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Biomedical subjects

C J Cockerell

Publications and source records attributed to C J Cockerell.

At least 55 records · Page 3Linked to original sources

Cutaneous malignant melanoma: classification and clinical diagnosis.

Cutaneous malignant melanoma (MM) is a treacherous disease which carries high mortality rates. However, when diagnosed early it is wholly curable. The incidence of MM is rising steadily. The most important clinical signs include the appearance of a newly acquired pigmented lesion or change in a preexisting one. Melanoma has been classified into subtypes which include melanoma in situ, lentigo maligna melanoma, nodular melanoma, acral lentiginous melanoma, desmoplastic melanoma, superficial spreading melanoma, and mucosal melanomas. Although these overlap, there are characteristic clinical features of each that are generally recognizable. Evaluation of pigmented lesions requires correlation of clinical findings with risk factors, family history and histology. A representative skin biopsy should be performed on any lesion suspected of being MM, even if the possibility is remote.

Biopsy↗

Biopsy technique for pigmented lesions.

The biopsy technique that should be used when sampling a pigmented lesion may not always be readily apparent. The final arbiter is whether the specimen that will be generated will be representative of the entire process so that an accurate and complete diagnosis will be able to be rendered. In some cases, melanoma may not be clinically suspected so that it is essential that any biopsy that is performed will detect these lesions.

Biopsy↗

Bacillary angiomatosis and other Bartonella species infections.

Infections with organisms of the genus Bartonella, for many years important only in South and Central America, have assumed significance in developing countries, especially in conjunction with the advent of the pandemic of the human immunodeficiency virus infection. New molecular and culture techniques have determined that these organisms cause new diseases such as bacillary angiomatosis as well as diseases the etiology of which have been unknown such as cat scratch disease. In this article, the microbiology, pathogenesis, histopathology and clinical manifestations of diseases caused by these organisms are discussed.

AIDS-Related Opportunistic Infections↗

Histopathology of peripheral nerves in cutaneous herpesvirus infection.

Cutaneous herpesvirus infection is a common viral disorder manifest by epidermal and/or mucosal vesicle formation. Though it is believed that the virus most likely resides in regional sensory ganglia following primary infection and that cutaneous involvement represents reactivation of a latent infection, the histopathology of cutaneous nerves in sites of disease has not been well characterized. In order to assess and characterize the pathologic changes of these nerves, we retrospectively examined 54 cases of cutaneous and mucosal herpesvirus infection as defined by the presence of diagnostic multinucleate epithelial giant cells that demonstrated viral cytopathic effect. Dermal nerves were evaluable in 48 of 54 cases. All cases showed perineural inflammation that consisted of a dense mixed lymphocyte-polymorphonuclear cell infiltrate. Twenty-six cases exhibited intraneural infiltrations accompanied by Schwann cell hypertrophy with nuclear eosinophilia and pyknosis. Frank neuronal necrosis was present in 21 cases, with viral cytopathic effect evident within neurons of four cases. The degree of peri- and intraneural inflammation correlated with the severity of the inflammatory response within the dermis in most cases; however, in eight cases there was inflammatory involvement of neurovascular structures distant from and out of proportion to dermal and epidermal changes. Immunoperoxidase staining using a polyvalent antibody to human herpesvirus was performed in two cases and demonstrated viral antigen within nerve twigs. This pattern of peripheral nerve twig inflammation, along with the occurrence of more distant neural involvement, may prove to have diagnostic implications and serve as a clue in the recognition of cutaneous herpesvirus infection, particularly in cases with subtle or absent epidermal alteration. Furthermore, the presence of inflammation within and around nerves as well as degenerative changes suggest that nerve twigs are not passive conduits for viral spread but may be directly involved in infection.

Antigens, Viral↗

Atypical fibroxanthoma with osteoclast-like multinucleated giant cells.

Atypical fibroxanthoma is a malignant fibrohistiocytic neoplasm that develops most commonly on sun-exposed skin of elderly individuals. A number of different variants have been described, ranging from a purely spindle cell type to a xanthomatous form. We recently observed an unusual variant of atypical fibroxanthoma in which there were numerous osteoclast-like multinucleated giant cells. Histologically, there was a diffuse spindle cell neoplasm in the dermis exhibiting fibrohistiocytic differentiation associated with inflammatory cells. The neoplastic spindle cells were markedly pleomorphic and many were in mitosis, some being tripolar and tetrapolar. In addition to these features, which are common in atypical fibroxanthoma, there were numerous multinucleated giant cells scattered throughout the lesion with features resembling normal osteoclasts. Epithelioid cells with features of histiocytes were seen in association with these cells. No osteoid was observed, however, that suggested monocyte-macrophage differentiation. The histologic appearance of this lesion was reminiscent of the giant cell variant of malignant fibrous histiocytoma, also termed malignant giant cell tumor of soft parts. Thus, osteoclast-like giant cells may be seen in atypical fibroxanthoma. These cells probably represent multinucleated histiocytes rather than true osteoclasts. It is important to recognize this variant to avoid confusion with other malignant soft tissue neoplasms.

Aged↗

Expression and mutation of the tumor suppressor gene p53 in AIDS-associated Kaposi's sarcoma.

Alteration of the p53 gene is the most frequent event reported in human cancer, and p53 mutations have been observed in various neoplasms, including certain forms of skin cancer. Therefore, we postulated that p53 may also be involved in Kaposi's sarcoma associated with AIDS (AIDS-KS). Expression of the p53 gene was examined in freshly isolated tumor biopsy specimens from 15 patients with AIDS-KS. p53 mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in both the AIDS-KS tumors and in normal skin control samples. p53 protein was detected in 4 of the 15 AIDS-KS specimens by immunohistochemical staining. Single-strand conformation polymorphism analysis PCR-products (PCR-SSCP) was used for detection of mutations of the p53 gene. One of the p53 positive AIDS-KS samples showed mobilized shifts in exon 6 suggestive of a mutation. Sequencing data showed the mutation to be located in codon 210. We examined other mechanisms that could stabilize p53 protein. SV40 large T antigen and adenovirus E1B protein were not found in the AIDS-KS specimens. MDM2, a p53-binding protein, was also detected in five of the AIDS-KS specimens, two of which also contained p53-positive cells. These observations suggest that the tumor suppressor gene p53 may be involved in the pathogenesis of AIDS-KS.

AIDS-Related Opportunistic Infections↗

Long-term efficacy and safety of Jessner's solution and 35% trichloroacetic acid vs 5% fluorouracil in the treatment of widespread facial actinic keratoses.

BACKGROUND: Few studies have examined the long-term efficacy of fluorouracil (FU) or chemical peels for the treatment of actinic keratoses (AK). Our earlier work examined the efficacy and safety of a medium-depth chemical peel compared with the standard regimen of topical FU in the treatment of widespread facial AK through 12 months. OBJECTIVES: To determine long-term efficacy of both treatments by extending our observations through 32 months. METHODS: Fifteen patients with severe facial actinic damage were treated on the left side with a single application of Jessner's solution and 35% trichloroacetic acid and on the right side with twice daily applications of 5% FU cream for 3 weeks. Parameters evaluated at 1, 6, 12, and 32 months included counts of visible AK, random skin biopsies from both treatment areas, development of intercurrent neoplasms, and surveys assessing sun exposure. RESULTS: Eight patients were available for reevaluation at 32 months. Both treatment sides showed a reduction in mean number of AK at 12 months followed by an increase in mean AK number between 12 and 32 months. Improvements in biopsies of clinically actinically damaged skin were seen in keratinocytic atypia, hyperkeratosis, parakeratosis, and inflammation at all treatment times during the study with both treatments. Three squamous cell carcinomas developed in the patients after initial treatment; one developed on the side treated with the peel, and two developed on the side treated with fluorouracil. Surveys failed to demonstrate an association between sun exposure and clinical response. CONCLUSION: Based on these findings, patient with widespread actinic keratoses treated with medium-depth chemical peel or with 5% FU should be reevaluated yearly or every 1.5 years for reappearance of AK and retreatment.

Administration, Topical↗

Actinic keratoses. Differential diagnosis and treatment.

Actinic keratoses are extremely common premalignant keratinocytic neoplastic lesions that develop primarily in fair-complexioned individuals during midlife or beyond. Genetic, occupational and other environmental factors predispose to the development of these lesions. Without treatment, a significant number may progress to fully developed neoplasms, especially squamous cell carcinoma, over a period of 20 to 50 years. The multistep theory of carcinogenesis is helpful in understanding the pathogenesis and progression of this important and highly prevalent lesion.

Aging↗

Langerhans' cell histiocytosis in adults.

Three cases of Langerhans' cell histiocytosis with unusual clinical and histopathologic features are described. The first two cases illustrate diagnostic pitfalls that underscore the importance of considering Langerhans' cell histiocytosis in the differential diagnosis of purpuric papular eruptions of the scalp and intertriginous areas, particularly in association with hypothalamic, pituitary, or liver disease. The third case is the first report of Langerhans' cell histiocytosis presenting as a vesicular eruption.

Adult↗

Eruptive melanocytic nevi after Stevens-Johnson syndrome.

Widespread melanocytic nevi may rarely appear suddenly after a severe bullous disease. We describe two patients in whom eruptive melanocytic nevi developed 3 weeks after a severe episode of Stevens-Johnson syndrome. Benign melanocytic proliferation may develop after a bullous dermatosis and should not be confused with malignant or metastatic melanoma.

Adolescent↗

Clinical and histologic spectrum of human T-cell lymphotropic virus type I-associated lymphoma involving the skin.

BACKGROUND: Adult T-cell leukemia/lymphoma (ATL) is associated with infection with human T-cell lymphotropic virus type I (HTLV-I). OBJECTIVE: The objective was to describe the clinical, histopathologic, and immunologic features in three patients with ATL involving the skin. METHODS: Clinical histories and skin biopsy specimens were reviewed. Immunophenotypic studies were performed on peripheral blood lymphocytes (three patients) and on skin biopsy specimens (one patient). RESULTS: Serologic testing in each patient was positive for HTLV-I. Specific cutaneous lesions of ATL were diverse. Histologic features included markedly epidermotropic lymphoid infiltrates and dermal aggregates of lymphocytes and macrophages resembling granulomas. One patient died 3 months after diagnosis; the other two are alive with residual lymphoma. CONCLUSION: A spectrum of clinical, histologic, and immunophenotypic features are seen in ATL involving skin. Those cases with a chronic course may resemble mycosis fungoides clinically and histologically. Serologic testing for HTLV-I is recommended in all patients with cutaneous lymphoma from endemic areas and in those with other risk factors for HTLV-I infection.

Adult↗

Calciphylaxis with histologic changes of pseudoxanthoma elasticum.

Calciphylaxis is a rare condition of widespread calcification of tissues and blood vessels with accompanying vascular thrombosis and ischemic necrosis. Most cases develop in association with hyperparathyroidism in patients with chronic renal failure. Pseudoxanthoma elasticum (PXE) is a hereditary condition of abnormal elastic tissue structure that leads to widespread abnormalities of the skin, retina, and visceral organs. Histologic changes of PXE have been observed as coincidental findings in several conditions such as following trauma to the skin manifest as isolated plaques often in scars. We observed histologic findings of PXE in a patient with chronic renal failure who developed fatal calciphylaxis. Complete evaluation failed to reveal evidence of systemic findings of PXE. Histologic changes of PXE may be seen in patients with calciphylaxis as a coincidental finding. Rapidly developing soft tissue calcification may lead to the expression of the characteristic histopathologic findings of PXE without evidence of classic clinical manifestations of PXE. Calciphylaxis should be added to the list of disorders that may lead to microscopic PXE-like changes.

Calciphylaxis↗

Acquired cutis laxa associated with a plasma cell dyscrasia.

Acquired cutis laxa (generalized acquired elastolysis) is characterized by skin laxity often with systemic involvement of the lungs, aorta, gastrointestinal tract, and pelvic organs. Although there have been many speculations regarding its pathogenesis, the etiology of this condition is still unclear. We describe a patient with generalized acquired cutis laxa associated with a plasma cell dyscrasia. Immunofluorescence studies were used to evaluate the pathogenesis of the elastolysis. Lesional skin was examined by direct and indirect immunofluorescence techniques for evidence of deposition of immunoglobulins on elastic fibers in the dermis. Direct immunofluorescence revealed deposition of IgG on elastic fibers in the dermis. Some patients with acquired cutis laxa have underlying lymphoreticular disorders such as plasma cell dyscrasia and may have immunoglobulins deposited on dermal elastic fibers. Immune-mediated mechanisms may play a major role in the pathogenesis of acquired cutis laxa in at least some cases.

Adult↗

Localization of human herpes-like virus type 8 in vascular endothelial cells and perivascular spindle-shaped cells of Kaposi's sarcoma lesions by in situ hybridization.

Kaposi's sarcoma (KS) is a neoplasm that develops as multifocal lesions characterized by a histological picture that includes irregularly shaped vascular spaces surrounded by perivascular and interstitial spindle-shaped cells, extravasated erythrocytes, and an inflammatory mononuclear cell infiltrate. Recently, the DNA sequences of a novel human gamma-herpesvirus-like (HHV-8) agent have been detected by polymerase chain reaction in KS associated with acquired immune deficiency syndrome (AIDS-KS), classical KS, and African endemic KS. The present study was done to identify the specific cells within KS tumors that contain the viral DNA. Fourteen skin biopsy specimens, including three classical KSs, six AIDS-KSs, three normal skin specimens, and two common warts from healthy individuals, were examined by polymerase chain reaction for the presence of the HHV-8 DNA sequences. HHV-8 DNA were present in all nine KS specimens but not detectable in the five non-KS tissue samples. Using in situ hybridization, we found the HHV-8 DNA sequences to be predominantly localized to the nuclei of endothelial cells lining the vascular slits and some perivascular spindle-shaped cells, in two of three KS and four of six AIDS-KS tissue sections examined. The HHV-8-positive cells of KS specimens were concurrently shown to also be positive for factor-VIII-related antigen by immunohistochemical staining. The presence of the DNA of HHV-8 in the nuclei of KS cells further supports the possibility that this agent may play a role in the pathogenesis of this tumor.

Cell Nucleus↗

Mucocutaneous neoplasms in patients with human immunodeficiency virus infection.

Neoplastic disorders of the skin are commonly encountered in patients with human immunodeficiency virus infection. As patients survive longer, they are at ever increased risk to acquire one of a number of different malignant neoplasms of the skin. These may be of many different types including epithelial, lymphoreticular, vascular, smooth muscle, and melanocytic. Because of the immunocompromised status of these patients, many of these disorders behave in more aggressive fashions and require more aggressive treatment.

HIV Infections↗

Papulonodular mucinosis associated with systemic lupus erythematosus: possible mechanisms of increased glycosaminoglycan accumulation.

BACKGROUND: The mechanism for the production of papulonodular mucinosis in patients with lupus erythematosus (LE) is not known. OBJECTIVE: Our purpose was to determine whether fibroblasts in a patient with LE and papulonodular mucinosis produced more mucin than normal fibroblasts and whether this mucin production could be stimulated by the patient's serum. METHODS: Skin fibroblasts from a patient with systemic LE and massive papulonodular mucin deposition, as well as normal fibroblasts, were incubated in the presence of serum from the patient or from a healthy volunteer. The production of glycosaminoglycan by fibroblasts was analyzed. RESULTS: Fibroblasts from the patient produced more glycosaminoglycan than did normal fibroblasts. Glycosaminoglycan production was increased in all cells when incubated in the presence of the patient's serum. CONCLUSION: Cutaneous mucin deposition in patients with papulonodular LE skin lesions is associated with increased glycosaminoglycan production by dermal fibroblasts. Our preliminary observations suggest glycosaminoglycan production by these fibroblasts appears to be stimulated by a factor, (or factors) in the patient's serum that is yet to be identified.

Adult↗