Basal cell carcinoma: when to treat it yourself, and when to refer

Basal cell carcinoma (BCC) is the most common skin cancer and frequently affects older adults. Most BCCs are seen on the sun-exposed skin of light-skinned individuals. Because early diagnosis reduces morbidity and the expense of treatment, it is essential that you are able to recognize these lesions. Their various clinical presentations determine the proper treatments, some of which may be carried out in your office and others which require referral. Several effective surgical and nonsurgical modalities are available. Selecting the best method is based on such factors as the type, size, and anatomic location of the lesion; cost of treatment; and your familiarity with the treatment.     

Induction of superoxide dismutase isozymes by tumor necrosis factor-alpha and lipopolysaccharide in cultured normal and hyperplastic gingival fibroblasts

We studied 722 reexcision scars of benign and malignant lesions (except melanocytic lesions) excised over a 24-month period. The formalin-fixed, paraffin-embedded tissue sections were examined histologically and immunohistochemically. The histological features of melanocytic hyperplasia were present in 59 cases (8%), 56 from the sun-exposed skin of the face and neck and three from the trunk [p < 0.00001]. The most common sites were the nose and lower eyelids, but the forehead was also frequently involved. Of the 59 patients, 41 were women (p < 0.0001). Basal cell carcinoma was the most frequent original lesion in both sexes (80%). No melanocytic hyperplasia was found in 663 cases (298 on the trunk and extremities and 365 on the head and neck). We have seen this reaction pattern following reexcision of melanocytic lesions as well. Thus, interpreting reexcision margins when lentigo maligna or similar lesions are reexcised may be fraught with difficulty. It is important for pathologists and dermatopathologists to recognize this phenomenon because histologically the presence of increased numbers of large melanocytes could be misinterpreted as melanoma in situ.     

Axillary basal cell carcinoma: a need for full cutaneous examination

Basal cell carcinoma is the most common skin malignancy. While this lesion most often occurs in sun-exposed areas of the skin, it can also develop in sites that are not usually exposed to sunlight or artificial ultraviolet radiation, such as the breast, palm or groin. A periodic complete examination of the skin should be performed to ensure that atypical presentations of basal cell carcinoma are not overlooked or misdiagnosed. Treatment options include curettage and desiccation, cryosurgery, surgical excision, radiotherapy and Mohs micrographic surgery.     

Paraneoplastic syndromes affecting the nervous system

Paraneoplastic syndromes can affect virtually any portion of the nervous system. Most paraneoplastic syndromes are believed to be caused by an autoimmune reaction to an "onconeural" antigen shared by the cancer and the nervous system. The immune reaction may retard growth of the cancer, but it also damages the nervous system. Specific autoantibodies found in some individual paraneoplastic syndromes are usually associated with specific tumors. Neurological disorders, clinically and pathologically identical to paraneoplastic syndromes, may occur in some patients without cancer, but paraneoplastic antibodies are not found in these patients. The diagnosis of a paraneoplastic syndrome is based on its increased incidence in patients with cancer, the occasional response of the neurological syndrome to treatment of the underlying cancer, or the presence of specific autoantibodies. Some paraneoplastic syndromes respond to treatment of the underlying cancer or to immunosuppression but, for most syndromes, no effective treatment exists.     

Active compression-decompression in cardiopulmonary resuscitation

A hypothesis is presented to explain the apparent difference in the radioresponsiveness of melanoma lesions whether they are located on the skin or in other parts of the body. The hypothesis states that the radiosensitivity of a cell may change when the cell adapts to live and grow in a different environment. The most important environmental factor that affects the radiosensitivity of cutaneous melanoma cells appears to be the partial pressure of oxygen in their immediate environment. By virtue of adapting to grow in an environment having a high partial pressure of oxygen, the melanoma cells located on the skin may have developed a better antioxidant defense mechanism than cells that metastasize to, and grow in, other parts of the body having lower partial pressures of oxygen such as lymph nodes, brain and viscera. Because some of the cell-damaging effects of both oxygen and ionizing radiation are mediated through a similar mechanism, the melanoma cells on the skin become cross-resistant to ionizing radiation because of their higher tolerance to oxygen toxicity.     

The importance of the ERCC1/ERCC4[XPF] complex for hypoxic-cell radioresistance does not appear to derive from its participation in the nucleotide excision repair pathway

BACKGROUND: The incidence of skin cancer is increasing at an alarming rate. OBJECTIVE: To discuss current epidemiologic data concerning the incidence, morbidity, environmental influences, predisposing, host conditions, precursor lesions, and prevention of melanoma and nonmelanoma (basal and squamous cell) skin cancer. METHODS: The current literature was reviewed in order to provide current epidemiologic data for melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). RESULTS: Skin cancer is exceedingly common and the incidence is rising rapidly. Although the mortality rate for nonmelanoma skin cancer (NMSC) is decreasing, that of melanoma is increasing. Both NMSC and melanoma are associated with significant morbidity. Whereas chronic sun exposure is the main cause of NMSC, the development of melanoma appears to be related to intense, intermittent sun exposure. Ozone depletion has contributed to rising incidence rates of both NMSC and melanoma. In contrast to NMSC, there is not a direct relationship between ultraviolet radiation and melanoma. Genetic susceptibility significantly increases the lifetime risk of acquiring melanoma. There is no precursor lesion for BCC. Precursor lesions for invasive SCC include actinic keratoses and SCC in situ. Melanoma may arise from benign nevi and dysplastic nevi. Prevention of melanoma and NMSC is extremely important since prognosis improves with early detection. Prevention may be achieved by educating patients and physicians how to detect skin cancers early and by decreasing or eliminating exposure to ultraviolet light. CONCLUSION: The incidence of skin cancer has reached epidemic proportions. Only through heroic efforts by health care professionals and the general public to prevent the development or progression of skin cancer will this epidemic be abated.     

Cutaneous adult myofibroma: a vascular neoplasm

Infantile myofibromatosis is a distinctive type of fibromatosis that usually develops during the immediate perinatal period. There are variants with solitary and multiple tumors. Lesions confined to the skin, soft tissue, and bone carry a good prognosis, showing spontaneous regression. The prognosis, however, is much less favorable when visceral lesions are present and the outcome may be fatal. Only recently it became obvious that there is an adult counterpart of infantile myofibromatosis, characterized by solitary lesions that have a predilection for involve the dermis and show no tendency to regression, although they have an entirely benign biological behavior. These lesions have been named cutaneous myofibroma or solitary myofibroma of adults. We have studied the clinical, histopathological and immunohistochemical characteristics of 53 examples of cutaneous adult myofibroma. In addition, 2 cases were examined ultrastructurally. The patients were mostly adults with ages ranging from 6-83 years. The lesions presented as solitary, usually painless nodules of variable duration on the skin, usually located on the extremities. Histopathologically, four patterns were identified: nodular or cellular type, multinodular or biphasic type, leiomyoma-like or fascicular type, and vascular type. A correlation between the histopathologic pattern and the lesional age was observed: vascular type of cutaneous adult myofibroma in early lesions, nodular and multinodular lesions in fully developed lesions, and leiomyoma-like or fascicular type in late lesions. Immunohistochemically, the spindle cells were desmin negative, but expressed immunoreactivity for vimentin, pan-smooth muscle actin, and alpha-smooth muscle actin. Ultrastructurally, neoplastic cells showed characteristics of undifferentiated mesenchymal cells with features of fibroblasts, myofibroblasts and pericytes. Primitive vascular formations were seen in the form of irregular clefts between adjoining cells. We conclude that cutaneous adult myofibroma is a little-known benign vascular neoplasm probably derived from myopericytes.     

Paraneoplastic syndromes

The importance of paraneoplastic syndromes is often underestimated in the horse. Clinically, paraneoplastic syndromes can cause greater morbidity than the actual physical presence of the malignant tumor. The appearance may be the first sign of a malignancy and may be so severe that appropriate therapy for the underlying cancer is not initiated. This article reviews some of the most common paraneoplastic syndromes that are likely to occur in the horse.     

Recognizing neoplastic skin lesions: a photo guide

Malignant lesions of the skin are common. Patients who develop squamous cell carcinoma and malignant melanoma often have recognizable precursor conditions. A few skin lesions resemble malignancies. Lesions that are growing, spreading or pigmented, or those that occur on exposed areas of skin are of particular concern. Knowing the similarities and differences between these lesions allows the primary physician to make a diagnosis in most cases by simple inspection and palpation. When in doubt, it is appropriate to perform an excisional biopsy of small lesions or punch biopsy of larger lesions. Removal of premalignant lesions will reduce the occurrence of malignant disease. Almost all skin cancers can be cured by early excision or destruction. For these reasons, physicians should be aware of the risk factors for skin cancer, educate patients about risk reduction and include skin inspection for premalignant and malignant lesions as a part of routine health maintenance examinations.     

Expression of E and P-cadherin by melanoma cells decreases in progressive melanomas and following ultraviolet radiation

The purpose of our study was to determine whether the degree of E- and P-cadherin expression in melanomas correlates with the invasive behavior of the clinical lesions from which the cell lines were derived. Cadherins comprise a family of calcium-dependent cellular adhesion molecules expressed on most cell types that form solid tissues. In the human epidermis, melanocyte cadherin expression may function to maintain the integrity of the epidermal-melanin unit. Employing both immunofluorescence microscopy and fluorescence-activated cell sorter analysis, we localized and quantitated E- and P-cadherin expression on melanoma cell lines derived from primary or metastatic lesions using the monoclonal antibodies HECD-1 and NNC-CAD-299, respectively. Human epidermal melanocytes isolated from neonatal foreskin were evaluated by similar techniques and served as a biologic control. Melanoma cell lines were isolated from primary or metastatic lesions of patients described as having "early," "intermediate," or "advanced disease." Melanoma E- and P-cadherin immunofluorescence, as quantified by fluorescence-activated cell sorter, varied inversely with disease progression. Selected log mean ratios of E-cadherin fluorescence, as compared to human epidermal melanocytes (arbitrarily = 1), ranged from 1.04 in the WM 35 melanoma cell line (low invasive potential) to 0.1 and 0.02 in the WM 983A and 1361A melanoma cell lines (derived from primary lesions with metastases), respectively. Although values for P-cadherin fluorescence were less, the trend of decreasing cadherin amounts with more advanced disease was observed. Melanoma cells appear to express E- and P-cadherin levels inversely related to disease progression. Ultraviolet radiation significantly decreased E- and P-cadherin expression in the human epidermal melanocytes and P-cadherin expression in the WM 35 melanoma cell line (p < 0.05). Although not statistically significant, E-cadherin expression in the WM 35 melanoma cell line decreased substantially. Thus, ultraviolet radiation may have a direct effect on human epidermal melanocytes and melanoma cell attachment through cadherins within the epidermis or tumor nodules.     

Response of melanocortin-4 receptor-deficient mice to anorectic and orexigenic peptides

Whether P/Q-type voltage-gated calcium channel (VGCC) antibodies are present in the serum of patients with paraneoplastic syndromes other than the Lambert-Eaton myasthenic syndrome (LEMS) and tumors other than small-cell lung cancer (SCLC) is controversial. Using a commercially available radioimmunoprecipitation assay kit, we examined the sera of 93 patients with paraneoplastic syndromes of the central nervous system (CNS), including 27 patients with paraneoplastic cerebellar degeneration (PCD) associated with tumors other than SCLC and 66 SCLC patients with paraneoplastic encephalomyelitis and sensory neuronopathy (PEM/SN). All PCD sera from patients with tumors other than SCLC were negative for P/Q-type VGCC antibodies. Eight of 66 (12%) SCLC patients with PEM/SN had P/Q-type VGCC antibodies; 4 had LEMS and the other 4 had no symptoms of LEMS or they were overlooked and, therefore, not examined electrophysiologically. In patients with paraneoplastic syndromes of the CNS, the detection of P/Q-type VGCC antibodies supports the diagnosis of LEMS; in our series, only 6% of patients with SCLC and PEM/SN may have had a false positive antibody result, or undiagnosed LEMS.     

Dysplastic nevi and other risk markers for melanoma

Risk markers for cancer are genetic or behavioral attributes that are statistically associated with increased incidence of cancer. Risk may be assessed either in case-control studies, or in cohort studies in which individuals with particular attributes are followed and cancer risk is determined by direct observation. Both of these methods have been used to determine the major risk markers for melanoma. The single most important risk marker is the presence on the skin of dysplastic nevi. Dysplastic nevi may be regarded as intermediate lesions of tumor progression, in that approximately 30% of melanomas arise in association with a precursor nevus, which is most commonly dysplastic. However, paradoxically, because they are vastly more numerous than melanoma, most dysplastic nevi are stable lesions that do not progress. Additional important melanoma risk factors include a family and/or personal history of melanoma. A third major category of risk markers includes indicators of acute and chronic exposure to the sun, including freckles, actinic skin damage, and a history of sunburn. Evaluation of these markers in oncological patients and their first-degree relatives can identify a population of individuals whose risk for melanoma ranges from several-fold to more than 100-fold greater than that of random population members. Efforts directed at early diagnosis in these individuals can result in recognition of melanomas in their early, curable stages.     

Skin manifestations of graft-versus-host reaction following bone marrow transplantation

We review the cutaneous manifestations of acute and chronic graft versus host disease (GvHD). Acute GvHD is characterized by initial itching, pain on pressure and erythema which begins on posterior auricular skin, palms and soles. The disease evolves into a typical but nonspecific maculopapular rash. Confluent rashes and follicular erythema may occur. Erosive oral lesions usually develop. The most severe variant of GvHD is toxic epidermal necrolysis, which often has a fatal outcome. The onset of chronic GvHD usually occurs more than 100 days after bone marrow transplantation and may be preceded by the acute form. The spectrum of skin changes includes lichenoid pruritic lesions with violaceous color and scleroderma-like skin involvement. Investigation of unknown rashes in these patients includes skin biopsy, which clearly differentiates leukocytoclastic vasculitis and erythema exsudativum multiforme with lymphocytic vasculitis from cutaneous manifestations of GvHD. Special stains may reveal bacteria and fungus in septicemic patients. The therapeutic options are discussed.     

Neurologic paraneoplastic syndromes with neurotologic manifestations

Evidence supports the hypothesis that autoimmune mechanisms are operational in the etiopathogenesis of certain neurologic paraneoplastic syndromes (PNSs), including paraneoplastic encephalomyelitis (PEM) and paraneoplastic cerebellar degeneration (PCD). The antibodies (Anti-Hu and Anti-Yo), the antigens (Hu and Yo), and complementary DNA clones encoding Hu and Yo, central to PEM and PCD, respectively, have been isolated. In contrast, the antigens, and antibodies if any, involved in autoimmune cochleovestibular dysfunction remain unknown. The temporal bone histopathology and neuropathology of 2 patients, 1 with PEM and 1 with PCD, who developed signs and symptoms of cochleovestibular dysfunction, are reviewed and contrasted to the literature. It is concluded that both auditory and vestibular symptomatology and pathologic alterations can be seen in association with neurologic PNSs and that studies using the antigens and antibodies involved in neurologic PNSs may provide a new perspective on the investigation of autoimmune cochleovestibular dysfunction.     

Sarcoid-like hepatic granulomas, associated with gastric neoplasia. Description of a case

Giant cell granulomas in liver biopsies is a relative common finding. Among the many causes of granulomatous lesions of the liver primary biliary cirrhosis and sarcoidosis are the most frequently diagnosed. On the other hand sarcoid-like granulomatous reaction can be encountered associated to malignant tumours. Purpose of the present paper is to describe a case of a sarcoid-like reaction of the liver associated to gastric adenocarcinoma. The patient was a 66 yr old man who underwent gastrectomy for a signet-ring cell adenocarcinoma. Pathological anamnesis was unremarkable. Liver function tests were within normal limits. Chest x ray was normal. A liver biopsy was performed during surgery as the liver presented an irregular surface. On histology giant cell granulomas with sarcoid-like features were seen in the hepatic parenchyma. Same reaction was present in the perigastric lymph nodes. The patient died immediately after surgery due to massive pulmonary embolism. No autopsy was performed. Among the possible diagnoses primary biliary cirrhosis, sarcoidosis and paraneoplastic sarcoid-like granulomatous reaction were considered. Primary biliary cirrhosis and sarcoidosis were excluded on the basis of the past clinical history of the patient, that was unremarkable; furthermore liver function tests performed preoperatively were within normal ranges. Thus paraneoplastic sarcoid-like reaction involving the liver was regarded as the most likely diagnosis.     

Cutaneous involvement in sarcoidosis. Relationship to systemic disease

Sarcoidosis is an antigen-mediated disease defined by granuloma formation in different organs. It involves mainly the mediastinal and peripheral lymph nodes, lungs, eyes, skin, liver, and spleen. Cutaneous lesions of sarcoidosis may be specific, showing histologically noncaseating granulomas, or nonspecific, most typically erythema nodosum. Frequently, both types of skin lesions are the means of presentation of the disease and may contribute to the diagnosis. A workup for systemic sarcoidosis should be undertaken in every patient with sarcoid cutaneous granulomas. Some types of cutaneous lesions have prognostic significance. Lupus pernio and plaques are associated with more severe systemic involvement and more chronic course, while erythema nodosum is the hallmark of acute and benign disease.     

Human acquired naevi are clonal

Naevi are nearly universal in humans, yet their cellular origin remains obscure. Understanding the cellular and molecular mechanisms involved in naevus development may be important in understanding the pathogenesis of malignant melanoma. This study aimed to discover whether human acquired naevi are premalignant by examining whether they are clonal. To determine clonality naevi were removed and separated into epithelial and naevus cell fractions and the DNA prepared and digested by a methylase-sensitive restriction enzyme. The highly polymorphic X-linked human androgen receptor (HUMARA) gene was then amplified by a polymerase chain reaction and examined by gel electrophoresis and autoradiography. In polyclonal cell populations both alleles are usually seen as two distinct bands, whilst clonal populations yield a single band. Using these techniques 35 junctional naevi, 11 compound naevi and one congenital naevus from 40 women were examined. Of these, 81% (37 out of 47) of the naevi were clonal, while all of the epithelial cell controls were polyclonal. These data are novel and have great importance for understanding the development of human acquired naevi and cutaneous malignant melanoma. Because monoclonality is a marker of neoplasia, or preneoplasia, our data support the hypothesis that common acquired naevi should be considered to be premalignant lesions, similar to colonic polyps. Such lesions may have undergone the first molecular step(s) in the development of cutaneous malignant melanoma. Understanding the events involved may lead to new methods of prevention and treatment.     

Urethroplasty for balanitis xerotica obliterans

PURPOSE: To report a 20-month-old child with a rapidly growing dome-shaped red nodule on the left lower eyelid. The lesion was diagnosed clinically as an hemangioma, but microscopy disclosed an epithelioid Spitz nevus. METHOD: Case report. RESULT: Histopathologic examination of the excised lesion disclosed a Spitz nevus (benign juvenile melanoma) of a chiefly epithelioid cell type. CONCLUSIONS: The differential diagnosis of eyelid skin nodules in children should include Spitz nevus. This uncommon nevus has many cytologic features in common with nodular malignant melanoma. Histologically, it may be difficult to distinguish between nodular malignant melanoma and Spitz nevus.     

Genetic and environmental contributions to size, color, shape, and other characteristics of melanocytic naevi in a sample of adolescent twins

The presence of melanocytic naevi is the strongest known risk factor for malignant melanoma. We have developed a computer imaging system with which it is possible to make quantitative measures of the size, color, and shape of pigmented lesions. The objective of this study was to examine the genetic and environmental contributions to these characteristics of naevi as measured by computer image analysis in a sample of adolescent twins. We captured video images of the 5 most atypical pigmented skin lesions (i.e., the largest, darkest, or most irregularly shaped) on each individual from 322 Australian adolescent twin pairs. Features extracted by computer image analysis for each lesion included color, size, symmetry, elongation, boundary irregularity, and edge distinctness. We found major genetic influences on the color and size of lesions accounting for between 40 and 80% of total variance. There were significant components of shared environmental influence (22-45% of total variance) for the color variables, with sun exposure the most obvious explanation. Differences between individuals in naevus color and size are largely genetic in origin although there are significant environmental contributions to color as well.     

Ultrastructural study of anti-tumor effects of tamoxifen in two malignant melanoma patients

In order to clarify the mode of action (tumor cell death) of tamoxifen in treatment for estrogen receptor (ER) negative malignant melanoma, we administered the usual adult dose (20 mg/day) or a low dose, 1/4 of the usual dose (5 mg/day), of tamoxifen for 2 months to 2 male patients and investigated ultrastructural changes in their melanoma cells from metastatic lesions before and after the treatment. After the 2-month administration, metastatic nodules in both patients were reduced in size by approximately 50%. Histologically, their reduced nodules presented coagulation necrosis around the blood vessels. Electron microscopy of the necrosis revealed that melanoma cells were degenerated and disappeared; numerous aggregated melanosomes, free melanosomes, granular endoplasmic reticula, and lysosomes were present in the extracellular matrix and in the space between collagen fibers. The remaining melanoma cells had swollen cytoplasm and mitochondria with vacuolar changes. Cristae of mitochondria had disappeared. There was no infiltration of lymphocytes into the nodules. The organic changes of necrosis lesions were not observed. Because our two patients were ER negative, these effects of tamoxifen could be attributable to an action not mediated by ER.