the upper dermis of the auricular rim. Chondrodermatitis typically occurs in elderly men where associations with underlying trauma and sun exposure have been postulated as potential inciting triggers. Its association as a marker of systemic disease is not well established. We describe 24 patients with CNH, in whom there were also significant underlying diseases largely associated with vascular injury including those of immune-based etiology and/or conditions which have been previously linked with granuloma annulare, another necrobiotic process of collagen. These patients with concomitant systemic disease were characteristically younger compared to the classic demographics described for CNH. In some cases, chondrodermatitis may represent an ischemic necrobiotic disorder of collagen, potentially defining an important sign of underlying systemic disease in younger patients.

Adolescent↗
PubMed2004

Parvoviral infection of endothelial cells and stromal fibroblasts: a possible pathogenetic role in scleroderma.

BACKGROUND: Systemic sclerosis (SSc) is a connective tissue disease (CTD) which differs from other CTDs by progressive irreversible fibrosis in lung, kidney, skin, and heart. It has a worse prognosis compared to several other CTDs. The pathogenesis may reflect a humorally mediated microangiopathy in concert with the overproduction of collagen triggered by immune-mediated cytokine production. Having previously demonstrated parvovirus B19 (B19) DNA in bone marrow and skin biopsies of SSc patients in the absence of B19 viremia, we sought to further elucidate a role for B19 in the pathogenesis of SSc. DESIGN: Twelve patients who fulfilled American College of Rheumatology criteria for a diagnosis of SSc were encountered. Ten were serologically screened for B19 infection. Solution phase polymerase chain reaction (PCR) for B19 DNA was performed on skin tissue from six patients, and in all biopsies, reverse transcriptase in situ PCR (RT in situ PCR) for B19 and tumor necrosis factor (TNF)-alpha mRNA was performed. B19 viral protein (VP2) expression was sought by immunohistochemistry and correlated to PCR findings and to light microscopy of hematoxylin and eosin-stained sections. Frozen tissue was also available on five of the patients. Two control groups were assessed for B19 and TNF expression comprising one with irrelevant primers and the other representing 18 cases of inflammatory skin lesions where the etiology was known and unrelated to B19 infection. In addition, frozen and paraffin-embedded tissues procured from skin lesions unrelated to B19 infection were assessed for B19 genome. In all cases, pretreatment with RNase was also performed to verify that any positive signal was indeed RNA based. RESULTS: Diffuse SSc was seen in seven patients, and limited disease in five. All patients had an antinuclear antibody--specifically, an antinucleolar, anticentromere, and/or anti-Scl 70 antibody. Eleven of the 12 had lung involvement, whereas eight patients had myocardial disease. Of 12 patients tested serologically, nine had B19-specific antibodies, which included immunoglobulin M (IgM)-specific antibodies in two cases. Solution phase PCR showed B19 DNA in the skin in three cases and in the bone marrow in three cases, including two in whom skin-based B19 DNA was observed. In all cases, RT in situ PCR demonstrated B19 and TNF-alpha mRNA in endothelia, fibroblasts, mast cells, and perivascular inflammatory cells. Immunohistochemistry to assess VP2 was either negative or equivocal. Immunofluorescent studies revealed prominent deposition of C5b-9 within the cutaneous vasculature from biopsies of all patients tested. The control samples were negative for B19 and TNF RNA and DNA. CONCLUSIONS: Parasitism of endothelia and fibroblasts by B19 with resultant enhanced TNF-alpha expression may be of pathogenetic importance in SSc even in the absence of demonstrable viremia. The vascular deposition of C5b-9 suggests a role for humoral immunity possibly induced by a state of endothelial neoantigenicity evoked by virally mediated cell injury. Treatment strategies include anti-viral therapy, including in the context of intravenous gamma-globulin and anti-TNF therapy.

Adult↗
PubMed2004

Cutaneous immunocytoma: a clinical, histologic, and phenotypic study of 11 cases.

Immunocytomas represent low grade B cell lymphomas related to marginal zone lymphoma but with a predominance of cells having plasmacytic features. Eleven patients presented with lesions compatible with primary cutaneous immunocytoma. The expression of CD2, CD3, CD5, CD20, CD21, CD23, CD43, CD56, CD79, and bcl-2 was analyzed immunohistochemically and of lambda and kappa light chains by an in situ hybridization assay. There were 6 men and 5 women ranging in age from 43 to 76 years. The most common clinical presentation was as extremity based clustered erythematous brown papules. Therapy with local irradiation or Rituximab resulted in lesional resolution. Underlying illnesses included Sjögren's syndrome, hepatitis C, ulcerative colitis, autoimmune thyroid disease, and rheumatoid arthritis. Four patients were taking medications previously associated with immune dysregulation. In two patients in whom a paraproteinemia was uncovered. The most common pattern light microscopically was perivascular small lymphocytic and plasmacellular infiltrates mimicking architecturally a reactive process. Phenotypic studies revealed a marginal zone (MZL) phenotype amid the small atypical lymphocytic infiltrate and highlighted a reactive background population of non-neoplastic T and B cells; light chain restriction was seen amid the plasma cells. In one case there was EBER staining of plasma cells while in another case in whom there was hepatitis C seropositivity staining of plasma cells for hepatitis C associated RNA transcripts was observed. Primary cutaneous immunocytoma appears to arise from a pre-existing state of reactive lymphoid hyperplasia. latrogenic and endogenous immune dysregulation including in the context of lymphotropic viral infections is implicated.

Adult↗
PubMed2004

Assessment of T-cell clonality via T-cell receptor-gamma rearrangements in cutaneous T-cell-dominant infiltrates using polymerase chain reaction and single-stranded DNA conformational polymorphism assay.

Discerning the pathologic significance of cutaneous T-cell infiltrates can pose a diagnostic challenge for dermatopathologists. Reactive conditions such as drug-associated lymphomatoid hypersensitivity and lymphomatoid lupus erythematosus can demonstrate lymphoid atypia and a phenotype resembling cutaneous T-cell lymphoma (CTCL). Further, lymphoid dyscrasias such as pityriasis lichenoides chronica, large plaque parapsoriasis, and atypical pigmentary purpura confuse the picture because they not only mimic CTCL but also represent prelymphomatous states with inherent malignant potential. Although the emergence of a dominant clone has been considered a clue indicative of a T-cell dyscrasia, there are reports concerning the identification of monoclonality in biopsies of reactive lymphoid infiltrates. We have conducted a modified single-stranded DNA conformational polymorphism (SSCP) assay using paraffin-embedded, formalin-fixed tissue on 92 T-cell-rich biopsies to determine the relative specificity and sensitivity of this methodology. In addition, laser capture microdissection (LCM) was performed on 22 of the 92 samples to isolate the area of interest and to compare its specificity and sensitivity with those SSCP assays performed without LCM. We found that monoclonality or oligoclonality is 86% specific for preneoplastic and neoplastic states, whereas the finding of polyclonality appears to be relatively specific for a reactive process. Some cases of reversible T-cell dyscrasia produced a molecular profile mimicking lymphoma or prelymphomatous states by virtue of monoclonality or oligoclonality. Although LCM appears to improve the sensitivity for detecting preneoplastic conditions, the relative specificity appears to be the same as that encountered with routine SSCP.

Clone Cells↗