Incidence of non-melanocytic skin cancer in Geraldton, Western Australia

To measure the rate at which non-melanocytic skin cancers develop, we conducted a population-based, longitudinal study in Geraldton, Western Australia. Subjects were residents of Geraldton, Western Australia, who were between 40 and 64 years of age and registered on the electoral roll in 1987. In 1987 and again in 1992, dermatologists examined participants for skin cancers. They examined all skin areas, apart from those covered by underwear or hair. Subjects were asked about skin cancers that they had had treated between the 2 surveys. When all skin cancers were counted, the incidence rates of basal cell carcinoma were 3,379 per 100,000 person-years in women and 7,067 per 100,000 in men; those of squamous cell carcinoma were 501 per 100,000 in women and 775 per 100,000 in men. Sixteen percent of men and 14% of women developed at least one basal cell carcinoma; 2.8% of men and 2.2% of women had at least one squamous cell carcinoma. Most incident skin cancers were diagnosed at the second examination. More than half of the subjects who had a skin cancer at the first examination developed another. Squamous cell carcinomas occurred almost exclusively on parts of the body that are usually exposed. Basal cell carcinomas were common on the head, neck and trunk but not on the forearms and backs of hands. A quarter of people with a skin cancer on an exposed site also had one on the trunk. Our results show that skin cancer is extremely common in this population and frequently undiagnosed. Multiple skin cancers occur commonly, and skin cancers on exposed sites often are associated with skin cancers on less exposed sites.     

Specific distribution patterns of hCDC47 expression in cutaneous diseases

hCDC47 is a human member of the MCM family, which has been implicated to be concerned with the regulatory machinery causing DNA to replicate once per cell cycle. In a previous paper, we described hCDC47 expression as being localized in the proliferative component of normal tissues, and showed greater expression in squamous cell skin carcinomas than in seborrheic keratosis. In the present study, we compared its expression in another type of skin tumor and various non-neoplastic cutaneous proliferative diseases. Two patterns of distribution of hCDC47-positive cells were observed. Keratoacanthomas showed a peripheral pattern in which only the cells located the basal cell layers were positive. Psoriasis vulgaris also showed this peripheral type of location, with the cells in the suprabasal layers also occasionally expressing hCDC47. Verruca vulgaris demonstrated a diffuse pattern, with positive epithelial cells distributed throughout the layers. Basal cell carcinomas also showed a similar pattern. The keratoacanthomas showed the highest hCDC47 positive cell rate (43.1%), followed by verruca vulgaris (42.5%), psoriasis vulgaris (23.4%), and basal cell carcinoma (17.3%). Our results suggest participation of hCDC47 in these proliferative disorders involving keratinocytes.     

Drug resistance to 5-aza-2''-deoxycytidine, 2'',2''-difluorodeoxycytidine, and cytosine arabinoside conferred by retroviral-mediated transfer of human cytidine deaminase cDNA into murine cells

Squamous metaplasia can be demonstrated in about 4% of all invasive carcinomas of the breast. Primary squamous cell carcinomas of the breast are rare, since they occur in less than 1% of all primary invasive breast carcinomas. In order to classify a breast tumor as a primary squamous cell carcinoma one must exclude an epidermal origin, especially from the nipple region and the possibility of metastatic infiltration of the breast by a squamous cell carcinoma from a different location. Causative and formal pathogenesis of primary squamous cell carcinoma of the breast is not clear. A pluripotent embryonal stem cell origin is discussed, considering the phylogenetic descent of the mammary gland from skin appendages. Squamous metaplasia is also suggested to be a precursor of squamous cell carcinoma. Here endocrine stimulation and chronic inflammation may both play an inductive role. The number of published cases of squamous cell carcinomas developing years and decades after implantation of silicon prostheses has increased in recent years. These tumors probably develop on top of squamous metaplasia induced by the inflammatory pseudocapsule. Estimating the prognosis and therapeutic management in patients with squamous cell carcinoma of the breast should follow the same guidelines as for other squamous cell cancers.     

Paraspinal calcinosis associated with progressive systemic sclerosis. Case report

The incidence of basal cell carcinoma and squamous cell carcinoma (non-melanoma skin cancer) is increasing in the U.K., and the importance of this has been recognized in the 'Health of the Nation' target of halting the annual increase in the incidence of skin cancer by the year 2005. An accurate assessment of incidence is necessary both in meeting this target and in planning skin cancer services. We have examined the ways in which basal cell carcinoma and squamous cell carcinoma are diagnosed and treated in Greater Glasgow and have determined how many of these tumours are, recorded by the West of Scotland Cancer Registry. Our results show that there is under-registration of both basal cell carcinoma and squamous cell carcinoma. Overall, 39 of 127 basal cell carcinomas (31%; 95% confidence interval [CI] 23-39%) and 11 of 25 squamous cell carcinomas (44%; CI 26-63%) were not registered by the cancer registry. We also showed that dermatologists rarely treat clinically suspicious tumours without obtaining pathological proof of the diagnosis. Accurate data collection by selected representative cancer registries is suggested as a possible solution.     

Keratoacanthoma: an unusual hand tumor

Keratoacanthoma is a common skin lesion of the head and neck, and is well described in the literature. It seldom presents to the Orthopedic surgeon as a hand tumor. The lesion does not require radical approach, but mimics squamous cell carcinoma which usually does. The clinical behavior and pathology, as well as the biological behavior of the tumor, are discussed. Fifteen cases treated by the authors are reported and their clinical and pathological course and treatment are discussed. Serious errors in treatment may arise from reliance on the histologic characteristics alone. Conservative treatment of keratoacanthoma should be avoided but radical excision of the part is unnecessary. Prompt and total excision is the treatment of choice, with closure either primarily or with split skin graft.     

Heterogeneity in endothelium-derived nitric oxide-mediated relaxation of different sized pulmonary arteries of newborn lambs

Extensive documentation has validated the role of UV irradiation as a tumor initiator and promoter, inducing both squamous and basal cell carcinomas. Human epidermis is a tissue which undergoes active metabolism of arachidonic acid to prostaglandins which is regulated by the action of prostaglandin H synthase (also known as cyclooxygenase). One mechanism for the promotional activity of UV light may involve its ability to induce prostaglandin formation. Work in our laboratory has demonstrated that acute exposure of human keratinocytes to UVB irradiation results in increased production of prostaglandin E2 (PGE2). When cultured human keratinocytes were examined after irradiation with 30 mJ/cm2 UVB in vitro, Western blot analysis showed a 6-fold increase in COX-2 protein which was evident at 6 h and peaked 24 h after irradiation. Furthermore, when human subjects were irradiated on sun-protected skin with up to four times their minimal erythema dosage (MED) and biopsied 24 h later, upregulation of COX-2 protein expression was observed via immunofluorescence microscopy. RNAase protection assays supported this observation, showing induction of COX-2 message which peaked at approximately 12 h following irradiation in vitro. Furthermore, human squamous cell carcinoma biopsies exhibited strongly enhanced staining for COX-2 protein via immunohistochemistry and Western analysis when compared to normal non-sun-exposed control skin. Together, these data demonstrate acute upregulation of COX-2 via UVB irradiation and suggest the need for further studies of COX-2 expression as a potential pharmacological target mediating human skin tumor development.     

Visual diagnosis of hematologic and oncologic diseases

Cancer-related problems are seen frequently by the emergency physician. More difficult presentations are seen with premonitory symptoms, paraneoplastic syndromes, and nonspecific lesions. Dermatologic paraneoplastic syndromes are numerous, nonspecific, and consist of hamartomatous growths, texture changes, new hair growth, or changes in skin color. Alteration of skin color may be of practically any color, localized or diffuse, and of sudden or indolent onset. Hormone production by tumors may lead to acne, hirsutism, gynecomastia, or a cushingoid appearance. Pruritus may herald the onset of leukemia or lymphoma and be intolerable, as with erythroderma. All suspicious presentations require thorough investigation for underlying disease. Metastasis to skin is not common and implies a poor prognosis if seen. Most metastases are seen on the head and neck, anterior chest wall, and abdomen. Basal cell and squamous cell carcinomas commonly occur in sun-exposed areas. Basal cell is locally destructive, whereas squamous cell occasionally metastasizes to local lymph nodes. Malignant melanoma is the leading fatal illness originating in skin, with a dramatic rise in incidence. It is classically described as asymmetric with irregular borders, is elevated, and shows color variegation; however, melanoma may present atypically, particularly in non-whites. Kaposi's sarcoma lesions are well-demarcated, symmetric, smooth nodules that appear purplish-brown, particularly if below the knee (owing to venous stasis). The closely interrelated structures of the eye and orbit are easily disturbed, leading to the presenting symptoms of visual disturbances, exophthalmos, pain, and ocular motility disorders. Primary tumors are not unusual and may include retinoblastoma, rhabdomyosarcoma, and melanoma. Equally common are metastatic lesions, most commonly lung and breast carcinoma. An estimation of the malignancy of bony lesions can be made by assessing the zone of transition, periosteal reaction, and bone destruction. A malignant lesion will more likely have a broad zone of transition, irregular periosteal reaction, and moth-eaten or permeative destruction of trabeculae. Metastatic bone lesions primarily occur in sites of persistent red marrow: skull, ribs, vertebrae, pelvis, and proximal humerus and femur. Bony lesions can be blastic or lytic in nature. Solitary pulmonary nodules that have not grown for 2 years can be assumed to be benign. Calcification seen on plain films are a strong (but not absolute) indication of benignancy. Lesions that are greater than 3 to 4 cm in diameter, have irregular contours, are cavitated with thick walls, have multiple peripheral nodules, and have lack of calcification are more likely malignant.     

West syndrome model: seek and you will find

The mRNA expression and autoregulation of expression of the three isoforms of transforming growth factor-beta (TGFbeta) were examined in the mouse skin carcinogenesis model by northern analyses. We found that TGFbeta3 mRNA levels followed a pattern similar to those of TGFbeta1 during carcinogenesis: the levels were somewhat low in normal skin but became highly overexpressed in late-stage papillomas and squamous cell carcinomas (15- to 20-fold higher than in normal skin). On the other hand, the TGFbeta2 mRNA levels remained relatively low in all benign and malignant tumors, even though the levels were higher than the nearly undetectable levels in normal skin. In a squamous cell carcinoma cell line (CH72), stable transfection and expression of a mutated simian TGFbeta1 cDNA producing bioactive TGFbeta1 significantly downregulated (mean greater than ten-fold) TGFbeta2 mRNA levels and modestly downregulated (about twofold) murine TGFbeta1 expression but had no effect on TGFbeta3 mRNA. In contrast, treatment of all CH72 clones with exogenous TGFbeta1, TGFbeta2, or TGFbeta3 either had no effect or slightly downregulated TGFbeta1 mRNA, upregulated TGFbeta2 mRNA expression an average of twofold to threefold, and strongly upregulated (mean 13- to 27-fold) TGFbeta3 mRNA levels. TGFbeta treatment of primary cultures of mouse skin keratinocytes upregulated all three TGFbeta mRNA levels slightly to moderately (1.3- to 5-fold). Thus, although TGFbeta1 and TGFbeta3 mRNA expressions were apparently coordinately upregulated during mouse skin carcinogenesis, the three TGFbeta mRNAs were differentially regulated by stable transfection of active TGFbeta1 versus exogenous TGFbeta treatment in CH72 cells and by TGFbeta treatments of normal keratinocytes versus carcinoma CH72 cells.     

Solitary choroidal metastasis as the first sign of metastatic lung carcinoid

The identification of malignancies associated with transplantation has led to enhanced vigilance and care in these patients, as well as insight into the pathogenesis of select malignancies. We report a case of Merkel cell carcinoma, an uncommon cutaneous malignancy of neuroendocrine origin, diagnosed in a 65-year-old Caucasian man 6 years after renal transplantation. While it is well known that transplant patients are at increased risk for squamous cell carcinomas of the skin, other types may also have an increased frequency. We suggest that Merkel cell carcinoma could have an increased incidence in the transplant population.     

Glycopathological study of eyelid tumors and pseudotumors

The expression of MUC1, Tn (GalNAc alpha 1-O-Ser/Thr) and sialosyl Tn (STn) (NeuAc alpha 2,6 GalNAc alpha 1-O-Ser/Thr) antigens, which are useful markers for the prognosis of cancer in other organs, was examined immunohistochemically in a series of 45 eyelid tumors and 5 pseudotumors: basal cell carcinoma, 18; squamous cell carcinoma, 11; sebaceous gland carcinoma, 6; seborrheic keratosis, 4; papilloma, 3; verruca vulgaris, 2; nevus, 1; and granuloma, 5. The MUC1 antigen was identified in all squamous cell and sebaceous gland carcinomas, but not in basal cell carcinoma or the benign tumors. The Tn antigen was expressed in all the sebaceous gland, half of the squamous cell, and only rarely in the basal cell carcinomas. The STn antigen was expressed in all seborrheic keratosis and in the majority of squamous cell carcinomas, but only rarely in sebaceous gland and basal cell carcinomas. Eyelid tumors are frequently associated with apomucin and mucin-carbohydrate antigens: the MUC1 glycoprotein appears to be related to the malignant potential of eyelid tumors, and may be a useful marker for the differential diagnosis of invasive tumors, including sebaceous gland and squamous cell carcinomas.     

Prevalence of human immunodeficiency virus infection, mortality rate, and serogroup distribution among patients with pneumococcal bacteremia at Denver General Hospital, 1984-1994

The hemagglutinating virus of Japan (HVJ)-liposome method involves the entrapment of DNA and nuclear protein within liposomes and the use of HVJ to enhance liposome fusion with cell membranes. This method has been used successfully for in vivo gene transfer to various types of tissue. In this study, we investigated whether this method transfers genes effectively to normal and malignantly transformed keratinocytes in vivo. We applied HVJ-liposome complex (HLC) containing the beta-galactosidase gene to the tape-stripped skin of hairless rats and detected the enzyme activity in the keratinocytes of the treated skin. Comparison of this method with the naked DNA injection method, which was shown recently to be useful for in vivo gene transfer to keratinocytes, demonstrated that the transfer efficiency of the latter was about 5 times higher than that of the former. We assessed the efficacy of the HVJ-liposome method for gene transfer to transformed keratinocytes by examining the effect of HLC containing the herpes simplex virus thymidine kinase gene on the growth of mouse squamous cell carcinomas. Local injection of HLC into the tumors followed by administration of ganciclovir to mice resulted in tumor growth inhibition. These results indicate that the HVJ-liposome method is suitable for in vivo gene transfer to keratinocytes; also that this method may prove a good tool for basic research into keratinocyte biology and future keratinocyte gene therapy.     

Beyond bloodletting

Marjolin's ulcer is a term used to describe squamous cell carcinomas which develop in chronic wounds. These carcinomas may also develop at the site of long-standing irritation, such as unstable burn scars. Development times for burn scar carcinomas of more than 30 years have been noted. This evaluation describes the treatment of 10 patients with burn scar carcinomas who have been treated using wide excision and closure of the defect with skin grafts or flaps, plus regional lymph node dissection if required. Results indicate a mean carcinoma development time of 26 years. Local recurrence occurred in only one patient.     

Genomic imprinting in the brain

Biopsies of cervix uteri from 166 patients with benign and malignant lesions (12 normal, 48 inflammatory lesion, 6 adenocarcinoma, 2 adenosquamous carcinoma and 98 from squamous cell carcinomas) were studied histochemically. The stains used were PAS with/without diastase, AB/PAS (pH 2.5) and OR/AB. In inflammatory lesions neutral mucin was predominent which was replaced by sialomucin and sulphomucin in endocervical polyps. In malignant lesions sulphomucin was predominent. Seventeen percent cases of squamous cell carcinomas needed reclassification after mucin staining. Of the fourteen large cell non-keratinizing squamous cell carcinomas, 12 were reclassified as squamous cell carcinoma with mucin secretion and 2 as adenosquamous carcinoma. One case of small cell non-keratinizing squamous cell carcinoma was reclassified as moderately differentiated adenocarcinoma. None of the keratinizing carcinomas had evidence of mucin secretion. Mucin histochemistry should be done routinely on non-keratinizing squamous cell carcinomas to pick up more cases of carcinoma with evidence of mucin secretion which can be missed on routine haematoxylin and eosin stains. Such carcinomas are known to pursue a more aggressive clinical course and have a poorer prognosis than non-mucin secreting type of squamous cell carcinoma.     

Immunohistochemical staining for desmogleins 1 and 2 in keratinocytic neoplasms with squamous phenotype: actinic keratosis, keratoacanthoma and squamous cell carcinoma of the skin

Desmosomes are intercellular junctions that have been shown to be down-regulated in certain types of carcinoma and that may play a role in suppression of invasion and metastasis. This paper describes an immunohistochemical study of three types of epidermal neoplasms with monoclonal antibody to desmoglein in order to determine how desmosomal staining correlates with the clinical, biological and histopathological features of these neoplasms. Actinic keratosis (AK) is the most common keratinocytic premalignant neoplasm that was reported to have a 10-20% rate of malignant transformation into squamous cell carcinoma (SCC). Keratoacanthoma (KA) is a benign neoplasm that involutes spontaneously after a few months of rapid growth. SCC is a malignant tumour capable of metastasis. Electron microscope studies of KA and SCC showed significantly reduced staining for desmosomes in SCC but not in KA. We have examined staining for desmoglein using the monoclonal antibody 33-3D, a mouse IgM monoclonal antibody, that recognizes the cytoplasmic domains of desmoglein (Dsg)1 and Dsg2 on frozen sections. Immunohistochemical staining of normal skin with this antibody revealed strong pericellular localization of the antigen, outlining the cell membranes of the keratinocytes. A series of 30 AKs, 12 KAs and 24 SCCs was stained immunohistochemically with 33-3D monoclonal antibody. All examined KAs showed extensive pericellular staining for Dsg. By contrast, juxtanuclear staining for Dsg was noted in 12 SCCs, and completely negative staining in seven SCCs. The five remaining SCCs showed focal pericellular staining for the Dsg marker. The most common finding in AK was focal pericellular staining for Dsg, with complete absence of staining in dysplastic areas (25 cases). In five cases negative pericellular staining in dysplastic areas was associated with juxtanuclear accumulation of the Dsg marker. A strong negative correlation between Dsg staining and degree of dysplasia was obtained. The Dsg pattern in KA is similar to normal epidermis and shows a clear difference between KA and SCC. AK has a limited loss of Dsg expression in a SCC-like pattern that is congruent with its premalignant nature. As the stain works on frozen tissue, it may be helpful for rapid differentiation in selected cases in cutaneous oncology and Mohs micrographic surgery. This antibody may also have great potential for the detection of the effects of chemopreventive agents in skin cancer.     

Characterization of corticotropin-releasing hormone (CRH) in human skin

We have confirmed the expression of CRH and CRH receptor type 1 genes in human skin, cultured HaCaT keratinocytes, squamous cell carcinoma, and melanoma cells. The size of CRH messenger ribonucleic acid (mRNA), estimated by Northern blot hybridization, was 1.5 kilobases. CRH peptide was identified by reverse phase high pressure liquid chromatography separation in both whole skin and cultured cells. Forskolin and dexamethasone at concentrations of 10 micromol/L stimulated and inhibited, respectively, CRH peptide production in squamous cell carcinoma and melanoma cells, but had no significant effect on the CRH mRNA level. In melanoma cells, stimulation of melanogenesis down-regulated CRH receptor type 1 mRNA expression, but was without effect on CRH mRNA production. We suggest that in human skin the CRH signaling system is both operative and under regulatory control.     

Histopathologic changes seen in esophagectomy specimens from the high-risk region of Linxian, China: potential clues to an etiologic exposure?

Esophageal cancer is one of the most fatal cancers worldwide and is characterized by great variation in rates among different populations. Linxian, a county in Henan Province, located in north-central China, has one of the highest rates of esophageal squamous cell carcinoma in the world. Most squamous cell carcinomas in low-risk populations are attributable to alcohol and tobacco consumption, but the causative agents in high-risk populations are less clear. The prevention and treatment of esophageal cancer in high-risk regions, such as Linxian, are limited by our inability to identify these agent(s). During a preliminary histological review, the authors noticed characteristic findings in the arteries, nerves, and lymph nodes of esophagectomy specimens from Linxian and wondered whether these findings might offer clues to the cause of squamous cell carcinoma (eg, polycyclic aromatic hydrocarbon exposure) in the Linxian population. The purpose of this study was to report these previously undescribed histopathologic changes and to compare their presence and severity with those found in esophageal squamous cell carcinomas and adenocarcinomas from a lower-risk population in the United States. Forty esophagectomies were reviewed, including 13 squamous cell carcinomas from Linxian and 21 squamous cell carcinomas and six adenocarcinomas from the United States. The presence and severity of arteriosclerosis and myxoid degeneration of nerves and the presence of anthracosis in periesophageal lymph nodes were recorded. The prevalence and severity of these findings in the three groups of esophagectomies were compared. The esophageal squamous cell carcinomas from Linxian, China, had a higher prevalence of arteriosclerotic vessels, nerves with myxoid degeneration, and anthracotic lymph nodes than the squamous cell carcinomas from the United States (Wilcoxon test, P < .04 for all comparisons). There were also significant differences in the prevalence of arteriosclerotic vessels and anthracotic lymph nodes between the esophageal squamous cell carcinomas from Linxian and the adenocarcinomas from the United States. Arteriosclerosis and the myxoid degeneration were significantly more severe in the esophageal squamous cell carcinomas from Linxian than in the esophageal squamous cell carcinomas or adenocarcinomas from the United States (Mantel trend test, P < .006 for all comparisons). Arteriosclerotic vessels, nerves with myxoid degeneration, and anthracotic lymph nodes can be seen in association with esophageal squamous cell carcinomas from the high-risk region of Linxian, China. These changes appear to be more prevalent and severe than those seen in association with esophageal squamous cell carcinomas or adenocarcinomas from a low-risk population in the United States. These characteristic changes may be causatively significant and may represent histological evidence of high-level environmental exposure to polycyclic aromatic hydrocarbons.     

Carcinomas of Bartholin''s gland. Histogenesis and the etiological role of human papillomavirus

In this study, we examine 10 primary carcinomas of Bartholin's gland, including seven squamous carcinomas, two adenoid cystic carcinomas, and one adenocarcinoma, as well as four non-neoplastic Bartholin's gland. Six of seven squamous cell carcinomas contained human papillomavirus (HPV) type 16 DNA detectable by the polymerase chain reaction; one of these demonstrated HPV type 16 by in situ hybridization. The two adenoid cystic carcinomas, the adenocarcinoma, and the non-neoplastic Bartholin's gland epithelium showed no evidence of HPV DNA by polymerase chain reaction or in situ hybridization. A panel of eight antibodies (Cam 5.2, B72.3, CEA, EMA, MCA, Lewis X, ER, and PR) demonstrate that the squamous, transition zone, duct, acinar, and myoepithelial cells or Bartholin's gland are antigenically distinct, and are similar to those reported in analogous areas of the uterine cervix. Squamous carcinoma and adenocarcinomas of Bartholin's gland are antigenically similar, and seem to arise from the transition zone of the Bartholin's gland duct. The origin of adenoid cystic carcinomas is more difficult to determine; it is distinct from squamous and adenocarcinomas and seems more likely to arise from myoepithelial cells. We conclude that adenocarcinoma and squamous cell carcinoma of Bartholin's gland arise in the transition zone of Bartholin's gland, which is similar to the transition zone of the uterine cervix. We also show that HPV is associated with Bartholin's gland carcinoma and may play a role in the genesis of malignancy.